Drugs affecting heart rate and arrhythmias/dysrhythmias Flashcards
Arrhythmia
Absence of rhythm
Dysrhythmia
Abnormal rhythm
What are the PSNS targets of the heart to control rate?
SA & AV nodes
What is the chemical transmitter for PSNS control of heart rate?
What is the pathway?
What is the target tissue receptor?
Acetylcholine
- Preganglionic (SC)
- ACh onto postganglionic nicitonic receptors
- ACh onto muscarinc receptors (M2, GPCR)
- decreased HR
Muscarinic receptor (SA)
What does PSNS ACh stimulation do to heart rate?
Slows/bradycardia
ACh acts on M2R to decrease cAMP, opening K+ channels
K+ efflux slows Na+ and Ca2+ in, delays repolarization, tf takes longer for SA to reach threshold
**M2R is GPCR**
What does SNS NA(+Adr) stimulation do to heart rate?
Increases/tachycardia, +contractility
NA acts on B1-aR to increase cAMP, opens Ca2+ channels, Ca2+ influx
Ca2+ influx in Phase 4 depolarization increases slope @ SA & AV - tf reach threshold faster, +firing rate, +conduction (rate and rhythm)
*can trigger dysrhythmias*
**B1-aR is GPCR(stimulatory)**
Atropine
- Muscarinic antagonist
- PSNS: blocks muscR, +HR (~60bpm)
At rest, in normal healthy individuals, neural drive comes significantly from the
PSNS
What are the SNS targets of the control of heart rate?
innervates SA node
conducting tussue
myocardial cells
What is the chemical transmitter for SNS control of heart rate?
What’s the ganglionic pathway?
What is the target tissue receptor?
Noreadrenaline (+ circulating adrenaline)
- Preganglionic neurons release ACh onto NicR
- Postganglionic neurons release NA onto B-aR (B1, GPCR) and myocardial cells
- +HR, +contractility
- +circulating adrenaline also activates alpha and B-aRs, w/ different selectivity to
Beta-adrenoceptors
What are the primary ativations by the SNS and PSNS at the heart?
PSNS - rate
SNS - rate and contractility
Noreadrenaline
- SNS: at B-aR, +HR, +contractility
alpha-1 adrenergic receptors
In smooth muscle (skin, sphincters, kidney, brain, bladder/uterus)
mediate contraction
activation = vasoconstriction
alpha-2 adrenergic receptors
In brain and spinal cord
Vascular smooth muscle cells of certain blood vessels (skin arterioles, veins)
Binds NA from SNS postganglion and adrenaline from adrenal medulla
beta-1 adrenoceptors
Cardiac tissue, cerebral cortex, kidney
Increase CO (+HR at SA, +contractility)
+renin from juxtaglomerular cells
Lipolysis in adipose tissue
beta-2 adrenoceptors
Smooth muscle (bronchi, GIT, uterus)
blood vessels (vasodilation)
Heart (+contraction, +CO, +HR @SA +contractility)
Proranalol
- Beta blocker/antagonist
- SNS: -HR (~10bpm)
What is unique about the resting potential the SA node?
It’s unstable due to a unique leaky Na+ channel which causes an I-funny current and spontaneous depolarization (Phase 4)
~60mV - +20mV
Ivabradine
- Targets SA leaky Na+ channels
- Trialled for angina - primary effect on rate
- Potential use for some dysrhythmias
Phase 0 of the SA action potential is
Ca2+ influx causing depolarization
(this is in contrast to ventricular APs where its Na+)
Phase 3 of the SA AP is
repolarization
K+ out
Same as ventricular AP
What is the resting membrane potential of the ventricular myocyte AP?
-90mV
Stable
Phase 4
What is Phase 0 of the ventricular AP?
Depolarization by Na+ influx
(remember: pacemaker cells use Ca2+ here)
What is Phase 1 of the ventricular AP?
Rapid repolarization by initial K+ efflux w/Ca2+ influx fighting K+ to extend AP
What is Phase 2 of the ventricular AP?
Plateau; Ca+ in and K+ out
What is Phase 3 of the ventricular AP?
Ca2+ gives up fighting against K+ coming out; tf get replarization by K+ efflux
Symptoms of dysrhthmia are
Shortness of breath, fainting, fatigue, chest pain
How does altered impulse formation cause dysrhythmia?
- abnormal pacemaker cell function
- abnormal AP generation (at sites other than SA)
- due to: changes in ionic environment or electrochemical balance; fibrosis (leads to oedmea)
How does altered impulse condiction cause dysrhythmia?
- Conduction block: ventricles beat, nothing from SA –> generate their own rhythm, rely on AV; causes slower rate
- Re-entry: circulation of electrical activity, sometimes localized; extra beats increase rate (Wolf-Parkinson-White: Bundle of Kent, extra pathway, can lead to re-entry)
How does triggered activity cause dysrhythmia?
- Early or late adter-depol, excessive SNS activation
- Stray currents in refractory period cause EADs by some active Ca2+ channels letting Ca2+ in; NA can do this
- Ca2+ overload can cause LADs in post-refractory relaxation phase (SNS overactivity)
What are the 4 major classes of antidysrhythmics?
- Na+ channel blockers
- B-aR antagonists
- K+ channel blockers
- Ca2+ channel blockers
What are the three types of Na+ channel blockers?
- 1A: moderate
- 1B: weak
- 1C: strong
How does a Class 1a Na+ channel blocker affect the ventricular AP?
e.g. quinidine
- moderate/intermediate block
- prolong repolarization
- increased effective refractory period (ERP)
- slows tachydys
How does a Class 1b Na+ channel blocker affect ventricular AP?
e.g. lignocaine
- Mild block
- Shortens repolarization (K+ channel)
- Decrease ERP
- Affects contraction quality (smaller APs)
Lignocaine
- Class 1b (mild) Na+ block (shortens repolarization and ERP)
- Local anaesthetic
- Intravenous antiarrhythmatic (ER)
How does a Class 1c Na+ channel blocker affect the ventricular AP?
e.g. flecainide
- Strong block
- Decreases slope of Phase 0 the most
- Repolarization stays the same
- No effect on ERP
What is the main action of Na+ channel blockers on the ventricular AP?
Reduce the Phase 0 (depolarization) slope and tf the peak
Variably change ERP
What is the main action of B-aR antagonists as antidysrhythmics?
Decrease rate and conduction
- inhibit SNS influence
- prevent B1aR effects on SA & AV
- decrease sinus rate
- decrease conduction velocity
- decrease aberrant pacemaker activity
- membrane stabilizing in Purkinje fibres (local anaesthetic type activity)
- can block Na+ channels too
What is the main action of K+ channel blockers as antidysrhythmics?
Delay Phase 3, prolong duration
- Stop K+ leaving
- Prolong AP through delayed Phase 3 repolarization
- decrease incidence of re-entry
- increase risk of triggered events (E/LADs) because prolonged Phase 3 allows greater potential Ca2+ interference
What is the main action of Ca2+ channel blockers as antidysrhythmics?
Reduce rate and conduction at SA and AV nodes
- Cardioselective: SA & AV tissue, Ca2+ channels
- Stop initiation of AP
- limit tachy
- slow conduction velocity
- increase refractoriness
What are the adverse effects of B-aR antagonist antidysrhythmics?
- bradycardia
- reduced exercise capacity
- hypotension
- AV conduction block
- bronchoconstriction
- hypoglycemia
Amiodarone
- Blocks K+ (antidysrhythmic), Na+, Ca2+ channels
- Blocks B-aR
Adverse effects:
- reversible photosensitization
- skin discolouration
- thryroid problems
- LT: pulmonary fibrosis
What are the adverse effects of Ca2+ channel blocker antidysrhythmics?
- facial flushing
- peropheral oedema
- dizziness
- bradycardia
- headache
- nausea
