A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition

226 CARDIAC DYSRHYTHMIAS
(as is not infrequently the case) and the patient actually has
VT, little or no harm results, in contrast to the use of verapamil
in VT.
Mechanism of action
Adenosine acts on specific adenosine receptors. A 1 -receptors
block AV nodal conduction. Adenosine also constricts bronchial
smooth muscle by an A 1 effect, especially in asthmatics. It
relaxes vascular smooth muscle, stimulates nociceptive afferent
neurones in the heart and inhibits platelet aggregation via
A 2 -receptors.
Adverse effects and contraindications
Chest pain, flushing, shortness of breath, dizziness and nausea
are common but short-lived. Chest pain can be alarming if
the patient is not warned of its benign nature before the drug
is administered. Adenosine is contraindicated in patients
with asthma or heart block (unless already paced) and should
be used with care in patients with WPW syndrome in whom
the ventricular rate during atrial fibrillation may be accelerated
as a result of blocking the normal AV nodal pathway and
hence favouring conduction through the abnormal pathway.
This theoretically increases the risk of ventricular fibrillation;
however, this risk is probably small and should not discourage
the use of adenosine in patients with broad complex
tachycardias of uncertain origin.
Pharmacokinetics
Adenosine is rapidly cleared from the circulation by uptake
into red blood cells and by enzymes on the luminal surface of
endothelial cells. It is deaminated to inosine. The circulatory
effects of a bolus therapeutic dose of adenosine last for 20–30
seconds, although effects on the airways in asthmatics persist
for longer.
Drug interactions
Dipyridamole blocks cellular adenosine uptake and potentiates
its action. Theophylline blocks adenosine receptors and
inhibits its action.
DIGOXIN
For more information on digoxin, see also Chapter 31.
Use
The main use of digoxin is to control the ventricular rate (and
hence improve cardiac output) in patients with atrial fibrillation.
Digoxin is usually given orally, but if this is impossible, or
if a rapid effect is needed, it can be given intravenously. Since
the t 1/2 is approximately one to two days in patients with normal
renal function, repeated administration of a maintenance
dose results in a plateau concentration within about three to six
days. This is acceptable in many settings, but if clinical circumstances
are more urgent, a therapeutic plasma concentration
can be achieved more rapidly by administering a loading dose.
The dose is adjusted according to the response, sometimes supplemented
by plasma concentration measurement.
Mechanism of action
1. Digoxin inhibits membrane Na /K adenosine
triphosphatase (Na K ATPase), which is responsible for
the active extrusion of Na from myocardial, as well as
other cells. This results in accumulation of intracellular
Na , which indirectly increases the intracellular Ca 2
content via Na /Ca 2 exchange and intracellular
Ca 2 storage. The rise in availability of intracellular Ca 2
accounts for the positive inotropic effect of digoxin.
2. Slowing of the ventricular rate results from several
mechanisms, particularly increased vagal activity:
• delayed conduction through the atrioventricular node
and bundle of His;
• increased cardiac output due to the positive inotropic
effect of digoxin reduces reflex sympathetic tone;
• small doses of digitalis sensitize the sinoatrial node to
vagal impulses. The cellular mechanism of this effect is
not known.
ATROPINE
Use
Atropine is administered intravenously to patients with
haemodynamic compromise due to inappropriate sinus
bradycardia. (It is also used for several other non-cardiological
indications, including anaesthetic premedication, topical
application to the eye to produce mydriasis and for patients
who have been poisoned with organophosphorous anticholinesterase
drugs; see Chapter 54).
Mechanism of action
Acetylcholine released by the vagus nerve acts on muscarinic
receptors in atrial and cardiac conducting tissues. This
increases K permeability, thereby shortening the cardiac
action potential and slowing the rate of increase of pacemaker
potentials and cardiac rate. Atropine is a selective antagonist
of acetylcholine at muscarinic receptors, and it thereby counters
these actions of acetylcholine, accelerating the heart rate
in patients with sinus bradycardia by inhibiting excessive
vagal tone.
Adverse effects and contraindications
Parasympathetic blockade by atropine produces widespread
effects, including reduced salivation, lachrymation and sweating,
decreased secretions in the gut and respiratory tract,
tachycardia, urinary retention in men, constipation, pupillary
dilatation and ciliary paralysis. It is contraindicated in
patients with narrow-angle glaucoma. Atropine can cause
central nervous system effects, including hallucinations.
Pharmacokinetics
Although atropine is completely absorbed after oral administration,
it is administered intravenously to obtain a rapid