what is the mechanism of action of dextromethorphan

What is the mechanism of action of dextromethorphan?

Jan 14, 2022 · Mechanism of Action. Dextromethorphan has multi-faceted pharmacodynamic and pharmacokinetic properties. The drug is a lipophilic molecule with an ionizable amine at one end. It is structurally related to alkaloid opioids such as morphine but does not interact with the mu receptor. It derives from levorphanol, first designed as a morphine alternative.

How effective is dextromethorphan?

Apr 19, 2020 · What is the mechanism of action of dextromethorphan? This agent crosses the blood-brain-barrier and activates sigma opioid receptors on the cough center in the central nervous system, thereby suppressing the cough reflex. The mechanism of action of dextromethorphan is as an Uncompetitive NMDA Receptor Antagonist and Sigma-1 Receptor …

Is Dextromethorphan a narcotic?

The mechanism of action of dextromethorphan is as an Uncompetitive NMDA Receptor Antagonist and Sigma-1 Receptor Agonist.

How does dextromethorphan work to suppress coughs?

Dec 31, 2015 · Mechanism of action. Dextromethorphan is an agonist of NMDA and sigma-1 receptors. 13 It is also an antagonist of α3/β4 nicotinic receptors. 12 However, the mechanism by which dextromethorphan's receptor agonism and antagonism translates to a clinical effect is not well understood. 9

What receptors does dextromethorphan work?

How does dextromethorphan work in the brain?

What type of drug is dextromethorphan?

Is dextromethorphan anticholinergic?

What is the action of ambroxol?

What is guanfacine mechanism of action?

Is dextromethorphan for dry cough?

How is dextromethorphan metabolized?

What are the side effects of dextromethorphan?

Is dextromethorphan an antihistamine?

Is dextromethorphan a dissociative anesthetic?

When is dextromethorphan contraindicated?

What is the difference between phenylephrine and dextromethorphan?

Dextromethorphan is a cough suppressant. It helps loosen congestion in your chest and throat, making it easier to cough out through your mouth. Phenylephrine is a decongestant that shrinks blood vessels in the nasal passages.

What is the name of the antihistamine that is used to treat a runny nose?

Promethazine HCl and Dextromethorphan Hydrobromide Syrup is a combination of an antihistamine and a cough suppressant used to treat cough, itching, runny nose, sneezing, and itchy or watery eyes caused by colds or allergies. Promethazine HCl and dextromethorphan hydrobromide syrup is available in generic form.

What is DXM cough suppressant?

Introduction: Dextromethorphan (DXM) is an over-the-counter (OTC) cough suppressant commonly found in cold medications. Illicit use of DXM is referred to on the street as “Robo- tripping” or "skittling." These terms are derived from the most commonly abused products, Robitussin and Coricidin.

How much dextromethorphan is needed for antitussive therapy?

The average dose necessary for effective antitussive therapy is between 10 and 45 mg, depending on the individual.

How long does it take for dextromethorphan to work?

Dextromethorphan's medicinal effects typically begin after 15 and 30 minutes, reach their maximum around 2 to 3 hours, and end at or before 6 hours.

How long does DXM affect your brain?

These effects can last as long as 6 hours.

Does dextromethorphan suppress cough reflex?

This agent crosses the blood-brain-barrier and activates sigma opioid receptors on the cough center in the central nervous system, thereby suppressing the cough reflex. The mechanism of action of dextromethorphan is as an Uncompetitive NMDA Receptor Antagonist and Sigma-1 Receptor Agonist.

How does dextromethorphan work?

At therapeutic doses, dextromethor phan acts centrally (meaning that it acts on the brain) as opposed to locally (on the respiratory tract ). It elevates the threshold for coughing, without inhibiting ciliary activity. Dextromethorphan is rapidly absorbed from the gastrointestinal tract and 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, depending on the individual. The International Society for the Study of Cough recommends "an adequate first dose of medication is 60 mg in the adult and repeat dosing should be infrequent rather than qds recommended."

Where does dextromethorphan enter the bloodstream?

Following oral administration, dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood–brain barrier. At therapeutic doses, dextromethorphan acts centrally (meaning that it acts on the brain) as opposed to locally (on the respiratory tract ).

How long does dextromethorphan stay in your system?

The duration of action after oral administration is about three to eight hours for dextromethorphan hydrobromide, and 10 to 12 hours for dextromethorphan polistirex. Around one in 10 of the Caucasian population has little or no CYP2D6 enzyme activity, leading to long-lived high drug levels.

How much does CYP2D6 increase the duration of action?

As CYP2D6 is a major metabolic pathway in the inactivation of dextromethorphan, the duration of action and effects of dextromethorphan can be increased by as much as three times in such poor metabolizers.

What is the metabolite of dextrorphan?

Dextromethorphan and its major metabolite, dextrorphan, also block the NMDA receptor at high doses, which produces effects similar to other dissociative anesthetics such as ketamine, nitrous oxide, and phencyclidine . It was patented in 1949 and approved for medical use in 1953.

What is DXM used for?

Dextromethorphan, often referred to as DXM, is a medication most often used as a cough suppressant in over-the-counter cold and cough medicines. It is sold in syrup, tablet, spray, and lozenge forms. It is in the morphinan class of medications with sedative, dissociative, and stimulant properties (at lower doses).

When did dextromethorphan become available?

During the 1960s and 1970s, dextromethorphan became available in an over-the-counter tablet form by the brand name Romilar. In 1973, Romilar was taken off the shelves after a burst in sales because of frequent misuse. A few years later, products with an unpleasant taste were introduced (such as Robitussin, Vicks-44, and Dextrotussion), but later the same manufacturers began producing products with a better taste. The advent of widespread internet access in the 1990s allowed users to rapidly disseminate information about dextromethorphan, and online discussion groups formed around use and acquisition of the drug. As early as 1996, dextromethorphan hydrobromide powder could be purchased in bulk from online retailers, allowing users to avoid consuming dextromethorphan in syrup preparations.

What is dextromethorphan used for?

It is a prodrug of dextrorphan and used as an antitussive drug for suppressing cough. It has a role as a NMDA receptor antagonist, a neurotoxin, a xenobiotic, an environmental contaminant, an antitussive, a prodrug and a oneirogen. It derives from a dextrorphan. It is an enantiomer of a levomethorphan.

How long does it take for dextromethorphan to work?

The duration of action is approximately 3-6 hours with conventional dosage forms.

How is DXM used?

The objective of the study was to assess driving with and without DXM ingestion. The effects of one-time maximum daily doses of DXM 120 mg versus a guaifenesin 400 mg dose were compared among 40 healthy subjects using a crossover design. Subjects' ability to drive was assessed by their performance in a driving simulator (STISIM Drive driving simulator software) and by conducting a standardized field sobriety test (SFST) administered 1-hr postdrug administration. The one-time dose of DXM 120 mg did not demonstrate driving impairment on the STISIM Drive driving simulator or increase SFST failures compared to guaifenesin 400 mg. Doses greater than the currently recommended maximum daily dose of 120 mg are necessary to perturb driving behavior.

What is DXM in medicine?

Dextromethorphan (DXM) is the dextro isomer of levomethorphan, a semisynthetic morphine derivative. Although structurally similar to other /CNS depressants/, DXM does not act as a mu receptor opioid (eg, morphine, heroin ). DXM and its metabolite, dextrorphan, act as potent blockers of the N-methyl-d-aspartate ( NMDA) receptor.

How to keep dextromethorphan hydrobromide?

Keep container tightly closed in a dry and well-ventilated place. / Dextromethorphan hydrobromide /

How long does dextromethorphan last in the atmosphere?

This corresponds to an atmospheric half-life of about 3.3 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm (1). Dextromethorphan is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions (2). Dextromethorphan contains chromophores that absorb at wavelengths >290 nm (2) and, therefore, may be susceptible to direct photolysis by sunlight (SRC).

What is the AUC of dextromethorphan?

A 30mg oral dose of dextromethorphan reaches a C max of 2.9 ng/mL, with a T max of 2.86 h, and an AUC of 17.8 ng*h/mL.

What is the therapeutic window of dextromethorphan?

13, 14, 12 It has a moderate therapeutic window, as intoxication can occur at higher doses. 10 Dextromethorphan has a moderate duration of action. 12 Patients should be counselled regarding the risk of intoxication. 10

What is the AUC of dextromethorphan?

A 30mg oral dose of dextromethorphan reaches a C max of 2.9 ng/mL, with a T max of 2.86 h, and an AUC of 17.8 ng*h/mL. 7

What is the drug used for dry cough?

Dextromethorphan is an NMDA receptor antagonist used to treat cases of dry cough.

Is dextromethorphan an agonist?

Mechanism of action. Dextromethorphan is an agonist of NMDA and sigma-1 receptors. 12 It is also an antagonist of α3/β4 nicotinic receptors. [A10589] However, the mechanism by which dextromethorphan's receptor agonism and antagonism translates to a clinical effect is not well understood. 9. Target.

Which drugs can be decreased when combined with Dextromethorphan?

Fluvoxamine. The metabolism of Fluvoxamine can be decreased when combined with Dextromethorphan. Formoterol. The metabolism of Formoterol can be decreased when combined with Dextromethorphan. Fosphenytoin. The metabolism of Fosphenytoin can be decreased when combined with Dextromethorphan. Fospropofol.

Can you increase the metabolism of dextromethorphan?

The metabolism of Dextromethorphan can be increased when combined with Fluocortolone. Fluorouracil. The metabolism of Dextromethorphan can be decreased when combined with Fluorouracil. Fluoxetine. The serum concentration of Dextromethorphan can be increased when it is combined with Fluoxetine.

Can sodium phosphate be used with dextromethorphan?

The therapeutic efficacy of Sodium phosphate, monoba sic can be decreased when used in combination with Dextromethorphan. Sodium phosphate, monobasic, unspecified form. The therapeutic efficacy of Sodium phosphate, monobasic, unspecified form can be decreased when used in combination with Dextromethorphan.

What is the mechanism of action of dextromethorphan?

Mechanism of Action/Mechanism of Toxicity. Dextromethorphan is the d-isomer of the codeine analog, methorphan. Unlike the l-isomer, it has no analgesic or addictive properties and does not act through the opioid receptors. The exact mechanism for the antitussive effect by dextromethorphan remains unclear and is likely multifactorial.

What is the metabolite of dextrorphan?

Dextromethorphan's main metabolite, dextrorphan, has NMDA receptor antagonist properties similar to ketamine and phencyclidine. This NMDA receptor antagonism is believed to result in a decreased reuptake of catecholamines. Dextromethorphan also inhibits the reuptake of serotonin.

What are the binding sites of DM and DO?

As detailed in Table 1, relative binding potencies at different antidepressant mechanistic sites vary between DM, DO, and ketamine, including at the NMDA receptor high affinity site (DO > DM > ketamine), phencyclidine (PCP) receptor site (DO > DM), σ 1 receptor (DO > ketamine ≥ DM), μ receptor (DO > DM), μ receptor potentiation (DM ≥ DO > ketamine), muscarinic receptors (DO > ketamine), calcium channel (DM > DO > ketamine), and 5HTT (DM >> DO >> ketamine), indicating DO to be relatively more potent than DM at NMDA, PCP, σ 1, μ, and muscarinic sites, DM more potent than DO at calcium channel and 5HTT sites, but DO and DM both more potent than ketamine ( Lauterbach, 2012 ). These effects generally occurred at or below micromolar concentrations, although DM and DO calcium channel blockade at 80 and 250 μM, respectively, cannot necessarily be discounted as nonphysiologic since DM and DO are concentrated in the brain up to 30 times plasma levels ( Werling, Lauterbach, et al., 2007 ). These different mechanisms apply differentially to the rapid-acting, conventional, and treatment-resistant activities of antidepressant treatments. In summary then, DM and DO bind to receptors that have been associated with antidepressant response at generally physiological tissue concentrations ( Lauterbach, 2011, 2012 ).

What is DM in medicine?

Dextromethorphan (DM) is an N -methyl- d -aspartate (NMDA) receptor antagonist and σ 1 receptor agonist used as an antitussive and in the treatment of pseudobulbar affect. DM shares properties with ketamine, an agent with demonstrated antidepressant properties in humans (Lauterbach, 2011, 2012; Zarate et al., 2010). Shared pharmacodynamic properties with ketamine, along with additional actions at other receptors, led to the initial consideration that DM may also possess antidepressant potential (Lauterbach, 2011), and that these properties may extend not only to major depressive disorder but also to treatment-resistant depression ( Lauterbach, 2011, 2012 ). Further, a rapid onset of antidepressant action that is similar to ketamine and different from conventional antidepressants may also be achieved (Lauterbach, 2011, 2012 ). These considerations are explored below.

What does DM stand for in ketamine?

Potencies based on data in the literature. DM, Dextromethorphan; DO, dextrorphan, IC50, concentration required to produce 50% inhibition ketamine; K

Is dextromethorphan a movement disorder?

Dextromethorphan has been implicated in a case of movement disorder [20 ].

Can dextromethorphan cause hyperexcitability?

Although generally safe, dextromethorphan can in some individuals cause nervous system adverse effects, including hyperexcitability, increased muscle tone, and ataxia. Respiratory depression can occur with excessive doses.

How long does DXM last?

The recommended safe dosages for the use of DXM vary between 15 mg and 30 mg taken within a four-hour period. Taking the medication in this dosage and at these recommended time periods will not result in any significant effects, and the antitussive effects will typically last throughout the timespan associated with this recommended use. Of course, individuals who abuse the drug will not adhere to this recommended schedule.

Why is DXM dangerous?

In addition, individuals who use DXM in high doses are at risk for harm due to poor judgment, impulsive behavior, or as a result of the perceptual disturbances that occur with the drug. For instance, an individual driving a car under the influence of a heavy dose of DXM would be more likely to get in an accident as a result of visual distortions that interfere with the person’s ability to drive. The DEA reports a number of serious accidents due to younger individuals being under the influence of DXM.

How old do you have to be to abuse DXM?

SAMHSA and the DEA report that the abuse of DXM can occur across all age groups, but it is primarily focused in younger individuals between the ages of 12 and 26. In addition, SAMHSA reports that younger females between the ages of 12 and 17 may be slightly more likely than younger males in the same age bracket to abuse these medications; however, younger males over the age of 18 are more likely than females in the same age bracket to abuse the drugs.

How many levels of abuse are there in DXM?

The Drug Enforcement Administration (DEA) reports that there are four levels or plateaus of abuse that occur with DXM. In its most recent release of its analysis of the effects of DXM abuse, the DEA listed DXM as a “drug of concern.” The four plateaus of abuse listed by the DEA include:

What is DXM used for?

Its intended use is to control coughing associated with allergies or illnesses, such as the flu, the common cold, bronchitis, and other lung disorders. It comes in a number of different forms, including chewable tablets, lozenges, syrups, capsules, and even dissolvable strips to be placed under the tongue.

What drugs contain DXM?

Medications that contain DXM include a number of familiar medications, such as Robitussin, NyQuil, Vicks Formula 44, etc. Street names for the drug include DXM, skittles, red devil, Robo, cousin, triple C, and a number of others. Some users commonly refer to abuse of this drug as Robo- tripping in reference to its being consumed in cough syrups (the term Robo being taken from the cough medicine Robitussin).

How to treat DXM?

Treatment for DXM abuse will consist of a number of different components, such as initial inpatient admission, medically assisted treatments ( e.g., medications for various symptoms), substance use disorder therapy (the foundation of treatment for any type of substance abuse issue), and participation in some form of social support. Some individuals will need additional treatments for co-occurring disorders and special interventions for specific needs, such as tutoring, job training, occupational therapy, speech therapy, etc.

What is the purpose of dextromethorphan?

Dextromethorphan is used to temporarily relieve cough caused by the common cold, the flu, or other conditions. Dextromethorphan will relieve a cough but will not treat the cause of the cough or speed recovery. Dextromethorphan is in a class of medications called antitussives.

How long can you take dextromethorphan?

Do not take more than the recommended amount of dextromethorphan in a 24-hour period. Refer to the package or prescription label to determine the amount contained in each dose. Taking dextromethorphan in large amounts can cause serious side effects or death.

What to tell your doctor about your prescription?

tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.

How to dispose of unneeded medication?

However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website ( http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

What to keep on a prescription list?

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

What is the phone number to call for poison control?

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

Can you take dextromethorphan and cough suppressants together?

Dextromethorphan comes alone and in combination with antihistamines, cough suppressants, and decongestants. Ask your doctor or pharmacist for advice on which product is best for your symptoms. Check nonprescription cough and cold product labels carefully before using 2 or more products at the same time. These products may contain the same active ingredient (s) and taking them together could cause you to receive an overdose. This is especially important if you will be giving cough and cold medications to a child.

What is DXM metabolite?

DXM’s active metabolite, Dextrorphan, a noncompetitive NMDA receptor antagonist, works in similar ways to ketamine and PCP.13This mechanism of action explains the similar psychotic symptomatology produced by all three compounds. Typical urine drug screens do not test for DXM and hence may not be considered by clinicians. At high concentrations, DXM can result as a false-positive for PCP on a drug screen, at which point mass spectrometry must determine which substance is present.6,14DXM is metabolized by the CYP2D6 system, so fast metabolizers (nearly 85% of the US population) may be more susceptible to abuse.15

What is DXM used for?

Dextromethorphan (3-methoxy-N-methylmorphinan), also known as “DXM” and “the poor man’s PCP,” is a synthetically produced drug that is available in more than 140 over-the-counter cough and cold preparations.1,2Dextromethorphan (DXM) has overtaken codeine as the most widely used cough suppressant due to its availability, efficacy, and safety profile when taken at directed doses.3When used at recommended dosing levels, cold and cough products containing DXM cause minor, if any, adverse effects.4The most significant cause of adverse effects is DXM abuse.5When the suggested dosing regimen of DXM is surpassed for recreational use, an abundance of psychiatric symptoms can result. The effects are dose-dependent and vary from mild motor and cognitive impairment to PCP-like para-psychotic symptoms such as delusions, dissociative states, paranoia, and visual hallucinations. This combination of symptoms can lead to impulsive or violent acts, such as assault, suicide, or homicide.6We report an interesting case of severe dextromethorphan use disorder with dextromethorphan-induced psychotic disorder in a 40-year-old Caucasian female, whose symptoms remitted only following treatment with a combination of an antipsychotic and mood stabilizer.

How many people took DXM in 2006?

Data collected between 2000–2010 on rates of abuse for cough and cold medication containing DXM describe a peak in DXM abuse in 2006 with 34,755 single substance exposures reported by the National Poison Data System.7,8Twelve states have prohibited the sale of DXM-containing products to minors, and the FDA has considered increasing sales restrictions.9However, the FDA’s Drug Safety and Risk Management Committee voted against scheduling DXM in 2010, citing the drug’s economic and public health benefits in reducing cough symptoms.10,11Additionally, preclinical and clinical evidence exists on the drug’s positive effects on seizures, pain, autism, depression, stroke, traumatic brain injury, methotrexate neurotoxicity, and Parkinson’s disease. DXM is also a component in the only FDA-approved treatment for pseudobulbar affect.12

What is the treatment for DXM?

Previously reported psychopharmacologic treatments include short-acting benzodiazepines or low-dose antipsychotics (haloperidol, risperidone, and quetiapine).6The efficacy of olanzapine has also been reported.16In this report, we describe the use of the unique combination of an antipsychotic (olanzapine) and a mood-stabilizer (divalproex ER) to control severe psychotic symptoms induced by DXM abuse.

What are the symptoms of DXM?

The next level (2.5–7.5 mg/kg) results in impairment of motor, cognitive, and perceptual functioning that is comparable to the combined use of alcohol and cannabis. A higher level (7.5–15 mg/kg) induces intense hallucinations, dissociative symptoms, and agitation similar to low-dose ketamine use. Concentrations greater than 15 mg/kg result in complete psychophysical dissociation similar to high-dose ketamine use, with notably violent behaviors, elevated temperatures, and possible death from cardiac or respiratory arrest.6Additionally, a profound withdrawal syndrome has been described consisting of severe vomiting, muscle aches, and diarrhea within the first week of detoxification, followed by night sweats, insomnia, anxiety, and cold intolerance for 3 weeks.2No withdrawal syndrome was observed during Ms. J.’s hospital stay, possibly due to reported habits of only binging monthly on DXM proximal to her hospitalization.

Is DXM a psychotic drug?

DXM is an easily available, typically inexpensive, over-the-counter medication with abuse potential. While some individual states limit the quantity of DXM sold or restrict sales to those over 18-years of age, there is currently no federal ban or restriction on sales. As an agent of abuse that is not detected on a standard urine drug screen, DXM is likely an underdiagnosed cause of substance-induced psychosis. Awareness of the drug’s potential for abuse must be propagated. Physicians should be aware of the psychiatric presentation of DXM abuse and consider this option in the differential diagnosis for patients, especially teenagers and young adults, exhibiting acute-onset of psychotic symptoms.

Can DXM be detected in urine?

The varied dose-dependent presentations of DXM-induced psychosis and lack of DXM detection on urine screening can make properly diagnosing DXM-induced psychosis challenging . Physicians need to include DXM intoxication in their differential when assessing patients presenting with the aforementioned symptoms. The risk of cardiac or respiratory arrest reinforces the need for a thorough substance use history when the context allows.

Overview

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Contraindications

Adverse effects

Overdose

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Pharmacology

Chemistry