Dextromethorphan

Dextromethorphan is a  potent NMDA antagonists used in many over-the-counter cough suppressants.

Other uses in medicine, range from pain relief, as either the primary analgesic, or an opioid potentiater, to psychological applications to the treatment of addiction.

It’s active metabolite is dextrorphan, an N-methyl-D-aspartate receptor antagonist, which in cases of intoxication can lead to hallucinations, out of her body sensations, disorientation, dissociation and inhibition of adrenergic reuptake leading to tachycardia, hypertension, and diaphoresis.

Sold in syrup, tablet, spray, and lozenge forms.

Is also used recreationally, and when used at high doses acts as a dissociative hallucinogen.

Multiple mechanisms of action, including actions as a nonselective serotonin reuptake inhibitor and a sigma-1 receptor agonist.

Major metabolite is dextrorphan, acts as an NMDA receptor antagonist at high doses,producing effects similar dissociative states.

Primary use is as a cough suppressant, for the temporary relief of cough.

Approved in the combination product dextromethorphan/quinidine for the treatment of pseudobulbar affect.

Side effects of dextromethorphan use can include: rash, itching, nausea, vomiting, drowsiness, dizziness, constipation, diarrhea, sedation, confusion, nervousness, and closed eye hallucinations.

Rarely associated with respiratory depression.

Less addictive than the other common weak opioid cough suppressant, codeine.

At doses three to 10 times the recommended therapeutic dose associated with:

Increased energy

Increased confidence

Mild nausea

Restlessness

Insomnia

Talking fast

Feelings of increased strength

Enlarged pupils/glazed eyes

At dosages 15 to 75 times the recommended therapeutic dose associated with:

Hallucinations, dissociation, vomiting, blurred vision, double vision, bloodshot eye, dilated pupils, sweating, fever, Bruxia, hypotension, hypertension, tachycardia, respiratory insufficiency, diarrhea, urinary retention, muscle spasms, euphoria, sedation, paresthesias, blackouts, impaired vision and focus, and skin rash.

Can produce psychological dependence.

An isomer of codeine and shares a similar chemical structure to PCP

Does not produce physical addiction.

Use of the drug over a long period of time can cause withdrawal symptoms that are similar to those of antidepressant discontinuation syndrome.

May be associated with disturbances in sleep, senses, movement, mood, and thinking.

Can trigger a histamine release in atopic children.

In children susceptible to allergic reactions dextromethorphan should be administered only if absolutely necessary.

The drug should not be taken with monoamine oxidase inhibitors due to the potential for serotonin syndrome due to a buildup of an excessive amount of serotonin in the body.

Can also cause serotonin syndrome when used with SSRI medicines.

Caution when taking dextromethorphan when drinking grapefruit juice or eating grapefruits, as compounds in grapefruit affect a number of drugs, including dextromethorphan, through the inhibition of the cytochrome p450 system in the liver, and can lead to excessive accumulation and prolonged effects.

Drug levels for this drug is done either by blood or by urine.

Dextromethorphan is the dextrorotatory enantiomer of levomethorphan, which is an opioid.

Likely functions as a prodrug to its nearly 10-fold more potent metabolite dextrorphan.

Dextrorphan is the true mediator of its dissociative effects.

Rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood–brain barrier.

Acts centrally as opposed on the respiratory tract to suppress cough.

Elevates the threshold for coughing.

Does not inhibit ciliary activity.

Converted into the active metabolite dextrorphan in the liver by the cytochrome P450 enzyme CYP2D6.

The average dose necessary for effective antitussive therapy is between 10 and 45 mg, with an adequate first dose of medication is 60 mg in the adult and repeat dosing should be infrequent.

The duration of action is about three to eight hours for dextromethorphan-hydrobromide, and 10 to 12 hours for dextromethorphan-polistirex.

Approximately 1in 10 of the Caucasian population has little or no CYP2D6 enzyme activity, leading to high and persistent drug levels.

It is a major metabolic catalyst involved is the cytochrome P450 enzyme known as 2D6, or CYP2D6.

Poor CYP2D6 metabolizers have a functional deficiency in this enzyme.

The duration of action and effects of dextromethorphan can be increased by as much as three times in such poor metabolizers of CYPD2D6.

Studies reveal 84% of Americans are fast metabolizers, 7% intermediate metabolizers, and almost 9% are slow metabolizers.

A large number of medications are potent inhibitors of CYP2D6 and include certain SSRIs and tricyclic antidepressants, some antipsychotics, and the commonly available antihistamine diphenhydramine.

It is also metabolized by CYP3A4.

An over-the-counter antitussive.

Often used as a substitute for marijuana, amphetamine, and heroin by drug abusers.

Commonly used as a recreational drug among young adults.