Class diuretics
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CLASS DIURETICS
Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSOR DEPT. OF PHARMACOLOGYSSIMS & RC.
CLASSIFICATION
DIRECTLY ACTING A) Acting on thick ascending loop of henle-
FUROSEMIDE, BUMETANIDE, TORSEMIDE, PIRETANIDE,ETHACRYNIC ACID, INDACRINONE(uricosuric drug)
B) Acting on proximal part of distal tubule THIAZIDE group- HYDROCHLORTHIAZIDE,
CHLORTHIAZIDE, BENZTHIAZIDE, POLYTHIAZIDE, CHLORTHALIDONE, METOLAZONE
CLASSIFICATION
C) Those acting on collecting ducts and tubules
AMILORIDE, TRIAMTERINEAldosterone antagonist-
SPIRONOLACTONE, EPLERENONEINDIRECTLY ACTINGOsmotic diuretics- MANNITOL,
GLYCEROLCarbonic anhydrase inhibitors-
ACETAZOLAMIDE, DORZOLAMIDE, ETHOXZOLAMIDE, METHAZOLAMIDE
70%
20%
5%
4.5%
0.5%Volume 1.5 L/dayUrine Na 100 mEq/LNa Excretion 155 mEq/day
100%GFR 180 L/day Plasma Na 145 mEq/LFiltered Load 26,100 mEq/day
Collecting duct
Thick Ascending Limb
Loop diuretics or High ceiling diuretic
Ethacrynic acid-ototoxicity, hepatotoxicity, hypochloremic alkylosis
Frusemide Bumetanide – 40 times potent Torsemide – three times potent and
long acting Indacrinone –gout patients
RENAL TUBULAR INTERSTITIUM LUMEN
Na+K+Cl-
TPC
Na+
H+
Na+
K+
PARACELLULAR DIFFUSIONNa+ K+ Mg++ Ca++
Cl-
+8 mV
RENAL TUBULAR INTERSTITIUM LUMEN
Na+K+Cl-
TPC
Na+
H+
Na+
K+
PARACELLULAR DIFFUSIONNa+ K+ Mg++ Ca++
Cl-
+8 mV
THICK ASCENDING LOOP
LOOP DIURETICS
Therapeutic uses
Oedematous conditions associated with CCF,
Cirrhosis of liver, renal disease including nephrotic syndrome
Hypertension Acute renal failure Toxicity of ions Mild hyperkalemiaNon-diuretic use-moderate
hypercalcemia
Adverse effects
Hyperuricemia Hypercalciuria and
hypomagnesaemia Hypokalemia Ototoxicity Hyperglycemia Hypersensitivity reactions
Drug interactions
Digitalis toxicity Elevated serum lithium levels Aminogycosides – increased
ototoxicity NSAIDs diminish the action Probenacid competative inhibition Cotrimoxazole –thrombocytopenia
THIAZIDES
MECHANISM OF ACTION Inhibit Na+ and Cl- transporter in distal
convoluted tubules Increased Na+ and Cl- excretion Weak inhibitors of carbonic anhydrase,
increased HCO3- excretion Increased K+/mg2+ excretion Decrease Ca2+ excretion
D C T Early DCT Late DCT
Na+
Cl-
LUMEN
K+
Na+
Cl-
THIAZIDES
THIAZIDES-Uses
Hypertension Congestive heart failure Hypercalciuria: prevent excess ca2+ excretion
to form stones in ducts Osteoperosis Nephrogenic diabetes insipidus Treatment of li+ toxicity
THIAZIDES-adverse effects
Hypokalemia Hyponatremia, hyperglycemia Diminished insulin secretion Elevated plasma lipids, hyperuricemia Hypercalcemia
K+ sparing diuretics
Spironolactone is a steroid compound, which is a competitive aldosterone antagonist.
It increases Na+ excretion and decreases K+ and urea excretion. Its diuretic action is weak and is achieved slowly.
K+ sparing diuretic
Prevent K loss caused by other diuretics in: HypertensionRefractory edemaPrimary aldosteronism- caused by increased production of aldosteroneHirsutism due to P C O D.Cirrhotic Edema
K-Sparing Diuretics
Collecting DuctNa Na
NaNa
Amiloride and Triamterene directly block the ENaC channel
Aldo
Spares potassium by decreasing the lumen-negative gradient that drives the expulsion of K/H into the lumen
Site of action: cortical collecting duct
Mechanism: Blocks E Na channels
Pharmacokinetics: Half-life = 3-5 hours
K K
K-Sparing Diuretics
Collecting Duct
Li
Li
Li
Li
Li
Amiloride blocks Li+ resorption through Na+ Channelsreduces lithium induced polyuria
They can be used to treat oedematous conditions including liver cirrhosis, as they cause hyperkalemia
Combined with thiazides to treat refractory oedema
K-Sparing Diuretics-side effects
Hyperkalemia-better to avoid K+ supplementation Drug interaction - do not use their combination,
since the potassium sparing effect is greater than additive
Caution with ACE inhibitors Reversible azotemia (triamterine) Triamterene nephrolithiasis.
Carbonic anhydrase inhibitors limited uses as diureticAcetazolamide prototype carbonic anhydrase inhibitor developed from sulfanilamide (caused metabolic
acidosis and alkaline urine)
Mechanism of CAIs
Carbonic anhydrase inhibitors inhibits carbonic anhydrase in renal proximal tubule
cells carbonic anhydrase catalyzes formation of HCO3-
and H+ from H2O and CO2 inhibition of carbonic anhydrase decreases [H+] in
tubule lumen less H+ for for Na+/H+ exchange increased lumen Na+, increased H2O retention
Carbonic anhydrase inhibitors-uses
Used to treat chronic open-angle glaucoma aqueous humor has high [HCO3-] Acute mountain sickness decrease CSF formation
and by decreasing pH Metabolic alkalosis they can produce
hyperchloremic acidosis Sometimes in epilepsy decreasing the pH Mostly used in combination with other diuretics in
resistant patients Alkalinisation of urine
Carbonic anhydrase inhibitors-S/E
Rapid toleranceIncreased HCO3- excretion causes metabolic acidosisDrowsiness, fatigue, CNS depressionParesthesia (pins and needles under skin)Nephrolithiasis (renal stones), K+ wasting
Osmotic diuretics
Mannitol (prototype), Urea, Glycerol, do not interact with receptors or directly block renal
transport activity dependent on development of osmotic
pressure Osmotic diuretics are not reabsorbed Increases osmotic pressure specifically in the
proximal tubule and loop of Henle Prevents passive reabsorption of H2o
Osmotic diuretics
Osmotic force in lumen > osmotic force of reabsorbed Na+
Increased H2o and Na+ excretionUsesTo treat oliguria state in shockCerebral edema and gloucoma Adverse effects Osmotic diarrhea- mannitol May worsen cardiac failure and pulmonary edema
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