Which route is most liable for first-pass metabolism?
D. Orally administered drugs reach the liver via the portal circulation. If hepatic metabolism is extensive, a large amount of drug will be removed during this first passage through the liver. Thus, even if a drug is extensively absorbed, first-pass removal will reduce its systemic availability. So, drugs administered parenterally may need lower dosage compared to the same compound taken orally. Apart from the liver, first pass metabolism also takes place in gut mucosa, muscle tissue, and lung parenchyma, albeit to a smaller extent.
Which of the following statements regarding treatment adherence is FALSE?
A. Non-adherence occurs in up to 40–60% of patients with schizophrenia at any time. Adherence is a multidimensional and dynamic concept and it is not useful to consider adherence vs non-adherence as the only categories in the spectrum. Non-adherence is not exclusive to psychosis; it has also been recorded in other psychiatric disorders including depression. In fact, adherence is a problem even in non-psychiatric but long-term illnesses such as diabetes and hypertension. Side-effects are major factors in causing non-adherence. Depot preparations have better adherence rates, largely due to direct supervision and non-reversibility.
If a young male is administered 400 mg of lithium once daily, the average time taken for lithium to reach a steady state in plasma is:
D. The time taken for a drug to reach the steady state is the function of its half-life. If the drug is given regularly within its half-life, it will reach a steady state in the plasma in about four to fi ve half-lives. In this case, Lithium has a half-life of nearly 24 hours. So if we give lithium once daily for 4 days, it would have reached a steady state, and a blood taken on the 4th or 5th morning 12 hours after the last dose will give the trough lithium level, which will be an estimate of the plasma level of lithium.
A 45-year-old man with schizoaffective disorder is on lithium, sertraline, lorazepam, and olanzapine. He develops low sodium levels and complains of extreme lethargy.
The most likely offending agent is:
A. Hyponatraemia has a well-known association with the use of antidepressants, especially SSRIs. Elderly people and those medically frail are worst affected. Hyponatraemia can also confuse the picture of depression by inducing lethargy and fatigue. The propensity to cause hyponatraemia seems to be a class effect of antidepressants – so replacing an SSRI with another SSRI will not eliminate the risk completely. Carbamazepine is also associated with SIADH and hyponatraemia. Lithium causes nephrogenic diabetes insipidus and sodium levels are either normal or marginally high as a result. Antipsychotics are also reported to be associated with hyponatraemia, although SSRIs are more likely to be associated with this phenomenon.
Which of the following predisposes to a nocebo effect?
E. Placebos can also have adverse effects. Some patients will not tolerate placebos despite the fact that they are inert, and suffer from adverse effects (called the nocebo phenomenon). Nocebo effects with medication include all complaints mistakenly attributed to the medication, such as symptoms of the illness itself, symptoms of stress and the emotional response thereto, symptoms that refl ect the patient’s normal physiology, and symptoms that reflect normal variations in health. Predisposing factors for a nocebo response include expectations of adverse effects at the onset of treatment, conditioning, wherein the patient learns from prior experiences to associate medication taking with certain somatic symptoms, predisposition due to gender (women complain more), neuroticism, hypochondriasis, a tendency to somatize, coexistent emotional disturbances, and situational and contextual factors that alter expectations or result in aversive conditioning.
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