1. What is high ceiling diuretic & Why?
HC diuretics are those, that produce peak diuretic. e,g-Frusemide, Bumetamide.
It is so called because they produce peak diuresis by excreting about 30% Na+ glomerular filtrate.
Common characteristic of loop diuretic-
Very potent.
Onset of action is rapid (2-3 min)
Short duration of action about 4 hours
No interfere with acid base balance
Inhibit Na+ & Cl- transport in the accending limb loop of henli.
Can act in severe renal & heart failure.
No need of combination to potentiate its action

2. Chemistry
Furosemide, bumetanide, and torsemide are sulfonamide derivatives.
Ethacrynic acid—not a sulfonamide derivative—is a phenoxyacetic acid derivative containing an adjacent ketone and methylene group. The methylene group (shaded) forms an adduct with the free sulfhydryl group of cysteine. The cysteine adduct appears to be an active form of the
drug.
Organic mercurial diuretics also inhibit salt transport in the thick ascending limb but are no longer used because of their high toxicity.

3. Mechanism of action
These drugs inhibit the luminal Na+/K+/2Cl- transporter in the thick ascending limb of Henle's loop. By inhibiting this transporter, the loop diuretics reduce the reabsorption of NaCl and also diminish the lumen-positive potential that derives from K+ recycling. This electrical potential normally drives divalent cation reabsorption in the loop, and by reducing this potential, loop diuretics cause an increase in Mg2+ and Ca2+ excretion. Prolonged use can cause significant hypomagnesemia in some patients. Since Ca2+ is actively reabsorbed in the distal convoluted tubule, loop diuretics do not generally cause hypocalcemia. However, in disorders that cause hypercalcemia, Ca2+ excretion can be greatly enhanced by combining loop agents with saline infusions.

5. Loop diuretics also have incompletely understood vascular actions
Loop diuretics also have incompletely understood vascular actions. Intravenous administration of furosemide to patients with pulmonary oedema caused by acute heart failure causes a therapeutically useful vasodilator effect before the onset of the diuretic effect. Possible mechanisms that have been invoked include decreased vascular responsiveness to vasoconstrictors such as angiotensin II and noradrenaline; increased formation of vasodilating prostaglandins; decreased production of the endogenous ouabain-like natriuretic hormone (Na+/K+ ATPase inhibitor), which has vasoconstrictor properties; and potassium channel-opening effects in resistance arteries.

6. Clinical use of loop diuretics or Frusemide:
Acute pulmonary edema and other edematous contidion.
Moderate hypertension.
Left venticular failure.
Congestive heart failure.
Acute renal failure.
Hypercalcemia & hyperkalemia.

7. Pharmacokinetics:
Route of administration ----Oral / iv. Absorption Rapidly from GIT Distribution Strongly protein bound & cross placenta. Onset of action hour(oral) & 30min (iv). Duration of action hours. Plasma half life----2 hours. Contraindication: Furosemide, bumetanide, and torsemide may demonstrate cross-reactivity in patients who are sensitive to other sulfonamides.
Hepatic cherosis Renal failure, Heart failure,

8. Adverse effect:
Due to fluid & electrolite imbalance- Hypovolumia, Hypotension, Hypokalemia, Metalic acidosis, Hyperurecimia. Not related to renal action: Ototoxicity, Nephrotoxicity, Myalgia (muscle pain), Hypersensitivity (skin rash, fever, jundice)
Due to primary action of drug- GIT disturbances, Depression of formed element in blood, Hepatic dysfunction.

9. Loop Diuretics: Dosages.
Drug Daily Oral Dose
Bumetanide 0.5–2 mg
Ethacrynic acid 50–200 mg
Furosemide 20–80 mg
Torsemide 2.5–20 mg