Pharm Antiarrhythmics

Quinidine is an antiarrhythmic drug that may also be used for the therapy of malaria. It is effective in treating certain types of malaria, particularly those caused by Plasmodium falciparum. Quinidine works by interfering with the DNA replication of the malaria parasite, ultimately leading to its death. In addition to its antimalarial properties, Quinidine is also used to treat certain types of cardiac arrhythmias.

Learning objective: describe the electrophysiological actions of quinidine.
Answer: C
Blockade of activated sodium channels is the distinctive feature of class Ia antiarrhythmic drugs.
The slope of phase zero of the cardiac action potential in normal atrial, Purkinje and ventricular
cells is dependent on sodium current. The higher the number of sodium channels that are in the
open state, the higher the sodium current and the steeper the slope of phase zero. By blocking
activated sodium channels (the number of channels that are blocked is dose-dependent) the
sodium current will be less intense and the slope of phase zero decreases.
A, B, D) By blocking K+ channels quinidine slow down repolarization and therefore action
potential duration is increased, the slope of phase 3 is decreased and the effective refractory
period is increased.
E) The slope of phase 4 is related to automaticity (the steeper the slope the higher the
automaticity). Most antiarrhythmic drugs decrease the slope of phase 4, unless toxic doses are
given.

Learning objective: describe the main adverse effects of amiodarone.
Answer: C
The sings and symptoms of the patient indicate a pulmonary disorder. Antimicrobial infection is
unlikely and diffuse bilateral infiltrated are consistent with pulmonary fibrosis. Amiodaroneinduced
pulmonary fibrosis is the most serious adverse effect of the drug. It occurs in 5-10% of
the population with a mortality of 5-10% of those affected.
A, B, D, E) All the other listed drugs may be used for sustained ventricular tachycardia
prophylaxis, but they do not cause pulmonary fibrosis.

Sotalol is the correct answer because it is a non-selective beta blocker that also blocks potassium channels. This dual mechanism of action helps to slow down heart rate and prolong the duration of the action potential, making it effective in treating certain types of arrhythmias.

Phenytoin is an anticonvulsant drug frequently used in the case of generalized tonic-clonic seizures. It is not commonly used as an antiarrhythmic drug, but it can be used in certain cases to treat arrhythmias.

Learning objective: describe the lupoid syndrome caused by procainamide.
Answer: E
The symptoms of the patient are consistent with drug-induced lupus (also called lupoid
syndrome) an autoimmune disorder that is quite similar to the idiopathic systemic lupus
erythematosus. The most common agent reported to cause the disorder are procainamide
(about one third of the patients taking the drug over one year period) and hydralazine. Other
drugs that can cause drug-induced lupus include chlorpromazine, isoniazid, methyldopa,
quinidine, sulfonamides and penicillamine. The drug-induced lupus syndrome onset can
occur as soon as one month of therapy, like in the present case. Unlike the idiopathic lupus,
drug-induced lupus typically improves rapidly after the discontinuation of the drug.
A) Quinidine can cause lupus but is not used to treat Wolff-Parkinson-White syndrome.
B, C, D, F) The risk of drug-induced lupus with these drugs is quite low.

Learning objective: describe the mechanism of quinidine-induced paradoxical tachycardia.
Answer: A
Quinidine is still sometimes used to maintain the normal sinus rhythm after cardioversion, but it
can cause paradoxical tachycardia, due to its antimuscarinic action on the heart, which increases
AV conduction.
B) Quinidine blocks, not activates, alpha-1 receptors so causing peripheral vasodilation. Even if
the decreased blood pressure usually causes reflex tachycardia in normal persons, this is not the
case in patients with atrial flutter since the SA node is no longer the main pacemaker.
C) By causing vasodilation quinidine actually decreases the stimulation of arterial baroreceptors
D, E) Quinidine can block, not activates, both calcium and potassium channels.

Learning objective: describe the therapeutic uses of procainamide.
Answer: D
Wolff-Parkinson-White (WPW) is a pre-excitation syndrome in which there is an accessory bypass tract (known as a Kent bundle) connecting the atria to the ventricle. An impulse can travel
down this pathway and excite the ventricle before the expected regular impulse through the AV
node. Hence the term pre excitation. WPW syndrome can occur in children and adult without
overt cardiac disease. The true incidence is unknown but varies in different reports from 0.1 to 3
per 1000 ECGs. About 20-30% of all supraventricular tachycardias are associated with WPW
syndrome.
DC cardioversion represents the treatment of choice for WPW syndrome. Medical therapy must
be used cautiously because it may unexpectedly increase the ventricular rate. Of the FDA
approved drugs, procainamide, which prolongs the refractory period of the accessory pathways,
is considered by many the drug of choice.
A, B, C) Digoxin, calcium channel blockers and beta-blockers may be dangerous by blocking the
AV node and redirecting impulses down the bypass tract.
E) Nifedipine has no direct action on the heart and the reflex tachycardia it induces may worsen
the arrhythmia.

Learning objective: describe the main adverse effects of lidocaine
Answer: A
Lidocaine is a drug of choice for ventricular arrhythmias associated with myocardial infarction and
the patient’s tachycardia was most likely ventricular in nature, since atrioventricular dissociation
was noted. Patient’s symptoms and sings are typical CNS effects of a high dose of lidocaine.
B, C) High doses of phenytoin or sotalol do not cause the pattern of symptoms and signs
exhibited by the patient.
D) Mexiletine is a lidocaine-like drug that is used only orally to prevent recurrence of ventricular
tachycardia.
E, F) These drugs are not used, and may be even contraindicated, in case of ventricular
tachycardia.

Amiodarone is the most effective antiarrhythmic drug for both supraventricular and ventricular arrhythmias. It is a class III antiarrhythmic medication that works by prolonging the duration of action potential and refractory period in cardiac tissues. It is used to treat a wide range of arrhythmias, including atrial fibrillation, ventricular tachycardia, and ventricular fibrillation. Amiodarone has a broad spectrum of activity and is considered a first-line therapy for many types of arrhythmias due to its efficacy and safety profile.

Learning objective: describe the main adverse effects of quinidine.
Answer: C
More than 100 drugs have been implicated to cause thrombocytopenia, but quinidine and
heparin are the two drugs that have the strongest association with this disorder. Quinidineinduced
thrombocytopenia appears to be immunologically mediated and usually develops within
12-24 hours from ingestion of the drug by a sensitized individual.
A, B, D, E, F) The risk of drug-induced thrombocytopenia with these drugs is quite low.

Learning objective: describe the use of beta-blockers for atrial fibrillation associated with
hypertrophic congenital hypertrophic cardiomyopathy.
Answer: D
The patient is likely affected by congenital hypertrophic cardiomyopathy, a disorder usually
inherited in an autosomal dominant pattern. Classic symptoms of the disease are angina (a
limited coronary blood flow reserve is present in hypertrophied states) and diastolic heart failure
(due to the reduced compliance of the hypertrophied left ventricle). Beta-blockers without partial
agonist activity (and calcium channel blockers that act on the heart, like verapamil and diltiazem)
are drugs of choice in this disease because they decrease cardiac contractility and increase
diastolic ventricular filling (by causing bradycardia). Beta-blocker are also indicated in atrial
fibrillation and therefore, in the present case, they are useful for both conditions.
A, B, C) All the listed drug can be used in atrial fibrillation, but in this case beta-blockers are
preferred (see explanation above)
E) Nitrates are contraindicated in hypertrophic cardiomyopathy since they reduce preload, which
is already low because of the reduced volume and compliance of the left ventricle)

Learning objective: describe the uses of propranolol in hyperthyroidism.
Answer: D
The patient presents with classical symptoms of hyperthyroidism. When a tachyarrhythmia is
associated with hyperthyroidism beta-blockers remain the drugs of choice, since many symptoms
of this disease are associated with sympathetic activation.
A, B, C, E) All the other listed drugs can be used to treat supraventricular arrhythmias, but in the
present case a beta-blocker is preferred (see explanation above)

Learning objective: identify the main contraindications of quinidine.
Answer: C
Class Ia and Ic antiarrhythmic drugs are absolutely contraindicated in case of poisoning with
tricyclic antidepressants as they share cardiotoxic and anticholinergic side effects with these
drugs. Moreover antiarrhythmic drugs that increase action potential duration are generally
contraindicated in patients with widened QRS complexes.
A, B) These drugs are indicated, not contraindicated, in case of ventricular arrhythmias.
D) Phenytoin is not contraindicated in ventricular arrhythmias even if its efficacy remains
controversial, except when arrhythmias are due to digitalis toxicity, .
E) Beta-blockers might be effective in treating tricyclic-induced arrhythmias even if they are not
drugs of choice because they can cause bradycardia and worsen tricyclic-induced hypotension.

Adenosine acts on acetylcholine sensitive K+ channels.

Learning objective: describe the electrophysiological actions of mexiletine.
Answer: B
The typical action of most antiarrhythmic drugs is the decreased slope of phase 4 in pacemaker
cells, which means a decrease in automaticity.
A, C) Mexiletine is a class 1b drug. These agents can decrease action potential duration (and so
refractoriness) in normal cardiac cells but they increase it in abnormal cells.
D) Phase 3 is due to movement of calcium across cardiac cell membrane. Class 1b drugs do not
affect calcium movement.
E) Antiarrhythmic drugs tend to decrease cardiac rate and therefore the interval between two
action potentials (i.e. the diastolic interval) is increased, not decreased.

Learning objective: choose the appropriate antiarrhythmic drug for a patient with an
atrioventricular nodal tachycardia resistant to amiodarone.
Answer: F
Atrioventricular nodal reentrant tachycardia is the most common form of supraventricular
reentrant tachycardia and is often due to a functional division of the AV node into two pathways
with different conduction characteristics. One is a fast conducting pathway and the other is a
slower conducting pathway. Neck pulsations are unique to this disorder. Medical treatment is
directed at slowing conduction in both pathways. Typical nodal blocking agents like betablockers,
Ca channel blockers, digoxin or adenosine are most effective on the slow pathway but
amiodarone or procainamide are preferred since they can affect both pathways.
A, B, C, D, E) All these drugs are minimally effective in supraventricular arrhythmias.

Learning objective: describe the main adverse effects of sotalol.
Answer: D
The electrocardiographic hallmark of polymorphic ventricular tachycardia is a long Q-T interval.
Prolongation of Q-T interval indicates prolongation of action potential duration, which is related to
a decreased outward potassium current during the phase 3 of the action potential. Long Q-T
interval is present prior to the onset of tachycardia and is due to hereditary or acquired potassium
channel defects. Hereditary Q-T syndromes are due to some rare mutations of the genes
encoding potassium channels. However the importance of the disorder in everyday practice is
related to its provocation by diseases or drugs that prolong Q-T interval. Diseases include
hypothyroidism, subarachnoid hemorrhage, myocarditis, hypokalemia and hypomagnesemia.
Drugs include class Ia and class III antiarrhythmic drugs, tricyclic antidepressants, neuroleptics,
some antihistamines, macrolide antibiotics and quinolones. All these drugs are able to increase
action potential duration by blocking or modifying potassium channels. High doses of these drugs
can trigger polymorphic ventricular tachycardia in patients at risk.
Sotalol is the only beta-blocker that can block potassium channels ( a property not related to beta
receptor blockade) and it can cause polymorphic ventricular tachycardia. Moreover the patient
was taking a quinolone and so was already at risk of developing the disorder.
A, C, D, E, F) (see explanation above).

Amiodarone is the correct answer because it is a class III antiarrhythmic drug that blocks inactivated (but not activated) Na+ channels. It also has additional effects on other ion channels, making it effective in treating a wide range of arrhythmias.