S10) Arrythmias & CVS Drugs

Question 1

Outline, briefly, the possible action of drugs on the cardiovascular system

Answer 1

CVS drugs can alter:

• The rate and rhythm of the heart
• The force of myocardial contraction
• Peripheral resistance and blood flow
• Blood volume

Question 2

What are arrhythmias/dysrhythmias?

Answer 2

Arrhythmias are abnormalities of heart rate or rhythm

Question 3

Provide 5 examples of arrhythmias

Answer 3

• Bradycardia
• Tachycardia (ventricular/supraventricular)
• Atrial flutter
• Atrial fibrillation
• Ventricular fibrillation

Question 4

Describe four causes of arrhythmia which manifest as tachycardia

Answer 4

• Ectopic pacemaker activity – latent pacemaker region activated due to ischaemia and dominates over SAN
• After depolarisations – abnormal depolarisations following the action potential
• Atrial flutter / atrial fibrillation
• Re-entry loop – conduction delay due to accessory pathway

Question 5

Describe two causes of arrhythmia which manifest as bradycardia

Answer 5

• Sinus bradycardia

I. Intrinsic SAN dysfunction

II. Extrinsic factors e.g. drugs (beta blockers, CCBs)

• Conduction block

I. Problems at AVN / bundle of His

II. Slow conduction at AVN due to extrinsic factors e.g. drugs

Question 6

When are delayed after-depolarisations likely to happen?

Answer 6

Delayed after-polarisations are more likely to happen if intracellular Ca²⁺ high

Question 7

When are early after-depolarisations likely to happen?

Answer 7

• Early after-polarisations are more likely to happen if AP prolonged
• Longer AP = longer QT

Question 8

Describe the re-entrant mechanism for generating arrhythmias

Answer 8

• Incomplete conduction damage (unidirectional block)
• Excitation can take a long route to spread the wrong way through the damaged area, setting up a circus of excitation

Question 9

How does atrial fibrillation occur?

Answer 9

Atrial fibrillation arises due to several small re-entry loops in the atria

Question 10

Briefly, explain how AV nodal re-entry occurs

Answer 10

Fast and slow pathways in the AV node create a re-entry loop

Question 11

Briefly, explain how ventricular pre-excitation occurs

Answer 11

An accessory pathway between atria and ventricles creates a re-entry loop such as in Wolff-Parkinson-White syndrome

Question 12

There are 4 basic classes of anti-arrhythmic drugs affecting the rate and rhythm of the heart.

What are they?

Answer 12

• Drugs that block voltage-sensitive Na⁺ channels
• β-adrenoreceptors antagonists
• Drugs that block K⁺ channels
• Drugs that block Ca²⁺ channels

Question 13

Describe the action of drugs which block voltage-dependant Na⁺ channels (Class I)

Answer 13

• Only blocks voltage-gated Na⁺ channels in open/inactive state, thus preferentially blocks damaged depolarised tissue
• Blocks during depolarisation but dissociates in time for next action potential

Question 14

In four steps, describe the action of β-adrenoreceptor antagonists (class II)

Answer 14

⇒ Act at β1-adrenoreceptors in the heart

⇒ Block sympathetic action

⇒ Decrease slope of pacemaker potential in SAN

⇒ Slows conduction at AVN

Question 15

Describe the effects of beta blockers

Answer 15

Beta blockers slow conduction in AV node:

• Prevent supraventricular tachycardias (decrease in SNS activity)
• Slows ventricular rate in patients with AF

Question 16

Explain why beta blockers are beneficial following myocardial infarction

Answer 16

• MI causes increased sympathetic activity
• β-blockers reduce O₂ demand, hence reducing myocardial ischaemia

Question 17

Describe the action of drugs that block K⁺ channels (class III)

Answer 17

• Block K⁺ channels
• Prolong the action potential
• Lengthens the absolute refractory period
• Preventing another action potential occurring too soon (can be pro-arrhythmic)

Question 18

Describe the actions of drugs that block Ca²⁺ channels (class IV)

Answer 18

• Decreases slope of action potential at SAN
• Decreases AV nodal conduction
• Decreases force of contraction (negative inotropy)
• Some coronary and peripheral vasodilation

Question 19

What is heart failure?

Answer 19

Heart failure is the chronic failure of the heart to provide sufficient output to meet the body’s requirements

Question 20

Identify 4 features of heart failure

Answer 20

• Reduced force of contraction or reduced filling
• Reduced cardiac output
• Reduced tissue perfusion
• Oedema

Question 21

Which types of drugs are used in the treatment of heart failure?

Answer 21

• Positive inotropes to increase cardiac output (not routinely used)
• Drugs which reduce work load of the heart (afterload and preload)

Question 22

Which drugs increase myocardial contractility in the treatment of heart failure?

Answer 22

• Cardiac glycosides
• β adrenoreceptor agonists

Question 23

In 5 steps, explain how cardiac glycosides increase myocardial contractility

Answer 23

⇒ Ca²⁺ is extruded via the Na⁺-Ca²⁺ exchanger

⇒ Cardiac glycosides block Na⁺/K⁺ ATPase

⇒ Rise in [Na⁺]_i decreases activity of Na⁺-Ca²⁺ exchanger

⇒ Causes increase in [Ca²⁺]_i

⇒ Increased force of contraction

Question 24

Cardiac glycosides may be used in heart failure when there are arrythmias.

Describe the action of cardiac glycosides on heart rate

Answer 24

• Action via CNS to increase vagal activity
• Slows AV conduction
• Slows the heart rate

Question 25

Describe two uses of β – adrenoreceptor agonists

Answer 25

- Cardiogenic shock - Acute but reversible heart failure *e.g. following cardiac surgery*

Question 26

Which drugs reduce the work load of the heart?

Answer 26

- ACE inhibitors - Diuretics - β – adrenoreceptor antagonists

Question 27

Describe the action of ACE-inhibitors

Answer 27

**Prevent the conversion of angiotensin I to angiotensin II:** - Reduce Na⁺ and H₂O reabsorption - Vasodilation of systemic vasculature

Question 28

Explain why ACE inhibitors are so useful in the treatment of hypertension

Answer 28

- Decrease **vasomotor tone** (blood pressure) - Reduce **afterload** of the heart - Decrease **fluid retention** (blood volume) - Reduce **preload** of the heart

Question 29

What is angina?

Answer 29

- **Angina** is a condition arising due to insufficient O₂ supply to the heart for a limited duration caused by artheromatous plaque formation in the coronary arteries - It results in heart tissue Ischaemia which presents as chest pain

Question 30

How does one treat angina?

Answer 30

- **Reduce the work load of the heart:** I. β blockers II. CCBs III. Organic nitrates - **Improve the blood supply to the heart:** I. Organic nitrates II. CCBs

Question 31

Describe the action of organic nitrates

Answer 31

- **Reaction of organic nitrates with thiols** in vascular smooth muscle causes NO_2- to be released - NO_2- is reduced to **nitrous oxide** - NO is a powerful **vasodilator**

Question 32

How does nitrous oxide cause vasodilation?

Answer 32

⇒ NO activates **guanylate cyclase** ⇒ Increases **cGMP** ⇒ Lowers **[Ca²⁺]_i** ⇒ Causes **relaxation** of vascular smooth muscle

Question 33

In four steps, describe the primary action of nitrous oxide

Answer 33

**Acts on venous system (venodilation):** ⇒ Reduced venous pressure ⇒ Reduced filling → reduced contractility (Starling’s Law) ⇒ Lowers O₂ demand ⇒ Reduces work load of the heart

Question 34

What is the secondary action of nitrous oxide?

Answer 34

Acts on **coronary collateral arteries** to improve O₂ delivery to the ischaemic myocardium

Question 35

Why do organic nitrates preferentially act on veins?

Answer 35

**Less endogenous nitric oxide in veins:** - Most effective on veins \> arteries - Little effect on arterioles

Question 36

Illustrate how venodilation by organic nitrates is a major contribution to their overall action

Answer 36

Question 37

Illustrate how the dilation of collateral coronary arteries by organic nitrates is only a minor contribution to their overall action

Answer 37

Question 38

Provide an example of an organic nitrate

Answer 38

Glyceryl trinitrate (**GTN spray** – sublingual)

Question 39

Why do we need antithrombotic drugs?

Answer 39

To treat certain heart conditions which carry an **increased risk of thrombus formation** *e.g. atrial fibrillation, AMI, mechanical prosthetic heart valves*

Question 40

What are the two types of antithrombotic drugs?

Answer 40

- Anticoagulants - Antiplatelet drugs

Question 41

Identify some anticoagulants and describe their actions

Answer 41

- **IV Heparin** – inhibits thrombin (short term) - **Oral Warfarin** – antagonises action of vitamin K (long term) - Other: fractionated subcutaneous heparin, oral thrombin inhibitors

Question 42

What is the most common antiplatelet drug and when is it given?

Answer 42

**Aspirin** – following AMI / in high risk of MI

Question 43

What is hypertension?

Answer 43

**Hypertension** is the persistent elevation of blood pressure

Question 44

What are the possible targets of hypertensive drugs?

Answer 44

- Lower **blood volume** - Lower **cardiac output** directly - Lower **peripheral resistance**

Question 45

Identify 5 hypertensive drugs and describe their respective actions

Answer 45

- **ACE-inhibitors** – decrease Na⁺ and H₂O retention and TPR - **CCBs** – vasodilation in vascular smooth muscle - **Diuretics** – decrease Na⁺ and H₂O retention - **β-blockers** – decrease cardiac output (not routinely used) - **α1 adrenoceptor antagonist** – vasodilation (not routinely used)