Essay On Antihypertensive & Cardiovascular Drugs


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Antihypertensive and Cardiovascular Drugs


Emergence of the use of diuretics and other Angiotensin Converting Enzyme inhibitors represents one of the greatest advance in modern medicine (Lehne, 2013). These drugs have dramatically helped in the treatment of arterial hypertension and congestive cardiac failure. The central role of diuretics in medicine hinges in the management of edema and hypertension due to their inherent capability of inducing renal excretion of both solutes and water. They function through selective interference of either active or passive ion transport channels in the segments of nephron (Lehne, 2013). Diuretics have an antihypertensive effect due to their ability to reduce plasma volume and extracellular fluid.

What are the basic processes of kidney filtration?

The three fundamental processes of kidney filtration entail glomerular filtration, tubular reabsorption and tubular secretion (Lehne, 2013). Glomerular filtration occurs in the glomerular with approximately 20% of plasma passing through the corpuscle at a given time (Edmunds & Mayhew, 2013). This process is driven primarily by hydraulic pressure within the capillaries in the glomerulus. Tubular reabsorption refers to the movement of water and other solutes from the renal tubules back to the blood. Other important solutes including amino acids, bicarbonate and glucose, are actively reabsorbed into the blood from the proximal tubule. Tubular secretion continues to take place even when there is reabsorption (Ford, Roach, & Roach, 2013). The process enables the kidney to eliminate toxins and other wastes from the body. All the substances secreted constitute urine and include trace amounts of glucose, urea, and ammonium ions among other solutes.

What are the actions of carbonic anhydrase inhibitors, osmotic diuretics, loop diuretics, thiazide diuretics, and spironolactone?

Carbonic anhydrase inhibitors are drugs which have the inhibitory effect on the active transport of bicarbonate ions from the proximal convoluted tubule (Ford, Roach, & Roach, 2013). The drugs lead to decreased sodium reabsorption thus more retention of the bicarbonate in the urine. They also inhibit the action of carbonic anhydrase. For example, acetazolamide results in the reduction of Hydrogen ion secretion and increased renal excretion of potassium and sodium ions.

Loop diuretics have inhibitory effects on the sodium-potassium-chloride transporter in the ascending limbs (Edmunds & Mayhew, 2013). The inhibitory effects have an effect on the increase of distal tubular concentration of sodium. Thiazide diuretics have inhibitory effects on the sodium-chloride symport in the distal tubule (Ford, Roach, & Roach, 2013). Osmotic diuretics are pharmacologically active substances which decrease the reabsorption of water and sodium ions thus leading to increased renal output. Spironolactone serves as the antagonist for aldosterone and function through binding to the aldosterone-dependent sodium-potassium ion symport in the distal convoluted tubule (Ford, Roach, & Roach, 2013). They find usage in the treatment of cardiovascular and renal diseases.

What are the associated toxicities of the above mentioned diuretics?

Carbonic anhydrase inhibitors, when used in an overdose, they have additive inhibitory effects on the enzyme thus increasing the accumulation of sodium carbonate in the blood. Thiazide diuretics contribute to lithium toxicity by decreasing renal secretion of the ions (Ford, Roach, & Roach, 2013). They also contribute to hypokalemia by increasing the elimination of potassium ions from the blood. Osmotic diuretics contributes to fluid overload in the glomerulus when used in high doses. Loop diuretics may lead to ototoxicity, hypokalemia, high plasma levels of uric acid allergic reactions (Edmunds & Mayhew, 2013). Spironolactone in high doses induces renal failure, hyperkalemia, skin disorders such as Stevens-Johnsons Syndrome, hypersensitivity, gastric bleeding among others (Lehne, 2013).

Thiazide diuretics are considered first-line therapy for hypertension. What are the advantages and disadvantages of this therapy?

Thiazide diuretics have assumed the role of first-line drugs in the treatment of hypertension. Among the factors contributing to their famous use is the availability of the drug in the blood 2 to three hours after intake (Lehne, 2013). Furthermore, these drugs are both cost-effective and efficient. Bioavailability and long plasma half-lives explain why they are the preferred choice. The disadvantages of the drugs are that they increase the retention of calcium and uric acid in the plasma. These drugs contribute to both hypokalemia and hypomagnesemia. Onset of type II diabetes mellitus is reported in patients who use thiazides for treatment of hypertension (Lehne, 2013).

What is the mechanism of action of ß-blockers?

Beta blockers have antagonistic effects on the sympathetic nerve stimulation. They also antagonize the circulating catecholamine at their receptors also known as the beta-adrenoceptors. Beta one receptors are found cardiac cells while beta two receptors are predominant in other organs of the body. In the kidney, they reduce the activity of the renin-angiotensin-aldosterone mechanism. Blockade of the receptors in the heart reduces the heart rate (Lehne, 2013).

What are their therapeutic uses in hypertension and heart disease?

Sympathetic nerve activation is one of the leading causes of elevated catecholamine in cardiovascular diseases (Ford, Roach, & Roach, 2013). The raised levels of catecholamine and their adverse effects can be inhibited by beta-blocker. Beta blocker functions by rebalancing the sympatho-vagal axis. The drugs also have the anti-arrhythmic activity which offers protection against cardiac failure. The antihypertensive effect of the beta-blockers is mediated via the blockade of B1 receptors (Ford, Roach, & Roach, 2013). Proposed mode of action includes suppression of sympathetic outflow, decrease in heart rate and suppressing release of renin from the juxtaglomerular renal cells.

What are their associated toxicities and contraindications?

Beta blocker is associated with potentially increased incidence of anaphylaxis perhaps due to the beta-adrenergic blockade. These drugs when used in above standard dosage or extensively lead to increase in cAMP levels in the blood, they decrease the renal vascular resistance (Edmunds & Mayhew, 2013). Contraindication arises from the cocaine abusers since it leads to coronary vasoconstriction (Ford, Roach, & Roach, 2013). There are increased risks of coronary vasospasm due to increased risk of myocardial infarction.

Explain the differences between selective and nonselective beta blockers?

Beta blockers such as propranolol, timolol maleate, and pindolol are non-selective in their mode of action. They are involved in the blockade of both Beta-1 and Beta-2 receptors with the subsequent effect in reduced renal and cardiac output. Second generation or selective Beta blockers such as metoprolol and esmolol hydrochloride have their effect on Beta-1 receptors, thus have their effect on the heart leading to decreased cardiac output (Lehne, 2013).

References
Edmunds, M. W., & Mayhew, M. S. (2013). Pharmacology for the primary care provider. St. Louis, Mo: Elsevier-Mosby.
Ford, S. M., Roach, S. S., & Roach, S. S. (2013). Roach's introductory clinical pharmacology. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins Health.
Lehne, R. A. (2013). Pharmacology for nursing care. St. Louis, Mo: Elsevier/Saunders.