724
P A R T 8
Drugs acting on the cardiovascular system
C
alcium channel blockers
Calcium channel blockers include amlodipine
(
Norvasc
), diltiazem (
Cardizem
), nifedipine (
Adalat
,
Nyefax
), perhexiline (
Pexsig
), and verapamil (
Cordilox
SR
,
Isoptin
).
Therapeutic actions and indications
Calcium channel blockers inhibit the movement of
calcium ions across the membranes of myocardial and
arterial muscle cells, altering the action potential and
blocking muscle cell contraction. A loss of smooth
muscle tone, vasodilation and decreased peripheral
resistance occur. Subsequently, preload and afterload
are decreased, which in turn decreases cardiac workload
and oxygen consumption.
Calcium channel blockers are indicated for the treat-
ment of variant angina, chronic angina, effort-associated
angina and hypertension. In variant angina, these agents
relieve coronary artery vasospasm, increasing blood flow
to the muscle cells. Research also indicates that these
drugs block the proliferation of cells in the endothelial
layer of the blood vessel, slowing the progress of the
atherosclerosis. Verapamil is also used to treat cardiac
tachyarrhythmias because it slows conduction more
than the other calcium channel blockers do. The drug
of choice depends on the person’s diagnosis and ability
to tolerate adverse drug effects. See Table 46.1 for usual
indications for each of these drugs.
Pharmacokinetics
These drugs are generally well absorbed after oral
administration, metabolised in the liver and excreted in
urine. They have an onset of action of 20 minutes and
duration of action of 2 to 4 hours. These drugs cross the
placenta and enter breast milk.
Contraindications and cautions
Calcium channel blockers are contraindicated in
the presence of allergy to any of these drugs
to avoid
hypersensitivity reactions
and with pregnancy or breast-
feeding
because of the potential for adverse effects on
the fetus or neonate.
Caution should be used with heart block or sick
sinus syndrome,
which could be exacerbated by the
conduction-slowing effects of these drugs
; with renal or
hepatic dysfunction,
which could alter the metabolism
and excretion of these drugs
; and with heart failure,
which could be exacerbated by the decrease in cardiac
output that could occur.
People with diabetes should be
careful when taking perhexiline as this drug can cause
hypoglycaemia and dose adjustment may be necessary
in the first few days.
Adverse effects
The adverse effects associated with these drugs are
related to their effects on cardiac output and on smooth
muscle. CNS effects include dizziness, light-headedness,
headache and fatigue. GI effects can include nausea and
hepatic injury related to direct toxic effects on hepatic
cells. Cardiovascular effects include hypotension, brady-
cardia, peripheral oedema and heart block. Skin effects
include flushing and rash.
Clinically important drug–drug interactions
Drug–drug interactions vary with each of the calcium
channel blockers. Potentially serious effects to keep
in mind include increased serum levels and toxicity
of cyclosporin if they are taken with diltiazem and
increased risk of heart block and digoxin toxicity if
they are combined with verapamil (because verapamil
increases digoxin serum levels). Both verapamil and
digoxin depress myocardial conduction. If any combina-
tions of these drugs must be used, the individual should
be monitored very closely and appropriate dose adjust-
ments made. Verapamil has also been associated with
Prototype summary: Diltiazem
Indications:
Treatment of variant angina, effort-
associated angina and chronic stable angina; also
used to treat essential hypertension and paroxysmal
supraventricular tachycardia.
Actions:
Inhibits the movement of calcium ions
across the membranes of myocardial and arterial
muscle cells, altering the action potential and
blocking muscle cell contraction, which depresses
myocardial contractility; slows cardiac impulse
formation in the conductive tissues, and relaxes
and dilates arteries, causing a fall in blood
pressure and a decrease in venous return; decreases
the workload of the heart and myocardial oxygen
consumption; relieves the vasospasm of the
coronary artery, increasing blood flow to the
muscle cells (variant angina).
Pharmacokinetics:
Route
Onset
Peak
Oral
30–60 mins 2–3 hours
SR, extended
release (ER)
30–60 mins 6–11 hours
IV
Immediate 2–3 mins
T
1/2
:
3.5 to 6 hours (SR), 5 to 7 hours (ER);
metabolised in the liver and excreted in urine.
Adverse effects:
Dizziness, light-headedness,
headache, asthenia, peripheral oedema, bradycardia,
atrioventricular block, flushing, rash, nausea.
