Why can nothing mix with an MAOI inhibitor?!


Question: hey not that i have an MAOI inhibitor but i always hear on what seems like every medication commercial CANNOT BE MIXED WITH MAOI INHIBITOR my question is what is an MAOI inhibitor for specifically and why can it not be mixed with anything? do other drugs negate its effects or do other drugs cause dangerous side effects when mixed?


Answers: hey not that i have an MAOI inhibitor but i always hear on what seems like every medication commercial CANNOT BE MIXED WITH MAOI INHIBITOR my question is what is an MAOI inhibitor for specifically and why can it not be mixed with anything? do other drugs negate its effects or do other drugs cause dangerous side effects when mixed?

http://en.wikipedia.org/wiki/Monoamine_o...

Monoamine oxidase inhibitors (MAOIs) are a class of powerful antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression, and have also shown efficacy in helping people who want to quit smoking.

Due to potentially lethal dietary and drug interactions, MAOIs had been reserved as a last line of defense, used only when other classes of antidepressant drugs (for example selective serotonin reuptake inhibitors and tricyclic antidepressants) have been tried unsuccessfully. Recently, however, a patch form of the drug selegiline, called Emsam, was developed. It was approved for use by the FDA on February 28, 2006.[1] When applied transdermally the drug does not enter the gastro-intestinal system as it does when taken orally, thereby decreasing the dangers of dietary interactions associated with MAOI pills.

Dangers
When ingested orally, MAOIs inhibit the catabolism of dietary amines. Sufficient intestinal MAO-A inhibition can lead to hypertensive crisis, when foods containing tyramine are consumed (so-called "cheese syndrome"), or hyperserotonemia if foods containing tryptophan are consumed. The amount required to cause a reaction exhibits great individual variation and depends on the degree of inhibition, which in turn depends on dosage and selectivity.

The exact mechanism by which tyramine causes a hypertensive reaction is not well understood, but it is assumed that tyramine displaces norepinephrine from the storage vesicles.[4] This may trigger a cascade in which excessive amounts of norepinephrine can lead to a hypertensive crisis. Another theory suggests that proliferation and accumulation of catecholamines causes hypertensive crises.

Tyrosine is the precursor to catecholamines, not tyramine. Tyramine is a breakdown product of tyrosine. In the gut and during fermentation tyrosine, an amino acid, is decarboxylated to tyramine. Ordinarily, tyramine is deaminated in the liver to an inactive metabolite, but when the hepatic MAO (primarily MAO-A) is inhibited, the "first-pass" clearance of tyramine is blocked and circulating tyramine levels can climb. Elevated tyramine competes with tyrosine for transport across the blood-brain barrier (via aromatic amino acid transport) where it can then enter adrenergic nerve terminals. Once in the cytoplasmic space, tyramine will be transported via the vesicular monoamine transporter (VMAT) into synaptic vesicles thereby displacing norepinephrine. The mass transfer of norepinephrine from its vesicular storage space into the extracellular space via mass action can precipitate the hypertensive crisis. Hypertensive crises can sometimes result in stroke or cardiac arrhythmia if not treated. This risk is generally not present with RIMAs. Both kinds of intestinal MAO inhbition can cause hyperpyrexia, nausea and psychosis if foods high in levodopa are consumed.

Chronic use of MAOIs may provide some antidepressant effects that are thought to be mediated by metabolism of tyramine to octopamine, a reaction catalyzed by phenyl-N-methyl transferase that normally converts dopamine to norepinephrine. Octopamine may then act as a "false transmitter" in that it is stored and released like the endogenous transmitter norepinephrine. However, it is a poor agonist of postsynaptic adrenoceptors while retaining agonist activity at presynaptic autoreceptors. This action reduces adrenergic transmission by diminishing postsynaptic receptor activation and by a presynaptic autoinhibitory effect. Finally, octopamine may serve as an agonist at a novel "trace amine" receptor expressed at low levels throughout the brain.

Examples of foods and drinks with potentially high levels of tyramine include fermented substances, such as Chianti and other aged wines, and aged cheeses. Liver is also a well-known source. (See a list of foods containing tyramine). Examples of levodopa-containing foods include broad beans. These diet restrictions are not necessary for those taking selective MAO-B inhibitors.

It deserves separate mention that some meat extracts and yeast extracts (Bovril, Marmite, Vegemite) contain extremely high levels of tyramine, and should not be used with these medications.

When MAOIs were first introduced, these risks were not known, and over the following four decades, fewer than 100 people have died from hypertensive crisis.[citation needed] Presumably due to the sudden onset and violent appearance of the reaction, MAOIs gained a reputation for being so dangerous that, for a while, they were taken off the market in America entirely. It is now known that, used as directed under the care of a qualified psychiatrist, this class of drugs remains a safe alternative for intermediate- to long-term use.

The most significant risk associated with the use of MAOIs, is the potential for interactions with over-the-counter and prescription medicines, illicit drugs and certain supplements (e.g. St. John's Wort). It is vital that a doctor supervise such combinations to avoid adverse reactions. For this reason, many users carry an MAOI-card, which lets emergency medical personnel know what drugs to avoid. (E.g. adrenaline dosage should be reduced by 75%, and duration is extended)

MAOIs should not be combined with other psychoactive substances (antidepressants, illicit drugs, painkillers, stimulants, etc.) except under expert care. Certain combinations can cause lethal reactions, common examples including SSRIs, tricyclics, MDMA, meperidine, tramadol and dextromethorphan. Agents with actions on epinephrine, norepinephrine or dopamine must be administered at much lower doses due to potentiation and prolonged effect. Purely opiate-acting analgesics, such as morphine and buprenorphine may be used safely with MAOIs, but may require a dosage adjustment.

Drug interactions
This section does not cite any references or sources. (December 2007)
Please improve this section by adding citations to reliable sources. Unverifiable material may be challenged and removed.

Sympathomimetics (e.g. pseudoephedrine in cold remedies)
Risk of hypertensive crisis
Reserpine, guanethidine, tricyclic antidepressants
Excitement
Increase in blood pressure and body temperature
Levodopa (L-DOPA)
Excitement
Hypertension
Anticholinergics (Henbane, Datura)
Risk of hallucination
Antihistamines, barbiturates, ethanol, opioids
Action of these drugs prolonged - risk of respiratory depression
Pethidine (Demerol)
Risk of high fever, sweating, excitement, delirium, convulsions, respiratory depression (MAOIs retard metabolism of pethidine, but not its demethylation, therefore excess norpethidine is formed).
Methylenedioxymethamphetamine (MDMA, "Ecstasy")
Risk of hypertensive crisis
Serotonin syndrome
Dextromethorphan (DXM, cough-syrup)
Serotonin syndrome
Imitrex/Sumatriptan, Migraine Medicine

List of MAOIs
Monoamine oxidase inhibitors include:

Isocarboxazid (Marplan)
Moclobemide (Aurorix, Manerix, Moclodura?)
Phenelzine (Nardil)
Tranylcypromine (Parnate contents 5 mg, Jatrosom contents 10 mg)
Selegiline (Selegiline, Eldepryl), and Emsam
Rasagiline (Azilect)
Nialamide
Iproniazid (Marsilid, Iprozid, Ipronid, Rivivol, Propilniazida)
Iproclozide
Toloxatone
Linezolid (Zyvox, Zyvoxid), an antibiotic of the oxazolidinone family, is a reversible, nonselective MAOI which has been known to induce serotonin syndrome post SSRI ingestion. Zyvox requires the same dietary precautions as other MAOI's
Many tryptamines have MAOI properties. Harmine (present in Harmal, Banisteriopsis caapi, and tobacco) is a powerful MAOI, which is often used as one of the ingredients of ayahuasca. Certain synthetic trytptamines such as AMT, 5-MeO-DMT or 5-MeO-AMT produce only minor MAO inhibition. The phenethylamine derivatives substituted with a sulfur at the 4-position, such as 2C-T-7 are quite potent MAO-A inhibitors[5], which makes them potentially dangerous when taken in large doses, or when combined with stimulants such as ephedrine or MDMA. Some deaths have occurred from such combinations.
Dienolide kavapyrone desmethoxyyangonin (MAOI-B)[





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