Pharmacology for Anaesthesia and Intensive Care

P1: PSB Printer: Yet To Come
9780521704632c21 CUFX213A/Peck 9780521618168 December 28, 2007 14:15

Section IVOther important drugs

Carbonic anhydrase

inhibitors

Osmotic and

loop diuretics

Thiazides

Collecting

duct

Aldosterone

antagonists

Loop of Henle

Distal

convoluted

tubule

Proximal convoluted

tubule

Bowman’s

capsule

K+ sparing

diuretics

Figure 21.1.Main sites of action of the diuretics.

Effects


Cardiovascular – thiazides appear to produce their antihypertensive effect by a

reduction in plasma volume and systemic vascular resistance, which is maximally

achieved at low dose.


Renal – they reduce renal blood flow and may cause a reduction in glomerular

filtration rate.


Biochemical – their actions on the kidney lead to various biochemical imbal-

ances. Hypokalaemia may provoke dangerous arrhythmias in those patients tak-

ing digoxin concurrently, although oral K+supplements usually maintain plasma

levels within normal limits. Combination with a K+sparing diuretic may help to

control plasma K+.Hypercalcaemia may result from reduced renal Ca^2 +excretion.

Thiazides may also precipitate a hypochloraemic alkalosis, hyponatraemia and

hypomagnesaemia. Thiazides and uric acid are secreted by the same mechanism

within the renal tubules. This competition leads to reduced uric acid excretion and

arise in plasma levels, which may precipitate gout.


Metabolic – reduced glycogenesis and insulin secretion coupled with enhanced

glycogenolysis tends to raise plasma glucose levels. These effects are most notice-

able in diabetic patients. Thiazides increase plasma cholesterol and triglyceride

levels.


Haematological – various blood dyscrasias are occasionally seen and include aplas-

tic and haemolytic anaemia, leucopenia, agranulocytosis and thrombocytopenia.