Nordgren: DRUGS- K and Ca channel blockers

Question 1

CE: Amiodarone

Answer 1

Prolong AP

*Also a NA channel blocker and weak blocker of Beta receptors and Ca channels > slows HR and AV node conduction (partial class 4 drug)

Question 2

ECE: Amiodarone

Answer 2

Peripheral vasodilation

Question 3

Toxicity: Amiodarone

Answer 3

1. Bradycardia and heart block in pts w/ preexisting SA/AV node disease–> slow HR
2. Drug accumulates in tissues
3. Blocks peripheral conversion of T4 to T3

Question 4

PK: Amiodarone

Answer 4

Stays in body and has effects for up to 3 months.

Substrate for CYP3A4–> level of drug influenced by other drugs that might inhibit cyp3A4.

Amiodarone also inhibits other p450s –> can lead to increased levels of statins, digoxin and warfarin

Question 5

TU: Amiodarone

Answer 5

1. Ventricular tachycardia (v. fib)

2. A. fibrillation and flutter

Question 6

What is the most important adverse effect of amiodarone?

Answer 6

dose related PULMONARY TOXICITY

Question 7

What are other adverse effects of amiodarone?

Answer 7

Related to tissue accumulation:

1. Abnormal liver function–> hypersensitivity hepatitis
2. Skin deposits > photodermatitis, gray-blue skin discoloration in sun-exposed areas
3. Corneal microdeposits (in nearly ALL patients), halos develop in peripheral visual fields, rarely optic neuritis leading to blindness
4. Hypo- and Hyperthyroidism

Question 8

CE: Dofetilide

Answer 8

1. Selective K channel blocker
2. Prolongs AP
3. Increase in QT interval (prolonged ERP in His-Purkinje system and ventricles)

Question 9

Toxicity: Dofetilide

Answer 9

Life-threatening ventricular arrhythmias

Question 10

PK: Dofetilide

Answer 10

100% bioavailable!

Hepatic metabolism via CYP3A4

Question 11

TU: Dofetilide

Answer 11

Maintain/restore normal sinus rhythm in a. fib.

Question 12

Dofetilide is contraindicated in?

Answer 12

long QT, bradycardia, hypokalemia

Question 13

CE: Ibutilide

Answer 13

1. Prolongs AP

2. Slow inward Na activator> delays repolarization > inhibits Na channel inactivation > increases ERP

Question 14

Toxicity: Ibutilide

Answer 14

1. Excessive QT interval prolongation and torsades de pointes
2. Can cause life-threatening ventricular arrhythmias

Question 15

PK: Ibutilide

Answer 15

Hepatic metabolism

Question 16

TU: Ibutilide

Answer 16

1. ACUTE conversion of a. flutter and a. fib to normal sinus rhythm

Question 17

Is ibutilide more effective at treating flutter or fib?

Answer 17

Flutter.

The mean time to termination is 20 mins so it’s not good for chronic treatment.

Question 18

CE: Verapamil

Answer 18

Blocks both activated and inactivated L type Ca channels

Question 19

Where does verapamil have it’s greatest effects?

Answer 19

In tissues that fire frequently, those less polarized, or nodal tissue.

Question 20

ECE: Verapamil

Answer 20

Peripheral vasodilation.

Question 21

Toxicity: Verapamil

Answer 21

AV block at large doses in pts w/ AV nodal disesase

Question 22

PK: Verapamil

Answer 22

Hepatic metabolism

Question 23

TU: Verapamil

Answer 23

1. Supraventricular tachycardia

2. A. fib/flutter (reduces ventricular rate, not convert back to sinus rhythm)

Question 24

Verapamil is contraindicated for what disease?

Answer 24

Wolff parkinson white

Question 25

CE: Diltiazem

Answer 25

Similar to verapamil but w/ more smooth muscle-relaxing effect and produces less bradycardia.

Question 26

ECE: Diltiazem

Answer 26

k

Question 27

Toxicity: Diltiazem

Answer 27

k

Question 28

PK: Diltiazem

Answer 28

k

Question 29

TU: Diltiazem

Answer 29

k

Question 30

MOA: Adenosine

Answer 30

Activation of inward rectifier K channels and inhibition of L type Ca channels > hyperpolarization and suppression of Ca dependent AP (nodal tissue)

Question 31

What does Adenosine do to AV conduction and AV refractory period?

Answer 31

Suppresses AV conduction and INCREASES AV refractory period

Question 32

What is the drug of choice for conversion of paroxysmal supraventricular tachycardia but NOT a. flutter and fibrillation?

Answer 32

Adenosine

Question 33

What are the SE of adenosine?

Answer 33

Related to vasodilatory properties of the drug. 1. flushing and HA 2. Hypotension that can develop rapidly (reversed quickly if you stop drug) 3. AV block

Question 34

How do methylxanthines relate to adenosine?

Answer 34

Methylxanthines (like caffeine), competitivley antagonize the binding of adenosine at its purinergic receptor

Question 35

Adenosine is contraindicated in patients with what condition?

Answer 35

2 and 3 AV block

Question 36

What is digitalis primarily used for?

Answer 36

1. Heart failure (primarily) | 2. Reducing ventricular rate when it is being driven by a high atrial rate (a. fib or flutter)

Question 37

What is the MOA of digitalis?

Answer 37

1. Activation of vagal efferent nerves in the heart > reduces conduction in the AV node 2. Inhibits Na/K/ATPase pump

Question 38

What effect does the inhibition of Na/K/ATPase pump have on cardiac cells?

Answer 38

Increaes the intracellular Na concentration > reverses action on Na/Ca exchanger > more Ca in the cell > improves cardiac contractility (Ca binds troponin)

Question 39

What is the net effect of increased contractility (d/t inhibition of Na/K/ATPase) have on HR?

Answer 39

Increased SV > increased Co> Decreased HR

Question 40

What does activation of vagal efferent nerves to the heart by digitalis do?

Answer 40

Reduces the conduction in the AV node > partial block > fewer impulses reach ventricles > ventricular rate falls

Question 41

How does a decrease in intracelluar K and an increase in intracellular Na contribute to afterpolarizations?

Answer 41

Contribute to the depolarization of RMP which contributes to afterdepolarizations at high doses.

Question 42

What are the SE of digitalis?

Answer 42

1. Exterme AV block (contraindicated in pts who have it already) 2. shouldn't be used by pts w/ impaired renal function b/c it's eliminated by hte kidenys

Question 43

Digitalis toxicity looks like what on an EKG?

Answer 43

Salvador Dali's checkmark moustache

Question 44

What should you ask before you initiate antiarrhythmic therapy?

Answer 44

1. Eliminate the cause if possible 2. Make a firm diagnosis 3. Determine the baseline condition 4. Questions the need for therapy