Pharm: Antiarrhythmic drugs Flashcards Preview

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Flashcards in Pharm: Antiarrhythmic drugs Deck (57):
1

Describe the cardiac conduction system

The sinoatrial node is the pacemaker, and is located in the wall of the right atrium. The SA stimulus spreads across the atria to the AV node, which has a 150ms delay. The his-Purkinje system then rapidly depolarizes the ventricles leading to cardiac contraction

2

How does the action potential from a cardiac pacemaker cell differ from a ventricular cell?

Pacemaker cells do not have rapid depolarization caused by fast sodium channels
Pacemaker cells also have spontaneous phase 4 depolarization unlike the ventricles

3

What are the major ionic fluxes associated with each phase of the action potential?

Phase 0: Na and Ca in
Phase 1: Transient K out
Phase 2: Plateau from Ca2+ in
Phase 3: K+ out
Phase 4: resting membrane (K+ permeable, but K in = K out)

4

Which direction does the concentration gradient favor for Na+, Ca2+ and K+?

Na+: In
Ca2+: In
K+: Out

5

Describe the states of the Na+ channels in cardiomyocytes

3 states, differing based on the conformation of the m (activation) and h (inactivation) gates.
Resting: m closed, h open
Activated: m and h open, only occurs for 1-2msec
Inactivated: m open, h closed

The channels are restored from inactivated to resting state with time and/or voltage

6

How does membrane potential alter the availability of sodium channels?

Fewer channels are available at higher potentials
Channels close between -55 and -75 mV

7

What is the primary determinant of the refractory period?

Action potential duration

8

What channels are not present in pacemaker cells that are found in normal myocytes?

Fast sodium channels

9

What factors increase the risk for arrhythmia?

Digitalis treatment
General anesthesia
Acute MI

10

What are the symptoms of cardiac arrhythmias?

Wilde range from asymptomatic to severe hemodynamic consequences with reduced cardiac output and death

11

What do all arrhythmias result from?

1) disturbed impulse formation
2) disturbed impulse conduction
3) a combination of both

12

What can alter the rate of phase 4 depolarization in cardiac pacemaker cells?

Hypokalemia, beta stimulation, and acidosis increase the rate of depolarization, thus reaching threshold faster
Beta blockade, vagal stimulation decrease the depolarization thus reaching the threshold slower

13

From where in the AP do EAD's originate? How are DAD's different?

EAD's originate from the plateau phase, more often in slow heart rates
DAD's originate from the resting potential, more often in high heart rates

14

How does re-entry occur?

A unidirectional block must be present
A loop is formed from conduction down a normal branch that can loop retrograde through the block slowly and then trigger another impulse down the normal branch

15

What is the general goal of anti-arrhythmic therapy?

Reduce ectopic pacemaker activity and/or modify conduction characteristics to disable re-entry circuits

16

What are the main pharmacological mechanisms for anti-arrhythmic drugs?

Na+ channel blockade
Blockade of sympathetic autonomic effects
Prolong the effective refractory period
Ca++ channel blockade

17

What pharmacological changes are beneficial in order to correct cells with abnormal automaticity?

Reduced phase 4 slope
Increase max Em
Increase threshold potential
Increase action potential durration

18

Why is it beneficial to prolong Na+ channel recovery time for arrhythmia treatment?

Prolonging recovery time may prevent re-entry, block tachycardia and prevent premature beats from occurring by decreasing the likelihood that a new action potential will fire

19

Describe use-dependent/state-dependent drug action

A drug binding with high affinity to the active and inactive channel, but dissociating from the resting channels
This in theory targets depolarized cells that are involved with tachyarrhthmias while leaving unaffected cells alone

20

What is the major danger of anti-arrhythmic drugs?

The do not act specifically, and can end up depressing conduction in normal cells leading to drug-induced arrhythmias
-Dosage, HR, acidosis, electrolytes and ischemia all impact the effect

21

Should anti-arrhythmic drugs be used in patients with asymptomatic or minimally symptomatic arrhythmias?

No. Increased mortality is associated with anti-arrhythmia treatment

22

What are the classes of anti-arrhythmic drugs?

I: Na+ channel blockers
II: beta blockers
III: Prolong action potential duration
IV: Ca++ channel blockers
Other

23

Describe the effect of class I anti-arrhythmic drugs

Reduced conduction velocity by blocking fast sodium channels, reduces the rate and magnitude of phase 0 depolarization

24

What are the 3 subclasses of class I antiarrhythmic drugs and how do they differ?

IA: intermediate kinetics, APD prolonged
IB: fast kinetics, APD decreased
IC: slow kinetics, APD unchanged

25

List the class IA anti-arrhythmic drugs

Procainamide
Quinidine
Disopyramide

26

List the class IB anti-arrhythmic drugs

Lidocaine
Mexiletine

27

List the class IC anti-arrhythmic drugs

Flecainide
Propafenone

28

What are the indications for procainamide?

Atrial and ventricular arrhythmias (rarely used today)
Drug of second or third choice for post-MI ventricular arrhythmias (lidocaine, amiodarone are preferred)

29

What is the metabolite of procainamide?

NAPA, which has class III activity

30

What are the adverse effects of procainamide?

Ganglion blocking properties
Hypotension
Anticholinergic effect
Induce torsade de pointes
Lupus erythematosus syndrome from chronic use (30% of patients)

31

Why are quinidines rarely used?

- They have many adverse events in and out of the heart
- Ganglion blocking & hypotension (worse than procainamide)
- Anticholinergic effects require combo therapy with drug slowing AV conduction
- Induce VFib, torade de pointes
- Chronic use causes cinchonism

32

What is the indication for lidocaine?

Post-MI arrhythmias
Ventricular tachycardia and fibrillation after cardioversion with ischemia/infarction
**Selectively inhibits conduction in depolarized cells

33

What are the adverse effects of lidocaine?

Least cardiotoxic Class I drug
Can cause hypotension
Local anesthetic properties: paresthesias, tremors, nausea, lightheadedness, hearing disturbances, slurred speech, convulsions

34

What is the difference between mexiletine and lidocaine?

Mexiletine is an orally active lidocaine analogue with a much longer half life
-Used off label for chronic pain

35

What are the indications for flecainide and propafenone?

Supraventricular arrhythmias in patients with otherwise normal hearts

36

What are the adverse effects of flecainide?

Increased mortality in patients with Vtach, MI, and ventricular ectopy

37

What channels/receptors are affected by propafenone?

Potent Na+ channel blocker
Also blocks K+ channels
Weak beta blocking activity

38

What is the typical non-selective beta blocker?

Propranolol

39

What is the typical selective beta 1 blocker?

Esmolol

40

How are beta blockers beneficial for treating arrhythmias?

Heart rate is reduced, thus decreasing intracellular Ca overload, pacemaker currents are slowed

41

What are the indications for beta blockers?

Prevent recurrent infarct, sudden death after MI
Exercise-induced arrhythmias
AFib, AFlutter, AV nodal reentry

42

What are the adverse effects of beta blockers?

Bradycardia, reduced exercise capacity, heart failure, hypotension, AV block
Bronchospasm
Lowered glucose, lowered HR

43

Patients with what conditions should NOT be treated with beta blockers?

Asthma, COPD
Diabetics: may mask tachycardia associated with hypoglycemia

44

What is the ECG manifestation of treatment with amiodarone, dronedarone, and sotalol?

QT prolongation on the EKG

45

Explain reverse use/state-dependence

Class III anti-arrhythmics have the least effect at fast heart rates, which is when their effects are most needed

46

What is the molecular mechanism of amiodarone?

Blocks K+ and Na+ channels, Ca++ channels weakly, and beta receptors

47

What are the indications for amiodarone?

Oral:
Recurrent ventricular tachycardia or fibrillation
Atrial fibrillation
IV: cardiac arrest, termination of Vtach, fibrillation

48

What pharmacokinetic parameter makes amiodarone treatment complicated?

Complex half life, takes very long to clear because it accumulates in several organs

49

What adverse effects are associated with amiodarone?

Bradycardia and heart block
Pulmonary toxicity, hepatic toxicity
Photodermatitis
Corneal microdeposits
Blocks T4 to T3
Hypo/hyperthyroidisms

50

What is the difference between amiodarone and dronedarone?

They are structural analogs, but dronedarone does not have iodine atoms attached

51

What are the indications for dronedarone?

Atrial fibrillation/flutter

52

What are the two classes of Ca channel blockers?

Dihydropyridines: nifedipine, nitrendipine
Non-dihydropyradines: benzothiazepine (diltiazem) and phenylalkylamine (verapamil)

53

What are the indications for verapamil?

Lowers heart rate and increases PR interval

Used for supraventricular arrhythmias (drug of choice)
Re-entry arrhythmias/tachycardias
Slowed ventricular rate in atrial flutter/fibrillation

54

What adverse effects are associated with verapamil?

Vasodilation and negative inotropy can cause hypotension, fibrillation in patients with Vtach
-AV block
-Heart block
-Constipation, nervousness, peripheral edema

55

What is adenosine used for?

Conversion of paroxysmal supraventricular tachycardia to sinus rhythm

56

Why doesn't adenosine kill patients?

It has an extremely short half life, so its effects are short lived

57

What are the non-pharmacologic anti-arrhythmic therapies?

Vagal maneuvers
Radiofrequency ablation/Cryoablation
Electrical cardioversion
Implantable cardioverter-defibrillators