indication

For treatment and relief of dry cough.

pharmacology

Dextromethorphan suppresses the cough reflex by a direct action on the cough center in the medulla of the brain. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist and acts as a non-competitive channel blocker. It is one of the widely used antitussives, and is also used to study the involvement of glutamate receptors in neurotoxicity.

mechanism of action

Dextromethorphan is an opioid-like drug that binds to and acts as antagonist to the NMDA glutamatergic receptor, it is an agonist to the opioid sigma 1 and sigma 2 receptors, it is also an alpha3/beta4 nicotinic receptor antagonist and targets the serotonin reuptake pump. Dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood-brain barrier. The first-pass through the hepatic portal vein results in some of the drug being metabolized into an active metabolite of dextromethorphan, dextrorphan, the 3-hydroxy derivative of dextromethorphan.

biotransformation

Hepatic. Rapidly and extensively metabolized to dextrorphan (active metabolite). One well known metabolic catalyst involved is a specific cytochrome P450 enzyme known as 2D6, or CYP2D6.

absorption

Rapidly absorbed from the gastrointestinal tract.

half life

3-6 hours

drug interactions

Desvenlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Dihydroquinidine barbiturate: Quinidine increases the toxicity of dextromethorphan

Fluoxetine: Combination associated with possible serotoninergic syndrome

Isocarboxazid: Possible severe adverse reaction

Moclobemide: Increased CNS toxicity

Paroxetine: Combination associated with possible serotoninergic syndrome

Phenelzine: Possible severe adverse reaction

Quinidine: Quinidine increases the toxicity of dextromethorphan

Quinidine barbiturate: Quinidine increases the toxicity of dextromethorphan

Rasagiline: Possible severe adverse reaction

Selegiline: Combination associated with possible serotoninergic syndrome

Sibutramine: Combination associated with possible serotoninergic syndrome

Terbinafine: Terbinafine may reduce the metabolism and clearance of Dextromethorphan. Consider alternate therapy or monitor for therapeutic/adverse effects of Dextromethorphan if Terbinafine is initiated, discontinued or dose changed.

Tramadol: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Tranylcypromine: Increased risk of serotonin syndrome. Concomitant use should be avoided.

Trazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Trimipramine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Venlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Vilazodone: Consideration should be given to avoiding the concomitant use of dextromethorphan and selective serotonin reuptake inhibitors (SSRI). Monitor for toxic effects of dextromethorphan (eg, CNS, Cardiovascular) if an SSRI is initiated or the dose is increased. SSRIs, other than fluoxetine and paroxetine, may be safer alternatives due to lesser CYP2D6 inhibition; however, the mechanism for the interaction is not fully understood, and caution is still advised.

Zolmitriptan: Use of two serotonin modulators, such as zolmitriptan and dextromethorphan, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.