MAOIs

Patients receiving monoamine oxidase inhibitors (MAOI) as antidepressant therapy have been especially subject to the hypertensive effects of vasoactive amines (52). These dietary amines have also been impHcated as causative agents ia migraine. Other aaturaHy occurring alkaloids (qv) have been recognized for centuries as possessing neurological stimulant and depressant properties. 

Monoamine Oxidase Inhibitors. MAOIs inactivate the enzyme MAO, which is responsible for the oxidative deamination of a variety of endogenous and exogenous substances. Among the endogenous substances are the neurotransmitters, norepinephrine, dopamine, and serotonin. The prototype MAOI is iproniazid [54-92-2] (25), originally tested as an antitubercular dmg and a close chemical relative of the effective antitubercular, isoniazid [54-85-3] (26). Tubercular patients exhibited mood elevation, although no reHef of their tuberculosis, following chronic administration of iproniazid. In... 

As of the mid-1990s, use of MAOIs for the treatment of depression is severely restricted because of potential side effects, the most serious of which is hypertensive crisis, which results primarily from the presence of dietary tyramine. Tyramine, a naturally occurring amine present in cheese, beer, wine, and other foods, is an indirecdy acting sympathomimetic, that is, it potently causes the release of norepinephrine from sympathetic neurons. The norepinephrine that is released interacts with adrenoceptors and, by interacting with a-adrenoceptors, causes a marked increase in blood pressure the resultant hypertension may be so severe as to cause death. 

Normally, dietary tyramine is broken down in the gastrointestinal tract by MAO and is not absorbed. In the presence of MAOI, however, all of its potent sympathomimetic actions are seen. Other side effects of MAOI include excessive CNS stimulation, orthostatic hypotension, weight gain, and in rare cases hepatotoxicity. Because the monoamine oxidase inhibitors exhibit greater toxicity, yet no greater therapeutic response than other, newer agents, clinical use has been markedly curtailed. The primary use for MAOIs is in the treatment of atypical depressions, eg, those associated with increased appetite, phobic anxiety, hypersomnolence, and fatigues, but not melancholia (2). 

When linezolid is used with antiplatelet drugs such as aspirin or die NSAIDs (see Chap. 18) diere is an increased risk of bleeding and thrombocytopenia When administered widi die MAOIs (see Chap. 31) the effects of the MAOIs are decreased. There is a risk of severe hypertension if linezolid is combined widi large amounts of food containingtyramine (eg, aged cheese, caffeinated beverages, yogurt, chocolate, red wine, beer, pepperoni). 

The term pasaon flower is used to denote many of the approximately 400 species of the herb. F saon flower has been used in medicine to treat pain, anxiety, and insomnia. Some herbalists use the herb to treat symptoms of parkinsonism. F saon flower is often used in combination with other herbs , such a valerian, chamomile, and hops, for promoting relaxation, rest and sleep. Although no adverse reactions have been reported, large doses may cause CNS depression. The use of passion flower is contraindicated in pregnancy and in patientstaking the monoamine oxidase inhibitors (MAOIs). Fission flower contains coumarin, and the risk of bleeding may be increased when used in patientstaking warfarin and pasaon flower. 

The TCAs, such as amitriptyline (Elavil) and dox-epin (Sinequan), inhibit reuptake of norepinephrine or serotonin at the presynaptic neuron. Drug classified as MAOIs inhibit the activity of monoamine oxidase a complex enzyme system that is responsible for breaking down amines. This results in an increase in endogenous epinephrine, norepinephrine and serotonin in the nervous system. An increase in these neurohormones results in stimulation of the CNS. The action of the SSRIs is linked to their inhibition of CNS neuronal uptake of serotonin (a CNS neurotransmitter). The increase in serotonin levels is thought to act as a stimulant to reverse depression. 

Orthostatic hypotension is a common adverse reaction seen with the administration of the MAOIs. Other common adverse reactions include dizziness, vertigo, nausea, constipation, dry mouth, diarrhea, headache, and overactivity. 

One serious adverse reaction associated with the use of the MAOIs is hypertensive crisis (extremely high blood pressure), which may occur when foods containing tyramine (an amino acid present in some foods) are eaten (see Home Care Checklist Avoiding Drug Food Interactions With MAOIs). 

If die tricyclics are administered witii the MAOIs, the patient is at risk for hypertensive episodes, severe convulsions, and hyperpyretic episodes. Use of the MAOIs must be discontinued at least 2 weeks before treatment witii the tricyclics begins. The tricyclics may prevent the therapeutic effect of many antihypertensives. When the tricyclics are administered with dicumarol, the risk for bleeding increases. 

AVOIDING DRUG-FOOD INTERACTIONS WITH MAOIs... 

If your patients are taking MAOIs, they need to avoid foods containing tyramine. Otherwise they may experience a life-threatening reaction, hypertensive crisis. Be sure to instruct ycur patients to avoid the following foods ... 

The MAOI antidepressant drag s are contraindicated in patients widi known hypersensitivity to die drug s, liver and kidney disease, cerebrovascular disease, hypertension, or congestive heart failure and in die elderly. These drag s are given cautiously to patients witii impaired liver function, history of seizures, parkinsonian symptoms, diabetes, or hyperthyroidism. 

Use of die MAOIs must be discontinued 2 weeks before the administration of die SSRIs. When the SSRIs are administered witii die tricyclic antidepressants, tiiere is an increased risk of toxic effects and an increased tiierapeutic effect. When sertraline is administered witii a MAOI, a potentially fatal reaction can occur. Sjymptoms of a serious reaction include hyper-tiiermia, rigidity, autonomic instability witii fluctuating vital signs and agitation, delirium, and coma Sertraline blood levels are increased when administered witii cimetidine. 

The effects of buspirone are decreased when the drug is administered with fluoxetine Increased serum levels of buspirone occur if the drug is taken with erythromycin or itraconazole Should any of these combinations be required, the dosage of buspirone is decreased to 2.5 mg BID, and the patient is monitored closely. Venlafaxine blood levels increase with a risk of toxicity when administered witii MAOIs or cimetidine There is an increased risk of toxicity when trazodone is administered with the phenothiazines and decreased effectiveness of trazodone when it is administered with carbamazepine Increased serum digoxin levels have occurred when digoxin is administered with trazodone There is a risk for increased phenytoin levels when phenytoin is administered witii trazodone... 

MAO Is The MAOIs are less frequently prescribed than other antidepressants, probably because of the risk of hypertensive crisis when food containing tyramine is ingested during M AOI therapy. Fhtients receiving MAOIs... 

If the patient is prescribed an MAOI, it is critical that the nurse give the patient a list of foods containing tyramine. When teaching the patient, the nurse emphas zesthe importance of not eating any of the foods on the list. (See Home Care Checklist Avoiding Drug-Food Interactions With MAOIs)... 

Emphasizes importance of avoiding foods containing tyramine (if MAOIs are prescribed) and provides written list of foods to avoid. 

There is an increase in anticholinergic effects when antihistamines are administered with the monamine oxidase inhibitors (MAOIs) and additive sedative effects if administered with central nervous system depressants (eg, narcotic analgesics or alcohol). When cimetidine and loratadine are administered together there is a risk for increased loratadine levels. 

The decongestants are contraindicated in patients with known hypersensitivity, hypertension, and severe coronary artery disease These drugs are also contraindicated in patients taking monoamine oxidase inhibitors (MAOIs). Naphazoline is contraindicated in patients with glaucoma. 

Additive sympathomimetic effects may develop when decongestants are administered with other sympathomimetic drug s (see Chap. 22). Use of the nasal decongestants with the MAOIs may cause hypertensive crisis. Use of a decongestant with beta-adrenergic blocking dragp may cause hypertension or bradycardia. When ephedrine is administered with theophylline, the patient is at increased risk for theophylline toxicity. 

Ephedra (sea grape, ma-huang, yellow horse) ephedra sinica Relieves colds, improves respiratory function, headaches, diuretic effects 3heart rate, psychosis l hedra should only be used after consulting with the physician. Many restrictions apply and the herb can cause serious reactions. Do not use with cardiac glycosides, monoamine oxidase inhibitor halothane, guanethidine, (MAOIs) or oxytocin. Do not use with 3. John s wort or in weight loss formulas. 

Gnkgo (maiden hair tree, kew tree) Ginkgo biloba Raynauds disease, cerebral insufficiency anxiety, stress, tinnitus, dementias, circulatory problems, asthma Rare if used as directed possible effects include headache, dizziness, heart palpitations, Gl effects, rash, allergic dermatitis Do not take with antidepressant drugs, such as the MAOIs, or the antiplatelet drugs such as coumarin, unless advised to do so by the primary care provider. 

By maintaining low concentrations of cytoplasmic noradrenaline, MAO will also regulate the vesicular (releasable) pool of transmitter. When this enzyme is inhibited, the amount of noradrenaline held in the vesicles is greatly increased and there is an increase in transmitter release. It is this action which is thought to underlie the therapeutic effects of an important group of antidepressant drugs, the MAO inhibitors (MAOIs) which are discussed in Chapter 20. 

Because of their lack of selectivity and their irreversible inhibition of MAO, the first MAOIs to be developed presented a high risk of adverse interactions with dietary tyramine (see Chapter 20). However, more recently, drugs which are selective for and, more importantly, reversible inhibitors of MAO-A (RIMAs) have been developed (e.g. moclobemide). These drugs are proving to be highly effective antidepressants which avoid the need for a tyramine-free diet. 

Iproniazid also prevents the reserpine syndrome in rats. Reserpine blocks vesicular uptake of monoamines which, as a consequence, leak from the storage vesicles into the cytosol. Although these monoamines would normally be metabolised by MAO, they are conserved when a MAO inhibitor (MAOI) is present, and so co-administration of reserpine and a MAOI leads to accumulation of monoamines in the neuronal cytosol. It is now known that, when the concentration of cytoplasmic monoamines is increased in this way, they are exported to the synapse on membrane-bound monoamine transporters. The ensuing increase in monoamine transmission, despite the depletion of the vesicular pool, presumably accounts for the effects of iproniazid on the behaviour of reserpine-pretreated rats. 

In 1958, another agent, imipramine, was discovered by chance to have beneficial effects in depression. This compound is not a MAOI and its actions were first described as a complete riddle . Axelrod s group in Washington (Hertting, Axelrod and Whitby... 

With the exception of tranylcypromine (a phenylcycloalkylamine), the first MAOIs (e.g. iproniazid, isoniazid, phenelzine, isocarboxazid) were derivatives of hydrazine (originally used as a rocket fuel) (Fig. 20.2). All are irreversible inhibitors of the enzyme and restoration of MAO activity requires the synthesis of new enzyme. 

As described above, because MAO is bound to mitochondrial outer membranes, MAOIs first increase the concentration of monoamines in the neuronal cytosol, followed by a secondary increase in the vesicle-bound transmitter. The enlarged vesicular pool will increase exocytotic release of transmitter, while an increase in cytoplasmic monoamines will both reduce carrier-mediated removal of transmitter from the synapse (because the favourable concentration gradient is reduced) and could even lead to net export of transmitter by the membrane transporter. That MAOIs increase the concentration of extracellular monoamines has been confirmed using intracranial microdialysis (Ferrer and Artigas 1994). 

The main problems with early, irreversible MAOIs were adverse interactions with other drugs (notably sympathomimetics, such as ephedrine, phenylpropanolamine and tricyclic antidepressants) and the infamous "cheese reaction". The cheese reaction is a consequence of accumulation of the dietary and trace amine, tyramine, in noradrenergic neurons when MAO is inhibited. Tyramine, which is found in cheese and certain other foods (particularly fermented food products and dried meats), is normally metabolised by MAO in the gut wall and liver and so little ever reaches the systemic circulation. MAOIs, by inactivating this enzymic shield, enable tyramine to reach the bloodstream and eventually to be taken up by the monoamine transporters on serotonergic and noradrenergic neurons. Fike amphetamine, tyramine reduces the pH gradient across the vesicle membrane which, in turn, causes the vesicular transporter to fail. Transmitter that leaks out of the vesicles into the neuronal cytosol cannot be metabolised because... 

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