05 Antidysrhythmic drugs

Question 1

5.01 CLASS 1a ANTIDYSRHYTHMIC

Disopyramide (similar: quinidine, procainamide) - actions

Answer 1

antidysrhythmic

Question 2

5.01 CLASS 1a ANTIDYSRHYTHMIC

Disopyramide (similar: quinidine, procainamide) - MOA

Answer 2

belongs to class Ia of the Vaughan Williams classification
blocks open and inactivated Na+ channels in the cell membrane (‘use-dependent’ action) to reduce the rate of phase 0 depolarisation, causing an increase in the effective refractory period and slowed AV conduction
also produces some slowing of action potential repolarisation (a class III action)

Question 3

5.01 CLASS 1a ANTIDYSRHYTHMIC

Disopyramide (similar: quinidine, procainamide) - abs/distrib/elim

Answer 3

given orally or IV
half-life 5-10h
half is excreted unchanged by the kidney, half is metabolised in the liver

Question 4

5.01 CLASS 1a ANTIDYSRHYTHMIC

Disopyramide (similar: quinidine, procainamide) - clinical use

Answer 4

supraventricular and (more usually) ventricular dysrhythmia

Question 5

5.01 CLASS 1a ANTIDYSRHYTHMIC

Disopyramide (similar: quinidine, procainamide) - adverse effects

Answer 5

atropine-like effects: blurred vision, dry mouth, constipation, urinary retention
negative inotropic action

Question 6

5.02 CLASS 1c ANTIDYSRHYTHMIC

Flecainide (similar: propafenone, encainide) - actions

Answer 6

antidysrhythmic

Question 7

5.02 CLASS 1c ANTIDYSRHYTHMIC

Flecainide (similar: propafenone, encainide) - MOA

Answer 7

belongs to class Ic of the Vaughan Williams classification
preferential block of open Na+ channels
reduces the rate of phase 0 depolarisation, causing an increase in the effective refractory period and slowed AV conduction
associates with and dissociates from Na+ channels more slowly than either Ia or Ib agents

Question 8

5.02 CLASS 1c ANTIDYSRHYTHMIC

Flecainide (similar: propafenone, encainide) - abs/distrib/elim

Answer 8

given orally or IV
half-life 20h
mostly excreted unchanged in urine
propafenone is metabolised more rapidly by the liver and has a shorter half-life (5-10h)

Question 9

5.02 CLASS 1c ANTIDYSRHYTHMIC

Flecainide (similar: propafenone, encainide) - clinical use

Answer 9

prevention and treatment of atrial fibrillation
ventricular tachyarrhythmias

Question 10

5.02 CLASS 1c ANTIDYSRHYTHMIC

Flecainide (similar: propafenone, encainide) - adverse effects

Answer 10

increases likelihood of dysrhythmia
may increase mortality due to ventricular fibrillation post-infarction
needs careful use and is suitable only for patients who do not have ischaemic or structural heart disease
negative inotropic action

Question 11

5.03 CLASS II ANTIDYSRHYTHMIC

β-adrenoceptor antagonist (bisoprolol, esmolol, propanolol, etc.) - actions

Answer 11

antidysrhythmic (also antihypertensive, antianginal)
block actions of catecholamines on β-adrenoceptors

Question 12

5.03 CLASS II ANTIDYSRHYTHMIC

β-adrenoceptor antagonist (bisoprolol, esmolol, propanolol, etc.) - MOA

Answer 12

block sympathetic drive, reducing pacemaker activity (phase 4) and increasing AV conduction time
reduce the slow inward Ca2+ current, which affects phase 2 of the action potential
propranolol has additional class I action

Question 13

5.03 CLASS II ANTIDYSRHYTHMIC

β-adrenoceptor antagonist (bisoprolol, esmolol, propanolol, etc.) - abs/distrib/elim

Answer 13

given orally or IV

Question 14

5.03 CLASS II ANTIDYSRHYTHMIC

β-adrenoceptor antagonist (bisoprolol, esmolol, propanolol, etc.) - clinical use

Answer 14

paroxysmal atrial fibrillation and other tachyarrhythmias
reduction of mortality after infarct (where dysrhythmias have a sympathetic input)

Question 15

5.03 CLASS II ANTIDYSRHYTHMIC

β-adrenoceptor antagonist (bisoprolol, esmolol, propanolol, etc.) - adverse effects

Answer 15

bronchoconstriction in asthmatic patients
cardiac slowing with possible heart block

Question 16

5.04 CLASS III ANTIDYSRHYTHMIC

Amiodarone (similar: sotalol, dronedarone, ibutilide) - actions

Answer 16

antidysrhythmic

Question 17

5.04 CLASS III ANTIDYSRHYTHMIC

Amiodarone (similar: sotalol, dronedarone, ibutilide) - MOA

Answer 17

class III drugs block K+ channels in the cell membrane to delay repolarisation and increase action potential duration
this increases the refractory period
amiodarone also blocks Na+ channels and β adrenoceptors so has class I and class II actions
sotalol is a β-adreno­ceptor antagonist that also has class II actions

Question 18

5.04 CLASS III ANTIDYSRHYTHMIC

Amiodarone (similar: sotalol, dronedarone, ibutilide) - abs/distrib/elim

Answer 18

long-acting
extensive tissue binding
half-life of several weeks
sotalol and ibutilide have half-lives of 5-10h

Question 19

5.04 CLASS III ANTIDYSRHYTHMIC

Amiodarone (similar: sotalol, dronedarone, ibutilide) - clinical use

Answer 19

atrial fibrillation and flutter
ventricular ectopic beats and ventricular tachyarrhythmias
ibutilide IV for acute treatment of atrial fibrillation and flutter

Question 20

5.04 CLASS III ANTIDYSRHYTHMIC

Amiodarone (similar: sotalol, dronedarone, ibutilide) - adverse effects

Answer 20

torsades de pointes (less likely with amiodarone than other class III drugs)
amiodarone may cause pulmonary fibrosis, liver damage, photosensitive skin rashes, thyroid malfunction

Question 21

5.05 CLASS IV ANTIDYSRHYTHMIC

Verapamil (similar: diltiazem) - actions

Answer 21

antidysrhythmic (also antihypertensive, antianginal)
blocks Ca2+ channels in both cardiac and smooth muscle so has both negative inotropic and smooth muscle relaxant actions

Question 22

5.05 CLASS IV ANTIDYSRHYTHMIC

Verapamil (similar: diltiazem) - MOA

Answer 22

blocks L-type voltage-gated Ca2+ channels, which are important in the action potential plateau, and in particular affects action potential propagation in the SA and AV nodes
shows use-dependence so is more active in tachyarrhythmias
decreases automaticity and slows AV conduction

Question 23

5.05 CLASS IV ANTIDYSRHYTHMIC

Verapamil (similar: diltiazem) - abs/distrib/elim

Answer 23

given orally (less commonly IV)
half-life 6-8h

Question 24

5.05 CLASS IV ANTIDYSRHYTHMIC

Verapamil (similar: diltiazem) - clinical use

Answer 24

supraventricular tachycardias
control of ventricular rate in atrial fibrillation

Question 25

5.05 CLASS IV ANTIDYSRHYTHMIC Verapamil (similar: diltiazem) - adverse effects

Answer 25

side effects due to smooth muscle relaxation: hypotension and dizziness, ankle oedema, constipation unwanted cardiac actions include heart block and bradycardia

Question 26

5.06 ADENOSINE RECEPTOR AGONISTS Adenosine (similar: regadenoson) - actions

Answer 26

antidysrhythmic

Question 27

5.06 ADENOSINE RECEPTOR AGONISTS Adenosine (similar: regadenoson) - MOA

Answer 27

activates G protein-coupled adenosine receptors action (on A1 receptors) is due to inhibition of Ca2+ channel opening and increased K+ channel opening (the effect is analogous to the action of ACh on cardiac muscarinic receptors) important actions are its negative chronotropic action on the SA node and slowed AV conduction

Question 28

5.06 ADENOSINE RECEPTOR AGONISTS Adenosine (similar: regadenoson) - abs/distrib/elim

Answer 28

given IV short duration of action half-life 10sec

Question 29

5.06 ADENOSINE RECEPTOR AGONISTS Adenosine (similar: regadenoson) - clinical use

Answer 29

termination of paroxysmal supraventricular tachycardia slowing of AV conduction to enable more precise diagnosis of supraventricular tachycardias coronary vasodilator to enable radionuclide myocardial perfusion imaging and cardiac stress testing

Question 30

5.06 ADENOSINE RECEPTOR AGONISTS Adenosine (similar: regadenoson) - adverse effects

Answer 30

side effects (e.g. flushing, chest pain, dyspnoea, bronchospasm) are short-lived because of rapid elimination of adenosine interacts with other drugs that exert effects on adenosine pathways (dipyridamole, theophylline)

Question 31

5.07 CARDIAC GLYCOSIDE Digoxin - actions

Answer 31

slows heart slows AV conduction prolongs AV node refractory period increases force of contraction in failing heart

Question 32

5.07 CARDIAC GLYCOSIDE Digoxin - MOA

Answer 32

inhibits Na+/K+ ATPase in plasma membrane the increased intracellular Na+ reduces Ca2+ extrusion, thus increasing intracellular Ca2+

Question 33

5.07 CARDIAC GLYCOSIDE Digoxin - abs/distrib/elim

Answer 33

given orally, usually with an oral or IV loading dose if rapid action is needed renal excretion plasma half-life ~36h

Question 34

5.07 CARDIAC GLYCOSIDE Digoxin - clinical use

Answer 34

atrial fibrillation heart failure (if diuretics and ACE inhibitors have not worked)

Question 35

5.07 CARDIAC GLYCOSIDE Digoxin - adverse effects

Answer 35

dysrhythmias, due to block of AV conduction and ectopic pacemaker action yellow vision nausea and vomiting

Question 36

5.07 CARDIAC GLYCOSIDE Digoxin - special points

Answer 36

narrow margin between effective dose and toxic dose decreased plasma K+ increases toxicity due to competition between K+ and digoxin for the Na+/K+ ATPase