POTASSIUM-SPARING DIURETICS 1.Aldosterone antagonists: Spironolactone and eplerenone: The spironolactone-receptor complex is inactive complex results in a failure to produce proteins (which is normally stimulate the Na + /K + exchange sites of the collecting tubule. Eplerenone may have less endocrine effects than spironolactone.  Spironolactone is completely absorbed orally and is strongly bound to proteins. It induces hepatic cytochrome P450.

Therapeutic uses: A.Diuretic: B.Secondary hyperaldosteronism: C.Heart failure: Spironolactone prevents the remodeling that occurs as compensation for the progressive failure of the heart. Side effect: Gastric upsets, gynecomastia, menstrual irregularities, and hyperkalemia.

2. Triamterene and amiloride: In contrast to spironolactone, their ability to block the Na + /K + exchange site in the collecting tubule does not depend on the presence of aldosterone. The side effects: Leg cramps and the possibility of increased blood urea nitrogen as well as uric acid and K + retention.

OSMOTIC DIURETICS: Mannitol and urea are simple, hydrophilic chemical substances that are filtered through the glomerulus result in some degree of diuresis due to their ability to carry water with them into the tubular fluid. They are not useful for treating conditions in which Na + retention occurs. Why? Osmotic diuretics are a mainstay of treatment for patients with increased intracranial pressure or acute renal failure due to shock, drug toxicities, and trauma. They should only be given intravenously. Adverse effects: Include extracellular water expansion and dehydration

CARBONIC ANHYDRASE INHIBITOR:  Acetazolamide inhibits the enzyme carbonic anhydrase in the proximal tubular epithelial cells.  They are much less efficacious than the thiazides or loop diuretics. CO 2 + H 2 O H 2 CO 3 H + +HCO 3– (bicarbonate)  The decreased ability to exchange Na + for H + in the presence of acetazolamide results in a mild diuresis. carbonic anhydrase

Therapeutic uses: a)Open-angle glaucoma: Acetazolamide, dorzolamide and brinzolamide decrease the production of aqueous humor, probably by blocking carbonic anhydrase in the ciliary body of the eye. b)Mountain sickness Adverse effects: Metabolic acidosis (mild), potassium depletion, renal stone formation, drowsiness, and paresthesia. It should be avoided in patients with hepatic cirrhosis.

β-ADRENOCEPTOR–BLOCKING AGENTS: Mechanism of action o Decreasing cardiac output. o They decrease sympathetic outflow from the central nervous system (CNS) o Inhibit the release of renin from the kidneys,

ACE INHIBITORS: Captopril, Enalapril, Lisinopril, benazepril, fosinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril They are recommended when the preferred first-line agents (diuretics or β-blockers) are contraindicated or ineffective.

Clinical uses: a)Hypertension b)Patients with diabetic nephropathy. c)Following a myocardial infarction d)Heart failure

Adverse effects: 1.Dry cough (indicate stopping the drug intake), rash, fever, altered taste, hypotension, and hyperkalemia. 2.Angioedema is a rare but potentially life- threatening reaction 3.Reversible renal failure can occur in patients with bilateral renal artery stenosis

ANGIOTENSIN II–RECEPTOR BLOCKERS (SARTONS): Losartan, Valsartan, Candesartan, eprosartan, irbesartan, telmisartan, and olmesartan. These drugs block the AT1 receptors ARBs do not increase bradykinin levels, decrease the nephrotoxicity of diabetes, making them an attractive therapy in hypertensive diabetics. Their adverse effects are similar to those of ACE inhibitors, although the risks of cough and angioedema are significantly decreased.

RENIN INHIBITOR Aliskiren can cause cough and angioedema but probably less often than ACE inhibitors. The main side effect is diarrhea at high doses.