Na+, K+, and Ca2+ Channel Blocker Drugs

Question 1

Amiodarone

Answer 1

MOA/Cardiac Effects: K+ channel blocker, prolonging effective refractory period (prolongs QT interval)

Extracardiac Effects: peripheral vasodilation

Toxicity: bradycardia, heart block in pts with pre-existing nodal disease, source of inorganic iodine (screws up thyroid)

PK: dose-related pulmonary toxicty, CYP3A4 hepatic metabolism

TU: reentry arrhythmias

Question 2

Dofetilide

Answer 2

MOA/Cardiac Effects: selective K+ channel blocker, prolongs effective refractory period (prolonging QT) primarily in ventricles

Extracardiac Effects:

Toxicity: lethal ventricular arrhythmias

PK: CYP3A4 hepatic metabolism

TU: a-fib, contraindicated in prolonged QT, bradycardia, hypokalemia

Question 3

Ibutilide

Answer 3

MOA/Cardiac Effects: K+ channel blocker (prolonging QT and refractory period), also Na+ channel blocker (slows depolarization)

Extracardiac Effects:

Toxicity: torsade de pointes

PK: hepatic metabolism

TU: a-fib and a-flutter, 20 min to effect

Question 4

“pine”s

Answer 4

MOA/Cardiac Effects: dihydropyridine Ca²⁺ channel blocker, effects primarily sm. muscle tissue causing relaxation

Extracardiac Effects: vascular sm. muscle relaxation

Toxicity: reflex tachycardia

PK:

TU: HTN

Question 5

Verapamil

Answer 5

MOA/Cardiac Effects: non-dihydropyridine L-type Ca²⁺ blocker, prolongs AP in nodal cells –> decrease HR

Extracardiac Effects: peripheral vasodilation (minimal)

Toxicity: AV node block, constipation, peripheral edema

PK: hepatic metabolism

TU: supraventricular tachycardia, a-fib and a-flutter, contradicted in Wolf-Parkinson-White (accessory pathway)

Question 6

Diltiazem

Answer 6

MOA/Cardiac Effects: non-selective L-type Ca2+ channel blocker, nodal cells (decrease HR) and vascular sm. muscle (vasodilation)

Extracardiac Effects: sm. muscle (vasodilation)

Toxicity: hypotension

PK: hepatic metabolism

TU: supraventricular tachycardia, a-fib, a-flutter, contradicted in Wolf-Parkinson-White syndrome (accessory pathway)

Question 7

Adenosine

Answer 7

MOA/Cardiac Effects: activation of K⁺ channels and inhibition of L-type Ca²⁺ channels. hyperpolarization of cells and suppression of Ca²⁺-dependent nodal tissue

Extracardiac Effects:

Toxicity: hypotension, a-fib, headache

PK: 10 second half life

TU: supraventricular tachycardia

Question 8

Digitalis

Answer 8

MOA/Cardiac Effects: inhibits Na⁺/K⁺ ATPase pump, indirectly inhibiting Na⁺/Ca²⁺ antiporter

contractile cells: more Ca²⁺ = positive inoptrope

vagal activation = negative chronotrope

Extracardiac Effects:

Toxicity: arrhythmias

PK:

TU: refractory CHF

Question 9

Procainamine

Answer 9

MOA/Cardiac Effects: IA Na⁺ channel blocker, slows AP upstroke, prolonges QRS, prolonges action potential depolarization through non-specific blocking of K⁺ channels

Extracardiac Effects: hypotension from reduced peripheral vascular resistance

Toxicity: torsade, lupus-like syndrome in long-term

PK: hepatic metabolism, renal excretion

TU: atrial and ventricular arrhythmias

Question 10

Quinidine

Answer 10

MOA/Cardiac Effects: IA Na⁺ channel blocker, prolongs QRS, prolongs action potential by non-specific K⁺ channel blockade

Extracardiac Effects: GI effects, cinchonism (headache, dizziness, tinnitus)

Toxicity: QT prolongation, torsade, arrhythmias, sycope

PK: hepatic metabolism, renal excretion

TU: rarely used

Question 11

Disopyramide

Answer 11

MOA/Cardiac Effects: IA Na⁺ channel blocker, prolongs QRS, blocks action potential depolarization through non-specific K⁺ channel blockade

Extracardiac Effects: atropine-like activity

Toxicity: heart failure

PK: loading dose not recommended

TU: ventricular arrhythmias

Question 12

Lidocaine

Answer 12

MOA/Cardiac Effects: IB Na⁺ channel blocker, selective depression of conduction in depolarized cells, little effect seen on EKG

Extracardiac Effects:

Toxicity: neurologic

PK: IV only, t_1/2 = 1-2 hr

TU: v-tach after cardioversion in acute ischemia

Question 13

Mexiletine

Answer 13

MOA/Cardiac Effects: IB Na⁺ channel blocker, orally active version of lidocaine, selective depression of conduction in depolarized cells, little effect seen on EKG

Extracardiac Effects:

Toxicity: neurologic

PK: PO

TU: diabetic neuropathy (off label)

Question 14

Tocainide

Answer 14

MOA/Cardiac Effects: lidocaine analogue, no longer sold in USA

Extracardiac Effects:

Toxicity:

PK:

TU:

Question 15

Flecainide

Answer 15

MOA/Cardiac Effects: IC Na⁺ channel blocker, slows AP upstroke, prolongs refractory period in AV node

Extracardiac Effects:

Toxicity:

PK:

TU: supraventricular tachycardias incl. a-fib, refractory v-tach last resort

Question 16

Propafenone

Answer 16

MOA/Cardiac Effects: IC Na⁺ channel blocker, slows AP upstroke,

Extracardiac Effects:

Toxicity: pro-arrhythmatic post-MI

PK:

TU: supraventricular tachycardias incl. a-fib

Question 17

Moricizine

Answer 17

MOA/Cardiac Effects: IC Na⁺ channel blocker, no longer available

Extracardiac Effects:

Toxicity:

PK:

TU:

Question 18

Propanolol

Answer 18

MOA/Cardiac Effects: nonspecific β1 and β2 antagonist

Extracardiac Effects:

Toxicity:

PK:

TU:

Question 19

Metoprolol

Answer 19

MOA/Cardiac Effects: β1 antagonist

Extracardiac Effects:

Toxicity:

PK:

TU:

Question 20

Acebutolol

Answer 20

MOA/Cardiac Effects: β1 antagonist

Extracardiac Effects:

Toxicity:

PK:

TU:

Question 21

Esmolol

Answer 21

MOA/Cardiac Effects: β1 antagonist

Extracardiac Effects:

Toxicity:

PK:

TU:

Question 22

Sotalol

Answer 22

MOA/Cardiac Effects: β1 antagonist

Extracardiac Effects:

Toxicity:

PK:

TU: