Na+ channel blockers and Beta blockers

Question 1

Digoxin

Answer 1

Na+/K+/ATPase pump inhibitor

positive inotrope –> increased intracellular Ca2+ (reduced NCX activity) –> increased contractility and SV

negative chronotrope –> prolongation of AP in SA node = decreased HR

**toxic side effects, not first line

Question 2

Class I Na+ channels blockers alter effective refractory period based on________.

Answer 2

non-specific K+ channel blockage

Question 3

moderate Na+ channel blockade

increased effective refractory period

Answer 3

Class IA

ie. quinidine

Question 4

weak Na+ blockade

decreased effective refractory period

Answer 4

Class IB

ie. lidocaine

Question 5

strong Na+ blockade

no net effect on effective refractory period

Answer 5

Class IC

ie. flecainide

Question 6

• inhibit sympathetic activation of cardiac automaticity

- used to prevent and treat supraventricular arrhythmias

Answer 6

Beta blockers

Question 7

Beta blockers effect on AV node conduction:

What would this look like on EKG?

Answer 7

Decreased AV node conduction

Increased PR interval

Question 8

Beta blockers effect on AV node refractory period:

Answer 8

Increased

Question 9

Beta blockers effect on ventricular conduction and repolarization:

Answer 9

little to none

Question 10

Beta blocker with some Class I activity

-AE: bronchospasm, bradycardia, fatigue

Answer 10

Propanolol

Question 11

Cardioselective B-blocker

-better for pts with asthma

Answer 11

Acebutolol

Question 12

Short acting B-blocker

-used intraoperatively and in acute arrhythmias

Answer 12

Esmolol

Question 13

Non-selective b-blocker

-prolongs action potential (delays slow outward K+ current)

Answer 13

Sotalol

Question 14

Class IA

Cardiac effects: slows AP, slows conduction, prolongs QRS, prolongs APD via non-specific K+ blockade

Extracardiac effects: ganglion blocking –> reduces peripheral vascular resistance can cause hypotension

Tox: excessive AP prolongation, long QT, TORSADES de POINTES arrhythmia and syncope, excessive slowing of conduction
-long term can cause lupus like syndrome

PK: metabolite (NAPA) has class III activity associated w/ TORSADES

• hepatic metabolism of NAPA and renal excretion
• NAPA has longer half-life than procainamide
• plasma protein binding 15-20%

Used in: atrial and ventricular arrhythmias
-2nd or 3rd line for sustained ventricular arrhythmias associated with acute MI

Answer 14

Procainamide

Question 15

Class IA
Cardiac effects: slows upstroke of AP, long QRS, long APD (non-specific K+ blockade), ANTIMUSCARINIC effects

Extracardiac effects: GI, cinchonism (HA, dizziness, tinnitus) at toxic conc.

Tox: long QT, TORSADES

PK: GI absorption, hepatic metabolism, renal excretion

Used in: rarely used d/t side effects and availability of less toxic drugs

Answer 15

Quinidine

Question 16

Class IA
Cardiac Effects: slow upstroke of AP, slow conduction, long QRS, long APD (via non-specific K+ blockade), antimuscarinic

Extracardiac effects: Atropin-like activity –> urinary retention, dry mouth, blurred vision, constipation

Toxicity: same as Quinidine. may precipitate HF de novo or in preexisting depression of LV function. Not first line in USA or in pts with HF.

PK: NO loading dose –> de novo HF.

• Hepatic metabolism, renal excretion.
• protein binding 50-60%

Used in: ONLY ventricular arrythmias in USA.

Answer 16

Disopyramide

Question 17

Class IB
Cardiac effects: selective depression of conduction in depolarized cells. Little effects on EKG in NSR.

Extracardiac effects: not much?, pretty well tolerated

Tox: one of the least toxic class I’s, neurologic: paresthesias, tremor, nausea of central origin, lightheadedness, hearing disturbances, slurred speech, and convulsions. These occur most commonly in elderly or otherwise vulnerable patients or when a bolus of the drug is given too rapidly

PK: extensive first pass hepatic metabolism –> only 3% of oral admin gets to plasma…… must give parenterally. Half-life 1-2 hours.

Used in: first line for V-tach and preventing V-fib AFTER cardioversion in acute ischemia
**prophylactic use may increase total mortality

Answer 17

Lidocaine

Question 18

Class IB
Cardiac effects: orally active congener of lidocaine

Extracardiac effects: good efficacy in relieving chronic pain –> esp d/t diabetic neuropathy and nerve injury (off-label)

Tox: predominantly neurologic, including tremor, blurred vision, and lethargy

PK: elimination half-life is 8–20 hours and permits administration two or three times per day

Uses: Ventricular arrhythmias, chronic pain (off label)

Answer 18

Mexiletine

Question 19

Class IB
Cardiac effects: selective depression of conduction of depolarized cells (not much change on EKG in NSR)

Lidocaine analog withOUT sig first pass metabolism

***not sold in USA

Answer 19

Tocainide

Question 20

Class IC
Cardiac effects: slows upstroke of AP, slows conduction. Potent Na+ and K+ blocker–SLOW unblocking kinetics. Does NOT prolong AP or QT.

Tox: severe exacerbation of arrhythmia in patients with preexisting ventricular tachyarrhythmias, previous myocardial infarction and ventricular ectopy

PK: half-life of approximately 20 hours. Elimination is both by hepatic metabolism and by the kidney

Uses: PVCs, supraventricular arrhythmias

Answer 20

Flecainide

Question 21

Class IC
Cardiac effects: slows upstroke of AP, slows conduction. Weak Beta-blocker. No effect on AP duration.

Tox: metallic taste and constipation

PK: metabolized in the liver, with an average half-life of 5–7 hours

Uses: supraventricular arrhythmias

Answer 21

Propafenone

Question 22

Class IC
Cardiac effects: Potent Na+ channel blocker, no prologation of AP.

used to treat ventricular arrhythmias

***not sold in USA

Answer 22

Moricizine

Question 23

Class II
Cardiac effects: non-selective beta antagonist. decreases heart rate, myocardial contractility, blood pressure, and myocardial oxygen demand

Tox: a lot; see Katzung’s

PK: Extensive first-pass effect, hepatically metabolized. Oral: ~25%; oral bioavailability may be increased in Down syndrome children; protein-rich foods increase bioavailability of immediate release formulations by ~50%

Uses: mostly HTN, also migraine prophylaxis

Answer 23

Propanolol

Question 24

Class II

Cardiac effects: β1, β2 antagonist, with intrinsic sympathomimetic (partial agonist) effect
-Lower BP • modestly lower HR

Uses: Hypertension • arrhythmias • migraine • may avoid worsening of bradycardia

PK: Oral •

Toxicity: Fatigue • vivid dreams • cold hands

Answer 24

Acebutolol

Question 25

Class II

Cardiac effects: Blockade of β1 > β2. Very brief cardiac β blockade

Uses: Rapid control of BP and arrhythmias, thyrotoxicosis, and myocardial ischemia intraoperatively

PK: Parenteral only • half-life ∼10 min •

Toxicity: Bradycardia • hypotension

Answer 25

Esmolol

Question 26

Class II (and III)

Cardiac effects: both β-adrenergic receptor-blocking (class 2) and action potential-prolonging (class 3) actions

PK: well absorbed orally with bioavailability of nearly 100%. It is NOT** metabolized in the liver (few drug-drug interaction) and is not*** bound to plasma proteins.
Excretion- predominantly by the kidneys. Half-life of approximately 12 hours

Uses: life-threatening ventricular arrhythmias

• maintenance of sinus rhythm in patients with atrial fibrillation
• approved for treatment of supraventricular and ventricular arrhythmias in the pediatric age group
• decreases the threshold for cardiac defibrillation.

Answer 26

Sotalol