Clinical Pharmacology and Therapeutics

228 CARDIAC DYSRHYTHMIAS
deficiency, since Mg 2 is predominantly an intracellular cation.
However, serial plasma magnesium determinations may be
useful in preventing excessive dosing with accumulation and
toxicity.
Mechanism of action
Mg 2 is a divalent cation and at least some of its beneficial
effects are probably due to the consequent neutralization of
fixed negative charges on the outer aspect of the cardiac cell
membranes (as for Ca 2 ). In addition, Mg 2 is a vasodilator
and releases prostacyclin from damaged vascular tissue
in vitro.
Adverse effects and contraindications
• Excessively high extracellular concentrations of Mg 2 can
cause neuromuscular blockade. Magnesium chloride
should be used with great caution in patients with renal
impairment or hypotension, and in patients receiving
drugs with neuromuscular blocking activity, including
aminoglycoside antibiotics.
• Mg 2 can cause AV block.
Pharmacokinetics
Magnesium salts are not well absorbed from the gastrointestinal
tract, accounting for their efficacy as osmotic laxatives
when given by mouth. Mg 2 is eliminated in the urine and
therapy with magnesium salts should be avoided or the dose
reduced (and frequency of determination of plasma Mg 2
concentration increased) in patients with glomerular filtration
rates 20 mL/min.
Drug interactions
Magnesium salts form precipitates if they are mixed with
sodium bicarbonate and, as with calcium chloride, magnesium
salts should not be administered at the same time as sodium
bicarbonate, or through the same line without an intervening
saline flush. Hypermagnesaemia increases neuromuscular
blockade caused by drugs with nicotinic-receptor-antagonist
properties (e.g. pancuronium, aminoglycosides).
Case history
A 16-year-old girl is brought to the Accident and Emergency
Department by her mother having collapsed at home. As a
baby she had cardiac surgery and was followed up by a paediatric
cardiologist until the age of 12 years, when she
rebelled. She was always small for her age and did not play
games, but went to a normal school and was studying for
her GCSEs. On examination, she is ill and unable to give a
history, and has a heart rate of 160 beats per minute (regular)
and blood pressure of 80/60 mmHg. There are cardiac
murmurs which are difficult to characterize. The ECG shows
a broad complex regular tachycardia which the resident
medical officer (RMO) is confident is an SVT with aberrant
conduction.
Question
Decide whether initial management might reasonably
include each of the following:
(a) i.v. verapamil.
(b) DC shock;
(c) i.v. adenosine;
(d) i.v. lidocaine.
Answer
(a) False
(b) True
(c) True
(d) False
Comment
This patient clearly has underlying heart disease and is
acutely haemodynamically compromised by the dysrhythmia.
It is difficult to distinguish SVT with aberrant conduction
from ventricular tachycardia, but if the RMO is correct,
then lidocaine will not be effective. Verapamil, while often
effective in SVT, is potentially catastrophic in this setting,
but a therapeutic trial of adenosine could be considered
because of its short duration of action. Alternatively (or
subsequently if adenosine is not effective, which would
suggest that the rhythm is really ventricular), direct current
(DC) shock is appropriate.
Case history
A 66-year-old man made a good recovery from a transmural
(Q-wave) anterior myocardial infarction complicated by mild
transient left ventricular dysfunction, and was sent home taking
aspirin, atenolol, enalapril and simvastatin. Three months
later, when he is seen in outpatients, he is feeling reasonably
well, but is worried by palpitations. His pulse is irregular, but
there are no other abnormal findings on examination and his
ECG shows frequent multifocal ventricular ectopic beats.
Question
Decide whether management might appropriately include
each of the following:
(a) consideration of cardiac catheterization;
(b) invasive electrophysiological studies, including provocation
of dysrhythmia;
(c) adding flecainide;
(d) stopping atenolol;
(e) adding verapamil;
(f) adding amiodarone.
Answer
(a) True
(b) False
(c) False
(d) False
(e) False
(f) False
Comment
It is important to continue a beta-blocker, which will
improve this patient’s survival. It is appropriate to consider
cardiac catheterization to define his coronary anatomy and
to identify whether he would benefit from some revascularization
procedure. Other classes of anti-dysrhythmic drugs
have not been demonstrated to prolong life in this setting. If
the symptom of palpitation is sufficiently troublesome, it
would be reasonable to consider switching from atenolol to
regular (i.e. racemic) sotalol.