Pharmacology Of Rhythm Control Flashcards
What is transmembrane potential?
Voltage difference across the cell membrane.
What is resting transmembrane potential?
Accumulation of negatively charged ions in a cell, maintained between -70mv to -90mv, determined by the accumulation of ions in a cell.
What are the phases of an action potential in a cardiac myocyte?
Phase 4
Phase 0
Phase 1
Phase 2
What is Phase 4 of an action potential?
Resting membrane potential, typically at -90mv in a cardiac myocyte. In this state, only K+ channels are open.
What is Phase 0 of an action potential?
Depolarisation stage where transmembrane potential becomes more positive due to opening of fast Na+ channels and influx of Na+ allows it to reach +30mv.
This triggers the Na+ channels of other cardiac cells to open and creates a wave of depolarisation.
What is Phase 1 of an action potential?
Fast Na+ channels close and slow K+ channels open to allow K+ efflux, causing a drop in the membrane potential.
What is Phase 2 of an action potential?
Plateau phase where slow K+ channels remain open but fast Ca2+ channels open. Entry of Ca2+ into cardiac myocyte causes the release of storage Ca2+ molecules from the sarcoplasmic reticulum and further increase in the positive intracellular concentration of ions.
What is Phase 3 of an action potential?
Hyperpolarisation/Repolarisation stage where Ca2+ channels close, but slow K+ remains open, and excess K+ efflux causes membrane potential to fall below -90mv
What is the refractory period?
Recovery period between action potentials to protect the neuron from repetitive stimulation.
What are the phases of an action potential in the SAN?
Phase 4: influx of Na+
Phase 0: influx of Ca2”+
Phase 3: influx of K+
What is automaticity?
Spontaneous activity by cells of the Sinoatrial node of the heart in phase 4 activity to generate action potentials and allow gradual changes in heart rate due to refractory periods. The SA node has the fastest phase 4 activity.
What is repolarisation?
Phases 1-3 in a cardiac myocyte which gradually returns the membrane potential back to the resting of the -90mv following depolarisation.
What is the location of the SA node?
In the right atrium at the junction with the Superior Vena Cava. It is responsible for establishing heart rate, maintained between 60-100 bpm.
What is the location of the AV node?
RIght atrium, found in the wall of the posteroinferior atrial septum. Maintains heart rate when SA node is non-functional between 40-60bpm
What is the location of the Purkinje fibres?
Located throughout the ventricles, that can maintain a heart rate of 20-40bpm.
What is the absolute refractory period?
Occurs following depolarisation where the neuron cannot produce new action potential cannot occur, even with a large stimulus. This period ends at the early part of depolarisation.
What is the effective refractory period?
The absolute refractory period in cardiac cells. There is a very small segment in phase 3 where a stimuli can cause minimal depolarisation, but not enough to propogate.
What is the relative refractory period?
Greater than normal stimulus is required to generate an action potential
What is the supranormal period?
Occurs in early phase 4 following relative refractory period, where the cardiac myocyte is in a highly excitable state that a weaker stimulus will cause a propagating action potenital.
This stage makes cardiac cells sensitive to arrythmias, therefore timing action potentials is important during electrical cardio version to avoid this.
What is the classification of anti-arrhythmic drugs?
Vaughan-Williams classification:
Class 1 drugs that block the Na+ channels.
Class 2 drugs that are beta blockers
Class 3 drugs that are K+ channel blockers
Class 4 drugs that are L-type calcium channel blockers
They alter action potentials and have the potential to worsen pre-existing arrhythmia, called proarrythmia.
What are Class 1 anti-arrythmia?
They generally block phase 0 Na+ channels to prolong repolarisation. It is divided into
Class 1a
Class 1b
Class 1c
They have the potential to lengthen the refractory period.
What are the Class 1a anti-arrythmic drugs?
Moderately block Na+ and K+ channels to block depolarisation and prolong repolarisation, which increases the effective refractory period.
Drugs in this class are Quinidine, Procainamide and Disopyramide.
What are the Class 1b anti-arrythmic drugs?
Lidocaine, Phenytoin, Mexiletine and Tociamide
They have a mild blocking effect on Na+ channels in phase 0, shortening the action potential. They shorten the repolarisation by blocking late phase Na+ channels in phase 2.
What are the Class 1c anti-arrythmic drugs?
Flecainide, Propefanone and Encainide.
They have a strong blocking effect on fast Na+ channels but they also inhibit the His-Purkinje system.
What are the Class 2 anti-arrythmia drugs?
Beta blockers which depress the SA node to reduce automaticity and contractility, in order to improve myocardial blood flow for oxygen demand and supply.
What are the non selective beta blockers?
Propranolol, timolol and nadolol.
What are the selective beta blockers?
Bisoprolol, metaproplol and atenonlol which act only on B1 receptors.
What are the Class 3 anti-arrythmia drugs?
Blocks phase 3 K+ channels to increase the duration of action potentials and the effective refractory period.
Amiodarone is a Class III used in supraventricular tachycardia and ventricular tachycardia.
What are the side effects of amiodarone?
Amiodarone is a Class III anti-arrythmia which blocks phase 3 K+ channels, but also blocks Na+ and Ca2+ channel.
It can lead to pulmonary fibrosis, cyanosis of skin and corneal microdeposits.
What are the Class 4 anti-arrythmia drugs?
Non dihydropyridine calcium channel blockers which are specific act centrally in the myocardium to reduce heart rate by preventing calcium influx during depolarisation .
Examples of this include amlodipine,verapamil and diltiazem which are used to treat supraventricular tachycardia and atrial fibrillation
What are the side effects of Class IV antiarrythmics?
They block non-dihydropyramidine receptors for Ca2+, reducing inotropy and pumping of heart.
Side effects are ankle oedema, face flushing, low blood pressure, slower heart rate and gastrointestinal—oesophageal disease.
What are the class 5 antiarhythmic drugs?
Atypical drugs such as adenosine, digoxin and magnesium sulphate.
How does digoxin work?
It inhibits the Na+/K+ ATPase pump which reduces heart rate and this increases activity of the Na+/Ca2+ exchanger. The increase in intracellular Ca2+ will increase inotropy.
Digoxin stimulates the parasympathetic vagus nerve for slower heart rate that is stronger.
When is digoxin used?
For patients with atrial fibrillation, atrial flutter or congestive heart failure. It has a long elimination time and a low therapeutic index, meaning it becomes toxic at low blood concentrations.
What are the side effects of digoxin?
It can lead to GI disturbances, gynaecomastia, abnormal cardiac rhythms, electrolyte imbalances and CNS disturbances.
How does adenosine work?
Acts on adenosine A1 and A2 receptors to on the AV node to inhibits AV node conduction, conduction velocity by inducing K+ influx and inhibiting Ca2+ influx. It’s given for supraventricular tachycardia.
When should Class 3 antiarrythmic drugs be avoided?
Class III antiarrythmic blocks K+ channels in phase 3.
—>Pregnancy
—>Severe bradycardia
—>Cardiogenic shock
—>Moderate to severe heart failure
When should Class 2 anti-arrythmia drugs be avoided?
Class II anti-arrythmia are beta blockers:
—>Asthma
—>Cardiogenc shock
—>Hypotension
—>AV block
—>Phaemochromocytoma which is untreated
What is lidocaine?
Class 1b antiarrythmic which mildly blocks Na+ channels and reduces the length of the refractory period. It is given for ventricular tachycardia when amiodarone is ineffective. It can cause paraesthesia, muscle twitching and seizures.
What is amiodarone?
Class 3 antiarrythmic drug which blocks potassium channels, and can also block Na+ channels, Ca2+ channels and beta-adrenergic receptors.
It is used to treat supraventricular tachycardia and ventricular tachycardia and has a slow onset but is a lipid-soluble drug.
What are the side effects of amiodarone?
Abnormal cardiac rhythm,
Causes corneal microdeposits
Contains iodine and can lead to hypothyroidism and hyperthyroidism
Pulmonary fibrosis
Skin cyanosis to a blue colour
Abnormal liver function test
How are tachyarrthmias treated?
Electrical cardioversion
Valsalva Manoeuvres
Medication
How is bradycardia treated?
Assess patients for any reversible causes such as:
Isoprenaline
Glucagon
Digoxin toxicity
Theophyllines
Use of pacing
