Antiarrhythmia Flashcards
What is the Sinoatrial node pacemaker potential
the rate of firing of the SA node set the heart - initiates the cardiac cycle
what do pacemaker cell membrane contain
HCN gated channels which are hyperpolarisation activation
what are the three phases of the myocardial heart potential
Phase 4 (prepotential), Phase 0, Phase 3
what happens in phase 4
- pacemaker Na+ influx, Ca2+ channels recover from inactivation
-pumps restore ion gradients
-activated by hyperpolarisation (phase 3)
-HCN mediates a ‘funny current’, stimulates K+ efflux, Na+ influx
-Na+ influx dominates causes slow depolarisation of membrane
-Reaches threshold, upstroke inactivates HCN
what happens during Phase 0
Ca2+ influx, upstroke of the slow pacemaker action potential
triggers at the threshold potential (~55mV)
Increase in movement of Ca2+ into cell
what happen during Phase 3
Ca2+ channels inactivated
delayed K+ efflux, increase in K+ efflux
causes hyperpolarisation
give the five steps of ventricular myocyte action potential
0) Na+ channel open
1) Na+ channel close, Fast K+ channel open
2) Ca2+ channel open, Fast K+ channel shut
3) Ca2+ channel close, slow K channels open
4) resting potential
how does the sympathetic nerves affect the heart rate
-Activation cause release of noradrenaline (binds to B1 adrenoreceptors on cardiac pacemakers and myocyte cell membrane
- increases opening of HCN channels in pacemaker cells
- increase Na+ influx and and Ca2+ influx increases
-increase slope of pre potential (phase 4)
=heart rate increases
How does the parasympathetic nerves affect the heart rate
-Activates the release of ACh (binds to muscarinc receptor)
-decrease opening HCN channels which decrease Na influx, and slows the opening of Ca2+ channel which decreases influx
-opens additional K+ channels (ligand-gated) which increases K+ efflux
-Hyperpolarises membrane and reduce slope of pre-potential
=heart rate decrease
How does vagal tone affect heart
-decrease heart rate
what two things affect heart rate
-vagal tone
-sympathetic tone
-intrinsic rate of firing of SAN cell = 100-110 APs
What is early after depolarisation
occurs when normal HR is low, suppressed by high heart rate
Occurs when AP is prolonged
-some Ca2+ channels inactivated during shoulder
-reactivates to give EAD
what is delayed after-depolarisation
seen at increased HR, associated with elevated calcium concentration
- Ca2+ activation of Na/K channel (depolarising)
-NaCa exchanger 3:1 electrogenic
- can cause toxic doses of cardiac glycosides
what is used to treat bradycardias
Atropine
Isoproterenol
Artifical pacemaker
what does atropine do
switch off vagal nerve, blocks vagal inhibition of sinuous and AV node
what does isoproterenol
activates B receptors (beta agonists)
what is adenosine used to treat
tachycardia
what is the mechanism of action for adenosine
dilates coronary vessels
reduces B adrenergic receptor mediated increase in myocardial contractility
depresses both sinoatrial and atrioventricular node activities
what is used to treat a-systole (heart electrical system fails entirely)
adrenaline + epinephrine
What is used to treat ventricular fibrillation
amiodarone + lignocaine
what are the adverse effects of atropine
anticholinergic = dry mouth, mydriasis
postural hypotension
how many class of antiarrhthymiac drugs are there which treats tachycardia
4
what is Class I drugs
Na channel blockers (2 classes)
what is an example of Class Ia drug and what is the mechanism of action
= quinidine, propatenone
lengthens action potential duration and refractory period
what is an example of Class Ib drug and what is the mechanism of action
=lidocaine
shorts action potential duration and refractory period
-blocks fast Na channels and slows phase 0 depolaristion
specifci effect on rapidly depolarising tissue (use dependent effects)
what are lidocaine adverse effects
hypotension, heart block, neurotoxicity, fits
what are the contra-indications of lidocaine
-Hepatic clearance decreased in elderly, people with heart failure and liver disease
Not absorbed via oral route and have a short half life
what are the two types of Beta-blocker
-Non cardioselective = also blocks B2 receptors = Propranolol
-Cardioselective= less potent blocks of B2 receptor =
Atenolol (B1 selective)
how do beta blockers treat tachycardia
-reduce intrinsic rate in sinus and AV node
-decreases Heart rate, blood pressure and cardiac work
-reduce renin secretion
what are the adverse effects of beta blockers
B1 effects = bradycardia + heart failure
B2 effects = excerbation of asthma, cool peripheries, muscular aches, worsening intermittent claudication
Others= Fatigue, Nightmare/sleep disturbances, withdrawal effects (angina & MI), Unawareness of hypoglycaemia
what is example of class III AntiArrhythmic and how do they work?
Amioderone = K+ channel blockers
prolongs action potential and refractory period, lengths QT interval
what is the indication for using a class III AA drugs
effective for ventricular and supra ventricular tachycardia
1st line treatment for ventricular fibrillation
improves survival in patients with recurrent ventricular tachycardia
what are the adverse effects of amioderone
-Thyroid disturbance
-Pulmonary fibrosis
-Pro-arrhythmias and torsade de points
-peripheral neuropathy
-hepatitis
-blue-grey skin discolouration
There are three subtypes for calcium channel blockers (Class IV)
- Dihydropyridines = predominately vascular effects
- Benzothiapines = mixed vascular + cardiac effects
- Phenylalkylamine = predominantly cardiac effects
what is the most prescribed Ca2+ channel blocker to treat arrhtythmias
verapamil (a Phenylalkylamine)
how does verapamil work
Slows phase 1/2 which slows calcium entry
reduce rate and conduction velocity in sinus and AV nodes
What are the adverse effects of verapamil
heart failure, hypotension, constipation, vasodilation, oedema and flushing
what is the contraindication for verapamil
myasthenia gravis
