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Diuretics: DR Mozna Talpur

The document discusses various classes of diuretic drugs, including their mechanisms of action, sites of action along the nephron, clinical uses, and adverse effects. It covers carbonic anhydrase inhibitors, loop diuretics, thiazide and thiazide-like diuretics, potassium-sparing diuretics, and osmotic diuretics. The classes are compared in terms of their mechanisms, effects on electrolytes, and indications for use.

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Shahid Hameed
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251 views33 pages

Diuretics: DR Mozna Talpur

The document discusses various classes of diuretic drugs, including their mechanisms of action, sites of action along the nephron, clinical uses, and adverse effects. It covers carbonic anhydrase inhibitors, loop diuretics, thiazide and thiazide-like diuretics, potassium-sparing diuretics, and osmotic diuretics. The classes are compared in terms of their mechanisms, effects on electrolytes, and indications for use.

Uploaded by

Shahid Hameed
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PPTX, PDF, TXT or read online on Scribd
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DIURETICS

Dr Mozna Talpur
DIURETICS

 Drugs causing net loss of Na+ and water in urine.


 Causes increase in urine volume due to increased
osmotic pressure in lumen of renal tubule.
 Causes concomitant decrease in extra-cellular volume
(blood volume)
DIURETICS
CLASSIFICATIONS

 Carbonic anhydrase inhibitors


 Loop diuretics

 Osmotic diuretics

 Potassium-sparing diuretics

 Thiazide and thiazide-like diuretics


CARBONIC ANHYDRASE INHIBITORS
CARBONIC ANHYDRASE INHIBITORS
 Acetazolamide
 Methazolamide
 Dichlorphenamide
 The enzyme carbonic anhydrase helps to make H+ ions available for
exchange with sodium and water in the proximal tubules
 MOA:
 block the action of carbonic anhydrase,
 thus preventing the exchange of H+ ions with sodium and water
 reduces H+ ion concentration in renal tubules
 Result:
 increased excretion of bicarbonate, sodium, water, & K+
 Resorption of water is decreased and urine volume is increased
CARBONIC ANHYDRASE INHIBITORS
 Clinical uses:
 Adjunct used with miotics in the long-term management of glaucoma.
 Edema
 Epilepsy
 High-altitude sickness
 Metabolic alkalosis but can cause hyperchloremic metabolic acidosis from HCO 3-
depletion.
 Acetazolamide is used in the management of edema secondary to heart failure
when other diuretics are not effective.
 CAIs are less potent diuretics than loop diuretics or thiazides—the metabolic
acidosis they induce reduces their diuretic effect in 2-4 days
CARBONIC ANHYDRASE INHIBITORS

Adverse Effects:
Metabolic acidosis
Anorexia
Hematuria Hypokalemia
Drowsiness
Melena Paresthesia
Urticaria
LOOP DIURETICS
LOOP DIURETICS
 Generally cause greater diuresis than thiazides; used
when they are insufficient.
 Can enhance Ca2+ and Mg2+ excretion

 Enter tubular lumen via proximal tubular secretion.

 Drugs that block this secretion (e.g. probenecid) reduces


efficacy
LOOP DIURETICS
 Bumetanide
 Ethacrynic acid

 Furosemide

 Ascending loop contains Na+ - K+ - 2Cl- cotransporter


from lumen to ascending limb cells
 Loop diuretic blocks cotransporter  Na+, K+, and Cl-
remain in lumen, excreted along with water.
 Increase renal prostaglandins, resulting in the dilation of
blood vessels and reduced peripheral vascular resistance
LOOP DIURETICS ̶ DRUG EFFECTS

 Potent diuresis and subsequent loss of fluid


 Decreased fluid volume causes:
 Reduced BP
 Reduced pulmonary vascular resistance
 Reduced systemic vascular resistance
 Reduced central venous pressure
 Reduced left ventricular end-diastolic pressure

 Potassium and sodium depletion


LOOP DIURETICS
 Clinical uses:
 Edema associated with heart failure or hepatic
or renal disease
 Control of hypertension

 Increase renal excretion of calcium in patients with


hypercalcemia
LOOP DIURETICS -- ADVERSE EFFECTS
Ototoxicity

CNS: Dizziness, headache, tinnitus, blurred vision


Metabolic:Hypokalemia, Hyponatrimia

Dehydration

GI: Nausea, vomiting, diarrhea


THIAZIDE AND THIAZIDE-LIKE DIURETICS

 Thiazide diuretics
 Hydrochlorothiazide
 Chlorothiazide
 Trichlormethiazide

 Thiazide-like diuretics
 Chlorthalidone
 Metolazone
THIAZIDE AND THIAZIDE-LIKE DIURETICS
MECHANISM OF ACTION
 Acts in the distal convoluted tubule.
 Inhibit tubular resorption of sodium, chloride, and potassium ions
 Result: water, sodium, and chloride are excreted

 Potassium is also excreted to a lesser extent


 Dilate the arterioles by direct relaxation

 Results:
 Lowered peripheral vascular resistance
 Sodium, water, chloride and potassium are excreted
THIAZIDE AND THIAZIDE-LIKE DIURETICS
PRECAUTIONS

 Thiazides should not be used if creatinine clearance is less


than 30 to 50 mL/min (normal is 125 mL/min)

 Metolazone remains effective to a creatinine clearance of


10 mL/min
THIAZIDE AND THIAZIDE-LIKE DIURETICS
CLINICAL USES

 Hypertension.
 Adjunct drugs in treatment of edema related to HF, hepatic cirrhosis,
corticosteroid therapy.
 Idiopathic hypercalciuria, Patients with calcium oxalate stones.
 Diabetes insipidus(Act As ADH, causes concentrated urine)
THIAZIDE AND THIAZIDE-LIKE DIURETICS
ADVERSE EFFECTS
 Metabolic: Hypokalemia, glycosuria, hyperglycemia,
Decrease insulin release from pancreas), hyperuricemia
(Contra indicated in gout)

 CNS: Dizziness, headache, blurred vision, paresthesias,


decreased libido.
 GI: Anorexia, nausea,vomiting, diarrhea

 GU: Impotence (Structural resemblance with


dihydrotestosterone so inhibits binding to receptors)

 Integumentary: Urticaria, photosensitivity


POTASSIUM-SPARING DIURETICS

 Amiloride
 Spironolactone

 Triamterene

Also known as aldosterone-inhibiting diuretics


POTASSIUM-SPARING DIURETICS
MECHANISM OF ACTION
 Interfere with sodium-potassium exchange in collecting ducts and
convoluted tubules

 Competitively bind to aldosterone receptors


 Block the resorption of sodium and water

 Prevent potassium from being pumped into the tubule, thus


preventing its secretion

 Competitively block the aldosterone receptors and inhibit its action

 Sodium and water are excreted


POTASSIUM-SPARING DIURETICS
CLINICAL USES
 spironolactone and triamterene
 Hyperaldosteronism
 Hypertension
 Reversing the potassium loss caused by potassium-losing drugs
 Certain cases of heart failure
 Liver failure

 Amiloride
 Treatment of HF
POTASSIUM-SPARING DIURETICS
ADVERSE EFFECTS

Hyperkalemia
GI: Cramps, nausea,vomiting, diarrhea
CNS: Dizziness, headache
Other: Urinary frequency, weakness, loss of libido.
POTASSIUM-SPARING DIURETICS
ADVERSE EFFECTS
Spironolactone

 Gynecomastia
 Amenorrhea

 Irregular menses

 Postmenopausal bleeding
OSMOTIC DIURETICS
 Osmotic agents (proximal tubule, descending loop
of Henle, collecting duct)
 Reduce pre-surgical or post-trauma intracranial pressure
 Prompt removal of renal toxins
 One of the few diuretics that do not remove large amounts
of Na+
 Can cause hypernatremia
OSMOTIC DIURETICS
 No interaction with transport systems
 All activity depends on osmotic pressure exerted in
lumen
 Blocks water reabsorption in proximal tubule,
descending loop, collecting duct
 Results in large water loss, smaller electrolyte loss 
can result in hypernatremia
DIURETICS
OSMOTIC DIURETICS -- INDICATIONS
 Used in the treatment of patients in the early, oliguric phase of ARF

 To promote the excretion of toxic substances

 Reduction of intracranial pressure

 Treatment of cerebral edema

 NOT indicated for peripheral edema


DIURETICS
OSMOTIC DIURETICS -- ADVERSE EFFECTS

 Convulsions

 Thrombophlebitis

 Pulmonary congestion

 Also headaches, chest pains, tachycardia, blurred vision, chills,


and fever
DIURETICS
OSMOTIC DIURETICS

 Mannitol

 Intravenous infusion only

 May crystallize when exposed to low temperatures—use


of a filter is required
Diuretic Example Site of action

Carbonic anhydrase
Acetazolamide PCT
inhibitors

Loop diuretics Furosimide Thick ascending loop

Thiazide diuretics Hydrochlorothiazide DCT

Potassium sparing DCT and collecting


Spironolactone
diuretics tubules

PCT, Descending loop


Osmotic Diuretics Manitol of henle and
collecting tubules
 They all block Na reabsorption along the tubule
 They all cause hypokalemia EXCEPT K sparing diuretics
 K sparing diuretics are antiandrogenic EXCEPT Eplerenone
 Loop diuretics cause sulfa allergy EXCEPT Ethacrynic acid
 Hyperglycemia mostly caused by Thiazides
 Only Thiazides cause hypercalcemia, all others cause
hypocalcemia
 Acidosis is seen with carbonic anhydrase inhibitors and K
sparing diuretics
 Alkalosis is seen in loop and Thiazides diuretics
 Hyperchloremia is seen only in carbonic anhydrase inhibitors
 Caffeine works on vasodilating the glomerular vessels unlike all
other diuretics which work on blocking Na reabsorption
 Carbonic anhydrase inhibitors paradoxically cause renal stones
because they result in basic urine (bicarbonateuria)

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