Drugs in the CVS

Question 1

Give two examples of an arrhythmia/dysarrhythmia

Answer 1

Bradycardia
Atrial flutter
Atrial fibrillation
Tachycardia
Ventricular fibrillation

Question 2

Describe how ectopic pacemaker activity can be triggered.

Answer 2

Damage to myocytes so they spontaneously depolarise, or in an MI where there is activity surrounding the site due to ischaemia (may dominate over the SAN).

Question 3

What is after depolarisation?

State the two types.

Answer 3

Abnormal depolarisation after an action potential has fired (triggered action potential).
Delayed/early after depolarisation

Question 4

Describe delayed after depolarisation and what intracellular condition can predispose it.

Answer 4

Initiate after repolarisation has finished, but before another should occur. If they reach the threshold they can trigger another action potential.

More likely with high intracellular calcium.

Question 5

Describe early after depolarisation.

Answer 5

When action potentials occur before another has finished.

More likely with a long action potential.

Question 6

What can cause a re-entry loop?

Answer 6

Conduction delay or accessory pathway

Question 7

If a unidirectional block causes a re-entry loop, what effect does this have on excitation?

Answer 7

It can take a long route to spread the wrong way around the circuit.

If there are a few in the atria they can cause atrial fibrillation.

Question 8

What are the four classes of anti-arrhythmics?

Answer 8

Block voltage sensitive Na+ channels
Beta adrenoceptor antagonists
Inhibit potassium channels
Inhibits calcium channels

Question 9

When are class I anti-arrhythmics (block voltage-sensitive Na+ channels) used?

Answer 9

Following a MI if the patient shows signs of ventricular tachycardia.
(not used prophylactically)

Question 10

Describe how class I anti-arrhythmics (block voltage-sensitive Na+ channels) work.

Answer 10

Block voltage-sensitive Na channels when they are open or inactive (use-dependent).
It dissociates rapidly for the next action potential, so stops multiple ones occurring in quick succession, but allow normal contraction.

Question 11

What are class II anti-arrhythmics (beta adrenoceptor antagonists) used for?

Answer 11

Prevents supraventricular tachycardia

Decrease O2 demand in MI

Question 12

How do class II anti-arrhythmics (beta adrenoceptor antagonists) work?

Answer 12

Inhibit beta-1 adrenoceptors in the heart, decreasing the slope of the pacemaker potential in the SAN as the HCN channel is inhibited. This reduces heart rate.
Can also decrease conduction in the AVN

Question 13

How do class III anti-arrhythmics (inhibit K+ channels) work?

Answer 13

Prolong the action potential, lengthening the absolute refractory period.
Theoretically prevent an action potential occurring too soon, but in reality are pro-arrhythmic and are therefore not generally used.

Question 14

Amiodarone is an exception in class III anti-arrhythmics. What is it used to treat?

Answer 14

Tachycardia associated with Wolff-Parkinson-White syndrome.

Question 15

How does a class IV anti-arrhythmic (Ca2+ channel inhibitor) work?

Answer 15

Decreases the slope of the pacemaker action potential at the SAN and decreases AVN conductivity (has negative ionotrophy).
Causes some coronary and peripheral vasodilation

Question 16

What are class IV anti-arrhythmics (Ca2+ channel inhibitor) used for?

Answer 16

They are generally not effective in preventing arrhythmias but can be used to treat hypertension.

Question 17

How can pharmacological adenosine be used to treat a serious arrhythmia?

Answer 17

Acts on A1 receptors at the AVN. The gamma subunit increases potassium conductance, hyperpolarising cells of conducting tissue.
Resets the rhythm by momentarily causing the heart to stop. Has a very short half life so doesn’t have a prolonged effect.

Question 18

What are the features of heart failure?

Answer 18

Decreased force of contraction
Decreased cardiac output
Reduced tissue perfusion
Oedema (peripherally or in the lungs)

Question 19

Give a class of drug which can be used to increase cardiac output in heart failure.

Answer 19

Cardiac glycoside (rarely used)
Beta-adrenoceptor agonist

Question 20

Describe how cardiac glycosides work.

Answer 20

Block Na/K ATPase.
As Ca is usually removed by NCX (driven by the concentration gradient of sodium), calcium in the cell will increase. This means that more is stored in the SR and released on initiation by an action potential, increasing the force of contraction.
They also increase vagal activity by acting at muscarinic receptors.
Also slow AV conduction and heart rate.

Question 21

Give an example of a condition which can be treated by cardiac glycosides.

Answer 21

Tachycardia

Heart failure

Question 22

What are beta-adrenoreceptor agonists used to treat?

Answer 22

Cardiogenic shock (sudden drop in CO)
Acute and reversible heart failure

Question 23

How do ACE inhibitors work?

Answer 23

Inhibit angiotensin converting enzyme which converts inactive angiotensin I to active angiotensin II. This would normally increase aldosterone release from the kidneys and vasopressin from the brain.
They therefore decrease blood volume (and therefore pressure) and lower vasomotor tone.

Question 24

How can organic nitrates be used to treat angina?

Answer 24

Convert NO2- to NO which is a powerful vasodilator.
It activates guanylate cyclase which increases cGMP production, upregulating PKG. This decreases calcium concentration
Primary action on the venous system which decreases preload, and has a secondary effect on collateral coronary arterys which increases delivery to the ischaemic myocardium.

Question 25

In what conditions are antithrombotics important prophylactically?

Answer 25

Atrial fibrillation
Acute MI
Mechanical prosthetic heart valves

Question 26

Describe how heparin works as an antithrombotic.

Answer 26

Inhibits thrombin, is an anticoagulant.

Question 27

Describe how warfarin works as an antithrombotic

Answer 27

Anticoagulant by inhibiting vitamin K action.

Question 28

Describe how aspirin works as an antithrombotic.

Answer 28

Antiplatelet.

Question 29

Give the targets for treating hypertension and a class of drug that will affect each.

Answer 29

Lower blood volume - diuretics/ACE inhibitors

Lower CO - beta blockers

Lower TPR - Calcium channel blockers/alpha-1 antagonist/ACE inhibitors