Block B Lectures 2 & 3 - Anti-arrhythmic Drugs Flashcards
What heart rate thresholds are considered irregular bradycardia and irregular tachycardia?
Irregular bradycardia - heart rate is below 60 b.p.m
Irregular tachycardia - heart rate is above 100 b.p.m
(Slide 4)
What are 5 examples of cardiac arrhythmias symptoms?
Answers Include:
Palpitations
Heart failure symptoms (such as edema)
Fatigue
Dyspnoea (breathing difficulties)
Dizziness
Angina
Syncope (fainting)
No symptoms! (helpful I know…)
(Slide 5)
What are 3 examples of things which can cause cardiac arrhythmias?
Ectopic beats
Heart block
Re-entry phenomenon
Note: These are all classified to the site of impulse formation or the site and degree of the conduction block
(Slide 6)
What are ectopic beats / automaticity?
Beats which arise from fibres or groups of fibres which are outside the normal pacemaker region (the sinoatrial (SA) node), leading to arrhythmias.
(Slide 6)
What is heart block?
An obstruction (block) in the heart’s electrical conduction system
(Slide 6)
What is re-entry phenomenon?
The return of the same impulse into a zone of the heart muscle which has been recently activated
(Slide 6)
What are 5 ways which cardiac arrythmias can be treated?
Pharmacological therapy
Direct Current (DC) cardioversion
Pacemaker therapy
Surgical therapy
Interventional therapy (ablation)
(Slide 7)
What is a Direct Current (DC) cardioversion?
a procedure which uses a defibrillator to deliver a controlled electric shock to your heart in order to try and return your heart rhythm back to normal.
(Slide 7)
What is a cardiac ablation?
A treatment for cardiac arrythmias, it uses thin, flexible tubes called catheters and heat or cold energy to create tiny scars in the heart. The scars block the faulty signals that cause irregular heartbeats.
(Slide 7)
What is a refractory period?
The time following excitation during which a second action potential cannot be elicited and conducted
(Slide 9)
What is membrane responsiveness?
The relationship between membrane activation voltage and the maximal rate of rise of the action potential
(Slide 9)
What 2 ways do antiarrhythmic drugs treat arrythmias?
They increase the refractory period, or slow the upstroke (rapid depolarisation phase) of action potentials, or both
(Slide 10)
What are electrical signals carried by?
Ions, such as Na+, K+ or Ca2+
(Slide 11)
Are sodium and calcium usually at high concentration inside or outside the cell?
Outside
(Slide 13)
Is potassium usually at a high concentration inside or outside the cell?
Inside
(Slide 14)
What does the occurrence of action potentials depend on?
The timing of the opening of Na+ and K+ channels, which itself is controlled by the membrane potential
(Slides 15 - 18)
How do sodium channels and the membrane potential make a positive feedback loop?
As when the membrane potential becomes positive, voltage gated sodium channels open, resulting in sodium flowing in, increasing the membrane potential, which opens even more sodium channels and so on
(Slide 17)
What are the steps of a non-cardiac action potential?
- Once membrane potential hits a threshold value, voltage gated Na+ channels open resulting in rapid depolarisation.
- Once membrane potential gets too positive, the Na+ channels close and voltage gated K+ channels open, resulting in repolarisation.
- The K+ channels stay open too long and membrane potential drops to below resting potential
- The K+ channels close and ion gradients (such as the Na+/K+ ATPase) restore resting membrane potential
(Slide 19)
What is responsible for the propagation of an action potential?
An action potential is responsible for its own propagation
(Slides 21 - 24)
What does the threshold value of an axon refer to?
The membrane potential at which an action potential is triggered
(Slide 24)
What is the speed at which an action potential moves along an axon called?
Its “conduction velocity”
(Slide 27)
What are the phases of a cardiac potential (0-4)?
Phase 0: Once the cell membrane potential hits a threshold value, rapid depolarisation occurs due to voltage gated Na+ channels opening
Phase 1: The Na+ channels inactivate, and potassium channels open, transporting potassium out of the cell resulting in a small repolarisation
Phase 2 (aka the plateau phase): Ca2+ channels open, allowing calcium to enter the cell. However the membrane potential change this causes is balanced out by K+ ions moving out of the cell
Phase 3: The Ca2+ channels close, but the potassium channels remain open, resulting in membrane potential decrease back to resting potential
Phase 4: Some potassium channels stay open, maintaining resting potential. Na⁺/K⁺ ATPase and Na⁺/Ca²⁺ exchangers restore ion gradients.
Phase 4 (Pacemaker cells): No true resting membrane potential exists in these cells and instead the membrane potential slowly rises towards threshold again. This is done by sodium and calcium channels opening, and potassium channels closing.
(Slide 29)
What cells are considered “pacemaker cells”?
Sinoatrial and atrioventricular cells
(Slides 29 and 30)
What is the difference between sinoatrial node and atrioventricular node cells compared to atrium, bundle of his and ventricle cells?
Sinoatrial node and atrioventricular
node cells are “slow conductor” cells which mainly use calcium channels during their action potential upstrokes
Atrium, bundle of his and ventricle cells are “fast conducting” cells which mainly use sodium channels
(Slide 30)
What is the consequence of sinoatrial node and atrioventricular node cells primarily using calcium channels to depolarise and atrium, bundle of his and ventricle cells primarily using sodium channels to depolarise?
That the sinoatrial and atrioventricular node cells can be targeted with calcium channel blockers and the atrium, bundle of his and ventricle cells can be targeted with sodium channel blockers
(Slide 30)
What are the 2 phases of the refractory period?
The absolute refractory period: Sodium channels are inactivated and no matter what stimulus is applied they will not re-open to allow sodium in and depolarise the membrane to the threshold of an action potential.
The relative refractory period: some of the sodium channels have re-opened from inactivation but the threshold is higher than normal, making it more difficult for the activated sodium channels to raise the membrane potential to the threshold of excitation
(Slide 31)
What is the Vaughan Williams classification of anti-arrhythmic drugs, and what phase of the cardiac cycle do they all target?
Class 1(blanket term): Fast sodium channel blockers which vary depolarisation and action potential duration. They target phase 0.
Class 1 is made up of classes 1A, 1B and 1C.
Class 2: Beta blockers. They target phase 2 and phase 4 (pacemaker cells)
Class 3: Potassium channel blockers. They target phase 3.
Class 4: Calcium channel blockers. They target phase 2.
(Slides 32 and 33)
What are 5 side effects which class I (or subclasses 1A, 1B and 1C) antiarrhythmic drugs can cause?
Answers Include:
Nausea
Vomiting
Haemolytic Anaemia (body breaks down blood cells faster than they can be replaced)
Thrombocytopenia (low platelet count)
Tinnitus
Lupus (body attacks healthy tissues)
Dizziness
Confusion
Seizures
Comas
Tremors
Ataxia
Rashes
Pro-arrythmia
(Slide 33)
What are 3 side effects which class II antiarrhythmic drugs can cause?
Answers Include:
Coronary Heart Failure
Bronchospasm
Bradycardia
Hypotension
(Slide 33)
What are 3 side effects which class III anti-arrhythmic drugs (like amiodarone) can cause?
Answers include:
Hepatitis
Pulmonary fibrosis
Thyroid disorders
Peripheral neuropathy (damaging of peripheral nerves)
Bronchospasm
(Slide 33)
What are 3 examples of side effects which class IV anti-arrhythmic drugs can cause?
Answers Include:
Atrioventricular block
Hypotension
Bradycardia
Constipation
(Slide 33)
What is an example of each class of antiarrhythmic drug?
Class 1: Quinidine (1A), Lidocaine (1B), Flecainide (1C)
Class 2: Propranolol, metoprolol
Class 3: Amiodarone, sotalol
Class 4: Verapamil, Dilitiazem
(Slide 33)
Which class of antiarrhythmic drug is stronger, 1A or 1C?
1C
(Slides 35 and 36)
What effect do class I antiarrhythmic drugs have and how do they do this?
They inhibit sodium channels, and reduce the rate of rise of an action potential (phase 0), slowing conduction velocity and some increase the refractory period.
(Slides 35 and 36)
What effect do class II antiarrhythmic drugs do and how do they do this?
They are beta blockers, they decrease cardiac automaticity and contractility partly by blocking β-adrenergic receptors and partly by direct effects on cardiac cell membranes.
They also have an antagonistic effects regarding catecholamines acting on calcium channels, which results in reduced automaticity of the heart, slows conduction in partially depolarised cells and decreases myocardial contractility.
(Slide 37)
What effects does the class III antiarrhythmic drug amiodarone have and how does it do this?
It inhibits potassium channels, which delays repolarisation, but also slightly inhibits sodium and calcium channels as well as blocking β-receptors (non-competitively) as well as α-receptors. These effects result in a strongly reduced ectopic automaticity.
(Slide 38)
What do class IV antiarrhythmic drugs like verapamil and diltiazem do?
They block L-type calcium channels, which results in a decreased sinoatrial and Purkinje fibre automaticity and slowing conduction through these. It also increases the refractory period of the atrioventricular node.
(Slides 39 and 40)
What are inotropic drugs?
A type of medication that helps the heart contract with more or less force
(Slide 42)
What are digoxin and digitoxin, and what do they do?
They are cardiac glycosides which increase the contractile force of the heart and are usually given to patients with atrial fibrillation.
They inhibit the Na+/K+-ATPase which is responsible for Na+/K+ exchange across the muscle cell membrane, which results in an increase in intracellular sodium, which results in an increase in intracellular calcium, which results in an increased force of myocardial contraction
(Slide 42)
What is an indirect effect of digoxin, and what does this lead to?
It increases vagal nerve activity, which facilitates muscarinic transmission to the heart.
This leads to a slowed heart rate and atrioventricular conductance and also prolongs the refractory period of the atrioventricular node.
(Slide 44)
