Dextromethorphane

Synthetic antitussive from the codeine derivatives group. Dextromethorphan is contained in numerous medicines and is one of the best-selling cough suppressants.

Pharmacologically, dextromethorphan is no longer classified as an opioid because it does not bind to any opioid receptor. Its action is thus not via μ-opioid receptors, unlike codeine and dihydrocodeine, but is due to antagonistic action at the cation channels of NMDA recept ors and agonistic action at the sigma receptors. Dextromethorphan is analgesic in certain neuropathic pain (e.g. diabetic polyneuropathy).

The active substance is quickly absorbed into the bloodstream via the gastrointestinal tract. The effect occurs already after 15-30 minutes and lasts for 3-6 hours. Metabolism occurs in the liver, excretion mainly via the kidney. Dextromethorphan is a substrate of CYP2D6 and is degraded by demethylation to the active metabolite dextromethorphan. Since CYP2D6 is subject to genetic polymorphism, the half-lives and renal elimination of dextromethorphan depend on the type of metabolism (see below CYP2D6: 90-95% of Europeans are fast metabolizers, 5-10% are slow metabolizers).

Dextromethorphan is used for the treatment of dry irritable cough and in when needed for the treatment of neuralgic pain.

Dextromethorphan should be avoided during breastfeeding as the active substance can be detected in breast milk. This can cause respiratory depression in the infant. During pregnancy, the pharmaceutical should be avoided, as there are not yet sufficient studies to rule out malformations.

Insomnia, nausea, dizziness and headaches . Inhibition of NMDA receptors carries the risk of psychotic side effects as well as abuse. Rapid metabolizers (UM) are at increased risk for these side effects because of higher plasma levels of dextrorphan compared with normal metabolizers.

Dextromethorphan is available in a fixed combination with quinidine which inhibits DMP degradation to dextrorphan!

The effects of centrally acting drugs are enhanced. Dextromethorphan should not be combined with the antihistamine terfenadine as life-threatening interactions may occur.

Nuedexta© (approved in the EU since June 2013)

In overdose, dextromethorphan has psychotropic effects and is therefore also abused as an intoxicant, especially by adolescents. Dextromethorphan is better tolerated than codeine, but is susceptible to drug-drug interactions.

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