Question

a.) Abigail is a 27-year old female who suffers from depression. Her doctor has recommended moclobemide as treatment. As she is interested in the drug, she does some research on it. The oral bioavailability of moclobemide is initially 56% due to hepatic first-pass metabolism by CYP2C19 and CYP2D6, but the metabolism is saturated after continuous steady-state dosing. Moclobemide’s halflife is 2 hours. Explain i) what will happen to moclobemide’s plasma concentration when saturation occurs, ii) what will happen to the bioavailability thereof, and iii) how long it would take to reach steady state. (4)

b.) Over the course of a few weeks, Abigail experiences several emotional changes in her life, including losing her mother, getting fired from her job, picking up several kilograms, and breaking up with her partner. Given the distress, she takes three times the dose of her moclobemide in the hope that it would help her emotional state, and goes to a beer festival with friends. After a few drinks, Abigail experiences heart palpitations and is rushed to the hospital. Explain the underlying reasons and pathological changes leading to her hospitalisation. (5½)

c.) After recovering, Abigail decides to seek help controlling her weight, and obtains a prescription for Belviq. Comment on the appropriateness of her taking Belviq for weight loss.

Answer 1

Bioavailability is the fraction of drug that reaches the systemic circulation from a given dose.First pass metabolism is a factor that affect bioavailability.When drugs are administered orally they have to pass via gut wall----->portal vein---->liver----->systemic circulation.During this passage certain drugs get metabolised and are removed or inactivated before they reach the systemic circulation.This process is known as first pass metabolism which can decrease the bioavailability ofthe drug and lead to diminished therapeutic response.

{a}

(i) when saturation occurs,moclobemide's plasma concentration increases as they reaches the systemic circulation.

(ii)When the drug reaches systemic circulation bioavailability also increases.

(iii) If constant dose of drug is given at constant intervals at its half life,plasma concentration of drug increases due to its absorption and falls due to elimination in each dosing interval.Finally the amount of drug eliminated will equal the amount of drug administered in the dosing interval.The drug is said to have reached steady state.It is attained after approximately 4-5 half lives.That is here it may takes 8-10 hours since the moclobemide's half life is 2 hours.

{b} Heart palpitation is are feelings of havin a fast beating ,fluttering or pounding heart.moclobemide is a reversible and selective MAO-A inhibitor with short duration of action.Full MAO activity restored within one to two days of stopping the drug.Here in this case cheese reaction occurs due to the consumption of tyramine rich beer.in MAO inhibited ptients these indirectly acting sympathomimetic amines escape degeneration in the intestinal wall and liver---->reaching into systemic circulation they displace and release large amounts of NA from transmitter loaded adrenergic nerve endings leads to hypertensive crisis which can be the reason for heart palpitation.

{c} BELVIQ is designed to feel full after you've eaten less food. This medication activates serotonin receptors in your brain. The serotonin receptors regulate hunger. When they signal your body to feel full, you may be able to eat less and lose weight.