AntiArrhythmics

Question 1

Cardiac glycoside:

Answer 1

Digoxin

Question 2

Digoxin: mech

Answer 2

Direct inhibition of Na+/K+ ATPase leads to indirect inhibition of Na+/Ca2+ exchanger/antiport. Increases intracellular Ca2+ –> positive inotropy. Stimulates vaguse nerve –> decreased HR

Question 3

Digoxin: use

Answer 3

CHF (increased contractility); atrial fibrillation (decreased conduction at AV node and depression of SA node)

Question 4

Digoxin: tox

Answer 4

Cholinergic - N/V, diarrhea, blurry yellow vision (think Van Gogh)
ECG - Increased PR, Decreased QT, ST scooping, T-wave inversion, arrhythmia, AV block
Can lead to hyperkalemia, which indicates poor prognosis
Factors predisposing to toxicity - renal failure (decreased excretion), hypokalemia (permissive for digoxin binding at K+ binding site on Na+/K+ ATPase, verapamil, amiodarone, quinidine, (decrease digoxin clearance; displaces digoxin from tissue-binding sites).

Question 5

Digoxin: antidote

Answer 5

Slowly normalize K+, cardiac pacer, anti-digoxin Fab fragments, Mg2+

Question 6

Na+ channel blockers (class I):

Answer 6

Slow or block conduction (especially in depolarized cells). Decrease slope of phase 0 depolarization and increase threshold for firing in abnormal pacemaker cells. Are state dependent (selectively depress tissue that is frequently depolarized (tachycardia)
Hyperkalemia causes increased toxicity for all class I drugs

Question 7

Class IA:

Answer 7

Quinidine, Procainamide, Disopyramide

“The Queen Proclaims Diso’s pyramid”

Question 8

Class IA: mech

Answer 8

Increased AP duration, increased effective refractory period (ERP), increased QT interval

Question 9

Class IA: use

Answer 9

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

Question 10

Class IA: tox

Answer 10

Cinchonism (HA, tinnitus with quinidine), reversible SLE-like syndrome (procainamide), HF (disopyramide), thromboycytopenia, torsades de pointes due to increased QT interval

Question 11

Class IB: drugs

Answer 11

Lidocaine, Mexiletine

Question 12

Class IB: mech

Answer 12

Decreases AP duration. Preferentially affect ischemic or depolarized Purkinje and ventricular tissue. Phenytoin can also fall into IB category.

Question 13

Class IB: uses

Answer 13

Acute ventricular arrhythmias (esp post-MI), digitalis-induced arrhythmias. IB is Best post-MI.

Question 14

Class IB: tox

Answer 14

CNS stimulation/depression, cardiovascular depression.

Question 15

Class IC: drugs

Answer 15

Flecainide, Propafenone. “Can I have Fries, Please.”

Question 16

Class IC: mech

Answer 16

Significantly prolongs refractory period in AV node.

Minimal effect on AP duration.

Question 17

Class IC: tox

Answer 17

Proarrhythmic, especially post-MI (contraindicated). IC is Contraindicated in structural and ischemic heart disease.

Question 18

Antiarrhythmics Class II:

Answer 18

Beta-blockers: Metoprolol, propranolol, esmolol, atenolol, timolol, carvedilol

Question 19

Class II: mech

Answer 19

Decrease SA and AV nodal activity by decreasing cAMP, Ca2+ currents. Suppress abnormal pacemakers by decreasing slope of phase 4.
AV node particularly sensitive - increases PR interval. Esmolol very short acting

Question 20

Class II: use

Answer 20

SVT, slowing ventricular rate during a-fib and a-flutter

Question 21

Class II: tox

Answer 21

Impotence, exacerbation of COPD and asthma, cardiovascular effects (bradycardia, AV block, CHF), CNS effects (sedation, sleep alterations). May mask signs of hypoglycemia.
Metoprolol can cause dyslipidemia. Propranolol can exacerbate vasospasm in Prinzmetal angina. Contraindicated in cocaine users (risk of unopposed alpha-adrenergic receptor agonist activity.) Treat overdose with glucagon, saline, atropine.

Question 22

Antiarrhythmics Class III:

Answer 22

K+ channel blockers: Amiodarone, Ibutilide, Dofetilide, Sotalol. “AIDS”

Question 23

Class III mech:

Answer 23

Increases AP duration, Increased ERP. Used when other antiarrhythmics fail. Increased QT interval.

Question 24

Class III use:

Answer 24

A-fib, a-flutter; ventricular tachycardia (amoidarone, sotalol)

Question 25

Class III tox:

Answer 25

Sotalol - torsades de pointes, excessive Beta blockade
Ibutilide - torsades de pointes
Amiodarone - pulmonary fibrosis, hepatotoxicity, hypothyroidism/hyperthyroidism (amiodarone is 40% iodine by weight), corneal deposits, skin deposits (blue/gray) resulting in photodermatitis, neurologic effects, constipation, cardiovascular effects (bradycardia, heart block, CHF).

Question 26

Antiarrhythmics - Class IV:

Answer 26

Ca2+ channel blockers: Verapamil, diltiazem

Question 27

Class IV: mech

Answer 27

Decreased conduction velocity, increased ERP, increased PR interval

Question 28

Class IV: use

Answer 28

Prevention of nodal arrhythmias (ex. SVT), rate control in atrial fibrillation

Question 29

Class IV: tox

Answer 29

Constipation, flushing, edema, CV effects (CHF, AV block, sinus node depression)

Question 30

Other antiarrhythmics:

Answer 30

Adenosine, Mg2+

Question 31

Adenosine: mech

Answer 31

Increases K+ out of cells –> hyperpolarizing the cell and decreasing Ca2+ current. Very short acting (~15 sec)

Question 32

Adenosine: use

Answer 32

Drug of choice in diagnosing/abolishing SVT

Question 33

Adenosine: tox

Answer 33

Flushing, hypotension, chest pain. Effects blocked by theophylline and caffeine

Question 34

Mg2+: use

Answer 34

Effective in torsades de pointes and digoxin toxicity