Androgens and Drugs for Erectile Dysfunction MCQs

The interaction between nitrates and phosphodiesterase inhibitors used in erectile dysfunction (tadalafil, sildenafil, vardenafil) is well known and very important to understand. Nitrates are converted to nitric oxide by vascular smooth muscle cells, and nitric oxide causes increased intracellular CGMP as a second-messenger. Increased GMP concentration leads to vascular smooth muscle relaxation. Additionally, GMP is metabolized within the cells by phosphodiesterase, and phosphodiesterase inhibitors will lead to increased intracellular GMP. GMP accumulation in vascular smooth muscle cells due to both enhanced synthesis (nitrates) and inhibited degradation (PDE inhibitors) is responsible for profound hypotension due to extreme vasodilatation when these drugs are used together. Reference: Basic & Clinical Pharmacology, Fourteenth Edition By Bertram G. Katzung Pg. no. 194

Decreases Vmax. Noncompetitive inhibitor decrease the Vmax. Noncompetitive inhibitors block enzyme activity with or without substrates bound, therefore the affinity is unaffected. The Vmax decreases because when the inhibitor is bound, it decreases the amount of active sites available for the substrate. Reference: Basic & Clinical Pharmacology by Bertram G. Katzung Fourteenth Edition Pg no. 22

This is a case of Paracetamol toxicity. Mechanism of toxicity of Paracetamol N-acetyl-p-benzoquinoneimine (NABQI) is a highly reactive arylating minor metabolite of paracetamol which is detoxified by conjugation with glutathione. When a very large dose of paracetamol is taken, glucuronidation capacity is saturated, more of the minor metabolite is formed-hepatic glutathione is depleted and this metabolite binds covalently to proteins in liver cells (and renal tubules) causing necrosis. Antidote: N-acetylcysteine

Ans. C. Alprostadil Alprastadil (pGEl) is directly injected into corpora cavernusa for erectile dysfunction' It acts by increasing arterial inflow" by vasodilation and reducing outflow by contracting the carporal smooth muscle that occludes draining venules.