indication

For treatment and management of pain (Systemic), also used as an Antidiarrheal and as a cough suppressant.

pharmacology

Codeine, an opiate agonist in the CNS, is similar to other phenanthrene derivatives such as morphine. Codeine, in combination with guaifenesin or iodinated glycerol, is used as a cough suppressant and, as a single agent or in combination with acetaminophen or other products, is used for pain control and as an antidiarrheal agent.

mechanism of action

Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Codeine's analgesic activity is, most likely, due to its conversion to morphine. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability.

toxicity

Respiratory depression, sedation and miosis and common symptoms of overdose. Other symptoms include nausea, vomiting, skeletal muscle flaccidity, bradycardia, hypotension, and cool, clammy skin. Apnea and death may ensue.

biotransformation

Hepatic. Codeine is a prodrug, itself inactive, but demethylated to the active morphine by the liver enzyme CYP2D6.

absorption

Well absorbed following oral administration with a bioavailability of approximately 90%.

half life

2-4 hours

drug interactions

Cimetidine: Cimetidine may decrease the therapeutic effect of codeine by decreasing its metabolism to its active metabolite, morphine. Monitor for changes in the therapeutic effect of codeine if cimetidine is initiated, discontinued or dose changed.

Dihydroquinidine barbiturate: Quinidine decreases the analgesic effect of codeine

Quinidine: Quinidine decreases the analgesic effect of codeine

Quinidine barbiturate: Quinidine decreases the analgesic effect of codeine

Terbinafine: Terbinafine may decrease the efficacy of Codeine by inhibiting active metabolite production. Consider an alternate analgesic or monitor for effectiveness of Codeine.

Triprolidine: The CNS depressants, Triprolidine and Codeine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.