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Diuretics (Overview (Proximal Convoluted Tubule (Reabsorbed= glucose,…
Diuretics
Overview
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Desc Loop of Henle
Reabsorbed= water, increasing osmolarity
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Asc Loop of Henle
Reabsorbed= sodium & potassium & chloride (by co-transporter), magnesium & calcium (via paracellular pathway)
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drugs that increase volume of urine excreted, for management of edema & hypertension
Distal Convoluted Tubule
Reabsorbed= sodium & chloride (by Na/Cl transporter), calcium (by Na/Ca exchanger)
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Collecting Tubule & Duct
Reabsorbed= water, sodium (through epithelial sodium channels [ENaC] after then by Na/K pump)
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Thiazides
Mechanism of Action
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thiazides must be excreted into tubular lumen to be effective since the site of action is on luminal membrane
diminished efficacy with concomitant use of NSAIDs (non-steroidal anti-inflammatory drugs) which reduce renal blood flow
Summary of Action
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decreases urinary Ca excretion (promote reabsorption of Ca in DCT) (loop diuretics increase Ca in urine)
Overview
sulfonamide derivatives, effective orally, secreted by organic acid secretory system of kidney
hydrochlorothiazide= more potent (required dose < than chlorothiazide), efficacy is comparable to chlorothiazide
Therapeutic Uses
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Hypercalciuria= useful for idiopathic hypercalciuria (excessive urinary Ca excretion), beneficial for patients with calcium oxalate stones in urinary tract
Diabetes insipidus= thiazides can substitute ADH in treatment of nephrogenic diabetes insipidus (kidney does not respond to ADH) by increasing reabsorption of water at PCT rather than in collecting tubules, producing hyperosmolar urine
Examples
Chlorothiazides, Hydrochlorothiazides
Adverse Effects
Hyponatremia= to prevent, diuretic dose can be lowered
Hyperuricemia= uric acid deposits in joints gouty attack in predisposed individuals, should be used with caution in patients with gout or high levels of uric acid
Hypokalemia= can predispose patients to digoxin toxicity (ventricular arrhythmias), manage by giving potassium-sparring diuretics or diet with K-rich foods
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Hyperglycemia= glucose intolerance due to impaired insulin release & tissue uptake of glucose, new-onset diabetes occur more often with thiazides
Loop Diuretics
Mechanism of Action
inhibit co-transport of Na/K/Cl, decreases reabsorption of these ions, act immediately even in patients with poor renal function/ lack response to other diuretics
Therapeutic Uses
Edema= reduces acute pulmonary edema & acute/chronic peripheral edema, useful in emergency because of rapid onset of action when given iv
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Overview
major action on asc LOH, have highest efficacy in Na & Cl excretion, produce large amounts of urine, administered orally/parenterally, duration of action is brief (2-4 hrs)
Adverse Effects
Acute hypovolemia= severe & rapid reduction in blood volume, possibility of hypotension & shock
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Hypomagnesemia= often in elderly, corrected by oral supplementation
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Ototoxicity= hearing loss, vestibular function may also be affected inducing vertigo
Examples
Furosemide= most commonly used; Bumetanide & Torsemide= more potent than furosemide; Ethacrynic acid= less used due to adverse effect profile (deafness)
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Osmotic Diuretic
Mechanism of Action
undergo little or no reabsorption, their presence results in higher osmolarity, prevent further water reabsorption
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Thiazides-Like
Overview
lack thiazide structure, but have unsubstituted sulfonamide group like thiazides, similar MOA, therapeutic uses & adverse effects
Examples
Chlorthalidone= long duration of action, used once daily; Indapamine= more potent than thiazides; Metolazone= lipid-soluble, long duration of action, significant anti-HPT action with minimal diuretic effects even at low dose