39 - Drugs Affecting Heart Rate, Dysrrhythmias Flashcards
Parasympathetic targets on the heart
SA node, AV node
Receptors on heart for parasympathetic nervous system
ACh muscarinic receptors
Heart response to parasympathetic stimulation
Bradycardia
How is it proven that there is a tonic level of sympathetic and parasympathetic stimulation of the heart?
Antagonising parasympathetic (atropine) or sympathetic (atenolol) causes increase or decrease in heart rate, respectively.
Parts of heart innervated by sympathetic nervous system
SA node, conducting tissue, myocardial cells
Receptors on heart for sympathetic stimulation
Beta adrenoceptors, stimulated by noradrenaline, or circulating adrenaline
Response to sympathetic stimulation of heart
Increase heart rate, increase force of contraction
Effect of ACh on the heart
Reduces heart rate
Does antagonising parasympathetic or sympathetic innervation have more effect on heart rate?
Parasympathetic
SA node pacemaker lowest membrane potential
-60mV
Phases of SA node depolarisation 1) 2) 3)
1) Phase 0 - Depolarisation. Ca2+ enters cell 2) Phase 3 - Repolarisation. K+ exits cell 3) Phase 4 - Spontaneous depolarisation. Na+, Ca2+ enter cell
Membrane channels responsible for phase 4 of Sa node depolarisation 1) 2)
1) If Na+ channel. Leak channel. 2) Ica. Calcium channel
Membrane channels responsible for phase 0 of SA node depolarisation
Ca2+ channels
Membrane channels responsible for phase 3 of SA node depolarisation
K+ channels
*Shape of SA node depolarisation
How does parasympathetic stimulation slow heart rate 1) 2) 3) 4) 5)
1) Muscarinic M2 receptors stimulated 2) G-protein attached to M2 decreases cAMP levels, leads to K+ channel opening. 3) Na+, Ca2+ channel fluxes slowed 4) Slowed phase 4, as slower to reach threshold for depolarisation. 5) Rate of conduction through heart is also slowed
How does sympathetic stimulation increase heart rate? 1) 2) 3) 4)
1) NA stimulates beta-adrenoceptor. 2) G-protein attached to adrenoceptor increases cellular cAMP, increasing Ca2+ channel opening 3) Increases slope of phase 4 in SA, AV nodes. 4) This causes increased firing (SA node), increased conduction time (AV node)
Potential side effect of sympathetic stimulation of heart
Dysrrhythmias
Resting ventricular membrane action potential
-90mV
Ventricular depolarisation 1) 2) 3) 4) 5)
1) Phase 0 - Depolarisation, Na+ into cell 2) Phase 1 - Rapid repolarisation, K+ out of cell 3) Phase 2 - Plateau, Ca+ into cell, K+ out 4) Phase 3 - Repolarisation, K+ out of cell 5) Phase 4 - Stable membrane potential at -90mV
*Shape of ventricular action potential
How are dysrrhythmias often detected?
Particularly forceful heart beat after missed beat
Symptoms of dysrrhythmias
Shortness of breath, fainting, fatigue, chest pain
How to properly diagnose dysrrhythmias
ECG. Look at rhythm (flutter, fibrillation), rate (bradycardia, tachycardia)
Mechanisms underlying dysrrhythmias 1) 2) 3)
1) Altered impulse formation. 2) Altered impulse conduction 3) Triggered activity.
Altered impulse formation 1) 2)
1) Abnormal generation of action potentials at sites other than SA node. 2) Impaired SA node action potential generation.
Altered impulse conduction 1) 2)
1) Conduction block - Failure to conduct action potential from atria to ventricles. Ventricles begin beating at own rate (~40bpm) 2) Re-entry - Extra beats from ventricles increase heart rate
Triggered activity
Early or late ventricular depolarisation after atrial depolarisation. If too much sympathetic stimulation, can result in depolarisation when cells are meant to be refractory
Four major classes of anti-dysrrhythmics
1) Na+ channel blockers 2) Beta-adrenoceptor antagonism 3) K+ channel blockade 4) Ca2+ channel blockade
Subtypes of Type 1 anti-dysrrhythmics 1) 2) 3)
1) Type 1a- Moderate block 2) Type 2a- Strong block 3) Type 3a- Weak block
Effect of type 1 anti-dysrrhythmics
Na+ channel blockade Reduce phase 0 slope and peak of ventricular action potential. Can alter effective refractory period
Effect of type 2 anti-dysrrhythmics
Beta adrenoceptor antagonism Decrease heart rate and conduction (SA node)
Effect of type 3 anti-dysrrhythmics
Delay phase 3 of ventricular action potential.
Effect of type 4 anti-dysrrhythmics
Ca2+ channel blockade. Most effective at SA and AV nodes. Reduce heart rate, contractility
Effect of type 1 anti-dysrrhythmic subtypes on effective refractory period 1) 2) 3)
1) Type 1a can increase effective refractory period 2) Type 1b decreases ERP 3) Type 1c has no effect on ERP
Lignocaine
Anaesthetic, anti-arrythmic.
Lignocaine effective dose for anti-arrhythmic activity
2-3ug/mL.
When is lignocaine used as an anti-arrythmic
Given as an IV in emergencies when need to restore heart rate quickly
How do class 2 anti-arrhythmics work?
Block sympathetic activity on SA and AV nodes (blockades adrenoceptors). Membrane stabilising in Purkinje fibres (inhibits Na+ channels, makes it harder to depolarise)
Adverse effects of class 2 drugs
– Bradycardia, reduced exercise capacity, hypotension, AV conduction block – Bronchoconstriction, hypoglycaemia
How do class 3 drugs work?
Prolong cardiac action potential by inhibiting K+ channels Slows phase 3 repolarisation. Decreases incidence of re-entry, but increases risk of triggered events
How do class 4 drugs work?
Cardioselective Ca2+ channel blockers. Act preferentially on SA, AV nodes. Slow conduction velocity, increase refractoriness
Side effects of type 4 drugs
Facial flushing, peripheral oedema, dizziness, bradycardia, headache, nausea
