L 58 Pharmacology of Dysrhythmia/HF/AF

Question 1

What is a dysrhythmia?

What are the 3 levels?

Answer 1

A disruption of cardiac electrical conduction, primarily at 3 levels:

1. Autonomic NS
2. Cardiac conduction systems
3. Heart muscles (e.g myocyte ion channels)

Question 2

How does blood get pumped around the body?

How many times per minute? (avg)

Answer 2

The blood gets pumped around the body by contraction of the atria and ventricles via depolarisation.
This occurs around 60 times per minute.

Question 3

2 determinants of heart rate

Answer 3

Parasymp and symp systems

Question 4

Parasympathetic effects on heart rate

Answer 4

Decreases heart rate

Question 5

Sympathetic effects on heart rate

Answer 5

Increases HR and contraction force

Question 6

What is the determinant of heart rhythm?

Answer 6

The cardiac conduction system that innervates the myocytes.

Question 7

Depolarisation creates an … …

Physiologically, an … … causes the muscle to … and to … blood.

Answer 7

Depolarisation causes an action potential

Physiologically an action potential causes the muscle to contract and to pump blood.

Question 8

Difference between action potential and ECG reading

Answer 8

Action potential occurs in an individual cell.
An ECG detects the overall electrical activity of the heart at the skin surface, which is the sum of all the cardiac cells firing.

Question 9

According to the Vaughan Williams classification, what are the follow 4 classes:

Answer 9

Class I:
Class II:
Class III:
Class IV:
Class I: sodium channel blockers
Class II: beta adrenergic blockers
Class III: potassium channel blockers
Class IV: calcium channel blockers

Question 10

Name 3 class I agents

Answer 10

Quinidine
Lidocaine
Flecainide

Question 11

Name 4 class II agents

Answer 11

Metoprolol
Bisoprolol
Sotalol
Carvedilol

Question 12

MoA of B blockers in dysrhythmias

Where to B blockers bind?

Answer 12

To decrease HR and conduction velocity which increases the refractory period.
B blockers bind to receptors in SA and AV nodes, conducting tissues and myocytes.

Question 13

What is the most commonly used B blocker in arrythmias?

… is also commonly used.These 2 are only used for specific indications…

Answer 13

Metoprolol = most commonly used
Bisoprolol = also commonly used
Sotalol and carvedilol = only used for specific indications.

Question 14

How do class III agents work?

Answer 14

Their main effect is to delay repolarisation and increase the ERP, which makes the celll less excitable

Question 15

Examples of class III agents

Answer 15

Amiodarone
Sotalol (which is also class II)

Question 16

Where can you see the effects of class III agents on an ECG?

Answer 16

You will see an increase in the QT interval.

Question 17

5x examples of Class IV agents

Which are NOT used? Why?

Answer 17

DHPs: amlodipine, felodipine, nifedipine (not used as antiarrythmatics as they are selective for vascular Ca2+ channels)
Diltiazem
Verapamil

Question 18

What is the main site of action for class IV agents?
What is their MoA?

Answer 18

Main site: SA and AV nodes

MoA: to decrease conduction velocity and prolong repolarisation

Question 19

What are the other effects of class IV agents? x3

Answer 19

Vasodilation, negative inotrope, decreased HR

Question 20

MoA of diltiazem

Answer 20

Binds to both vascular and myocardial Ca2+ channels, so is a vasodilator and cardiac depressant

Question 21

Verapamil is selective for…

It is also used in…

Answer 21

Verapamil = selective for myocardium

Is also used in angina as well as an antiarrhythmatic

Question 22

Action of amiodarone (+ class)
Indications
PK: (absorption/bioavail, t0.5, metabolised by …)

Answer 22

Block potassium channels in cardiac tissues (Class III)
Indications: rhythm control, tachyarrythmias
PK:
- Absorption and bioavail vary between people.
- T0.5 = ~14-59 days
- Metabolised by CYP3A4 and CYP2C8

Question 23

Interactions of amiodarone

Answer 23

Inhibits many CYP enz, and reduces clearance of many drugs (warfain, statins, dabigatran)

Question 24

Important side effects of amiodarone x5

Answer 24

Blue-grey skin discolouration
Thyroid toxicity (hypo/hyperthyroidism)
Pulmonary fibrosis
Arrythmias (bradycardia, heart block, TdP)
Increased LFTs

Question 25

Action of flecainide (+ class)

Indications

Answer 25

Blocks Na+ channels in cardiac tissue (class 1c)
Indications: rhythm control for supraventricular and ventricular arrythmias.

Question 26

Special populations for flecainide

Answer 26

Cap the dose in elderly and those with renal/hepatic impairment

Question 27

Important side effects of flecainide x2

Answer 27

Proarrhythmic, HF exacerbation

Question 28

Action of sotalol (+ class)

Answer 28

Indications
B blocker and blocks potassium channels (Class II and III)
Indications: rhythm control but NOT used for rate control

Question 29

Important side effects fo sotalol
When to avoid sotalol
Drug interactions with sotalol:

Answer 29

Side effects: proarrythmia
Avoid in: HF and severe renal impairment, asthma
Drug interactions: cardiodepressant CCBs

Question 30

What is the main fact about PK for sotalol?

Answer 30

Requires dose adjustment in renal disease as it is excreted unchanged by kidneys

Question 31

Examples of drugs that cause or exacerbate arrhythmias (non-exhaustive list, but x5)

Answer 31

Anti-arrythmics
Macrolides
Some quinolones
Antipsychotics
Hydroxychloroquine