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23 Cards in this Set
- Front
- Back
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What are the different types of MAOIs?
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1. Hydrazine derivatives (phenelzine)
-These are irreversible inhibitors of MAO, require new enzyme synthesis to restore function. 2. Nonhydrazine derivatives (tranlcypromine) -These are reversible (though very slowly) inhibitors of MAO 3. Reversible inhibitors of MAO (Moclobemide) 4. Selective inhibitors of MAO-B (selegiline) |
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What is the importance of MAO-A?
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It is important for the metabolic degradation of catecholamines and 5-HT in neural or target tissues. Hepatice MAO-A inactivated circulation monoamines.
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What is the importance of MAO-B?
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It is more selective for dopamine in the CNS.
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Pharmacologically what occurs in patients on MAOIs?
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They have elevated levels of all brain monoamines as well as elevated norepinephrine in peripheral adrenergic terminals.
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Describe the time of onset of the effect of MAOIs
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Maximal inhibition is reached within several days. However, teh antidepressant effects of these drugs may be delayed for 2-3 weeks.
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What are the adverse side effects of MAOIs?
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1. CNS
-Excessive CNS stimulation, including insomnia, agitation, irritability, ataxia, and seizure 2. Peripheral vascular effects -Orthostatic hypotension, dizziness. It is uncertain if this is related to MAO inhibition. 3. Anticholinergic action -Urinary tention, constipation, dry mouth, blurred vision |
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Describe the interactons of MAO inhibitors and sympathomimetic amines
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The effects of indirectly acting sympathomimetic amines, i.e., amphetamine and tyramine are markedly potentiated. The concentration of catecholamines in nerve endings is increased after MAO-A inhibition and therefore, indirectly acting amines can release greater amounts. In addition, many of the indirectly acting amines are metabolized in the liver by MAO-A. Since their liver metabolism is inhibited, higher concentrations will be available for exerting their pharmacological effects.
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What common drugs contain sympathomimetic amines?
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Over the counter medications, such as cold and hay fever remedies
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Explain the cheese reaction
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Most cheeses, wine, and other foods that have been aged contain tyramine. Since the tyramine is not metabolized in a patient on an MAOI, and can release the supranormal amounts of catecholamines stored in nerve endings, hypertensive crisis may result in patients on an MAO inhibitor for depression (known as the “cheese reaction”). Patients must adhere to a diet that does not include tyramine containing foods.
Hypertensive cheese reaction may not be associated with reversible monoamine oxidase inhibitors. Tyramine will still release sympathetic amines but the elevated amines will compete with the drug for the MAO-A and displace the MAOI from the enzyme, resulting in metabolism of the released norepinephrine. Therefore, the MAO-A is still functional unlike the irreversible inhibitors. However, the “cheese reaction” has occurred with reversible MAOIs. |
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What effect do MAOIs have on drug breakdown?
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There is prolongation of the half-lives of drugs that must undergo oxidative deamination in the liver which is inhibited by MAOIs. MAOIs may potentiate the effect of alcohol, sedative-hypnotics and analgesics. Severe reactions may occur if patients taking MAOIs are given meperidine. Patients on MAOIs should never be given meperidine, but may be given other narcotics for analgesia.
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What drugs are SRIs?
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Citalopram
Fluoxetine Fluvoxamine Paroxetine Sertraline |
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How do SRIs work?
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They block the presynaptic neuronal reuptake of serotonin from the synaptic cleft and have a very weak effect on norepinephrine reuptake pump.
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What differentiates the SRIs?
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All the available SRIs appear to be relatively equivalent with respect to efficacy and side effect profile although they do have different binding affinities for the uptake pump. The differences between these medications are the half-life of the parent compount, presence or absence of active metabolites, and which and to what degree they inhibit cytochrome P450 enzymes.
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Describe the pharmacological effects of SRIs.
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The blocking the presynaptic pumps leads to both the therapeutic effects by down regulation of presynaptic serotonin receptors resulting from the large amounts of serotonin in the synaptic clefs as well as the adverse effects resulting from serotonin stimulation of post synaptic receptors. Most of these drugs do not have significant effects on muscarinic or adrenergic post synaptic receptors.
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Describe the half-life of fluoxetine
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Half-life: 72 hours
Half-life of the active metabolite norfluoxetine: 7-15 days Such a long half-life presents two problems: 1) a patient does not reach steady-state of medication for many weeks after a full dose is reached and 2) if there is significant side effect, the drug takes a long time to be eliminated from the body. |
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Describe the half-life of sertraline
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Half-life: 24 hours
Half-life of the active metabolite: 72 hours |
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Describe the half-life of paroxetine
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Half-life: 24 hours
No active metabolite |
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Which drugs effect CYP2D6? What is the effect?
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Paroxetine, fluoxetine, sertraline inhibit CYP2D6. Inhibition of the enzyme decreases the rate of many drugs, including tricyclic antidepressants, antiarrhythmics, haloperidol, propanolol, codein, and many other drugs that are metabolized by 2D6. Enzyme inhibition may convert extensive metabolizers into poor metabolizers.
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Which drugs effect CYP3A4?
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Clinically significant inhibition by norfluoxetine which it metabolizes. This enzyme is induced by St. John's Wart.
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Which drugs effect CYP1A2?
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Inhibited by fluvoxamine which it metabolizes.
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Compare the side effects of SRIs to tricyclics?
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The side effect profile of the serotonergic reuptake blockers compared to the tricyclcs is one of the reasons for their current popularity. Unlike the tricyclics, the SRIs have no significant anticholinergic effects and, therefore, do not cause dry mouth, constipation or blurred vision.
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Describe the side effect profile of SRIs
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-Nausea
-Vomiting -Nervousness/restlessness/anxiety -Sleep disruption -Potentially severe headaches -Difficulty reaching orgasm or delayed ejaculation (most common) -Weight gain in some patients Like all drugs, the SRIs have a side effect profile and can cause nausea and vomiting (GI disturbances), nervousness/restlessness/anxiety, and sleep disruption. They can cause severe headaches although it is unclear if that is more likely to occur in a population that is predisposed to |
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Describe the drug-drug interactions of SRIs
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The SRIs have significant effect on the cytochrome P450 system, and so are frequently associated with drug-drug interactions. The SRIs inhibit the 1A2, 2D6, or 3A4 isoenzymes and thus the use of SRIs can increase the plasma levels of other medications.
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