Week 9 - Drugs and the CVS Flashcards
1
Q
What can drugs be used to treat in the CVS?
A
- Arrhythmias (e.g. bradycardia, atrial fibrillation, atrial flutter)
- Heart failure
- Angina
- Hypertension
- Risk of thrombus formation
2
Q
What can drugs in the CVS alter?
A
- The rate and rhythm of the heart
- The force of myocardial contraction
- Peripheral resistance and blood flow
- Blood volume
3
Q
What are some possible causes of arrhythmia?
A
- Ectopic pacemaker activity
- After-depolarisation
- Re-entry loop
4
Q
How can ectopic pacemaker activity cause arrhythmia?
A
- 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
5
Q
What are after-depolarisations?
A
- 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
6
Q
What is arrhythmia?
A
When the heart beat is irregular or abnormal
7
Q
What are re-entry loops?
A
- 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
8
Q
What are the 4 basic classes of CVS drugs?
A
- Drugs that block voltage-sensitive sodium channels
- β-adrenoceptor antagonists
- Drugs that block K+ channels
- Drugs that block Ca2+ channels
9
Q
How do drugs that block voltage-sensitive sodium channels work?
A
- 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
10
Q
When can lidocaine be used?
A
- 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
11
Q
How do β-adrenoceptor antagonists work?
A
- 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)
12
Q
When can β-blockers be used?
A
- 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
13
Q
How do drugs that block K+ channels work?
A
- 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
14
Q
Give an example of a drug that blocks K+ channels
A
Amiodarone
- Has other actions in addition to blocking K+ channels
- Used to treat tachycardia associated with Wolff-Parkinson-White syndrome
15
Q
How do drugs that block Ca2+ channels work?
A
- 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
16
Q
What is adenosine?
A
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
17
Q
What is heart failure?
A
Chronic failure of the heart to provide sufficient output to meet the body’s requirements
18
Q
What are the features of heart failure?
A
- Reduced force of contraction
- Reduced cardiac output
- Reduced tissue perfusion
- Oedema
19
Q
What type of drug can be used to treat heart failure?
A
- 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
20
Q
How do cardiac glycosides work?
A
- 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
21
Q
Describe the use of β-adrenoceptor agonists
A
- Acts on β1-receptors
- Uses:
- – Cardiogenic shock
- – Acute but reversible heart failure
- E.g. dobutamine
22
Q
How do ACE inhibitors work?
A
- 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
23
Q
How can angina be treated?
A
- 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
24
Q
How do organic nitrates work?
A
- 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
25
Q
Which heart conditions are associate with an increased risk of thrombus?
A
- Atrial fibrillation
- Acute MI
- Mechanical prosthetic heart valves
26
Q
What are some antithrombotic drugs?
A
- 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)
27
Q
What is hypertension associated with?
A
- Associated with increases in blood volume
- – Na+ and water retention by the kidneys
- Or an increase in total peripheral resistance
28
Q
What are some possible targets for hypertension drugs?
A
- Lower blood volume
- Lower cardiac output directly
- Lower peripheral resistance
29
Q
Which drugs can be used to treat hypertension?
A
- 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
