K+ and Ca2+ Antiarrhythmics

Question 1

Primary role of K+ in myocyte action potential?

Answer 1

repolarization (phase 3)

Question 2

Common EKG effect of all class III drugs with prolonged repolarization?

Answer 2

prolonged QT

Question 3

Class III antiarrhythmic

prolongs AP

also potent Na+ channel blocker

weak Beta and Ca2+ blocker

slows HR and AV node conduction

Answer 3

Amiodarone

Question 4

Extracardiac effects of Amiodarone

Answer 4

peripheral vasodilation

Question 5

Toxicity of Amiodarone

Answer 5

Bradycardia and heart block in pts w/ preexisting SA or AV node disease

Drug accumulation in tissue (LONG half life)

Blocks peripheral conversion of thyroxine (T4) to triiodothyronine (T3)–source of inorganic iodine

Question 6

PK if Amiodarone:

Answer 6

Hepatic metabolism

Major metabolite is bioactive — long last effects

• pulm toxicity
• abnormal liver function
• skin deposits
• corneal microdeposits (halos, optic neuritis, blindness)
• hypo/hyper thyroidism

CYP3A4 drug interactions

inhibits several P450s –> icr. levels of other drugs (ie. warfarin, statins, digoxin)

Question 7

Uses of Amiodarone:

Answer 7

V tach
V fib
A fib
A flutter

Question 8

Most important adverse effect of Amiodarone:

Answer 8

dose related Pulmonary Toxicity

Question 9

Class III

Very selective K+ blocker

Maintenance and restoration of NSR in a fib

Answer 9

Dofetilide

Question 10

Dofetilide

Class?

Toxicity?

PK?

Use?

Answer 10

Class III (very selective K+ blockade)

Tox: life threatening ventricular arrhythmias

PK: 100% bioavailability, hepatic met. CYP3A4

Use: a fib

contraindications: long QT, bradycardia, hypokalemia

Question 11

Class III

also slow inward Na+ ACTIVATOR –> delays repolarization (inhibits Na+ inactivation, increasing ERP)

Toxicity: long QT, torsades –> life threatening ventricular arrhythmias

PK: hepatic

Use: acute conversion of a fib/flutter in NSR

Answer 11

Ibutilide

Question 12

Target channel for Class IV drugs?

Answer 12

L-type Ca2+

• VSM relaxation
• decreased cardiac contractility (less Ca2+ available to bind troponin)

Question 13

Class IV drugs effect on nodal cells?

Answer 13

• decreased HR

- decreased conduction (especially AV node)

Question 14

Therapeutic indications for Class IV?

Answer 14

HTN (arteriole SM relaxation)

Angina (decreased afterload–decreased O2 demand)

Arrhythmias (decreased depol rate, decreased conduction velocity)

Question 15

What are the two subclasses of Class IV drugs?

How do they differ?

Answer 15

1. Dihydropyridines – smooth muscle selective –> can cause reflex cardiac stimulation
2. Non-dihydropyridines – more selective for myocardium

**Diltiazem does both – able to reduce arterial pressure without same degree of reflex cardiac stimulation

Question 16

Class IV drugs should not be used in conjunction with?

Answer 16

Beta blockers

Question 17

Non-DHP Class IV

more specific for myocardium

used in SVT, a fib/flutter

Contraindicated in WPW

Answer 17

Verapamil

Question 18

Non-DHP Class IV

More equivalent selectivity for vascular and myocardial SM

Answer 18

Diltiazem

Question 19

Activates K+

inhibits Ca2+ L type

results in hyperpolarization and suppression of nodal tissue

used for SVT

not effective for a fib/flutter

Answer 19

Adenosine

***contraindicated in 2 and 3 deg AV block

Question 20

Inhibits Na+/K+/ATPase pump

improves contractility (reverses NCX–> more Ca2+ in cell)

Decreases HR

activates vagal efferents to heart

primarily used in HF (also a fib/flutter)

Answer 20

Digoxin

Question 21

Digoxin toxicity on EKG looks like?

Answer 21

Salvadore Dalis mustache

increased PR

flattened T-wave

Decreased QT