Flashcards in L16. Drugs affecting Heart Rate and Dysrhythmias Deck (30):
What is the parasympathetic influence on the heart?
Parasympathetic: Regulating role in resting HR (rest and digest system)
Acts via ACh on Muscarinic Receptors
Affect the RATE on both the SA and AV nodes
By affecting K+ channels
What is the sympathetic influence on the heart?
Sympathetic is important to recruitment in Flight of Fight mode
Acts via adrenaline and noradrenaline on the heart and vasculature (mainly by B1 receptors)
On the SA node and on myocardial cells to affect the RATE and the FORCE of contractility
Tachycardia and positive INOTROPIC action
By affecting Ca+ Channels
What does the electrical activity of the heart depend on?
The balance and operation of ion channels
Describe the sino-atrial pacemaker action of the SA cells
Cells of the SA node have pacemaker activity meaning they depolarise spontaneously (no need to an action potential trigger) at a regular rate.
Without regulation it beats at 100 beats per minute
What is the resting membrane for a SA pacemaker cell?
-60 mV meaning that it is greatly negative on in the inside of the cell vs. positive on the outside. (There is a tendency for positive ions to flow into the cell)
Draw the SA action potential and describe the phases of it
Phase 0: Depolarisation where Ca channels open and flow into the cell
Phase 3: Repolarisation: K+ channels open and let K+ out
Phase 4: Spontaneous depolarisation (pacemaker) that lets Na and Ca in
How does the parasympathetic nervous system affect the atrial action potential?
ACh transmission to Muscarinic receptors of the heart leads to the opening of K channels: extends repolarisation
This leads to more K flowing out to the cell meaning it is harder for the Na and Ca to flow.
ACh binds to GPCR and decreases cAMP
= takes longer to reach threshold
How does the sympathetic nervous system affect the atrial action potential?
Noradrenaline and adrenaline bind to B1 receptors (GPCRs) leading to increased cAMP and opens Calcium channels
Opening Calcium channels speeds up the depolarisation phase (steeper slope of phase 4)
= increased rate of firing from the SA node
Risk: trigger dysrhythmia
What is the resting membrane potential of ventricular cells?
Much lower than atrial at -90 mV (takes more energy for Na and Ca to move through) and hence a more rapid depolarisation is required to reach threshold.
Draw and describe the phases of the ventricular action potential,
Phase 0: Rapid Depolarisation: Na channels in
Phase 1: Rapid repolarisation: K+ out
Phase 2: Plateau: Ca in and K out
Phase 3: Repolarisation: K+ out (Ca channels close)
Phase 4: Stable membrane potential
What does the term dysrhythmia mean? What are the signs and symptoms of it?
An abnormal rhythm of heart beating
Palpatations, can be more forceful contractions or dropped beats.
Can either be benign or fatal
Symptomes are nonspecific: shortness of breath, fainting, fatigue, chest pain
What are the three main mechanism of dysrhythmia formation?
1. Altered FORMATION of the impulse
2. Altered route/BLOCKAGE of the impulse
3. Triggered events
What affects the formation of the impulse?
- Automacy of the pacemaker cells damaged or altered
- Abnormal generation of APs at sites other than the SA (or AV) nodes
What are the mechanisms of conduction block?
1. Damage or death of cells making up the conduction pathway (Eg. Infarction)
2. SA failure means the AV node has to pick up the automated setter of pace (slower rate)
3. Reentry: impulses flow backwards through the system (creating loops) through damaged tissue: increased rate and/or extra beats
What are some considerations when treating dysrhythmia?
Consider the no treatment option (many treatment drugs have arrhythmic activity)
Make an accurate diagnosis (ECG)
Manage underlying causes of the arrhythmia
What are the major drug classes used to treat Dysrrhymia?
1. Na channel blockers (3 subclasses)
2. Beta adrenoreceptor antagonists
3. K channel blockers
4. Ca channel blockers
- Adenosine, cardiac glycosides, electrolyte supplements
- DC shock and defibrillation
- Implantable pacemakers
What are the Na Channel Blockers aiming to achieve in dysrhythmia? (Class I)
Extend the time for depolarisation (reduce the slope of phase 0) by making it difficult for Na to enter the cell (and depolarise it)
Three types: depending on the degree of blockage
What is the effective refractory period? (ERP)
The period of time between depolarisation (phase 0) and repolarisation (end of phase 3) where the cell is unable to respond to another action potential/trigger.
What are the three subclasses of Na channel blockers?
All of them decrease the slope of phase 0 (depolarisation)
1. Quinidine: moderate block that prolongs repolarisation (increases ERP)
2. Lidocaine: mild block (decreases ERP by shortening repolarisation)
3. Flecaninide: strong block (doesn't affect ERP or repolarisation)
What are the adverse effects of Na channel blockers?
Dose-dependent side effects: Diarrhoea, nausea, headache and dizziness are also common side effects
IA: Tachycardia, dry mouth, constipation, Numbness, CVD depression: has low therapeutic window
IC compounds can cause increased risk of sudden death in patients with a prior history of myocardial infarction or sustained ventricular arrhythmias.
Depends on the method of administration
What do the beta adrenoreceptor antagonists aim to do in dysrhythmic patients? (Class II)
Decrease the rate and conduction of the SA (and AV) nodes by inhibiting sympathetic influence on cardiac activity.
- decrease sinus rate, conduction velocity
- membrane stabilising effects
What is an example of beta blockers used for dysrhythmia?
Non selective: propanolol and nadolol
B1 selective: Atenolol and metoprolol
What are the adverse effects of beta blockers?
Bradycardia, reduced exercise capacity, hypotension, AV conduction blockage
Bronchoconstriction (for some non-specific types of blockers - cannot be used for asthmatics) and hypoglycemia
What is the aim of administering K channel blockers for patients with dysrhythmia? (Class III)
Block K out and so make it difficult for the cell to repolarise: prolongs phase 3
By prolonging the action potential there is a decrease of re-entry
What is the risk in prolonging phase 3 by K channel blockers?
It increases the period where the cell is excitable and risks triggered events.
Give an example of a K channel blocker used in dysrhythmia
Amiodarone: which also blocks Na and Ca and B adrenoreceptors
What are the adverse effects of K channel blockers?
Reversible photosensitisation, skin discolouration,
Amiodarone has Class I, II, III and IV actions and has potentially dangerous side effects like pulmonary fibrosis and hypothyroidism
What are the Ca channel blockers seeking to achieve? (Class IV)
Reduce the rate of conduction by acting on SA and AV nodes (cardioselective)
Block L-type calcium channels located on the vascular smooth muscle, cardiac myocytes, and cardiac nodal tissue (SA and AV). They also regulate pacemaker currents and in phase 0 of the action potentials.
Therefore they cause vascular smooth muscle relaxation, decreased myocardial force generation (negative inotropy), decreased heart rate (negative chronotropy), and decreased conduction velocity within the heart (negative dromotropy).
What is an example of Ca channel blockers?