diuretics
DESCRIPTION
DIURETICS. Prof. Hanan Hagar Pharmacology Department. Classification of diuretics. Carbonic Anhydrase Inhibitors Loop Diuretics Thiazides Potassium-Sparing Diuretics Osmotic Diuretics. SITES OF ACTION OF DIURETICS. Thiazide diuretics. Mechanism of action: - PowerPoint PPT PresentationTRANSCRIPT
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DIURETICS
Prof. Hanan HagarPharmacology Department
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Classification of diuretics
Carbonic Anhydrase Inhibitors Loop Diuretics Thiazides Potassium-Sparing Diuretics Osmotic Diuretics
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SITES OF ACTION OF DIURETICS
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Thiazide diuretics
Mechanism of action:acts via inhibition of Na/Cl co-transporter on the luminal membrane of distal convoluted tubules
Efficacy: Moderate 5% natriuresisDrugs as: chlorothiazide-hydrochlorothiazide
Metolazone
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Distal convoluted tubules
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Mechanism of action of thiazide diuretics
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Pharmacokinetics:
Given orally, slow of onset long duration of action (40 h)are secreted by active tubular secretory system of the kidney
may interfere with uric acid secretion and cause hyperuricemia
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Pharmacological effects:
urinary NaCl excretion
urinary K excretion (Hypokalemia)
urinary magnesium excretion
urinary calcium excretion
calcium re-absorption hypercalcemia
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Thiazide diuretics
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Uses:
Treatment of essential hypertension (cheap-well tolerated)
Treatment of mild heart failure (to reduce extracellular volume).
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Uses:
Nephrolithiasis due to
hypercalciuria (to increase calcium
re-absorption and decrease renal
calcium stones)
Nephrogenic diabetes insipidus
(decrease blood volume and GFR)
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Adverse effects:
Fluid and electrolyte imbalanceHyponatremiaHypovolemia (volume depletion)HypokalemiaMetabolic alkalosis.Hyperuricaemia (gout)Hypercalcemia HyperglycaemiaHyperlipidemia
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Potassium sparing diuretics
Drugs: Spironolactone. Triamterene. Amiloride.given by oral administration
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Act in collecting tubules and ducts by inhibiting Na re-absorption and K & H secretion (K-sparing effect) by either:
Inhibition of Na influx through Na channels in the luminal membrane (triamterene – amiloride).
Mechanism of action
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Or by antagonizing cytoplasmic aldosterone receptors (mineralocorticoid receptors Spironolactone).
Spironolactone : is a synthetic steroid that acts as a competitive antagonist for aldosterone.
Mechanism of action
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COLLECTED TUBULES (CT)
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urinary Na excretion
urinary K excretion
hyperkalemia
H secretion (acidosis)
Pharmacodynamics:
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Therapeutic uses:
Drug of choice for patients with
hepatic cirrhosis
In mineralocorticoid
hypersecretion e.g. Conn’s
syndrome
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Therapeutic uses:Secondary hyperaldosteronism: (CHF, hepatic cirrhosis, nephrotic syndrome).
Treatment of hypertension (combined with thiazide or loop diuretics to correct for hypokalemia).
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Adverse Effects
Hyperkalaemia.
Metabolic acidosis.
Gynaecomastia
GIT upset and peptic ulcer
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Contraindications:
Hyperkalaemia: as in chronic renal failure, K+ supplementation, -blockers or ACE inhibitors.
liver disease (dose adjustment is needed).
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Osmotic diuretics
Mannitol
Poorly absorbedGiven intravenously.Not metabolizedExcreted by glomerular filtration without being
re-absorbed or secreted within 30-60 min.
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Mannitol
Acts in proximal tubules & descending loop of Henle by osmotic effect.
Retains water within the tubules (water diuresis).
Has a secondary effect on reducing sodium re-absorption.
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Therapeutic Uses:
Cerebral edema (increased intracranial pressure).
Glaucoma.Acute renal failure due to shock, trauma, drug toxicities (maintain urine flow- preserve kidney function).
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Adverse Effects:
Extracellular water expansion (extracts water from cells)
Dehydration
Hypernatremia
Headache, nausea, vomiting
Adequate water replacement is required.
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Therapeutic applications of diuretics
Treatment of hypertension:Treatment of hypertension:o Thiazide diureticso used alone or in combination with beta-
blockers at low-dose (fewer side effects)o In presence of renal failure, loop
diuretic is used.Edema StatesEdema States Thiazide diuretic is used
in mild edema with normal renal function
o Loop diuretics are used in cases with impaired renal function.
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Congestive Heart failureCongestive Heart failure Thiazides may be used in only mild
cases with well-preserved renal function
Loop diuretics are much preferred in severe cases especially when GF is lowered
In life-threatening acute pulmonary edema, furosemide is given IV.
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Renal failureRenal failure Thiazides are used till GFR ≥ 40-50 ml/min Loop diuretic are used below given values,
with increasing the dose with as GFR goes down.
Diabetes inspidusDiabetes inspidus Large volume(>10 L/day) of dilute urinethiazide diuretics reduces urine volumeHepatic cirrhosis with ascitesHepatic cirrhosis with ascites Spironolactone is of choice.
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Diuretics Mechanism of action
Effects
CA inhibitorsAcetohexamideDorzolamide
Inhibition of NaHCO3
reabsorption in PCT
Urinary Na HCO3, KUrinary alkalosisMetabolic acidosis
Osmotic diureticMannitol
Osmotic effect in PCT & DLH
Urine excretion Little Na
Loop diureticsFurosemide
Na/K/2Cl transporter in TAL the most
effective
Urinary Na, K, Ca, Mg
Thiazide diuretics
hydrochlorothiazide
Na and Cl cotransporter in
DCT
Urinary Na, K, Mg BUT↓ urinary Ca (hypercalcemia)Metabolic alkalosis
K-sparing diureticSpironolactone.
competitive antagonist of aldosterone in
CCT
↑ Urinary Na↓ K, H secretionMetabolic acidosis
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Diuretics Uses
CA inhibitorsAcetohexamideDorzolamide (topically) for glaucoma
Glaucoma, epilepsyMountain sickness
Osmotic diureticMannitol
• Cerebral edema• Acute renal failure
Loop diureticsFurosemide
Acute pulmonary edema (Drug of choice)Heart failureHyperkalemia, Hypercalcemia
Thiazide diuretics
hydrochlorothiazide
Commonly usedHypertension, heart failure, hypercalciuria, kidney stones, diabetes inspidus
K-sparing diureticSpironolactone.
Hepatic cirrhosis(Drug of choice)
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Diuretics Side effectsCA inhibitorsAcetohexamideDorzolamide
Metabolic acidosis , Urinary alkalosisHypokalemia
Osmotic diureticMannitol
Extracellular water expansionDehydrationHypernatremia
Loop diureticsFurosemide
Hypokalemia,hypovolemia, hyponatremia, hypomagnesemia, hypocalcemiaPrecipitate gout, alkalosis
Thiazide diuretics
hydrochlorothiazide
Hypokalemia, hyponatremia, hypovolemia, hypomagnesemia, hypercalcemiaAlkalosis, precipitate goutHyperlipidemia, hyperglycemia
K-sparing diureticSpironolactone.
Gynaecomastia Hyperkalaemia, Metabolic acidosis.GIT upset and peptic ulcer