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Hypertension - Diuretics
- Thiazide e.g. Hydrochlorothiazide
- Thiazide-like e.g. Chlorthalidone
- Loop e.g. Frusemide
- Selective Aldosterone Blocker e.g. Eplererone
- Potassium sparing e.g. Spironolactone
Hypertension - Diuretics - MOA
- - increase sodium excretion, ␣reduction in plasma volume and cardiac output.
- - reduction in peripheral resistance, (mechanism is unclear)
Hypertension - Thiazide and Thiazide-like diuretics
- - Inhibit absorption of sodium and chloride in the proximal segment of the distal convoluted tubule by binding to the chloride-binding site of the Na+-Cl-
- - Promote renal excretion of water, sodium, chloride, potassium and magnesium
- - Decrease excretion of uric acid and calcium
- - Thiazides are less potent than loop diuretics and have a longer half-life
- - Often regarded as belonging to the thiazide diuretics class as it acts at the same place in the renal tubules and has a similar effect, although they have different chemical structures.
- o Indapamide is often used as a first-line treatment of mild to moderate essential hypertension.
- o At low doses, it appears to decrease vasoconstriction mediated through adrenaline and noradrenaline which leads to decreased total peripheral resistance (TPR) ␣ decreased BP.
- o At high doses, it works on the proximal part of the distal tubule in the kidney, inhibiting the inc Na+/Cl- (as well as Cl- & water) (much like a thiazide diuretic). This leads to decreased cardiac output resulting in decreased BP.
Thiazides & thiazide-like diuretics - interactions
- - Can aggravate digoxin toxicity
- - Can aggravate lithium toxicity
- - Increases hyperglycaemic effect of corticosteroids
- - NSAIDs (decreased natriuresis and reduced
- antihypertensive effect)
Indapamide (thiazide-like) - care exercised if taking
- - digoxin (increase toxicity in presence of abnormal plasma K+),
- - lithium (decrease renal clearance and create Li- toxicity),
- - or if patient has gout (decreased uric acid clearance by kidney).
Hypertension Loop diuretics
- - Loop Diuretic is actively secreted into the lumen of the nephron proximal tubule cells (PCT)
- - In the ascending Loop of Henle they inhibit the Na+-K+- 2Cl- transporter thus preventing reabsorption of sodium and chloride
- - Loss of fluid volume from the blood␣spontaneous feedback to increase release of aldosterone (hormone that normally further increases activity of Na+/K+ ATPase pump, resulting in even more loss of K+
- - Also decreases uric acid excretion & increases serum uric acid.
Loop diuretics - Indications
- - Oedema (peripheral and pulmonary) associated with chronic renal failure, chronic liver cirrhosis and hypertension (usually associated with renal or cardiac failure)
- ␣ Used for Syndrome of inappropriate ADH secretion (SIADH)
- ␣ Loop diuretics enhance excretion of calcium and magnesium by interfering with reabsorption ␣ thus can be used for hypercalcaemia
Loop diuretics - Cautions and Warnings
- - Loop diuretics should be used with caution in patients with possible electrolyte disturbances, prostatic hypertrophy or pregnancy (Category C).
- ␣Co-Administration of a K+ sparing diuretic can help to prevent development of hypokalaemia in vulnerable patients. Diuretics are not potent enough to be used as monotherapy in CCF (Congestive Cardiac Failure).
- ␣Hypokalaemia or hyperkalaemia can aggravate digoxin toxicity (many patients requiring diuretics, especially loop diuretics, may be on
- Digoxin® concurrently).
Potassium-sparing diuretics Aldactone - MOA
- - Aldosterone Antagonists - competitive antagonists to Aldosterone for the distal renal collecting tubule/duct receptors ␣ decreased Na+ reabsorption in renal collecting tubules/ ducts, and increased retention (decreased excretion) of K+.
- - weak diuretics, so work best as an adjunctive therapy.
Potassium-sparing diuretics - e.g. spironolactone - Indications
- - Used to treat hyperaldosteronism, liver cirrhosis (because aldosterone is not being metabolized), and may be combined with a loop or thiazide diuretic in treating hypertension or CCF in patients losing K+.
- - Prevention and treatment of diuretic-induced hypokalaemia
- Main adverse effect
- ␣ Hyperkalaemia.
Beta - Blockers
Atenolol - cardioselective
Carvedilol - only one used in CCF (CHF)
- - blockers inhibit the binding of catecholamines (e.g adrenaline, noradrenaline, dopamine) at the Beta 1
- adrenoreceptor site in the heart
- o Pharmacologically, blockade of Beta 1 receptors decreases rate, conduction velocity, myocardial contractility and cardiac output
- o Anti-hypertensive effect results from decreased cardiac output without a reflex increase in peripheral vascular resistance;
- - diminished sympathetic outflow from the vasomotor centre in the brain to the peripheral blood vessels; reduced renin release by the kidney
- o They also have direct effect on the heart itself (blocking the ␣1adrenoceptor-mediated increase in rate (chronotropicity) and force (inotropicity) of cardiac contractions).
- o ␣1-blockade can also decrease conduction velocity within the heart, therefore some ␣-blockers such as sotalol can be prescribed for certain tachyarrhythmias.