Core pharmacology

Class Group

Diuretic - Loop

Introduction

Sulfonamide derivative

Indications Uses

Oedema of cardiac, renal or hepatic origin, Renal insufficency
Hypertension
Raised ICP
Hypercalcaemia

Presentation

Photosensitive solution 10mg/ml
20/40/500mg tabs, Syrup

Mechanism of action

Diuresis
Inhibition of active chloride ion reabsorption in PCT and ascending limb of LoH
↓ reabsorption of NaCl → ↓ tonicity in the renal medulla → ↓water reabsorption and diuresis.
Other effects are mediated by the induction of the COX-2 enzyme which assists in synthesis of prostaglandins.

Physiological effects

Pulmonary and systemic vasodilation
Diuresis ↑ RBF and ↑ corticomedullary blood flow
↓O₂ demand in the LoH (ischaemic
protection)

Adverse Effects Toxicity

↓ K+/Na+/Cl-/Ca++, Hyper- urea/glu/chol, Metabolic alkalosis
Tox: Deafness, Pancreatitis
BM depression
Interstitial nephritis (worse with aminoglycoside)

Absorption

PO/IV/SL/IM. PO BA 50% Onset PO/SL 30-60mins, IV 5 mins .
Dur PO/SL 6-8hrs, IV 2hrs

Protein binding

91-99% (Albumin)

Volume of distribution

0.1L/kg

Metabolism

Renal to glucuronide
Minimal hepatic

Excretion

80% unchanged in urine

Half-life

0.5-2hrs. ESRF: 9hrs

Route And Dose

20-2000mg daily
PO/IV/SL/IM.