L52 – Anti-arrhythmic Drugs Flashcards Preview

MBBS I CPRS > L52 – Anti-arrhythmic Drugs > Flashcards

Flashcards in L52 – Anti-arrhythmic Drugs Deck (126):
1

Assign the following ECG landmark with the cardiac cycle: P wave

depolarization of atria in response to SA node triggering

2

Assign the following ECG landmark with the cardiac cycle: PR interval

delay of AV node (time lapse between atrial, ventricular contraction)

allow filling of ventricles

3

Assign the following ECG landmark with the cardiac cycle: QRS complex

depolarization of ventricles >> triggers main pumping contractions

4

Assign the following ECG landmark with the cardiac cycle: ST segment

beginning of ventricle repolarization

5

Assign the following ECG landmark with the cardiac cycle: T wave

ventricular repolarization

6

Assign the following ECG landmark with the cardiac cycle:QT interval

duration of action potential in ventricle

7

Explain the action of sympathetic activation causing a change in pacemaker potential/ depolarization.

Sympathetic activation increases slope of pacemaker depolarization

(right) Sympathetic activation > hyperpolarization-activated L type funny channels OPEN EARLIER > Increase Na+ influx > steeper slope

8

Explain the action of parasympathetic activation causing a change in pacemaker potential/ depolarization.

Parasympathetic activation (vagus nerve) > increase K+ permeability in pacemaker phase (IKAch open) > DECREASE slope of phase 4 pacemaker potential

9

What are 3 ways to regulate pacemaker activity?

Change any of:
1) Threshold potential
2) Maximum diastolic potential
3) Slope of phase 4/ pacemaker depolarization

10

Compare the effects of parasympathetic and sympathetic activation on phase 4 depolarization?

Sympathetic = increase slope

Parasympathetic = decrease slope

11

Compare the speed of transmission between Non-nodal tissue and nodal tissu.

- Non-nodal tissue: usually Na+ current >> faster transmission

- Slow-response tissue (e.g. AV node): Ca2+
current >> slower transmission

12

What 2 factors are important in the regulation of impulse propagation?

Magnitude of depolarizing current

Geometry of cell-cell electrical connections

13

Explain how Geometry of cell-cell electrical connections can influence impulse propagation?

more gap junction proteins (governs direction of propagation) at ends than side of cardiac cells


impulse spread along cells 2-3 times faster than across cells

14

What 2 abnormalities can lead to arrhythmia?

Abnormal automaticity

Abnormalities in impulse conduction

15

Classification of arrhythmia?

1) Supraventricular: divided into atrial / nodal
2) Ventricular

16

Name some causes of arrhythmia?

DIE HAI

Drug toxicity
Infection
Electrolyte abnormalities

Hypoxia
Autonomic influences
Ischaemia

17

Where are the sites of Abnormalities in impulse conduction?

atrial (A) / ventricular (V) / junctional (AV)

18

How does a decrease in rate of impulse conduction lead to uncoordinated cardiac contraction?

Decrease rate of conduction >> impulse conduction easy to be blocked >> atria and ventricles have different impulses >> no longer coordinated

19

What are the 2 types of impulse conduction block?

Simple block

Transient block

20

What is simple impulse conductance block due to? Where does the simple block usually occur?

 Myocardial infarction>> dead muscle
 Altered ionic balance

Most commonly in atrioventricular (AV) node

21

What is Transient impulse conductance block due to?

Hypoxia > Insufficient O2

22

What is the result of a transient block?

Weaker force of contraction
Initially same rhythm

23

How does a transient block of impulse lead to unidirectional block and fibrillation?

Transient block > impulses not synchronized > when tissue recovers conduction, impulse can be transmitted BACKWARDS causing unidirectional block

This triggers RE-ENTRY (circus movement) in different parts of the heart > Fibrillation

24

Abnormal automaticity is observed when the resting potential is...?

reduced resting membrane potential (decreased membrane K+ conductance
>> Vm more positive / less negative)

25

What 2 things can enhance abnormal automaticity?

 Enhanced by sympathetic nerve activity >> tachycardia

 Enhanced by hypokalemia >> activate less Na+ channel causing bradycardia

26

Extra heart beats are triggered by ___?

afterdepolarizations

27

Why is long QT indicative of Early Afterdepolarization (EAD)?

prolonged repolarization phase >> Long QT

28

What are the 2 types of afterdepolarization?

EAD - early afterdepolarization
DAD - Delayed afterdepolarization

29

Compare the electrolyte abnormalities that cause EAD and DAD?

EAD = Reduction of repolarizing K+ currents

DAD = increased intracellular Ca2+ level

30

What is early afterdepolarization?

Another depolarization occurs BEFORE repolarization is complete

31

What is DAD?

another depolarization occurs AFTER repolarization but
sooner than normal

32

Compare the abnormal automaticity in EAD and DAD?

EAD = depolarize BEFORE complete repolarization

DAD = depolarize AFTER complete repolarization but sooner than normal

33

In which phases of non-nodal cardiac cycle does EAD occur?

phase 2 (plateau)

phase 3 (rapid repolarization)

34

What is polymorphic ventricular tachycardia/ Torsades de Pointes?

uncoordinated impulses generated in all parts of heart

35

What causes polymorphic ventricular tachycardia?

Caused by EAD

triggers functional re-entry and circus movement

because of the heterogeneity of AP durations across the ventricular wall **many AP each with different timing**

36

2 Therapeutic goals of Anti-arrhythmic drugs?

 Terminate ongoing arrhythmia

 Prevent arrhythmia

37

What are some acute therapies for arrhythmia?

intravenous administration,

defibrillation device

38

What is the Vaughan-Williams Classification for Antiarrhythmic drugs?


Natalie Borrows Kelvins Car

Class I - Sodium channel blockers

Class II- B-adrenergic receptor blockers

Class III - Potassium channel blockers

Class IV - Calcium channel blockers

39

Describe the m (outer) and h (inner) gates of sodium channel during resting potential?

Resting (closed):
m gates closed, h gates
opened

40

Describe the m (outer) and h (inner) gates of sodium channel during threshold to activation?

m gates open, h gates
remain open

41

Describe the m (outer) and h (inner) gates of sodium channel during Inactivation?

m gates remain open, h gates close

>> then recover to resting

42

Na+ channel blockers preferentially bind to during which phases?

Bind preferentially to pore area when channel is:
1) activated (open)
2) inactivated

(i.e. when m gates are open)

43

What is the effect of Class I antiarrhythmic drug on tachycardia?

Block Na channel during activated or inactivated state > Decrease Na+ conduction velocity > Decrease slope of depolarization > Block Tachycardia

44

What is the relationship between the frequency of Na channel activation and the degree of channel block by Class I drug?

more frequently the channels are activated, the greater is the degree
of block

45

What are the 3 subtypes of Class I drugs?

Class Ia
Class Ib: rapid kinetics
Class Ic: Slow kinetics

46

Name some Class Ia sodium channel blockers?

Procainamide
Quinidine
Disopyramide

47

Name some Class Ib sodium channel blockers?

Lidocaine
Mexiletine

48

Name some Class Ic sodium channel blockers?

Flecainide
Encainide
Propafenone

49

Compare the rate of dissociation from Na channels between Class I a,b,c drugs?

Ia = intermediate rate
Ib = rapid
Ic = slow

50

What period of cardiac cycle does Class Ia drug increase?

effective refractory period

51

Explain the action of Class Ia drug given it is non-selective?

Also block K+ channels > decrease rate of repolarization > increase duration of AP to prevent extra beat

52

What is the adverse effect of Class Ia drug? (think K+)

Risk of EAD due to Reduction of repolarizing K+ currents
+
Anticholinergic effect

= risk of inducing
torsades de pointes arrhythmia/polymorphic ventricular tachycardia

53

What is the gross effect of Class Ia drug?

-Inhibit increase in automaticity

-Moderate decrease in conduction

-Decrease rate of repolarization = increase duration of AP/ ERP

54

Adverse effect from long term use of procainamide?

lupus-related symptoms, e.g. arthralgia, arthritis

55

Adverse effect of procainamid and quinidine (less with disopyramide)?

Gastrointestinal disturbances, e.g. diarrhea / constipation, nausea, vomiting

56

Rank each of the class Ia drugs on their effects on lowering force of contraction?

disopyramide > quinidine >
procainamide

57

What does Class Ib drugs block?

preferentially block premature beats

58

What is the action of Class Ib on sodium channels? (which state, when...)

Selective for inactivated (refractory) Na+ channels > suppress depolarized cells

Dissociate RAPIDLY within the time frame of normal heartbeat
(before next impulse from SA node)

59

Explain why Class Ib drugs can cause CNS disturbances?

Affect faster-acting Na+ channels in central nervous system for impulse conduction

60

What are some adverse effect symptoms of Class Ib drug?

CNS disturbances
e.g. tremor,
nausea,
drowsiness,
disorientation,
convulsions

61

What is the gross effect of class Ic drugs?

Decrease conduction even at normal HR

62

What is the interaction between Class Ic drug and Na channels?

dissociate slowly from Na+ channels (still blocked when next impulse comes)

63

What are some adverse effects of Class Ic drugs (flecainide, propafenone)

Proarrhythmia

Worsen Heart failure

64

How does class Ic drug cause pro-arrhythmia as adverse rxn?

Decrease in HR = decrease cardiac output

Increase incidence of
sudden death especially in presence of severe heart failure

65

What is the adverse reaction caused by propafenone (class Ic)? (think heart failure and chemical structure)

structurally similar to propranolol

can act as weak B -adrenergic receptor blocker > -ve inotropic effect > worsens
heart failure

66

What are the gross effects of Class II drugs?

B blockers oppose B-adrenergic stimulation


 SA : lower heart rate
 AV: Increase nodal conduction time (slow down)
 Ventricle: lower intracellular Ca2+ overload

67

Can Class II drugs prevent DAD?

Yes

68

2 types of B-blockers?

Selective B1-adrenergic receptor blockers, e.g.:
 Metoprolol
 Esmolol

Non-selective β-adrenergic receptor blockers, e.g. propranolol

69

Why does esmolol have a short half life?

Rapidly metabolized by erythrocyte esterases

70

When are selective B1-adrenergic receptor blockers used?

primarily used for intraoperative, acute arrhythmias

>> need IV admin.

71

When are Non-selective B-adrenergic receptor blockers used?

arrhythmia induced by
adrenaline-induced hypokalemia

**associated with severe stress e.g. acute MI, resuscitation from cardiac arrest

72

What is the action of Non-selective B-adrenergic receptor blockers?

Antagonize both B1- and B2-adrenergic receptors

73

Which groups of patients cannot use Class II drugs?

Heart failure

Asthma or COPD

Diabetes

74

Why cant class II drugs be used in patients with HF?

B blocker decreases both force and rate of contraction

75

Why cant class II drugs be used in patients with asthma or COPD?

B blocker can cause bronchospasm

76

Why cant class II drugs be used in patients with diabetes?

B blocker can cause hypoglycaemia by inhibiting glycogenolysis in liver

77

What are the gross effects of Class III drugs?

Decrease rate of repolarisation
+
Decrease normal automticity and disable re-entry

> increase AP duration/ ERP

78

What does Dodetilide block?

Potent, “pure” blocker for the rapid delayed
rectifier potassium channel

79

Adverse effect of Dodetilide?

Reduced rate of repolarization > risk of EAD and torsades de pointes

80

Dodetilide is avoided in which patients?

hypokalemia
advanced renal failure
Taking inhibitors of renal cation transport

81

What are the gross effects of Amiodarone?

Broad spectrum:
- K+ channel blockade
- Block inactivated Na+ channel
- Weak adrenergic block
- weak calcium channel block

82

What is the commonly used drug for most kinds of arrythmia?

Amiodarone

83

What are some adverse effects of Amiodarone on the heart?

Low incidence of torsades de pointes

May cause bradycardia and heart block >> chance of arrhythmia

84

What are some adverse effects of Amiodarone on organs other than the heart? Why ?

Due to Iodine:

Skin >> photosensitivity
Eye - corneal deposits >> visual problems
Thyroid >> hypo- / hyper-thyroidism
Lung >> pulmonary fibrosis
Liver >> hypersensitivity hepatitis

85

What are the symptoms of photosensitivity?

skin rashes, grey-blue skin discoloration following sun exposure

86

What are some drug interactions of Amiodarone?

Metabolized by cytochrome P450 (CYP3A4):

Plasma level of amiodarone can be increased or decreased by drugs interacting with CYP3A4

87

What is the interaction between Amiodarone and cimetidine?

Cimetidine inhibits CYP3A4 >> increase Amiodarone plasma level

88

What is the interaction between Amiodarone and Rifampin?

Rifampin induces CYP3A4 >> Decrease amiodarone plasma
level

89

What is the interaction between Amiodarone and drugs that depend on CYP 3A4 for metabolism?

Amiodarone increases the plasma levels of drugs that depends on CYP3A4 for metabolism (e.g. statins, warfarin, digoxin)

90

What influence does Amiodarone have on cardiac devices?

Need to increase pacing and defibrillation threshold

91

What is the action of Dronedarone?

Same mechanisms of actions as amiodarone > broad spectrum

92

Why is Dronedarone taken after eating?

Absorption increases 2- to 3-fold when taken with food

93

What are some adverse effects of Dronedarone?

Pro-arrhythmia (bradycardia and heart block)

Low incidence of iodine adverse effects

Low incidence of torsades de pointes

94

What is the action of Sotalol?

class III antiarrhythmic drug with class II
action

95

What is he mixture in Sotalol?

Racemic mixture of:
 d-sotalol
 l-sotalol (contains B -adrenergic receptor blocking activity)

96

What patient group is Sotalol used for?

Treat supraventricular and ventricular
arrhythmias in the pediatric age group

97

Adverse Effect of Sotalol?

1 ) Pro-arrhythmia (risk of torsades de pointes)
2) Block β >> depress left ventricular function

caution in patients with heart failure

98

Effect of Sotalol on cardiac devices?

decrease threshold for cardiac defibrillation

99

Gross action of Class IV drugs? (CCB)

Decrease in :
HR
AV nodal conduction velocity
Calcium overload (thus effective against DAD)

100

How could Class IV/ CCBs cause heart failure?

AV block
Hypotension
Decrease force of heart contraction

>> all can lead to HF

101

Does CCBs cause peripheral edema?

Yes

102

Class IV drugs are avoided in which patient groups?

hepatic dysfunction

ventricular tachycardia

103

Explain how CCBs can cause centricular tachycardia?

Cause Hypotension >. reflex tachycardia >> cardiac arrest

104

Which anti-arrhythmic drugs are rate control?

Class Ic, II

105

Which anti-arrhythmic drugs are Rhythm control?

Class Ia/b, III, IV

106

Explain how adenosine can decrease normal automaticity?

Activate presynaptic purinergic receptors on sympathetic nerve terminals > decrease release of noradrenaline

107

Explain how adenosine can decrease calcium overload?

Activate A1 receptors on SA and AV nodes > inhibit adenylyl cyclase > decrease intracellular cAMP production > decrease calcium overload

108

Explain how adenosine can decrease conduction velocity?

Activate K channels in SA and AV nodes > increase maximal diastolic potential (more hyperpolarized) > prolong phase 4/ pacemaker depolarization > decrease conduction velocity

109

Adenosine is potentiated and inhibited by what?

Potentiate ( drug A boosts the effects of drug B ) by dipyridamole

Inhibited by Caffeine

110

Why do adverse effects of Adenosine rapidly resolve?

Rapid uptake into cells for metabolism > short half life in blood

111

Why does Adenosine cause flushing, hypotension + chest pain and shortness of breathe?

activate A2 receptors in vascular smooth muscle >> decrease calcium release >> VASODILATION

> Flush
> Hypotension >> reflex hyperventilation

112

Gross effect of Cardiac
glycosides: e.g. digoxin?

Parasympathomimetic effects:
Decrease in both
- heart rate
- conduction velocity (especially at AV node)

113

Which two electrolytes can be taken to treat arrhythmia?

K
Mg

114

How could cardiac glycosides cause DAD?

Inhibit Na+-K+ ATPase activity > increase ntracellular Na+
level >> less Ca2+ expulsion by Na+/Ca2+ exchanger >> increase
intracellular Ca2+

> DAD/ ectopic beats

115

Adverse effects of cardiac glycosides?

GI disturbances, e.g. diarrhea, nausea, vomiting

CNS disturbances, e.g. drowsiness, disorientation

116

Risk of DAD is increased by which electrolyte imbalances?

 Hypokalemia
 Hypercalcemia
 Hypomagnesmia

117

Name one muscarinic receptor antagonist>

Atropine

118

How does Atropine manage bradycardia?

Block muscarinic receptor = decrease vagal influence

Increase HR and conduction veolcity (esp. at AV node)

119

Name some side effects of Atropine after OD or repeated dosing?

 Tachycardia
 Dry mouth
 Dilation of pupils
 Constipation

120

List some non-pharmacological therapy of cardiac arrhythmia?

Pacemaker
Electrical cardioversion
Implantable cardioverter-defibrillator

Heart surgery (Maze procedure)

Catheter Ablation

121

Route of administration of drug for emergency arrhythmia?

IV

122

Why is combo therapy given for arrhythmia?

prevent adverse effects

123

What are 3 signature symptoms of Arrhythmia?

Palpitations
Syncope (dizzy)
Cardiac arrest

124

If patient has arrhythmia and syncope, which antiarrhythmic drug should you NOT use?

hypotension: do not give IV (CCB)

125

If patient has arrhythmia and cardiac arrest, which antiarrhythmic drug should you NOT use?

Ic (Na channel blocker, slow response)
II (B-adrenergic)
III (Potassium channel blocker)
IV (CCB)

126

For decreasing long-term mortality in asymptotic patients, which antiarrhythmic drug should be used?

Avoid pro-arrhythmic ones
e.g. Class III, class Ic

Decks in MBBS I CPRS Class (78):