Week 9 - Drugs

Question 1

What may result in ectopic pacemaker activity?

Answer 1

• Damaged myocardium becoming depolarised, and firing APs

- Ischaemia activating a latent pacemaker region

Question 2

What are “after-depolarisations”?

Answer 2

Abnormal depolarisations following an action potential

Question 3

What usually causes delayed after-depolarisations, and what is their consequence?

Answer 3

Usually triggered by increased intracellular calcium levels, which results in an early action potential, and hence tachycardia.

Question 4

What are the three main causes of an arrhythmia?

Answer 4

1. Ectopic pacemaker activity
2. After-depolarisations
3. Re-entry loop

Question 5

What usually causes early after-depolarisations, and what is their consequence?

Answer 5

Prolonged action potential

Long QT syndrome

Question 6

What is a re-entry loop?

Answer 6

If there is incomplete conduction damage (unidirectional block), excitation will travel the wrong way through the damaged area, creating a short circuit.

Question 7

What causes atrial fibrillation?

Answer 7

Several re-entry loops in the atria, resulting in uncoordinated contraction.
Could also be due to ectopic excitation, however.

Question 8

What is the difference between supraventricular tachycardia and ventricular tachycardia?

Answer 8

Supraventricular = tachycardia resulting from problem in atria or AV node.
Ventricular = problem originates in ventricles, Purkinjie fibres or bundle of Hiss.

Question 9

What types of drug can be used to treat arrhythmias?

Answer 9

1. Voltage-sensitive Na+ channel blockers (class I)
2. B-blockers (class II)
3. Potassium channel blockers (class III)
4. Calcium channel blockers (class IV)
5. Adenosine

Question 10

Give an example of a class I anti-arrhythmic drug

Answer 10

Lidocaine

Question 11

What is the mechanism of lidocaine, a class I anti-arrhythmic drug?

Answer 11

Use-dependent voltage-sensitive Na+ channel blocker.

Blocks damaged areas of myocardium which are depolarised, and hence likely to fire APs.

Question 12

In what situations may lidocaine be used?

Answer 12

After an MI, to prevent VF.

Question 13

Give an example of a class II anti-arrhythmic drug, and state what the general function of these drugs is.

Answer 13

Propanolol.

B-adrenoreceptor antagonists (B-blockers)

Question 14

Explain the mechanism by which B-blockers decrease heart rate, in reference to the pacemaker potential.

Answer 14

Act on B1-adrenoreceptors in the heart, hence decreasing sympathetic activity.
This means the slope of the pacemaker potential is decreased, and hence it takes longer to reach an AP threshold –> HR down.

Question 15

How do B-blockers reduce ischaemia?

Answer 15

Reduce HR, so reduce O2 demand.

Question 16

Apart from slowing heart rate, what else do B-blockers do?

Answer 16

Slow conduction at AV node, thus preventing supraventricular tachycardia.

Question 17

What class of anti-arrhythmic drugs are potassium channel blockers?

Answer 17

Class III

Question 18

What is the mechanism of potassium channel blockers?

Answer 18

Prolong the action potential, hence lengthening absolute refractory period, which delays the next action potential - i.e. slow heart rate.

Question 19

Why are potassium channel blockers now usually not the choice drugs for tachycardia?

Answer 19

They can be pro-arrhythmic.

Question 20

Give an example of a potassium channel blocker which IS still used.
What is it used for?

Answer 20

Amiodarone

Used to treat Wolff-Parkinson-White syndrome, in which extra conduction pathway leads to re-entry loops.

Question 21

What class of anti-arrhythmic drugs does Verapamil belong to?
What is their general action?

Answer 21

Class IV

Calcium channel blockers

Question 22

What is the mechanism of calcium channel blockers?

Answer 22

Similar to B-blockers -
- decrease slope of pacemaker potential
- decrease AV nodal conduction
But also have -ve inotropic effect

Question 23

What is the mechanism of adenosine?

Answer 23

Acts on a1-adrenoreceptors at the AV node
Enhances K+ conductance, which results in hyperpolarisation.
This briefly stops the heart so it can “reset”.

Question 24

What are the two major types of positive inotropes?

Answer 24

Cardiac glycosides

B-adrenoreceptor agonists

Question 25

Do positive inotropes work long-term? | When are they used?

Answer 25

No - increase cardiac output, but this stresses heart, so no real effect on long-term survival. Used in palliative care to improve quality of life.

Question 26

Give an example of a cardiac glycoside

Answer 26

Digoxin

Question 27

How do cardiac glycosides act to increase the force of contraction of the heart?

Answer 27

Block Na+/K+-ATPase, hence Na+ is no longer extruded. This means that a Na+ concentration gradient is not established, and therefore Na+ no longer enters the cell via NCX. In turn, this means that Ca2+ does not leave the cell via NCX, and builds up --> stronger contraction.

Question 28

Apart from a +ve inotropic effect, what other effect do cardiac glycosides have?

Answer 28

``` Increase vagal (parasympathetic) activity, therefore slowing the heart. Thus only used in tachycardia. ```

Question 29

Give an example of a B-adrenoreceptor agonist.

Answer 29

Dobutamine

Question 30

When might B-adrenoreceptor agonists be used?

Answer 30

Cardiogenic shock | Acute, but reversible, cardiac failure.

Question 31

Name 3 types of drug which are used to reduce the workload of the heart.

Answer 31

ACE-inhibitors B-blockers Diuretics

Question 32

What is the mechanism of ACE-inhibitors?

Answer 32

Block "angiotensin converting enzyme", preventing production of angiotensin II. This reduces both preload and afterload of heart, as it prevents angiotensin II acting as a vasoconstrictor and stimulating water retention.

Question 33

What are the two general mechanisms by which angina may be treated?

Answer 33

Reduce workload of the heart, hence reducing O2 demand. | Improving blood supply, hence increasing O2 supply.

Question 34

What 3 types of drug may be used to treat angina?

Answer 34

1. B-blockers 2. Organic nitrates 3. Calcium channel antagonists

Question 35

Give an example of an organic nitrate

Answer 35

Glyceryl trinitrate

Question 36

How do organic nitrates cause vasodilation?

Answer 36

React with thiols in the vascular smooth muscle, to release NO2-, which is reduced to NO (nitric oxide). NO activates guanylate cyclase, which increases cGMP. In turn, this reduces the concentration of Ca2+ in the cell, hence reducing the smooth muscle contraction.

Question 37

What is the primary site of organic nitrate action?

Answer 37

The venous system --> venodilation | This reduces preload

Question 38

Where else, apart from the venous system, may organic nitrates act? Why is this beneficial?

Answer 38

The collateral coronary arteries. | Means vessels providing a route around blockage can accommodate more blood.

Question 39

What conditions make it more likely for blood clots to develop?

Answer 39

Atrial fibrillation After an MI If you have prosthetic heart valves

Question 40

Which two types of drug may be used to prevent blood clot formation?

Answer 40

Anticoagulants | Antiplatelet drugs

Question 41

Compare and contrast heparin and warfarin.

Answer 41

Both anticoagulants. Heparin - only used short-term. Inhibits thrombin. Warfarin - can be used long-term. Antagonises action of vitamin K.

Question 42

Name a common antiplatelet drug.

Answer 42

Aspirin

Question 43

What may cause hypertension?

Answer 43

Increase blood volume | Increased TPR

Question 44

What are the 3 main ways that hypertensive drugs act?

Answer 44

- Reduce blood volume - Reduce TPR - Reduce cardiac output

Question 45

Which 5 types of drug may be used to treat hypertension?

Answer 45

1. Diuretics 2. ACE-inhibitors 3. B-blockers 4. Calcium channel blockers 5. a1 - adrenoreceptor antagonists