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Antiarrhythmic Drugs: Dr. Sachana KC 1 Year Resident Department of Anesthesia
Antiarrhythmic Drugs: Dr. Sachana KC 1 Year Resident Department of Anesthesia
Dr. Sachana KC
1st year Resident
Department of Anesthesia
Overview
Normal cardiac AP
Classification of Anti-arrhythmic Drugs
MOA
Amiodarone
Pharmacokinetics
Uses and doses
Drug interactions
Side effects
Interactions
Cardiac Electrophysiology
The cardiac action potential results from the interplay of multiple inward
and outward currents via specific ion channels responsible for each of
the five phases.
Lidocaine
Tocainide
Contd…
Class I A drugs
lengthen both the action potential duration and the effective
refractory period by sodium channel inhibition and prolonged
repolarization owing to potassium channel blockade.
Eg; quinidine, procainamide, disopyramide, moricizine
Contd…
Class IB drugs
less powerful sodium channel blockers and, unlike class IA drugs,
shorten the action potential duration and refractory period in
normal cardiac ventricular muscle.
In ischemic tissue, lidocaine may block adenosine triphosphate
(ATP)–dependent channels, preventing ischemia-mediated
shortening of ventricular depolarization.
Ex ; lidocaine, mexiletine, tocainide, phenytoin
Contd…
Class IC drugs
Are potent sodium channel blockers - markedly decrease the rate of
phase 0 depolarization and speed of conduction of cardiac impulses.
Little effect on the duration of the cardiac action potential and the
effective refractory period in ventricular myocardial cells but do
shorten the duration of the action potential in Purkinje fibers.
Inhomogeneity effects - may contribute to the proarrhythmic effects.
Ex; flecainide, propafenone
Contd…
Class II drugs
are beta-adrenergic antagonists.
Class IV drugs
calcium channel blockers : inhibits inward slow calcium ion currents
that may cause tachycardia.
Used for treatment of supraventricular tachyarrhythmias and
idiopathic ventricular tachycardia. (verapamil, diltiazem )
The dihydropyridine calcium blockers (nifedipine, nicardipine,
nimodipine) do not have antiarrhythmic action.
Effects Of Anti-arrhythmic Drugs
Proarrhythmic Effects
This is described as bradyarrhythmias or tachyarrhythmias that
represent new cardiac arrhythmias associated with antiarrhythmic
drug treatment.
These include :
Torsades de pointes (most common),
Incessant ventricular tachycardia,
Wide complex ventricular rhythm.
Torsades de Pointes
Bioavailability- 22 to 95 %.
Absorption is enhanced with food.
Lipid soluble and is stored in high concentrations in fat and muscle, liver, lungs,
& skin.
Plasma peak concentrations, 3 to 7 hours after single oral dose.
Minimal first-pass effect.
Elimination by hepatic excretion.
Therapeutic blood concentrations of amiodarone are 1.0 to 3.5 mg/mL.
Extensive hepatic metabolism with Desethylamiodarone as a metabolite.
Contd…
Maintenance dose:
After the first 24 hours, continue the maintenance infusion rate of
0.5 mg/min; may increase infusion rate to achieve effective
arrhythmia suppression.
Supplemental infusions: 150 mg over 10 minutes (15 mg/min) for
breakthrough episodes of ventricular fibrillation (VF) or
hemodynamically unstable ventricular tachycardia (VT)
Contd…
Long-term treatment
Secondary prevention of life-threatening VT.
For patients who have survived sustained VT & with left ventricular
dysfunction
For primary prevention of SCD
As an adjunct to reduce the frequency of ICD shocks
Contd…
Treatment of atrial fibrillation, although the FDA has not approved this
indication.
Hypertrophic cardiomyopathy
Non-ischemic dilated cardiomyopathy
Ventricular tachyarrhythmia during and after resuscitation from cardiac
arrest.
Asymptomatic ventricular arrhythmias after myocardial infarction
Contd…
Acute treatment
IV amiodarone for the emergency treatment of VT
Onset of action with IV therapy in less than 30 minutes
ACLS recommended for the initial treatment of hemodynamically
stable wide-complex tachycardia.
In patients who require long-term treatment, intravenous dosing should
be switched to oral dosing.
Hemodynamically unstable atrial fibrillation, AF with rapid ventricular
rates and AF with impaired renal function.
Contd…
Side effects is seen more in patients with – if daily maintenance dose exceeds
400 mg.
Therapeutic blood concentrations- 1.0 to 3.5 mg/mL so > 3.5 mg/mL is toxic.
Pulmonary Toxicity
Most serious side effect of amiodarone is pulmonary alveolitis (pneumonitis)
Incidence is 5% to 15% of amiodarone treated patients.
Contd…
Withdrawal of amiodarone
Supportive care
Corticosteroids
Toxicity is reversible.
Cardiovascular
GI
Gastrointestinal side effects of amiodarone include nausea, anorexia, and
constipation. These symptoms often are dosage related and usually improve
when the dosage is reduced.
Ocular, Dermatologic, Neurologic, and Hepatic
Corneal micro-deposits – Occur 100% if used longer than 6 months.
Optic neuropathy has been found in 1.8% of patients treated with
amiodarone.Discontinuation shows improvement in visual acuity.
Visual impairment is unlikely.
Photosensitivity and rash develop in up to 10% of patients.
Rarely, cyanotic discoloration (slate-gray pigmentation) of the face that persists
even after the drug is discontinued.
Neurologic toxicity – peripheral neuropathy, tremors, sleep disturbance,
headache, or proximal skeletal muscle weakness.
Mild increases in plasma transaminase concentrations- may cause fatty liver
infiltration.
Endocrine
Amiodarone-induced hyperthyroidism
Inhibit the peripheral conversion of T4 to T3
Slight increase in T4, reverse T3, and thyroid-stimulating hormone (TSH) and
a slight decrease in T3 levels
Reverse T3 concentration, used as an index of drug efficacy
Treatment –
Surgical thyroidectomy provides prompt metabolic control.
Bilateral superficial cervical plexus blocks have been described for
anesthetic management of subtotal thyroidectomy in these patients.
Copyright@ : Baruah MP, Singh RJ. Effects of drugs on thyroid function. Thyroid Research and Practice. 2012 Jan 1;9(1):3.
Protocol of treatment of amiodarone-
induced thyroid disease
Type 1 Amiodarone induced thyrotoxicosis
Thioamides (carbimazole 30-60 mg/day or methimazole 30-40 mg/ day)
in combination with potassium-perchlorate (1 g/day for 16-40 days).
Discontinue amiodarone if possible.
After restoration of euthyroidism and normalization of urinary iodine
excretion, definitive treatment of the underlying thyroid abnormalities by
either radioiodine or thyroidectomy.
If amiodarone cannot be withdrawn and medical therapy is unsuccessful,
consider total thyroidectomy.
Copyright@ : Baruah MP, Singh RJ. Effects of drugs on thyroid function. Thyroid Research and Practice. 2012 Jan 1;9(1):3.
Contd…
Amiodarone-induced hypothyroidism
In presence of underlying thyroid abnormalities (usually Hashimoto’s
thyroiditis), amiodarone therapy can be continued, and levothyroxine
replacement to be started.
In presence of apparently normal thyroid gland, and if amiodarone cannot be
discontinued, levothyroxine replacement is initiated.
If amiodarone is withdrawn, strict follow-up is required for possible
spontaneous restoration of euthyroidism. A short course of potassium
perchlorate (1 g/day for 10-30 days) can be given to accelerate return to
euthyroidism.
Copyright@ : Baruah MP, Singh RJ. Effects of drugs on thyroid function. Thyroid Research and Practice. 2012 Jan 1;9(1):3.
Drug Interaction
Antidepressants:
Trazodone, an antidepressant, is metabolized primarily by CYP3A.
QT interval prolongation and TdP have been reported with the
coadministration of trazodone and amiodarone.
Antibiotics:
Rifampin is a potent inducer of CYP3A. Administration of rifampin
concomitantly with oral amiodarone has been shown to result in
decreases in serum concentrations of amiodarone and
desethylamiodarone.
Contd…
Immunosuppressives:
Cyclosporine(CYP3A substrate) administered in combination with oral
amiodarone has been reported to produce persistently elevated plasma
concentrations of cyclosporine resulting in elevated creatinine, despite
reduction in dose of cyclosporine.
HMG-CoA Reductase Inhibitors:
Simvastatin (CYP3A substrate) in combination with amiodarone has
been associated with reports of myopathy/rhabdomyolysis.
Figure : Important Amiodarone intreaction
Contraindications
Followed regularly.
Assess ongoing need.
Efficacy of the drug.
Appropriateness of dosage.
Adverse effects.
Potential drug interactions.
Figure : Pharmacokinetics of Antiarrythmic drugs
References