Opioid Analgesics (8-24-15)

Question 1

Morphine

Answer 1

• Indication: severe and acute pain (MI, cancer, trauma, post-op, sickle cell crisis, kidney stones, back pain)
• MOA: STRONG ANALGESIC, MU AGONIST
• Drug action: actions in CNS, cause sedation, drowsiness, euphoria, pupil constrict
• Contraindications: morphine withdrawal complicates hepatitis C, suppressing IFN-alpha immunity and enhancing virus replication
• Toxicity/side-effects: constipation (mu in myenteric plexus), addiction, tolerance; overdose causes death by respiratory depression (naloxone is antidote)
• Drug Interactions: Triprolidine (additive CNS depression), Trovafloxacin (morphine decreases levels so decreases efficacy), Rifampin (decreases effect of morphine); alcohol

*Withdrawal: cessation of dosing, not fatal in neurologically healthy pt w/o heart or lung problems; increase in metabolism, shedding cells in organs

Question 2

Methadone

Answer 2

• Indication: similar to morphine, cough suppression in terminal lung cancer, opioid dependence treatment
• MOA: STRONG ANALGESIC, MU AGONIST, delta agonist, glutamate (NMDA) antagonist, neuronal Ach antagonist.
• Drug action: Firm occupancy of opioid R decreases desire for other opioid intake; NMDA: unknown, Ach: reduce dynamic hearing range
• Contraindications: ???
• Toxicity/side-effects: ???

*Note: methadone abstinence syndrome: slower onset, longer, less severe

Question 3

Meperidine

Answer 3

(DEMEROL)

• Indication: moderate/severe pain, biliary spasm, renal colic
• MOA: STRONG ANALGESIC, Kappa receptor, K+ channels, muscarinic R dopamine transporter
• Contraindications: ???
• Toxicity/side-effects: from metabolite norpethidine, serotonin syndrome (excess 5HT at CNS and PNS), seizure, dysphoria, tremor, respiratory depression

Question 4

Hydromorphone

Answer 4

(DILAUDID)

• Indication: similar to morphine, moderate to severe pain, dry hacking cough in bronchitis
• MOA: MODERATE ANALGESIC, MU AGONIST, delta agonist
• Contraindications: ???
• Toxicity/side-effects: ???

*Note: used recreationally for numbness and euphoria (mu inhibits GABA in presynaptic terminal so increases DA release)

Question 5

Codeine

Answer 5

• Indication: mild/moderate pain, cough, diarrhea, IBS, narcolepsy
• MOA: MODERATE ANALGESIC, MU AGONIST
• Contraindications: ???
• Toxicity/side-effects: euphoria, itching, urinary retention, depression, constipation, erectile dysfunction

*Withdrawal: if it is suddenly stopped -> physical dependence; used recreationally (in cough syrup)

Question 6

Pentazocine

Answer 6

• Indication: mild/moderate pain, dental extraction
• MOA: Agonist-antagonist: Mu antagonist, delta agonist, kappa agonist
• Contraindications: ???
• Toxicity/side-effects: hallucinations, psychotomimetic effects, cardiovascular effects; injection site necrosis and sepsis
• Drug interactions: antagonizes analgesic effects of morphine and meperidine

*Withdrawal: two enantiomers: (-) = kappa agonist, + mu antagonist; (+) = gamma agonist

Question 7

Naloxone

Answer 7

(NARCAN)

• Indication: treating opioid overdose in EMERGENCIES (get patient breathing; NALTREXONE is for long-term treatment of dependency), congenital insensitivity to pain (CIP), de-personalization disorder (DPD)
• MOA: NARCOTIC ANTAGONIST (pure competitive antagonist: no activity on opioid-R); mu, delta, and kappa antagonist
• Drug action: reverses effects of opioids (respiratory depression, sedation, hypotension); reverses psychomimetic and dysphoric effects of agonist-antagonists
• Contraindications: ???
• Toxicity/side-effects: change in mood, trembling, change in heart rhythm, block action of pain-lowering endorphins (no respiratory dep, pupillary constriction, or psychotomimetic effects)

*Note: DPD - naloxone ends out-of-body experiences