Monoamine oxidase inhibitors – Drug Studies & Nursing Implications

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Monoamine oxidase inhibitors

MAOIs (Monoamine oxidase inhibitors)

GENERAL DESCRIPTION

MAOIs were the first class of drugs that have antidepressant effects. They may be classified as hydrazide chemically. Now these drugs have been little use because of their toxicity and lethal drug-food and drug-drug interaction.

Isocarboxazid, phenelzine, tranylcypromine which are all irreversible inhibitors of both MAO A and MAO B (non-selective) which in turn makes them effective for treatment of depression.

Another example of MAOI which is a big different from the rest is Selegiline and meclobemide which are selective inhibitors of MAO B and A respectfully. Therefore shown to be effective in reducing the symptoms of Parkinson’s disease which results from depletion of dopamine.

MAOI may be good choice as first or second line treatment of depression but practically it is last choice because it not only have high drug-drug interaction but also have drug-food interaction. MAO enzyme present in gut there they play an important role in breakdown of monoamine ingested and food. Inhibition of MAO enzyme can’t metabolize tyramine which is contained in foods that have been aged or fermented. Built up tyramine is taken up into synaptic nerve terminals and act as a catecholamine releasing agent and large amount of catecholamines caused by tyramine cause hypertensive crisis and potentially a stroke.  So with MAOI tyramine containing food must be avoided.

Class Generic Name Brand Name
 

 

 

 

MAOIs (Monoamine Oxidase inhibitors)

Isocarboxazid Marplan
Phenelzine Nardil
Tranylcypromine Parnate
Selegiline Emsam
Moclobemide Amira, Clobemix, Depnil

 

MECHANISM OF ACTION

MAOIs work by elevating certain neurotransmitter in the brain. At presynaptic serotonergic neuron, this interact with postsynaptic neuron which have postsynaptic receptors which are 5-HT. serotonin is synthesized from amino acid tryptophan by serotonergic neurons. These serotonin is stored in vesicles for regulated release.

At presynaptic noradrenergic neuron, this interact with postsynaptic neuron which have postsynaptic receptors which are β and α1. Norepinephrine is synthesized from amino acid tyrosine by noradrenergic neurons and stored in vesicles awaiting regulated release.

When serotonin and NE release from the neuron they stimulate their receptors and at the same time they transported back to their neurons by a process called reuptake. Serotonin is reuptake by serotonin transporter or SERT and norepinephrine is transported back to their neuron by norepinephrine transporter or NET. Once both chemicals reabsorb they partially repacked in synaptic vesicles in partially broken down into inactive metabolites by an enzyme monoamine oxidase or MAO.

Monoamine oxidase is mitochondrial enzyme that degrades monoamine such as serotonin and epinephrine. MAO enzyme are of two types MAO A and MAO B. They are distributed in brain, gut and liver. MAO A preferably metabolize serotonin but also metabolize norepinephrine and dopamine while MAO B preferably metabolizes dopamine. Therefor inhibition of MAO A may cause antidepressant effects. So mechanism of action of MAOIs is, inhibiting the MAO enzyme preventing breakdown of monoamine neurotransmitter ultimately increasing the availability of these chemicals.

PHARMACOKINETICS

MAOIs are orally active. It is readily absorbed from the gastrointestinal tract. It is metabolized by liver and by acetylation. Reversible MAOI have shorter duration of action than irreversible MAOI. The plasma clearance of MAOI is rapid so plasma drug levels are not yet clear.

INDICATIONS

Depression with anxiety

Anxiety with panic attack or multiple somatic symptoms

Atypical depression with hypersomnia, lethargy, hyperphagia

Cautionary use with TCAs where TCAs does not affect alone.

Parkinson’s disease (Selegiline)

Post-traumatic stress disorder

Obsessive compulsive disorder

Hysteroid dysphoria

CONTRAINDICATIONS

Tyramine containing foods

Hepatic failure

Renal failure

Cerebrovascular disease

Pheochromocytoma

Porphyria

Epilepsy

SIDE EFFECTS & ADVERSE EFFECTS

Decrease drug metabolism in the liver

Prevent breakdown of food, alcohol, fruits

Orthostatic hypotension

Weight gain

Sexual dysfunction

Headache

Migraine

Dry mouth

Oedema

Serotonin syndrome

Hypertensive crisis

Psychotic reaction

Withdrawal symptoms may be include agitation, restlessness, panic attack and insomnia

DRUG INTERACTION

MAOIs may cause serotonin syndrome when given concurrently with other antidepressants such as SSRIs, TCAs

MAOIs may cause seizure when given with carbamazepine concurrently

Hypertensive crisis may cause when MAOIS given with pseudoephedrine, phenylephrine

MAOIs when taken with tyramine containing food then can cause hypertensive crisis or potentially a stroke.

NURSING INTERVENTIONS

Enquire the complete health history of the patient including allergy, drug interactions, and family background of depression

Check lab test for CBC, blood glucose, BUN, creatinine, platelets, electrolytes, LFT

Check and identify if any neurological disorder like seizure etc.

Monitor blood pressure and pulse before and during treatment

Administer medicine at night or bed time to avoid drowsiness at day time

Observe mood swing during the treatment

Observe s/s for serotonin syndrome, if any

Observe cardiovascular or neurologic s/s for any disorder, if any

Avoid to administer MAOIs with tyramine containing food

Observe sleep-wake cycle of the patients.

PATIENT EDUCATION

IF taken MAOIs, forbid patient to take any fermented or aged food or containing tyramine.

Advise to take medicine at night or bed time to avoid drowsiness at day time and take morning dose early to avoid insomnia.

Advise patient not to discontinue treatment because it may take 2-4 weeks to start antidepressant effects

Inform the patients about the possible side effects of medication specially serotonin syndrome which may be life threatening.

Report immediately if feeling bradycardia, urinary retention, blurred vision, chest pain, and diaphoresis.

Advice to take care and slow change of posture due to dizziness and danger of fall or injuries.

Avoid driving if feeling drowsiness or dizziness.

Do not breast breast feed while taking medicine.

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