Diuretics Flashcards
Mention diuretics utilizing organic acid secretion
Loop
Thiazides
CAEI
Mention diuretics utilizing organic base secretion
Amiloride
Triamterene
Mention diuretics utilizing glomerular filtration to reach site of action
Osmotic diuretics
Mention diuretics utilizing peritubular circulation to reach site of action
Spironolactone
Eplerenone
Mention drugs acting at proximal tubule
CAEI
Osmotic diuretics
Mention drugs acting at distal tubule
Thiazide (early)
Spironolactone/eplerenone (late + collecting duct)
Mention drugs acting as loop of Henle
Loop
Osmotic diuretics
Site of action of diuretics
Intra-nephron
Dsecribe mechanism of action of Loop diuretics
Inhibit 2Cl-/K+/Na+ reabsorption, leading to excretion of 20% of Na+, also dec medullary hypertonicity leading to failure if reabsorption of water by des loop of Henle & collecting duct ubder ADH effect.
Inc PGs secretion leading to VD in afferent arteriole & inc GFR
Effect of loop on electrolytes
Inhibit Ca & Mg reabsorption
Increase exchange of Na in nephron for K or H in blood in DCT, leading to hypokalemia & alkalosis
Application of venodilator action of loop
Used in acute pulmonary edema
Describe districution & t1/2 of loop diuretics
Highly bound to plasma proteins
Short t1/2
Describe absorption of loop diuretics
Frusemide absorption is variable
Bumetandine & torsedmide are almost completely absorbed
Describe elimination of loop diuretics
Frusemide is excreted unchanged by kidney upto 65%
Bumentadine & torsemide are extensively metabolised hepatically
Mention emergency indications of loop diuretics
Potent dehydrating agent in hypertensive encephalopathy & acute pulmonary edema.
Electrolyte disturbances: hypercalcemia, hyperkalemia, hypervolemic dilutional hyponatremia, distal renal tubular acidosis.
Mention indications of loop in edema
REFRACTORY edema
CHF, renal insufficiency, acute renal failure (inc blood flow), liver cirrhosis after full dose of spironolactone
Mention metablic & electrolyte adverse effect of loop diuretics
Hypovolemia, shock, collapse, hemoconcentration & thrombosis Hypokalemia & alkalosis Hypocalcemia Hyperuricemia Hypomagnesemia
Mention adverse effects of loop diuretics
Ototoxicity (esp w aminoglycosides)
Interstitial nephritis (esp w cephalosporins)
Cross hypersensitivity with sulphonamides
Myalgia w bumetanide
Descibe pharmacokinetic causes of refractoriness to loop diuretics & their treatment
- Defective absorption in decompensated HF (Give IV loop)
- Defective PPB in hypoalbuminic state, mix diuretic with albumin prior to effusion
- Dec in diuretic excretion by acid secretory system in renal impairment due to accumulation of acids (inc dose of frusemide 5 folds)
Describe pharmacokinetic causes of refractoriness to loop & treatment
- Hypertrophy of distal tubular cells inc Na reabsorption (add thiazide)
- Na is reabsorbed in exchange for K in distal tubule (add spironolactone)
Decsribe mechanism of action of thiazide
Inhibit active NaCl reabsorption in early part of DCT, excretion if 5-10% of Na, dec plasma volume and cardiac output
Vasodilation 2ry to dec Na level in blood vessel wall, delayed.
Initial hypovolemic response is necessary for delayed response
Describe effect of thiazide on blood electrolyte
Inc Na reabsorption in exchange for K or H in late part of distal tubule, hypokalemia & alkalosis
Increase Ca reabsorption & Mg excretion
Mention therapeutic uses of thiazide diuretics
Hypertension
CHF
Nephrogenic type of DI
Idiopathic hypercalcuria & Ca stones (with amyloride)
Mechanism of action of thizaide in HTN
Initially diuresis —> dec blood volume
Persistent effect due to VD
Preferred in elderly dec risk of osteoporosis
Mechanism of action of thizaide in nephrogeinc type of DI
Paradoxical dec in urine output with chronic uses may be due to dec PG & dec GFR thus urine volume decreases.
Mechanism of action of thizaide in hypercalcuria
Dec GFR, inc Ca tubular reabsorption, dec Ca in urine.
Mention adverse effects of thiazide
- Hypokalemia & alklaosis more than loop
- Hyperuricemia
- Hyperlipidemia inc LDL & dec HDL (coronary sclerosis)
- Hypomagnesemia & hyponatremia
- Impotence
- Hypersensitivity (sulphonamide derivative)
- Glucose intolerance (interfere with insulin secretion)
Mention contraindications of thiazides
Edema of renal impairment & liver cell failure
Mention thiazide preparation which:
- Can be used in renal impairment
- Used inHTN with less metabolic side effects
- Indapamide
2. Metolazone
Describe the 2 mechanisms of action of K retaining diuretics & members which utilise each mechanism
- Indirect, antagonizing binding of aldosterone to its receptor, thus prevent formation of protein which stimulates Na pump (delayed, spironolactone/eplerenone)
- Direct, block Na channels directly (amiloride, triameterene)
Mention effect of spironolactone on Mg
Inhibit its excretion
Mention inidcations of K retaining diuretics
CHF, added to loop or ACEI to dec mortality (30%)
Edema of liver cirrhosis
Hypokalemia & hypomagnesemia
GR: Spironolactone is used in edema of liver cirrhosis
As liver cirrhosis is associated with hyperaldosteronism, and it doesn’t cause hypokalemia or acidosis
GR: Triameterene & amiloride are preferred in hypokalemia
As they are rapid & short acting, thus daily dose adujstment is possible
GR: K sparing & losing diuretics are comines
To potentiate their diuretic action and anatagonizse their hypokalemic effect (more effective than K & Mg supplemets)
Mention adverse effects of K sparing diuretics
Hyperkalemia & metabolic acidosis
Gynecomastia due to antiandrogenic effect of spironolactone but not eplerenone
Describe mecahnsim of action of mannitol
Mannitol is freely filtered by GF and nor reabsorbed leading to inc osmotic pressure in nephron and water retenion thus urine volume is increased, the increased osmotic pressure partially prevents Na reabsorption by to much lesser extent than water.
Mention the clinical application:
Mannitol prevents Na reabsorption to much lesser extent than H2O
Ineffective in edematous states with Na overload
Describe the role of Mannitol as dehydrating agent
- Decrease intracranial pressure rapidly in cerebral edema caused by head injury or brain surgery
- Rapid decrease of intraocular pressure in acute congestive glaucoma
Mannitol is used fir prophylaxis of …..
Why?
Acute renal failure
Maintaining high urine flow, preventing concentration of toxic agents which cause renal damage
Describe mechanism of action of CAEI
Inhibit carbonic anhydrase enzyme causing inhibition of of Na/H exchange and inhibit NaHCO3 reabsorption resulting alklaline urine diuresis and metabolic acidosis due to loss of NaHCO3
Mention inidcations of CAEI
- Emphysema & sickness of high altitude (acidosis)
- Epilepsy (acidosis)
- Glaucoma (dec formation of aqueous humour, Methozolamide)
Mention adverse effects of CAEI
- Metabolic acidosis (drowsiness) & refractoriness to diuretic effect
- Calcium & phosphate stones
- Hypersensivity (sulphonamide derivatives)
Mention site of vasopressin receptors
V1A & V2: perpherally, modulate BP & renal function reapectively
V1A & V1B: central nervous system
Mention indications of vaptans
Euvolemic hyponatremia (SIADH), hypervolemic hyponatremia
Mention drugs which cause marked reduction in GFR in renal hypoperfusion states
ACEI, inhibit efferent arteriole VC
NSAIDs, inhibit afferent arteriole VD
…… toxicity is enhanced with ……
Lithium
Loop & thiazide