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Section IIICardiovascular drugs
Metabolic – unlike other antihypertensives it has no effect on lipid profile or glucose
control.
Haematological – nicorandil inhibits in vitro ADP-induced platelet aggregation (in
asimilar manner to nitrates), which is associated with an increase of intraplatelet
cGMP.
Miscellaneous – giant oral apthous ulcers have been reported with its use.Kinetics
Nicorandil is well absorbed from the gut with insignificant first-pass metabolism.
The main metabolic route is denitration with 20% excreted as metabolites in the
urine. The elimination half-life is 1 hour, although its actions last up to 12 hours, but
neither is increased in the presence of renal impairment. It is not plasma protein-
bound to any significant extent.Calcium channel antagonists
Despite their disparate chemical structures, the Ca^2 +channel antagonists are all
effective in specifically blocking the entry of Ca^2 +through L-type channels while leav-
ing T-, N- and P-type Ca^2 +channels unaffected. The L-type channel is widespread
in the cardiovascular system and is responsible for the plateau phase (slow inward
current) of the cardiac action potential. It triggers the internal release of Ca^2 +and
is regulated by cAMP-dependent protein kinase. The T-type channel is structurally
similar to the L-type channel and is present mainly in cardiac cells that lack a T-
tubule system, that is, SA node and certain types of vascular smooth muscle. They
are not present in ventricular myocardium. N-type channels are only found in nerve
cells.
Calcium channel antagonists have variable affinity for L-type channels in
myocardium, nodal and vascular smooth muscle resulting in variable effects. They
are all useful in the treatment of essential hypertension, although some are also
particularly useful in the treatment of angina or arrhythmias.Verapamil
Verapamil is a racemic mixture and a synthetic derivative of papaverine.Presentation and uses
Verapamil is available as 20–240 mg tablets, some prepared as modified release and as
an oral suspension containing 40 mg/5 ml. The colourless intravenous preparation
contains 2.5 mg.ml–1.Itisused for certain supraventricular arrhythmias (not in
atrial fibrillation complicating WPW syndrome) and angina. It has been used to
treat hypertension although its negative inotropic properties limit its usefulness in
this setting.