MODULE 4

PHARMACOLOGY, TOXICOLOGY,
BIOPHARMACEUTICS & PHARMACOKINETICS

RIZZA A. CALUAG
PERIPHERAL NERVOUS SYSTEM
• PERIPHERAL NERVES
• collection of nerves and ganglia scattered throughout the brain
• consist of 12 pairs of cranial nerves, 31 pairs of spinal nerve and
their branches to the entire body
CRANIAL NERVES:
I. OLFACTORY NERVE
II. OPTIC NERVE
III. OCCULOMOTR NERVE - Oh, Oh, Oh, To Touch And Feel Virgin Girl’s
IV. TROCHLEAR NERVE Vagina, Ah! So Heavenly
V. TRIGEMINAL NERVE
VI. ABDUCENS NERVE
VII. FACIAL NERVE
VIII. AUDITORY OR VESTIBULOCOCHLEAR NERVE MAJOR DIVISIONS OF PNS:
IX. GLOSSOPHARYNGEAL NERVE ▪SOMATIC
X. VAGUS NERVE
XI. SPINAL ACCESSORY NERVE ▪AUTONOMIC
XII. HYPOGLOSSAL NERVE
▪ ENTERIC
AUTONOMIC NERVOUS SYSTEM
SYMPATHETIC PARASYMPATHETIC
Major NE ACh
Neurotransmitter
Receptors Alpha, Beta, Dopamine Muscarinic, Nicotinic
Major Response Fight, Fright, Flight Rest and Digest
Origin Thoracolumbar Cranio (III,VII,IX,X)-sacral (III,IV)
Neurotransmitter
- Preganglionic - ACh - ACh
- Postganglionic - NE - ACh
Length of fibers
- Preganglionic - Short - Long
- Postganglionic - Long - Short
AUTONOMIC NERVOUS SYSTEM
SYMPATHETIC PARASYMPATHETIC
Organ effects:
• Eyes Mydriasis Miosis
• Heart Inc. HR, CO, BP (+++) Dec. HR, CO, BP (---)
• Lungs Bronchodilation Bronchoconstriction
• Urine output Urinary Retention Urination
• Motility Constipation Diarrhea
Ejaculation Erection
SYMPATHETIC NERVOUS SYSTEM
1. Synthesis
• (-) metyrosine
2. Storage
• (-) reserpine
3. Release
• (-) Bretylium,
Guanethidine
4. Receptor binding
5. Removal
1. Diffusion
2. Metabolism
3. Reuptake
SYMPATHETIC NERVOUS SYSTEM
RECEPTORS LOCATION EFFECTS
• Alpha-1 Blood vessels Vasoconstriction
Eyes Mydriasis (ciliary muscle constriction)
Sphincter Constriction – urinary retention
Penis/seminal vesicles Ejaculation
Agonists Antagonists
Nonselective Dipivefrin Irreversible
- Phenoxybenzamine
- prodrug of EPI; for glaucoma
Reversible
- Phentolamine, Tolazoline

Selective Phenylphrine “-ZOSINS”

Phenylpropranolamine
Xylometazoline
Oxymetazoline
Midodrine
Methoxamine
SYMPATHETIC NERVOUS SYSTEM
RECEPTORS LOCATION EFFECTS
• Alpha-2 Neurons (CNS) Inhibition of NE release
Platelets Aggregation
Fat cells Inhibition of Lipolysis

Agonists Antagonists
Nonselective Dipivefrin Irreversible
- Phenoxybenzamine
- prodrug of EPI; for glaucoma
Reversible
- Phentolamine, Tolazoline

Selective Clonidine Yohimbine

Methyldopa
Guanfacine
Guanabenz
SYMPATHETIC NERVOUS SYSTEM
RECEPTORS LOCATION EFFECTS
• Beta-1 Heart Increased HR (chronotropic); Inc. force of
contraction (Inotropic); Inc. conduction
velocity (dromotropic)
Kidneys Increase renin secretion

Agonists Antagonists
Nonselective Isoproterenol All “-OLOL” not starting with BEAM

Selective Dobutamine “-OLOL” BEAM

SYMPATHETIC NERVOUS SYSTEM
RECEPTORS LOCATION EFFECTS
• Beta-2 Lungs Bronchodilation
Uterus Tocolytic effect
Bladder Relaxation – urinary retention
Liver Increase glycogenolysis
Agonists Antagonists
Nonselective Isoproterenol All “-OLOL” not starting with
BEAM
Selective “-terol” NONE
SYMPATHETIC NERVOUS SYSTEM
RECEPTORS LOCATION EFFECTS
• Beta-3 Fat cells Increase Lipolysis
SYMPATHETIC NERVOUS SYSTEM
RECEPTORS LOCATION EFFECTS
• Dopa-1 Renal Blood Vessels Vasodilation

Agonists Antagonists
Nonselective Dopamine
Selective Fenoldopam
SYMPATHETIC NERVOUS SYSTEM
RECEPTORS LOCATION EFFECTS
• Dopa-2 Neurons (CNS) Increase Dopamine release

Agonists Antagonists
Nonselective Dopamine
Selective Bromocriptine Antipsychotics
PARASYMPATHETIC NERVOUS SYSTEM
1. Synthesis
• (-) Hemicholinium
2. Storage
• (-) Vesamicol
3. Release
• (-) Botox
4. Receptor binding
5. Removal
1. Diffusion
2. Metabolism
3. Reuptake
PARASYMPATHETIC NERVOUS SYSTEM
RECEPTOR LOCATION EFFECT
M-1 Upper GIT Acid secretion
Cholinergic nerves Stimulation
M-2 Heart (-) inotropic, chronotropic, dromotropic
Cholinergic nerves Stimulation
M-3 Exocrine Glands (salivary, Increase secretions (salivation,
sweat, lacrimal, bronchial, lacrimation, etc.)
intestinal, etc) Bronchoconstriction
Increase motility~diarrhea
Miosis

D- IARRHEA
U- RINATION
M- IOSIS
B- RADYCARDIA
B-RONCHOCONSTRICTION
E- MESIS/ EXCITATION
L- ACRIMATION
S-ALIVATION/ SWEATING
PARASYMPATHETIC NERVOUS SYSTEM
RECEPTOR LOCATION EFFECT
Nm Neuromuscular endplate Muscle contraction
Nn CNS ganglia CNS Stimulation
 PARASYMPATHETIC AGONISTS

DIRECT-ACTING INDIRECT-ACTING

CHOLINE ESTERS ALKALOIDS REVERSIBLE IRREVERSIBLE

ALCOHOL CARBAMATES ORGANOPHOSPHATES

1. Acetylcholine 1. Pilocarpine
2. Bethanechol 2. Muscarine
3. Methacholine 3. Nicotine
4. Carbachol

EDROPHONIUM ‘-tigmines” ‘-phates

PARASYMPATHETIC NERVOUS SYSTEM

CHOLINOCEPTOR ANTAGONIST

MUSCARINIC Antagonist NICOTINIC Antagonist

Red as a beet
Hot as hell
Dry as a bone Ganglion Neuromuscular
Blind as bat
Mad as hatter blockers junction blockers
 ANTI-ULCER DRUGS
• H-2 BLOCKERS
– Cimetidine, Ranitidine, Famotidine, Nizatidine
• PROTON PUMP INHIBITORS
– Omeprazole, Lansoprazole, “-prazoles”
• ANTACIDS
– NaHCO3, NaCO3
• SUCRALFATE
• BISMUTH
– HELIDAC Bismuth subsalicylate, tetracycline and metronidazole
• MISOPROSTOL
 NSAIDs

Drug Classes: Examples

propionic acid derivative ibuprofen
pyrrolealkanoic acid derivative tolmetin
phenylalkanoic acid derivative flubiprofen
indole derivative indomethacin
pyrazolone derivative phenylbutazone
phenylacetic acid derivative diclofenac
Fenamate meclofenamate acid
Oxicam piroxicam
naphthylacetic acid prodrug nabumetone
Salicylate ASA
 Drugs used in GOUT
• COLCHICINE
– acute gouty arthritis
• INDOMETHACIN
• OXAPROZIN
• ALLOPURINOL
– chronic tophaceous gout
• URICOSURIC AGENT
– PROBENECID
– SULFINPYRAZONE
 ANTI-ASTHMA DRUGS
• Bronchodilators
- β2 agonist – “-TEROL”
- Methylxanthines – Theophylline
- Anticholinergics/Antimuscarinics
• Anti-inflammatory agents
- Leukotriene modifiers – Zileuton, Zafirluskast,
Montelukast
- Glucocorticoids
• Mast cell stabilizers
»Nedocromil
»Cromolyn
Antihistamines
1. 1st Generation Antihistamines
a. Ethanolamines:
Carbonoxamine, Dimenhydrinate, Diphenhydramine, Doxylamine
b. Ethylaminediamines:
Pyrilamine, Tripelennamine
c. Piperazine:
Hydroxyzine, Cyclizine, Meclizine
d. Alkylamines:
Brompheniramine, Chlorpheniramine
e. Phenothiazines:
Promethazine
f. Methylpiperidine:
Cyproheptadine
Antihistamines
2. 2nd Generation Antihistamines
a. Piperidines:
Fexofenadine
b. Miscellaneous:
Loratidine, Cetirizine
GENERAL ANESTHETICS

TYPES/ROUTES OF ADMINISTRATION
1. Inhalational
2. Intravenous
3. Rectal (rare)
INHALATIONAL ANESTHETICS

Gas Volatile liquids

Nitrous oxide Halothane, enflurane,
isoflurane, desflurane,
sevoflurane, and
methoxyflurane
 INTRAVENOUS ANESTHETIC
1. barbiturates (thiopental, methohexital)
2. benzodiazepines (midazolam, diazepam)
3. opioid analgesics (morphine, fentanyl,
sufentanil, alfentanil, remifentanil);
4. propofol;
5. ketamine; and
6. miscellaneous drugs (droperidol, etomidate,
dexmedetomidine).
 LOCAL ANESTHETICS
• ROUTES One “i” – ESTER
– Topical Two “i” – AMIDE
– Infiltration
– Field block Most cardiotoxic – BUPIVACAINE
– Nerve block
Most Neurotoxic – LIDOCAINE,
– Intravenous regional
CHLORPROCAINE
Hemolytic anemia – PRILOCAINE
Limited use – COCAINE
Sedative-Hypnotics/Anxiolytics

1.Benzodiazepines
2.Barbiturates
3.Z-drugs (Zolpidem, Zaleplon, Eszopiclone)
4.Ramelteon
5.Buspirone
 ANTIEPILEPTIC DRUG CLASSIFICATIONS
BARBITURATES HYDANTOINS SUCCIMIDES
Phenobarbital Phenytoin Ethosuximide
Primidone Mephenytoin Methsuximide
Mephobarbital Ethotoin Phensuximide
Fosphenytoin Zonisamide

OXAZOLIDINEDIONES BENZODIAZEPINE MISCELLANEOUS

Paramethadione Clonazepam Lamotrigine
Trimethadione Diazepam Felbamate
Gabapentin
TYPE DRUG OF CHOICE Carbamazepine
Valproic acid
Absence ETHOSUXIMIDE Phenacemide
Absence W/ Grand Mal VALPROIC ACID Topiramate
Grand Mal PHENYTOIN/CARBAMAZEPINE Tiagabine
Levetiracetam
Myoclonic Seizure VALPROIC ACID
Febrile Seizure PHENOBARBITAL
Status Epileptics LORAZEPAM (current); DIAZEPAM (old)
 ANTIPARKINSONIAN DRUGS
1. LEVODOPA + CARBIDOPA
2. DOPAMINE RECEPTOR AGONISTS
- Bromocriptine, Pergolide, Pramipexole, Ropinirole
3. MAO-B INHIBITORS
- Selegiline, Rasageline
4. COMT INHIBITORS
- Entacapone, Tolcapone
5. AMANTADINE
6. ANTICHOLINERGICS
- Benztropine mesylate, Biperiden, Trihexyphenidyl
ANTIPSYCHOTICS
 Atypical Anti-psychotics

• Dibenzoxazepine – Loxapine
• Dibenzodiazepine – Clozapine
• Benzisoxazole – Risperidone
• Thienobenzodiazepine – Olanzapine
• Fluorophenylindole – Sertindole
 ADRs - ANTIPSYCHOTICS
• Seizures – Clz, Chlorpromazine
• Agranulocytosis – Clozapine
• Cardiotoxicity – Thioridazine
• Prolong QT interval – Ziprasidone, Sertindole
• Cornea/Lens deposit – Chlorpromazine
• Retinal deposits – Thioridazine
• Neuroleptic Malignant Syndrome
 ANTIDEPRESSANTS
 Selective Serotonin Re-uptake Inhibitors (SSRI)
 FLUOXETINE, SERTRALINE, CITALOPRAM
 Tricyclic antidepressants (TCA)
 IMIPRAMINE, AMOXAPINE, AMYTRIPTYLINE, DESIPRAMINE
 Monoamine oxidase inhibitors (MAOI)
 PHENELZINE, ISOCARBOXAZID, TRANYLCYPROMINE,
MOCLOBEMIDE
 Serotonin-2 Antagonists/Reuptake Inhibitors (SARI)
 TRAZODONE, NEFAZODONE
 NE and Dopamine Reuptake Inhibitors (NDRI)
 BUPROPION
 Noradrenaline Reuptake Inhibitors (NaRI)
 REBOXITINE
 ANTI-HYPERTENSIVE AGENTS
1. Diuretics
2. Sympathoplegic agents (B-blockers, alpha1
blockers, alpha2 agonists)
3. Calcium Channel Blockers
4. Direct vasodilators
5. Agents that block production or action of
angiotensin (ACEi, ARBs)

BASIC & CLINICAL PHARMACOLOGY - 12th Ed.

NATRIURETICS – Increase Na excretion
SITE EXAMPLE S/E
THIAZIDE Distal Convulated •Bendroflumethiazide -Hyponatremia
-mild to moderate Tubule (Naturetin) -Hypokalemia
HTN •Chlorothiazide (Diuril) -Hypercalcemia
- CHF •Trichlorome (Diurese) -Hyperuricemia
- Liver /Renal •HCTZ (Hydrodiuril) -Hyperglycemia
Disease •Hydroflume (Saluron) -Hyperlipidemia
- D. insipidus

LOOP Thick Ascending Loop -Furosemide (Lasix) -Ototoxixity

of Henle -Torsemide (Demodex) -Hyperuricemia
-Bumethanide (Bumex) -Decrease magnesemia
-Ethacrynide (Edecrin) -Hypokalemia
-Metabolic alkalosis
K-SPARRING Late Distal Tubule & -Spironolactone (Aldactone -Hyperkalemia
Collecting Tubule -Eplenerone(Inspra) -Menstrual abnormalities
-Amiloride(Midamor) -Gynecomastia
-Triamterene (Dyrenium)
AQUARETICS – Increase water excretion
SITE EXAMPLE S/E
OSMOTIC Proximal Tubule -Mannitol -Dehydration
AGENTS & Descending -Glycerin.-Isosorbide -Hypernatremia
Loop of -Urea
Henle

CARBONIC Proximal Tubule -Brinzolamide (Azopt) -GI upset

ANHYDRASE -Acetazolamide (Diqmox) -Urinary infrequency
INHIBITOR -Methazolamide -Metabolic acidosis
(Neptazone) -Renal calculi
-Dorzolamide -Drowsiness
Vasodilators
- Relax smooth muscle, ↓ TPR
- Reflex stimulation of heart
- used with Diuretic or Beta blocker

ORAL, LONG TERM HTN

- Minoxidil
- Hydralazine

PARENTERAL, HTN EMERGENCY

- Sodium nitroprusside
- Diazoxide
- Fenoldopam
 CALCIUM CHANNEL BLOCKER
- highly protein bound
- Large volume of distribution
Verapamil - 5.5 L/kg
Diltiazem - 5.3 L/kg
Nifedipine - 0.8 L/kg

Clinical Manifestation
• Hypotension- peripheral vasodilation
• Bradycardia - AV & SA node block
ACE INHIBITORS

- “-PRIL”
- Potent vasodilator

Use: HTN, CHF, diabetic nephropathy

Use: tx. Mild to moderate HTN

ADR: *Anorexia *Hyperkalemia

*Polyuria *Oliguria
*idiosyncratic dry cough
ARBs
- “-sartan”
- used alone or in combination therapy
-↓cough & angioedema
Examples:
Candesartan - Atacard®
- C/I to pregnancy = fetal abnormalities
Irbesartan - Avapro®
- assoc. w/ fetal abnormalities & death
Losartan - Cozaar®
Telmisartan - Micardis®
Episartan - Teveten®
Olmesartan – Benecar®
Valsartan - Diovan®
ALPHA2 AGONISTS
↓ sympathetic outflow
Anti-HTN axn = stimulate a2 adrenoceptor & (-)
release of catecholamines

Ex. Methyldopa (Aldomet®)

Clonidine (Catapres®)
Guanabenz
Guanfacine
 Adrenoceptor antagonists
a. BETA BLOCKERS – “OLOL”
b. Alpha-1 blockers
“-zosin”
Use: HTN & BPH
Syncope – in 1st time adm of alpha1-
blocker
1st dose phenomenon
mgt of syncope: dose should be small and at bed time.

BASIC & CLINICAL PHARMACOLOGY - 12th Ed.

ANTIANGINAL DRUGS
• Organic nitrates
• Calcium Channel blockers
• Beta blockers
• Ivabradine & Nicorandil
hypertensive patients
- monotherapy with slow release or long acting CCB or
Refractory cases- CCBs Beta blockers
- refractory to organic nitrates normotensive patients - with angina & normal BP
Acute treatment of - DOC: Nitroglycerin
Vasospastic angina - alternative: Propranolol with nifedipine
DOC: verapamil/diltiazem Unstable Angina Pectoris
*aspirin – inhibits thromboxane formation
*cilostazol – antiplatelet with vasodilating effect, inhibit
PDE3
*clopidogrel – inhibit adenosine diphosphate pathway
ANTIARRHYTHMIC DRUGS
Type I – NA Type II – Beta Type III – K Type IV – Ca
IA – Quinidine, -”OLOL” except Bretylium Verapamil
Procainamide, Sotalol Amiodarone Diltiazem
Dysopiramide Dronaderone CI: Nifedipine
IB – Lidocaine, Sotalol
Mexiletine,
Phenytoin
IC – Moricizine,
Flecainide,
Propafenone
THYROID AND ANTITHYROID DRUGS

HYPOTHYROIDISM HYPERTHYROIDISM
• Myexedema • Thyrotoxicosis
• Cretenism • Grave’s disease
• Hashimoto’s disorder • Exopthalmos
• Endemic goiter
• Sporadic goiter

Drugs: Drugs:
1. Thioamides – Methimazole & PTU
1. Levothyroxine – DOC
2. Ipodate and Iopanoic acid
2. Liotrix 3. Iodine 131
3. Desiccated Thyroid 4. Propranolol
5. Thyroidectomy
INSULIN DOC for Type I DM

Rapid Acting Insulin lispro

Insulin aspart
Insulin glulisine
Short Acting Regular Soluble insulin
Intermediate Acting NPH or Isophane
Long Acting Insulin Glargine
Insulin Detemir
Oral Hypoglycemic Agents Secretagogues
Sulfonylurea 1st Gen – Tolbutamide,
Chlorpropramide, Tolazamide
2nd Gen – Glibenclamide,
Glipizide, Glimepiride
Meglitinides Repaglinide, Nateglinide
Thiazolidinediones Troglitazone, Pioglitazone,
Rosiglitazone
Alpha-glucosidase inhibitors Acarbose, Voglibose, Miglitol
Dipeptidylpeptidase inhibitor Sitagliptin
Euglycemic Agents insulin sensitizer
Metformin ADR: laxative effect – diarrhea
appetite suppression – anorexia
abdominal pain

Phenformin Withdrawn due to lactic acidosis

Summary of important DOC
DRUG INDICATION
Epinephrine 1st line cardiac stimulant, anaphylactic shock
Norepinephrine 1st line inotropic agent in the Mx of septic shock
Dobutamine 1st line drug for cardiogenic shock
Salbutamol / albuterol 1st line bronchodilator in acute asthma attacks
Loratadine / Fexophenadine Only antihistamine allowed for pilots
Methylphenidate DOC for ADHD
Amphetamine Alternative for ADHD
Phenoxybenzamine DOC for carcinoid syndrome
Beta blockers DOC for CSAP (chronic stable angina pectoris)
Atropine DOC for cholinergic toxicity
Summary of important DOC
DRUG INDICATION
Pralidoxime, DOC for organoPO4 poisoning
Diacetylmonoxide, atropine
Ipratropium, Oxytropium, DOC bronchodilator for COPD
Tiotropium
Dantrolene DOC Malignant hyperthermia
Sucralfate DOC for stress-induced ulcer in critically-ill
patients
Methotrexate 1st line DMARDS in RA
Colchicine 1st line Tx in acute gout
Allopurinol 1st line hypourcemic agent in chronic gout
Aspirin,325 mg/day 1st line in the primary and secondary prevention of acute
thrombotic events
Summary of important DOC
DRUG INDICATION
-statins 1st line in Hypercholesterolemia

Fibrates 1st line in hypertriglyceridemia

Carbonic anhydrase inhibitors 1st line in open angled glaucoma

Thiazide diuretics 1st line Tx in HTN (as monotherapy or combination

therapy) and in nephrogenic diabetes insipidus
Na Nitroprusside 1st line in HTNsive emergencies
ACE-inhibitors Base Tx component of CHF, 1st line Mx of HTN in CKD
and DM Px and 1st line for albuminuria
Amyl nitrite Initial Mx of CN- poisoning
Lidocaine 1st line in ventricular tachycardia assoc. With digitalis
toxicity and post-MI
Amiodarone 1st line in ventricular tachycardia
Summary of important DOC
DRUG INDICATION
Adenosine 1st line in acute supraventricular tachycardia
MgSO4 1st line in Torsades de pointes
SABA 1st line reliever in BA and alternative reliever in
COPD
LABA 1st line controller (with inhaled GC) for COPD
Locally-acting inhaled GC 1st line controller for BA
Systemic GC (parenteral) 1st line in status asthamticus
Levo-thyroxine 1st line in hypothyroidism
Summary of important DOC
DRUG INDICATION
Thioamides (PTU, 1st line in hyperthyroidism
methimazole)
Perchlorate DOC in amiodarone-induced hyperthyroidism
Metformin 1st line initial Tx of type 2 DM esp. among
obese Px
Lithium 1st line Tx and prevention of bipolar disorder
Lorazepam DOC for Status epilepticus
Isoflurane Preferred anesthetic in neurosurgery
Diazepam DOC to prevent and arrest convulsion in
anesthetic toxicity
Summary of important DOC
DRUG INDICATION
Pen G (2-4 M units IM) DOC for syphilis
Metronidazole Pseudomembranous colitis
Streptomycin 2nd line forTB, for MultiDrug Resistant TB
Co-trimoxazole DOC for Pneumocystis carinii pneumonia
Dapsone, Rifampin, WHO triple Tx for lepromatous type of
Clofazimine leprosy
Dapsone, Rifampin DOC for tuberculoid type of leprosy
Amphotericin B Systemic mycoses
BIOPHARMACEUTICS

POINTS TO REMEMBER
• PHARMACOKINETICS
- “what the body does to the drug”
- study of how drugs move into, through and out of the body
including delivery to their target sites; deals with ADME

LIBERATION- Delivery of active pharmaceutical ingredient

from a dosage form into a solution
ABSORPTION - the drug’s uptake from the site of
administration to the systemic circulation
DISTRIBUTION - the drug’s movement to various sites
after entering systemic circulation
METABOLISM - the drug’s conversion to metabolites
EXCRETION - the drug’s removal from the body
 TRANSPORT MECHANISMS
ABSORPTION EXAMPLE
MECHANISM
Passive Diffusion Weak organic acids & bases, organic
non-electrolytes, urea, aminopyridine

CONVECTIVE PORE Inorganic & organic electrolytes (ions of

TRANSPORT opposite charge of the pore lining)

ACTIVE TRANSPORT Na+, K+, Fe2+, Ca2+, B vitamins

FACILITATED Vit B12
TRANSPORT
ION PAIR Quaternary ammonium compounds
ENDOCYTOSIS ADEK, Ferritin, Insulin, Parasite eggs,
certain amino acids
 ↑GET, ↓GER, ↓ABS ↓GET, ↑GER, ↑ ABS

Fatty meal Cold foods

Hot meal Mild exercise
Stress Motility
Lying on the left side Lying on the right side
Heavy exercise Standing position
Anti motility
ISOENZYME DRUG SUBSTRATE

CYP1A1 Theophylline, Amitriptyline, Imipramine

CYP2B6 Cyclophosphamide, Methadone
CYP2C9 Warfarin, Tolbutamide, Phenytoin, Piroxicam, NSAID-Ibuprofen, Diclofenac

CYP2C19 Omeprazole, Mephenytoin, Diazepam, Imipramine

CYP2D6 TCAs - Amitriptyline, Imipramine, Desipramine

SSRI – Fluoxetine
Antipsychotics – Haloperidol, Thioridazine
β-blockers – metoprolol, propranolol
Debrisoquin (antihypertensive) – injected; a substrate to determine CYP2D6
in patients with poor metabolism
CYP2E1 Acetaminophen, Ethanol/Alcohol, Halothane
CYP3A4 Ketoconazole, Amitriptyline
Benzodiazepines – Alprazolam
Atorvastain, Lovastatin, Simvastatin
Azithromycin, Clarithromycin
Triazolam, Midazolam
Ca2+ blockers – verapamil, diltiazem, felodipine
Protease inhibitors – ritonavir, saquinavil, indinavir
Anxiolytic – Buspirone
BIOACTIVATED METABOLITE
Enalapril → Enalaprilat
Sulindac → active sulfide
Levodopa → dopamine
Prontosil → sulfanilamide
Hetacillin → ampicillin
Sulfasalazine → sulfapyridine + aminosalicylic acid

REACTIVE METABOLITE
Acetaminophen → NAPQI
Benzopyrene → Reactive
Malathion → Malaoxon
parathion→ Paraoxon
 Enzyme Inducers Enzyme Inhibitors
Phenobarbital Metronidazole
Phenytoin Allopurinol
Rifampicin Grape fruit Juice
Isonizaid
Carbamazepine Cimetidine
Chronic Alcoholism Disulfiram
Charcoal boiled Food Acute alcoholism
St John’s Wort Chloramphenicol
Ketoconazole
Erythromycin
Valproic acid
• ACUTE ALCOHOL • CLARITHROMYCIN
• VERAPAMIL • CIPROFLOXACIN
• PHENYLBUTAZONE • CHLORAMPHENICOL
• FLUCONAZOLE • CIMETIDINE
• METYL KETO • DISULFIRAM
• ITRACONAZOLE • ENOXACIN
• INDINAVIR • ALLOPURINOL
• ERYTHROMYCIN • DILTIAZEM
 Isoniazid metabolism - acetylation

plasma half- Effect

life

Slow acetylators Egyptians 140 to 200 peripheral neuritis and drug-

Western minutes induced systemic lupus
Europeans erythematosus syndrome)

Fast acetylators Eskimos 45 to 80 develop isoniazid-associated

Asians minutes hepatitis
(acetylhydrazine)

68
• BIOPHASE– Actual site of pharmacologic action of drugs
in body
• STEADY STATE- rate of drug leaving the body = rate of
drug entering the body
• Depot phase - A portion of a prolonged release dosage
form which liberates the drug from the form at a slower
rate that is unrestricted absorption rate
• Absolute BioA- This refers to the systemic availability of a
drug after extravascular administration compared to IV
dosing.
• BIOWAIVER- This term is applied to a regulatory approval
process in which an application is approved based on
experience of equivalence of a generic drug
bioequivalence/in vivo equivalence testing.
• Dose dumping- It is the term used to
describe the accidental fast release of drug
from a sustained release dosage form
• Residual Method/ Feathering-- This
refers to a graphical method for
separation of exponents such as
separating the absorption rate constant
from the elimination rate constant.
• Flip-flop Model-- This is observed upon
topical or rectal route of administration
where the absorption is slower than the
elimination.
 ZERO ORDER FIRST ORDER

RATE CONSTANT Ko K

Constant amount per Constant Fraction per

unit time unit time
independent on dependent on
concentration of concentration of
reactant reactant

Concentration vs Time Linear graph Hyperbola

Examples Alcohol, Suspension Most of the drugs

ZERO ORDER FIRST ORDER

InC = -kt + lnCo

C = -Kot + Co
LogC = -kt + LogCo / 2.3

-Ko = Y2-Y1 / X2-X1 -K = 2.3 (Log Y2-LogY1) / X2-X1

t1/2 = 0.5 Co / Ko t1/2 = 0.693 / K

Co = C + Kot lnCo = lnC + Kt

t = C- Co / Ko t = lnC- lnCo / K
 CREATININE CLEARANCE EQUATION

A. COCKCROFT AND GAULT

(140-Age)(BW in kg)
(72)(serum conc. in mg/dL)

female = CrCl x 0.85

unit: mL/min
 CREATININE CLEARANCE EQUATION

B. JELLIFE EQ
CrCl
98-[(0.8)(Age in years - 20]

serum creatinine in mg/dL

females = CrCl x 0.90

 BIOPHARMACEUTICS CLASSIFICATION OF DRUGS

CLASS 1 INCREASE SOLUBILITY, DILTIAZEM,

INCREASE PERMEABILITY PROPRANOLOL,
ACETAMINOPHEN
CLASS 2 DECREASE SOLUBILITY, GLIPIZIDE, NIFEDIPINE
INCREASE PERMEABILITY KETOCONAZOLE

CLASS 3 INCREASE SOLUBILITY, INSULIN, ACYCLOVIR

DECREASE PERMEABILITY

CLASS 4 DECREASE SOLUBILITY, TAXOL, HCTZ

DECREASE PERMEABILITY
TOXICOLOGY
 ZOOTOXINS
Poison Sources Notes

Latrotoxin Black widow spider/ produces cholinergic signs & symptoms

Hourglass spider Tx: Calcium gluconate, antivenom
(Latrodectus mactans)
5-Hydroxytryptamine Scorpion (Centuroides neurotoxin
sculpturatus) -Tx: Barbiturate & IV anti venom
Bee venom Hymenoptera (bee, wasps, red ants (formic acid)
ants) -anaphylactic reaction
-Tx: Diphenhydramine & steroids
Hyaluronidase Snakes first aid: suction & tourniquet, incision (w/in
20 mins to remove 20%)
-Tx: antivenom
77
 ZOOTOXINS
Poison Sources Notes

Tetrodotoxin Amphibians (toads, newts, frogs Tx: Barbiturates, Diazepam (convulsions),

(Bufotoxin)), puffer fishes Ca gluconate, Propranolol

Cantharidin Blister fly/ Spanish fly -local irritants, aphrodisiac

Clupeotoxin Oysters, sardines (Venerupin) sharp metallic taste, abdominal pain,

anchovies vomiting, & diarrhea
Scromboid toxin Tuna (Saurine) -confused with MSG reactions
Mackerel (Gemblid) -may be caused by dolphin (non-scromboid)

Ciguatoxin Fish organs (liver) most common poison from ingested fish

78
MUSHROOM TOXINS
Group Source/s
Toxin
I Amanitotoxins, -hepatotoxins
cyclopeptides -Tx: Thioctic acid, Dextrose, Penicillin (interface with albumin
binding), Vitamin K, Dexamethasone
IA Orellanine, orelline -nephrotoxins
-Tx: Charcoal hemoperfusion
II Muscimol, Ibotenic acid -Hallucinogens, anticholinergic signs & symptoms
-Tx: Physostigmine
III Gyrometrin -hepatotoxin
Gyrometra esculenta -hydrolyzes to form monomethylhydrazine
-Tx: Pyridoxine HCl, Methylene blue (methemoglobinemia)
IV Muscarine -parasymphathetic overstimulation
-Tx: Atropine
V Coprine -Disulfiram reaction
-Tx: IV NSS, Dopamine or NE for hypotension
VI Psilocin, psilocybin -Hallucinogens
79 -Tx: Diazepam
MICROBIAL TOXINS
Poison Source/s Notes

Enterotoxin Staphylococcus aureus -most common cause of food poisoning

-causes TSS
Diphtheria Corynebacterium diphtheria -protein synthesis inhibitor in nerves,
cytotoxin heart, & kidney cells
C. enterotoxin Vibrio cholera causes rice water stool
E. enterotoxin E. coli traveller’s diarrhea (ETEC)
Endotoxins Mostly from Gram (-) lipoidal, low toxicity, high dose to
become lethal
Typhoid Salmonella typhosa typhoid fever
Peyer's patches
Proteus Proteus species causes UTI
80
PRACTICE QUESTIONS
1. Laughing gas/Nitrous Oxide is a:
A. General anesthetic
B. Caustic
C. Disinfectant
D. Local anesthetic
2. Excretion of basic drugs is most efficient when
A. Urine is basic
B. Urine is acidic
C. Urine is neutral
D. NOTA
3. Which of the following pairs is CORRECT?
A. b1 and M1 receptors – heart
B. b2 and M3 receptors – lungs
C. a1 and M2 receptors – pupils
D. A and B only
E. A and C only
4. Main therapeutic use of oxytocin
A. decrease pain during menstruation
B. prevent galactorrhea
C. decrease uterine contraction
D. induction of labor
• 5. What is the most commonly used local
anesthetic?
A. Bupivacaine
B. Procaine
C. Lidocaine
D. Etidocaine
6. Spironolactone is MOST similar in action to
A. Eplerenone
B. Hydrochlorothiazide
C. Metolazone
D. Bumetanide
• 7. Location of alpha receptors:
I. Blood vessels III. Heart
II. Prostate IV. Bladder sphincter
A. I and II only D. I, II and III only
B. I and IV only E. I, II and IV only
C. II and III only
8. Field of toxicology concerned with the effects and
management of substances in patients of accidental
or intentional intoxication:
A. Forensic toxicology
B. Clinical toxicology
C. Medical toxicology
D. Mechanistic toxicology
9. Renin Inhibitor
A. Acetazolamide
B. Aliskiren
C. Losartan
D. Diltiazem
10. NSAID are all weak acids, except:
A. Indomethacin
B. Piroxicam
C. Nabumetone
D. Ketorolac
11. Calcium sensitizer
A. Milrinone
B. Digoxin
C. Dobutamine
D. Levosimendan
12. Volume of distribution is the apparent volume of
body fluid necessary to dissolve a given amount of
drug to a concentration equal to that achieved in
plasma. VD is used to estimate:
A. Loading Dose
B. Maintenance Dose
C. Renal Clearance
D. Total Clearance
13. MAO-B Inhibitor used in parkinsonism
A. Rasageline
B. Selepen
C. Moclobemide
D. Entacapone
14. An irreversible α-nonselective blocker?
A. Phentermine
B. Phenoxybenzamine
C. Phentolamine
D. Phenmetrazine
15. DOC for malignant hyperthermia
A. Dantrolene C. Pyridoxine
B. Succinylcholine D. Epinephrine
16. Also known as primary adrenal insufficiency, a rare
disorder that occurs when the adrenal glands do not
produce enough cortisol and aldosterone
A. Grave’s disease
B. Cushing’s syndrome
C. Cretinism
D. Addison’s disease
• Graves disease is an autoimmune disorder that leads to
overactivity of the thyroid gland (hyperthyroidism). An
autoimmune disorder is a condition that occurs when the
immune system mistakenly attacks healthy tissue.]
• CUSHING’S a metabolic disorder caused by
overproduction of corticosteroid hormones by the adrenal
cortex and often involving obesity and high blood
pressure.
• Cretinism is a condition of severely stunted physical and
mental growth due to untreated congenital deficiency of
thyroid hormones (congenital hypothyroidism) usually due
to maternal hypothyroidism.
17. Differences in bioavailability are most frequently
observed with drugs are administered by which of
the following routes?
A. subcutaneous C. oral
B. intravenous D. sublingual
18. Effective therapy to rattle snake bite:
A. Suction and tourniquet
B. Antivenin
C. Antivenin, suction and tourniquet
D. None of these
19. Displacement of a drug from plasma binding sites
would usually be expected to:
A. decrease tissue levels of the drug
B. increase tissue levels of the drug
C. decrease the volume of distribution of the drug
D. decrease the metabolism of the drug
20. It is the choice of professional poisoners.
A. nitrate
B. naphthalene
C. oxalate
D. arsenic
21. The richest source of vitamin K
A. Green leafy vegetables
B. Organ meats
C. Citrus fruits
D. Rice polishing
22. DMARD of choice for RA:
A. Indomethacin C. Auranofin
B. Methotrexate D. Aspirin
23. Preferred Anesthetic for labor:
A. Methoxyflurane C. Isoflurane
B. Sevoflurane D. Halothane
24. Treatment of Nocturnal Enuresis:
A. Fluoxetine C. Tranylcypromine
B. Imipramine D. Entacapone
25. Beta-Blocker for patient with Bronchial asthma?
A. Carvedilol C. Labetalol
B. Metoprolol D. Propranolol
26. Which of the following diuretic is also indicated for
glaucoma and mountain sickness?
A. Thiazide Diuretics
B. Loop Diuretics
C. Carbonic Anhydrase Inhibitor
D. K+-Sparing Diuretics
27. Treatment for Chocolate brown
blood/Methemoglobinemia:
A. Methylene Blue C. Sodium thiosulfate
B. Sodium nitrite D. Amyl nitrite
28. The following is/are true about Sympathetic
Nervous System:
I. Maintains digestive processes and elimination of
wastes
II. Also referred to as “Adrenergic System”
III. Neurotransmitter: Acetylcholine
IV. “Fight or Flight” response
A. I only C. II & IV only
B. I & II only D. All of these
29. Which of the following statement/s concerning the
Parasympathetic Nervous System is/are correct?
I. The parasympathetic division is involved in accommodation
of near vision, movement of food, and urination.
II. Acetylcholine is the neurotransmitter mainly released by the
postganglionic parasympathetic fibers.
III. The preganglionic fibers of the parasympathetic division are
long compared to those of the sympathetic nervous system.
IV. The postganglionic fibers of the parasympathetic division
are long compared to those of the sympathetic nervous
system.
A. I only C. I, II & III only
B. I & II only D. All of these
• 30. Epinephrine is considered as the first line drug
for the management of anaphylaxis and
anaphylactic shock for which of the following
mechanism/s?
I. Inhibition of Histamine release by Beta-2 receptor
activation
II. Beta-2 activation due to bronchodilation
III. Alpha-1 antagonism leading to vasodilation
IV. Alpha-1 agonism leading to vasoconstriction
A. I only C. I, II, & III only
B. I & II only D. I, II, & IV only