Morphine

Classification Opioid. (Pure Opioid Agonist). Natural – found in the seed pod of poppy plant Papaver somniferum
MOA (brief) Activate opioid receptors: Mu and Kappa receptors. Relieves pain without affecting other senses such as touch,
sight, smell, hearing and LOC. More effective against constant dull pain rather than sharp, intermittent pain.
Effects Produced: 1) Analgesia 2) Euphoria 3)sedation 4) cough suppression 5) biliary colic 6) Emesis (give promethazine or
prochlorperazine) 7) Miosis (pinpoint)
8.) Respiratory depression – Is what usually causes death (especially in combo w/ alcohol, barbs, benzos). May
last 4-5 hrs. If RR is <12 breaths per min, delay morphine – esp with asthma or emphysema. If 2-4 breaths per
min, hypoxia and patient can go into shock. Resp dep can be reversed with opioid antagonist Naloxone or
Nalmefene w/ ventilator support. Resp dep varies w/ route – 7 min after IV, 30 min after IM, 90 min after SQ
9) Constipation – produced by CNS & GI tract give stool softener (docusate), laxative (senna), or osmotic laxative
(Na+ phosphate)
10) Orthostatic hypotension – blunts baroreceptor reflex
11) Urinary retention
12) Tolerance/Dependence – tolerance develops to euphoria, sedation, analgesia & resp dep. Little tolerance to
constipation and miosis. Cross tolerance btw opioid agonists but not btw barbs, ETOH, benzos, and gen
anesthetics
13) Physical dependence – occurs w/ continued use by adaptive cellular change. Morphine physical dependence
is intense but brief due to short half-life but w/ methadone physical dep is longer but less intense.
Dosage/Route PO, IM, IV, SQ, epidural, intrathecal. IM, IV, SQ, and PO regular lasts 4-5 hr; PO ER lasts 24 hr; epidural and
intrathecal last up to 24 hr; IM/SQ painful and unreliable; IV injected slowly over 4-5 min. PO doses larger than
parental due to 1st pass effect (may need to lower in pts w/ liver dz). Epidural and intrathecal is usually admin for
spinal analgesia w/ epidural being preferred analgesia. Action is rapid & can last up to 24 hr.
 Dosing is individualized
 Sharp stabbing pain need higher doses; dull pain needs lower doses
 Lower doses: elderly b/c of dec liver fcn, neonates b/c of bbb immaturity,
 Should be used on a fixed schedule rather than PRN
Adverse Effects Schedule II drug. Overdose: Naloxone
Precaution pts: Pts w/ respiratory problems, pregnancy (physical dependence of fetus), labor/deliver (suppress uterine contractions
and cause respiratory depression in neonates); head injury, liver impairment, hypotension, urinary problems or BPH
Drug Interactions CNS depressants, Anticholinergics (constipation and urinary retention), hypotensive drugs, MAOIs, Opioid Agonist-
antagonists
Other Can be used in pregnancy – does not cause birth defects
Drug Class/Specific Agents Drug Info Route, Etc

Pure Opioid Agonists (STRONG)

Fentanyl 100x’s more potent than morphine Can be given by transdermal patch
Alfentanil & Sufentanil 1000x’s more potent than morphine Used in hospice. IV
Remifentanil 100x’s more potent than morphine
Meperidine Not used much b/c of short ½ life
Methadone Used b/c of long ½ life
Heroin C1 controlled subst. (no medical use) Lipid sol – crosses bbb more readily than others.
Hydromorphone (Dilaudid) PO, rectal supp, soln
Oxymorphone Rectal supp, parental soln, IV, IM, SQ
Levorphanol PO, IV, IM

POA (Moderate to Strong) Main difference is amt of analgesia

and resp depression produced
C II: Codeine, Oxycodone
C III: Hydrocodone,
Propoxyphene

Agonist-Antagonist Opioids Agonists at kappa receptors and

antagonists at mu receptors
Pentazocine (C IV) Not used in MI due to inc CO (in PO; little to no euphoria but does mediate physical
contrast to pure opioid agonist) dependence; usually in combo w/ naloxone
Nalbuphine IV, IM, SQ
Butorphanol For headaches, was freq abused, IV, IM, nasal; rarely carried in pharmacies anymore
Buprenorphine IV, IM

Opioid Antagonists Used for opioid OD, to reverse resp

dep (post-op), & in opioid addiction
Naloxone (Narcan) No effect if admin in absence of IV, IM, SQ; can trigger withdrawal Sx in pts w/ physical
opioids. dependence; can block and reverse effects of opioids
Naltrexone Used to treat chronic alcoholism
Nalmefene
Nonopioid Centrally Acting Analgesics MOA
Relieve pain by mechanisms largely or completely unrelated to opioid
receptors; do not cause resp depression, dependence, or abuse.
Tramadol: WEAK agonist of mu rec. mostly works by blocking uptake of NE and
5HT3 thereby activating the monoaminergic spinal inhibition of pain.
Naloxone will partially block Tramadol’s effect.

Clonidine: Pain relief is delivered through continuous epidural infusion.

Relieves pain by binding to pre & postsynaptic α2 rec in the spinal
cord & blocks pain signals from the periphery to the brain.

Ziconotide: Centrally acting analgesic w/ intrathecal admin. NOT 1 st line agent

due to adverse rxn (hallucinations, confusion, muscle injury)
Muscle Relaxants MOA (says he won’t ask MOA) Adverse Effects Uses/Other
2 Groups:
For Muscle Spasm (1) Unclear. May result primarily Used to relieve localized spasm
from sedative properties, not by resulting from muscle injury. Not
specifically controlling muscle used for spasticity or other
tone. muscle disorders resulting from
CNS pathology (except
Diazepam).
Diazepam (Valium) Promotes presynaptic inh by CNS depression – sedation, (see above) not muscle relaxer –
enhancing effects of GABA lightheaded, dizzy; physical is benzodiazepine; can give you
dependence with life-threatening high
withdrawal if not done slowly
Tizanidine Agonist at the presynaptic α2 rec Same as above + hepatotoxic – (see above)
check LFT prior to use.
Metaxalone Also hepatotoxic
Chlorzoxazone Marginally effective & can cause
fatal hepatic necrosis
Others: Cyclobenzaprine, Cyclo: causes marked drowsiness
Carisoprodol, Methocarbamol Caris: just became ctrled subst.
Orphenadrine, Baclofen

Drugs for Spasticity (2) Used for movement disorders of

CNS origin (spasticity); disorders
w/ heightened muscle tone,
spasm, & loss of dexterity
Baclofen Acts w/in the spinal cord to Abrupt d/c of intrathecal dose MS, usually SCI, cerebral palsy
suppress hyperactive reflexes can cause rhabdomyolysis, multi-
involved in reg of muscle organ failure, death
movemt
Diazepam (listed in 1st group) (listed in 1st group) Preferred in pts w/ marginal
strength
Dantrolene Acts directly on skeletal muscle; Hepatotoxicity MS, SCI, cerebral palsy; treats
 does not allow muscle to malignant hyperthermia (life-
contract; can decrease strength threatening increase in temp)
Sedative-Hypnotics:

Class & Specific Agents MOA Adverse Effects Uses/Other

Barbiturates Bind to and enhance GABA rec
Thiopental, Secobarbital High abuse potential; rarely used Strong resp dep, tolerance, dec response to other drugs (inc
Phenobarbital anymore dependence, DOC for suicide hepatic synthesizing enzymes)

Benzodiazepines Enhance effects of GABA Confusion, anterograde amnesia Uses: anxiety, insomnia, general
Diazepam, Lorazepam, anesthesia, seizure disorders,
Midazolam, Clonazepam, muscle spasm, panic disorders,
Clorazepate, Alprazolam alcohol withdrawal

Benzo-like Drugs Enhances GABA, but does not Some daytime drowsiness insomnia
Zolpidem (Ambien) bind to benzo receptors
Eszopiclone (Lunesta)CIV E: only drug with no limit to how
long it can be taken
Pyrazolopyrimidines Works the same way as zolpidem Approved only for short-term
Zaleplon (C IV) but quick onset and short DOA insomnia

Melatonin Agonist Activates MT1 & MT2 rec for Amenorrhea, Galactorrhea, Avoid during preg/lact
Ramelteon melatonin; can inc levels of reduced libido, fertility problems
prolactin & dec levels of
testosterone

Miscellaneous Sed-Hyp
Chloral Hydrate (C IV) CNS dep similar to barbs Tolerance, withdrawal w/ sleep Prodrug that is rapidly
disruption and nightmares metabolized to active form in
liver

Trazodone Used for induction of sleep

Antihistamines
Benzodiazepines

Classification benzodiazepines
Drug Names Diazepam, Lorazepam, Midazolam, Clonazepam, Clorazepate, Alprazolam, Triazolam, Oxazepam
MOA (brief) Potentiate the actions of GABA (intensify GABA’s effects only, not direct GABA agonists)
MOA (detailed) Enhance the actions of GABA by binding to specific rec in the supramolecular structure known as the GABA rec-
chloride channel complex. Since the amount of GABA in the CNS is finite, there is a built-in limit to the depth of CNS
depression the benzodiazepines can produce. This is why they are much safer than barbiturates, which directly
mimic GABA. Benzos readily cross the bbb (lipid soluble). Benzos metabolites are pharmacologically active, so the
effects of the drugs persist long after the parent drug has disappeared.
Pharmacology Reduce anxiety; Promotes sleep; induce muscle relaxation
Dosage/Route PO (have no effect on heart & bv); IV (can produce profound hypotension and cardiac arrest); all benzos can be PO
Adverse Effects Confusion; anterograde amnesia (impaired recall of events that take place after dose) – especially w/ Triazolam;
may exacerbate obstructive sleep apnea (OSA); CNS depression – with little to no resp dep; paradoxical effects:
insomnia/excitation, euphoria/heightened anxiety & rage; abuse; death from OD has never been documented
When is it used? Anxiety; insomnia; induction of general anesthesia (D,L,M)M is for conscious sedation; seizure disorders (D, L, clona,
clora); muscle spasm (D); panic disorder (A, L, clona); withdrawal from alcohol
Metabolic Effects Certain benzos go through very little hepatic metabolism & can be used in pts w/ liver disease (L,O,T)
Selective Uses Triazolam – sleep (b/c rapid onset); Estazolam – for someone waking up after falling asleep (slower onset);
Lorazepam – (L,O,T) good in elderly b/c it does not accumulate w/ repeated dosing
Overdose - Gastric lavage followed by activated charcoal & saline cathartic & possibly dialysis if Sx are severe.
- Flumazenil: competitive benzo rec antagonist & will reverse sedative effects but NOT resp dep. Give IV
slowly over 30 seconds and can be repeated every min PRN. 1 st dose is 0.2 mg, 2nd dose 0.3 mg 3rd dose and
all subsequent doses are 0.5 mg.
Epilepsy: refers to a group of disorders characterized by excessive excitability of neurons in the CNS. Seizure: general term that applies to all
types of epileptic events. Convulsion: applies only to abnormal motor phenomena. For example: jerking movements during tonic-clonic attack.

Types of Seizures:

Partial (focal): begins in the cerebral cortex and undergoes limited spread to adjacent cortical areas.

1. Simple Partial Seizures – no LOC; symptoms determined by brain region affected – motor Sx (thumb twitching), sensory Sx (local
numbness, auditory, visual or olfactory), autonomic Sx (nausea, flushing, urinary incontinence, salivation), psychoillusory Sx (feeling of
unreality, fear, or depression); lasts 20-60 sec
2. Complex Partial Seizures – characterized by impaired consciousness and lack of responsiveness (motionless/fixed gaze); followed by
period of automatism (repetitive, purposeless movements such as lip smacking & hand wringing); lasts 1-2 min
3. Secondary Generalized Seizures – begin as #1 or #2 and then evolved into generalized tonic-clonic seizures; LOC (according to book);
lasts 1-2 min

Generalized: conducted widely through the hemispheres; May be convulsive or non-convulsive; Produce LOC.

1. Tonic-Clonic (Grand Mal) – neuronal discharge spreads through both hemispheres of cerebral cortex; period of muscle rigidity (tonic)
followed by synchronous muscle jerks (clonic); cause urination, not defecation; convulsions may be preceded by a loud cry caused by
forceful expiration of air across the vocal cords; lasts 90 seconds or less; followed by period of CNS depression - “postictal state”
2. Absence (Petit Mal) – brief LOC (10-30 sec); mild, symmetric motor activity (eye blinking) or may occur w/ no motor activity. Pt may
experience hundreds of attacks per day; occur primarily in children and cease during early teens.
3. Atonic – sudden loss of muscle tone; if seizure activity is limited to muscles of the neck = head drop, if muscles of limbs and trunk are
involved = “drop attack” (collapse); occur mainly in children
4. Myoclonic – sudden muscle contractions that last for 1 second; may be limited to one limb (focal) or may involve entire body (massive)
5. Status Epilepticus – (SE) persists for 30 min or longer; Several types including generalized convulsive SE (may be life threatening),
absence SE, and myoclonic SE
6. Febrile – common in children ages 6 mo – 5 yrs; typically manifest as generalized tonic-clonic of short duration; does not increase risk for
developing epilepsy later in life.
Mixed Seizures (LGS) Lennox-Gastaut Syndrome: severe form of epilepsy; usually develops during preschool years; developmental delay and a
mix of partial and generalized seizures; Seizure types include partial, atonic, tonic, generalized tonic-clonic, atypical absence; difficult to treat

Antiepileptic Drugs (AED):

AEDs can suppress discharge of neurons within a seizure focus and suppress propagation of seizure activity from focus area to other areas.

AEDs act through 4 basic mechanisms:

1. Suppression of Na+ influx: bind to Na+ channels while they are in inactivated state to prolong channel inactivation, thus decreasing the
ability of neurons to fire at high frequencies. (seizures that depend on high frequency discharge are suppressed)
2. Suppression of Ca2+ influx: calcium influx promotes NT release at axon terminal. Block Ca 2+ = block transmission.
3. Antagonism of Glutamate: glutamate is primary excitatory NT in CNS. Block its receptors=suppression of neuronal excitation.
4. Potentiation of GABA: decrease neuronal excitability and suppress seizure activity

Seizure Type Traditional AEDs Newer AEDs

Partial: Simple, complex, and secondary Carbamazepine Oxcarbazepine
generalized Phenytoin Gabapentin
Valproic Acid Lamotrigine
Primidone Levetiracetam
Pregabalin
Topiramate
Tiagabine
Zonisamide
Primary Generalized:
Tonic-Clonic Same as above & Phenobarbital (rarely) Lamotrigine
Topiramate

Absence Ethosuximide (DOC) Lamotrigine

Valproic Acid (obtain baseline LFT’s)

Myoclonic Valproic Acid Topiramate

**red = drugs that suppress Na+ influx. **blue =drugs that suppress Ca++ influx. **green=glutamate antagonist – also Felbamate (not listed)
***Valproic Acid has 3 MOAs: sodium, calcium, and GABA

AEDs that potentiate the effects of GABA:

1. Barbiturates
2. Benzodiazepines
3. Gabapentin
4. Tiagabine
5. Vigabatrin

Phenytoin

Classification AED (most widely used and 1st drug to suppress seizures w/out depressing the entire CNS
MOA (brief) Blockade of hyperactive Na+ channels
Therapeutic Range NARROW (the capacity of the liver to metabolize phenytoin is very limited)
Adverse Effects Gingival hyperplasia (excess swelling, tenderness, bleeding of gums – 20% and can be reduced w/ proper hygiene)
Drug Interactions INC plasma levels: Diazepam, Valproic Acid, alcohol (acute). DEC plasma levels: Carbamazepine, phenobarbital,
alcohol (chronic)
When is it used? Epilepsy, Cardiac Dysrhythmias
Metabolic Effects ½ life shortens the longer the pt takes the drug