Week 9 - Drugs and the CVS Flashcards Preview

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Flashcards in Week 9 - Drugs and the CVS Deck (29):

What can drugs be used to treat in the CVS?

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


What can drugs in the CVS alter?

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


What are some possible causes of arrhythmia?

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


How can ectopic pacemaker activity cause arrhythmia?

- 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


What are after-depolarisations?

- 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


What is arrhythmia?

When the heart beat is irregular or abnormal


What are re-entry loops?

- 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


What are the 4 basic classes of CVS drugs?

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


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

- 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


When can lidocaine be used?

- 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


How do β-adrenoceptor antagonists work?

- 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)


When can β-blockers be used?

- 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


How do drugs that block K+ channels work?

- 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


Give an example of a drug that blocks K+ channels

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


How do drugs that block Ca2+ channels work?

- 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


What is adenosine?

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


What is heart failure?

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


What are the features of heart failure?

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


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

- 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


How do cardiac glycosides work?

- 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


Describe the use of β-adrenoceptor agonists

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


How do ACE inhibitors work?

- 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


How can angina be treated?

- 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


How do organic nitrates work?

- 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


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

- Atrial fibrillation
- Acute MI
- Mechanical prosthetic heart valves


What are some antithrombotic drugs?

- 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)


What is hypertension associated with?

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


What are some possible targets for hypertension drugs?

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


Which drugs can be used to treat hypertension?

- 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