Week 9 - Drugs and the CVS

Question 1

What can drugs be used to treat in the CVS?

Answer 1

• Arrhythmias (e.g. bradycardia, atrial fibrillation, atrial flutter)
• Heart failure
• Angina
• Hypertension
• Risk of thrombus formation

Question 2

What can drugs in the CVS alter?

Answer 2

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

Question 3

What are some possible causes of arrhythmia?

Answer 3

• Ectopic pacemaker activity
• After-depolarisation
• Re-entry loop

Question 4

How can ectopic pacemaker activity cause arrhythmia?

Answer 4

• Damaged area of myocardium becomes depolarised and spontaneously active
• It can dominate over the SA node, if it fires action potentials faster than the SA node

Question 5

What are after-depolarisations?

Answer 5

• After-depolarisations = abnormal depolarisations following the action potential
• Can be delayed or early
• Delayed is more likely if intracellular [Ca2+] is high
• Early: can lead to oscillations, more likely to happen if the action potential is prolonged

Question 6

What is arrhythmia?

Answer 6

When the heart beat is irregular or abnormal

Question 7

What are re-entry loops?

Answer 7

• Conduction delay
• Accessory pathway
• It is where there is incomplete conduction damage
• – The block only allows excitation to travel in 1 direction
• – This sets up a circuit of excitation
• It is possible to get several small re-entry loops in the atria
• – This leads to atrial fibrillation

Question 8

What are the 4 basic classes of CVS drugs?

Answer 8

• Drugs that block voltage-sensitive sodium channels
• β-adrenoceptor antagonists
• Drugs that block K+ channels
• Drugs that block Ca2+ channels

Question 9

How do drugs that block voltage-sensitive sodium channels work?

Answer 9

• Only blocks voltage-gated Na+ channels in open or inactive state
• This prevents another action potential firing soon after
• Dissociates rapidly in time for the next action potential
• Use-dependent block
• E.g. local anaesthetic lidocaine

Question 10

When can lidocaine be used?

Answer 10

• Sometimes used following MI if patient shows signs of ventricular tachycardia
• Damaged areas of myocardium may be depolarised and fire automatically
• More Na+ channels are open in depolarised tissue, so lidocaine can block them
• – This prevents automatic firing of depolarised ventricular tissue

Question 11

How do β-adrenoceptor antagonists work?

Answer 11

• They block sympathetic action by acting at the β1-adrenoceptors in the heart
• They cause a decrease in the slope of the pacemaker potential in the SA node
• E.g. proprnaolol, atenolol (β-blockers)

Question 12

When can β-blockers be used?

Answer 12

• Following MI
• – MI causes increased sympathetic activity
• – β-blockers prevent ventricular arrhythmias which may be partly due to increased sympathetic activity
• To reduce myocardial ischaemia
• – By reducing oxygen demand
• Prevent supraventricular tachycardias
• – By slowing conduction in AV node

Question 13

How do drugs that block K+ channels work?

Answer 13

• Prolong the action potential by blocking K+ channels
• This lengthens the absolute refractory period
• In theory, this prevents another action potential occurring too soon
• – In reality, can be pro-arrhythmic due to early after-depolarisation

Question 14

Give an example of a drug that blocks K+ channels

Answer 14

Amiodarone

• Has other actions in addition to blocking K+ channels
• Used to treat tachycardia associated with Wolff-Parkinson-White syndrome

Question 15

How do drugs that block Ca2+ channels work?

Answer 15

• Decrease slope of pacemaker action potential at SA node
• Decrease AV nodal conduction
• Decrease force of contraction
• The dihydropyridine Ca2+ channel blockers aren’t effective in preventing arrhythmias, but do act on vascular sooth muscle to cause vasodilation
• E.g. verapamil

Question 16

What is adenosine?

Answer 16

An anti-arrhythmic drug

• Administered intravenously
• Doesn’t belong in any of the classes previously mentioned
• Acts on A1 receptors at AV node
• – This enhances K+ conductance, because the βγ-subunit directly opens K+ channels
• – This hyperpolarises cells on conductance tissue

Question 17

What is heart failure?

Answer 17

Chronic failure of the heart to provide sufficient output to meet the body’s requirements

Question 18

What are the features of heart failure?

Answer 18

• Reduced force of contraction
• Reduced cardiac output
• Reduced tissue perfusion
• Oedema

Question 19

What type of drug can be used to treat heart failure?

Answer 19

• Positive inotropes increase cardiac output
• – E.g. cardiac glycosides, β-adrenergic agonists
• Drugs which reduce workload of the heart
• – Reduce afterload and preload
• – E.g. ACE inhibitors, β-adrenoceptor antagonists

Question 20

How do cardiac glycosides work?

Answer 20

• Block Na+/K+ ATPase
• Causes a rise in intracellular [Na+]
• This leads to a decrease in activity of Na+-Ca2+ exchanger
• Causes an increase in intracellular [Ca2+] (more is stored in SR)
• Hence more Ca2+ can be released for each action potential, so there is an increased force of contraction
• Can also cause increased vagal activity
• – Action is via CNS
• – Slows AV conduction, hence slowing the heart rate

Question 21

Describe the use of β-adrenoceptor agonists

Answer 21

• Acts on β1-receptors
• Uses:
• – Cardiogenic shock
• – Acute but reversible heart failure
• E.g. dobutamine

Question 22

How do ACE inhibitors work?

Answer 22

• Inhibit the action of angiotensin converting enzyme
• – Prevents the conversion of angiotensin I to angiotensin II
• – Angiontensin II acts on the kidneys to increase Na+ and water reabsorption, and acts as a vasoconstrictor
• Decrease vasomotor tone
• Reduce afterload of the heart
• Decrease fluid retention, so there is decreased blood volume
• Reduce preload of the heart

Question 23

How can angina be treated?

Answer 23

• Reduce the workload of the heart:
• – β-adrenoceptor blockers
• – Ca2+ channel antagonists
• – Organic nitrates
• Improve the blood supply to the heart
• – Organic nitrates
• – Ca2+ channel antagonists

Question 24

How do organic nitrates work?

Answer 24

• Reaction of organic nitrates with thiols (-SH) in vascular smooth muscle causes NO2- to be released
• NO2- is reduced to NO
• – NO is a powerful vasodilator
• – It lowers intracellular [Ca2+], causing relaxation of vascular smooth muscle
• Primary action:
• – Causes venodilation
• – This causes more blood to be stored in the veins
• – It lowers preload, hence reducing the workload of the heart
• – The heart fills less, so the force of contraction is reduced
• – This lowers O2 demand
• Secondary action:
• – Acts on coronary arteries to improve O2 delivery to the ischaemic myocardium
• – Acts on collateral arteries rather than arterioles

Question 25

Which heart conditions are associate with an increased risk of thrombus?

Answer 25

• Atrial fibrillation
• Acute MI
• Mechanical prosthetic heart valves

Question 26

What are some antithrombotic drugs?

Answer 26

• Anticoagulants
• – Heparin (inhibits thrombin, used acutely for short term action)
• – Fractionated heparin (subcutaneous injection)
• – Warfarin (antagonises action of vitamin K, can be used long term)
• Antiplatelet drugs
• – Aspirin (following acute MI or high risk of MI)

Question 27

What is hypertension associated with?

Answer 27

• Associated with increases in blood volume
• – Na+ and water retention by the kidneys
• Or an increase in total peripheral resistance

Question 28

What are some possible targets for hypertension drugs?

Answer 28

• Lower blood volume
• Lower cardiac output directly
• Lower peripheral resistance

Question 29

Which drugs can be used to treat hypertension?

Answer 29

• Diuretics
• – Decrease Na+ and water retention in the kidney, hence decreasing blood volume
• ACE-inhibitors
• – Decrease Na+ and water retention by kidney
• – Decrease total peripheral resistance by vasodilation
• β-blockers
• – Decrease cardiac output
• Ca2+ channel blockers that are selective for vascular smooth muscle
• – Cause vasodilation
• α1-adrenoceptor antagonist
• – Vasodilation