Antiarrhythmic Drugs Flashcards
Describe the ventricular action potential
Phase 0 - rapid depolarisation when Na+ enters
Phase 1 - partial depolarisation where Na+ channels become inactivated
Phase 2 - plateau caused by inward Ca2+ currents opposing the outwards K+ movement
Phase 3 - repolarisation due to closing of the L-type and unopposed K+ current
Phase 4 - resting membrane potential determined by K+ permeability
Describe the pacemaker potential
No resting membrane potential. The funny current is activated by HCN channels moving Na+ into the cell and when this reaches -50mv it reaches the threshold to generate an action potential. HCN channels inactivate and the upstroke is caused by opening of L-type Ca2+ channels. The downstroke is caused by opening of K+ channels.
What is the difference between atrial fibrillation and supra ventricular tachycardia?
Atrial fibrillation is irregularly irregular whereas supra ventricular tachycardia is regular but tachycardic
What are delayed after-depolarisations?
Mainly caused by an increase in Ca2+ which reverses NCX allowing Na+ to enter and depolarise the cell early.
Early after-depolarisation occurs before the action potential has completed and can be potentates by hypokalaemia or drugs that increase the QT interval (class III antiarrhythmics)
What are re-entry loops?
An impulse re-excites regions after the refractory period has subsided causing a continuous circulation of action potentials that would usually cancel each other out. As a result of structural abnormality or MI
What physiological action can cause ectopic pacemaker activity and what does this cause?
Activation of the sympathetic system and can cause tachycardias
What causes heart block?
Fibrosis/ischaemic damage to the conducting system
How do class I drugs work?
Na+ channel blockers - bind to open Na+ channels and keep them inactivated but dissociates in time for the next action potential so prevents early APs
Name a class IA drug
Quinidine, procainamide
Name a class IB drug
Lidocaine, phenytoin
Name a class IC drug
Flecainide, propafenone
What are the ADRs for flecainide?
Pro arrhythmic
CNS - dizziness, drowsiness
GI - nausea, vomiting
Describe the pharmacokinetics for flecainide
Oral, CYP2D6, renal excretion
How do beta blockers achieve a chronotrophic effect?
They decrease the slope of the pacemaker potential
Name the major class III antiarrhythmic
Amiodarone - binds to K+ channels and prolongs the refractory period
What are the ADRs of amiodarone?
Hepatic injury, pulmonary fibrosis, thyroid disease, increased LDLs
Name a Ca2+ channel blocker
Verapamil, diltiazem - decrease the inwards current of Ca2+ causing a decrease in the slope of the action potential and also reduces the force of contraction
How would you treat a supra ventricular tachycardia?
Vagal manoeuvres
IV adenosine/verapamil
How does adenosine work?
Binds to A1 receptor which is Gi and reduces cAMP thus increases K+ efflux and leads to hyperpolarisation
How would you manage chronic AF?
Anticoagulant
Rate control - beta blocker/verapamil (consider adding digoxin/amiodarone)
Rhythm control - cardioversion (+amiodarone) or pharmacological cardioversion (flecainide)
How would you treat acute AF?
Anti coagulation
Emergency cardioversion (+amiodarone) or pharmacological cardioversion (flecainide)
Control rate - verapamil/bisprolol (digoxin/amiodarone second line)
How would you treat ventricular tachycardia?
Amiodarone/lidocaine, shock
What are the ADRs for verapamil?
Constipation, hypotension, ankle swelling, heart failure
How does digoxin work? (Cardiac glycoside)
Has a positive inotrphic effect by blocking Na+/K+ ATPase. This increases intracellular Na+ which reverses the NCX pump so more Ca2+ is stored in the SER and available during contraction
It also has a negative chronotrophic effect by increasing vagaries activity g
