Antiarrhytmic Drugs Vb

Front 1

Describe class I antiarrhythmic drugs

Back 1

-Primary effect of this class of drugs is to slow conduction by reducing the depolarizing current that flows through Na+ channels during phase 0 of the action potential of atrial and ventricular muscle. These drugs also decrease the pacemaker current (I_f) in ectopic pacemaker cells.
-The class IA drugs also decrease the delayed rectifier K current (I_K) to prolong repolarization and the refractory period

Front 2

What class is disopyramide?

Back 2

Class IA

Front 3

Describe the atrial effects of disopyramide

Back 3

-Effective for the chronic oral therapy of atrial flutter and fibrillation in patients without ventricular dysfunction
-A therapeutic option for these arrhythmias
-For rhythm control, NOT rate control
-Mechanism is probably by prolonging the atrial refractory period because it blocks I_K
-Block of I_Na leading to slowing of conduction and eventual conduction block in reentrant circuits may also be involved
-Has a vagolytic effect which may allow more impulses to reach the ventricle if atrial fibrillation occurs while a patient is being treated with this drug
-To prevent this increase in ventricular rate, digoxin has been administered because digoxin increases vagal activity to the AV node

Front 4

Describe the ventricular effects of disopyramide

Back 4

Disopyramide is not used for therapy of ventricular arrhythmias. It should never be administered to patients with ventricular disease because of substantial negative inotropic effects in these patients

Front 5

Describe the effect of disopyramide on the ECG sinus rate

Back 5

-Therapeutic plasma levels may increase sinus rate slightly due to a vagolytic effect. Toxic plasma levels may depress sinus rate and cause severe sinus bradycardia

Front 6

Describe the effect of disopyramide on the ECG PR interval

Back 6

Therapeutic plasma levels have little effect on the PR interval

Toxic plasma levels may cause AV block

Front 7

Describe the effect of disopyramide on the ECG QRS duration

Back 7

Therapeutic concentrations widen the QRS complex due to slowing of conduction in the ventricle. If conduction is severely depressed, reentrant ventricular tachycardia may occur as a toxic effect of the drug

Front 8

Describe the effect of disopyramide on the ECG QT interval

Back 8

Prolonged and prolongation can be associated with ventricular tachycardia (torsades)

Front 9

Describe the administration, absorption, and elimination of disopyramide

Back 9

-Well absorbed after oral administration (bioavailability reported as 60%)
-It is not administered intravenously
-Approximately 40-60% of the drug is eliminated unchanged in the urine
-The remainder is metabolized in the liver

Front 10

Describe the toxic effects of disopyramide

Back 10

-Can cause arrhythmias and conduction disturbances
-Precipitates congestive heart failure in patients with depressed ventricular and should never be given to these patients

Front 11

Describe Quinidine

Back 11

-Class IA
-The oldest antiarrhythmic drug
-An optical isomer of quinine (an antimalarial drug)
-Its use in clinical therapy has rapidly changed during the past 10 years from one of the most widely used drug to a little used drug in the US
-It is still widely used in Europe

Front 12

Describe the effect of Quinidine on atrial arrhythmias

Back 12

Atrial flutter and fibrillation - Has been used to terminate atrial flutter or fibrillation and/or prevent their recurrence after termination of these arrhythmias by cardioversion
-Can still encounter patients taking quinidine and digoxin for these arrhythmias for these arrhythmias for many years but there are few cardiologists who would prescribe it today for therapy of a new patient

Supraventricular tachycardia - Has been used as therapy for atrial tachycardias

Front 13

Describe the effect of Quinidine of ventricular arrhythmias

Back 13

-Quinidine has been used for the chronic oral therapy of ventricular premature depolarizations and tachycardia
-No longer used for the therapy of any ventricular arrhythmias

Front 14

Describe the effects of Quinidine on the electrocardiogram

Back 14

Similar to those described for disopyramide

Front 15

Describe the toxicity of Quinidine

Back 15

-Cardiovascular toxicity (similar to disopyramide)
-Cinchonism - tinnitus, visual distrubances, vertigo, diplopia, nausea, vomiting, diarrhea

Front 16

Describe Procainamide

Back 16

-Class IA
-Structurally related to the local anesthetic procaine
-The second antiarrhythmic drug introduced for clinical use
-Clinical use has now diminished

Front 17

Describe the use of Procainamide on cardiac arrhythmias and the ECG

Back 17

-Rarely used for the chronic oral therapy of either atrial or ventricular arrhythmias
-Still used for the IV therapy of severe ventricular arrhythmias in the emergency setting, in the hospital, such as after an acute myocardial infarction, if the first line drugs have failed or if there is a contraindication for use
-The effects on the ECG are similar to those of disopyramide

Front 18

Describe the administration and elimination of Procainamide

Back 18

a. Administration of procainamide; IV and oral preparations are available

b. Procainamide elimination - 50-60% is excreted unchanged by the kidneys; the rest is acetylated by the liver

c. Procainamide toxicity- Cardiovascular toxicity is similar to that of disopyramide and quinidine

Front 19

Describe lidocaine

Back 19

-Class IB
-Blocks sodium channels and reduced pacemaker current in ectopic pacemakers
-Does not block the delayed rectifier K channels

Front 20

Describe the effects of Lidocaine on cardiac arrhythmias

Back 20

-Ineffective and not used for therapy of any supraventricular arrhythmias (atrial tachycardia, atrial premature depolarizations, atrial flutter and fibrillation)
-Can be effective for acute treatment of serious ventricular arrhythmias, esp for those caused by recent myocardial infarction
-Use in limited to "in hospital" treatment because it is only administrated IV
-Arrhythmias are often caused by reentry in ischemically damaged regions of the ventricles where myocardial cells have reduced membrane potentials and weak Na currents
-The Na channel blocking effects of lidocaine, particularly at the rapid rates of tachycardia, can cause conduction block in reentrant pathways in ischemic regions without significantly impairing conduction in normal regions

Front 21

Describe the effects of Lidocaine on the ECG

Back 21

Sinus rate: No effect at any level
PR interval: Therapeutic or toxic plasma levels have little effect
QRS duration: Little or no effect at therapeutic or toxic concentration during sinus rhythm
QT interval: Unchanged at therapeutic or toxic concentrations, no torsades de pointes

Front 22

Describe the administration of Lidocaine

Back 22

-Therapeutic plasma levels can be attained safely with a single IV injection
-Blood level falls rapidly below the minimum effective concentration in 15-40 min
-To maintain a therapeutic plasma concentration a constant rate infusion must be started after the initial injection
-Not effective when given orally because it undergoes extensive first pass metabolism

Front 23

Describe the elimination of Lidocaine

Back 23

-Less than 10% is excreted as unmetabolized drug by kidney
-Remainer is metabolized by liver (oxidative deethylation and hydrolysis)
-Factors affecting metabolism
-Hepatic blood flow: as hepatic blood flow decreases, the rate of metabolism of lidocaine decreases and the plasma levels increase
-Lidocaine pharmacokinetics in patients with renal failure does not differ from those of normals

Front 24

Describe Lidocaine toxicity

Back 24

-Usually not manifested on cardiovascular system
-Usually does not have negative inotropic effects
-Much less cardiovascular depression than Class IA or IC drugs
-Most prominent toxic effects are on the CNS
a) CNS depression initially with moderately elevated plasma levels of lidocaine
b) Higher concentrations - muscular fasciculations and then tonic-clonic convulsions

Front 25

Describe Flecainide

Back 25

-Class IC
-Fluorinated analog of procainamide
-Blocks Na channels, reduced the pacemaker current in ectopic pacemakers and has little effect on the delayed rectifier K channels

Front 26

Describe the effect of Flecainide on atrial arrhythmias

Back 26

-Effective against most atrial arrhythmias (atrial tachycardia, flutter, and fibrillation)
-For rhythm control, not rate control
-Used for the treatment of atrial arrhythmias in patients with otherwise normal hearts but should never be given to a patient with ventricular disease
-Mechanism of action is likely related to a decrease in Na current that causes conduction block in reentrant pathways

Front 27

Describe the effect of Flecainide on ventricular arrhytmias

Back 27

Flecainide is contraindicated for therapy of ventricular arrhythmias because of its depression of ventricular function and a proarrhythmic effect

Front 28

Describe the effects of Flecainide on the ECG

Back 28

-Similar to those of Class IA drugs
-Exception is that there is little change in the QT interval
-A vagal blocking action has not been described

Front 29

Describe the administration, absorption, and elimination of Flecainide

Back 29

-Approved for use only by oral route
-Well absorbed from GI tract
-Most of drug is metabolized by the liver

Front 30

Describe the adverse effects of Flecainide

Back 30

-Cardiovascular toxicity, sinus bradycardia, and AV block
-Flecainide may promote serious ventricular arrhythmias. Mechanism is likely to be the slowing of conduction in the ventricles which the drug causes by Na channel blockade, leading to reentrant excitation. Since it does not cause prolong QT it does not cause torsades
-Negative inotropic effect, particularly in patients with depressed LV dunction

Front 31

What class of drug is Propafenone

Back 31

Class IC

Front 32

Describe the effect of Propafenone on cardiac arrhythmias and the ECG

Back 32

-Similar to those of flecainide
-Primarily blocks I_Na but, in addition, it also has some weak L type Ca channel blocking effects and some beta receptor blocking effects
-Therapeutic use is for the treatment of supraventricular arrhythmias, including atrial flutter and fibrillation (rhythm control)
-Same constraints on its use apply as those indicated for flecainide, it should not be used for therapy of ventricular arrhythmias or be used in patients with atrial arrhytmias who also have ventricular disease
-Effects on ECG are similar to those of flecainide

Front 33

Describe the administration and elimination of Propafenone

Back 33

-Administration is by the oral route although there is a large first pass metabolism
-Inactivation is mainly by hepatic metabolism to active and inactive metabolites

Front 34

Describe the adverse effects of Propafenone

Back 34

i. Ventricular proarrhythmia when treating atrial arrhythmias in patients with ventricular disease
ii. Conduction disturbances similar to flecainide
iii. Some negative inotropic effects particularly in patients with depressed LV function