Pharm: Antiarrhythmics

Question 1

Class I

Answer 1

Sodium channel blockers
Slow or block conduction (especially in depolarized cells)
Decrease slope of phase 0 depolarization
State dependent: selectively depress tissue that is frequently depolarized (e.g. tachycardia)

Question 2

Class IA

Answer 2

Quinidine, Procainamide, Disopyramide (the prom queen disappeared)

Mechanism: ^ AP duration, ^ effective refractory period in ventricular AP, ^ QT interval

Use: atrial and ventricular arrhythmias, especially re-entrant and ectopic SVT and VT

Side effects: cinchonism (headache, tinnitus with quinidine), reversible SLE-like syndrome (procainamide) , heart failure (dysopyramide), thrombocytopenia, torsades de pointer due to ^QT interval

Question 3

Class IB

Answer 3

Lidocaine, Mexiletine, Phenytoin

Mechanism: v AP duration, preferentially affect ischemic or depolarized Purkinje and ventricular tissue

Use: acute ventricular arrhythmias (esp. post-MI), digitalis-induced arrhythmias

Side effects: CNS stimulation/depression, cardiovascular depression

Question 4

Class IC

Answer 4

Flecainide, Propafenone

Mechanism: significantly prolongs effective refractory period in AV node and accessory bypass tracts, but no effect on it in Purkinje and ventricular tissue. AP duration unchanged.

Use: SVTs, including A-fib. Last resort for refractory VT.

Side effects: pro-arrhythmic, esp. post-MI (contraindicated)

Question 5

Class II

Answer 5

beta-blockers
Metoprolol, propanolol, esmolol, atenolol, timolol, carvedilol

Mechanism: v SA and AV nodal activity by v cAMP, v Ca currents. Suppress abnormal pacemakers by v slope of phase 4. AV node is particularly sensitive - ^ PR interval. Esmolol very short acting.

Use: SVT, ventricular rate control for a-fib and atrial flutter

Side effects: Impotence, exacerbation of COPD and asthma, cardiovascular effects (bradycardia, AV block, HF), CNS effects (sedation, sleep alterations). May mask hypoglycemia.
Metoprolol can cause dyslipidemia
Propanolol can exacerbate vasospasm in Prinzmetal angina
Cause unopposed a1-agonism (except nonselective carvedilol and labetalol)
Treat b-blocker overdose with saline, atropine, glucagon

Question 6

Class III

Answer 6

Potassium channel blockers
Amiodarone, Ibutilide, Dofetilide, Sotalol (AIDS)

Mechanism: ^ AP duration, ^ effective refractory period, ^ QT interval, markedly prolonged depolarization (Ik)

Use: A-fib, atrial flutter, ventricular tachycardia (amiodarone, sotalol)

Side effects:
Sotalol - torsades de pointes, excessive beta blockade
Ibutilide - torsades de pointes
Amiodarone - pulmonary fibrosis, hepatotoxicity, hypothyroidism/hyperthyroidism (amiodarone is 40% iodine) acts as hapten (corneal deposits, blue/gray skin deposits resulting in photo dermatitis ), neurologic effects, constipation, cardiovascular effects (bradycardia, heart block, HF) - check patient's PFTs, LFTs, TFTs - lipophilic and has class I, II, III, and IV effects

Question 7

Class IV

Answer 7

Calcium channel blockers
Verapamil, diltiazem

Mechanism: v conduction velocity, ^ effective refractory period, ^ PR interval - slow rise of AP and prolonged repolarization at AV node

Use: prevention of nodal arrhythmias (e.g. SVT), rate control in a-fib

Side effects: constipation, flushing, edema, cardiovascular effects (HF, AV block, sinus node depression)

Question 8

Digoxin

Answer 8

Cardiac glycoside
Mech: directly inhibits Na/K ATPase –> indirect inhibition of Na/Ca exchanger –> ^ Ca –> positive inotropy
Stimulates vagus nerve –> vHR
Use: HF (^contractility), a-fib (v conduction at AV node and depression of SA node)
Side effects: Cholinergic (nausea, vomiting, diarrhea, blurry yellow vision, arrhythmias, AV block), Can lead to hyperkalemia
Factors predisposing toxicity: renal failure (v excretion), hypokalemia (permissive for digoxin binding at K binding site on Na/K ATPase), drugs that displace digoxin from tissue binding sites and v clearance
Antidote: normalize K, cardiac pacer, anti-digoxin Fab fragments, Mg2+

Question 9

Adenosine

Answer 9

^ K out of cells –> hyperpolarization and v Ca
SVT
short acting
Side effects: flushing, hypotension, chest pain, sense of doom, bronchospasm

Question 10

Arrhythmia and drug

Answer 10

A-fib: ibutilide or dofetilide (immediately), amiodarone (maintenance), anti-coagulants
PVST: adenosine IV
VT w MI: amiodarone
VF: cardioversion, amiodarone
TdP: Mg2+
WPW: radio ablation