P1: PSB Printer: Yet To Come
9780521704632c21 CUFX213A/Peck 9780521618168 December 28, 2007 14:15
21 Diuretics
Miscellaneous – impotence, rash and photosensitivity occur rarely. Bendrofluazide
may precipitate pancreatitis.
Interactions – the hypokalaemia produced by thiazides may prolong the duration
of action of non-depolarizing muscle relaxants. Non-steroidal anti-inflammatory
drugs antagonize the effects of thiazides.Kinetics
Bendroflumethazide is well absorbed from the gut in contrast with chlorothiazide,
which is incompletely and variably absorbed. They both produce effects within 90
minutes of oral administration although bendroflumethazide has twice the dura-
tion of action at 18–24 hours. The lower lipid solubility of chlorothiazide results in
elimination solely via the kidney – none being metabolized, unlike bendrofluazide,
which is 70% metabolized in the liver to active metabolites, the rest being eliminated
unchanged in the urine.Loop diuretics (furosemide, bumetanide)
Loop diuretics (carboxylic acid derivatives) are used in severe heart failure to reduce
peripheral and pulmonary oedema. They are also used in chronic and acute renal
failure.Mechanism of action
Loop diuretics inhibit Na+and Cl−reabsorption in the thick ascending limb of the
loop of Henle and to a lesser extent in the early part of the distal tubule. This impairs
the action of the counter-current multiplier system and reduces the hypertonicity
of the medulla, which reduces reabsorption of water in the collecting system. The
thick ascending part of the loop of Henle has a large capacity for NaCl reabsorption,
so when ion reabsorption is blocked the effects are marked.Effects
Cardiovascular – like thiazides they produce arteriolar vasodilatation which
reduces systemic vascular resistance. The preload is also reduced ahead of any
change that could be attributed to a diuresis.
Renal – in contrast with the thiazides an increase in renal blood flow is seen with
blood being diverted from the juxtaglomerular region to the outer cortex.
Biochemical – the disturbances seen are similar to those induced by the thiazides
and include hyponatraemia, hypokalaemia, hypomagnesaemia, and a hypochlo-
raemic alkalosis. In contrast with the thiazides the loop diuretics may precipitate
hypocalcaemia due to increased Ca^2 +excretion. Hyperuricaemia is sometimes
seen and occasionally precipitates gout.
Metabolic – hyperglycaemia is less common than with thiazides. Loop diuretics
increase plasma cholesterol and triglyceride levels although these usually return
to normal during long-term treatment.