Session 10-Arrhythmias And CVS Drugs Flashcards
What are the causes of arrhythmias?
Tachycardia
Bradycardia
What are the tachycardic causes of arrhythmias?
- ectopic pacemaker activity
- afterdepolarisations
- atrial fibrillation
- re-entry loop
What are the bradycardic causes of arrhythmias?
- sinus bradycardia
- conduction block
When are delayed after-depolarisations more likely to occur?
If intracellular Ca2+ is high
What can early after-depolarisations lead to?
Oscillations
When are early after-depolarisations likely to occur?
If AP is prolonged (longer AP -> longer QT)
What can a long QT interval be due to and what can it lead to?
Due to iron channel abnormalities
Lead to ventricular fibrillation
Describe how a re-entry loop can generate arrhythmia
- conduction block through damaged area
- incomplete conduction damage - excitation takes long route to spread wrong way through damaged area, setting up circuit of excitation
What do multiple re-entrant circuits in the atria lead to?
Atrial fibrillation
What can lead to multiple re-entry loops in the atria?
Mitral valve stenosis -> stretching and volume overload in atria -> damage and fibrosis and over-excitation of atria -> multiple re-entry loops
In which ways do anti-arrhythmic drugs work?
- block voltage-sensitive sodium channels
- antagonists of beta-adrenoceptors
- block potassium channels
- block calcium channels
What is an example of a drug which blocks voltage-sensitive Na+ channels?
Local anaesthetic lidocaine
Describe when drugs which block voltage-sensitive Na+ channels are used
Only blocks channels in open or inactive state - preferentially blocks damaged depolarised tissue
Why do drugs which block voltage-sensitive Na+ channels have little effect in normal cardiac tissue?
It dissociates rapidly - blocks during depolarisation but dissociates in time for next AP
When is the only time lidocaine is used following MI?
If patient shows signs of ventricular tachycardia
What does the binding of lidocaine to voltage-sensitive Na+ channels do?
Prevents automatic firing of depolarised ventricular tissue
Give two examples of beta-adrenoceptor antagonists
Propranolol
Atenolol
What do beta-adrenoceptor antagonists do in the heart?
Block sympathetic action (act at beta1-adrenoceptors in the heart)
True or false: beta-blockers slow conduction in AV node
TRUE
What effects does slowing conduction in AV node have in patients?
- can prevent supraventricular tachycardias
- slows ventricular rate in patients with AF
Why are beta-blockers used following MI?
- MI causes increased sympathetic activity and beta blockers prevent ventricular arrhythmias
- reduces O2 demand so reduces myocardial ischaemia
What do drugs blocking K+ channels do and what effect does this have?
Prolong action potential by blocking K+ channels -> lengthens absolute refractory period
Why are drugs which block K+ channels not generally used?
In theory should prevent another AP occurring too soon but in reality can be pro-arrhythmic
What is the one exception of drugs blocking K+ channels and what is it used to treat?
Amiodarone - blocks Ca2+ channels, beta blocker and slows down rise of AP
Treats tachycardia associated with Wolff-Parkinson-White syndrome and suppresses ventricular arrhythmias post MI
What is Wolff-Parkinson-White syndrome?
Re-entry loop due to extra conduction pathway
What are the effects of drugs which block Ca2+ channels?
- decreases slope of AP at SA node
- decreases AV nodal conduction
- negative inotropy
Which Ca2+ channel blockers are ineffective in the heart and where do they work instead?
Dihydropyridine Ca2+ channel blockers don’t prevent arrhythmias but act on vascular smooth muscle
Which drug doesn’t fit into any of the anti-arrhythmic classes but is useful for terminating supra-ventricular tachycardia?
Adenosine
What does adenosine act on and what effect does this have?
Acts on alpha-1 receptors at AV node and enhances K+ conductance (hyperpolarises cells of conducting tissue and prevents re-entry loops)
What are the features of heart failure?
- reduced force of contraction or reduced filling
- reduce cardiac output
- reduced tissue perfusion
- oedema
What are the two types of drugs used in the treatment of heart failure?
- positive inotropes to increase cardiac output
- drugs which reduce work load of heart (reduce afterload and preload)
Why are positive inotropes not usually used to treat heart failure?
Don’t improve long-term survival
Which drugs increase cardiac contractility?
Cardiac glycosides
Beta-adrenergic agonists
What is the prototype of cardiac glycosides and what does it block?
Digoxin blocks Na+/K+ ATPase
How do cardiac glycosides work?
- Ca2+ extruded via NCX
- cardiac glycosides block Na+/K+ ATPase pump
- leads to rise in intracellular Na+
- leads to decrease in activity of NCX
- causes increase in intracellular calcium as more Ca2+ is stored in SR
- increased force of contraction
How do cardiac glycosides affect heart rate?
Increase vagal activity -> slows AV conduction -> slows heart rate
When can beta-adrenoceptor agonists be used?
To treat cardiogenic shock and acute but reversible heart failure
Which drugs reduce workload of the heart?
- ACE inhibitors
- beta blockers
- diuretics
How can ACE inhibitors be used to treat heart failure?
- decreases vasomotor tone -> decreases blood pressure -> reduces afterload of heart
- decreases fluid retention -> decreases blood volume -> reduces preload of heart
What is angina?
Due to narrowing of coronary arteries, occurs when O2 supply to heart doesn’t meet its need (limited duration so no myocyte death) -> chest pain with exertion
How is angina treated?
- reduce workload of heart
- improve blood supply to heart
Which drugs reduce work load of the heart to treat angina?
Beta-adrenoceptor blockers
Ca2+ channel antagonists
Organic nitrates
Which drugs improve blood supply to the heart?
Organic nitrates
Ca2+ channel antagonists
How do organic nitrates work?
Organic nitrates react with thiols (-SH groups) in vascular smooth muscle, causing NO2- to be released and this is reduced to NO (vasodilator)
How does nitric oxide cause vasodilation?
- NO activates guanylate cyclase
- increases cGMP
- lowers intracellular Ca2+
- causes relaxation of vascular smooth muscle
What is the primary action of organic nitrates in terms of alleviating symptoms of angina?
Acts on venous system (venodilation lowers preload) - reduces workload, heart fills less, force of contraction reduced, lowers O2 demand
What is the secondary action of organic nitrates in terms of alleviating symptoms of angina?
Acts on coronary collateral arteries to improve O2 delivery to ischaemic myocardium
Why do organic nitrates preferentially act on veins?
Less endogenous nitric oxide in veins
Which heart conditions carry an increased risk of thrombus formation?
Atrial fibrillation
Acute MI
Mechanical prosthetic heart valves
What are two important anticoagulants and how do they work?
1) heparin (IV) - inhibits thrombin
2) warfarin (orally) - antagonises action of vit K
What is an example of an antiplatelet drug and when is it used?
Aspirin - following acute MI or high risk of MI
What is hypertension associated with?
Increased blood volume (Na+ and water retention by kidneys)
Increased TPR
Which drugs are used to treat hypertension and what are their effects?
1) ACE inhibitors (decrease Na+ and water retention by kidney, decrease TPR)
2) Ca2+ channel blockers selective for vascular smooth muscle (vasodilation)
3) diuretics (decrease Na+ and water retention by kidney)
4) beta blockers (not routinely used, decrease CO)
5) alpha1-adrenoceptor antagonist (not routinely used, vasodilation)
