Pharmacokinetics: Oral:parenteral potency – methadone, codeine>meperidine, pentazocine>morphine. Morphine does not readily cross the BBB and is present in only small amounts in breast milk; opposite is true for heroin. Metabolism is primarily by glucuronide conjugation with marked first-pass effect (morphine). The metabolite formed is active.

Strong agonists

• Morphine

• Heroin – More potent than morphine and better access to CNS (lipophilic).

• Medperidine – Mu agonist; anti-muscarinic actions but less constipating than morphine. Is not antitussive. Used during labor because has no adverse effects on labor time. Seizure-producing (no MAOs).

• Methadone – Longer half-life than morpine. Same side effects as morphine (lots of GI activity). Strong mu agonism. Cross-tolerance between methadone and other opioids.

• Fentanyl – Analogs of meperidine. Short duration of action. Good for post-operative analgesia. More potent than morphine. No histamine release.

Moderate agonists

• Codeine – Antitussive. Less potent and less efficacious than morphine. Excitatory effects in some children.

• Propoxyphene – Has efficacy and potency somewhere between aspirin and codeine. No antitussive action.

Mild agonists (antidiarrheals) – Diphenoxylate & Loperamide

Partial agonist – lower addictive liability and fewer side effects; more psychomimetic activity

• Buprenorphine – Partial mu agonist/kappa antagonist; more potent than morphine but less efficacious (maximal effect decreased); scheduled drug; may be useful in opiate detoxification.

Agonist-antagonists (mixed) – lower addictive liability and fewer side effects; more psychomimetic activity

• Petazocine – Kappa agonist; disappointment; has similar respiratory effects to morphine; anxiety/nightmares; contraindicated in cardiac patients (increases workload).

• Butorphanol – Kappa agonist/mu antagonist; more potent than morphine; low abuse potentital; psychmimetic effects; contraindicated in cardiac patients (increases workload).

• Nalbuphine – Can be used in cardiac patients.

Pure antagonists – Used for narcotic poisoning, reducing side effects of opioids, reversal of neonatal respiratory distress, opioid addiction treatment, treatment of alcoholism (naltrexone reduced craving).

• Naloxone/Naltrexone – Short duration of action; NOT good for barbituate poisoning because it is specific for opioid receptors; treatment for alcoholism; liver function must be monitored; naloxone is DOC for treatment of opioid poisoning.

Antitussive – Dextromethorphan – Not active at opioid receptors; works at central cough site.

Category: Pharmacology Notes