10. Arrythmias & drug actions Flashcards
What are some causes of tachycardia?
Afterdepolarisations
Atrial flutter/ fibrillation
Re-entry loop
Ectopic pacemaker activity
What are some causes of bradycardia?
- Sinus bradycardia- drugs, sick sinus syndrome
- Conduction block
When are delayed after-depolarisations most likely to occur?
When [Ca2+] is high - DIGOXIN overdose
When are early after-depolarisations most likely to occur?
Prolonged action potential with lengthened QT inverval- hypokalaemia
What is AV node re-entry?
Fast and slow pathways in the AV node create a re-entry loop for continuous depolarisation
What is ventricular pre-excitation?
Accessory pathway between atria and ventricles creates a re-entry loop
- Wolf parkinson White syndrome
What are the 4 classes of drugs that affect CV rate and rhythm?
- Block V-gated Na+ channels
- B-adrenoceptor antagonists
- K+ channel blockers
- Ca2+ channel blockers
What is an example of a voltage-gated sodium channel blocker?
Lidocaine
What effect does lidocaine have on normal cardiac tissue?
Little effect as blocks during depolarisation, which is followed by a refractory period anyway.
Dissociates quickly before following action potential is generated.
When is lidocaine used?
Following MI if the patient has signs of ventricular tachycardia when damaged areas of myocardium may be depolarised and fire automatically.
What effects do B1 antagonists have?
Slow conduction at AV node
Reduces O2 demand
Why are B1-antagonists used following MI?
MI causes increased sympathetic activity with increases risk of arrythmia.Beta blockers prevent ventricular arrythmias.
Reduces oxygen demand, reducing myocardial ischaemia.
Othen than following an MI, when else are beta-blockers used?
- Prevent supraventricular tachycardias
- Patients with AF - slow ventricular rate
What effect to K+ channel blockers have?
Prolong the action potential by lengthening the absolute refractory period.
Why are K+ blockers rarely used?
Pro-arrythmic, likely to lead to after depolarisations.
Which is the only K+ blocker that is used, how does this differ to the others?
Amiodarone
Lacks specificity, also blocks B1 receptors and calcium channels.
What is amiodarone used to treat?
Tachycardia associated with wolf-parkinson-white syndrome (re-entry)
Suppressing ventricular arrythmias following MI
How do Ca2+ blockers affect the action potential?
Decrease the slope of the AP at the SA node.
Decreases AV node conduction and force of contraction
What are dihydropyridines?
CCB that is not effective in preventing arrythmias but act on vascular smooth muscle to cause vasodilation.
E.g Amlodipine
What is the MOA of adenosine?
Acts on A1 receptors at AV node to enhance K+ conductance, hyper polarising cells of conducting tissue.
Very short half life
What is adenosine used to treat?
Anti-arrythmic - terminating re-entrant SVT
What approach is taken when treating HF?
Aiming to reduce the workload of the heart rather than increase its contractility as better outcomes in the long run. Positive inotropes not routinely used.
What drugs increase myocardial contractility?
Cardiac glycosides - improve symptoms but not long term outcome
B-adrenoceptor agonists
What is an example of a cardiac glycoside?
Digoxin
What is the MOA of digoxin?
Inhibits Na+/K+ ATPase which leads to a rise in intracellular [Na+] and decreases the activity of NCX. This increases intracellular [Ca2+] and increases inotropy.
How can cardiac glycosides affect heart rate?
Increase vagal activity:
- Slow AV conduction
- Slows HR
When are cardiac glycosides used?
In HF when there is an arrhythmia - e.g AF
What is an example of a B1 adrenoceptor agonist?
Dobutamine
When is dobutamine used?
Cardiogenic shock
Acute but reversible HF (following surgery)
What drugs function to reduce the workload of the heart?
ACE Inhibitors
B-adrenoceptor antagonists
Diuretics
How do ACE inhibitors reduce the cardiac workload?
Inhibiting AngII formation:
Decrease fluid retention - reduce preload
Decrease vasomotor tone - reduce after load
What drug is often used if ACE inhibitors are not tolerated?
Angiotensin II receptor antagonists
What are the aims of angina treatment?
- Reduce workload of the heart (oxygen demand)
2. Improve blood supply of the heart
What drugs are used in angina to reduce the workload?
beta blockers
CCBs
Organic nitrates
What drugs are used to treat angina by improving the blood supply to the heart?
Organic nitrates
CCBs (vasodilation)
What is an example of an organic nitrate?
Glyceryl trinitrate (GTN)
What is the MOA of organic nitrates?
Organic nitrates react with tools in VSMCs to cause NO2- to be released.
NO2- is reduced to NO, a potent vasodilator.
How does NO lead to vasodilation?
Stimulates guanylate cyclase, which converts GTP to cGMP, which activates PKG, PKG decreases intracellular calcium conc, causing relaxation of the VSMC.
What is the primary action of organic nitrates?
Acts on venous system primarily - venodilation lowers preload
Less filling therefore contractility reduced (Starling) which lowers oxygen demand.
What is the secondary action of organic nitrates?
Acts on coronary collateral arteries to improve oxygen delivery to the ischaemic myocardium (minor contribution).
Note: there are not many coronary collateral arteries, end arteries.
What blood vessels do organic nitrates NOT affect?
Arterioles
Why do organic nitrates preferentially act on veins?
Less endogenous NO present, so most marked effect,
Little effect on arteries but no effect on arterioles.
When might anti-thrombotic drugs be given?
Atrial fibrillation
Acute MI
Mechanical prosthetic valves
What is heparin, when is it used?
Anticoagulant that inhibits thrombin.
Used acutely for short term action - given IV
How does warfarin act as anticoagulant, when is it used?
Antagonises the action of vitamin K
Given orally
Give an example of an anti-platelet drug?
Aspirin
When is aspirin given?
Following acute MI or high risk of MI
