P: Drugs for Heart Failure and Dysrhythmias - Week 5 Flashcards
Name the 2 locations in the heart that have cels that can generate rhythmic activity. Which site is the principle site?
- sino-atrial Node (SA node): principle site
- atrio-ventricular node (AV node)
Which site in the heart is responsible for setting the heart rate?
SA node
How does the sympathetic division of innervation affect the SA node?
makes the SA node fire faster, because it allows more sodium into the cells, so it’ll get to the threshold for action potential more quickly
How does sympathetic and parasympathetic stimulation affect contractility of the heart?
parasympathetic = little to no effect
sympathetic = increased contractility due to increased calcium. The higher calcium results in a harder/stronger contraction (the muscles squeeze more forcefully)
List the steps on the hypertension continuum
hypertension – endothelial dysfunction – atherosclerosis – CAD – myocardial ischaemia – coronary thrombosis – stroke, myocardial infarction – arrhythmia and loss of muscle – remodelling – ventricular dilation – congestive heart failure – end stage hear disease
For the parasympathetic division of neural control of HR and contractility, describe the following:
A: location
B: receptor and neurotransmitter used
C: mechanism
D: effect on heart rate/contractility
A: SA node and AV node
B: Acetylcholine; Muscarinic (M2) receptors
C: Gi reduces cAMP, opening K+channels
D: decreases heart rate only
For the sympathetic division of neural control of HR and contractility, describe the following:
A: location
B: receptor and neurotransmitter used
C: mechanism
D: effect on heart rate/contractility
A: SA node, conducting tissue and myocardial cells
B: Noradrenaline; Beta-1 receptors (also circulating hormone - adrenaline)
C: Gs increases cAMP, increases Ca2+
D: increases heart rate AND contractility
What can over-stimulation of the sympathetic division of neural control of heart rate and contractility lead to?
dysrhythmia
Describe the SA cells
a group of specialised cells that have an unstable membrane potential
Do excitable cells tend to have higher or lower membrane potential? What does this mean?
Lower membrane potential (around -80 to -90mV). This means that most of the ions aren’t moving and you have ‘electrochemical stability’
Compare the resting membrane potentials of the SA node and Ventricle of the heart (phase 4)
SA node: -60mV; unstable membrane potential
Ventricle: -90mV; stable
Describe the depolarisation process of the SA node, including the phases
spontaneus depolarisation. If (I-funny) occurs and sodium and calcium come in. then:
Phase 0: depolarization, calcium in
Phase 3: repolarization, potassium out
Describe the depolarisation process of the ventricle, including the phases
Phase 0: Rapid depolarisation, Na+ and some CA2+ in
Phase 1: rapid repolarisation, K+ out
Phase 2: plateau Ca2+ in, K+ out
Phase 3: repolarization, K+ out
Describe the 4 major classes of drugs used to control heart rate, their molecular mechanisms and their outcomes:
- Class 1 - Na+ channel block (reduce phase 0 depolarization)
- Class 2 - B-adrenoceptor antagonism (slow the rate)
- Class 3 - K+channel blockade (extended repolarization phase)
- Class 4 - CA2+ channel blockade (affects refractory period)
Name and describe the unclassified drugs that can be used to control heart rate
Atropine: increase HR by blocking ACh
Adenosine: similar to parasymp stimulation
Cardiac glycosides
Electrolyte supplements
Why should you consider the no treatment option for arrhythmia?
Many arrhythmics have proarrhythmic activity and may worsen arhhythmias and cause sudden death
How do Na+ channel blockers target the corresponding Na+ channels
They selectively target the region where Na+ channels are open more frequently
In what state do Na+ channel blocker drugs typically bind Na+ channels?
They bind Na+ channels in their activated (open) state = ‘use-dependent channel block’
How can we further classify Na+ channel blocker drugs?
Based on dissociation time of drug from channel
Class 1a: moderate Na+ channel block
Class 1b: mild
Class 1c: marked Na+ channel block (so i guess blocks it a lot)
How does Lignocaine act as a Na+ channel blocker?
provides a rapid blockade of activated and inactivated Na+ channels
For what purpose is lignocaine typically used?
- often used in px post myocardial infarction. Is also used intravenously in emergency situations
Also used for ventricular dysrhythmias and fibrillation
Describe the outcome/effect of lignocaine
- depresses conduction and excitability in heart (slows it down, allowing cells a chance to recover)
- local anaesthetic actions on all excitable cells
List 5 adverse effects for lignocaine in order of increasing dosage that causes it
4ug/ml: lip and tongue numbness
7ug/ml: visual disturbance
8ug/ml: muscular twitching
15ug/ml: coma
25ug/ml: cardiovascular depression
How can we more safely apply lignocaine as an anaesthetic?
topically. But if it gets into systemic circulation, it’ll affect cardiac exciteability and sensory + motor nerve function