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Quinaglute Overdose, Contraindications and Information - Quinidine Gluconate
OVERDOSE
Overdoses with various oral
formulations of quinidine have been well described. Death has been
described after a 5-gram ingestion
by a toddler, while an adolescent
was reported to survive after ingesting 8 grams of quinidine.
The most important ill effects
of acute quinidine overdoses
are ventricular arrhythmias and hypotension. Other signs and symptoms
of overdose may include
vomiting, diarrhea,
tinnitus, high-frequency
hearing loss, vertigo,
blurred vision, diplopia,
photophobia, headache,
confusion, and delirium.
Arrhythmias: Serum quinidine levels can be conveniently assayed
and monitored, but the electrocardiographic QTc
interval is a better
predictor of quinidine-induced ventricular
arrhythmias.
The necessary treatment
of hemodynamically unstable polymorphic
ventricular tachycardia (including torsades de pointes) is
withdrawal of treatment
with quinidine and either immediate
cardioversion
or, if a cardiac pacemaker
is in place or immediately available, immediate
overdrive pacing. After pacing or cardioversion,
further management must be guided by the length of the QTc
interval.
Quinidine-associated ventricular
tachyarrhythmias with normal
underlying QTc intervals have not been adequately studied. Because
of the theoretical possibility of QT-prolonging effects that might
be additive to those
of quinidine, other antiarrhythmics with Class I (disopyramide,
procainamide) or Class III activities should (if possible) be avoided.
Similarly, although the use of bretylium in quinidine overdose
has not been reported, it is reasonable to expect that the a-blocking
properties of bretylium might be additive
to those of quinidine, resulting in problematic hypotension.
If the post-cardioversion QTc
interval is prolonged,
then the pre-cardioversion polymorphic ventricular
tachycardia was
(by definition) torsades de pointes. In
this case, lidocaine
and bretylium are unlikely to be of value, and other Class I antiarrhythmics
(disopyramide, procainamide) are likely to exacerbate the situation.
Factors contributing to QTc
prolongation (especially hypokalemia
and hypomagnesemia) should be sought out and (if possible) aggressively
corrected. Prevention of recurrent torsades may require sustained
overdrive pacing or the
cautious administration
of isoproterenol (30-150 ng/kg/min).
Hypotension: Quinidine-induced hypotension
that is not due to an arrhythmia is likely to be a consequence
of quinidine-related a-blockade and vasorelaxation. Simple repletion
of central volume
(Trendelenburg positioning, saline infusion) may be sufficient therapy;
other interventions reported to have been beneficial in this setting
are those that increase peripheral vascular resistance,
including a-agonist catecholamines (norepinephrine, metaraminol)
and the Military Anti-Shock Trousers.
Treatment:
To obtain up-to-date information about the treatment
of overdose, a good resource is your certified Regional Poison-Control
Center. Telephone numbers of certified poison-control centers are
listed in the Physicians' Desk Reference (PDR). In
managing overdose, consider the possibilities of multiple-drug overdoses,
drug-drug interactions, and unusual drug
kinetics in your patient.
Accelerated removal: Adequate studies of orally-administered
activated charcoal in human
overdoses of quinidine have not been reported, but there are animal
data showing significant
enhancement of systemic
elimination following this intervention, and there is at least one
human case
report in which the elimination
half-life of quinidine
in the serum was apparently
shortened by repeated gastric
lavage. Activated charcoal
should be avoided if an ileus
is present; the conventional dose
is 1 gram/kg, administered every 2-6 hours as a slurry
with 8 mL/kg of tap water.
Although renal elimination
of quinidine might theoretically be accelerated by maneuvers to
acidify the urine,
such maneuvers are potentially
hazardous and of no demonstrated
benefit.
Quinidine is not usefully removed from the circulation
by dialysis.
Following quinidine overdose, drugs that delay elimination
of quinidine (cimetidine, carbonic-anhydrase inhibitors, thiazide
diuretics) should be withdrawn unless absolutely required.
CONTRAINDICATIONS
Quinidine is contraindicated in patients who are known to be allergic
to it, or who have developed thrombocytopenic purpura
during prior therapy with quinidine or quinine.
In the absence of a
functioning artificial
pacemaker, quinidine
is also contraindicated in any patient
whose cardiac rhythm
is dependent upon a junctional or idioventricular
pacemaker, including
patients in complete atrioventricular block.
Quinidine is also contraindicated in patients who, like those with
myasthenia gravis, might be adversely affected by an anticholinergic
agent.
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