Pharmacy Foundations Part 1

Nervous System

Common Receptors, Substrates and Drugs

Receptor Substrate Agonist Action Drug Agonists Antagonist action Drug Antagonists

Muscarinic ACh ⇧ SLUDD Pilocarpine, bethanechol ⇩ SLUDD Atropine, Oxybutynin

Nicotinic ACh ⇧ HR, BP Nicotine Neuromuscular Neuromuscular blockers

blockade (ex. rocuronium)

Alpha-1 Epi, NE Smooth muscle Phenylephrine, dopamine Smooth muscle 𝛼-1 blockers (ex.
vasoconstriction (dose-dependent) vasodilation Doxazosin, Carvedilol,
⇧ BP ⇩ BP phentolamine)

Alpha-2 Epi, NE ⇩ release of Epi, NE Clonidine, brimonidine ⇧ BP, HR Ergot alkaloids,

⇩ BP, HR yohimbine

Beta-1 Epi, NE ⇧ myocardial Dobutamine, ⇩ CO, HR Metoprolol - 𝜷1 selective

contractility, CO, HR isoproterenol, dopamine Propranolol, Carvedilol -
(dose-dependent) Non-selective

Beta-2 Epi Bronchodilation Albuterol, terbutaline, Bronchoconstriction Propranolol, Carvedilol -

isoproterenol Non-selective

Dopamine Dopamine Renal, cardiac & Levodopa, pramipexole Renal, cardiac & 1st gen antipsych
CNS effects CNS effects (haloperidol),
Metoclopramide

Serotonin Serotonin Platelet, GI & Triptans Platelet, GI & Ondansetron,

psychiatric effects psychiatric effects 2nd gen antipsych
(quetiapine)

Enzymes
Enzyme Endog. Effects Drug Examples Drug Action

Acetylcholinesterase Breaks down Donepezil, rivastigmine, Blocks acetylcholinesterase → ⇧ ACh

acetylcholine galantamine Tx of Alzheimer’s disease

Angiotensin- Converts angiotensin I ACE-I (Lisinopril, ramipril) Inhibits production of angiotensin II → ⇩

converting enzyme to angiotensin II vasoconstriction & ⇩ aldosterone secretion
(ACE) Tx of HTN, HF, CKD

Catechol-O- Breaks down COMT Inhibitors Blocks COMT to prevent peripheral breakdown
Methyltransferase levodopa (Entacapone) of levodopa → ⇧ DOA of levodopa
(COMT) Tx of Parkinson disease

Cyclooxygenase Converts arachidonic NSAIDs (ASA, ibuprofen) Blocks COX to ⇩ prostaglandins &
(COX) acid to prostaglandins thromboxane A2;
and thromboxane A2 Tx of pain/inflammation; ⇩ platelet
activation/aggregation
Monoamine oxidase Breaks down MAO-I (phenelzine, Blocks MAO → ⇧ catecholamine levels
(MAO) catecholamines tranylcypromine, linezolid, Tx of depression
(DA, NE, Epi, 5-HT) isocarboxazid, selegiline,
rasagiline, methylene blue)

Phosphodiesterase Breaks down cGMP, a PDE-5I (sildenafil, tadalafil) Competitively binds to same active site as
(PDE) smooth muscle cGMP on PDE-5 → prevents breakdown of
relaxant cGMP & prolongs smooth muscle relaxation
Tx of erectile dysfunction

Vitamin K epoxide Converts vitamin K to Warfarin Blocks vitamin K epoxide reductase → ⇩

reductase active form required production of clotting factors II, VII, IX, X
for production of select Tx or prevent blood clots
clotting factors

Xanthine oxidase Breaks down Allopurinol Blocks xanthine oxidase → ⇩ uric acid
hypoxanthine & production
xanthine into uric acid Tx of gout attacks

Drug Interactions

Pharmacodynamics: Pharmaco + Dyanmics

● “Pharmaco” refers to a drug // “Dynamic” refers to an activity – type of process or change
● Pharmacodynamics = effect that a drug has on the body
○ Effect can be therapeutic (morphine provides pain relief when it binds to mu receptor)
○ Effect can be toxic (excessive morphine can be fatal)
● PD drug interactions can occur when two or more drugs are given together – effects can be:
○ Additive (such as more sedation)
○ Antagonistic (one drug blocks the effect of another drug)
○ Synergistic, with an amplified effect (more than additive)

Risk with Concurrent use of Benzodiazepines & Opioids

Due to the heightened fatality risk when opioids & benzodiazepines are taken together, the FDA added a
boxed warning to all drugs in both classes
Warning: Risks from Concomitant use with Opioids
● Concomitant use of benzodiazepines & opioids may result in profound sedation, respiratory
depression, coma & death
○ Limit concomitant prescribing of these drugs to patients for whom alternative treatment
options are inadequate
○ Restrict dosages & durations to the minimum require
○ Monitor patients for signs & symptoms of respiratory depression & sedation

Pharmacokinetics: Pharmaco + Kinetics

● “Pharmaco” refers to a drug // “Kinetic” refers to motion
● Pharmacokinetics = affect the body has on the drug as it goes through the ADME processes
○ Absorption: typically occurring in the small intestine with oral drugs
○ Distribution: through the blood & dispersed throughout the tissues
○ Metabolism: including enzymatic reactions
○ Excretion: removal of the drug or end products (metabolites) from the body
● PK drug interactions occur when 1 drug alters the ADME of another drug – harmful or beneficial
 Prodrugs & active metabolites
Capecitabine → Fluorouracil Fosphenytoin → Phenytoin Example Safety Considerations
Codeine, by itself & in combo products such as Tylenol #3
Tramadol → Active metabolite Primidone → Phenobarbital • Risk of toxicity with ultra-rapid metabolizers (UMs) of CYP2D6
due to more rapid conversion to morphine
Codeine → Morphine Levodopa → Dopamine
- Do not use codeine in UMs of 2D6
Colistimethate → Colistin Valacyclovir → Acyclovir • Risk of poor analgesia with poor metabolizers (PMs) of CYP2D6
- Use alternative analgesic in PMs of 2D6
Cortisone → Cortisol Valganciclovir → Ganciclovir Clopidogrel (Plavix)
• Risk with CYP2C19 inhibitors, which can block conversion to
Prednisone → Prednisolone Famciclovir → Penciclovir
the active form
Isavuconazonium sulfate → Isavuconazole - Do not use with CYP2C19 inhibitors – omeprazole &
esomeprazole (can decrease antiplatelet effects)
Lisdexamfetamine → Dextroamphetamine • Risk with PMs of CYP2C19 (low conversion to active form with
reduced antiplatelet activity)
Clopidogrel → Active metabolite - Use alternative P2Y12 inhibitor in PMs of 2C19

Common CYP Inhibitors

G ❤ PACMAN

Grapefruit Effects on Substrates

• Decreased metabolism
Protease Inhibitors (especially ritonavir) • Increased serum levels & clinical effects
• INhibitors = INcreased effects/levels/ADRs/toxicities
Azole antifungals Effects on Prodrugs
• Decreased conversion to active drug (⇩ serum levels & clinical effects)
Cyclosporine, Cobicistat Recognizing the Problem
• Perform therapeutic drug monitoring
Macrolides (not azithromycin) • Monitor for therapeutic effect
Possible actions: ⇩ dose of substrate (unless prodrug), use alternate
Amiodarone (& dronedarone) drug to avoid combo

Non-DHP CCBs (Verapamil, Diltiazem)

Common CYP Inducers

PS PORCS

Phenytoin Effects on Substrates

• Increased metabolism
Smoking • Decreased serum levels & clinical effects
• InDucers = Decreased effects/levels
Phenobarbital Effects on Prodrugs
• Increased conversion to active drug (⇧ serum levels & clinical effects)
Oxcarbazepine Recognizing the Problem
• Perform therapeutic drug monitoring
Rifampin (& rifabutin, rifapentine) • Monitor for therapeutic effect
Possible actions: ⇧ dose of substrate (unless prodrug), use alternate
Carbamazepine (also auto-inducer)

St. John’s Wort

 Lab Monitoring

Therapeutic Drug Levels

Drug Therapeutic Range

Carbamazepine 4-12 mcg/mL

Digoxin 0.8-2 ng/mL (AF) 0.5-0.9 ng/mL (HF)

Gentamicin, Tobramycin (traditional dosing) Peak: 5-10 mcg/mL Trough: < 2 mcg/mL

Lithium 0.6-1.2 mEq/L (up to 1.5) – drawn as a trough

Phenytoin/Fosphenytoin 10-20 mcg/mL (if albumin is low, calculate corrected level)

- Free phenytoin - 1-2.5 mcg/mL

Procainamide 4-10 mcg/mL

NAPA (procainamide active metabolite) 15-25 mcg/mL

Combined 10-30 mcg/mL

Theophylline 5-15 mcg/mL

Valproic Acid 50-100 mcg/mL (up to 150 in some patients)

Vancomycin Trough: 15-20 mcg/mL: serious infections Trough: 10-15 mcg/mL for others

Warfarin INR 2-3 (2.5-3.5 for mechanical mitral valves)

Drug References

Locating Guidelines for Common Conditions

Anticoagulation Cardiovascular Disease

Guidelines from the American College of Chest Physicians Guidelines from the American College of
(CHEST guidelines) Cardiology/American Heart Association (ACC/AHA)
• Stroke Prevention in Atrial Fibrillation • Acute Coronary Syndromes • Heart Failure
• Venous Thromboembolism • Atrial Fibrillation • Hypertension
• High cholesterol

Diabetes Oncology

• American Association of Clinical Endocrinologists (AACE) • American Society of Clinical Oncology (ASCO)
• American Diabetes Association (ADA) • National Comprehensive Cancer Network (NCCN)

Pulmonary Conditions Infectious Diseases

• Asthma: Global Initiative for Asthma (GINA) & National • Infectious Diseases Society of America (IDSA)
Heart, Lung & Blood Institute (NHLBI) • HIV/AIDS: US Dept. of Health & Human Services
• COPD: Global Initiative for Chronic Obstructive Lung • Sexually transmitted infections: CDC
DIsease (GOLD)
 Pregnancy/Women’s Health Pediatrics

• American College of Obstetricians & Gynecologists (ACOG) • American Academy of Pediatrics (AAP)

Psychiatric Conditions Vaccines

• American Psychiatric Association (APA) Diagnostic & • Advisory Committee on Immunization Practices (ACIP)
Statistical Manual of Mental disorders, 5th edition (DSM-5) • Centers for Disease Control (CDC)

Renal Disease

• Kidney Disease Improving Global Outcomes (KDIGO)

“Color” Drug References

Orange Book (FDA) Red Book, Pediatrics (AAP)
List of approved drugs that can be interchanged with generics Summaries of pediatric infectious diseases, antimicrobial
based on therapeutic equivalence treatment & vaccinations

Pink Book (CDC) Red Book, Pharmacy

Information on epidemiology & vaccine-preventable diseases Drug pricing information

Pink Sheet (Pharma Intelligence) Yellow Book (FDA)

News reports on regulatory, legislative, legal & business Information on the health risks of international travel,
developments required vaccines & prophylaxis medications

Purple Book (FDA) Green Book (FDA)

List of biological drug products, including biosimilars Information on approved animal drug products

Drug Formulations & Patient Counseling

Patch Frequency
Daily • Methylphenidate (Daytrana) • Rotigotine (Neupro)
• Nicotine (NicoDerm CQ) • Selegiline (Emsam)
• Rivastigmine (Exelon) • Testosterone (Androderm)

Daily • Lidocaine (Lidoderm) • Nitroglycerin

(special instructions) - 1-3 patches (prn), on for 12H, off for 12H - On for 12-14H, then off for 10-12H

Twice Daily • Diclofenac

Every 72H • Fentanyl (If it wears off after 48H, can change to Q48H)

Weekly • Estradiol (Climara) • Donepezil (Adlarity)

• Estradiol/Levonorgestrel • Buprenorphine (Butrans)
• Ethinyl estradiol/norelgestromin (Xulane, Zafemy) • Clonidine (Catapres-TTS)
• Ethinyl estradiol/Levonorgestrel (Twirla)

Twice Weekly • Estradiol (Alora, Vivelle-Dot) • Oxybutynin (Oxytrol)

 Intravenous Medication Principles

Drugs with Leaching/Adsorption/Absorption issues with PCV containers

Leach Absorbs To Take In Nutrients OR (LATTIN)
- Lorazepam, Amiodarone, Tacrolimus, Taxanes, Insulin, Nitroglycerin

Diluent Incompatibility
Drugs Incompatible with Outrageous Bakers Avoid Salt
NS - Oxaliplatin, Bactrim, Amphotericin B, Synercid (Quinupristin/Dalfopristin)

Drugs Incompatible with A DIAbetic Can’t Eat Pie

D5W - Ampicillin, Daptomycin (Cubicin), Infliximab (Remicade), Amp/Sulbactam
(Unasyn), Caspofungin (Cancidas), Ertapenem (Invanz), Phenytoin (Dilantin)

Common Drugs with Filter Requirements

My GAL Is PAT who has a MaP

Golimumab (Simponi) Isavuconazonium Phenytoin Mannitol (> 20%)

Amphotericin B (lipid forms) Amiodarone Parenteral Nutrition – 1.2
Lipids – 1.2 micron Taxanes (Paclitaxel, Docetaxel) micron

Do NOT Refrigerate Drugs

Dear Sweet Pharmacist, Freezing Makes Me Edgy!

Dexmedetomidine SMX/TMP Phenytoin – crystallizes Furosemide – crystallizes

Metronidazole Moxifloxacin Enoxaparin

Protect from Light During Administration

Protect Every Necessary Med from Daylight
Phytonadione (vitamin K) Epoprostenol Nitroprusside Micafungin Doxycycline
 Answering Case-Based Questions

Drugs & Conditions that Alter Vital Signs

Vital Sign Increased Decreased

Drugs Conditions Drugs Conditions

Blood Pressure • Stimulants (ADHD, weight loss) • Renal insufficiency/failure • Antihypertensives • Anaphylaxis
(BP) • Decongestants • Pregnancy • Vasodilators • Blood loss
• NSAIDs • Excess salt intake • Opioids • Infection
⇧: Hypertension • Caffeine, cocaine • Adrenal tumors • Benzos • Dehydration
⇩: Hypotension
• Antidepressants • Anesthetics (orthostatic
• Immunosuppressants; ESAs • Phosphodiesterase hypotension)
• Steroids inhibitors
• Oral contraceptives

Heart Rate • Stimulants (ADHD, weight loss) • Afib, ventricular tachycardia • Beta-blockers • Arrhythmias
(HR) • Decongestants • Hyperthyroidism • Non-DHP CCBs (sinus bradycardia)
• Beta-agonists • Anemia • Digoxin • Hypothyroidism
• Theophylline • Dehydration • Clonidine, guanfacine
⇧: Tachycardia • Anticholinergics (TCAs, • Anxiety, stress, pain • Antiarrhythmics (Class III)
⇩: Bradycardia
antihistamines) • Hypoglycemia • Opioids
• Bupropion • Infection • Sedatives
• Antipsychotics • Drug withdrawal • Anesthetics
• Excess caffeine/nicotine • Serotonin syndrome • Neuromuscular blockers
• Illicit drug use • Acetylcholinesterase
• Vasodilators - cause reflex tachy inhibitors

Respiratory Rate • Stimulants • Asthma, COPD • Opioids • Hypothyroidism

(RR) • Anxiety, stress • Sedatives
⇧: Tachypnea • Ketoacidosis, Pneumonia
⇩: Resp. depression

Temperature (Temp) • Inhaled anesthetics (malignant • Fever, Trauma • Exposure to cold

hyperthermia) • Hyperthyroidism • Hypothyroidism
⇧: Hyperthermia • Antipsychotics (NMS) • Cancer • Hypoglycemia
⇩: Hypothermia • Topiramate • Serotonin syndrome

Where to start for case-base questions – Look for medication therapy problems
• Untreated medical condition • Therapeutic duplication • Improper use of medication
• Medications used without indication • Lack of patient understanding • Failure to receive medication
• Improper drug selection • Drug allergy • Adverse drug reaction
• Dose too low/too high • Drug interaction • Nonadherence
 Calculations

Liquid (Volume) Solid (Weight)

tsp (t) 5 mL 1 kg 2.2 pounds

tbsp (T) 15 mL 1 oz 28.4 g

1 fl oz ~30 mL (29.57 mL) 1 pound 454 g

1 cup 8 oz 1 grain (gr) ~65 mg (64.8 mg)

~240 mL (236.56 mL)

1 pint 16 oz 473 mL Height Conversion

1 quart 2 pints 946 mL Inch 2.54 cm

1 gallon 4 quarts 3785 mL Meter (m) 100 cm

Milliequivalents (mEq) and Millimoles (mmol)

K+, Na+ & monovalent ions 1 mEq = 1 mmol

Ca++ & other divalent ions 1 mEq = 0.5 mmol

Rounding
Never round until LAST STEP of multistep calculation
- If the number > 4 → round DOWN (ex. 347.48 → 347)
- If the number < 5 → round UP

Setting Up Proportions
● Match both numerators & both denominators
○ Every item in the left numerator (drug, route, units) must match to every item in the right
numerator (except the values of the numbers)
○ Every item in the left denominator must match to every item in the right denominator
(except the values of the numbers)
● Match numerator & denominator of each fraction
○ Items in the left fraction (numerator & denominator) must match, and items in the right
fraction (numerator & denominator) must match (except the value of the numbers)

Drug-Dose Conversions
Aminophylline/ • A → T – multiply by 0.8 // T → A – divide by 0.8
Theophylline • ATM (Aminophylline → Theophylline Multiply)

Calcium salts • 1 gram calcium carbonate = 400 mg elemental calcium

• 1 gram calcium citrate = 210 mg elemental calcium

Insulin • Most insulins are 1:1

• Twice daily NPH → glargine (Lantus, Toujeo): use 80% of NPH dose
 • Toujeo → glargine (Lantus, Basaglar) or detemir (Levemir): use 80% of Toujeo dose

Lithium salts • 5 mL lithium citrate syrup = 8 mEq of lithium ion

• 8 mEq of lithium ion = 300 mg lithium carbonate tablets/capsules

Loop diuretics • Furosemide 40 mg = Torsemide 20 mg = Bumetanide 1 mg

Potassium chloride • KCl 10% = 20 mEq/15 mL

IV:PO conversions • Furosemide 1 : 2 • Levothyroxine 0.75 : 1 • Metoprolol 1 : 2.5

Statins Pharmacists Rock At Saving Lives and Preventing Fatty deposits

(Dyslipidemia) • Pitavastatin 2 mg • Lovastatin 40mg
• Rosuvastatin 5 mg • Pravastatin 40mg
• Atorvastatin 10 mg • Fluvastatin 80mg
• Simvastatin 20mg

Drug mg mg elemental iron % elemental iron

Ferrous sulfate 325 65 20%

Ferrous sulfate, dried 160 50 30%

Iron salts
Ferrous fumarate 324 106 33%

Ferrous gluconate 324 38 12%

Carbonyl iron 90 90 100%

Polysaccharide iron complex 150 150 100%

Ferric maltol 30 30 100%

Drug IV/IM (mg) Oral (mg)

Morphine 10 30
Opioids
Hydromorphone 1.5 7.5

Oxycodone — 20

Hydrocodone — 30

Codeine 130 200

Fentanyl 0.1 —

Meperidine 75 300

Oxymorphone 1 10

Least Potent → Most Potent

Cute Hot Pharmacists and Physicians Marry Together & Deliver Babies
 Cortisone 25 mg
Short-acting
Hydrocortisone 20 mg

Prednisone
Steroids 5 mg
Prednisolone Intermediate-acting

Methylprednisolone
4 mg
Triamcinolone

Dexamethasone 0.75 mg Long-acting &

highest potency
Betamethasone 0.6 mg

Ratio Relationships
4:8 = 4/8 → 1/2 or, 1 part to 2 parts

Common IV Fluids
● Normal saline (NS): 0.9% (w/v) NaCl in water
○ 1/2NS: 0.45% (w/v) NaCl in water
○ 1/4NS: 0.225% (w/v) NaCl in water
● D5W: 5% (w/v) dextrose in water
● D20W: 20% (w/v) dextrose in water

Dissociation Particles vs. Valence

 Calories Provided by Macronutrients
Carbs (Bread, rice) 4 kcal/gram
Usual Diet
Fat (Butter, oil) 9 kcal/gram

Protein (Fish, meat) 4 kcal/gram

Corn syrup solids, cornstarch, sucrose Premixed solutions that contain carbs,
fats & proteins
EN Formulas Borage oil, canola oil, corn oil
Examples of EN formulas: Ensure,
Casein, soy, whey Osmolite, Jevity, Glucerna

Dextrose Monohydrate 3.4 kcal/gram

Glycerol/Glycerin 4.3 kcal/gram

PN Formulas Injectable Lipid Emulsion (ILE) 10% 1.1 kcal/mL

Injectable Lipid Emulsion (ILE) 20% (Intralipid, Smoflipid) 2 kcal/mL

Injectable Lipid Emulsion (ILE) 30% 3 kcal/mL

Amino Acid Solutions (Aminosyn, FreAmine) 4 kcal/gram

Height in Inches
Ex. Patient is 5 feet, 6 in. tall (5’6”). How many in. tall is the patient? Ex. Patient is 6’3”. How many inches tall is the patient?

• 1 ft = 12 inches → 5 ft = 60 inches • 6 ft x 12 inches/ft = 72 inches

• Next, add additional 6 inches → 5’6” = 66 inches • Next, add additional 3 inches → 6’3” = 75 inches
• For IBW calculation, patient is 6 inches over 5 feet • For IBW calculation, patient is 15 inches over 5 feet

Final Volume of Compounded IV Solutions

● Explicit instructions
○ Ex: 5 mL Keppra vial diluted in 100 mL NS…. do not include volume of the 5 mL additive
● Language stating that a specific volume is “added to” some volume of fluid
○ Example: 10 mL CaCl2 & 10 mL MVI is added to 500 mL D5W (use 520 mL)
● Rounding instructions are such that either method will yield the correct answer or volumes of
additive are not provided
● Language stating that a specific volume’s added “to make 1L” or “for a final volume of 1L”

Interpreting ABGs
Acid-Base Disorder pH Primary Disturbance Compensation Summary

Respiratory alkalosis ⇧ ⇩ PCO2 ⇩ HCO3- pH > 7.45; PCO2 < 35

Respiratory acidosis ⇩ ⇧ PCO2 ⇧ HCO3- pH < 7.35; PCO2 > 45

Metabolic acidosis ⇩ ⇩ HCO3- ⇩ ­PCO2 pH < 7.35; HCO3- < 22

Metabolic alkalosis ⇧ ­⇧­HCO3- ­⇧ PCO2 pH > 7.45; HCO3- > 26

 Step 1: Is it an acidosis or alkalosis? • ⇩ pH = acidosis • ⇧ pH = alkalosis

Step 2: What other values are abnormal? • Respiratory: • Metabolic:

- ⇩ PCO2 = alkalosis - ⇧ HCO3- = alkalosis
- ⇧ PCO2 = acidosis - ⇩ HCO3- = acidosis

Step 3: Which of the following abnormal • Example: ⇩ pH, ⇧ PCO2 & normal HCO3-
values in step 2 matches the pH in step 1? - pH = acidosis & ⇧ PCO2 = acidosis → Respiratory acidosis

Step 4: What if both PaCO2 & HCO3 are • Usually only one of the values will match the pH & the other will go in the
abnormal? opposite direction as expected from pH → compensation
• Example: ⇩ pH, ⇩ PCO2 & ⇩ HCO3-
- pH = acidosis, ⇩ HCO3- = acidosis, & ⇩ PCO2 = alkalosis
- Metabolic acidosis with some degree of respiratory compensation
Keys to remember:
Metabolic: bicarbonate always the saME as pH (⇩ & ⇩) Respiratory: bicarbonate is reverse of pH (⇧ & ⇩)

Biostatistics

Central Tendency Calculations

Example: DPB (in mmHg) reduction for 9 patients in a trial
3, 2, 3, 8, 6, 3, 4, 4, 3

Put the numbers in order ↓ Mean = 4 (36 / 9 = 4)

2+3+3+3+3+4+4+6+8

Mode = 3 (# that occurs most frequently) Range = 6 (highest value (8) minus smallest value (2)

Median = 3 (value in the middle of the ordered list)

Interpreting Confidence Intervals

● The values in the CI range are used to determine whether significance has been reached
● Determining statistical significance using CI alone (without a p-value) is required for the exam
Comparing Difference Data (MEANS)
● Difference data is based on subtraction [ex. difference in Δ FEV1 between roflumilast & placebo
(below) was 38 (46-8 = 38)]
● The result is statistically significant if the CI range does not include zero (zero is not present in
the range of values); for example:
○ 95% CI: difference in ΔFEV1 (18-58 mL) does not include zero (statistically significant)
○ 95% CI: difference in ΔFEV1/FVC(-0.26-0.89) includes zero(not statistically significant)
Lung Function Roflumilast (N = 745) Placebo (N = 745) Difference (95% CI)

Δ FEV1 (mL) 46 8 38 (18-58) – doesn’t cross zero

Δ FEV1/FVC (%) 0.314 0.001 0.313 (-0.26-0.89) – crosses zero

Comparing Ratio Data (RELATIVE RISK, ODDS RATIO, HAZARD RATIO)
● Ratio data is based on division [ex. ratio of severe exacerbations between roflumilast & placebo
 (below) was 0.92 (0.11/0.12)]
● The result is statistically significant if the CI range does not include ONE (one is not present in
the range of values); for example:
○ 95% CI: RR of severe exacerbations(0.61-1.29) includes 1 (not statistically significant)
○ 95% CI:RR of mod exacerbations(0.72-0.99) does not include 1(statistically significant)
Exacerbations Roflumilast (N = 745) Placebo (N = 745) Relative Risk (95% CI)

Severe 0.11 0.12 0.92 (0.61-1.29) – crosses one

Moderate 0.94 1.11 0.85 (0.72-0.99) – doesn’t cross one

Rounding Rules for NNT & NNH

Normal rounding rules do not apply
NNT Anything greater than a whole number, round UP to next whole number NNT = 34.1 → round UP to 35
- Avoids overstating the potential benefit of an intervention

NNH Anything greater than a whole number, round DOWN to next whole number NNH = 41.9 → round DOWN to 41
- Avoids understating the potential harm of an intervention.

Compounding & Hazardous Drugs

USP Compounding Chapters

Non-Sterile Sterile
(orals, topicals, nasals) (IV drugs, eye drops)

Hazardous Non-Hazardous Hazardous Non-Hazardous

USP 795 and 800 USP 795 USP 797 and 800 USP 797

Interpreting USP Terminology

Acronym Meaning Common Terms

CSPs Compounded Sterile Products IVs or other drugs that require sterile manipulation

SVP Small Volume Parenteral IV bag or container containing < 100 mL

LVP Large Volume Parenteral IV bag or container containing > 100 mL

PPE Personal Protective Equipment Garb (gown, gloves, mask); “don” means to put on & “doff” is to take off

PEC Primary Engineering Control Sterile hood that provides ISO air 5 for sterile compounding

LAFW Laminar Airflow Workbench Type of sterile hood (PEC); parallel air streams flow in one direction

C-PEC Containment Primary Engineering Control Ventilated (negative pressure) chemo hood used for HDs

BSC Biological Safety Cabinet Chemo hood (Class II or III for sterile HD), a type of C-PEC

SEC Secondary Engineering Control ISO 7 “buffer room” where the sterile hood (PEC) is located

C-SEC Containment Secondary Engineering Control Ventilated (neg. pressure) buffer room for HDs (room where C-PEC is)
 SCA Segregated Compounding Area Designated space that contains ISO 5 hood but is not part of a cleanroom suit
(air is not ISO-rated)

C-SCA Containment Segregated Compounding Area Ventilated (neg. pressure) room used for HDs; not in a cleanroom suit (air is
not ISO-rated)

CAI Compounding Aseptic Isolator “Glovebox” for non-HDs, a closed-front sterile hood (PEC)

CACI Compounding Aseptic Containment Isolator “Glovebox” for HDs, a type of closed-front C-PEC

RABS Restricted Access Barrier System “Glovebox”/closed-front sterile hood (includes CAIs and CACIs)

CSTD Closed System Transfer Device Device preventing escape of HD/vapors when transferring (ex. vial → syringe)

CVE Containment Ventilated Enclosure Ventilated “powder hood” for non-sterile products (can be used for HDs if USP
800 standards are met)

ISO Air Quality Inside the PEC

PEC provides ISO 5 air quality for sterile compounding. Air coming directly out of HEPA filter = first air, which
Direct is cleaner than the rest of the air in the sterile hood. To prevent contamination of CSPs during compounding,
compounding injection port of the vial & syringe needle must be kept in first air
area & first air ● Do not obstruct first air, especially the area where the needle enters the vial or ampule
● Do not block airflow from the HEPA filter with hands or supplies
● Place items correctly inside the PEC to avoid creating turbulence which can lead to contamination

● Wipe off the outside of all materials (ex. vials, syringes) with 70% isopropyl alcohol (IPA) before
bringing them into the PEC
Prevent ● Open packages along the designated tear line, if present; do not rip open packages or punch needles
contamination or syringes through the wrappers which contaminates the air with particles
by keeping air ● Compound at least 6 in inside hood to prevent exposing CSPs to dirtier ISO 7 air from the SEC
in PEC clean ● Move waste out of PEC shortly after it is created; do not let it accumulate inside the hood
Most contamination to CSPs comes from the compounding staff, largely from inadequate hand hygiene &
garbing; correct technique is essential

Positive pressure non-hazardous

 Hazardous Key Drugs on NIOSH List
Antineoplastic Drugs Chemotherapeutics Abortifacients Mifepristone, Misoprostol

Antibiotics Chloramphenicol Anticoagulants Warfarin

Antifungals Fluconazole, Voriconazole Antivirals Cidofovir, Ganciclovir, Valganciclovir

Acne Isotretinoin Antiarrhythmics Dronedarone

BPH Dutasteride, Finasteride Antiretrovirals Abacavir, Entecavir, Zidovudine

Depression Paroxetine Chemoprotectant (Cardiac) Dexrazoxane

Diabetes Exenatide, Liraglutide Bisphosphonates Pamidronate, Zoledronic Acid

Dyslipidemia Lomitapide Gout Colchicine

Hepatitis Ribavirin Iron Overload Deferiprone

Heart Failure Ivabradine, Spironolactone Hyperthyroidism Methimazole, Propylthiouracil

Migraine Dihydroergotamine Insomnia Temazepam, Triazolam

Schizophrenia Ziprasidone Parkinson Disease Apomorphine, Rasagiline

Autoimmune Azathioprine, Acitretin Leflunomide, Fingolimod, Teriflunomide

Transplant Cyclosporine, Mycophenolate, Tacrolimus, Sirolimus

Seizures/Epilepsy Clobazam, Clonazepam

Carbamazepine, Oxcarbazepine, Eslicarbazepine, Phenytoin, Fosphenytoin
Divalproex, Topiramate, Zonisamide, Vigabatrin

PAH Ambrisentan, Bosentan, Macitentan, Riociguat

Hormonal Agents Androgens (testosterone), Estrogens (estradiol), Progesterones (medroxyprogesterone)

Oxytocin, Dinoprostone, Ulipristal, SERD/SERMS (Fulvestrant, Tamoxifen)

Negative pressure hazardous

 The HLB Number → Scale range is 0-20 (midpoint is 10)
● Surfactants with low HLB number (< 10) are more lipid-soluble & are used for water-in-oil (w/o)
emulsions
● Surfactants with high HLB number (< 10) are more water-soluble & are used for oil-in-water
(o/w) emulsions

Excipients to be Avoided in Some Patients

Excipient AVOID IN Alternative

Alcohol, used as a solvent Children Select alternative solvent

Aspartame (contains phenylalanine), Phenylketonuria (PKU), not able to Select alternative sweeteners
used as a sweetener metabolize phenylalanine

Gelatin, used to form capsule shells Vegetarians & vegans, anyone who Hypromellose capsule shells are made from
wishes to avoid pork cellulose & are vegan & vegetarian

Gluten, used as a starch (filler) Celiac disease, anyone who wishes Starch can come from non-gluten sources
In wheat, barley & rye to avoid gluten (ex. corn, potato, tapioca)

Lactose, used as a sweetener, to Lactose intolerance or lactose Content may/may not cause symptoms
compress tablets and/or as a filler/diluent allergy (intolerance) as the amount can be small
Select alternative (with allergy) depending
on the purpose

Preservatives (ex. benzyl alcohol) Neonates Use preservative-free formulations

Sorbitol, used as a sweetener IBS – can cause GI distress in IBS Select alternative sweeteners

Sucrose (table sugar), used as a Diabetes

sweetener & coating

Xylitol, used as a sweetener Do not use in dogs – can cause Select alternative sweeteners
xylitol toxicosis (hypoglycemia &
liver damage)
Can cause GI upset in humans

Use of Suppositories
Vaginal Used to treat conditions inside the vagina, such as a Candida infection, or conditions related to the
suppositories female reproductive system such as HRT for menopausal symptoms

Rectal suppositories Used either to treat a local condition, such as hemorrhoids or distal ulcerative colitis, or treat a
systemic condition, such as pain & fever in a patient who cannot take PO meds (ex. APAP suppository)
- These bypass PO route & largely avoid first-pass metabolism

Suppository bases Must be hard enough to be briefly handled, but soft enough to melt easily once inserted
- Storying suppository in the refrigerator can make insertion easier
 Beyond-Use Dates for Non-Sterile Compounded Products
Formulation Beyond-Use Date Storage

Non Aqueous Formulations (ex. drug in petrolatum) Not later than 6 months (180 days) Store at RT

Water-Containing Oral formulations (ex. oral Not later than 14 days when stored at Store in refrigerator
suspension) controlled cold temperatures

Water-Containing Topical/Dermal & Mucosal Liquid & Not later than 30 days Store at RT
Semisolid Formulations (ex. cream or lotion)

Determining CSP Risk Level

Area Requirements Risk Level Characteristics Examples

Inside a Cleanroom

Low • < 3 sterile ingredients (including diluent) Reconstituting a single-dose vial of

• NMT 2 entries → 1 sterile container/ device ABX with sterile water & transferring it
• Limited to transferring, measuring & mixing to a NS IV bag
manipulations

ISO 5 PEC Medium • > 3 sterile ingredients OR Preparing parenteral nutrition

ISO 7 buffer area • Multiple doses of a sterile product
ISO 7 ante area (HD) withdrawn from the same vial to make Using a MDV of ABX & transferring
ISO 8 ante area (non-HD) several CSPs of the same product (a batch) single-doses to several NS IV bags for
• Complex aseptic manipulations multiple patients (batch)

High • Non-sterile ingredients Non-sterile bulk drug powder or

• Non-sterile equipment non-sterile equipment to make a prep
that will be terminally sterilized

Sterile components were held outside

of ISO 5 air for > 1 hour

Outside of a Cleanroom

ISO 5 PEC in an SCA Low-risk • Same characteristics as low-risk Reconstituting a SDV of ABX with
ISO 5 PEC in an C-SCA CSPs with sterile water & transferring to a small
< 12H BUD IV bag in a CAI in an SCA in a satellite
pharmacy (not in a cleanroom)

Clean, uncluttered, Immediate • Only for emergency administration Provide stat IV drug administration in a
functionally separate area Use • Must be for administration within 1 hour medical setting or ambulance

Beyond-Use Dates for Sterile Compounded Products

CSP Risk Level Room Temp BUD Refrigerated BUD Frozen BUD

Low 48 hours 14 days

Medium 30 hours 9 days 45 days

High 24 hours 3 days

Low-risk CSPs prepared in ISO 5 PEC or C-PEC 12 hours 12 hours N/A
in an SCA or C-SCA (not in cleanroom)

Immediate Use 1 hour N/A N/A

Renal & Liver Disease

Renal Disease

Drugs that Cause Kidney Disease

Aminoglycosides Cisplatin Loop diuretics Polymyxins Vancomycin

Amphotericin B Cyclosporine NSAIDs Radiographic Contrast Dye Tacrolimus

CrCl vs. GFR

CrCl • Cockcroft-Gault
140 − (𝑝𝑎𝑡𝑖𝑒𝑛𝑡 𝑎𝑔𝑒)
𝐶𝑟𝐶𝑙 (𝑚𝐿/𝑚𝑖𝑛) = 72 𝑥 𝑆𝐶𝑟
𝑥 𝑤𝑒𝑖𝑔ℎ𝑡 (𝑘𝑔) 𝑥 (0. 85 𝑖𝑓 𝑓𝑒𝑚𝑎𝑙𝑒)
• Use ABW if < IBW // Use IBW if normal weight (by BMI) // Use AdjBW if overweight (by BMI)

GFR • Not commonly calculated by pharmacists, but may be reported with a basic metabolic panel (BMP)
• CKD-EPI & MDRD equations are used
• Used for staging kidney disease & for dosing select drugs (SGLT2Is & metformin)
• For exam, if GFR is not provided, CrCl provides an estimate to determine CIs & dose adjustments

ACE-Inhibitors & ARBs for Albuminuria

Who? Recommended in patients with hypertension & albuminuria

Why? To prevent kidney disease progression

How? Inhibit renin-angiotensin-aldosterone system (RAAS), causing efferent arteriolar dilation

What? Reduce pressure in the glomerulus, decrease albuminuria & provide cardiovascular protection

Drugs that require ⇩ dose or ⇧ interval in CKD

Anti-Infectives • Aminoglycosides (⇧ dosing interval primarily)
• Beta-lactams (except nafcillin, dicloxacillin, oxacillin, ceftriaxone)
• Fluconazole
• Quinolones (except moxifloxacin)
• Vancomycin

Cardiovascular Drugs • LMWHs (enoxaparin) • Rivaroxaban (for AF)

• Dabigatran (for AF) • Apixaban (for AF)

GI Drugs • H2RAs (famotidine, ranitidine) • Metoclopramide

Other • Bisphosphonates • Lithium

 Drugs Contraindicated in CKD
CrCl < 60 mL/min • Nitrofurantoin

CrCl < 50 mL/min • TDF-containing products (Truvada, Complera, Destrigo, Stribild, Symfi/Lo)
• Voriconazole IV (due to the vehicle)

CrCl < 30 mL/min • TAF-containing products (Bikarvy, Descovy, Genvoya, Odefsey, Symtuza)

• Dabigatran (DVT/PE) • NSAIDs

• Rivaroxaban (DVT/PE)

GFR < 30 mL/min/1.73 • Metformin (CI < 30, do not start if < 45)

Other • Meperidine • SGLT2Is

Drugs that RAISE potassium levels

• ACE-Inhibitors/ARBs, Aliskiren • Drospirenone-containing COCs
• Aldosterone receptor antagonists • Potassium Supplements
• Canagliflozin • Potassium-containing IV fluids (including PN)
• SMX/TMP • Transplant drugs (cyclosporine, everolimus, tacrolimus)

Steps for Treating SEVERE Hyperkalemia

Mechanism Intervention Route Onset Notes

Stabilize the heart Calcium gluconate IV 1-2 min Does not ⇩ potassium; stabilizes myocardial cells to prevent
(preferred) arrhythmias
Prevent arrhythmias Calcium chloride

Move it Regular insulin IV 30 min Given with glucose or dextrose to prevent hypoglycemia

Shift K intracellularly Dextrose IV Stimulates insulin secretion, but does not shift K intracellularly
on its own

Sodium bicarbonate IV Used when metabolic acidosis is present

Albuterol Nebulized Monitor for tachycardia & chest pain

Remove it Furosemide IV 5 min • Eliminates K in the urine – monitor volume status

Eliminate K from the Sodium polystyrene PO or 2-24H • Binds K in the GI tract

body sulfonate rectal • Due to AE (GI necrosis), used for emergency only
• PO may take hours-days to work
• Rectal = faster onset – used in acute (emergency) treatment

Patiromer PO ~7H • Binds K in the GI tract

• Delayed onset limits use in life-threatening emergencies

Sodium zirconium PO 1H • Binds K in the GI tract

cyclosilicate • K+ binder with fastest onset; may be preferred for
emergencies

Hemodialysis Immediate • Removes K from the blood

• Takes several hours to set up/complete dialysis
• Other methods generally used in conjunction
 Hepatitis & Liver Disease

Comparison of Hepatitis Viruses

Hepatitis A Hepatitis B Hepatitis C

Acute vs. Chronic Acute Both Both

Transmission Fecal-oral Blood & bodily fluids Blood & bodily fluids

Vaccine Yes Yes No

First line Supportive PEG-INF or NRTIs (tenofovir or entecavir) Treatment naive: DAA combo

Other treatments DAA combo + Ribavirin (RBV)

DAA Mechanisms & Regimens

Mechanism Name Clue Agents

NS3/4A -previr (P for PI) Glecaprevir Voxilaprevir

Protease Inhibitors Grazoprevir

NS5A Replication Complex -asvir (A for NS5A) Elbasvir Pibrentasvir

Inhibitors Ledipasvir Velpatasvir

NS5B Polymerase Inhibitors -buvir (B for NS5B) Sofosbuvir

Lab Tests for Liver Disease

Background Cirrhosis = advanced fibrosis (scarring) of liver – usually irreversible
- Most common causes: Hepatitis C & alcohol

Clinical Presentation Symptoms: yellowed skin, yellowed whites of eyes, N/V/D, loss of appetite, malaise

Acute liver toxicity, including from drugs: ⇧ AST/ALT

Objective Criteria
Chronic liver disease (ex. cirrhosis)
LFTs = AST, ALT, Tbili - ⇧ AST/ALT, ⇧ Alk Phos, ⇧ Tbili, ⇧ LDH, ⇧ PT/INR
& Alk Phos - ⇩ albumin

Alcoholic liver disease

- ⇧ AST > ⇧ ALT
- AST will be DOUBLE the ALT
- ⇧ gamma-glutamyl transpeptidase (GGT)

Hepatic encephalopathy: ⇧ ammonia

Jaundice: ⇧ Tbili

Drug-Induced Liver Injury

APAP (⇧ doses, acute or chronic) Amiodarone Isoniazid Methotrexate Nefazodone

Ketoconazole (oral) Nevirapine NRTIs Propylthiouracil Valproic Acid

 Immunizations & Travelers

Immunizations

Live vaccinations – COZY IV RM

• Cholera • Intranasal influenza • Rotavirus
• Oral typhoid • Varicella • MMR
• Zoster
• Yellow fever

Vaccine Timing & Spacing

General Rules for • Vaccines can usually be given at the same time (same visit/same day)
All Vaccines - Exception: Patients with asplenia: Prevnar & Menactra should be separated by 4 weeks
• Multiple live vaccines can be given on same day or (if not given on same day) spaced 4 weeks apart
- Exception: No separation required for oral rotavirus vaccines
• If a vaccine series requires > 1 dose, the intervals between doses can be extended without restarting
the series, but they should not be shortened in most cases

Live Vaccines & • MMR & Varicella-containing vaccines require separation from antibody-containing products (ex. blood
Antibody transfusions, IVIG), the recommended spacing is:
- Vaccine → 2 weeks → antibody-containing product
- Antibody-containing product → 3 months or longer → Vaccine
• Simultaneous administration of vaccine & antibody (in the form of immunoglobulin) is recommended for
post-exposure PPX of certain diseases (ex. HepA, HepB, rabies, tetanus)

Invalid Contraindications to Vaccination

Vaccinations may be given, if indicated, in the following situations
● Mild acute illness (slight fever, mild diarrhea)
● Current antimicrobial treatment (some exceptions: see varicella, intranasal flu, oral typhoid)
● Previous local skin reaction (mild/moderate) from a vaccine
● Allergies: bird feathers, penicillin, allergies to products not in the vaccine
● Pregnancy (except live vaccines), breastfeeding, preterm birth
● Recent tuberculin skin test
● Immunosuppressed person in the household, recent exposure to the disease or convalescence
● Family history of adverse events to the vaccine

Influenza Vaccine Tips

Recommended Annually • All patients age > 6 months, unless CI
• Any vaccine can be used within the FDA indications

Age 6 mo - 8 YO • Give 2 doses (4 weeks apart)

Patients with egg allergy • Can receive any age-appropriate inactivated flu product, even if severe allergy symptoms
• Egg-free products include Flublok (age > 18 YO) & Flucelvax (grown in a cell culture &
approved for age > 6 months)
• If using a flu vaccine other than Flublok or Flucelvax in a patient with a severe egg allergy,
vaccine should be administered in a medical setting under supervision of a healthcare provider
• Do not administer live flu vaccine (FluMist)

Pregnant patients • Can receive any age-appropriate inactivated flu vaccine

Patients > 65 YO • Fluzone High-Dose & Fluad

 Travelers

Drugs for Travelers’ Diarrhea

Prophylaxis Bismuth subsalicylate 524-1050 mg PO QID (with meals & at bedtime)
- Do not use with ASA allergy, pregnancy, child < 16 YO, gout, anticoagulants
Antibiotics (rifaximin preferred)

Treatment Mild TD: Loperamide or bismuth subsalicylate

Moderate TD: Loperamide + Antibiotics
- Azithromycin or a quinolone (if low resistance)
- Rifaximin as an alternative
Severe TD (including dysentery): Antibiotics + Loperamide
- Azithromycin preferred – 1000 mg x 1 dose
- Quinolones or rifaximin as alternatives (if no dysentery present)

Travel Vaccines
Inactivated vaccines Live Vaccines

Food & water Food & water

• Hepatitis A (Havrix, VAQTA) • Cholera - PO (Vaxchora)
• Hepatitis A/B (Twinrix) • Typhoid-PO (Vivotif)
• Polio (IPOL) Insects
• Typhoid-IM (Typhim Vi) • Yellow Fever-SC (YF-VAX)
Blood & bodily fluids
• Hepatitis B (Engerix-B, Heplisav-B, Recombivax HB)
• Meningococcal (Menactra, Menveo, or MenQuadfi)
• Hepatitis A/B (Twinrix)
Insects
• Japanese Encephalitis (Ixiaro)

Infectious Diseases

Infectious Diseases I: Background & Antibiotics by Drug Class

Gram Stain for Bacterial Organisms

● Gram positive (+): thick cell wall & stain dark purple or bluish from the crystal violet stain
● Gram negative (-): thin cell wall & take up the safranin counterstain → pink or reddish color
Gram positive (+) Gram negative (-)

Cocci → Clusters and Pairs & chains Cocci

• Clusters - Neisseria sp.
- Staphylococcus sp. (MSSA, MRSA)
• Pairs & chains Coccobacilli
- Streptococcus pneumoniae (diplococci) - Acinetobacter baumannii
- Streptococcus sp. (Strep. pyogenes) - Bordetella pertussis
- Enterococcus sp. (VRE) - Moraxella catarrhalis
Rods Rods Rods
- Listeria monocytogenes • Colonize gut “enteric” • Do not colonize gut
- Corynebacterium sp. - Proteus mirabilis - Pseudomonas aeruginosa
- E. coli - Haemophilus influenzae
- Klebsiella sp. - Providencia sp.
- Serratia sp.
- Enterobacter cloacae
- Citrobacter sp.

Anaerobes Anaerobes Curved or spiral shaped rods

- Peptostreptococcus - Bacteroides fragilis - H. Pylori, Campylobacter sp.,
- Propionibacterium acnes - Prevotella sp. Treponema sp.,
- Clostridioides difficile, Clostridium sp. - Borrelia sp., Leptospira sp.

Atypicals

- Chlamydophila sp. - Mycoplasma pneumoniae - Legionella sp. - Mycobacterium tuberculosis

Culture & Susceptibility

1. Identify the organism Collect specimen, gram-stain, culture

2. Determine MIC Susceptibility testing – lowest concentration with no growth is MIC

3. Interpretation Susceptible (S), intermediate (I) or resistant (R) to the antibiotic

Key Features of Beta-Lactams

Penicillins

Class Effects • All should be avoided in patients with a beta-lactam allergy

- Exception: treatment of syphilis during pregnancy or in patients with poor
compliance/follow-up – desensitize & treat with Penicillin G Benzathine
• All PCNs increase risk of seizures if accumulation occurs (ex. failure to dose adjust renally)

Penicillin VK
• First line for pharyngitis (strep throat) & mild nonpurulent skin infections

Amoxicillin
• First line for acute otitis media (peds dose: 80-90 mg/kg/day)
• DOC: infective endocarditis PPX before dental procedures (2 grams PO x 1, 30-60 min before)
• Used in H. Pylori treatment
Outpatient (PO)
Amoxicillin/Clavulanate
• First line for acute otitis media (peds dose: 90 mg/kg/day)
• First line for bacterial sinusitis (if ABX indicated)
• Use lowest dose of clavulanate to ⇩ diarrhea

Dicloxacillin
• Covers MSSA only
• No renal dose adjustment needed

Penicillin G Benzathine
 • DOC for syphilis (2.4 million units IM x 1)
• Not for IV use – can cause death
Inpatient
(Parenteral) Nafcillin & Oxacillin
• Covers MSSA only
• No renal dose adjustment needed

Piperacillin/Tazobactam
• Only PCN active against Pseudomonas
• Extended infusions (4 hours) can be used to maximize T > MIC

Cephalosporins

Class Effects • All should be avoided in patients with a beta-lactam allergy (even PCN allergy)
- Exception: pediatric patients with acute otitis media & mild PCN allergy
• Risk of seizures if accumulation occurs (ex. failure to dose adjust renally)

Cephalexin (Keflex) (1st gen)

• Common uses: skin infections (MSSA), pharyngitis (strep throat)
Outpatient (PO)
Cefuroxime (2nd gen)
• Common uses: acute otitis media, community acquired pneumonia (CAP)

Cefdinir (3rd gen)

• Common uses: acute otitis media

Cefazolin (1st gen)

• Common uses: surgical prophylaxis

Cefotetan, Cefoxitin (2nd gen)

Inpatient • Anaerobic coverage (B. fragilis)
(Parenteral) • Common uses: surgical prophylaxis (GI procedures)
• Cefotetan can cause disulfiram-like reaction with alcohol ingestion

Ceftriaxone, Cefotaxime (3rd gen)

• Common uses: CAP, meningitis, spontaneous bacterial peritonitis, pyelonephritis
• Ceftriaxone: no renal dose adjustment; do not use in neonates (age 0-28 days)

Ceftazidime (3rd gen) // Cefepime (4th gen)

• Active against Pseudomonas

Ceftolozane/tazobactam, Ceftazidime /avibactam

• Used for MDR Gram negative organisms (including Pseudomonas)

Ceftaroline (5th gen)

• Only β- lactam active against MRSA
• Common uses: CAP, SSTIs

Carbapenems

Class Effects • All active against ESBL-producing organisms & Pseudomonas (except ertapenem)
• All should be avoided in patients with a beta-lactam allergy (even PCN allergy)
• Seizure risk (with higher doses, failure to dose adjust renally, or use of imipenem/cilastatin)
 Do NOT Cover • Atypicals, MRSA, VRE, C. difficile, Stenotrophomonas
• ErtAPenem does not cover PEA: Pseudomonas, Enterococcus, or Acinetobacter

Common Uses • Polymicrobial infections (ex. severe diabetic foot infections)

• Empiric therapy when resistant organisms are suspected
• ESBL-positive infections
• Resistant Pseudomonas or Acinetobacter (except Ertapenem)
• ALL are IV only – Ertapenem must be diluted in normal saline (NS)

Key Features of Other Antibiotics

Aminoglycosides

Class Effects • Kill Gram - pathogens & are synergistic with 𝜷-lactams for some Gram +
- Generally have low resistance & drug cost
• Concentration-dependent activity – have post-antibiotic effect
- Bacterial killing continues after serum level drops below MIC

Risks • Notable toxicities that require monitoring: nephrotoxicity, ototoxicity

- Hearing loss, tinnitus, balance problems – may be irreversible

Concentration-dependent killing → give larger doses less frequently (extended interval dosing)
- Gives kidneys time to recover between doses

Dosing Strategy • If underweight: use ABW for dosing // If obese: use AdjBW for dosing
• Traditional Dosing: Gentamicin/Tobramycin: 1-2.5 mg/kg/dose Q8H (CrCl > 60: Q8H)
• Extended Interval Dosing: Gentamicin/Tobramycin: 4-7 mg/kg/dose

Drug Peak Trough

Gentamicin (G + synergy) 3-4 mcg/mL < 1 mcg/mL

Gentamicin, Tobramycin 5-10 mcg/mL < 2 mcg/mL

Amikacin 20-30 mcg/mL < 5 mcg/mL

Quinolones

Common Uses • Varies by agent – pneumonia, UTIs, intra-abdominal infections, travelers’ diarrhea

Respiratory • Levofloxacin, Moxifloxacin

Quinolones • Reliable Strep. Pneumo activity (in pneumonia)

Antipseudomonal • Ciprofloxacin, Levofloxacin

Quinolones • Used for Pseudomonas infections (including pneumonia)

Moxifloxacin • ONLY one that is not renally adjusted (do not use for UTIs)

IV to PO ratio • 1:1 → Levofloxacin & Moxifloxacin

Profile Review Tip • Caution with CVD, ⇩ K/Mg & with other QT prolonging drugs
- Azole antifungals, antipsychotics, methadone, macrolides
• Avoid in patients with seizure history or if using seizure drugs
• Avoid in children, pregnancy/breastfeeding
 Counseling • Causes: Photosensitivity, hypo or hyperglycemia, CNS effects (seizures), QT prolongation
• Avoid sun exposure, separate from polyvalent cations, monitor BG
• Watch for tendon rupture, neuropathy, CNS or psychiatric side effects

Macrolides

Common Uses • All macrolides: CAP, an alternative to beta-lactams for pharyngitis

• Azithromycin: COPD exacerbations, pertussis, chlamydia (pregnant patients), prophylaxis for MAC –
mycobacterium avium complex, severe travelers’ diarrhea (including dysentery, diarrhea w/ blood)
• Clarithromycin: H. Pylori treatment regimens
• Erythromycin: ⇧ gastric motility → used for gastroparesis

Common Z-Pak dose • Two 250 mg tablets PO x 1, then 250 mg PO daily x 4 days

QT Prolongation • Caution with CVD, ⇩ K/Mg & with other QT prolonging drugs
- Azole antifungals, antipsychotics, methadone, quinolones

Drug Interactions • Clarithromycin, Erythromycin: strong CYP3A4 inhibitor

- Simvastatin & Lovastatin = contraindicated (⇧ risk of muscle toxicity)

Counseling • Causes: QT prolongation, GI upset (take with food)

Tetracyclines

Common Uses • Doxycycline, Minocycline: CA-MRSA skin infections, acne

• Doxycycline:
- First line for tick borne illness (Lyme disease, Rocky Mountain Spotted Fever) & chlamydia
- Option for: CAP, COPD exacerbations, bacterial sinusitis, VRE UTI
• Tetracycline: H. Pylori treatment regimens

Risks • Do NOT use in children < 8 YO, pregnancy/breastfeeding

• Causes: Photosensitivity, drug interactions due to binding
• Doxycycline: take with full glass of water & remain upright for 30 min after to avoid GI irritation
• Minocycline: drug-induced lupus erythematosus (DILE)

Sulfonamides

Common Uses • CA-MRSA skin infections, UTI, Pneumocystis Pneumonia (PCP)

Ratio • 5:1 ratio of SMX/TMP → Dose based on TMP

• SS tablet: 80 mg TMP
• DS tablet: 160 mg TMP – usual dose = 1 tablet BID

Sulfa allergy • Most sulfa allergies occur with SMX/TMP (rash/hives common)
• Rarely, severe skin reactions (SJS/TEN) can occur
- If rash is accompanied by fever or systemic symptoms, seek emergency care

Risks • ⇧ INR with warfarin → use alternative ABX when possible

• Strong CYP2C9 inhibitor (warfarin = substrate)
• Avoid in sulfa allergy, pregnancy/breastfeeding
• Causes: Photosensitivity, crystals in urine (take with full glass of water), risk of hyperkalemia

Nitrofurantoin

DOC • Uncomplicated UTI

 Do not use • CI when CrCl < 60

Dosing • MacroBID = BID; Macrodantin = QID

Counseling • Take with food to prevent nausea, cramping; can discolor urine

Commonly Used Drugs for Specific Pathogens

MRSA • Vancomycin (use alt. if MIC > 2) • SMX/TMP (CA-MRSA SSTIs)
Methicillin-resistant staph aureus • Daptomycin (not in pneumonia) • Doxycycline, Minocycline (CA-MRSA SSTIs)
• Linezolid, Ceftaroline • Clindamycin (CA-MRSA SSTIs)

MSSA • Dicloxacillin, Nafcillin, Oxacillin

Methicillin-susceptible staph aureus • Amoxicillin/Clavulanate, Ampicillin/Sulbactam
• Cefazolin, Cephalexin (other 1st & 2nd gen)

Pseudomonas • Piperacillin/Tazobactam • Carbapenems (except ertapenem)

• Ceftazidime (3rd) • Aztreonam
• Cefepime (4th) • Ciprofloxacin, Levofloxacin
• Ceftolozane/Tazobactam • Tobramycin
• Ceftazidime/Avibactam • Colistin, Polymyxin B

VRE • Penicillin G, Ampicillin (E. faecalis only) Cystitis only ↓

Vancomycin-resistant Enterococcus • Linezolid, Daptomycin Doxycycline, Nitrofurantoin, Fosfomycin

HNPEK • Beta-lactam/beta-lactam inhibitors • Carbapenems

(Haemophilus, Neisseria, Proteus, E. coli, • Cephalosporins (except 1st gen) • Aminoglycosides, Quinolones, SMX/TMP
Klebsiella)

CAPES • Piperacillin/Tazobactam • Aminoglycosides

(Citrobacter, Acinetobacter, Providencia, • Cefepime (4th) • Colistin, Polymyxin B
Enterobacter, Serratia) • Carbapenems

Atypicals • Azithromycin, Clarithromycin • Doxycycline, Minocycline

(Legionella, Chlamydia, Mycoplasma, • Quinolones
Mycobacterium avium)

G- anaerobes • Beta-lactam/beta-lactam inhibitors • Moxifloxacin (reduced activity)

(B. fragilis) • Cefotetan, Cefoxitin • Metronidazole
• Carbapenems

CRE • Ceftazidime/Avibactam • Meropenem/Vaborbactam

Carbapenem-resistant G- rods • Colistin, Polymyxin B • Imipenem/Cilastatin/Relebactam

ESBL • Carbapenems
Extended-spectrum 𝛽-lactam • Ceftolozane/Tazobactam
producing G- rods • Ceftazidime/Avibactam
(E.coli, Klebsiella, Proteus mirabilis)

C. difficile • Vancomycin (oral), Fidaxomicin, Metronidazole

 No renal dose adjustments
Dicloxacillin, Nafcillin, Oxacillin Ceftriaxone Doxycycline Moxifloxacin

Azithromycin, Erythromycin Clindamycin Metronidazole Linezolid

Infectious Diseases II: Bacterial Infections

Perioperative Antibiotic PPX

● Pre-Operative (Prior to surgery)
○ Infuse ABX (cefazolin, cefuroxime) within 60 min before 1st incision
○ If quinolone or vancomycin used, start infusion 120 min before 1st incision
● Intra-operative (During surgery):
○ Can give another dose for longer surgeries (> 4H) or if there is major blood loss
● Post-Operative (After surgery): ABX usually not needed; if used, DC within 24H
Surgical Procedure Recommended ABX Beta-lactam allergy

Cardiac or vascular Cefazolin or cefuroxime

Clindamycin or
Orthopedic Cefazolin Vancomycin
(ex. joint replacement, hip fracture)

GI Cefazolin + metronidazole or Clindamycin or Metronidazole +

(ex. appendectomy, colorectal surgery) Cefotetan or AMGs or Quinolone
Cefoxitin or
Ampicillin/Sulbactam

Meningitis: Empiric therapy

Cover the most common bacteria
- Streptococcus pneumoniae & Neisseria meningitidis for most adult patients
- Add coverage for Listeria monocytogenes in neonates, age > 50 YO & immunocompromised
- Add Vancomycin in patients > 1 month old for double coverage of streptococcus pneumoniae
Age < 1 month (neonates) Age 1 month to 50 years Age > 50 YO or immunocompromised

Ampicillin (for Listeria coverage) Ceftriaxone or Cefotaxime Ampicillin (for Listeria coverage)
+ Cefotaxime (no ceftriaxone) + Vancomycin + Ceftriaxone or Cefotaxime
or + Vancomycin
Gentamicin
Do not use ceftriaxone in neonates due to ability to cause biliary sludging

Acute Otitis Media (AOM)

Observation for 48-72 hours for patients > 6 months with non-severe AOM
- Non-severe: otalgia < 48H, no otorrhea, temperature < 102.2℉ (39℃) and:
- Age 6-23 months: symptoms in one ear only
- Age > 2 years: symptoms in one or both ears
- If symptoms do not improve, or worsen, use ABX

Outpatient CAP Assessment & Treatment

Step 1: Comorbidities (chronic heart, lung, liver, renal disease; DM, alcoholism, malignancy, asplenia)
Step 2: Decide if the patient falls into the category of “Healthy” or “High-Risk”
Step 3: Choose regimen – look for allergies, drug-disease interactions, DDIs & culture results
 Patient Characteristics Recommended Empiric Therapy

Healthy • Amoxicillin high dose: 1 gram TID OR

No comorbidities • Doxycycline OR

• Azithromycin, Clarithromycin (if local pneumococcal resistance is < 25%)

High-Risk • Amoxicillin/clavulanate, Cefpodoxime or Cefuroxime PLUS

• Azithromycin, Clarithromycin or Doxycycline OR
With comorbidities
• Moxifloxacin, Levofloxacin (monotherapy)
Usual duration of treatment: 5-7 days

HAP/VAP Treatment
Empiric therapy • Piperacillin/tazobactam OR • Meropenem OR
• Cefepime OR • Aztreonam OR
Pseudomonas + MSSA • Levofloxacin OR • Imipenem/cilastatin

MRSA risk ADD Vancomycin or Linezolid

Pseudomonas risk / Double coverage for pseudomonas with 2 of the following: PLUS Vancomycin or Linezolid
MDR risk (1): Piperacillin/Tazobactam, Cefepime, Ceftazidime, Aztreonam, Imipenem/cilastatin, Meropenem
(2): Levofloxacin, Ciprofloxacin, Tobramycin, Amikacin, Gentamicin

MRSA risk factors MDR G - pathogens + MRSA risk factors

• IV ABX use within 90 days • IV ABX use within 90 days

• MRSA prevalence in hospital unit > 20% or unknown • Prevalence of G - resistance in hospital unit > 10%
• Prior MRSA infection or positive MRSA nasal swab • Hospitalized > 5 days prior to onset of VAP

Key Points for RIPE therapy for TB

Monitor Infection • Sputum sample (for culture), symptoms & chest X-ray (are lungs clearing up?)

ALL RIPE Drugs • ⇧ LFTs, including total bilirubin – monitor baseline & monthly

Rifampin • Orange bodily secretions

• Strong CYP450 inducer (can rifabutin use if unacceptable DDIs)
• Flu-like symptoms
• Risk for Hemolytic anemia (+ Coombs test)

Isoniazid (INH) • Peripheral neuropathy: give with pyridoxine 25-50 mg PO QD

• Monitor for symptoms of DILE
• Risk for Hemolytic anemia (+ Coombs test)

Rifampin & Isoniazid • ⇧ uric acid – do not use with acute gout

Pyrazinamide • Visual damages (requires baseline & monthly vision exams)

• Confusion, hallucinations

Ethambutol • Sputum sample (for culture), symptoms & chest X-ray (are lungs clearing up?)
 C. Difficile Diarrhea Recommendations:
• When infection is suspected, DC unnecessary ABX & other possible causative agents if possible
• Isolate patients – single room with dedicated bathroom; use contact precautions
• Diagnosis: + C. difficile stool toxin (enzyme immunoassay + glutamate dehydrogenase test) or PCR
• Adjunct bezlotoxumab: considered in high risk (⇩ recurrence, but does not treat active infection)
- Age > 65 YO
- Immunocompromised status
- Severe presentation and/or experiencing 2nd episode of CDI within past 6 months
Treatment - 10 days
Initial, non-severe/severe Fidaxomicin 200 mg PO BID x10D (pref) Vancomycin 125 mg PO QID x10D

Non-severe: WBC < 15,000 & SCr < 1.5 Metronidazole 500 mg PO TID x10D (non-severe only & if other options not available)

First recurrence Fidaxomicin 200 mg PO BID x10D Vancomycin 125 mg PO QID x10D
followed by tapered & pulsed regimen

Second/subsequent recurrence Vancomycin in tapered & pulsed regimen Fidaxomicin 200 mg PO BID x10D

Vancomycin 125 mg PO QID x10D followed Fecal microbiota transplantation

by Rifaximin 400 mg PO TID x20D

Fulminant/Complicated Disease Vancomycin 500 mg PO/NG/PR QID PLUS Metronidazole 500 mg IV Q8H
Hypotension, shock, ileus, toxic megacolon

Sexually-Transmitted Infections
STI Organism Symptoms

Chlamydia Chlamydia trachomatis, intracellular obligate Discharge or asymptomatic

gram -

Gonorrhea Neisseria gonorrhoeae, a gram - diplococci Discharge or asymptomatic

Genital Warts HPV strains 6 & 11 Single or multiple pink/skin-toned lesions

Latent Syphilis Treponema pallidum, a spirochete Asymptomatic

Primary Syphilis Painless, smooth genital sores (chancre)

Trichomoniasis Trichomonas vaginalis, a flagellated Yellow/green, frothy vaginal discharge with pH

protozoan > 4.5; soreness, pain with intercourse

Bacterial Vaginosis Gardnerella vaginalis Clear, white/gray vaginal discharge with fishy
odor with pH > 4.5; little or no pain

Syphilis: PCN Desensitization

Syphilis must be treated with PCN in select patients with an allergy because doxycycline, is not suitable
● A pregnant patient cannot take doxycycline due to the adverse effects on the fetus
● Poor compliance/follow-up at risk for treatment failure with a BID regimen that’s taken for 14-28D
Per CDC, follow these steps:
1. Confirm allergic reaction with a skin test
2. Temporarily desensitize the patient with an approved desensitization protocol
3. Treat with IM Penicillin G benzathine (Bicillin L-A)
 Lyme Disease vs. Ringworm
Lyme Disease Ringworm

• Bacterial (spirochete) infection – spread by ticks • Fungal infection

- Borrelia burgdorferi, Borrelia mayonii - Tinea corporis

Erythema migrans: • 1+ reddish, raised rings

• “Bull’s-eye” rash – round, red, central clearing as it expands, achy joints, fever • Can be itchy
• Diagnosis: enzyme immunoassay (EIA) identifies antibodies • Treatment: clotrimazole or another antifungal
• Treatment: Doxycycline 100 mg PO/IV BID

Infectious Diseases III: Antifungals & Antivirals

Key issues with Azole Antifungals

Class Effects • ⇧ LFTs
• Hypokalemia
• QT prolongation (except Isavuconazonium – causes QT shortening)
• Many drug interactions

Drug-Specific Concerns • Fluconazole: only azole that requires renal dose adjustment
• Ketoconazole: hepatotoxicity has led to liver transplantation
• Itraconazole: can cause HF
• Voriconazole: can cause visual changes & phototoxicity
• Posaconazole:
- Tablet dose DOES NOT EQUAL suspension dose (different bioavailability)
- Take with food

IV Administration • IV to PO ratio = 1:1

• Drugs with SBECD vehicle: voriconazole & posaconazole

Human Immunodeficiency Virus

Preferred initial ART regimens in treatment-naive adults

Brand Generic Components Pearls

One Pill, Once Daily (Single Tablet Regimens) Most preferred regimens contain 2 NRTIs & 1 INSTI
• Emtricitabine/TDF (Descovy) or Emtricitabine/TAF (Truvada) make
Biktarvy Tenofovir AF/Emtricitabine/ up the NRTI backbone in most regimens
NRTI: TAF, E, INSTI: B Bictegravir • Lamivudine & Emtricitabine are interchangeable but should not be
used together (both are cytosine analogs & are antagonistic)
Triumeq Dolutegravir/Lamivudine/ Dovato (1 NRTI & 1 INSTI) is an exception to the above
NRTI: L, A, INSTI: D Abacavir • Do not use in treatment naive patients if HIV RNA > 500,000
copies/mL, there is known HepB co-infection (or status unknown) or
Dovato Dolutegravir/Lamivudine HIV genotypic testing is not available
NRTI: L, INSTI: D Triumeq contains abacavir – extra testing required
• Test for HLA-B*5701 allele before using – positive result indicates
Two Pills, Once Daily (for most) higher risk for severe hypersensitivity reaction & any
abacavir-containing product is contraindicated
Tivicay + Truvada Dolutegravir/Emtricitabine/ Fixed-dose combos have less flexibility with renal dosing
NRTI: TDF, E, INSTI: D Tenofovir DF • Bikarvy, Triumeq, Dovato, Truvada, Descovy
- Do not use if CrCl < 30 mL/min
 Tivicay + Descovy Dolutegravir/Emtricitabine/ - Bikarvy – individual components of these drugs can be given
NRTI: TAF, E, INSTI: D Tenofovir AF separately to allow for more flexible renal-dose adjustments

Key Features of Drugs used in ART

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)

All NRTIs • Warnings: lactic acidosis & hepatomegaly with steatosis (fatty liver)
- Boxed Warning for zidovudine
• Common side effects: nausea, diarrhea, headache, ⇧ LFTs

HBV & HIV Coinfection • Severe HBV exacerbation can occur if emtricitabine, lamivudine & tenofovir products are DC’d
Boxed Warnings • Do not use Epivir-HBV for HIV (contains a ⇩ dose of lamivudine)

Abacavir • Boxed Warning: risk for hypersensitivity reaction (HSR)

- Screen for HLA-B*5701 allele before starting
- Contraindicated if positive (higher risk of HSR)
- Epzicom (Abacavir/Lamivudine)
- Triumeq (Dolutegravir/Lamivudine/Abacavir)
- Ziagen (Abacavir)
- Patients must carry a medication card indicating that HSR (ex. fever, rash, N/V/D, fatigue,
dyspnea, cough) is an emergency
- Never re-challenge patients with a history of HSR
• Consider avoiding with CVD due to potential ⇧ risk of MI

Emtricitabine • Hyperpigmentation of the palms of the hands or soles of the feet

Tenofovir formulations • Renal impairment: acute renal failure & Fanconi syndrome (renal tubular injury & abnormal electrolyte)
(⇧ risk with TDF) • ⇩ dose with renal impairment & avoid other nephrotoxic drugs (ex. NSAIDs)
• ⇩ bone mineral density: consider calcium/vitamin D supplementation & DEXA scan if at risk
• Monitor lipids if switching from TDF to TAF for an improved side effect profile
- TAF has a higher risk of lipid abnormalities
• TDF: do not start if CrCl < 50
- Cimduo (TDF/Lamivudine)
- Destrigo (TDF/Lamivudine/Doravirine)
- Symfi, Symfi Lo (TDF/Lamivudine/Efavirenz)
- Truvada (TDF/Emtricitabine)
- Atripla (TDF/Emtricitabine/Efavirenz)
- Complera (TDF/Emtricitabine/Rilpivirine)
- Stribild (TDF/Emtricitabine/Elvitegravir/Cobicistat)
• TAF: do not start if CrCl < 30
- Biktarvy (TAF/Emtricitabine/Bictegravir)
- Descovy (TAF/Emtricitabine)
- Odefsey (TAF/Emtricitabine/Rilpivirine)
- Genvoya (TAF/Emtricitabine/Elvitegravir/Cobicistat)
- Symtuza (TAF/Emtricitabine/Darunavir/Cobicistat)

Zidovudine (Retrovir) • Hematologic toxicity: neutropenia & anemia (⇧ MCV is a sign of adherence)
• Myopathy

Didanosine & Stavudine • Pancreatitis, peripheral neuropathy (can be irreversible)

Integrase Strand Transfer Inhibitors (INSTIs)

Side effects & • All INSTIs: HA, insomnia, diarrhea, weight gain, rare risk of depression & suicidal ideation in pateints with
 Warnings pre-existing psychiatric conditions
• Bictegravir, Dolutegravir: ⇧ SCr (by inhibiting tubular secretion) with no effect on GFR
• Raltegravir, Dolutegravir
- ⇧ CPK, myopathy & rhabdomyolysis
- Hypersensitivity reaction: syndrome of rash, fever & symptoms of allergic reaction
• Dolutegravir:
- Preferred drug treatment of HIV during pregnancy
- Hepatotoxicity (especially if coinfection with hepatitis B or C)
• Cabotegravir IM: injection site reactions

Drug Interactions with • Take INSTIs 2 hours before or 6 hours after: Al, Ca, Mg, iron-containing products
Polyvalent Cations • Exceptions:
- Dolutegravir & Bictegravir can be taken with oral calcium or iron if also taken with food
- Dose separation with raltegravir may not be effective – avoid polyvalent cations if possible

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

All NNRTIs • Hepatotoxicity & rash, including SJS/TEN: highest risk with nevirapine

Efavirenz • Psychiatric symptoms (depression, suicidal thoughts)

• CNS effects (impaired concentration, abnormal dreams, confusion) – generally resolve in 2-4 weeks
• ⇧ total cholesterol & triglycerides

Rilpivirine • Depression
• ⇧ SCr with no effect on GFR
• Do not use if viral load > 100,000 copies/mL and/or CD4 count < 200 (higher failure rate)

Drug Interactions • Major CYP3A4 substrates

- Rilpivirine & doravirine: do not use with strong CYP3A4 inducers
- Phenytoin, Rifampin, Rifapentine, Carbamazepine, Oxcarbazepine, Phenobarbital, SJW
• Efavirenz & etravirine: moderate CYP3A4 inhibitors
• Rilpivirine & acid suppressants
- Do not use with PPIs
- Separate H2RAs – take H2RAs at least 12 hours before or 4 hours after
- Separate antacids – take antacids at least 2 hours before or 4 hours after

Protease Inhibitors (PIs)

All PIs • Metabolic Syndrome: hyperglycemia/insulin resistance, dyslipidemia (⇧ LDL, ⇧ TGs), ⇧ body fat
- ⇧ CVD risk (lower risk with atazanavir & darunavir)
• Hepatic dysfunction: ⇧ LFTs, hepatitis and/or exacerbation of preexisting hepatic disease
• Hypersensitivity reactions: rash (including SJS/TEN), angioedema, bronchospasm, anaphylaxis
• Common side effects: diarrhea, nausea

Atazanavir • Hyperbilirubinemia – “Bananavir” (jaundice or scleral icterus): reversible, does not required DC
• Requires acidic gut for absorption
- Antacids: take 2 hours before or 1 hour after
- H2RAs: avoid or take 2 hours before or 10 hours after
- PPIs: avoid with unboosted; take boosted at least 12 hours after
- Dose should not exceed omeprazole 20 mg or equivalent

Darunavir, Fosprenavir, • Caution with sulfa allergy

Tipranavir

Lopinavir/Ritonavir • PO solution contains 42% alcohol: can cause disulfiram reaction with metronidazole
 Tipranavir • Intracranial hemorrhage

CYP3A4 Drug All PIs are major CYP3A4 substrates – most are strong CYP3A4 inhibitors
Interactions Do not use with PIs:
• Alfuzosin
• Colchicine
• Dronedarone
• Lovastatin & Simvastatin
• CYP3A4 Inducers
- Phenytoin, Rifampin, Rifapentine, Carbamazepine, Oxcarbazepine, Phenobarbital, SJW
• Anticoagulants/antiplatelets: Apixaban, Rivaroxaban, Edoxaban, Ticagrelor
- Warfarin is not CI but monitor INR closely
• Direct-acting antivirals (DAAs) for hepatitis C
- NS3/4A Protease Inhibitors: Glecaprevir, Grazoprevir, Voxilaprevir
- NS5A Replication Complex Inhibitors: Elbasvir, Ledipasvir, Pibrentasvir, Velpatasvir,
- NS5B Polymerase Inhibitors: Sofosbuvir
• Some hormonal contraceptives
• Steroids (systemic, intranasal, inhaled – increased risk of Cushing’s syndrome)

Pharmacokinetic Boosters (Enhancers)

All PK Boosters • CYP3A4 inhibitors – inhibit ART metabolism, which ⇧ (boosts) ART level & therapeutic effects
• Ritonavir & Cobicistat are not interchangeable – do not use both together

Ritonavir • Is a PI but is used as a booster because it is a strong inhibitor & not very well tolerated at higher doses
needed for antiretroviral activity → booster dosing is lower than treatment dosing
• PO solution contains 43% alcohol: can cause disulfiram reaction with metronidazole

Cobicistat • ⇧ SCr with no effect on GFR

Drug Interactions Strong CYP3A4 inhibitors, also inhibit CYP2D6, P-gp and OAT transporters
Do not use with PK Boosters:
• Alfuzosin, Tamsulosin
• Colchicine (with hepatic or renal impairment)
• Lovastatin & Simvastatin
• Tyrosine kinase inhibitors (TKIs) (“nibs”)
• CYP3A4 Inducers
- Phenytoin, Rifampin, Rifapentine, Carbamazepine, Oxcarbazepine, Phenobarbital, SJW
• Azole antifungals (especially isavuconazonium, itraconazole, voriconazole)
• CV drugs: Amiodarone (ritonavir only), Dronedarone, Eplerenone, Ivabradine, Ranolazine
• PDE-5 Inhibitors used for pulmonary HTN (Tadalafil, Sildenafil)
• Any narrow therapeutic index drug that is highly dependent on CYP3A4 for clearance

Comparison of PrEP vs. PEP

PrEP PEP

BEFORE high risk activity AFTER exposure, start within 72H & continued for 28 days

PO drug taken daily: Truvada or Descovy or More drugs needed! Actual possible exposure!
IM drug taken monthly x2 dose then Q2 mo: Cabotegravir Truvada PLUS
Dolutegravir (Tivicay) or Raltegravir (Isentress)

Note* Descovy is not indicated for females

 Cardiovascular Conditions

Dyslipidemia

Drugs that can raise LDL and/or TGs

⇧ LDL & TGs ⇧ LDL only ⇧ TGs only Conditions

• Diuretics • Fibrates • IV lipid emulsions • Obesity, poor diet

• Efavirenz • Fish oils (except Vascepa) • Propofol • Alcohol use disorder
• Immunosuppressants • SGLT2s • Clevidipine • Hypothyroidism; DM
(cyclosporine, tacrolimus) • Bile acid sequestrants • Smoking
• Atypical antipsychotic • Alcohol • Renal/liver disease
• Protease Inhibitors • Nephrotic syndrome

Statin Intensity selection

Statin Benefit Group Patient Criteria Statin Treatment

Secondary Prevention

Clinical ASCVD CHD, stroke/TIA, PAD High intensity statin

Primary Prevention

Severe dyslipidemia Baseline LDL > 190 mg/dL High intensity statin

Age 40-75 with diabetes Multiple ASCVD risk factors High intensity statin
PLUS LDL 70-189
Regardless of ASCVD risk Moderate intensity statin

Age 40-75 without diabetes 10-year ASCVD risk > 20% High intensity statin
PLUS LDL 70-189
10-year ASCVD risk 7.5-19.9% + risk enhancing factors Moderate intensity statin

Statin Equivalent Doses

Pitavastatin 2mg Atorvastatin 10mg Lovastatin 40mg Fluvastatin 80mg

Rosuvastatin 5mg Simvastatin 20mg Pravastatin 40mg Pharmacists Rock At Saving Lives and Preventing Fatty deposits

Managing Myalgias
Muscle Damage presents as muscle soreness, tiredness or weakness that is symmetrical
- Usually occurs within 6 weeks of starting treatment (can develop at any time)
• Myalgias: muscle soreness & tenderness
• Myopathy: muscle weakness + CPK elevations
• Myositis: muscle inflammation
• Rhabdomyolysis: muscle symptoms with a very high CPK (> 10,000 IU/L) + muscle protein in the urine
→ can lead to acute renal failure
Reduce the risk • Avoid drug interactions, including OTCs
• Do not use simvastatin 80 mg/day
• Do not use gemfibrozil + statin
 If myalgias occur • Hold statin, check CPK, investigate other causes
• After 2-4 weeks, rechallenge with same statin at same or ⇩ dose
- Most patients who did not tolerate a statin will tolerate it when rechallenged or
will tolerate a different statin
• If myalgias return, DC statin
- Once symptoms resolve, use low dose of different statin (gradually ⇧ dose)

Hypertension

Screening & Diagnosis of HTN

BP assessments should be based on an average of at least 2 readings on 2 separate occasions
DO DON’T

• Go to the bathroom & empty bladder • Talk

• Sit in chair (both feet on floor) & relax for at least 5 minutes • Sit or lie down on an examination table
• Use correct cuff size • Drink caffeine, exercise or smoke 30 minutes prior
• Support arm at heart level (resting on desk) • Use a finger or wrist monitor (less accurate)
• Wait 1-2 minutes in between measurements

Self-monitoring (bring device & BP log to clinic visits)

- Ambulatory BP monitoring device: wear during daily activities; obtains readings Q15-60 min day & night
- Home BP monitoring device: records the average of 2-3 readings in the morning and/or evening before
eating or taking any medications

Drugs that increase BP

Stimulants Agents that ⇧ Na & water retention Other

• Amphetamines & ADHD drugs • NSAIDs • Erythropoiesis-stimulating agents

• Caffeine, cocaine • Immunosuppressants (cyclosporine) • Oral contraceptives
• Decongestants (phenylephrine) • Systemic steroids - High estrogen doses
• Antidepressants • Oncology agents
- MAOIs, SNRIs, TCAs - Bevacizumab, Sunitinib

Treatment Principles of HTN

When to start • Stage 2 HTN (SBP > 140 or DBP > 90)
treatment • Stage 1 HTN (SBP 130-139 or DBP 80-89) + any of the following:
- Clinical CVD (stroke, HF, or coronary heart disease)
- 10-year ASCVD risk > 10%
- Does not meet BP goal after 6 months of modifications

BP goal < 130/80 mmHg

Initial drug • Non-black: Thiazide, DHP CCB, ACE-I, ARB

selection • Black: Thiazide, DHP CCB
• CKD Stage 3 and/or albuminuria: ACE-I, ARB
• Start 2 first-line drugs when baseline SBP & DBP > 20/10 mmHg above goal (ex. > 150/90)

Monitoring Check BP every month & titrate medication if not at goal

 Key IV HTN Medications
Nicardipine Diltiazem Esmolol Metoprolol tartrate Chlorothiazide Enalaprilat

Clevidipine Verapamil Propranolol Labetalol Hydralazine Nitroglycerin, Nitroprusside

Stable Ischemic Heart Disease

Treatment Approach for Stable Ischemic Heart Disease – A, B, C, D, E

A: Antiplatelet & antianginal drugs B: BP & beta-blockers C: Cholesterol & cigarettes (cessation)

D: Diet & diabetes E: Exercise & education

Acute Coronary Syndromes

Comparing UA, NSTEMI, STEMI

UA NSTEMI STEMI

Cardiac enzymes Negative Positive Positive

ECG changes None or transient ischemic changes ST segment elevation

(ST segment depression or prominent T-wave inversion) (> 2 contiguous leads)

Blockage Partial blockage Complete blockage

Drug Treatment options for ACC – MONA-GAP-BA

MONA GAP BA

• Morphine • GPIIb/IIIa antagonists • Beta Blockers

• Oxygen • Anticoagulants • ACE-inhibitors
• Nitrates • P2Y12 inhibitors
• Aspirin (ASA)
- NSTE-ACS: MONA-GAP-BA +/- PCI
- STEMI: MONA-GAP-BA + PCI or fibrinolytic (PCI preferred)

Drugs for Secondary Prevention after ACS

Aspirin (ASA) • 81 mg per day used indefinitely, unless contraindicated

P2Y12 Inhibitor • Medical management: Ticagrelor or Clopidogrel with ASA 81 mg for at least 12 months
• PCI-treated: Clopidogrel, Ticagrelor or Prasugrel with ASA 81 mg for at least 12 months
- Continuation of DAPT beyond 12 mo may be considered in those who are tolerating DAPT and
are not at high risk of bleeding following coronary stent placement

Nitroglycerin • Indefinitely (SL tablets or spray PRN)

Beta Blocker • 3 years; continue indefinitely in patients with HF or if needed to manage HTN
 ACE-I • Indefinitely in patients with EF < 40%, HTN, CKD, or DM; consider for all MI patients with no CI

Aldosterone • Indefinitely in patients with EF < 40% & symptomatic HF or DM receiving target doses of ACE-I and
Antagonist beta blocker
• CI: significant renal impairment (SCr > 2.5 in men; SCr > 2 in women) or hyperkalemia (K > 5)

Statin • Indefinitely – high intensity statin for most patients

• Patients > 75 YO: consider moderate or high intensity statin

Chronic Heart Failure

Signs/Symptoms of Heart Failure

Labs/Biomarkers • ⇧ BNP (normal: < 100 pg/mL)
• ⇧ NT-proBNP (normal: < 300 pg/mL)
Used to distinguish between cardiac & non-cardiac causes of dyspnea

General • Shortness of breath • Fatigue/weakness • Cough • Reduced exercise capacity

Left-sided • Orthopnea: SOB when lying flat • Crackles/rales

• Paroxysmal nocturnal dyspnea • S3 gallop
• Hypoperfusion (renal impair, cool extremities)

Right-sided • Ascites: abdominal fluid accumulation • Peripheral edema

• Jugular venous distention • Hepatomegaly
• Hepatojugular reflux

Drugs that cause or worsen HF – Drug InformaTion NATION

DPP4is Alogliptin, saxagliptin

TNF inhibitors Adalimumab (Humira), Etanercept (Enbrel)

Non-DHP CCBs Diltiazem, verapamil

Antiarrhythmics CLASS I CLASS III:

• IA: Disopyramide, Quinidine, Procainamide • Dronedarone, Sotalol, Ibutilide
• IB: Lidocaine, Mexiletine
• IC: Flecainide, Propafenone Dofetilide, Amiodarone = preferred for HF

TZDs Pioglitazone → ⇧ risk of edema

Antifungal Itraconazole

Interferons Avonex, Rebif

Oncology Drugs Anthracyclines (ex. Doxorubicin)

NSAIDs NSAIDs
 Guideline-Directed HFrEF Treatment
Initial medications, recommended for all patients without contraindications

Angiotensin receptor & neprilysin inhibitor ⇩ morbidity & mortality

(ARNI), ACEi, or ARB • ARNI is preferred > ACEi/ARB to further ⇩ morbidity & mortality

Beta Blockers ⇩ morbidity & mortality

• Control HR & reduce arrhythmia risk

ARAs ⇩ morbidity & mortality in NYHA Class II-IV HF

• Must meet eGFR, SCr, and potassium criteria for use

SGLT2s ⇩ morbidity & mortality

• Must meet eGFR criteria for use

Loop Diuretics • Reduce blood volume → ⇩ edema & congestion – symptom relief

Additional medications, add on in select patients

Bidil (isosorbide dinitrate/hydralazine) ⇩ morbidity & mortality in African Americans w/ NYHA III-IV

Ivabradine (Corlanor) ⇩ risk of hospitalization in stable NYHA Class II-III with resting HR > 70 bpm
in NSR on maximally tolerated dose of beta blockers

Digoxin Provides small ⇧ in CO, improves symptoms & ⇩ hospitalizations; consider

in symptomatic despite GDMT

Vericiguat ⇩ risk of hospitalization & CV death after HF hospitalization or need for IV

Soluble guanylate cyclase (sGC) stimulator diuretics

Potassium Chloride Formulations

XR capsules Contents can be sprinkled on a small amount of applesauce or pudding
Klor-Con Sprinkle, Micro-K

XR tablets • K-Tab, Klor-Con: swallow whole; do not chew, crush, cut or suck on tablet
K-Tab, Klor-Con 10, Klor-Con • Klor-Con M: if difficult to swallow, can cut in half or dissolve in water (stir for 2 minutes &
M10/M15/M20 drink ASAP); do not chew, crush or suck on tablet

PO packet Dissolve contents in water & drink ASAP

Klor-Con

PO solution • KCl 10% = 20 mEq/15 mL

KCl 10% = 20 mEq/15 mL • Mix each 15 mL with 6 oz of water

Arrhythmias

SA Node & arrhythmias

● Rate & rhythm of heartbeat are set by the rapidly firing cells in the SA node
● Arrhythmia is caused by a disruption somewhere in the conduction system
○ SA node can be firing at an abnormal rate or rhythm
○ Scar tissue from a prior heart attack can block & divert signal transmission
○ Another part of the heart may be acting as the pacemaker
 QT Prolonging Agents
Antiarrhythmics • Class IA, Class IC, Class III

Anti-infectives • Antimalarials (ex. Hydroxychloroquine)

• Azole antifungals (all except isavuconazonium)
• Macrolides, Quinolones, Lefamulin

Antidepressants • SSRIs (highest risk with Citalopram, Escitalopram)

• TCAs, Mirtazapine, Trazodone, Venlafaxine

Antiemetics • 5-HT3 receptor antagonists (ex. Ondansetron)

• Droperidol, Metoclopramide, Promethazine

Antipsychotics • 1st gen: Haloperidol, Chlorpromazine, Thioridazine

• 2nd gen: (highest risk with Ziprasidone)

Oncology Medications • Androgen deprivation therapy (ex. Leuprolide)

• Tyrosine kinase inhibitors (TKIs) (ex. nilotinib)
• Oxaliplatin

Other • Cilostazol, Donepezil, Fingolimod, Hydroxyzine, Loperamide

• Methadone, Ranolazine, Solifenacin, Tacrolimus

Vaughan Williams Classification

Double Quarter Pounder, Lettuce, Mayo, Fries, Please! Because Dieting During Stress Is Always Very Difficult
CLASS I
● IA: Disopyramide, Quinidine, Procainamide
● IB: Lidocaine, Mexiletine
● IC: Flecainide, Propafenone
CLASS II: Beta-blockers
CLASS III: Dronedarone, Dofetilide, Sotalol, Ibutilide, Amiodarone
CLASS IV: Verapamil, Diltiazem

AF: Rate vs. Rhythm Control vs. Stroke Prophylaxis

Rate Control Patient remains in AF & takes medications to control ventricular rate (HR)
- Beta-blockers (preferred) or Non-DHP CCBs (sometimes digoxin)

Rhythm Control Goal is to restore & maintain NSR

- Class IA, Class IC, Class III antiarrhythmic drugs or electrical cardioversion
- IC: Flecainide, Propafenone
- III: Amiodarone, Dronedarone, Dofetilide, Sotalol
If AF is permanent, avoid rhythm control strategy with antiarrhythmic drugs (risks >> benefits)

Stroke Prophylaxis Clots can form when in AF → can embolize (causing a stroke) when patient returns to NSR
- For many patients, it is safer to remain in AF with rate control than to try to restore NSR – may
require anticoagulation for stroke prevention, depending on CHA2DS2-VASc score
- DOACs (apixaban, rivaroxaban) are preferred over warfarin in non-valvular AF
When a rhythm control strategy is chosen, restoration & maintenance of NSR are not guaranteed –
decision for long-term anticoagulation will depend on patient’s clot risk
Stroke

Signs & Symptoms of Stroke – ACT F.A.S.T

● Face drooping – Ask them to smile. Does one side of the face droop or is it numb? Uneven?
● Arm weakness – Ask them to raise both arms. Does one arm drift downward?
● Speech difficulty – Ask to repeat a simple sentence. Words slurred? Sentence correct?
● Time to call 911 – If they show any symptoms above, even if they go away, call 911 ASAP!!

Bleeding Risks with Alteplase

Alteplase breaks up existing clots → breaking up a clot increases risk of bleeding
Before treatment, check that the patient isn’t already at a high bleeding risk – select
conditions/drugs are contraindications – ABCD
● Active internal Bleed (ex. ICH)
● Risk of internal bleed due to other Conditions
○ Severe HTN (BP > 185/110 mmHg)
■ If this is the only CI to treatment, BP should be lowered to < 185/110 mmHg with
IV meds (ex. Labetalol, Nicardipine) before proceeding with alteplase
○ Other conditions (ex. Head trauma)
○ Labs [ex. Elevated INR (> 1.7), aPTT (> 40 sec), low platelet count (< 100,000)]
○ Drug interactions (ex. Anticoagulant use)

Anticoagulation & Blood Disorders

Anticoagulation

Clotting cascade
 Warfarin Inhibits factors II, VII, IX & X Unfractionated Heparin (UFH) Equal anti-Xa & anti-IIa activity

Rivaroxaban Inhibits factor Xa (direct) LMWHs More anti-Xa >> anti-IIa activity
Apixaban
Edoxaban

Fondaparinux Inhibits factor Xa (indirect) Argatroban, Bivalirudin – IV Inhibits thrombin (IIa) directly
Dabigatran – PO

DOACs vs. Warfarin

● DOACs have less drug interactions, less or comparable bleeding & shorter duration of action
compared to warfarin
● DOAC dosing is based on the indication & kidney/liver function – there is no need to adjust the
dose based on INR (as with warfarin)
● DOACs are preferred for stroke prevention in AF
○ BUT – if there is mod-severe mitral stenosis or a mechanical heart valve, use warfarin
● DOACs are preferred for VTE treatment
○ BUT – if patient has antiphospholipid syndrome or a mechanical heart valve, use
warfarin

Conversion Between Anticoagulants

From warfarin to another PO • Rivaroxaban when INR < 3
anticoagulant, stop warfarin & convert • Edoxaban when INR < 2.5
to → • Apixaban when INR < 2
READ • Dabigatran when INR < 2

From oral Xa inhibitors to warfarin • Stop Xa inhibitor → start parenteral anticoagulant & warfarin at next dose
→ • Edoxaban only: refer to package labeling for conversion recommendations

From dabigatran to warfarin → • Start warfarin 1-3 days before stopping dabigatran (determined by renal function)

Warfarin Tablet Colors

Please Let Greg Brown Bring Peaches To Your Wedding
Pink (1 mg) Brown/Tan (3 mg) Teal (6 mg)

Lavender (2 mg) Blue (4 mg) Yellow (7.5 mg)

Green (2.5 mg) Peach (5 mg) White (10 mg)

Foods High in Vitamin K (Warfarin)

Spinach (cooked) Brussel sprouts Kale Green onion Endive

Broccoli Collard greens Turnip greens Swiss chard Parsley

Other: asparagus, cabbage, canola oil, cauliflower, coleslaw, lettuce, watercress, some teaks
 Risk factors for VTE
Modifiable Non-modifiable

• Acute medical illness • Increasing age

• Immobility • Cancer or chemotherapy
• Medications (SERMS, drugs containing estrogen, ESAs) • Previous VTE
• Obesity (BMI > 30 kg/m2) • Inherited or acquired thrombophilia (antithrombin deficiency, factor
• Pregnancy & postpartum period V Leiden, antiphospholipid syndrome, protein C or S deficiency)
• Recent surgery or major trauma • Certain disease states (HF, nephrotic syndrome, respiratory failure)

CHA2DS2VASc Score – only used on nonvalvular Afib

CHA2DS2VASc Scoring Score

Risk Factor Points 0

C Congestive (chronic) HF (HFpEF or HFrEF) 1 1

H HTN 1 2

A Age > 75 years 2 3

D DM 1 4

S Hx of Stroke, TIA, or thromboembolism 2 5

V Vascular disease (prior MI, PAD, or aortic plaque) 1 6

A Age 65-74 yrs 1 7

Sc Sex category (female only) 1 8

Consider anticoagulation for CHA2DS2VASc: Score > 2 men / > 3 in women
- DOAC recommended over warfarin

Anemia

Assessing & Treating Iron deficiency anemia

Lab Findings • ⇩ Hgb • ⇩ reticulocyte count • ⇩ ferritin
• ⇩ MCV (< 80 fL) • ⇩ serum iron • ⇩ TSAT
• ⇧ TIBC

Treatment: • Common dosing: 1 tablet once daily or every other day

Oral Iron Therapy • Take on an empty stomach (1H before or 2H after meals) for best absorption
• Avoid H2RAs & PPIs
• Sustained-release or enteric-coated formulations cause less GI irritation but are not
recommended due to poor absorption

Goals • ⇧ in serum Hgb observed after 1-2 weeks; continue treatment for 3-6 months or until iron
stores return to normal
 Drugs that can Cause Hemolytic Anemia
Immune-mediated (+Coombs Test) G6PD deficiency (AVOID)

• Penicillins • Isoniazid • Quinidine • Dapsone • Pegloticase • Quinidine

• Cephalosporins • Levodopa • Quinine • Nitrofurantoin • Rasburicase • Quinine
• Rifampin • Methyldopa • Sulfonamides • Primaquine • Methylene blue • Sulfonamides

Sickle Cell Disease

Vaccinations are essential to prevent infection in SCD

Routine Childhood • Haemophilus influenzae Type B (Hib)
Series • Pneumococcal conjugate [PCV13 (Prevnar 13) or PCV15 (Vaxneuvance)]

Additional Vaccines • Meningococcal conjugate series + routine boosters

for Functional • Meningococcal serogroup B (Bexsero, Trumenba) – age > 10 YO
Asplenia • Pneumococcal vaccines – give one of the following: – age > 19 YO
- PCV20 (Prevnar 20) x 1
- PCV15 (Vaxneuvance) x 1, then PPSV23 (Pneumovax 23) x 1 > 8 weeks later

Eyes, Ears, Nose & Skin Conditions

Allergic Rhinitis, Cough & Cold

Diphenhydramine (Benadryl) - First-generation antihistamine, but used for many indications such as:
Treatment of acute allergic reactions (+ epinephrine, depending on severity)

Prevention of allergic reactions (included in most premedication regimens for high-risk drugs)

Allergic rhinitis Cough (has antitussive properties) Motion sickness

Sleep (sedating) Dystonic reactions (anticholinergic properties)

Wide range of effects → can worsen some disease states: BPH, Constipation, Dementia, Glaucoma

Cough & Cold Combo Products

Contains “__” Agent Example

D Decongestant (ex. phenylephrine) Mucinex D = guaifenesin + pseudoephedrine

PE Phenylephrine Sudafed PE

DM Dextromethorphan Robafen DM = guaifenesin + dextromethorphan

AC Codeine G Tussin AC = guaifenesin + codeine

Guaifenesin Mucolytic (thins out mucus) Mucinex

Antihistamine Diphenhydramine, chlorpheniramine, brompheniramine Night-time products & some anytime products contain
 Common Conditions of the Eyes & Ears

Medications that increase intraocular pressure (IOP)

• Anticholinergics • Decongestants (pseudoephedrine)
(Antihistamines, Oxybutynin, Tolterodine, • Chronic steroids, especially eye drops (prednisolone)
Benztropine, Scopolamine, Trihexyphenidyl, TCAs) • Topiramate (Topamax)

Strategies for Glaucoma Treatment

Reduce aqueous humor production • Beta Blockers, like timolol
(make less fluid) • Carbonic anhydrase inhibitors, like dorzolamide

Increase aqueous humor outflow • Prostaglandin Analogs, like latanoprost

(move fluid out)

Or, do both (often achieved with add-on treatment) • Alpha-2 agonists, like brimonidine

Why do most eye drops BURN?

Most bottles of eye drops contain multiple doses. Since the bottles are being put in the eyes, the bottle
must remain free from contamination. A preservative is often added to prevent the growth of
microorganisms. The most common preservative used in eye drops is benzalkonium chloride (BAK)
● Preservatives are toxic to bacteria & are irritating to the sensitive tissues in the eyes which
leads to burning/stinging after administration
● Contact lenses trap drug & preservatives against surface of eyes, making irritation worse
○ Remove lenses before using drops & wait 15 min after administration before reinserting
○ Important with drops containing BAK – can damage the eyes when used with contacts
● Some drops have PF forms for those unable to tolerate side effects – Example: Cosopt PF

Common Drugs Known to Cause Vision Changes or Damage

Retinal changes/retinopathy • Chloroquine
• Hydroxychloroquine

Intraoperative floppy iris syndrome (IFIS); • Alpha Blockers (ex. tamsulosin)

causes difficulty in cataract surgery

Optic neuropathy • Amiodarone (+ corneal deposits)

• Linezolid
• Ethambutol

Color Discrimination • Digoxin (with toxicity) – yellow/green

• PDE-5 Inhibitors (ex. sildenafil) – green tinge around objections
• Voriconazole – color vision changes

Vision loss/abnormal vision • Digoxin (with toxicity) – blurriness, halos

• PDE-5 Inhibitors – vision loss (one or both eyes; can be permanent)
• Voriconazole – abnormal vision, photophobia
• Isotretinoin – ⇩ night vision, dryness, irritation
• Topiramate – visual field defects
• Vigabatrin – permanent vision loss (high risk)
 Common Skin Conditions

Drugs that can discolor skin & secretions

Brown Brown/Black/Green Brown/Yellow Yellow/Green Orange/Yellow

• Entacapone • Iron (black stool) • Nitrofurantoin • Propofol • Sulfasalazine

• Levodopa • Methocarbamol • Metronidazole • Flutamide
• Methyldopa • Tinidazole
• Riboflavin (B12)

Red Red/Orange Orange/Purple/Red Blue Blue/Gray

• Anthracyclines • Phenazopyridine • Chlorzoxazone • Methylene blue • Amiodarone

• Deferasirox (urine) • Rifampin • Mitoxantrone • Chloroquine
• Rifapentine

Acne Treatment Summary

First-line Alternative

Mild • Topicals: BPO or retinoid OR Add topical retinoid or BPO, switch to another
• Topicals: combination* retinoid, topical dapsone or clascoterone

Moderate • Topicals: combination* OR Other combination*, switch PO ABX, add combined

• PO ABX + BPO + topical retinoid (+/- topical ABX) OCP or spironolactone (females) or PO isotretinoin

Severe • Topicals: combination* + PO ABX OR Switch PO ABX, add combined OCP or spironolactone
• PO isotretinoin (females) or PO isotretinoin (if not previously tried)
*Topical combo includes: (BPO + topical ABX), (BPO + retinoid) or (BPO + retinoid + topical ABX)

Time to Burn TTB:

TTB (with sunscreen in min) = SPF x TTB (without sunscreen)

Pulmonary Conditions & Tobacco Cessation

Pulmonary Arterial Hypertension

Select Drugs can cause PAH

Cocaine Methamphetamine/amphetamine Weight-loss drugs (diethylpropion, phendimetrazine, phentermine)

Fenfluramine SSRI use during pregnancy (⇧ risk of persistent pulmonary HTN of a newborn)

Drugs that cause PF

Amiodarone/Dronedarone Bleomycin Busulfan Carmustine Lomustine
 Asthma

Asthma Diagnostic Criteria

Measure baseline FEV1 with spirometry → Give albuterol → measure post-bronchodilator FEV1
A FEV1 increase > 12% post-bronchodilator is consistent with asthma diagnosis (considered “reversible”)

Recognizing & Understanding Inhaled Delivery Devices

Features MDIs DPIs

Brand name ID HFA, Respimat or no suffix (Symbicort, Dulera) Diskus, Ellipta, Pressair, HandiHaler, RespiClick, Flexhaler

Dose delivery Aerosolized liquid Fine powder

Propellant Some use a propellant (HFA) No propellant

Administration Slow, deep inhalation while pressing the canister Quick, forceful inhalation (breath-activated dose; no
(hand-breath coordination) - hold for 10 seconds need to press anything) - hold for 10 seconds

Spacer CAN be used CANNOT be used

Helpful in patients incapable of hand-breath
coordination & decreases risk of thrush (ICS)

Shaking prior to Required for all products Do not shake

use except: QVAR, Alvesco & Respimat

Priming Before first use & if not used for a certain period of time Not needed except Flexhaler (prior to first use)

With a spacer, more drug gets into the lungs

● Spacers are helpful for children & anyone that has difficulty with hand-breath coordination
(ex. Pressing down on the inhaler while breathing in at the same time) with an MDI
● Spaces reduce the risk of thrush from inhaled corticosteroids (ICS)
● Common spacers: AeroChamber, OptiHaler, OptiChamber

COPD

Key Differences of COPD vs. Asthma

Feature COPD Asthma

Age of onset Usually > 40 years Usually < 40 years

Smoking history Usually > 10 years Uncommon

Sputum production Common Infrequent

Allergies Uncommon Common

Symptoms Persistent Intermittent & variable

Disease Process Progressive, worsens over time Stable, does not worsen over time

Exacerbations Common complication Common complication

First-line treatment Bronchodilators Inhaled corticosteroids (ICS)

 Tobacco Cessation

Nicotine Patch, Gum & Lozenge Dosing

Nicotine Patch (NicoDerm CQ)
8-10 week schedule

Starting dose

Number of cigarettes > 10 ➔ 21 mg x 6 weeks ➔ 14 mg x 2 weeks ➔ 7 mg x 2 weeks

per day
(1 pack = 20 cigarettes) < 10 ➔ 14 mg x 6 weeks ➔ 7 mg x 2 weeks

Nicotine Gum/Lozenge (Nicorette/Nicorette Mini)

12 week schedule

Starting dose
> 9 pieces/day in 1st 6 weeks

1st cigarette timing < 30 min ➔ 4 mg Q1-2H x 6 weeks ➔ 4 mg Q2-4H x 3 weeks ➔ 4 mg Q4-8H x 3 weeks
after waking?
> 30 min ➔ 2 mg Q1-2H x 6 weeks ➔ 2 mg Q2-4H x 3 weeks ➔ 2 mg Q4-8H x 3 weeks

Treatment Considerations for Tobacco Cessation

● All smokers should be offered meds unless it is contraindicated, pregnancy or an adolescent
● Combination of nicotine patch + gum, lozenge or bupropion is more effective than patch alone
Weight Gain Depression

USE Gum, Lozenge & Bupropion SR Bupropion SR

(all delay weight gain)

Dentures Asthma/COPD Skin Conditions Seizures

AVOID Gum Inhaler or Spray Patch Bupropion SR & Varenicline

Key Counseling Points

Nicotine Patch • At start of each day, remove a new patch from a pouch; save pouch to throw away used pouches
(NicoDerm CQ) • Remove the backing & apply sticky side of patch to a clean, dry, relatively hairless area of the skin
- Press the patch firmly onto the skin for ~10 seconds
• Wear for 24H (especially if cravings begin when you wake up)
Use gum or - Vivid dreams or trouble sleeping occur: remove prior to bed (after ~16H) & apply new one in morning
lozenges to help • Discard patch by folding the sticky ends together, place it back in the pouch & put it in a trash can with a lid
with cravings while to keep away from children & pets
using the patch • Wash your hands after applying (and removing) the patch
• Rotate the application site → do not apply to the same site for at least 1 week
- Skin reactions can occur but generally go away in a few days
• Never cut the patch or wear more than 1 patch at a time

Nicotine Gum • Chew slowly until there is a tingle or peppery flavor in the mouth
(Nicorette) • Park it between the cheek & gum
• When tingle or flavor goes away, begin chewing slowly again until it returns, then park gum again
• Repeat until most of the flavor or tingle is gone (~30 minutes)
• Do not eat or drink 15 minutes before or during use
 Endocrine Conditions

Diabetes

Diagnosis Criteria for Diabetes

Type II Diabetes A1C > 6.5 FPG > 126 mg/dL OGTT > 200 mg/dL

Prediabetes A1C 5.7-6.4 FPG 100-125 mg/dL OGTT 140-199 mg/dL

Glycemic Targets in Diabetes

A1C Preprandial (mg/dL) 1-hour PPG (mg/dL) 2-hour PPG (mg/dL)

Not Pregnant <7 80-130 < 180

Pregnant < 95 < 140 < 120

Diabetes Complications
Microvascular Disease Macrovascular Disease

• Retinopathy • Coronary artery disease (CAD), including MI

• Diabetic kidney disease (nephropathy) • Cerebrovascular disease, including stroke (CVA)
• Peripheral neuropathy, ⇧ risk of foot infections & amputations • Peripheral artery disease (PAD)
• Autonomic neuropathy
- Gastroparesis, loss of bladder control, ED Same as atherosclerotic CV disease (ASCVD)

Treatment Algorithm for Diabetes

 Insulin Dosing
Type I Diabetes - Calculate TDD: 0.5 units/kg/day (using ABW)
- Divide TDD into 50% basal & 50% bolus
- Divide bolus evenly among 3 meals (can allocate more for larger meals)

Type II Diabetes - To start, add basal: 10 units daily or 0.1-0.2 units/kg/day

- If FPG not at goal or A1c above goal, add bolus
- 4 units or 10% of basal dose once daily prior to largest meal

Insulin Conversions/Calculations
- Most insulins are 1 : 1
- Twice daily NPH → glargine (Lantus, Toujeo): use 80% of NPH dose
- Toujeo → glargine (Lantus, Basaglar) or detemir (Levemir): use 80% of Toujeo dose

Insulin Administration
Example: A patient is taking 35 units of Lantus daily, how many Lantus Solostar pens should be
dispensed for a 30 day supply?
1. 35 units/day x 30 days = 1050 units of insulin needed
2. Lantus 100 units/mL x 3 mL per pen = 300 units per pen
3. 1050 units needed x (1 pen/300 units) = 3.5 pens → 4 pens

Insulin Stability – Most insulin is stable at RT for 28 days including rapid-acting

Humalog Mix 50/50 & 75/25 PENS Humulin 70/30 PEN 10 days

Humulin N PEN Novolog Mix 70/30 PEN 14 days

Apidra, Humalog, Novolog, Ademelog, Lyumjev, Fiasp VIALS & PENs Humalog Mix 75/25 VIAL 28 days

Lantus, Basaglar, Semglee VIALS & PENs Novolog Mix 70/30 VIAL

Novolin R U-100, Novolin N, Novolin 70/30 PENS Humulin R U-500 PEN

Humulin R U-100, Humulin N, Humulin 70/30 VIALS 31 days

Humulin R U-500 VIAL 40 days

Novolin R U-100, Novolin N, Novolin 70/30 VIALS Levemir VIAL & PEN 42 days

Tresiba (degludec) PEN Toujeo (glargine) PEN 56 days

Drugs that affect blood glucose

Hypoglycemia Hyperglycemia

• Beta blockers☆☆ Quinolones☆☆ • Beta blockers☆☆ Quinolones☆☆ • Antipsychotics

• Tramadol • Diuretics (loops, thiazides) (olanzapine, quetiapine)
• Insulin • Tacrolimus, Cyclosporine • Statins
• Sulfonylureas • Protease Inhibitor • Steroids
• Meglitinides • Niacin • Cough syrups
• Alcohol (if also taking insulin or sulfonylureas)
 Treatment of DKA & HHS
Fluids Initial: NS 1L/hr

DKA: BG: 200 mg/dL / HHS: BG: 300 mg/dL: → switch to 5% dextrose + 0.45% NaCl

Insulin IV regular insulin: 0.1 U/kg IV bolus → 0.1U/kg/hr continuous infusion

- Alt: 0.14 U/kg/hr continuous infusion

Potassium Insulin shifts K+ into cells → K+ will ⇩ – monitor & keep serum level between 4-5 mEq/L

Acidosis Treat if pH < 6.9; may be corrected by fluids – give sodium bicarbonate if needed

Summary of Drug Safety Issues in Diabetes

AVOID agent If this condition is present

GLP-1s, • Cancer (thyroid, including medullary thyroid) • Pancreatitis

GIP/GLP-1 • Gastroparesis, GI disorders • Renal insufficiency (eGFR or CrCl < 30) – (exenatide)

DPP4i • Heart failure (saxagliptin & alogliptin) • Pancreatitis

SGLT2s • Genital infection/UTI • Hypotension/dehydration

• Ketoacidosis (can occur when BG < 250) • Osteopenia/osteoporosis (Canagliflozin – ⇩ BMD, fracture)
- DC 3 days prior to surgery • Peripheral neuropathy, PAD, foot ulcers (Canagliflozin)

Metformin • Renal insufficiency (eGFR or CrCl < 30) • Lactic acidosis (⇧ risk: renal impair, alcoholism, hypoxia)

Sulfonylureas • Hypoglycemia • Weight gain/obesity

• Sulfa allergy, severe • Renal insufficiency (eGFR or CrCl < 30) – (glyburide)

Insulin • Hypoglycemia • Weight gain/obesity

• Hypokalemia

Meglitinides • Hypoglycemia • Weight gain/obesity

TZDs • Heart failure • Weight gain/obesity

• Osteopenia/osteoporosis (fractures)

Pramlintide • Hypoglycemia • Gastroparesis, GI disorders

Thyroid Disorders

Signs & Symptoms of Hypothyroidism

Cold intolerance/sensitivity Dry skin Constipation Bradycardia Memory & mental impairment

Goiter (due to ⇩ iodine intake) Fatigue Weight gain Muscle cramps Coarse hair or loss of hair

Menorrhagia (heavy menstrual periods) Myalgias Depression Weakness Voice changes

 Drugs & Conditions that can CAUSE Hypothyroidism
Interferons Amiodarone Carbamazepine

Tyrosine kinase inhibitors (ex. sunitinib) Lithium Hashimoto’s Disease

- Interferons & Amiodarone can also cause hyperthyroidism

Levothyroxine Tablet Colors

Orangutans Will Vomit On You Right Before They Become Large, Proud Giants
25 mcg – orange 75 mcg – violet 100 mcg – yellow 125 mcg – brown 150 mcg – blue 200 mcg – pink

50 mcg – white 88 mcg – olive 112 mcg – rose 137 mcg – turquoise 175 mcg – lilac 300 mcg – green

Signs & Symptoms of Hyperthyroidism

Heat intolerance or sweating Weight loss Thinning hair

Agitation, nervousness, irritability, Frequent bowel movements or Exophthalmos (protrusion of

anxiety diarrhea eyeballs), Diplopia

Fatigue & Muscle weakness Insomnia Goiter (possible)

Palpitations & Tachycardia Tremor Light or absent menstrual periods

Signs & Symptoms of Thyroid Storm

Fever (> 103℉) Tachycardia Profuse sweating Delirium Psychosis

Dehydration Tachypnea Agitation Coma

Systemic Steroids & Autoimmune Conditions

Systemic Steroids (PO, IV) Dose Equivalence

Cortisone 25 mg Short-acting

Hydrocortisone 20 mg

Prednisone
5 mg
Prednisolone Intermediate-acting

Methylprednisolone
4 mg
Triamcinolone

Dexamethasone 0.75 mg Long-acting &

highest potency
Betamethasone 0.6 mg
Steroids Least Potent → Most Potent
Cute Hot Pharmacists and Physicians Marry Together & Deliver Babies
Treating Acute Inflammation with Steroids
Give a high dose initially (to quickly reduce inflammation), then taper the dose down to treat the remaining
infection while preventing a rebound attack – Example: Medrol therapy pack
Before Breakfast After Lunch After Dinner At Bedtime

Day 1 2 tablets 1 tablet 1 tablet 2 tablets

Day 2 1 tablet 1 tablet 1 tablet 2 tablets

Day 3 1 tablet 1 tablet 1 tablet 1 tablet

Day 4 1 tablet 1 tablet 1 tablet

Day 5 1 tablet 1 tablet

Day 6 1 tablet

Immunosuppression from Steroids

A patient is immunosuppressed when using > 2 mg/kg/day or > 20 mg/day of prednisone or
prednisone equivalent for > 2 weeks
● Immunosuppressed patients cannot receive live vaccines & have a high risk of infection
● Due to HPA axis suppression, the steroid will need to be tapered slowly to allow the adrenal
gland to resume normal cortisol production; if not, patient is risk for Addisonian Crisis
● Many ways to taper steroids:
○ Common method is to reduce dose by 10-20% every few days
○ Tapers can last 7-14 days depending on condition being treated

Drugs that can cause drug-induced lupus erythematosus (DILE)

My Pretty Malar Marking Probably Has A TransIent Quality
Methimazole Methyldopa Procainamide Anti-TNF agents Isoniazid

Propylthiouracil Minocycline Hydralazine Terbinafine Quinidine

Drug-Induced Raynaud’s
⇩ blood flow to fingers → ⇧ cyanosis & pain
● Beta-blockers
● Bleomycin, Cisplatin
● Sympathomimetics (via vasoconstriction): amphetamines, pseudoephedrine, & illicit drugs
 Male & Female Health

Contraception & Infertility

Select Contraceptive Types

Product Type Description

General tips for contraceptive names:

• “Lo” indicates < 35 mcg of estrogen – less estrogen causes less estrogenic side effects
• “Nor” in the name indicates it contains norethindrone
• “Fe” indicates an iron supplement is included
• “24” indicates a shorter placebo time: 24 active + 4 placebo = 28 day cycle

Combination Oral Contraceptive (COC) Pills

Monophasic Formulations Provides same dose of progestin & estrogen throughout active pill days
- Example: Junel 1/20 contains 1 mg norethindrone & 20 mcg EE

• Junel Fe 1/20 • Sprintec 28 • 21/7 pill pack contains 21 active hormonal pills, 7 inactive pills
• Microgestin Fe 1/20 • Yasmin 28
• Loestrin 1/20 • Cryselle-28
• Nortrel 1/35 • Portia-28
• Zovia 1/35 E • Apri
• Levora • Aviane
• Ocella

• Loestrin 24 Fe • Yaz • 24/4 pill pack contains 24 active hormonal pills, 4 inactive pills
• Minastrin 24 Fe • Nikki
• Beyaz

Lo Loestrin Fe • 24/2/2 pill pack contains 24 active combined hormonal pills, 2 pills of just EE & 2
inactive pills (with iron); very low dose estrogen used (EE 10 mcg)

Biphasic, Triphasic Formulations “Phasic” refers to the hormone dose being delivered in phases – beginning of name
indicates # of phases throughout the cycle

• Tri-Sprintec • Nortrel 7/7/7 • 3 different weeks (7/7/7) or “tri” indicates a triphasic formulation
• Ortho Tri-Cyclen Lo • Velivet, Trivora

Quadriphasic Formulations Hormone doses change over 26 days (4 phases of estradiol valerate & progestin
dienogest) followed by 2 placebo pills to mimic menstrual cycle & minimize
Natazia menstrual bleeding

Extended Cycle Formulations Period occurs every 3 months

Jolessa • 84 days of EE + LNG (progestin) followed by 7 days of placebo

• Seasonique • Camrese • 84 days of EE + LNG (progestin) followed by 7 days of low dose EE

• Amethia • Camrese Lo

Continuous Formulations No inactive pills (taken continuously) – no period occurs

Amethyst • 28 days of EE + LNG (progestin) with no placebo pills

Drospirenone Containing Formulations Mild potassium sparing diuretic to reduce bloating & other effects
 • Yasmin 28 • Beyaz • Nextellis • Contraindicated in renal or liver disease
• Yaz • Ocella • Safyral • Monitor potassium, kidney function during use
• Nikki • Loryna • Syeda

Patches (contain estrogen & progestin)

Transdermal patch Higher AUC than pills

Xulane, Zafemy, Twirla • Weeks 1-3: apply once weekly → week 4: off

Rings (contain estrogen & progestin)

Vaginal Ring Lower AUC than pills

• Insert monthly: in x 3 weeks – remove x 1 week
NuvaRing, EluRyng, Haloette, Annovera • Annovera: reusable; wash & store when removed, then reinsert – use for 1 year

Progestin-Only Pills (Mini-Pill/POP)

Errin, Camila, Nora-BE, Incassia • Errin, Camila, Nora-BE contain a fixed dose of norethindrone
- Take active tablet daily (no placebo days)
Slynd • Slynd = drospirenone-only

Injection (contains progestin only)

Depo-Provera • Contains depot medroxyprogesterone acetate (DMPA) – injected Q3 months

- 150 mg IM or 104 mg SC
• “Pro” in names indicates in contains a progestin

Severe & Rare Adverse Effects of Estrogen

The dose of estrogen in birth control pills used to be much higher – with a higher risk of clotting
- To be safe, patients should be able to recognize symptoms of a DVT, PE & less common clots
ACHES
Abdominal pain that is severe Can indicate a ruptured liver tumor or cyst, mesenteric or pelvic vein thrombosis, or the pain could
be due to liver or gallbladder problems or an ectopic pregnancy

Chest pain • Sharp, crushing, or heavy pain can indicate a heart attack
• Shortness of breath can indicate a PE

Headaches Sudden & severe with vomiting or weakness/numbness on one side of body can indicate a stroke

Eye problems Blurry vision, flashing lights or partial/complete vision loss can indicate a blood clot in the eye

Swelling or sudden leg pain Can indicate a DVT

Infertility Drugs Act Like Endogenous Hormones to Trigger Ovulation

⇧ LH/FSH → ovulation (release of egg)

● Clomiphene acts as estrogen to ⇧ LH/FSH → cause ovulation

● Aromatase inhibitors suppress estrogen to ⇧ FSH → cause ovulation
● Gonadotropin drugs act as LH, FSH or hCG (similar to LH) → cause ovulation

GOOD: infertility drugs trigger ovulation (release of egg)

GOOD?: they can trigger release of multiple eggs & increase risk of multiple births
 Drug Use in Pregnancy & Lactation

Common Teratogens
Acne Isotretinoin, Topical retinoids

Antibiotics Quinolones, Tetracyclines

Anticoagulants Warfarin

Dyslipididemia, HF & HTN Statins, ACE-I, ARBs, Sacubitril/Valsartan, Aliskiren

Hormones Most: estradiol, progesterone (including megestrol), raloxifene, Duavee, testosterone, contraceptives

Migraine Dihydroergotamine, ergotamine

Other Hydroxyurea Lithium Methotrexate Misoprostol

NSAIDs Paroxetine Ribavirin Thalidomide

Topiramate Weight loss drugs Divalproex/Valproic acid

Osteoporosis, Menopause & Testosterone Use

Risk Factors for Osteoporosis

Patient Characteristics Lifestyle Factors

• Advanced age • Smoking

• Ethnicity (White & Asian are at ⇧ risk) • Excessive alcohol intake (> 3 drinks per day)
• Family history • Low calcium intake
• Sex (Female > Male) • Low vitamin D intake
• Low body weight • Physical inactivity

Medical Diseases/Conditions Medications

• Diabetes • Anticonvulsants (carbamazepine, phenytoin, phenobarbital)

• Eating disorders • Aromatase inhibitors
• GI diseases (ex. IBD, celiac disease, gastric • Depo-medroxyprogesterone
bypass, malabsorption syndromes) • GnRH (gonadotropin-releasing hormone) agonists
• Hyperthyroidism • Lithium
• Hypogonadism in men • PPIs (⇧ gastric pH, ⇩ calcium absorption)
• Menopause • Steroids (> 5 mg QD of prednisone or equivalent for > 3 mo)
• RA, autoimmune diseases • Thyroid hormones (in excess)
• Others (epilepsy, HIV/AIDS, Parkinson disease) • Others (loop diuretics, SSRIs, TZDs)
Long-term use of steroids is the major drug-contributing factor to poor bone health
 Diagnosis of Osteoporosis with a T-score
What is a T-score?

• Compares the patient’s measured BMD to the average peak BMD of a healthy, young, white adult of the same score
• A DEXA (or DXA) measures BMD so a T-score can be determined
• T-score are negative: a score at or above -1 correlates with stronger (denser bones), which are less likely to fracture

Who should have BMD measured?

• Women > 65 YO & men > 70 YO • Younger patients at high risk for fracture

Interpreting T-score results

Normal > -1

Osteopenia (low bone mass) -1 to -2.4

Osteoporosis < -2.5

Calcium & Vitamin D Supplementation

Calcium • Recommended daily intake for most is 1000-1200 mg elemental calcium
- Do not exceed 500-600 mg of elemental calcium per dose

Calcium carbonate (Tums) Calcium citrate (Citracal)

- 40% elemental calcium - 21% elemental calcium
- Absorption: acid-dependent - Absorption: not acid-dependent
- Must take with meals - Can take with or without food

Vitamin D • Required for calcium absorption

• Deficiency: serum vitamin D [25(OH)D] < 30 ng/mL
• Treat deficiency with vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol)
- Cholecalciferol: 125-175 mcg (5000-7000 IU) daily
- Ergocalciferol: 1250 mcg (50,000 IU) weekly

Drug Summary for Osteoporosis Treatment & Prevention

Bisphosphonates • First-line for treatment or prevention in most patients
• PO administration: stay upright for 30 min (60 min for ibandronate) & drink 6-8 oz of water
• Side effects: esophagitis, hypocalcemia, GI effects
• Rare (but serious) side effects
- Atypical femur fractures
- Osteonecrosis of the jaw (ONJ): jaw bone becomes exposed & cannot heal due to
decreased blood supply
• Formulations:
- PO: given weekly/monthly
- IV: given quarterly/yearly (if GI side effects or adherence issues with PO)
• Treatment duration: 3-5 years in low risk of fracture (due to risk of femur fractures & ONJ)

Denosumab (Prolia) • Alternative to bisphosphonates – SC administration Q6 months

• Side effect: hypocalcemia

Teriparatide (Forteo) • Recommended for very high-risk patients only – SC administration daily
Abaloparatide (Tymlos) • Side effect: hypercalcemia
 Raloxifene (Evista) • Alternative to bisphosphonates if high risk of vertebral fractures
Bazedoxifene/Estrogens • Increased risk for VTE & stroke
(Duavee) • Raloxifene can be used if low VTE risk or high breast cancer risk
- Side effect: vasomotor symptoms
• Bazedoxifene/Estrogens can be used in women with an intact uterus for prevention
- Also used as treatment for vasomotor symptoms
- Side effect: increased risk of breast cancer

Last line or not • Estrogen (+/- progestin) for prevention only in postmenopausal women with vasomotor
recommended symptoms – use lowest possible dose for shortest duration of time
• Calcitonin treatment only if other options not suitable (less effective & risk of cancer with
long-term use)

Hormone Therapy: Health Risks & Appropriate Use

Estrogen • Most effective treatment for vasomotor symptoms
• Women with a uterus: use in combo with a form of progesterone (ex. a progestin)
- Unopposed estrogen increases the risk of endometrial cancer
• Associated with significant safety risks, including boxed warnings for:
- VTE, stroke, dementia & breast cancer (bigger concern in the elderly)

Progestin • Progestins (drospirenone, norethindrone, levonorgestrel) can be given as a combo pill with estrogen or as a
separate tablet, most commonly medroxyprogesterone (MPA)
• Can cause mood disturbances, which may be intolerable; if taken intermittently, spotting can occur
• Micronized progestins (ex. Prometrium) are considered to be safer than synthetic progestins (MPA)

Criteria for use • Healthy, symptomatic women who are within 10 years of menopause, < 60 YO & no CI to use
of Hormone • Extending treatment beyond age 60 may be acceptable (ex. patient has osteoporosis) if the lowest possible
Therapy dose is used & the woman is advised of safety risks
• Consider QoL priorities & personal risk factors (ex. age, time since menopause, risk of blood clots, heart
disease, stroke & breast cancer)
- Patients with risk factors should use non-hormonal treatment (SSRIs, SNRIs, gabapentin, pregabalin)

Sexual Dysfunction

Drugs that Cause ED/Sexual Dysfunction

• Alcohol • Antipsychotics
• Antidepressants: SSRIs & SNRIs (including ⇩ libido) - First-Generation (ex. Chlorpromazine)
• Antihypertensives: - Prolactin-raising Second-Gen (ex. Risperidone, Paliperidone)
- Beta blockers, Clonidine, Thiazides • BPH Meds: Finasteride, Dutasteride & Silodosin (retrograde ejaculation)

PDE-5 Inhibitor Dosing Guide

Agent Typical Starting Dose Reduce dose if: ⇩ starting dose by 50%

Sildenafil (Viagra) 50 mg → 25 mg

Tadalafil (Cialis) 10 mg > 65 YO 5 mg

Using an alpha-blocker
Vardenafil (Levitra) 10 mg Using a CYP3A4 inhibitor 5 mg
Severe renal or liver disease
Avanafil (Stendra) 100 mg 50 mg
 Benign Prostatic Hyperplasia (BPH)

Drugs that can worsen BPH

• Drugs with anticholinergics effects: • Centrally-acting anticholinergics (ex. Benztropine)
- Antihistamines (ex. diphenhydramine) • Caffeine
- Decongestants (ex. pseudoephedrine) • Diuretics
- Phenothiazines (ex. prochlorperazine) • SNRIs
- TCAs (ex. amitriptyline) • Testosterone products

Urinary Incontinence

Anticholinergic Side Effects

Peripheral Dry mouth Urinary retention Constipation Dry eyes/blurred vision Tachycardia

Central Sedation Dizziness Cognitive impairment

Anticholinergics – Decreasing Risk of Dry Mouth

Dry mouth is a major reason patients fail to comply with anticholinergic treatment
Choosing a treatment that minimizes dry mouth can improve adherence
● Try XR formulations (lower risk than IR formulations)
● Try oxybutynin gel or patch (lower risk than oral formulations)
● Beta-3 agonists have lower incidence of dry mouth & can be helpful in patients who cannot
tolerate anticholinergics
● Try non-drug options to help with symptoms
○ Avoid mouthwashes with alcohol, use ice chips, water, sugar-free candy or gum

Special Populations

Acute & Critical Care Medicine

Dopamine Dosing
Dopamine stimulates different receptors depending on the dose
Type of Dose Dose Receptor stimulated Effect

Low (renal) dose 1-4 mcg/kg/min Dopamine-1 agonist Renal vasodilation

Medium dose 5-10 mcg/kg/min 𝜷1 agonist Positive inotropic effect

High dose 10-20 mcg/kg/min 𝛼1 agonist Vasopressor effect

 General principles for treating septic shock:
● Target mean arterial pressure (MAP) of > 65 mmHg
○ MAP = [(2 x DBP) + SBP]/3
● Fill the tank
○ Optimize preload: IV crystalloids (balanced fluids such as Lactated ringers preferred)
● Squeeze the pipe & kick the pump
○ 𝛼1 agonist activity (peripheral vasoconstriction) → ⇧ SVR
○ 𝜷1 agonist activity to ⇧ myocardial contractility & CO

Two Common Causes of ICU Infections

Mechanical Respirators → air flows into trachea through endotracheal tube placed via mouth or nose (intubation)
ventilation - ⇧ time on ventilator = ⇧ risk of infections (lung)
- Pseudomonas thrive in the moist air in the ventilator

Indwelling urinary Intubated patients have catheters inserted to drain urine – Foley catheters = most common type
catheter - ⇧ time with Foley catheter = ⇧ risk of bladder infection

Treating ADHF
Note: Beta blockers should only be stopped if hypotension & hypoperfusion are present
VOLUME OVERLOAD: Patients with edema (pulmonary or LE), JVD and/or ascites
● Loop Diuretics
● Vasodilators can be added (NTG, Nitroprusside)
HYPOPERFUSION: Patients with ⇩ renal function, altered mental status and/or cool extremities
● Inotropes (dobutamine, milrinone)
● If patient becomes hypotensive, consider adding a vasopressor (dopamine, norepinephrine,
phenylephrine)
● Note: avoid vasodilators: can ⇩ BP & worsen hypoperfusion
Patients with both VOLUME OVERLOAD & HYPOPERFUSION – A combination of agents above

Pediatric Conditions

Drugs Not Generally Recommended in Pediatrics

Contraindicated Not Generally Recommended

• Codeine in age < 12 YO • Aspirin in children & teenagers

• Tramadol in age < 12 YO • Quinolones
• Promethazine in age < 2 YO • Tetracyclines in age < 8 YO
• Ceftriaxone in neonates (0-28 days) • OTC teething meds containing benzocaine in age < 2 YO
• OTC cough & cold meds in age < 2 YO (per FDA)
● Codeine is CI in age < 12 YO & < 18 YO after tonsillectomy/adenoidectomy
○ Rx cough & cold meds that contain codeine & hydrocodone in age < 18 YO
● Quinolones – can have adverse effects on cartilage, bone & muscle
● Tetracyclines – not recommended in < 8 YO – can stain teeth & deposit into bone & cartilage
○ Exception: in tick-borne Rickettsial diseases (Rocky Mountain spotted fever)
Cystic Fibrosis

Administering the inhaled medications in correct order is critical to maximize absorption/effect

Order Intervention Purpose

1st Inhaled bronchodilators (ex. albuterol) Open the airways

2nd Hypertonic saline (ex. HyperSal) Mobilizes mucus to improve airway clearance

3rd Dornase alfa (Pulmozyme) ⇩ viscosity of mucus to promote airway clearance

4th Chest physiotherapy Mobilizes mucus to improve airway clearance

5th Inhaled antibiotics Controls airways infection

Most patients will require PO meds (ex. pancreatic enzyme products, azithromycin) – given at any time

What’s in a Name?
Enzymes are proteins that break bonds & speed up chemical reactions
- Generic name usually ends in “-ase”
Lungs: Dornase alfa (Pulmozyme) – indicates that its an enzyme
- Breaks DNA strands into smaller pieces, thinning the mucus to make it easier to cough up
GI Tract: Pancrelipase
- Pancrelipase contains the enzymes lipase, protease, & amylase that are needed to break down
fats, proteins & starches
- Zenpep: identifies that it is a pancreatic enzyme product (PEP)
- Creon: comes from the generic name pancrelipase
- Viokase: indicates that it is an enzyme by the suffix (slightly different spelling)

Common Issues with Pancreatic enzyme products (PEP)

Pancreatic enzyme replacement helps patients with CF digest food, maintain weight & improve
nutrient absorption
● PEP formulations are not interchangeable – commonly used: Creon, Viokace, Zenpep
● Viokace: only PEP that is a tablet – non-enteric coated & MUST be given with a PPI
● All other PEPs are capsules
○ Do not crush or chew contents of the capsules
○ Delayed-release capsules with enteric-coated microspheres or microtablets may be
opened & sprinkled on soft, acidic foods (pH < 4.5) like applesauce
■ Avoid foods with high pH such as dairy
○ Do not retain the capsule contents in the mouth – swallow immediately & follow with
water to avoid mucosal irritation & stomatitis
● Take PEPs before or with all meals & snacks – high-fat meals may require higher doses
○ Use 50% of the mealtime dose with snack
● Protect from moisture; dispense in original container, do not refrigerate
○ Exceptions to dispensing: Zenpep & some Creon strengths
 Transplant

Transplant Drugs: What’s Used & When

Induction • Basiliximab – an interleukin-2 (IL-2) receptor antagonist
Immunosuppression • Antithymocyte globulin – in patients at higher risk of rejection
• High-dose IV steroids

Maintenance • Calcineurin inhibitors (CNIs) – tacrolimus (preferred) or cyclosporine

Immunosuppression - Belatacept as an alternative to a CNI
• Adjuvant medications given with a CNI (to achieve adequate immunosuppression while
decreasing the dose & toxicity of individual agents)
- Antiproliferative agents (mycophenolate or azathioprine)
- mTOR inhibitors (everolimus or sirolimus)
• Steroids at lower or tapering doses

Boxed Warnings for Transplant Drugs

Infection Risk • Transplant drugs suppress the immune system to prevent it from attacking the transplanted organ
– flip side is that immune system is suppressed & this increases risk of different types of infections
• Sometimes, PPX is needed, which can include same drugs used for OIs when CD4+ count is low

Cancer Risk • A healthy immune system suppresses some types of cancers, including lymphomas, melanoma &
non-melanoma skin cancers. Kaposi’s sarcoma is another type of cancer that occurs with a
severely depressed immune system but is mostly seen in HIV

“Only Experienced • Transplant drugs require experienced physicians. This is especially important when drugs are
Prescribers...” started. The transplant team includes several types of highly skilled practitioners, including
pharmacists who have specialized in managing transplant drugs

Vaccine-Preventable Illness in Transplant Recipients

● Required vaccines are given pre-transplant if not UTD
● Inactivated vaccines can be given 3-6 months post-transplant (once immune system recovers
from induction immunosuppression), except for flu vaccine – can be given 1 mo post-transplant
● Live vaccines cannot be given post-transplant
Important vaccines for Transplant Recipients
Influenza • Inactivated, not live, annually

Pneumococcal • PCV20 (Prevnar 20) x 1 or

Adults > 19 YO • PCV15 (Vaxneuvance) x 1, followed by PPSV23 (Pneumovax 23) x 1 > 8 weeks later

Varicella • High risk for serious varicella infections, with very high risk of disseminated disease if infection occurs
• Vaccine pre-transplant
• Vaccinate close contacts – small risk transmission could occur, ACIP states benefits outweigh risk of
transmission
• If a vaccinated household contact develops a rash they are considered contagious & must avoid
contact with the transplant recipient & contact their physician
• If transplant patient develops a rash, they need to be seen right away
 Weight Loss

Drugs/conditions that can cause weight gain

Antipsychotics Diabetes Drugs TCAs
(Clozapine, olanzapine, risperidone, quetiapine) (Insulin, sulfonylureas, meglitinides, TZDs) (amitriptyline, nortriptyline)

Divalproex/valproic acid Gabapentin, Pregabalin Lithium

Mirtazapine Steroids Hypothyroidism

Drugs/conditions that can cause weight loss

ADHD Drugs GLP-1s SGLT2s
(amphetamine, methylphenidate) (exenatide, liraglutide) (canagliflozin, empagliflozin)

Bupropion Pramlintide Roflumilast

Topiramate Tirzepatide Hyperthyroidism, Celiac Disease, IBD

Prescription weight loss drugs: avoid/use caution

AVOID Caution

Pregnancy Avoid ALL weight loss drugs

Hypertension Contrave Qsymia

(Naltrexone/Bupropion) (Phentermine/Topiramate ER)

CI with uncontrolled BP (bupropion) Monitor HR (phentermine)

Depression Contrave
(Naltrexone/Bupropion)

Young adults & adolescents: suicide risk (bupropion)

Seizures Contrave Qsymia

(Naltrexone/Bupropion) (Phentermine/Topiramate ER)
Lowers seizure threshold (bupropion) Must taper off slowly if used (topiramate)

Taking Opiods Contrave

(Naltrexone/Bupropion)

Blocks opioid receptors (naltrexone)

Pain/Related Conditions

Pain

Acetaminophen OVERDOSE
Antidote for acetaminophen overdose is N-acetylcysteine (NAC, Acetadote)
● Glutathione precursor (⇧ glutathione)
● Administered intravenously or orally
○ Using solution for inhalation or injectable formulation
The Rumack-Matthew nomogram uses the serum acetaminophen level & time since ingestion to
determine whether hepatotoxicity is likely (and the need for NAC)

NSAIDs & the Ductus Arteriosus

Before birth, the ductus arteriosus (DA) connects the pulmonary artery to the aorta, allowing
oxygenated blood to flow to the baby, bypassing the immature lungs
● Do NOT use NSAIDs in the third trimester of pregnancy – can prematurely close the DA
○ After birth, the DA should close on its own
○ In some cases, it remains patent (open) & NSAIDs can be used to help it close
● IV NSAIDs (indomethacin, ibuprofen) must be administered within 14 days of birth to close a
patent ductus arteriosus (DA)

Opioid Boxed Warnings

Addiction, abuse & misuse can lead to overdose & death

Respiratory depression, which can be fatal

Use of any opioid with BZDs or other CNS depressants, including alcohol, can ⇧ risk of death

Morphine ER capsules (Kadian), Nucynta ER, oxymorphone ER & hydrocodone ER capsules

- Do not consume alcohol: can cause ⇧ drug plasma levels, which can lead to potentially fatal OD

Accidental ingestion/exposure of even one dose in children can be fatal

- Never give this medication to anyone else (includes patches)

Crushing, dissolving or chewing long-acting products can cause potentially fatal dose

Life-threatening neonatal opioid withdrawal can occur with prolonged use during pregnancy

Opioids & Chronic Non-Cancer Pain

Opioids are not first-line for chronic pain treatment & should not be used routinely
- In some cases, they have benefit & when used, follow safe use recommendations:
• Establish & measure goals for pain & function – reaching low pain rather than no pain may be reasonable
• If using opioids, start with immediate-release – start low & go slow
• Evaluate risk factors for opioid-related harm routinely
• Pharmacists should check their state’s PMP database – Look for high dosages & multiple prescribers
• Use adjunctive medications to enable a lower opioid dose
• Avoid benzodiazepines, except in rare cases – Use together quadruples risk of OD death
• Follow-up, taper the dose, consider discontinuation
Opioid Allergy
The common drugs in the same chemical class that cross-react with each other have cod or morph in
the name. Buprenorphine has norph instead of morph
● In a true opioid allergy, use an agent in a different chemical class
○ Symptoms: difficulty breathing, severe drop in BP, serious rash, swelling of face, lips,
tongue & larynx
Codeine Morphine Buprenorphine
Hydrocodone Hydromorphone Heroin (diacetyl-morphine)
Oxycodone Oxymorphone
What to do if a morphine-type allergy is reported?
- Make sure it is an actual allergy, not nausea or itching
- Seems to be accurate, chose drug in a different chemical class, such as methadone or fentanyl
- Meperidine is also in a different class, but no longer recommended as an analgesic

Opioid-induced respiratory depression (OIRD) Risks

● History of previous overdose
● Substance use disorder
● Using large doses (> 50 mg morphine or equivalent)
● Use with BZDs, Gabapentin, Pregabalin
● Comorbid illnesses, such as respiratory or psychiatric disease
Naloxone should be readily available to patients with elevated risk for OIRD

Opioid-Induced Constipation (OIC)

● Opioids reduce GI tract peristalsis, making it difficult to have a bowel movement
● Unlike CNS depression, OIC does not improve over time without treatment
○ Must be anticipated & treated
● Stimulant (senna, bisacodyl) or osmotic (PEG) laxatives are typical first line treatments
○ + stool softener (docusate)
○ Bisacodyl comes as a tablet (for PPX) or suppository (for treatment)
● If laxatives are not sufficient, specific meds for OIC that counteract the effects of the opioid
receptor in the gut (PAMORAs) can be used
● Lubiprostone could be considered (24 mcg BID) following a trial of laxatives or PAMORAs

Opioid OVERDOSE Management

● Signs & symptoms of OD: extreme sleepiness, slow or shallow breathing, fingernails or lips
turning blue/purple, extremely small “pinpoint” pupils, slow HR or BP
● If OD is suspected, give naloxone & call 911
● If a person is not breathing or struggling to breathe, life support measures should be performed
● If there’s a question about whether to give naloxone, give it – fatality could result from not
● Opioids last longer than naloxone, monitor closely for respiratory depression repeat doses PRN
● Naloxone is available in two options:
Narcan • Onset of action is slower than injection
(nasal spray) • Single-use nasal spray is 4 mg administered in ONE nostril
- Repeat doses in alternating nostrils may be needed

Naloxone • Generic formulation available in multiple size vials

(injection) • Separate syringe will be needed
- May need to repeat doses Q2-3 minutes until emergency services arrives
 Migraine

Common Migraine Triggers

Hormonal Changes in Women • Fluctuations in estrogen can trigger headaches
- Monophasic oral contraceptives can keep estrogen levels more constant & help
reduce MAM
• Progestin-only contraceptive methods are recommended for migraine WITH aura due
to stroke risk with estrogen-containing contraceptives

Foods • Common offenders: alcohol (especially beer & red wine), aged cheeses, chocolate,
aspartame, overuse of caffeine, monosodium glutamate (MSG), salty & processed foods

Stress • Major cause of migraines

Sensory Stimuli • Bright lights, sun glare, loud sounds & certain scents (pleasant or unpleasant odors)

Changes in Wake-Sleep Pattern • Either missing sleep or getting too much sleep (including jet lag)

Changes in the Environment • A change of weather or barometric pressure

Triptan Formulations
Tablet ODT Nasal Spray/Powder SC Injection

• ALL triptans • Rizatriptan (Maxalt-MLT) Spray (ONE nostril) Prefilled Syringe

• Zolmitriptan (Zomig ZMT) • Sumatriptan (Imitrex) • Sumatriptan (Imitrex)
• Zolmitriptan (Zomig) Autoinjector
Powder (EACH nostril) • Sumatriptan (Imitrex STATdose)
• Sumatriptan (Onzetra Xsail) • Sumatriptan (Zembrace SymTouch)
● Sumatriptan SC (Zembrace SymTouch): can repeat 4x per day
● Sumatriptan SC (Imitrex, Imitrex STATdose): can repeat x1 after 1H
● Sumatriptan tablet: can repeat x1 after 2H
● Sumatriptan nasal spray (Imitrex): can repeat x1 after 2H

Gout

Medications that Increase uric acid

• Aspirin, lower doses • Calcineurin inhibitors • Select chemotherapy (with tumor lysis syndrome)
• Niacin (cyclosporine, tacrolimus) • Select pancreatic enzyme products (PEP)
• Pyrazinamide • Diuretics (loops, thiazides)

Gout Treatment Basics

Treat acute pain with • Colchicine • NSAIDs (often with a high starting dose)
anti-inflammatory drugs • Steroids (including intra-articular injections)

Treat chronically to prevent • Xanthine oxidase inhibitor (XOI): allopurinol (preferred) or febuxostat
future attacks An acute flare can occur when an XOI is started, so give initially with colchicine or NSAID

If XOI didn’t work well enough • Add probenecid or lesinurad to daily XOI
& UA remains > 6 mg/dL • Replace XOI with IV pegloticase (Krystexxa)
 Oncology

Oncology I: Overview & Side Effects Management

Dosing Considerations for Select Highly Toxic Drugs

Drug Maximum Doses Reason

Bleomycin Lifetime cumulative dose: 400 units Pulmonary toxicity

Doxorubicin Lifetime cumulative dose: 450-550 mg/m2 Cardiotoxicity

Cisplatin Dose per cycle not to exceed 100 mg/m2 Nephrotoxicity

Vincristine Single dose “capped” at 2 mg Neuropathy

Chemoman & Major Toxicities of Common Chemotherapy Drugs

N – Nitrosoureas (Lomustine, Carmustine)
● Neurotoxicity

C – Platinum-Based (Cisplatin, Carboplatin)

● Nephrotoxic/Ototoxic

M – Methotrexate
● Mucositis

B – Bleomycin, Busulfan, Lomustine, Carmustine

● Pulmonary toxicity

D – Doxorubicin & other anthracyclines

● Cardiotoxic

Immunotherapy: targeting CTLA-4 or PD-1/PD-L1

(Ipilimumab, Atezolizumab, Durvalumab, Nivolumab, Pembrolizumab)
● Autoimmune Syndromes (widespread effects)

IP – Ifosfamide, Cyclophosphamide
● Hemorrhagic Cystitis

V – Vinca Alkaloids (Vincristine, Vinblastine, Vinorelbine)

T – Taxanes (Paclitaxel, Docetaxel)
● Peripheral neuropathy

BMS – Bone Marrow Suppression (common in many agents)

● Alkylators (Ifosfamide, Cyclophosphamide)
● Anthracyclines (Doxorubicin, Daunorubicin)
● Platinum-Based (Cisplatin)
● Taxanes (Paclitaxel, Docetaxel)
● Camptothecins (Irinotecan, Topotecan)
● Epipodophyllotoxins (Etoposide, Teniposide)
● Anti-metabolites (Folic acid, Pyrimidine & Purine analogues)
● Vinca Alkaloids (Vinblastine, Vinorelbine)
 Chemotherapy Adjunctive Treatment
Chemo Drug Adjunctive Treatment Indication for Adjunctive Treatment

Cisplatin Amifostine (Ethyol) & hydration • Prophylaxis to prevent nephrotoxicity

Doxorubicin Dexrazoxane • Prophylaxis to prevent cardiomyopathy

Fluorouracil Leucovorin or Levoleucovorin • Given with 5-FU to enhance efficacy (as a cofactor)

Fluorouracil or Capecitabine Uridine triacetate • Antidote: use within 96H for an OD or to treat
severe, life-threatening or early-onset toxicity

Ifosfamide Mesna (Mesnex) & hydration • Prophylaxis to prevent hemorrhagic cystitis

Irinotecan Atropine • Prevent or treat acute diarrhea

Loperamide • Treat delayed diarrhea

Methotrexate Leucovorin or Levoleucovorin • Prophylaxis to protect cells from toxicity (ex.

myelosuppression, mucositis) after high doses
Glucarpidase • Antidote: use within 48-60H for patients with
methotrexate-induced AKI & delayed MTX clearance

Myelosuppression Recovery
Blood Stem Cell leads to:
Red Blood • ⇩ RBCs → anemia (⇩ Hgb/Hct) Treatment - Erythropoiesis-Stimulating Agents (ESAs)
Cells • Symptoms: weakness/fatigue - Epoetin alfa (Epogen, Procrit)
• Can resolve on its own or with RBC infusion - Darbepoetin alfa (Aranesp)

Platelets • ⇩ platelets → thrombocytopenia

• Symptoms: bleeding
• Platelet transfusion if very low (< 10,000)

White Blood • ⇩ WBCs → leukopenia (⇩ immune response) Treatment - Colony-stimulating factor (CSF)
Cells • Symptoms: fever/infection - Filgrastim (Neupogen)
- Pegfilgrastim (Neulasta)

Irinotecan – I-RUN-TO-THE-CAN
● Irinotecan causes cholinergic excess, including acute diarrhea with abdominal cramping
○ Atropine, classic anticholinergic drug, can be given to prevent acute diarrhea
○ Pilocarpine, classic cholinergic drug, causes salivation
■ Used for xerostomia (dry mouth) & lacrimation (for dry eyes)

Oncology II:

Reduce Doxorubicin Toxicity

1. Keep track of lifetime cumulative dose for each patient
(Doxorubicin dose in mg/m2/cycle) x (total # of cycles received) = cumulative dose in mg/m2
- Ex. (Doxorubicin 50 mg/m2/cycle) x (6 cycles) = 300 mg/m2
2. Lifetime max cumulative doxorubicin dose = 450-550 mg/m2
3. Monitor LVEF before & after treatment (using echocardiogram or MUGA scan)
4. Dexrazoxane may be considered when the doxorubicin cumulative dose > 300 mg/m2
 Which Folate Analog & When?
Folic acid antagonists are used in oncology & rheumatologic diseases to alter autoimmune processes
In Autoimmune • Dose of methotrexate is much lower (5-25 mg WEEKLY)
Diseases: • Folic acid 1-5 mg QD = recommended for PPX to ⇩ MTX side effects (GI, hematologic, hepatic)
• Leucovorin is NOT used unless the patient does not respond to folic acid

In Oncologic • Dose of methotrexate is much higher (> 40 mg/m2) & may be given with other chemotherapy
Diseases: Q2-3 weeks, allowing the patient to recover between doses
• To rescue a patient from high-dose MTX toxicity, a reduced form of folate must be started after the
MTX has a chance to kill the cancer cells. Leucovorin or Levoleucovorin is given.
• Regular folate (folic acid) is NOT effective in rescue of high-dose MTX
• Folic acid is used with pemetrexed & pralatrexate to ⇩ side effects

Hints for Understanding Monoclonal Antibodies in Oncology

Substem Examples Target MOA Common Toxicities

“ci” BevaCIzumab Vascular endothelial Inhibits growth of blood vessels • Inhibition of blood vessel growth → HTN →
CIrculatory RamuCIrumab growth factor Used to treat certain solid tumors proteinuria
System (VEGF) or VEGF such as colon cancer & non-small • Hemorrhage or thrombosis may occur
receptor cell lung cancer (NSCLC) • Impaired wound healing (d/t ⇩ blood flow)

“tu” CeTUximab Epidermal growth Inhibits growth factor from • EGFR → epidermis → skin toxicity (acne
TUmor PaniTUmumab factor receptor binding to the surface of tumor form rash)
(EGFR) cell & promoting cell growth • Development of rash is correlated with
Used to treat certain solid tumors response to therapy
such as colon cancer

“tu” TrasTUzumab Human epidermal Inhibits growth factor from • Cardiotoxicity

TUmor PerTUzumab growth factor binding to the surface of tumor
receptor (HER2) cell & promoting cell growth
Used to treat certain solid tumors
such as breast cancer

“tu” RiTUximab Cluster of Binds to antigens expressed on • CD antigens are expressed on normal &
TUmor BrenTUximab differentiation specific hematopoietic cells & malignant, hematopoietic cells → suppression
(CD20, CD30) causes cell death of specific hematopoietic cells → BMS → ⇧ risk
antigens expressed Used to treat certain hematologic for reactivation of viral infections
on cell surface of malignancies such as non-Hodgkin • BrenTUximab vedotin = antibody-drug
hematopoietic cells lymphoma, Hodgkin lymphoma & conjugate (ADC) – antibody binds to cell →
multiple myeloma enables cytotoxic drug to enter

“li” IpiLImumab Immune system Interferes with body’s ability to • Patient’s immune system becomes overactive
Immune PrembroLIzumab (PD-1, PD-L1, “down-regulate” immune system → potentially life-threatening immune-mediated
System CTLA-4) – results in increased immune reactions such as colitis, hepatic toxicity,
recognition of tumor antigens thyroid dysfunction, myocarditis – requires
Used to treat certain solid tumors steroid treatment
such as NSCLC & melanoma
 Psychiatric Conditions

Depression

Drugs that Can Cause or Worsen Depression

ADHD Medications • Atomoxetine (Strattera)

Analgesics • Indomethacin

Antiretrovirals • Efavirenz (in Atripla) • Rilpivirine (in Complera, Odefsey)

Cardiovascular medications • Beta Blockers (especially propranolol)

Hormones • Hormonal Contraceptives • Anabolic steroids

Other • Antidepressants • Systemic steroids

• Benzodiazepines • Varenicline
• Ethanol • Interferons

Conditions • Stroke • Hypothyroidism

• Parkinson disease • Low vitamin D levels
• Multiple Sclerosis (MS) • Metabolic conditions (ex. hypercalcemia)
• Dementia • Malignancy
• Infectious diseases • Overactive bladder

DSM-5 Criteria for Depression

At least FIVE of the following symptoms are present during the same two week period
Must have 1 of the following 4 additional symptoms

• Depressed mood • Sleep – increased/decreased • Concentration – decreased

• Loss of interest or pleasure • Guilt or feelings of worthlessness • Appetite – increased/decreased
• Energy – decreased • Suicidal ideation
• Psychomotor agitation or retardation

MAO Inhibitors – Keep them Separated

To avoid serotonin syndrome or hypertensive crisis:
Two-week washout is required between MAOI &: SSRIs SNRIs TCAs Bupropion

Five-week washout required when changing from: Fluoxetine → MAO Inhibitor

Selecting the BEST Antidepressant

● Antidepressant selected should incorporate patient-specific information & history
● Did it work? If an antidepressant was taken at a reasonable dose for 4-8 weeks & did not work
well, do not use it again
● Was it well-tolerated? Do not choose a treatment that was poorly tolerated in the past
● Does the patient have comorbid conditions that make a drug a good or poor choice?
 Cardiac/QT Risk Sertraline preferred

• Do not choose a QT prolonging drug/dose

- High doses of citalopram or escitalopram
• Watch for additive QT effects when SSRIs, SNRIs, TCAs, mirtazapine
or trazodone are used with other QT prolonging drugs

Smoker Bupropion SR = FDA-approved for smoking cessation

Peripheral neuropathy or pain Consider Duloxetine

Taking serotonergic antidepressants • Avoid multiple serotonergic agents due to risk of serotonin syndrome
• ⇧ bleed risk with anticoagulants, antiplatelets, NSAIDs, ginkgo,
garlic, ginger, ginseng, glucosamine, fish oils

Seizure disorder/at risk for seizures • Do not use Bupropion

(bulimia/anorexia, recent alcohol or sedative withdrawal)

Pregnant • Do not use Paroxetine

• Mild-moderate depression: psychotherapy = first line
• Severe depression: certain SSRIs are first line
- Citalopram, Escitalopram, Fluoxetine, Sertraline

Daytime Sedation • Do not take sedating drug early in the day

- Paroxetine, Mirtazapine, Trazodone
• Activating medications taken in the morning are preferred
- Fluoxetine, Bupropion

Insomnia • Do not take activating drug later in the day

- Fluoxetine, Bupropion
• Sedating medications taken at night are preferred
- Paroxetine, Mirtazapine, Trazodone

Sexual Dysfunction • High risk: SSRIs & SNRIs

• Lower risk: Bupropion & Mirtazapine

Schizophrenia/Psychosis

Medications/Recreational Drugs that can Increase Psychotic Symptoms

Medications Illicit Substances

• Anticholinergics (centrally-acting, high doses) • Bath salts (synthetic cathinones, MDPV)

• Dextromethorphan • Cannabis
• Dopamine or dopamine agonists (Requip, Mirapex, Sinemet) • Cocaine, especially crack
• Interferons • Lysergic acid diethylamide (LSD, hallucinogenics)
• Stimulants, especially if already at risk (includes amphetamines) • Methamphetamine, ice, crystal
• Systemic steroids (typically with lack of sleep – ICU psychosis) • Phencyclidine (PCP)
 Selecting an Antipsychotic
● Based on several considerations, including PMH & side effects
● SGAs have metabolic side effects – weight gain, ⇧ cholesterol, ⇧ TGs ⇧ BG
○ Drugs with higher metabolic risks should be avoided in Diabetes & CV disease
● Some SGAs can also cause dose-related EPS
● Prolactin levels can ⇧, causing gynecomastia, galactorrhea, sexual dysfunction & amenorrhea
● Clozapine has highest efficacy but multiple warnings (agranulocytosis, seizures, myocarditis)
○ Can be tried after failure with at least 2 other antipsychotics (at least 1 SGA)
Metabolic syndrome – EPS ⇧ Prolactin levels QT prolongation
⇧ weight, ⇧ BG, ⇧ lipids

Highest • Olanzapine (Zyprexa) • FGAs • FGAs • Thioridazine

Risk • Quetiapine (Seroquel) • Paliperidone - ⇧ doses • Paliperidone • Haloperidol
• Paliperidone (Invega) • Risperidone - ⇧ doses • Risperidone • Chlorpromazine
• Risperidone (Risperdal) • Ziprasidone
• Clozapine - myocarditis
& cardiomyopathy

Some risk ⇧ weight • Aripiprazole - children • Aripiprazole

• Clozapine (Clozaril) • Lurasidone - dystonias • Paliperidone
• Brexpiprazole (Rexulti) • Ziprasidone • Risperidone
• Asenapine • Asenapine
• Cariprazine (Vraylar) • Iloperidone (Fanapt)
• Lumateperone (Caplyta)

Lowest • Aripiprazole (Abilify, Aristada) • Quetiapine – preferred • Lurasidone

Risk • Ziprasidone (Geodon) • Olanzapine • Olanzapine
• Lurasidone (Latuda) • Quetiapine
• Asenapine (Saphris, Secuado) • Cariprazine (Vraylar)
• Lumateperone (Caplyta)

Antipsychotic Treatment Considerations

When assessing treatment resistance or evaluating the best option for a partial response, it is important to
evaluate whether the patient’s had an adequate trial (6 weeks min), including whether the dose is
adequate & whether the patient has been taking the medication has prescribed
Did it work (ex. quieted voices down) & was it • If drug was being taken & did not work well, do not use it again
well tolerated? • Do not choose a treatment that was poorly tolerated in past
- Painful dystonia or TD with Haloperidol
- Painful gynecomastia with Paliperidone, Risperidone

Cardiac risk/QT prolongation risk • Do not choose a QT prolonging drug

- Ziprasidone, Haloperidol, Thioridazine, Chlorpromazine

History of movement disorder (ex. Parkinson) • Do not choose a drug with high risk of EPS
- FGAs, Paliperidone, Risperidone (with higher doses)

• Quetiapine = preferred

Overweight/metabolic risks • Do not choose a drug that worsens metabolic issues

(ex. ⇧ TGs) - Olanzapine, Quetiapine

• Lower risk: Aripiprazole, Ziprasidone, Lurasidone & Asenapine

Nonadherence or experiencing homelessness • Choose long-acting injection (see below)

 STAT! • Haloperidol (Haldol) IV or IM
Acute psychosis (and refusing PO meds) - Sometimes in combo with lorazepam + diphenhydramine
• Alternatives:
- Ziprasidone (Geodon) – IM
- Olanzapine (Zyprexa) – IM

Chronic Treatment: • Long acting IM-injection

- Paliperidone (Invega Hafyera) – Q6 months
Not adherent to daily PO treatment or swallowing - Paliperidone (Invega Trinza) – Q3 months
difficulties - Aripiprazole lauroxil (Aristada) – Q4-8 weeks
- Paliperidone (Invega Sustenna) – Q4 weeks
- Aripiprazole (Abilify Maintena) – Q4 weeks
- Haloperidol (Haldol Decanoate) – Q4 weeks
- Olanzapine (Zyprexa Relprevv) – Q2-4 weeks
- Risperidone (Risperdal Consta) – Q2 weeks
- Fluphenazine decanoate – Q2 weeks

• ODT (not adherent or difficulty swallowing)

- Aripiprazole (Abilify) – ODT
- Olanzapine (Zyprexa Zydis) – ODT
- Risperidone ODT
• Sublingual
- Asenapine (Saphris) – No food/drink for 10 min
• Oral liquids
- Aripiprazole (Abilify)
- Fluphenazine
- Haloperidol
- Risperidone (Risperdal)
• Patch
- Asenapine (Secuado)

Chronic Treatment: • FGA or SGA oral tablets (or other formulations)

Adherent to daily PO treatment

Failure with 2 or more antipsychotics • Clozapine (Clozaril) – tablet

• Clozapine (Versacloz) – suspension
 Bipolar Disorder

DSM-5 Criteria for Bipolar Disorder – What is mania?

Definition

Abnormally elevated or irritable mood for at least a week (or any duration if hospitalization is needed)

Symptoms

• Inflated self-esteem • Needs less sleep

• More talkative than normal • Jumping from topic to topic
• High-risk, pleasurable activities • Easily distracted
- Ex. buying sprees, sexual indiscretions, gambling • Increase in goal-directed activity

Diagnosis

• Exhibits > 3 symptoms

• If mood is only irritable, exhibits > 4 symptoms

Lithium Conversions
● 5 mg lithium citrate syrup = 8 mEq of lithium ion
● 8 mEq of lithium ion = 300 mg lithium carbonate tablets/capsules

Example: A patient is taking 450 mg of lithium carbonate BID, but reports difficulty swallowing capsules.
How many mL of lithium citrate syrup should be given for each dose? (Round to nearest tenth).
● Determine how many mEq of lithium are required for each dose.
300 𝑚𝑔 𝑙𝑖𝑡ℎ𝑖𝑢𝑚 𝑐𝑎𝑟𝑏𝑜𝑛𝑎𝑡𝑒 450 𝑚𝑔 𝑙𝑖𝑡ℎ𝑖𝑢𝑚 𝑐𝑎𝑟𝑏𝑜𝑛𝑎𝑡𝑒
8 𝑚𝐸𝑞 𝑙𝑖𝑡ℎ𝑖𝑢𝑚 𝑖𝑜𝑛
= 𝑋 𝑚𝐸𝑞 𝑙𝑖𝑡ℎ𝑖𝑢𝑚 𝑖𝑜𝑛
→ X = 12 mEq lithium ion

● Next, determine how many mL of lithium citrate syrup are required.

12 𝑚𝐸𝑞 8 𝑚𝐸𝑞
𝑋 𝑚𝐿
= 5 𝑚𝐿 → X = 7.5 mL of lithium syrup per dose

Attention Deficit Hyperactivity Disorder (ADHD)

Treatment of ADHD
Stimulants are first line • Methylphenidate (Concerta, Daytrana, Ritalin)
Take in the morning - Jornay PM = taken in evening
• Lisdexamfetamine (Vyvanse)
• Dextroamphetamine/amphetamine (Adderall, Adderall XR)

Non-stimulants are second line • Atomoxetine (Strattera)

Take if risk of abuse

Add-on medications • Guanfacine ER (Intuitiv)

Can also be used alone • Clonidine ER (Kapvay)

To help sleep at night • Clonidine IR (Catapres)

• Diphenhydramine (OTC, 25-50 mg)
• Melatonin (OTC, 2-5 mg)
 Patient-friendly formulations for stimulants
● Young children (& others) who cannot swallow capsules or tablets can use alternative
long-acting formulations or capsules that can be opened
○ When putting capsule content in food, use a small amount of food (do not warm the
food), eat the food right away; do not chew the beads
Capsule Some capsule contents can be sprinkled on a small amount of applesauce
- Ex. Adderall XR, Ritalin LA
Vyvanse capsule contents can be mixed in water, orange juice or yogurt

Chewable tablet Vyvanse, QuilliChew ER

ODT Cotempla XR- ODT, Adzenys XR-ODT (ER), Evekeo ODT (IR)

Patch Daytrana, Xelstrym

Suspensions Quillivant XR, Dyanavel XR

Anxiety Disorders

Drugs That Cause Anxiety

• Albuterol (used too often or incorrectly) • Bupropion • Illicit drugs (cocaine, LSD, etc.)
• Antipsychotics (aripiprazole, haloperidol) • Caffeine (high doses) • Levothyroxine (if therapeutic OD)
• Stimulants (Amphetamine, Methylphenidate) • Theophylline • Steroids
• Decongestant (ex pseudoephedrine)

Safe Use of Benzodiazepines

BZDs are highly sedating & often not preferred due to safety concerns
Anxiety • Most anxiety is due to depression – SSRIs & SNRIs are preferred

• If used, consider a BZD with a longer half-life & less risk of abuse
- Clonazepam, Lorazepam, Diazepam

Sleep • First-line: non-pharmacologic treatment

• Second-line: non-BZD hypnotics – like zolpidem (fewer safety issues than BZDs)

• If used, consider Temazepam

Elderly or Patients with • If used, consider BZDs that undergo glucuronidation

Liver Impairment - L-O-T drugs – Lorazepam, Oxazepam, Temazepam

Seizures • Injectable BZDs or Diazepam rectal gel (Diastat AcuDial)

- Diazepam rectal gel can be administered by a caregiver at home
 Sleep Disorders

Drugs that can WORSEN Insomnia

• Acetylcholinesterase inhibitors • Atomoxetine • Fluoxetine
- (ex. donepezil) • Bupropion - If taken too late in day
• Alcohol • Caffeine • Steroids
• Antiretrovirals (ex. Emtricitabine, INSTIs) • Decongestants • Stimulants
• Aripiprazole • Diuretics (due to nocturia) • Varenicline

Chronic Insomnia NOTE***

Eszopiclone & Zolpidem = used in all three groups
Help falling asleep Help staying asleep Help falling AND staying asleep

Neurologic Conditions

Parkinson Disease

Parkinson Disease Symptoms

Pathophysiology:
Less dopamine → less instructions to the brain → movement problems (called the TRAP symptoms)
TRAP Symptoms Additional Symptoms

• Tremor when resting • Small, cramped handwriting

• Rigidity in legs, arms, trunk & face (mask-like face) • Shuffling walk, stooped posture
• Akinesia/bradykinesia – lack of/slow start in movement • Depression, anxiety (psychosis in advanced disease)
• Postural instability – imbalance, falls • Constipation, incontinence
● Tremor is often the first noticeable symptom & usually starts in one hand or foot (on just one side,
unilateral) & eventually spreads to both sides
● Resting tremor means it appears when hand isn’t moving

Dopamine Blocking Drugs that can Worsen PD

● Phenothiazines (ex. prochlorperazine) used for psychosis, nausea, agitation
● Butyrophenones (haloperidol, droperidol) used for psychosis & behavior disorders or nausea
● First & second-gen antipsychotics (risperidone at higher doses, paliperidone)
● Metoclopramide (a renally-cleared drug that can accumulate in elderly patients)

PD Treatment Principles
● Primary Treatment: replace dopamine
○ Give precursor to dopamine that becomes DA in the brain (that’s levodopa in Sinemet)
○ Give a dopamine agonist that acts like dopamine
○ Give other drugs for specific symptoms (ex. benztropine for resting tremor)
 Alzheimer’s Disease

Key Drugs that Worsen Dementia

• Antiemetics • Barbiturates • Peripheral anticholinergics
- Promethazine - Phenobarbital, Butalbital - Including incontinence & IBS drugs
• Antihistamines • Benzodiazepines • Skeletal muscle relaxants
- Diphenhydramine, Doxylamine - Alprazolam, Clonazepam - Baclofen
• Antipsychotics • Central Anticholinergics • Other CNS depressants
- Chlorpromazine, Aripiprazole - Benztropine - Opioids, sedative hypnotics

Seizures/Epilepsy

Drugs that can LOWER the seizure threshold

• Bupropion • Varenicline • Meperidine ★ • Quinolones ★
• Clozapine • Carbapenems (especially imipenem) ★ • Penicillins ★ • Tramadol ★
• Theophylline • Lithium ★
★ = high doses & renal impairment increases risk

Diastat Acudial Dispensing

Given to patients who are at risk of long-lasting seizures – not usually in urgent medical care (facility)
Each package contains two rectal syringes prefilled with diazepam rectal gel
● Syringes MUST be dialed to the right dose & locked BEFORE DISPENSING
○ Syringes come in 2.5, 10 & 20 mg
Pharmacist instructions for locking in the dose are included on a card in the package:
Hold the barrel of the syringe in one hand with the cap facing down & the dose window visible
Do not remove the cap

Use the other hand to grab the cap firmly & turn to adjust the dose

Confirm the correct dose shows in the window – hold the locking ring at the bottom of the syringe barrel &
push upward to lock both sides of the ring

Repeat these steps with the second syringe in the case

● Once locked, the green band should say “READY,” & the syringe cannot be unlocked
● When counseling, check both syringes with the patient before they leave the pharmacy to ensure
they are dialed & locked

Lamictal Starter Kits By Color

● Lamotrigine doses need to be just right
○ Too much leads to a higher risk of severe rash
○ Too little leads to seizures
● The colorized starter kits are helpful to make sure the right dose is selected
Orange Blue Green

• Standard starting dose • Lower starting dose • Higher starting dose

• Use if no interacting medications • Use if taking valproic acid • Use if taking an enzyme inducer:
- Carbamazepine, phenytoin, phenobarbital,
primidone (and not taking valproic acid)
 Phenytoin/Fosphenytoin Administration
IV Phenytoin • Do not exceed 50 mg/min (slow infusion)
• Monitor BP, respiratory function & ECG
• Requires a filter
• Dilute in NS, stable for 4H, do not refrigerate

NG-tube Phenytoin • Enteral feedings (tube feeds) ⇩ phenytoin absorption

• Hold feedings 1-2H before & after administration

IV FOSphenytoin • Do not exceed 150 mg PE/min

• Monitor BP, respiratory function & ECG
• Lower risk of purple glove syndrome than phenytoin

AED Cousins
Some AEDs have “family members” with similar side effects & safety considerations
Carbamazepine, Oxcarbazepine & • Hyponatremia, Rash
Eslicarbazepine • Enzyme induction

Gabapentin & Pregabalin • Weight gain, Peripheral edema, Mild euphoria

• Used mainly for neuropathic pain

Phenobarbital & Primidone • Sedation, Dependence/Tolerance/OD risk

• Enzyme induction

Topiramate & Zonisamide • Weight loss, Metabolic acidosis

• Nephrolithiasis & oligohidrosis / hyperthermia (in kids)

Adjusting Phenytoin Doses

● Phenytoin has Michaelis-Menten Kinetics (saturable kinetics)
● If the enzymes have become saturated, a small ⇧ in dose can cause a large ⇧ in drug level
● If albumin is low (< 3.5 g/dL), & CrCl > 10, adjust the total level with this formula:
𝑇𝑜𝑡𝑎𝑙 𝑝ℎ𝑒𝑛𝑦𝑡𝑜𝑖𝑛 𝑚𝑒𝑎𝑠𝑢𝑟𝑒𝑑
𝑃ℎ𝑒𝑛𝑦𝑡𝑜𝑖𝑛 𝑐𝑜𝑟𝑟𝑒𝑐𝑡𝑖𝑜𝑛 = (0.2 𝑥 𝑎𝑙𝑏𝑢𝑚𝑖𝑛) + 0.1
● Free levels do not require correction

Select AEDs with Enzyme induction or inhibition

Enzyme Inducers Enzyme Inhibitor

● Carbamazepine ● Fosphenytoin ● Valproic acid (⇧ lamotrigine)

● Oxcarbazepine ● Phenobarbital
● Phenytoin ● Primidone

Vitamins on AEDs
Supplement with:
● All AEDs: calcium & vitamin D
● Women of childbearing age: folate
● Valproic acid: possibly carnitine
● Lamotrigine & Valproic acid: if alopecia develops, supplement with selenium & zinc
 Gastrointestinal Conditions

Gastroesophageal Reflux Disease & Peptic Ulcer Disease

Drugs that can WORSEN GERD symptoms

ASA/NSAIDs Estrogen products Nicotine replacement therapy

Bisphosphonates Fish oil products Steroids

Dabigatran Iron supplements Tetracyclines

H2RA & PPI Formulations to Know

OTC ODT PO Solution/Suspension Injection

H2RA Cimetidine Cimetidine Famotidine

Famotidine Famotidine
Nizatidine

PPI Esomeprazole Lansoprazole Lansoprazole Esomeprazole

Lansoprazole Omeprazole Packets for suspension Pantoprazole
Omeprazole Esomeprazole
Omeprazole
Pantoprazole

Drugs with Decreased (⇩) Absorption with GERD Medications

Drugs that require an acidic gut Oral drugs/drug classes that antacids bind
(absorption ⇩ by antacids, H2RAs & PPIs)

• Antiretrovirals: Rilpivirine (NNRTI), Atazanavir (PI) • Antiretrovirals: INSTIs – Bictegravir, Elvitegravir,

• Antivirals: Ledipasvir, Velpatasvir/Sofosbuvir (Epclusa) Dolutegravir, Raltegravir
• Azoles: Sporanox (Itraconazole capsules), Ketoconazole • Bisphosphonates
- Posaconazole PO suspension – H2RAs & PPIs only • Isoniazid
• Cephalosporins (PO): Cefpodoxime, Cefuroxime • Levothyroxine
• Iron products • Mycophenolate
• Mesalamine • Quinolones
• Risedronate DR (Atelvia) • Sotalol
• Tyrosine kinase inhibitors: Dasatinib, Erlotinib, Pazopanib • Steroids (especially Budesonide)
• Tetracyclines

Constipation & Diarrhea

Drugs that cause constipation

• Antacids (aluminum & calcium-containing) • Drugs with anticholinergic effects:
• Antidiarrheals - Antihistamines (Diphenhydramine)
• Clonidine - Antispasmodics (Baclofen)
• Colesevelam - Phenothiazines (Prochlorperazine)
• Iron - TCAs (Amitriptyline)
• Opioids - Incontinence drugs (Oxybutynin)
• Sucralfate (contains aluminum complex) • Non-DHP CCBs (especially verapamil)
 Which OTC to Recommend for Constipation
Most adults Pregnancy Iron-induced OIC Fast relief – Adults Fast relief – Kids

Fiber/Psyllium Fiber/Psyllium Stool softener Stimulant Bisacodyl or Glycerin suppository

(Metamucil) (Metamucil) (docusate) or (senna, bisacodyl) or Glycerin suppository
Bulk forming laxatives Osmotic (PEG)

Drugs that cause diarrhea

• Acetylcholinesterase inhibitors (donepezil) • Colchicine
• Antacids containing magnesium • Drugs used for constipation (laxatives)
• Antibiotics (broad-spectrum) • Misoprostol
- May also be infectious – C. difficile • Mycophenolate
• Antidiabetics (metformin, GLP-1 agonists) • Prokinetic drugs (metoclopramide, cisapride)
• Antineoplastics • Protease Inhibitors (especially nelfinavir)
- Irinotecan, Capecitabine, Fluorouracil, • Roflumilast
Methotrexate, TKIs • Quinidine

Inflammatory Bowel Disease

Maintenance of remission
CD UC

Mild disease Oral budesonide for < 3 months Mesalamine (5-ASA) rectal and/or oral
After this treatment, DC or change to preferred
thiopurine or methotrexate

Anti-TNF agents Anti-TNF agents

• Adalimumab (Humira) • Adalimumab (Humira)
Moderate/severe disease • Infliximab (Remicade) • Infliximab (Remicade)
• Certolizumab (Cimzia) • Golimumab (Simponi)

Thiopurine (azathioprine, mercaptopurine) Thiopurine (azathioprine, mercaptopurine)

Methotrexate Cyclosporine

Ustekinumab (Stelara) Ustekinumab (Stelara)

Refractory to treatments Integrin receptor antagonists Integrin receptor antagonists

and/or steroid dependent • Vedolizumab (Entyvio) • Vedolizumab (Entyvio)
• Natalizumab (Tysabri)
Janus kinase inhibitor
• Tofacitinib (Xeljanz)
 Motion Sickness

Scopolamine (Transderm Scop) Counseling

For N/V due to motion sickness or anesthesia/surgery
● Apply at least 4 hours before needed or the night before surgery
● Press firmly to skin behind ear for 30 seconds
● Try to avoid placing the patch over hair, or when the patch is removed, hair may be removed too
● Lasts 3 days – if continued treatment needed, remove & place a new patch behind other ear
● Wash hands after applying
Do NOT drive; high level of drowsiness, dizziness & confusions
- These anticholinergic side effects are worse & not well-tolerated in elderly (avoid when possible)

Pharmacy Foundations Part 2

Medication Safety & Quality Improvement

Common Methods to Reduce Medication Errors

DO NOT USE Potential Problem Use Instead

U, u (unit) Mistaken for “0”, the number “4”, or cc Write “unit”

IU (international unit) Mistaken for IV or the number “10” Write “international unit”

Q.D, QD, q.d., qd (daily) Mistaken for each other Write “daily”
Q.O.D, QOD, q.o.d., qod (every other day) Period after the Q mistaken for “I” and Write “every other day”
the “O” mistaken for “I”

Trailing zero (X.0 mg) Decimal point is missed resulting in a Write X mg

Lack of leading zero (.X mg) 10-fold dosing error Write 0.X mg

MS Can mean morphine sulfate or Write “morphine sulfate”

magnesium sulfate
MSO4 and MgSO4 Confused with one another Write “magnesium sulfate”

High-Alert Medications
Drugs with a heightened risk of causing significant patient harm if used in error
Anesthetics, inhaled or IV (ex. propofol) Insulins

Antiarrhythmics IV (ex. amiodarone) Magnesium sulfate injection

Anticoagulants/antithrombotics (ex. heparin, warfarin) Neuromuscular blocking agents (ex. Vecuronium)

Chemotherapeutics (ex. methotrexate) Opioids

Epidural/intrathecal drugs Oral hypoglycemics (ex. sulfonylureas)

Hypertonic saline (> 0.9% NaCl) Parenteral nutrition

Immunosuppressants (ex. cyclosporine) Potassium chloride & Phosphate for injection

Inotropes (ex. digoxin) Sterile water for injection

 Safe Injection Practices
Never administer an oral solution/suspension intravenously – fatal errors have occurred
- Use PO syringes (difficult or impossible to attach to a needle for IV injection) & label PO syringes “For ORAL Use Only”

Never reinsert used needles into a MDV or solution container

- SDV are preferred, especially when medications will be administered to multiple patients

Needles used for withdrawing blood or any other bodily fluid, or used for administering medications or other fluids should preferably
have “engineered sharps protection” which reduces the risk of an exposure incident by a mechanism such as drawing the
needle into the syringe barrel after use

Never touch the tip or plunger of a syringe

Disposable needles that are contaminated should never be removed from their original syringes, unless there is no other option
- Throw the entire needle/syringe assembly (needle attached to the syringe) into red plastic sharps container

Immediately discard used disposable needles or sharps into a sharps container without recapping

Sharps containers should be easily accessible & not allowed to overfill – they should be routinely replaced

Drug Allergies & Adverse Drug Reactions

Intolerance or allergy?
Gather enough information to determine the type of reaction
Example: A patient reports getting a stomach ache from varenicline
Scenarios:
- I did not eat anything until dinner because varenicline made me nauseous (intolerance)
- I got nauseous, felt dizzy & had trouble breathing (allergy)
Intolerances
● Less serious complaints, such as nausea or constipation
● Since the drug bothers the patient, it should be avoided, if possible
Allergies
● An immune system response & range from mild (ex. pruritus) to severe (ex. anaphylaxis)
● Can present in different ways, example:
○ Facial swelling, bronchoconstriction and/or drop in BP
○ Weakness, fever & rash

Drugs Most Associated with Photosensitivity

Amiodarone PO & topical retinoids Quinolones Sulfa drugs Tetracyclines

Methotrexate Diuretics (thiazide & loops) St. John’s wort Tacrolimus Voriconazole

Drugs Most Associated with Severe Cutaneous Adverse Reactions

Allopurinol Carbamazepine Lamotrigine Sulfasalazine Nevirapine

Amoxicillin, Ampicillin Phenytoin Ethosuximide Vancomycin Sulfamethoxazole

 Counseling Points for Epinephrine Auto-Injectors
EpiPen • Remove from the carrying case & pull off the blue safety release
• Keep thumb, fingers & hand away from the orange (needle) end of the device
• Inject into the middle of the outer thigh at a 90 degree angle
• Hold the needle firmly in place while counting to 3
• Remove the needle and massage the area for 10 seconds
• After the injection, the orange tip will extend to cover the needle
- If the needle is visible, it should not be reused

All epinephrine • It is normal to see liquid remaining in the device after injecting
auto-injectors • Call for emergency help because additional care may be needed
• A second dose (in the opposite leg) may be given, if needed, prior to arrival of medical help
• Refrigeration is not required
• All products can be injected through clothing
• Check the device periodically to make sure the medication is clear & not expired

A Penicillin Allergy or Not?

● Although 10% of people report a penicillin “allergy,” the CDC reports the true incidence of
IgE-mediated (type I hypersensitivity) reactions to penicillin as < 1%
● When a “penicillin allergy” is reported, other broad-spectrum antibiotics are often used, which
increases resistance, cost & possible side effects
● When allergies are disproven (by skin testing or by comprehensive allergy history review), the
allergy label in the medical record should be removed.
For immediate-type reactions (ex. anaphylaxis), a skin test can assess the risk:
● Patients with a negative result should be given a PO drug “challenge” dose before full
treatment dose
● Patients with a positive test should avoid use of the drug
○ Remember: penicillin is the only acceptable treatment or pregnant or non-adherent
patients with syphilis – if a skin test is positive, desensitize & administer penicillin
● Skin testing should not be performed for severe cutaneous adverse reactions (SJS/TEN)
Many cephalosporins can be safely tolerated in patients with a mild penicillin allergy.
- In Acute Otitis Media (AOM) patients with an allergy to penicillin/amoxicillin, give:
- Cefdinir, cefpodoxime, ceftriaxone or cefuroxime

Pharmacokinetics

Drug Absorption
Drug
↙↘

Oral IV
↓ ↓
Stomach ↓
↓ ↓
Small Intestine ↓
Enterohepatic recycling ↱ ↓ ↓

Liver → Systemic Circulation

 Dose adjustments for Michaelis-Menten Kinetics
● Most drugs follow first-order (linear) kinetics
○ At SS, doubling the dose approximately doubles the serum concentration
● Some drugs (phenytoin, theophylline & voriconazole) follow Michaelis-Menten (non-linear,
saturable or mixed-order) Kinetics
○ Doubling the dose of these drugs can more than double the serum concentration
■ Using a proportion to calculate a new dose is not appropriate
■ Dosing adjustments must be made cautiously to avoid toxicity
● Phenytoin should be adjusted in 30-50 mg increments

Pharmacogenomics

Does a Positive or Negative Test Require Action?

AVOID the drug when these pharmacogenomic tests are POSITIVE
● HLA-B: positive test indicates ⇧ risk of hypersensitivity
● KRAS mutation: positive test (often called “KRAS mutant”) predicts poor response
AVOID the drug when these pharmacogenomic tests are NEGATIVE
● HER2 expression: negative result indicates poor response

Drugs that Require Testing (or are strongly recommended)

● Abacavir & abacavir-containing drugs (Triumeq, Epzicom) (HLA-B*5701)
● Carbamazepine (HLA-B*1502)
● Azathioprine (TPMT)
● Cetuximab & other EGFR inhibitors (KRAS)
● Trastuzumab & other HER2 inhibitors (HER2 gene)

Dietary Supplements, Natural & Complementary Medicine

Differences Between Dietary Supplements & Drugs

● Supplement safety is the manufacturer’s responsibility, which should be proven prior to release
● After release, the FDA can remove a supplement if it is found to be unsafe
○ In contrast, drugs must be proven safe & EFFECTIVE to FDA prior to release
● Supplements cannot claim to treat, cure or mitigate (lessen) a condition (ex. ‘Melatonin treats
insomnia’ is not appropriate)
○ In contrast, drug claims are based on FDA approval (ex. ‘Zolpidem treats insomnia’ is
appropriate)
Supplements • The Supplement Facts label is similar to the label required on food products
- Includes ingredients, quantities, serving size, servings/container, calories, calories from
fat, total fat, saturated fat, cholesterol, sodium, carbohydrates, dietary fiber, sugars,
protein, vitamin A, vitamin C, calcium & iron
- Calcium & iron only when present in measurable amounts

OTC Drugs • The OTC Drug Facts label includes:

- Ingredients, purpose, uses, warnings, instructions, excipients & allergic reaction alerts/warnings
• OTC drugs can include a package insert similar to prescription drugs
- Depends on the product’s approval process

Prescription Drugs • Much more detailed information – in package insert

 Toxicology & Antidote

N-acetylcysteine (NAC) Treatment

● N-acetylcysteine (Acetadote) mechanism: free radical scavenger & precursor to glutathione
(GSH), ultimately increasing GSH
○ GSH converts to NAPQI to mercapturic acid which can be safely excreted
● Treatment: use the Rumack-Matthew nomogram to determine need for NAC (IV or oral)
○ Oral NAC (using injectable or inhalation solution): high dose given one, then lower dose
for 17 doses – repeat the dose if emesis occurs within 1H of administration
○ IV NAC: three infusions over a total of 21H

Organophosphate Overdose
SLUDD Symptoms Treatment Causes

• Salivation • Atropine: blocks the effects of ACh Organophosphates include pesticides

• Lacrimation • Pralidoxime (Protopam): reactivates cholinesterase
• Urination • Atropine & Pralidoxime: may be used in combination People working on farms are at risk
• Diarrhea (DuoDote)
• Defecation

Overdose? Mixed Overdose? Matching Symptoms to the Antidote

In OD situations, it is not always known what substance was taken or if it was more than one substance
- Symptoms & labs (toxidromes) guide the treatment until more information is known
Possible Actions
● Always treat the most life-threatening overdose first (substance causing impair ABCs)
○ Somnolence, shallow labored breathing or pinpoint pupils could be an opioid OD
■ Naloxone should be administered
○ If opioids & APAP were both ingested, naloxone is given first
● Check an acetaminophen level & use the Rumack-Matthew nomogram to determine if NAC
should be given
● Check glucose levels & if hypoglycemic, give dextrose injection or (if a family member is
providing) can inject glucagon
○ Oral carbohydrates can be given if alert & conscious
● Tachycardia, seizures or severe agitation can be from multiple causes – give benzodiazepines
● QT prolongation can be caused by TCAs
○ Check ECG & give sodium bicarbonate if QRS is widened