Antiarrhythmics

Question 1

What are the different phases of cardiac action potential?

Answer 1

Phase 0 - upstroke indicated by NaPhase 2 - plateau dictated by Ca2+Phase 3 - repolarization dictated by K+Phase 4 – resting membrane potential

Question 2

What are the different classes of anti arrhythymatics.

Answer 2

• Class I - Na channel blockers
• Class II - Beta blockers
• Class III - K channel blockers
• Class IV - non dihydropyridine Ca channel blockers

Question 3

What are the use of these different classes of antiarrythymics?

Answer 3

Class I and IIIare used for rhythym control and affect the cardiac AP at the atrias, ventricles and the His-Purkinje system whereas Class II and IV are for rate control at the SA and AV node.

Question 4

How does Class I antiarrythymics exhibit their MOA?

Answer 4

Na channel blockers so they reduce the velocity of the upstroke of AP in atria and ventricles, hence slows the AP.This leads to decrease automaticity of ectopic pacemaker and reduce excitability of cardiac tissues.

Question 5

What kind of Na channels do class I antiarrythymics bind to?

Answer 5

Open or inactivated Na channels, they dont bind well to resting Na channels, as result they have use dependence properties which meanswhich means tissues undergoing frequent depolarization are the most susceptible to blockage by them

Question 6

What are the effects of class I on SA and AV nodes?

Answer 6

NONE, does not effect funny Na current

Question 7

ECG changes of class I drugs?

Answer 7

Widened QRS due to decrease CV of AP

Question 8

Binding strength of 1A, 1B and 1C

Answer 8

IC>IA>IB

Question 9

Examples of Class IA

Answer 9

QuninidineProcainamideDisopyramide

Question 10

Properties of 1A

Answer 10

• Intermediate binding affinity and intermediate use dependence
• Also block K channels, prolong duration of phase 2, 3 and AP duration

Question 11

What is an additional use of 1A?

Answer 11

Treats WPW syndrome – Wolf Parkinson White syndrome, type of supraventricular tachycardia, consist of extra signals passing through outside the AV node, block arrhythmias thru accessory pathway

Question 12

What are the adverse effects of Qunidine?

Answer 12

Cinchonism and thrombocytopenia

Question 13

What are the adverse effects of procainamide?

Answer 13

Causes drug induced lupus, also causes a decrease in inotropy at high concentrations so it can exacerbate HF

Question 14

What are the adverse effects of disopyramide?

Answer 14

Exacerbate heart failure, at toxic concentrations this drug has anti inotropic effects

Question 15

Adverse effects of all 1A?

Answer 15

QT prolongation - precipitates torsades arrhythmia and syncope.Anything that blocks K channels prolongs QT intervalIronically most of the anti arrythymics are also arrythymogenic, they can lead to the development of arrhythmias!

Question 16

What are the examples of Class IB?

Answer 16

Lidocaine

Phenytoin -anti-epileptic that shows antiarrythymic properties Mexiletine

Question 17

What are the properties of 1B?What are they particularly useful against?

Answer 17

• Lowest binding affinity, modest effect on upstroke of AP
• Decreased AP duration by decreasing phase 2 and 3 duration, preferentially affect ischemic or depolarized purkinje and ventricular tissue
  As a result they are more selective to ventricle cells and HIS Purkinge system, makes them useful in treating ventricular arrythymias and ischemic dead tissue

Question 18

What is the most common cause of death post MI?What drug should be used?

Answer 18

Ischemia induced ventricular arrythymias, class IB antiarrythymics

Question 19

What are the adverse effects of class 1B?

Answer 19

Neurological (paresthesia, tremor, convulsions)

Question 20

What are examples of 1C?

Answer 20

Propafenone Flecainide

Question 21

What are the properties of 1C?

Answer 21

• Strong binding affinity for Na+ channel – strong use dependence, drastic slowing of phase 0 upstroke
• Do not affect cardiac AP duration since K channels are untouched
• QRS is significantly prolonged
  Can be used to treat atrial fibrillation, they can maintain and restore normal sinus rhythym. Can also be used in ventricular and supraventricular arrhythymias

Question 22

What are the adverse effects of 1C?

Answer 22

Contraindicated in pts with history of structural or ischemic heart disease (proarrythmic effects) since these drugs tight bindly it may delay conduction speed that is out of proportion of the prolongation of the refractory period, this can lead to arrhythmias due to reentrant loops.

Question 23

Compare and contrast AP duration as a result of administering 1A, 1B and 1C antiarrhythmics.

Answer 23

Class 1A inhibit K channels as well so they significantly prolong the duration of APClass 1B has the least binding tendency to Na channels, they prolong the duration of the APClass 1C has NO effect on duration of AP!

Question 24

What are examples of Class II anti arrhythymatics?

Answer 24

Since they are beta blockers their ending is “-olol”
Esmolol -this is given IV to treat intra operative rather acute arrhythmias)
Metoprolol -cardio specific beta 1 antagonists
Propranolol andTimolol -Non selective beta 1 and beta 2 antagonist
Carvedilol -Partial alpha antagonist properties

Question 25

Explain the use of beta blockers as anti arrhythymics.

Answer 25

Block arrhythmia promoting adrenergic stimuli in the SA node, beta blockers decrease heart rhythym. * First line of treatment to control atrial fibrillation and atrial flutter * Prevent acute supraventricular arrythymias * Prevent rapid ventricular response.

Question 26

What is rapid ventricular response and what specific drug is used to treat this?

Answer 26

Rapid ventricular response happens when there are too many signals coming from the atria to the AV node, in response to all these signals the AV node causes tachycardia, this process is called rapid ventricular response.A specific beta blocker that is used for this purpose is metoprolol – it prevents ventricular response to atrial fibrillation and flutter. However it is important to know that this does not fix the cause of atrial fibrillation, hence it is only used for rate control.

Question 27

What are the adverse effects of beta blockers?

Answer 27

Heart block and bradyarrhythmias

Question 28

Examples of Class III Antiarrythymics.

Answer 28

``` Potassium channel blockers, ends with "-tilide" Sotalol - also a beta blocker and also a Class III anti arrythymic Dofetilide Ibutilide Amiodarone* - shares properties of class I, II, III, and IV, it also blocks Na channels, it also has weak beta adrenergic and Ca channel blocking effects. ```

Question 29

What are the effects of class III?

Answer 29

Block K channels --> prolonging phase 2 and 3 of cardiac action potential --> prolonged refractory period

Question 30

What are class III used for?

Answer 30

Can be used for all three: atrial fibrillation/atrial flutter, ventricular arrhythymia and supraventricular arrhythymia

Question 31

What class does Amiodarone belong to?

Answer 31

Shares properties of class I, II, III, and IV, it also blocks Na channels, it also has weak beta adrenergic and Ca channel blocking effects

Question 32

What are the side effects of amiodarone?

Answer 32

* Neurological - tremor, ataxia, peripheral neuropathy, sleep disturbances * Gray corneal microdeposits – these usually asymptomatic Large amounts of iodine, this is because amiodarone is a iodine compound --> can cause hyper or hypothyroidism, need to do a thyroid test before starting patients on Amiodarone * Pulmonary fibrosis, can lead to restrictive lung disease, pulmonary fibrosis can be potentially fatal * Can cause heart block and heart failure * Hypersensitivity hepatitis – liver function tests have to be monitored * Gray-blue skin discoloration due to skin deposits * Photodermatitis * Inhibitor of CYP450 - increase concentrations of many drugs such as warfarin * Low incidence of Torsades* in contrast to others

Question 33

What are the side effects of sotalol, dofetilide, and ibutilide?

Answer 33

Induce torsades

Question 34

Examples of Class IV Antiarrythymics.

Answer 34

DiltiazemVerapamil

Question 35

Examples of Class V Antiarrythymics.

Answer 35

* Digoxin * Magnesium * Adenosine

Question 36

Digoxin.

Answer 36

* Digoxin - antiarrhythmic properties * Parasympathomimetic effects via direct stimulation of the vagus nerve --> AV nodal inhibition - similar to beta and calcium blockers * Treats atrial fibrillation (and flutter) * Prevents rapid ventricular response in atrial fib and flutter (rate control)

Question 37

Magnesium.

Answer 37

Magnesium - antiarrhythmics, treats torsades de pointes, even if the serum Mg levels are normal, Mg does this by interacting with a wide number of channels such as Na channels, K channels and Na-K ATPase

Question 38

Potassium

Answer 38

Potassium -Hyperkalemia - induces arrhythmias, ascending weakness and paralysis * Peaked T waves with Shortened QT interval Hypokalemia - induce arrhythmias, * Severe muscle weakness, renal abnormalities, and glucose intolerance * U waves at end of T wave * Decreased T wave

Question 39

Where does adenosine exert its effect as an anti arrhythmic?

Answer 39

At A1 receptors found on myocardium and at SA and AV nodes, primary MOA is at the SA and AV nodes

Question 40

Explain adensoine's MOA.

Answer 40

A1 receptor interaction - increases outward K+ current --- Hyperpolarization, suppressed Ca2+ dependent AP at the SA and AV node.AV node is affected mostly, increases AV node refractory period. 

Question 41

What is the main adverse effect of adenosine?

Answer 41

Can cause transient high grade heart block - direct AV node inhibiton - but short lived since t1/2 is only 10sDecreases AV conduction

Question 42

What is the no. 1 indication of adenosine?What is its other use?

Answer 42

Treats Supraventricular arrhtymias – no.1 indication of adenosine is to treat Paroxysmal Supraventricular tachycardia to back to normal sinus rhythymVasodilator, increases coronary dilation (mediated by binding to A2 receptors) - helpful in cardiac testing

Question 43

What drugs strongly interfere with adenosine MOA?

Answer 43

Adenosine's actions are inhibited by caffiene and theophylline (methylxanthines)

Question 44

What are other side effects of adenosine?

Answer 44

* Cutaneous flushing * Shortness of breath * Chest pain * Impending sense of doom * Headache * Hypotension