- Inhibitors of Na+ & Cl- reabsorption.
- By inhibiting Na+ K+ 2Cl- cotransporter on thick ascending limb.
- Hence, excreting Na2+.
- Na2+ excretion continues even if ECF is less & hence causes dehydration & hypotension.
- Na2+ excretion accompanies increased H+ & K+ loss.
- May cause metabolic alkalosis.
- Produces vasodilator action, directly or indirectly by releasing renal factor.
- Potentiates thiazides action.
- Reduces edema due to cardiac failure, hepatic disease, nephrotic syndrome.
- Eg: Acute pulmonary edema, cerebral edema, acute chronic renal failure, pregnancy & idiopathic edema.
- Drug of choice for acute left ventricular failure is I/V Furosemide.
- Useful in Barbiturate poisoning, salicylate poisoning.
Nondiuretic action of Loop Diuretics:
- As an antihypertensive.
- Idiopathic calcium urolithiasis.
- Hyponatremic states due to water retention.
- Hypokalemia – Combined with potassium-sparing diuretics.
- Hyponatremia, dehydration & metabolic acidosis.
- Hyperglycemia, hyperuricemia, Hypomagnesemia .
- Weakness, fatigue, dizziness, cramps & myalgia.
- Prostatic hypertrophy, ototoxicity, cardiac arrest after IV injection.
- Hepatic insufficiency, gastric upset.
- Orthostatic hypotension.
- Potent oral diuretic.
- Has halogenated sulfamoyl benzene ring common to Thiazide diuretics.
- Acts on thick ascending loop of Henle, blocking Na+-K+ 2Cl– symport.
- Furosemide attaches to Cl- binding site of protein (Na+ K+ 2Cl-) inhibiting its transport function.
- 160 mg furosemide – Cirrhosis & portal hypertension.
- Excretion of Na+, K+, Cl-, PO4.
- IV administration increases renal blood flow.
- Increases PGE2 synthesis in kidneys – Has locally protective & vasodilator effect.
- In physiological or pharmacological stress – Counteracts intrarenal vasoconstriction.
- Excessive chloride loss →hypochloremic alkalosis.
- K+ loss→ Hypokalemia. (Less marked with Furosemide than Thiazides).
- Little change in Urine pH. Potent renin releasers.
Blood vessels & BP:-
- IV furosemide dilates peripheral vasculature.
- Lowers the arterial BP.
- Rapid venous pooling of blood.
- Reducing cardiac preload & afterload.
- ↑ blood uric acid, ↑ blood urea & disturbances of glucose tolerance.
- ↑ Ca++ & Mg++ excretion.
- Absorbed orally.
- Bioavailability 60-100%.
- Food reduces bioavailability.
- Onset of action is quick & short.
- Low lipid solubility.
- Excreted within 4 hours.
- 50% excreted unchanged, rest conjugated with glucuronide in kidney.
- 3 times more potent than furosemide.
- Oral absorption more rapid & complete.
- 80% metabolized in liver.
- t1/2= 3.5 hrs.
- Duration of action= 4-8 hrs.
- Used in hypertension & edema.
- 40 times more potent than furosemide.
- Onset & duration and its effect on electrolyte excretion are similar to furosemide.
- 80% absorption.
- Metabolized in liver & its half-life is not prolonged in renal insufficiency.
- Max. diuresis within 2-3 hrs after giving orally.
- Used in edematous states, especially in patients allergic to sulphonamides.
- Less used because prone to cause adverse effects (Ototoxicity mainly)similar to those of furosemide.
- Potentiate all other antihypertensives.
Hypokalaemia induced by these diuretics:
- Enhances digitalis toxicity.
- Produces polymorphic ventricular tachycardia with quinidine and other antiarrhythmics.
- Potentiates competitive neuromuscular blockers and reduces sulfonylurea action.
- Loop diuretics + aminoglycoside antibiotics – both ototoxic and nephrotoxic → additive toxicity.
- Cotrimoxazole + loop diuretics- thrombocytopenia.
- Indomethacin/ NSAIDs + Loop diuretics- diminishes diuretic and antihypertensive effect of loop diuretics.
- Probenecid + furosemide and thiazides competitively inhibit tubular secretion of furosemide and thiazides.
- Serum lithium level rises when diuretic therapy
- Furosemide and warfarin/ Clofibrates: Displacement of plasma protein binding of warfarin
- Hyperglycemia, Hypomagnesemia, acidosis, Hypokalemia, Ototoxicity & Hyperuricemia are adverse effects can be caused by Loop Diuretics
- The usual maximum dose of furosemide and spironolactone in patients with cirrhosis and portal hypertension is Furosemide 160 mg and spironolactone 400 mg
- Loop diuretic is the mechanism of action of bumetanide
- Loop diuretics are most likely to result in contraction alkalosis
- Loop diuretics act on Thick ascending limb
- Ethacrynic acid causes increased concentration of Na’ & Cl– in urine with normal bicarbonate
- Furosemide is used in pulmonary edema
- Ethacrynic acid is not used due to Ototoxicity
- Loop diuretics interact with cefotaxime
- IV fluid with furosemide is given in Hypercalcemia
- Drug of choice for acute left ventricular failure is I/V Furosemide
- Furosemide is excreted unchanged in urine
- Diuretics of choice for acute pulmonary edema is Loop diuretics
- The site of action of the loop diuretic furosemide is Thick ascending limb of loop of Henle