Diuretics 1: Thiazides Flashcards
Pharmacokinetics of thiazide diuretics
- Well absorbed orally
- Must be secreted by organic Acid secretory system (OASS) in PCT to act from inside the nephron
- Therefore, decreased renal function decreases it’s diuretic effect
- Also Probenecid inhibits its diuretic effect by inihbiting OASS
- Thiazide leads to decreased uric acid secretion (by competing with uric acid with OASS)
Describe mechanism of diuretic effect of thiazide diuretics
Moderate efficiacy:
* Blocks Na+/Cl- transporter
* NaCl reabsorption decreases
* luminal NaCl increases
* leading to diuresis
* Excess NaCl reaches late DCT, where some Na+ is reabsorbed in exchange for K+ & some H+ excretion
effect of Thiazides on Electrolytes & Acid base balance
- Hypokalemia
- Hypovolemia
- Hyponatemia
- Hypochloremia
- Hypomagnesemia
- Alkalosis
- Hypercalcemia
explain how thiazide diuretics cause Hypercalcemia
- Enhances passive Ca2+ reabsorption from PCT
- enhances Na+ Ca2+ exchange from DCT
enumerate theraputic uses of Thiazide diuretics
- Hypertension
- Heart failure
- Edema
- idiopathic hypercaluria (hypocalcemia & osteoperosis)
- Nephrogenic Diabetes Insipidus (NDI)
Explain why in hypertension, sometimes Loop diuretics are prefered instead of Thiazide diuretics
hypetensive effect of Thiazide diuretics is impaired in low GFR (<30 ml/min)
True or false, thiazide Diuretics can only be used in hypertension using up to Diuretic dose
False, can even be used sub-diuretic doses
other antihypertensive drugs that can be used with Thiazide diuretics
- Minoxidil (vasodilator)
- Hydralazine (Vasodilator)
- ACE inhibitors
describe Mechanism of Thiazide Antihypertensive effect
DD (Dilator Diuretic):
Arteriolar VD:
* K+ channel opener –> Hyperpolarisation
* Depletion of Na+ & Water from arteriolar wall —> decreases Pressor effect of Adrenaline & Angiotensin II
* Prostaglandins
Diuretic –> decreases blood volume –> temporary antihypertensive effect
Antihypertensive effect of thiazides can be Antognized by:
NSAIDs;
by inhibiting Prostaglandin synthesis which is one of the key factors in VD caused by Thiazides
describe mechanism of Thiazide diuretics in treating heart failure
- Arterial VD: decreased Peripheral resistance –> Decrease Afterload
- Diuretic: Decreased blood volume –> decreased Venous return –> decreased preload
Types of edema treated by thiazide diuretics
- Cardiac
- Hepatic
- Renal
- Premenstural
adverse effects & toxicity of Thiazide diuretics
- Hypokalemia
- Hypovolemia
- hyponatrema
- Hypochloremic Alkalosis
- Hypomagesemia
- Hypercalemia
- Hyperuricemia (worsens gout)
- Hyperglycemia (hypokalemia–> imparied release of insulin)
- Hyperlipidemia
- Hypersensitivity and cross allergy
- Fetotoxic
How to prevent hypokalemia caused by Thaizide diuretics
- Fruit juice
- Intremittent use of least effective dose
- KCL supplementation (solution less irritant than tablets)
- Add a Potassium sparing diuretic: Spironolactone
Contraindications of thiazide diuretics
- Digitalis toxicity –> Hypokalemia (hypercalcemia, hypomagnesemia)
- with Corticosteroids –> hypokalemia
- Advanced liver disease
- Advanced kidney disease
- Diabetes mellitus (due to hyperglycemia)
- Gout (due to hyperuricemia)
- Fetotoxic (pregnency)
