Heart Failure Drugs MCQs

Scorpion sting is a dreadful medical emergency. Scorpion stings cause a wide range of symptoms, from severe local reactions to cardiovascular, respiratory and neurological manifestations. Alpha-receptors play a vital role in the pathogenesis of cardiac failure and pulmonary edema due to scorpion sting. Prazosin is a selective alpha-1 adrenergic receptor blocker. It dilates veins and arterioles, thereby reducing preload and left ventricular impedance without rise in heart rate and renin secretion. It also inhibits sympathetic outflow in the central nervous system. It enhances insulin secretion, which is inhibited by venom action. It has also been found useful even in cases with hypotension. Thus, its pharmacological properties can antagonize the hemodynamic, hormonal and metabolic effects of scorpion venom action

Ans: A. Delayed diastolic depolarization Acetyl choline decreases heart rate primarily by inhibiting the spontaneous depolarization of cells in SA node; also known as diastolic depolarization. This is achieved by inhibition of the funny current in the SA node. Effect of acetylcholine on cardiovascular system Heart rate Ach inhibits funny current generation in the decreases pacemaker cells of SA node AV conduction Ach blocks L type calcium channels in the AV decreases node Atrial contraction Atrium is supplied by cholinergic fibers more than decreases > the ventricles. Ach opens potassium channels ventricular and decreases cyclic AMP in the myocardial cells. contraction Ach increases calcium in endothelial cells, which Vasodilation stimulates calcium dependent ENOS and releases NO which causes vasodilation.

Explanation: Digoxin is a positive inotrope used in HFrEF to improve symptoms and reduce hospitalizations due to heart failure. However, large clinical trials have shown it has no significant impact on overall mortality . Explanation of other options: B) Beta-blockers, C) ACE inhibitors, D) H-ISDN: All of these are pillars of HFrEF therapy with robust evidence from clinical trials demonstrating significant mortality benefit . Key Takeaways: Drugs that reduce mortality in HFrEF include ACEIs/ARBs/ARNIs, beta-blockers, MRAs, and SGLT2 inhibitors. Digoxin improves symptoms but not survival.

Mannitol is very helpful in lowering of intraocular pressure in cases of Acute congestive glaucoma. MOA: Increases the extracellular oncotic pressure hence extracting water from cells and tissues. Uses Its indications are: Increased intracranial or intraocular tension (acute congestive glaucoma, head injury, stroke, etc To maintain GFR and urine flow in impending acute renal failure To counteract low osmolality of plasma and ECF due to rapid haemodialysis or peritoneal dialysis (dialysis disequilibrium). Mannitol is contraindicated in renal insufficiency, acute tubular necrosis, anuria, pulmonary edema; acute left ventricular failure, CHF and cerebral haemorrhage.(Options A,C,D ruled out) The most common side effect is headache. Nausea and vomiting may occur; hypersensitivity reactions are rare.

CYP3A4/5 Carryout biotransformation of largest number(nearly 50%) of drugs. In addition to the liver, these isoforms are expressed in the intestine (responsible for first pass metabolism at this site) and kidney as well. Inhibition of this isoenzyme by erythromycin, clarithromycin, ketoconazole, itraconazole is responsible for the important drug interaction with terfenadine, astemizole and cisapride which are its substrates. Verapamil, ritonavir and a constituent of grapefruit juice are other important inhibitors. Enzyme inhibitors [ Virat Kohli Can't Call Every Indians ] V alproate K etoconazole C imetidine C iprofloxacin/ C larithromycin E rythromycin I NH Enzyme Inducers [GPRS Cell Phone] G - Griseofulvin P - Phenytoin R - Rifampicin S - Smoking Cell - Carbamazepine Phone - Phenobarbitone

Explanation: It will take 80 hours before the drug can be safely restarted. The Plasma half-life (t½) of a drug is the time taken for its plasma concentration to be reduced to half of its original value. In the scenario, the digoxin serum concentration of 4 ng/ml is significantly above the therapeutic range. Starting at 4 ng/mL , it would take: 1 half-life (40 hrs) → 2 ng/mL 2 half-lives (80 hrs) → 1 ng/mL (within therapeutic range) Since the therapeutic range is ≤1 ng/mL , the drug can be safely restarted after 80 hours . Therefore, we should wait at least 80 hours before resuming treatment, considering digoxin's half-life of 40 hours.

While therapeutic targets in heart failure with reduced ejection fraction (HFpEF) are relatively abundant and guided by the targets of disease modification, trials in heart failure with preserved ejection fraction (HFpEF) have been largely disappointing. Overall, symptom management and blood pressure control are the goals in HFpEF treatment now. ACE inhibitors (option A) have been studies in many mechanistic studies and have shown no convincing mortality benefit. Similarly, angiotensin receptor blockers (option B) were studied in the CHARM-Preserved and I-PRESERVE studies and were found to have no mortality benefit. Sildenafil (a phosphodiesterase-5 inhibitor) was shown to improve filling pressures and RV function in patients with HFpEF, but did not show mortality benefit. Reference: Basic & Clinical Pharmacology, Fourteenth Edition By Bertram G. Katzung Pg no. 248

The methylxanthines have positive chronotropic and inotropic effects. At low concentrations, these effects appear to result from inhibition of presynaptic adenosine receptors in sympathetic nerves increasing catecholamine release at nerve endings. The higher concentrations (> 10 μmol/L, 2 mg/L) associated with inhibition of phosphodiesterase and increases in cAMP may result in increased influx of calcium. At much higher concentrations (> 100 μmol/L), sequestration of calcium by the sarcoplasmic reticulum is impaired. Reference: LANG’ Basic & clinical pharmacology by Bertram G. Katzung, Susen B. Masters and Anthony J. Trevor 12 th edition. Chapter 20- Drugs used in asthma by Dr. Homer A. Boushy, MD. Page no. 345