Drugs Affecting HR & Arrhythmias Flashcards
Describe the parasympathetic control of HR?
Targets: SA node & AV node
Chemical Transmitter: ACh
Receptors: Muscarinic
Response: slows rate (bradycardia)
The effect of muscarinic receptor blockade on HR in healthy young men shows that with administration of a drug like atropine, heart rate increases with dose.
Describe the sympathetic control of HR?
Targets: innervates SA node, conducting tissue and myocardial cells.
Chemical Transmitter: NA; circulating hormones- adrenaline
Receptors: beta-adrenoceptors
Response: increase HR (tachycardia); Increases force (+ inotropic effect)
The effect of Beta- adrenoceptor blockade with a drug such as propanolol on HR in healthy young men is that HR decreases with dosage.
In terms of HR, which nervous system has more input?
Parasympathetic innervation has a greater influence on resting heart rate.
Briefly explain the neural control of HR?
- Parasympathetic division decreases rate - muscarinic receptors
- Sympathetic division increases rate - adrenoceptors
- Autonomic nerves regulate intrinsic pacemaker activity of the heart
Explain parasympathetic slowing of the SA node.
- Parasympathetic division decreases rate - muscarinic receptors
- Sympathetic division increases rate - adrenoceptors
- Autonomic nerves regulate intrinsic pacemaker activity of the heart
Explain the sympathetic acceleration of the SA node.
NA (and Adrenaline)
- beta1-adrenoceptors
- G-protein coupled: increase cAMP leading to opening of Ca2+ channels
Ca2+ entry:
- increased slope of phase 4 depolarisation (SA & AV nodes)
- increased rate of firing (SA node) and more rapid conduction (AV node): can trigger dysrhythmias
What are the typical phases of the ventricular action potential?
Resting membrane potential: -90mV
Phase 0: depolarisation; Na+ in Phase 1: rapid repolaraisation; K+ out Phase 2: plateau; Ca2+ in, K+ out Phase 3: repolarisation; K+ out Phase 4: stable membrane potential
What is an abnormal cardiac rhythm?
Dysrhythmia (Arrhythmia): any variation from the noraml rhythm of the heart beat
- described as palpitation or fluttering in chest
- sensed by more forceful contraction after a missed beat
- at least inconvenient and at worst fatal
Symptoms: shortness of breath, fainting, fatigue, chest pain
Proper diagnosis requires ECG: rhythm (flutter/fibrillation) & rate (bradycardia/ tachycardia)
What are some possible mechanisms for underlying dysrhythmias?
Altered impulse formation:
- automaticity of pacemaker cells
- abnormal generation of action potentials at sites other than the SA node
Altered impulse conduction:
- conduction block: ventricles adopt own slower rate
- re-entry: extra beats increase rate
Triggered activity:
- early or late after-depolarisation: excess sympathetic activation
There are four main classes of anti-dysrhythmics, what are they?
- sodium channel blockers
- beta-adrenoceptor antagonists
- potassium channel blockers
- calcium channel blockers.
Explain the class of drug: Na+ Channel Blockers
Effect ventricular action potential: Class 1a (quinidine) - moderate Na+ block - prolongs repolarisation - increases ERP
Class 1b (lignocaine)
- mild Na+ block
- shorten repolarisation
- decreases ERP
Class 1c (flecainide)
- marked Na+ block
- same repolarisation
- no effect on ERP
Concentration-dependent Side-effects:
Local anaesthetic - safe with topical/local application
Explain the class of drug: Beta-Adrenoceptor Antagonists
Inhibit sympathetic influence on cardiac electrical activity
- prevent beta1-adrenoceptor effects on SA and AV nodes
- decrease sinus rate, conduction velocity and aberrant pacemaker activity.
Membrane stabilizing effects in Purkinje Fibres
- similar to Class 1 antiarrhythmics
Adverse effetcs:
- bradycardia, reduced exercise capacity, hypotension, AV conduction block
- bronchoconstriction, hypoglycaemia
Explain the class of drug: K+ Channel Inhibitors
Prolong cardiac action potential
- slowing of Phase 2 repolarisation
- decrease incidence of re-entry
- increase risk of triggered events
Example: Amiodarone
- also blocks Na+, Ca+ and beta-adrenoceptors
- reversible photosensitization, skin discoloration and hypothyroidism
- pulmonary fibrosis with long term use.
Explain the class of drug: Ca2+ Channel Blockers
Cardioselective Ca2+ channel Blockers (Verapamil) act preferentially on SA & AV nodal tissue
- Ca2+ for initiation of action potential
- atrial tachycardias
- Slow conduction velocity and increased refractoriness
- Facial flushing, peripheral oedema, dizziness, bradycardia, headache, nausea.
What are some strategies for managing dysrhythmias?
Always consider the no treatment option: many antiarrythmics have proarrythmic activity and may worsen arrythmias and cause sudden death
Before starting treatment:
- make an accurate diagnosis
- where possible manage underlying causes such as drugs, ionic balance, ischemia, infarct or fibrosis.
Other drugs and approaches incude:
- adenosine, cardiac gylcosides, electrolyte supplements
- DC shock, defibrillators
- implantable pacemakers
