Cardio L8 Drug therapy 1 Flashcards Preview

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Flashcards in Cardio L8 Drug therapy 1 Deck (78):
1

Mechanism of Cardiac AP:

Phase 4 (Diastolic period)
Phase 0
Phase 1
Phase 2
Phase 3

2

Phase 4 (Diastolic period)
Process
Notes

• Inward K current and Na/K pump current
• Na, Ca channels closed
• Inward current in nodal cells gradually depolarizes cells


→Due to Ii and NCK

3

Phase 0
Process
Notes

Na channels open Inward current causes rapid depolarisation to >+40 mV

4

Phase 1
Process
Notes

Initial rapid repolarization
Gives rise to notch, not seen in nodal tissue
Due to I10,Icl

5

Phase 2
Process
Notes

Plateau mainly due to:
1. Outward K currents
2. Inward Na, Ca and NCX currents

6

Phase 3
Process
Notes

Repolarization
Increasing K current (s)
Inactivation of inward Na, Ca currents

7

Electrical activation sequence

Abnormalities in electrical behaviour will give rise to abnormalities in contraction. The risk arises from a reduced ability to pump blood.

8

Normal Sinus Rhythm:

ECG (EKG) shows sequence of activation starting in SA node and atria and passing to ventricles via the AV node and his-Purkinje system.
Note the normal ECG characteristics:
1. Regular narrow complex
2. Rate 60-100 bpm
3. Each QRS has a P wave with constant delay
4. T wave ‘normal’

9

Atrial flutter

Atrial re-entry (with conduction block?)

10

Atrial fibrillation

Like flutter but on a finer physical scale

11

Paroxysmal supraventricular tachycardia

Episodic VT from nodal re-entry

12

Ventricular tachycardia

High V rate – possibly atrial driven or re-entrant

13

Polymorphic ventricular tachycardia

Episodic VT from nodal re-entry

14

Ventricular tachycardia

High V rate – possibly atrial driven or re-entrant

15

Polymorphic ventricular tachycardia

VT with unstable ECG

16

Ventricular fibrillation

Fine re-entry and fatal

17

Causes of arrhythmias:

Abnormality in action potential
Abnormality in conduction
Abnormality in excitability

18

Abnormality in action potential


1. Genetic (channelopathies)
2. Ischemia
3. Electrolyte disturbances
4. Drugs

19

Abnormality in conduction

1. Anatomy
2. Ischemia, infarct
3. Electrolyte disturbances
4. Secondary to AP and electrical
5. Drugs

20

Abnormality in excitability

1. Increased sympathetic drive
2. Surgery
3. Drugs

21

Early after depolarization

Prolonged action potential duration
Membrane oscillations

22

Delayed after-depolarization

1. Abnormal oscillatory Ca release from SR (caused by Ca overload)
2. Elevated cytosolic Ca causes (late) inward current by channels and Na/Ca exchange
• Leading to oscillatory depolarization of cell membrane

23

Re-entry prerequisites:

1. Unidirectional conduction block or inhomogeneous conduction in circuit
2. The refractory period in healthy tissue is shorter than the time taken for conduction of re-entering AP
3. The re-entered beat must pass the conduction defect before the next normal AP arrives

24


What determines refractory period?

1. Action potential Duration
2. Average Membrane Potential
3. Recovery time of Sodium Channel (from inactivation)
4. In nodal tissue with less Na current, recovery of Ca current plays a role.

25

Mechanism of Action of Antiarrhythmic Drugs:

To stop automaticity
To stop re-entry

26

To stop automaticity function


1. Can increase membrane threshold
2. Hyperpolarize membrane
3. Block sympathetic activity
4. Inhibit sodium entry
5. Inhibit calcium entry

27

To stop re-entry function

1. Convert Unidirectional Block to Bidirectional Block
2. Abolish Unidirectional Block

28


Objectives of antiarrhythmic therapy:

Improve Ventricular Function
Prevent progression to VF
May not need to treat PCV –

29

Improve Ventricular Function

why

• Symptomatic
• Slowing Ventricular rate → thereby increasing ventricular filling. This should help increase cardiac output.
• Make contraction more efficient

30

Prevent progression to VF

Prophylactic

31

May not need to treat PCV –

If infrequent

32

Class Ia: example

Quinidine

33

Class Ia: function

Prolong AP duration and reduce upstroke
Decrease sodium entry into the cell

34

Class Ia: MOA

Bind to inactivated Na channel in a use-dependent manner.

35

Class Ia: process

Slow binding and unbinding to and from receptors
→Also slows phase 4 depolarization and suppresses propagation of automaticity.

36

Class Ia: useful in

Ventricular arrhythmias
Prevention of paroxysmal recurrent atrial fibrillation (triggered by vagal overactivity).

37

Class Ib:Example

Lignocaine

38

Class Ib function

Decrease AP duration and reduce upstroke
Suppress automaticity:
1. Prolong refractory period (bind to inactive state)
2. Decrease conduction (especially in ischemic and therefore more depressed tissue)
3. Decrease Na influx

39

Class Ib useful for

Treatment (and prevention) during and immediately after myocardial infarction.

40

Class Ib risk

A systole
Ventricular tachycardias

41

Class Ic: example

Propafenone

42

Class Ic: function

Blocks sodium entry
Minimal change in action potential duration
Suppress automaticity
Increase refractory period

43

Class Ic: useful in

WPW syndrome and recurrent tachyarrhythmias arising in abnormal conduction system

44

Class Ic: contraindicated in + why

Decrease cardiac contractility – hence contraindicated immediately post MI
→ Flecainide may inhibit CPVT via SR release block

45

Class Ii: example

Atenolol

46

Class Ii: type II agents are

Beta-Blocker

47

Class Ii: action

Suppress automaticity (decreased sympathetic rdrive:
1. Shorten action potential duration
2. Prolong refractory period
3. Decrease conduction in SA and AV nodes
4. Hemodynamic depression especialy if heart failure is present (with some exceptinos)

48

Class Ii: use

• In supraventricular tachycardias
• Improves survival post MI

49

Class III example

Amiodarone

50

Class III function

Prolong action potential duration (secondary to K channel blockade)
Prolong refractory period

51

Class III characterised

Less haemodynamic depressant (but watch out)

52

Class III undesired possible effects

1. Sotalol → is also Beta blocker
2. Bretylium → adrenergic neurone blocker

53

Class III useful for

• Wolff-parkinson-White syndrome
• Ventricular tachycardias and atrial fibrillation

54

Class Iv example

Verapamil

55

Class Iv MOA

Calcium channel blockers

56

Class Iv function

Block AV node (good for supraventricular tachyarrhythmia, bad if AV node already blocked)
May reduce O2 demand and cardiac work

57

Class Iv may affect

Ventricular arrhythmias but not very useful for this purpose.

58

Class Iv useful for

Can prevent recurrence of paroxysmal supraventricular tachycardia
Reduce ventricular rate in patients with atrial fibrillation

59

Class Iv perferential for

Cardiac (verapamil and diltiazem) vs. vascular Ca channels (nifedipine).

60

SA Node drugs

Beta-blockers, atropine, digitalis

61

Atrial muscle drugs

Quinidine, amiodarone, digitalis, disopyramide, procainamide, flecainide

62

AV node drugs

Beta-blockers, verapamil, digitalis

63

Bypass tract drugs

Quinidine, disopyramide, amiodarone, flecainide, procainamide, digitalis

64

Ventricle drugs

Lignocaine, quinidine, Beta-blockers, amiodarone, disopyramide, amidarone,mexiletine, breylium, sotalol, tocainine

65

Physiological agents

Magnesium
Adenosine

66

Magnesium function

Reduces calcium entry through the sarcolemma
Plays an important role in the intracellular space as an agent, which binds ATP and is involved in regulating metabolic processes.

67

Magnesium depeleted in

Ischemic cells

68

Magnesium valuable in

Ventricular arrhythmias in ischemic cells, especially if there is hypomagnesemia

69

Adenosine use for

SVT

70

Adenosine enhances

K current in atrial tissues

71

Adenosine side effects

Transient flushing
Breathlessness

72

Vagal Stimulants example

digoxin

73

Vagal Stimulants classified as

Class V

74

Vagal Stimulants function

Suppress AV conduction
Decrease ventricular rate

75

Vagal Stimulants dont always

Stop arrhythmias

76

Vagal Stimulants used in

Supraventricular tachyarrhythmias

77

Side effects:
Antiarrhythmic agents

may be pro-arrhythmic

78

Antiarrhythmic agents may be pro-arrhythmic
Incidence:

1. Inhomogeneity in conduction and refractoriness
2. Prolongation of action potential duration (Early after depolarization)
3. Apparent, due to lack of efficacy
4. Pre-existing severe cardiomyopathy

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