Thiazide Diuretics

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Prepared by
Hindi Salem Alharbi
Supervised by
Dr. Vasudevan Mani Kumara
DEFINTIONS
Diuretics are chemicals that increase the volume
of the urine excreted by the kidney through
increase the rate of urine formation. Reduce the
extracellular fluid volume by promoting the
excretion of Na+or Cl-or HCO3-ions which
constitute the main electrolytes of the
extracellular fluid.
• Natriuresis- increased sodium excretion
• Kaliuresis- Increased Potassium excretion
CLASSIFICATION
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Carbonic Anhydrase Inhibitors
Acetazolamide,Dorzolamide
Osmotic Diuretic
Glycerine,Mannitol
Loop Diuretics
Frusemide,Bumetanide,Torasemide,Ethacrynic acid
Thiazide and thiazide related Diuretics
Hydrochlorothiazide,polythiazide,Metolazone,Indapamide
Potassium Sparing Diuretics
– Aldosterone Antagonist
• Spironolactone,Canrenone, Eplerone
– Direct Acting
• Triamterene, Amiloride (more potent)
SITE OF ACTIONS
Carbonic An-hydrase Inhibitors
Thiazide diuretics
SITE OF ACTION
Osmotic Diuretics
Potassium Sparing Diuretics
Loop Diuretics (High Ceiling)
THIAZIDE AND THIAZIDE-RELATED
DIURETICS
Thiazide and related Diuretics
-Chlorothiazide (the only thiazide for
parenteral use)
-Chlorthalidone
-Hydrochlorothiazide,Bendroflumethiazide
-Indapamide (non-thiazide Sulfonamide)
-Metolazone
-Polythiazide, Benzthiazide
-Quinethazone
THIAZIDE AND THIAZIDE-RELATED
DIURETICS
Thiazide diuretics are sulfonamide compounds.
Orally efficacious, have a moderate natriuretic effect,
and have few adverse effects in most patients.
All thiazide diuretics are secreted in the proximal
tubule but their site of action is the distal tubule.
They compete with uric acid for secretion (the same
system secretory mechanism)
hyperuricemia
THIAZIDES MECHANISMS OF ACTION
Thiazide diuretics inhibit re-absorption of
Na+and consequently Cl-in the distal
convoluted tubule by inhibition of Na+/ Clco transport system present in the luminal
membrane (saluretic).
They lead to loss of 5-8% of the load of
sodium.
THIAZIDES MECHANISMS OF ACTION
NaCl-rich tubular fluid reaching late distal tubule
and collecting duct stimulates exchange of Na+
and K+.
Increased Na+ delivery leads to increased secretion
of K+ and H+ by duct.
By this process, thiazides produce a kaliuretic
effect, causing hypokalemic metabolic alkalosis.
THIAZIDES MECHANISMS OF ACTION
Unlike other diuretics,
Thiazides ↑ Mg+ excretion and Ca2+ reabsorption in distal convoluted tubule and
thus ↓ Ca2+ excretion in urine.**
**This is the basis for thiazides use in kidney
stones caused by excessive calcium in the urine.
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Action of thiazides depends in part on renal PGs
synthesis; therefore, actions of thiazides can be
inhibited by NSAIDs under certain conditions.
THIAZIDES MECHANISMS OF
ACTION
Thiazides
ADVERSE EFFECTS AND DRUG-INTERACTIONS
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Hypokalemia.
hypokalemic metabolic alkalosis.
Hyperglycemia
Hyprelipedemia.
Hyperuricemia (may precipitate gout).
Cross-reactivity with sulfonamides may result in
hemolytic anemia, thrombocytopenia & acute
necrotizing pancreatitis.
Weakness, fatigability and paresthesias may
occur.
CLINICAL INDICATIONS
-Hypertension
-Congestive Heart Failure
-Cirrhosis
-Nephrolithiasis (kidney stones) due to idiopathic
hypercalciuria
-Nephrogenic Diabetes Insipidus (insufficient level of ADH)
-Nephrotic Syndrome
-Pulmonary Edema
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Hydrochlorothiazide is the most commonly used diuretic
and Polythiazide has a much longer half life and duration
of action (DOA) than HCTZ.
THIAZIDE-LIKE DIURETICS
Indapamide and Metolazone are slightly different
in structures from thiazide diuretics, but similar
in actions.
Indapamide is generally used in the treatment of
CHF and hypertension.
Metolazone may be more effective than Thiazides
in patients with impaired renal function.
Metolazone is sometimes combined with loop
diuretic to treat patients with diuretic
resistance.
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