Lecture 16 Flashcards
What is resting membrane potential?
The electrical potential across a plasma membrane is determined by two main factors:
- The distribution of ions across the membrane.
- The selective permeability of the cell membrane.
What is the major determinant of resting membrane potential?
Potassium
What is a fast depolarizing cell?
Cardiac myocyte - has a quick action potential
What is part of the intrinsic conduction system?
- Fast depolarizing cell
- Slow depolarizing cell
What drives cell excitation?
Autonomic sympathetic drive combined with intrinsin pacemaker
Where are slow depolarizing cells found?
SA/AV node
What are slow depolarizing cells?
Pacemaker cells
What causes an increase in membrane potential?
Influx of sodium, efflux of potassium
What is refractory period?
The cell has been activated, it cant be reactivated.
What is the absolute refactory period?
No response to excitary stimuli - cant be further activated. Good situation for cells
What is the relative refractory period?
Cell can be triggered to activate early
How to arythmia drugs affect the refractory period?
Dugs that extend refractory period
Thinking about sympathetic/ parasympathetic control of heart function. What would vagal nerve stimulation do to the resting membrane potential?
Make it become more negative
What is Tachyarrhythmia
> 100 bpm
Bradyarrhythmia
<60 bpm
What is Supraventricular?
Originating in the atrium or atrioventricular node
What is ventricular?
Originating in the ventricle
What is the narrow complex (QRS part)?
describes supraventricular
What is broad complex?
Describes ventricular
What is heart block?
Impulse origininating in the SA node is impeaded partially or completely
What is persisitant or paroxysmal?
Intermittent attacks - they come and go
What is the mechism of arrhythmias?
- Heart rate faster or slower
- Site of origin: supraventricular/ ventricular
- Complexxes on ECG: narrow/ broad
- Cardiac rhythm: regular/ irregular
How do we get an arrhythmias?
- Abnormal conduction: becomes slow or blocked - may be due to ischemia
- Abnormal automaticty: ischemic tissue becomes damaged and fires
- Re-enrty: circle of cells go round and fire off in addition to normal pacemaker
What must happen to the refractory period or the conduction velocity for re-entry to occur?
Refractory period must shorten. Conduction velocity must decrease. The conduction velocity is reduced due to depolarization. Cells are within refractory period.
What is conduction velocity?
Speed at which it moves
What is phase 0 of action potential of cardiac cells?
rapid depolarisation (inflow of Na+)
What is phase 1 of action potential of cardiac cells?
partial repolarisation (inward Na+ current deactivated, outflow of K+)
What is phase 2 of action potential of cardiac cells?
plateau (slow inward calcium current) - calcium interacts with myosin resulting in contraction
What is phase 3 of action potential of cardiac cells?
repolarisation (calcium current inactivates, K+ outflow)
What is phase 4 of action potential of cardiac cells?
pacemaker potential (Slow Na+ inflow, slowing of K+ outflow) ‘autorhythmicity’
What are class I antiarrhythmic drugs?
block sodium channels
- Ia (quinidine, procainamide, disopyramide) increaes AP
- Ib (lignocaine) decrease AP
- Ic (flecainide) elongates AP duration
Where do class II drugs have thier effect?
On nodal tissues (SA node)
How do the class II drugs work?
Rhythm control drugs - reduce rate of firing and sensitivity to noradrenaline
What are class II antiarrhythmic drugs?
ß-adrenoceptor antagonists (atenolol, sotalol)
- Important in the resting membrane potential
What are class III antiarrhythmic drugs?
prolong action potential and prolong refractory period (suppress re-entrant rhythms) (amiodarone, sotalol)
What are class IV antiarrhythmic drugs?
Calcium channel antagonists. Impair impulse propagation in nodal and damaged areas (verapamil)
Are beta blockers rate or rhythm controling drugs?
Rate control drugs
Give an example of a class IA sodium channel blocker?
Qunidine
Give an example of a class IB sodium channel blocker?
Lidocaine
Give an example of a class IC sodium channel blocker?
Flecanide
How do sodium channel blockers work?
The principal effect of reducing the rate and magnitude of depolarization by blocking sodium channels is a decrease in conduction velocity
How do beta blockers (Class II antiarrhythmic) drugs work?
- Inhibit sympathetic driven electrical activity
- Sympathetic drive increases conduction velocity
- Increases aberrant pacemaker activity (ectopic beats).
- Decrease sinus rate
- Decrease conduction velocity
-Increase APD and the ERP
What is the primary role of potassium channels in cardiac action potentials?
Cell repolarization
How do potassium channel blockers (Class III Antiarrhythmics) work?
- Block the potassium channels that are responsible for phase 3 repolarization
- Since these agents do not affect the sodium channel, conduction velocity is not decreased
- Prolongation of the action potential duration and refractory period, combined with the maintenance of normal conduction velocity, prevent re-entrant arrhythmias
Name three potassium channel blockers
-Amiodarone
- Sotalol
- Dronedarone
What are the therapeutic uses for amiodarone?
Supraventrular and ventricular arrhythmias
What are the therapeutic uses for sotalol?
Ventriclar arrhythmias; atrial flutter and fibrilation
What are the therapeutic uses for dronedarone?
Atrial flutter and fibrillation conversion, occasionally SVGT
What drives cell excitation?
Autonomic sympathetic drive combined with intrinsin pacemaker
What controls heart rate?
Sympathetic and parasympathetic influences
What controls heart rate at rest?
Parasympathetic
What are the sympathetic fibres?
Noradrenaline
Where does sympathetic fibre noradrenaline act?
B1 receptors
What happens when noradrenaline binds to B1 receptors?
Increase the permeability of the nodal cell plasma membrane to Na and Ca - increase the heart rate
What is the parasaympathtic fibre?
Aceytylecholine
Where does acytylcholine bind?
Muscarinic 2 receptors
What happens when acetylecholine binds to M2 recepyors
Increases the permeability to K and decreases the Na and Ca permeability so reduced heart rate
What affects pacemaker rate?
Tempertaure and Ph
What is vagal stimulation?
Parasympathetic innervation - acetylecholine acting on M2 receptors
What is the neuro-hormonal influences of parasympatehetic stimulation?
- Makes the resting potential more negative
- Pacemaker current slower
- Raise the threshold
What is the neuro-hormonal influences of the sympathetic stimulation?
Catecolamines make the resting potential more excited and speed up the pacemaker current and lower the threshold for discharge.
How does adenosine work?
- Negative inotrpic
- Reduce rate of firing
- Reduce conduction velocity
How does atropine work?
- Muscarininc receptor antagonist
- Reduce the effect of excessive vagal activation on the heart
- Negative inotrpic
- Redcuce rate of firing
- Reduce conduction velocity
What affect does digoxin have in heart failure patients?
- Increase inotropy
- Increase ejection fraction
- Decrease preload
- Decrease pulmonary congestion/ oedema
What affect does digoxin have in arrythmia patients?
- Decrease AV nodal conduction
- Decrease ventricular rate in atrial flutter and fibrillation
- Increased intracellular calcium lengthens phase 4 and phase 0 of the cardiac action potential, which leads to a decrease in heart rate
