Question
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- (a) Describe the Mechanism of action, newer liposomal formulations, uses and adverse effects of Amphotericin B. ( 4 mark(s)
- (b) Selective Estrogen Receptor Modulators. 4 mark(s)
Answer
a) Amphotericin B — mechanism, liposomal formulations, uses, adverse effects Mechanism: binds ergosterol directly in the fungal cell membrane, forming pores that disrupt membrane integrity — fungicidal. Selectivity depends on ergosterol-versus-cholesterol binding preference (real but imperfect, particularly affecting renal tubular cells).
Liposomal formulations: encapsulate amphotericin B in a lipid carrier, substantially reducing off-target renal tubular binding while preserving (and in visceral leishmaniasis, improving, via preferential reticuloendothelial uptake) antifungal efficacy — allowing higher doses with lower nephrotoxicity than conventional amphotericin B.
Uses: severe systemic/invasive fungal infections (candidiasis, aspergillosis, cryptococcal meningitis), visceral leishmaniasis (particularly liposomal formulation).
Adverse effects: nephrotoxicity (dose-limiting for conventional formulation), infusion-related reactions (fever, chills, rigors), hypokalemia, hypomagnesemia.
b) Selective Estrogen Receptor Modulators Tissue-selective drugs acting as estrogen agonists in some tissues, antagonists in others. Tamoxifen — antagonist in breast (ER-positive breast cancer), partial agonist in endometrium/bone. Raloxifene — antagonist in breast/endometrium, agonist in bone (postmenopausal osteoporosis). Clomiphene — hypothalamic antagonist (ovulation induction in anovulatory infertility).