DIURETICS
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Transcript of DIURETICS
Prepared by Dr Rasol . M. Hasan
BackgroundPrimary effect of diuretics is to increase solute
excretion, mainly as NaCl
Certain disease states may cause blood volume to increase outside of narrowly defined limitsHypertensionCongestive heart failureLiver cirrhosisNephrotic syndromeRenal failure
Dietary Na restriction often not enough to maintain ECF and to prevent edema diuretics needed
REVIEW OF KIDNEY STRUCTURE
NEPHRON SITES OF ACTION OF DIURETICS
TYPES OF DRUGS*Drugs that modify salt excretion1)Carbonic anhydrase inhibitors2)Loop diuretics3)Thiazide diuretics.4)K+ sparing diuretics.5)Osmotic diuretics. *Drugs that modify water excretion1)ADH agonists2)ADH antagonists.3)Osmotic diuretic.
SITE OF DRUG ACTIONS CARBONIC ANHYDRASE INHIBITORS (work in
proximal tubule)LOOP DIURETICS (ascending limb of loop)THIAZIDE DIURETICS (distal convolutedtubule)POTASSIUM-SPARING DIURETICS (collecting
tubule) OSMOTIC (proximal tubule, descending loop of Henle,
collecting duct)
NEPHRON SITES OF ACTION OF DIURETICS
Sites of diureticsProximal.c.tubule= 60-70%Ascending loop Henle= 20-30%Distal c. tubule = 5-8%Cortical collecting ducts = 2-5%
TYPES AND NAMES OF DIURETICS
Osmotic agents Mannitol Proximal tubule
Descending loop
Collecting duct
Carbonic anhydrase inhib.
Acetazolamide,dorzolamide,brinz
Proximal tubule
Thiazides Hydrochlorothiazide,metolazone
Distal convoluted tubule
Loop diuretic Ethacrynic acid
Furosemide,Bumetanide,Toresa
Loop of Henle
K+ - sparing Spironolactone
Amiloride,triamterene
Eplerenone
Collecting tubule
GENERAL BACKGROUND OF DIURETICS
Pattern of excretion of electrolytes (how much of which type) depends on class of diuretic agent
Maximal response is limited by site of action
Effect of two or more diuretics from different classes is additive or synergistic if there sites or mechanisms of action are different
CARBONIC ANYDRASE INHIBITORS
Block carbonic-anhydrase in the cytoplam and brush borders.
C.anhyd.Inh plays an imp. role in the secretion of CSF and aqueous humor.
Major renal effect is BICARBONATE DIURESIS.
Useful for treating glaucoma and metabolic alkalosis.
CNS--acidosisHyperventilation->Protect against High altitude Sickness.
LOOP DIURETICSGenerally cause greater diuresis than
thiazides; used when they are insuffficientInhibit co-transport of Na+,K+ and Cl- AND
excrete Ca+,and Mg+.Short Acting (4 hours)Efficacy of these durgs decreases with
NSAIDS.and (e.g. probenecid).
THIAZIDE DIURETICSActive by Oral Route.Inhibit NaCl transport in early segments of
DCT.Magnitude of effect is lower because work on
distal convoluted tubule (only recieves 5-8% of filtrate)
Cause decreased Ca excretion hypercalcemia reduce osteoporosis
POTASSIUM-SPARING DIURETICS
Have most downstream site of action (collecting tubule)
Reduce K loss by inhibiting Na/K exchangeNot a strong diuretic because action is
furthest downstreamOften used in combination with thiazide
diuretics to restrict K loss.
OSMOTIC DIURETICSNo interaction with transport systemsAll activity depends on osmotic pressure
exerted in lumenBlocks water reabsorption in proximal tubule,
descending loop, collecting ductResults in large water loss, smaller
electrolyte loss can result in hypernatremia,and hyperkalemia.
ADH AGONISTS & ANTAGONISTSAGONISTS facilitates reabsorption from the
collecting tubules.Reduces urine volume and increase its
concentrationANTAGONISTS oppose the action of ADH.Can cause significant water retention &
dangerous hyponatremia.
THERAPEUTIC USES:CARBONIC ANHYDRASE INHIBITORS
Cystinuria (increase alkalinity of tubular urine)Glaucoma (decrease ocular pressure)Acute mountain sicknessMetabolic alkalosis
LOOP DIURETICSHypertension, in patients with impaired renal
function Congestive heart failure (moderate to severe) Acute pulmonary edema Chronic or acute renal failure Nephrotic syndrome Hyperkalemia Chemical intoxication (to increase urine flow)
THIAZIDE DIURETICSHypertension Congestive heart failure (mild) Renal calculi Nephrogenic diabetes insipidus Chronic renal failure (as an adjunct to loop
diuretic) Osteoporosis
POTASSIUM-SPARING DIURETICS
Chronic liver failure with ascitesCongestive heart failure, when hypokalemia is a problem
OSMOTIC AGENTS Reduce pre-surgical or post-trauma intracranial
pressure Prompt removal of renal toxins
Reduces intraocular pressure in Acute Glaucoma.
ADH AGONISTS..Pituitary Diabetes Insipidus
ANTAGONISTS…SIADH
Adverse Effects Diuretics Symptoms
HYPOVOLEMIA loop diureticsthiazides
lassitudethirstmuscle crampshypotension
HYPOKALEMIA acetazolamidesloop diureticsthiazides
muscle weaknessparalysisarrhythmia
HYPERKALEMIA triamterenesSpironolactoneAmiloride
arrhythmiamuscle crampsparalysis
HYPONATREMIA thiazidesfurosemides
CNS symptomscoma
METABOLIC ALKALOSIS,
loop diureticsthiazides
arrhythmiaCNS symptoms
ADVERSE EFFECTS
METABOLIC ACIDOSIS
acetazolamides Kussmaul respirationsmuscle weakness neurological symptoms,lethargy coma seizures Stupor
HYPERCALCEMIA thiazides gout tissue calcificationfatigue depression confusion anorexia
HYPERURICEMIA loop diureticsthiazides
Gout
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