Tyramine is present in certain food substances and can cause hypertensive crises if consumed by a patient on monoamine oxidase inhibitors. Choose the site of action of tyramine from the following options:
A. Tyramine is a monoamine naturally occurring in many food substances. Generally, most ingested tyramine undergoes a complete breakdown in the periphery due to the action of MAO-A enzyme in gut mucosa and liver. When a patient is taking MAO-A inhibitor drugs, tyramine escapes such degradation and enters the brain through amino acid transport. It uses the norepinephrine reuptake channels, and gains entry to presynaptic neurons. Here, tyramine stimulates release of all bound monoamines, especially norepinephrine, leading to a hypertensive reaction. This is called the cheese reaction as tyramine is abundant in mature cheeses.
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Which one of the following antidepressants can block the neuronal uptake of tyramine and potentially reduce the risk of tyramine–MAOI interaction?
D. As tyramine gains entry to presynaptic neurons via the norepinephrine transporter, blocking this reuptake transporter can prevent tyramine action, at least theoretically. Tricyclic antidepressants act via blockade of this transporter. Hence the incidence of cheese reaction due to tyramine is less in those who are on tricyclic antidepressants before the commencement of MAO-A inhibitors. However, such combination is not advisable as the potential to cause serotonin syndrome is very high. SSRIs and L-tryptophan can increase the risk of serotonin syndrome many fold when coprescribed with MAO-A inhibitors.
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Which one of the following mood stabilizers can potentiate GABA transmission by increasing GABA release, reducing GABA metabolism, and increasing GABA receptor density?
D. The mechanism of action of lithium remains speculative. Valproate increases gamma-aminobutyric acid (GABA) release and reduces GABA metabolism. It increases neuronal responsiveness to GABA and also increases GABAB receptor density. Carbamazepine prolongs sodium channel inactivation, leading to a secondary increase in calcium channel inactivation. This is linked to reduced glutamatergic neurotransmission. Carbamazepine also has adenosine antagonistic properties. Lamotrigine acts via membrane stabilization while vigabatrin is a GABA transaminase inhibitor.
Which one of the following benzodiazepines has partial agonistic action at some receptors, leading to fewer withdrawal symptoms?
D. Clonazepam has partial agonistic action at certain benzodiazepine receptors, leading to fewer withdrawal symptoms. Clonazepam is a high-potency drug (0.25 mg clonazepam is equated to 5 mg diazepam); it is shown to be effective in panic disorder and social phobia (but is not recommended for long-term therapy). In bipolar type 1 disorder, clonazepam may result in a prolonged remission phase and reduced depressive relapses when used as an adjuvant to lithium or lamotrigine, respectively.
A patient presents with recurrent episodes of feeling detached and unreal. A pharmacological agent that can worsen the above symptoms is:
D. Caffeine can worsen depersonalization. Experimental induction of depersonalization and derealization has been tried using caffeine. SSRIs are used in treating established cases of depersonalization disorder. However, paradoxically, some times initiation or discontinuation of SSRIs can produce depersonalization experiences. Lamotrigine and clonazepam are used in treating symptoms of depersonalization.
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