K+ and Ca2+ Blockers

Question 1

specifically what channels are blocked by class III drugs?

Answer 1

class III drugs are the K blockers and they specifically boock the inward rectifier K+ channels

Question 2

what phase of the actionpotential is altered by K blockers? How?

Answer 2

phase 3 - repolarization

slows repolarization down, thus increasing AP duration and effective refractory period

Question 3

If the AP is prolonged by K blockers, what’s a side effect common to all of them?

Answer 3

prolonged QT

Question 4

If K blockers prolong the time that the cell is unexcitable, what are they apricularly useful for/

Answer 4

useful in suppressing reentry arrhythmias

Question 5

What are the three K blockers we know/

Answer 5

Amiodarone
Dofetilide
Ilbutilide

Question 6

What are the cardiac effects of amiodarone?

Answer 6

blocks a lot…

prolongs AP as a K blocker, but also a potent Na blocker, weak beta blocker and weak Ca blockers, so you also get slowed heart rate and slowed AV node conduction

Question 7

What are the extracardiac effects of amiodarone/

Answer 7

peripheral vasodilation

Question 8

What are the main toxicities of amiodarone?

Answer 8

the most important is dose related pulmonary toxicity
others include
1. abnormal liver functions, hypersensitivity hepatitis
2. skin deposits leading to photodermatitis
3. corneal microdeposits in nearly ALL patients - halos develop in peripheral visual fields, rarely leads to blindness
4. hypo and hyperthyroidism

Question 9

How is amiodarone metabolized?

Answer 9

mainly hepatic metabolism to a bioactive metabolite

note - effects will last 1-3 months past cessation!

Substrate for CYP3A4 - so will be influenced by inducers!

inhibits several p450s and can increase concentrations of other drugs

Question 10

what is amiodarone used for?

Answer 10

ventricular tachycardia including v fib! also atrial fibrillation and flutter

Question 11

What are the cardiac effects of dofetilide?

Answer 11

it’s a VERY selective K blocker, so you get prolonged AP and increase QT interval.

Question 12

What is the main toxicity of dofetilide?

Answer 12

life-threatening ventricular arrhythmias because of the long QT

Question 13

What are the pharmacokinetics of dofetilide?

Answer 13

100% bioavailable! hepatic metabolism via CYP3A4

Question 14

What is the main therapeutic use of dofetilide?

Answer 14

maintenance and restoration of normal sinus rhythm in atrial fibrillation

DON”T USE in people with long QT, bradycardia or hypokalemia

Question 15

What are the cardiac effects of ibutilide?

Answer 15

prolong AP as K blocker. Also slows inward Na activator , so delayed repolarization further.

also inhibits Na channel inactivation, which increases the ERP?

Question 16

What is the main toxicity for ibutilide?

Answer 16

excessive QT prolongation and torsades de pointes. can cause life threatening ventricular arrhythmias

Question 17

How is ibutilide metabolized?

Answer 17

hepatic metabolism

Question 18

What’s the main therapeutic use of ibutilide?

Answer 18

acute conversion of a flutter and a fib to normal sinus. more effective in flutter - 20 minutes mean time to termination

Question 19

What type of Ca2+ channels are specifically blocked by Class IV drugs? WHere are the channels located?

Answer 19

L type - located on vascular smooth muscle, cardiac myocytes and SA/AV nodes

Question 20

What are the effects of Class IV drugs on smooth muscle?

Answer 20

the channels are responsible for regulating the influx of calcium into the muscle cells, which in turn stimualtes smooth muscle contraction and cardiac myocyte contraction, so blockin gCa entry causes vascular smooth muscle vasodilation

Question 21

What are the effects of Class IV drugs on cardiac myocytes?

Answer 21

Ca2+ influx is responsible for the slow repolarization (plateau) of the action potential, so blocking Ca2+ entry shortens phase 2 of the AP and reduces the force of contraction because there’s less Ca2+ available to bind troponin

Question 22

What are the effects of Class IV drugs on nodal cells?

Answer 22

the L-type Ca channels play an important role in pacemaker current and in phase 0 of the action potential

blocking Ca entry causes a decreased HR and decreased conduction velocity in the AV node

Question 23

Why can Class IV drugs be used for HTN?

Answer 23

because of their smooth muscle vasodilatory effects

decreases systemic vascular resistance and thus lowers arterial blood pressure

Question 24

Why can class IV drugs be used in angina?

Answer 24

because they cause vasodilation and decrease HR, the systemic vasodilation reduces arterial pressure which reduces ventricular afterload, thus decreasing oxygen demand

decreased HR and contractility also lead to decreased oxygen demand

can also dilate coronary arteries and prevent vasospams, thereby increasing O2 supply to the myocardium

Question 25

What are the two sublcasses of class IV drugs?

Answer 25

dihydropyridines and non-dihydropyridines

Question 26

How do the dihydropyridines and non-dihydropyridines differ?

Answer 26

in their selectivity for catrdiac vs. vascular L type Ca 2+ channels dihydropyridines = vascular type Non-dihydropyridines = cardiac type (and some vascular)

Question 27

What are the two non-dihydropyridines we need to know?

Answer 27

Verapamil and Diltiazem

Question 28

How do Verapamil and Diltiazem's mechanisms of action differ?

Answer 28

verapamil is relatively selective for myocardium and less effective as a systemic vasodilator drugs - treat angina and arrhythmias Diltiazem has selectivity for both myocardium and vascular Ca2+ channels. So it's used to treat angina, arrhythmias and HTN (without causing the same degree of reflexive cardiac stimulation as dihydropyridines)

Question 29

What are the main side effects of dihydropyridines?

Answer 29

related to vasodilation = flushing, headache, excessive hypotension, edema, and reflexive tachycardia

Question 30

What are the side effects of non-dihydropyridines?

Answer 30

excessive bradycardia, impaired electrical conduction and depressed contractility

Question 31

Who should NOT be given non-dihydropyridines?

Answer 31

those with preexisting bradycardia, conduction defects or heart failure caused by systolic dysfunciton

Question 32

What other type of antiarrhythmic should the Class IV drugs NOT be given with?

Answer 32

beta blockers - the calcium blockade will augment the effects of the beta blockade

Question 33

What is the mechanism of action for adenosine?

Answer 33

It activates inward rectifier K channels and inhibits L-type Ca2+ channels, resultin gin hyperpolarization and suppression of Ca2+ dependent action potentials in nodal tissue this suppresses AV conduction and increases AV rereactory period

Question 34

What is adenosine used for?

Answer 34

it's the drug of choice for prompt ocnversion of paroxysmal supraventricular tachy cardia note - doesn't work for a fib or a flut

Question 35

What are the side effects of adenosine?

Answer 35

flushing and headache can produce arterial hypotentsion Ab block

Question 36

What does caffein do to adenosine?

Answer 36

xanthines like caffein will competitively antagonize the binding of adenosine to its receptor, so it will be less effective

Question 37

Adenosine is contraindicated in what patients?

Answer 37

paitents with 2 or 3 degree AV block.

Question 38

What is the primary use for digitalis (digoxin)?

Answer 38

heart failure

Question 39

What arrhythmias is digoxin also helpful for?

Answer 39

atrial fibrillation and flutter - it will reduce the ventricular rate being driven by these two.

Question 40

What is the mechanism for Digitalis to improve cardiac contractility?

Answer 40

It inhibits the Na/K/ATPase pump such that intracellular Na concentration increases. This then reverses the action of the Na/Ca exchanger such that you have more Ca in the cell and thus higher contractility, increasing stroke volume and cardiac output

Question 41

What is the mechanism digitlis uses to the rate of conduction in SA and AV node?

Answer 41

activation of vagal efferent nerves

Question 42

What are the side effects of digitalis?

Answer 42

extreme AV block (because of the vagal effects on the AV) drug interactions with all the other antiarrhythmics, NSAIDS and diuretics

Question 43

Who shouldn't you give digoxin to?

Answer 43

people with AV block already people with wolf parkinson white people with impaired renal function

Question 44

What does digitalis toxicity look like clinically?

Answer 44

GI distress, hyperkalemia, life-threatening arrhythmias (increased automaticity and AV nodal blockade)

Question 45

What does digitalis toxicity look like on EKG?

Answer 45

an increased PR interval, plattened T waves and decreased QT interval - like a mustache or checkmark after the R wave

Question 46

What are the 4 questions you should always find an answer for before starting an anriarrhythmic drug?

Answer 46

1. eliminate the cause if possible 2. make a firm diagnosis 3. determine the baseline conduction 4. questions th need for therapy.e