| What is the principle of diuretics action? | They increase the urine flow and excretion of Na+ (natriuresis), most clinical uses are for reducing extracellular fluid volume by decreasing total body NaCl. |
| What are sites of action of diuretics? | 5 main classes:
Loop (act on ascending Henle's Loop)
Thiazide (act on distal convoluted tubule)
Carbonic-Anhydrase Inhibitors (on proximal convoluted tubule)
Potassium-Sparring Diuretics (Cortical collecting tubule aldosterone sensitive principal cells [aldosterone antagonists and Na+ channel blockers])
Osmotic Diuretics (proximal convoluted tubules and descending henle's loop) |
| What are the mechanisms of action of diuretics? | Inhibiting kidney's ability to reabsorb Na thus losing water (loop diuretics)
enhancing excretion of sodium and water (thiazide diuretics)
Blocking exchange of sodium for potassium excreting sodium furthermore (Potassium-Sparring Diuretics) |
| What are loop diuretics? | Most effective type of diuretics excludes 20-25% of filtered salt and water.
They inhibit Sodium-Potassium-Chloride cotransporter in luminal membrane in thick ascending limb of the loop, prevent the body from reabsorbing sodium at ascending henle's loop leading to diuresis and natriuresis, also reduces Ca2+ and Mg2+ reabsorption.
Secondary effect is increasing renal synthesis of PGs resulting in increased blood supply to the kidney
Thus decreased blood volume and vasodilation together will lead to decrease blood pressure and ameliorate edema.
They are used when intensive diuresis is required.
Increase Ca excretion important for hypercalcemia pt. |
| What are types of loop diuretics? | Lasix/Furosemide/Bumetanide (Sulfonaminde derivative, admin PO/IV, onset of action IV 2-5 min, IM 10-20 min, PO 20-40 min, short duration (3-6 hours)
Ethacrynic acid (only loop diuretic not sulfonamide derivative [phenoxyacetic acid], used in case of allergies to sulfonamide, but causes ototoxicity so rarely used) |
| What are therapeutic uses of loop diuretics? | Management and treatment of fluid overload conditions (pulmonary edema [vasodilation activity when admin IV], Chronic congestive HF [decrease ECM], HTA) |
| What are thiazide diuretics? | Low Ceiling Diuretics, inhibit sodium-chloride transporters in distal portion of nephron stops reabsorption, this portion is involved in only 5% of reabsorption so less efficacy of drugs than loop diuretics in diuresis and natriuresis.
They also increase calcium reabsorption increasing blood calcium |
| What are therapeutic uses of thiazide diuretics? | Widely used in management of CVD and renal diseases, prescribed for HTA and can be used for edema w/HF.
Helpful in pt w/nephrolithiasis w/hypercalciuria |
| What are names of thiazide diuretics? | Hydrochlorothiazide (HCTZ/Esidrex, bioavailability 70%, t1/2 2.5 hours, eliminated urine, action 6-12 hours PO not IV), Indapamide (low dose antihypertensive, diuretic and vasodilator property, action for 36 hours, PO) |
| What are carbonic anhydrase inhibitor drugs? | Decrease sodium bicarbonate reabsorption by proximal tubule inhibiting carbonic anhydrase, retains bicarbs and potassium and decreased sodium reabsorption.
Drugs belonging to it (acetolamide [ophthalmo use tx of glaucoma, decrease intraocular pressure, much less efficacy than loop and thiazide diuretics] |
| How is mechanism of action of carbonic anhydrase inhibitor drugs? | Carbonic anhydrase usually convert bicarb to CO2 and water which are absorbed into tubular cells and reconverted into bicarcb, inhibitors stop this process thus lose bicarb which carries with it sodium, water and potassium |
| What are potassium sparring diuretics? | Promote diuresis without causing potassium loss:
They include:
1- Aldosterone antagonists.
2-Epithelial sodium channel blockers. |
| What are aldosterone antagonists potassium sparring diuretics? | Aldosterone normally adds sodium channels to principal cells in the collecting duct of the nephron, but the Aldosterone antagonists block the aldosterone receptors and therefore preventing the reabsorption of sodium and water and prevents therefore K+ and H+ secretion.
Spironolactone=Aldactone |
| What are epithelial sodium channel blockers potassium sparring diuretics? | These drugs directly prevent sodium from entering the epithelial sodium (ENaC) channels, which are found in the apical membrane of the collecting tubule.
Amiloride and Triamterene
They are primarily used to prevent and treat hypokalemia induced by thiazides and loop diuretic
The most characteristic adverse effect of the potassium-sparing diuretics is hyperkalemia |
| Table of Potassium Sparring Diuretics? | . |
| What are osmotic diuretics? | Adding substances that increase the osmolarity of tubular fluid causing prevention of water reabsorption and thus water excretion (not Na+ so not very useful in treating conditions of Na+ retention, more for tx of pt w/ increased intracranial pressure)
Mannitol is an example given IV (not PO) |
| What are the general therapeutic uses of diuretics? | HF (primary use of diuretics, reduce pulmonary/systemic congestion and edema, long term reduces the afterload promoting systemic vasodilation improving ventricular ejection)
HTA (able to reduce blood volume, CO and systemic vascular resistance) |
| Table of pharmacokinetics of diuretics? | . |
| Scheme of changes in urinary composition of diuretics? | . |
| Table of side effects and drug interaction w/diuretics? | . |
