Antiarrhythmics

Question 1

Class 1

Answer 1

Sodium channel blockers

Question 2

1a

Answer 2

Quinidine
Procainamide
block fast Na+ channels (↓ INa)
Preferentially in the open or activated state—“state-dependent” blockade
Increase action potential duration (APD) and effective refractory period

Question 3

Quinidine

Answer 3

Nas channel blockade
Muscarinic receptor blockade,
which can ↑ HR and AV conduction.
cause vasodilation via alpha block with possible reflex
tachycardia.
Orally effective
wide clinical use in many arrhythmias; in atrial fibrillation, need initial digitalization to slow AV conduction.
Adverse effects: cinchonism (GI, tinnitus, ocular dysfunction, CNS excitation), hypotension, prolongation of QRS and ↑ QT interval associated with syncope (torsades).
Drug interactions: hyperkalemia enhances effects and vice versa
; dis- places digoxin from tissue binding sites, enhancing toxicity

Question 4

Procainamide

Answer 4

Less muscarinic blockade
(SLE)–like syndrome (30% incidence) more likely with slow acetylators;
hematotoxicity (thrombocytopenia, agranulocytosis);
CV effects (torsades)

Question 5

Class 1b

Answer 5

Lidocaine
Mexiletine
block fast Na+ channels (↓ INa)

Block inactivated channels—preference for tissues partly depolarized (slow conduction in hypoxic and ischemic tissues). This results in an increased threshold for excitation and less excitability of hypoxic heart muscle.
↓ APD—due to block of the slow Na+ “window” currents, but this increases diastole and extends the time for recovery.

Question 6

Class 1c

Answer 6

Flecainamide
l Block fast Na+ channels (↓ INa), especially His-Purkinje tissue l No effect on APD
l No ANS effects
o Limited use because of proarrhythmogenic effects, leading to ↑ in
sudden death post-MI and when used prophylactically in VT

Question 7

Uses

Lidocaine

Answer 7

Lidocaine
o Post-MI
o Open-heart surgery
o Digoxin toxicity
o Side effects: CNS toxicity (seizures); least cardiotoxic of conven- tional anti-arrhythmics
o IV use because of first-pass metabolism
− Mexiletine
o Same uses as lidocaine
o Oral formulations

Question 8

Class II

Answer 8

BETA BLOCKERS
l Prevent β-receptor activation, which would normally ↑ cAMP l
↓ SA and AV nodal activity
l ↓ Slope of phase 4 (diastolic currents) of AP in pacemakers
l Drugs:
– Propranolol (nonselective) and the cardioselective drugs: acebutolol and esmolol
– Uses:
o Prophylaxis post-MI and in supraventricular tachyarrhythmias (SVTs)
o Esmolol (IV) is used in acute SVTs

Question 9

Class III

Answer 9

K channel blockers
↓ IK (delayed rectifier current) slowing phase 3 (repolarization) of AP l ↑ APD and ERP, especially in Purkinje and ventricular fibers
l Drugs:
− Amiodarone
o Mimics classes I, II, III, and IV
o Increase APD and ERP in all cardiac tissues
o Uses: any arrhythmias
o t1/2 >80 days
o Binds extensively to tissues (large Vd and multiple effects)
Prolong s QT
But no torsades
o Side effects:
Pulmonary fibrosis
Blue pigmentation of the skin (“smurf skin”) Phototoxicity
Corneal deposits
Hepatic necrosis
Thyroid dysfunction
− Sotalol:
o ↓ IK, slowing phase III
o Non-selective beta blocker: β1 blockade, leading to ↓ HR, ↓ AV conduction
Use :life threatening ventricular arrhythmia
Side effect: Torsades
Dofelitide

Question 10

ClassIV

Answer 10

Ca2+ CHANNEL BLOCKERS
l Block slow cardiac Ca2+ channels l ↓ phase 0, ↓ phase 4
l ↓ SA, ↓ AV nodal activity
l Drugs:diltiazem
Verapamil
Uses: supraventricular tachycardias
o Side effects: constipation (verapamil), dizziness, flushing, hypoten- sion, AV block
o Drug interaction:
Additive AV block with β-blockers, digoxin Verapamil displaces digoxin from tissue-binding site

Question 11

Adenosine

Answer 11

Activates adenosine receptors: causes Gi-coupled decrease in cAMP − ↓ SA and AV nodal activity
DOC for paroxysmal supraventricular tachycardias and AV nodal arrhythmias
− Administered IV: t1/2 <10 seconds
− Side effects: flushing, sedation, dyspnea
− Adenosineisantagonizedbymethylxanthines(theophyllineandcaffeine)

Question 12

Magnesium

Answer 12

− Use:torsades
− Drugs causing torsades include:
o Potassium-channel blockers (class 1A and class III)
o Antipsychotics (thioridazine)
o Tricyclic antidepressants

Question 13

Quinidine

Answer 13

An increase in AV conduction is characteristic of quinidine, which exerts quite marked blocking actions on muscarinic receptors in the heart.
Thus, an atrial rate, formerly transmitted to the ventricles in a 2:1 ratio, may be transmitted in a 1:1 ratio after quinidine.
This effect of quinidine can be offset by the prior administration of an antiarrhythmic drug that decreases AV nodal conduction, such as digoxin or verapamil.
adenosine and esmolol (a beta blocker) are very short-acting agents used IV only.