Arrhythmia Flashcards
What controls the cardiac muscle contractions?
Pacemaker cells ≈ self-excitable (autorythmic) ≈ SAN in RA (by sulcus terminalis, between SVC and coronary sinus) ≈ myogenic ≈ determines HR ≈ chronotropy
What adjusts the control of contractions?
Hormonal, neuronal and local factors ≈ ∆ SAN ≈ ∆ adjacent cell depolarisation + contraction ≈ depolarisation propagation wave ≈ ∆ contractility ≈ ∆ chronotropy + inotropy + lusitropy
What are the three types of cardiac action potentials and what are the distinguished by?
Distinguished by spontaneous pacemaker activity + speed of depolarisation
1) Pacemaker potentials
- Spontaneous depolarisation
- Slow depolarisation
- Driven by calcium slowly
2) Non-pacemaker potentials
- Rapid depolarisation
- Driven by sodium rapidly and prolonged by calcium
3) His-Purkinje potentials
- Rapid depolarisation
- Spontaneous depolarisation
- Driven by sodium rapidly and prolonged by calcium
What is the membrane potential changes in nodal tissue?
Sinoatrial node depolarisation occurs through 3 phases with a unique waveform
- No true resting potential
- Regular, spontaneous APs
- Depolarising currents carried by L-type CaVG
- Slower AP ≈ ’slow response AP’
Phase 1: If ≈ Na+ open at -60mV ≈ Na+ in;
-50mv ≈ T-type CaVg open ≈ Ca++ in;
Phase 2
-40mV ≈ L-type CaVf open ≈ Ca++ in
Phase 3
+ 20mV ≈KVg open ≈ K+ efflux ≈ repolarisation
What is the membrane potential changes in atrial and ventricular cardiac tissue?
Phase 0: - Rapid depolarisation due to NaVg opening at -75mV ≈ gNa+ ≈ Na+ in
Phase 1: - NaVg close ≈ reduced gNa+
Phase 2: - L-type CaVg open @ 10mV ≈ gCa++ ≈ Ca++ in ≈ plateau
Phase 3: - Rapid repolarisation: gCa++ ≈ increased IC Ca++ ≈ K+ channels open ≈ gK+ efflux - L-type CaVg close ≈ reduced gCa++
Phase 4: - Stable resting membrane potential where gK+ > gNa+ (50:1)
What is the effect of hypoxia on heart rate and why?
Cellular hypoxia ≈ depolarises the cell ≈ ∆ phase 3 hyper-polarisation ≈ reduced pacemaker rate ≈ bradycardia
What effects do the respective functional divisions of the ANS have on pacemaker activity?
1) PSNS: Vagus nerve (CN X) —> SAN + AVN
- ACh @ M2R ≈ Gai ≈ reduce cAMP ≈ reduce rate of phase 0 depolarisation + hyperpolarise membrane potential (= increase extent + duration of opening of K+ channels ≈ increase gK+)
2) SNS: Sympathetic chain ≈ sympathetic nerves —> atria + ventricles
- NA @ ß1R ≈ Gas ≈ increase cAMP ≈ increase rate of phase 0 depolarisation ≈ increase gCa++ + increase gNa+ via funny channels
What is the electrical conduction pathway in the heart?
Coordinated electrical activity: pacemaker activity of SAN (RA) ≈ initiate process ≈ depolarisation spreads due to functional syncytium (electrically connected via GAP junctions) ≈ SAN in RA —> internodal pathway + interatrial pathway —> AVN (critical delay ≈atrioventricular flow) —> L + R Bundle of His (interatrial septa) —> Purkinje fibres
What is a dysrhythmia (arrhythmia)?
Conditions where co-ordinated sequence of electrical activity in the heart is disrupted ≈
- ∆ in heart cells
- ∆ in conduction of impulse through heart
- ∆ in heart cells + ∆ impulse conduction through heart
What are the classifications of dysrhythmias (arrhythmias)?
Dysrhythmias (arrhythmia) classified by origin site of abnormality + speed (tachycardia or bradycardia)
- Atrial (supra-ventricular)
- Junctional (associated with the AV node)
- Ventricular - Tachycardia or bradycardia
What are the four broad categories of event which can be used to physiologically classify a dysrhythmia (arrhythmia)?
- Ectopic pacemaker activity (Intrinsic ability to set AP)
- Delayed after-depolarisations (pumping out Ca++ and Na++ in via NCX and Na+, K+-ATPase where Na+ out and K+ in ≈ cell trying to pump calcium out and sodium in h/e ∆ pumps ≈ increased Na+ ≈ increased depolarisation AP during plateau period)
- Circus re-entry (impulses pass down conduction pathway h/e block in impulse circulating tissue)
- Heart block (Nodal tissue block ≈ atria and ventricles beat at different rhythms)
How are antidysrhythmic drugs classified?
Vaughan Williams system
How can the Vaughan Williams System for Antidysrhythmic drugs be transposed onto the action potential of a cardiomyocyte?
Vaughan Williams system can go on anti-clockwise to the cardiomyocyte action potential
Class 1 @ Na+ (stage 0)
- Lidocaine
- Procainamide
- Flecainide
Class 2 @ K+ rectifier (stage 4)
- Bisoprolol
- Atenolol
- Propanolol
Class 3 @ K+ out (Stage 3)
- Amiodarone
- Sotalol
Class 4 @ Ca2+ in (Stage 2)
- Diltiazem
- Verapamil
When do sodium channel blockers work?
Binds domains of voltage-gated sodium channels ≈ block if ion channels in open state (use-dependent sodium channel blockers), refractory or resting
What are the clinical uses of class 1 antidysrhythmics?
Sodium channel blockers
What are the indications for Procainamide (class 1a)?
- Ventricular dysrhythmia
- Prevention of recurrent atrial fibrillation triggered by vagal overactivity
What are the indications for Lidnocaine (class 1b)?
- Treatment and prevention of ventricular tachycardia
- Treatment of ventricular fibrillation during and immediately after MI
What are the indications for Flecainide (class 1c)?
- Suppress ventricular ectopic beats
- Prevent paroxysmal AF associated with abnormal conducting pathways
- Prevent recurrent tachycardias associated with abnormal conducting pathways
Which class of Sodium channel blockers is the best blocker?
1c e.g. flecainide
Which class of Sodium channel blockers is the best at increasing the refractory period?
1a e.g. procainamide
What is the MOA ß-blockers?
Competitive antagonist of ß1-adrenoceptor ≈ reduced cAMP production≈ reduced PKA ≈ reduced +Pi with Ca++-ATPase ≈ reduced contractility of cardiomyocytes
Block ß1 receptors ≈ block depolarisation of pacemaker cells; reduced calcium entry in phase 2 of cardiac action potential; increased refractory period of AV node (prevent recurrent attacks of supra-ventricular tachycardias) ≈ reduced chronotropy and inotropy ≈ reduced CO
What are the clinical uses of ß-blockers?
Give an example of a ß-blocker
Sotalol, bisoprolol, atenolol
- Post-MI (reduce mortality)
- Prevent recurrence of tachycardias increased by sympathetic activity
What are the MOA of potassium blockers? (Class 3 in Vaughan Williams System)
- Drug goes into ion channel ≈ closure of activation gate ≈ stabilises channel in the inactivation forms
Amiodarone: prolongs the cardiac action potential by prolonging refractory period
What impact does a Potassium channel blocker have on the action potential?
Increases the refractory period
Which drug is indicated in the treatment of WPW Syndrome?
Amiodarone
What are the indications for Amiodarone Rx?
- Tachycardia associated with WPW Syndrome
- Supraventricular tachycardia + ventricular tachyarrhythmia
What are the indications for Sotalol Rx?
- Supraventricular dysrhythmias
- Suppresses ventricular ectopic beats + short runs of ventricular tachycardia
What is the MOA of calcium channel blockers?
CCBs (rate-limiting) e.g. Verapamil or Diltiazem ≈ block cardiac voltage-gated L-type calcium channels ≈ slow conduction through nodal tissue reliant on calcium currents (SAN + AVN) ≈ shorten plateau of cardiac AP and reduce force of contraction of the heart
What are the clinical uses of class 4 drugs regarding arrhythmias?
- Prevent recurrence of SVTs
- Reduce ventricular rate in patients with atrial fibrillation provided they do not have WPW
Which drug is contraindicated in Wolff-Parkinson White Syndrome?
Verapamil due to impulses coming down BoK causing ventricular tachycardia/fibrillation
Why would diltiazem be dangerous to give in Wolff-Parkinson-White Syndrome?
Diltiazem is used to block L-type CaVg ≈ reduce depolarisation in nodal tissue however in WPW Syndrome ≈ Bundles of Kent provide alternative pathway ≈can cause ventricular fibrillation ≈ deadly
How does adenosine work?
Produced endogenously ≈ binds A1 adrenoreceptor ≈
i) Go ≈ linked to cardiac potassium channels ≈ hyper polarises cardiac conducting tissue ≈ slows heart rate ≈ decreases pacemaker activity
ii) Gi ≈inhibits Gs ≈ reduced AC activation ≈ reduced cAMP ≈ reduced PK phosphorylating calcium ≈ reduced calcium influx
What is the MOA of digoxin?
Cardiac glycoside ≈ increase vagal efferent activity to heart ≈ parasympathomimetic ≈ reduces SAN firing rate + reduces conduction velocity of electrical impulses through AVN ≈ reduced chronotropy + reduced dromotropy
What happens if there is an increased concentration of digoxin?
Toxic concentrations ≈ inhibits Na+,K+-ATPase ≈ reduced effect of Na+ out ≈ electrochemical gradient ∆ ≈ increased Na+ IC ≈depolarisation + firing rate of AP ≈ ectopic beats
