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Dr. Sanooz
Antidysrhythmic drugs
Pharmacokinetics:
•Nearly complete oral bioavailability
•Onset of action within 1–3 hours
•Peak effect within 1–2 hours
•The plasma half-life is 6 hours
•Primarily hepatic metabolism.
•Therapeutic serum concentrations are 2– 4 μg/mL.
Clinical Uses
•The use of quinidine is limited by the poor side
effect profile and the availability of equally or
more efficacious agents.
•Used in combination with other agents such as
mexilitine for the control of ventricular
arrhythmias
•May be useful in the patients with short QT
syndrome
Adverse Effects
Diarrhea, upper-gastrointestinal distress, light-headedness
relatively common adverse effects include fatigue, palpitations, headache, angina-
like pain, and rash.
These adverse effects are dose-related and reversible with cessation of therapy.
Thrombocytopenia may also occur.
The cardiac toxicity : AV and intraventricular block, ventricular tachyarrhythmias,
and depression of myocardial contractility.
Ventricular proarrhythmia with loss of consciousness- “quinidine syncope,”
Large doses of quinidine can produce- cinchonism(ringing in the ears, headache,
nausea, visual disturbances or blurred vision, disturbed auditory acuity, and
vertigo)
Larger doses can produce confusion, delirium, hallucinations, or psychoses.
Quinidine can also cause hypoglycemia
Contraindications
Complete AV block with a junctional or idioventricular escape
rhythm
Congenital QT prolongation
Congestive heart failure
Hypotension
Drug Interactions:
Quinidine increases the plasma concentrations of digoxin,
requiring a downward adjustment in the digoxin dose.
Procainamide
•Derivative of the local anesthetic agent Procaine
•longer half-life, does not cause CNS toxicity at therapeutic
plasma concentrations, and is effective orally
•Procainamide is effective in the treatment of
supraventricular, ventricular, and digitalis-induced
arrhythmias
•Its use is limited by its short serum half-life and frequent
side effects when used chronically.
•The ECG changes are similar to quinidine.
Pharmacokinetics:
•Highly bio-available (75%–95%)
•Onset of action of 5–10 minutes
•Peak response following an oral dose is 60–90 minutes
•Plasma half-life of 2.5–4.5 hours (6–8 hours for the
sustained release preparation)
•Metabolized hepatically
•50%–60% is excreted unchanged in the urine
•The primary metabolite Nacetylprocainamide (NAPA) is cardioactive with class III
properties and is eliminated unchanged in the urine.
Clinical Uses
Drug Interactions.
•Cimetidine inhibits the metabolism of procainamide.
•Simultaneous use of alcohol will increase the hepatic clearance of
procainamide.
•The simultaneous administration of quinidine or amiodarone may
increase the plasma concentration of procainamide.
Class IB
Lidocaine
local anesthetic
blocks sodium channels, binding to channels in both the open
and inactivated state.
like other class 1B agents acts preferentially in diseased tissue
causing conduction block and interrupting reentrant tachycardias
Electrophysiological Actions
SA node and atrium:
has no effect on the sinus rate and weak effects on atrial tissue.
AV node:
minimal effects on the conduction velocity and ERP of the AV node.
His-Purkinje system and ventricular muscle:
reduces membrane responsiveness and decreases automaticity.
in very low concentrations slows phase 4 depolarization in Purkinje fibers.
In higher concentrations, automaticity may be suppressed, and phase 4
depolarization eliminated.
Electrocardiographic Changes:
PR, QRS, and QT intervals are usually unchanged
QT interval may be shortened in some patients
At usual doses, lidocaine does not depress myocardial function, even in the face of
CHF.
Pharmacokinetics
•extensive first pass metabolism, not used orally.
•onset of action is immediate
•plasma half-life of 1–2 hours
•Elimination primarily via liver (90%) with the rest unchanged in
the urine.
•Therapeutic serum levels range from 1.5–6.0 μg/mL.
•clearance is reduced by CHF, hepatic dysfunction, and
•concomitant treatment with cimetidine or beta-blockers.
Clinical Uses :
•Ventricular arrhythmias
•Lidocaine’s use has decreased as amiodarone is frequently
being used
Adverse Effects:
•CNS toxicity is the most frequent adverse effect.
•Paresthesias, disorientation, and muscle twitching, psychosis,
respiratory depression, and seizures.
•Myocardial depression at very high doses.
Contraindications:
hypersensitivity to local anesthetics of the amide type
severe hepatic dysfunction or a previous history of grand mal
seizures due to lidocaine.
Electrocardiographic Changes:
increases the PR, QRS, and to a lesser extent, the QTc intervals.
Pharmacokinetics:
Well absorbed
bioavailability of 85%–90%.
Oral absorption may be inhibited by milk and milk-based formulas.
The onset of action is 1– 2 hours
serum half-life of 12–30 hours
primarily metabolized in the liver and excreted in the urine.
Therapeutic serumconcentrations are 0.2–1.0 μg/mL.
Clinical Uses:
•Atrial arrhythmias- particularly those supported by reentrant
mechanisms
•Life threatening ventricular arrhythmias
•the second-line drug after digoxin for therapy of fetal
arrhythmias
•second line drug for SVT in children who are not well controlled
on beta-blockers
- Used with caution in patients with congenital heart disease
Adverse Effects:
Most adverse effects are observed within a few days of initial drug
administration
dizziness, visual disturbances, nausea, headache,dyspnea , Worsening
of heart failure, prolongation of the PR and QRS intervals
Contraindications:
Preexisting second- or third-degree heart block.
cardiogenic shock
Pharmacokinetics:
nearly 100% absorbed following an oral dose
serum half-life of 2–10 hours
metabolized in the liver with nearly one-third of the drug excreted unchanged
in the urine
Therapeutic serum concentration 0.06–0.10 μg/mL.
Clinical Uses:
supraventricular arrhythmias
life threatening ventricular arrhythmias in the absence of structural
heart disease.
used with caution in patients with congenital heart disease due
to the increased risk of ventricular proarrhythmia
AV node:
decrease in AV conduction velocity and an increase in the AV nodal refractory
period.
Electrocardiographic Changes:
The PR interval is prolonged with no change in the QRS interval.
The QT interval may be shortened
Clinical Uses:
•Useful for wide spectrum of arrhythmias
•Usually the initial therapy for SVT in all age groups
•Several forms of ventricular ectopy/ tachycardia including the
suppression of symptomatic PVCsa nd catecholamine dependent
Idiopathic VT.
•Propranolol is the drug of choice for treating patients with the
congenital long QT syndrome.
Atenolol
Clinical Uses:
•All supraventricular tachycardias
•Control of ventricular ectopy
•Drug of choice for the initial therapy of SVT
Nadolol
Clinical Uses:
treatment of various forms of supraventricular tachycardia and
long QT syndrome
Clinical Uses:
acute treatment of supraventricular and ventricular
tachyarrhythmias
acutely lowering blood pressure
Esmolol
•short acting
•Intravenously administered β1 selective adrenoceptor blocking
agent
• It does not possess membrane-stabilizing activity or
sympathomimetic activity
CLASS III
Drug Interactions:
Amiodarone interferes with the metabolism of many drugs,
most notably warfarin and digoxin
Sotalol
•Nonselective β-adrenoceptor blocking properties in addition to
class III actions via potassium channel blockade
•The β-blocking effects are most evident at lower doses
•Action potential prolonging effects predominating at higher doses.
AV node:
•decreases conduction velocity and prolongs the effective refractory
period in the AV node.
His-Purkinje system and ventricular muscle:
•inhibition of the delayed rectifier potassium channel results in a
prolongation of the effective refractory period in His-Purkinje
tissue.
•prolongs repolarization and increases the ERP of ventricular
muscle.
Contraindications:
severe heart failure or poor ventricular function.
patients with hypokalemia or prolonged QT intervals
Dofetilide
AV node:
slows conduction through the AV node and prolongs the AV nodal
refractory period.
Clinical Uses:
acute termination of supraventricular tachycardia that utilizes
the AV node
ADR
flushing, chest pain, and dyspnea.
Adenosine may induce profound bronchospasm in
patients with known reactive airway disease. atrial
fibrillation
Contraindications:
asthmatic patients
Known hypersensitivity to adenosine
Drug Interactions:
Methylxanthines (such as theophylline) antagonize the effects of
adenosine via blockade of the adenosine receptors and
necessitate increased doses.
Magnesium Sulfate
Extravagal:
A direct depressant action on SA and A-V nodes.
Electrophysiological properties
• The resting membrane potential (RMP), is progressively
decreased (shifted towards isoelectric level) with increasing doses
• excitability is enhanced at low doses (due to reduction of gap
between RMP and threshold potential) but depressed at toxic
doses
• The rate of 0 phase depolarization is reduced.
• This action is most marked in A-V node and bundle of His.
• delayed after-depolarizations result
• The SA and A-V node automaticity is reduced at therapeutic
concentrations by vagal action which hyperpolarizes these cells
and reduces their phase-4 slope
Effective refractory period (ERP):
Excitability: Enhanced at low doses but depressed at high doses
Conduction: A-V conduction is demonstrably slowed by therapeutic
doses due to a reduction in the rate of 0 phase depolarization. At
high doses, intraventricular conduction in PFs is also depressed by
uncoupling of gap junctions.
ECG : Therapeutic doses of digitalis produce changes in the ECG. These
are accentuated at high doses—may also produce arrhythmias.
The changes are:
• Decreased amplitude or inversion of T wave.
• Increased P-R interval (slowing of A-V conduction), A-V block at toxic
doses.
• Shortening of Q-T interval (reflecting shortening of systole).
Mechanism of action
• Inhibition of Na+K+ ATPase is clearly involved in the toxic
actions of digitalis.
• At high doses, there is depletion of intracellular K+;
• toxicity is partially reversed by infusing K+.
Blood vessels
Digitalis has mild direct vasoconstrictor action
Does not affect HF patients
No prominent effect on BP
No significant effect on coronary circulation