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9780521704632c15 CUFX213A/Peck 9780521618168 December 28, 2007 13:25
Section IIICardiovascular drugs
Renal – despite an increase in renal blood flow, fluid retention, oedema, and a
reduction in urine output is often seen. This may be overcome by concurrent
administration of a diuretic.
Gut–nausea and vomiting are common.
Miscellaneous – peripheral neuropathy and blood dyscrasias. A lupus erythemato-
sus type syndrome is occasionally seen after long-term use and may be more
common in slow acetylators and women. It may require long-term corticosteroid
therapy.Kinetics
Hydralazine is well absorbed from the gut but is subject to a variable first-pass
metabolism resulting in an oral bioavailability of 25–55% depending on the acetyla-
tor status of the individual. The plasma half-life is normally 2–3 hours but this may be
shortened to 45 minutes in rapid acetylators. It is 90% protein-bound in the plasma.
Upto 85% is excreted in the urine as acetylated and hydroxylated metabolites, some
of which are conjugated with glucuronic acid. It crosses the placenta and may cause
afoetal tachycardia.Minoxidil
Presentation and uses
Minoxidil is prepared as 2.5–10 mg tablets, a 2% solution for intravenous use and a
5% lotion. It is used for severe hypertension and alopecia areata.
Itsmechanism of action and principal effects are essentially the same as those
of hydralazine. The mechanism by which it stimulates the hair follicle is poorly
understood. It may also precipitate hypertrichosis of the face and arms and breast
tenderness. It does not cause a lupus erythematosus-type reaction.Kinetics
Minoxidil is well absorbed from the gut and has an oral bioavailability of 90%. It is not
protein-bound in the plasma. Its plasma half-life is only 3 hours but its hypotensive
effects may last for as long as 3 days. It undergoes hepatic glucuronide conjugation
and is subsequently excreted in the urine.Diazoxide
This vasodilator is chemically related to the thiazide diuretics.Presentation and uses
Diazoxide is available as 50 mg tablets and as a solution for intravenous injection
containing 15 mg.ml−^1 .Itisused intravenously to treat hypertensive emergencies
associated with renal disease at 1–3 mg.kg−^1 up to a maximum dose of 150 mg,