indication

For the management of postoperative pain and the maintenance of general anesthesia.

pharmacology

Alfentanil is a synthetic opioid analgesic. Alfentanil interacts predominately with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, alfentanil exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Alfentanil may increase the patient's tolerance for pain and decrease the perception of suffering, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Alfentanil depresses the respiratory centers, depresses the cough reflex, and constricts the pupils.

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. Alfentanil'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

Symptoms of overexposure include characteristic rigidity of the skeletal muscles, cardiac and respiratory depression, and narrowing of the pupils.

biotransformation

The liver is the major site of biotransformation.

absorption

For intravenous injection or infusion only.

half life

90-111 minutes

route of elimination

Only 1.0% of the dose is excreted as unchanged drug; urinary excretion is the major route of elimination of metabolites.

drug interactions

Cimetidine: Increases the effect of the narcotic

Erythromycin: The macrolide, erythromycin, may increase the effect and toxicity of alfentanil.

Fluconazole: Increases the effect and toxicity of alfentanil

Itraconazole: Itraconazole may increase the effect and toxicity of alfentanil.

Ketoconazole: Ketoconazole may increase the effect and toxicity of alfentanil.

Rifampin: Rifampin reduces levels and efficacy of alfentanil

Telithromycin: Telithromycin may reduce clearance of Alfentanil. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Alfentanil if Telithromycin is initiated, discontinued or dose changed.

Tranylcypromine: Possible increased risk of serotonin syndrome.

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

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of alfentanil by decreasing its metabolism. Monitor for increased anesthetic and respiratory depressant effects and consider using lower alfentanil doses or alternate anesthetic.