L 58 Pharmacology of Dysrhythmia/HF/AF Flashcards
What is a dysrhythmia?
What are the 3 levels?
A disruption of cardiac electrical conduction, primarily at 3 levels:
- Autonomic NS
- Cardiac conduction systems
- Heart muscles (e.g myocyte ion channels)
How does blood get pumped around the body?
How many times per minute? (avg)
The blood gets pumped around the body by contraction of the atria and ventricles via depolarisation.
This occurs around 60 times per minute.
2 determinants of heart rate
Parasymp and symp systems
Parasympathetic effects on heart rate
Decreases heart rate
Sympathetic effects on heart rate
Increases HR and contraction force
What is the determinant of heart rhythm?
The cardiac conduction system that innervates the myocytes.
Depolarisation creates an … …
Physiologically, an … … causes the muscle to … and to … blood.
Depolarisation causes an action potential
Physiologically an action potential causes the muscle to contract and to pump blood.
Difference between action potential and ECG reading
Action potential occurs in an individual cell.
An ECG detects the overall electrical activity of the heart at the skin surface, which is the sum of all the cardiac cells firing.
According to the Vaughan Williams classification, what are the follow 4 classes:
Class I: Class II: Class III: Class IV: Class I: sodium channel blockers Class II: beta adrenergic blockers Class III: potassium channel blockers Class IV: calcium channel blockers
Name 3 class I agents
Quinidine
Lidocaine
Flecainide
Name 4 class II agents
Metoprolol
Bisoprolol
Sotalol
Carvedilol
MoA of B blockers in dysrhythmias
Where to B blockers bind?
To decrease HR and conduction velocity which increases the refractory period.
B blockers bind to receptors in SA and AV nodes, conducting tissues and myocytes.
What is the most commonly used B blocker in arrythmias?
… is also commonly used.These 2 are only used for specific indications…
Metoprolol = most commonly used
Bisoprolol = also commonly used
Sotalol and carvedilol = only used for specific indications.
How do class III agents work?
Their main effect is to delay repolarisation and increase the ERP, which makes the celll less excitable
Examples of class III agents
Amiodarone Sotalol (which is also class II)
Where can you see the effects of class III agents on an ECG?
You will see an increase in the QT interval.
5x examples of Class IV agents
Which are NOT used? Why?
DHPs: amlodipine, felodipine, nifedipine (not used as antiarrythmatics as they are selective for vascular Ca2+ channels)
Diltiazem
Verapamil
What is the main site of action for class IV agents? What is their MoA?
Main site: SA and AV nodes
MoA: to decrease conduction velocity and prolong repolarisation
What are the other effects of class IV agents? x3
Vasodilation, negative inotrope, decreased HR
MoA of diltiazem
Binds to both vascular and myocardial Ca2+ channels, so is a vasodilator and cardiac depressant
Verapamil is selective for…
It is also used in…
Verapamil = selective for myocardium
Is also used in angina as well as an antiarrhythmatic
Action of amiodarone (+ class)
Indications
PK: (absorption/bioavail, t0.5, metabolised by …)
Block potassium channels in cardiac tissues (Class III)
Indications: rhythm control, tachyarrythmias
PK:
- Absorption and bioavail vary between people.
- T0.5 = ~14-59 days
- Metabolised by CYP3A4 and CYP2C8
Interactions of amiodarone
Inhibits many CYP enz, and reduces clearance of many drugs (warfain, statins, dabigatran)
Important side effects of amiodarone x5
Blue-grey skin discolouration Thyroid toxicity (hypo/hyperthyroidism) Pulmonary fibrosis Arrythmias (bradycardia, heart block, TdP) Increased LFTs
Action of flecainide (+ class)
Indications
Blocks Na+ channels in cardiac tissue (class 1c) Indications: rhythm control for supraventricular and ventricular arrythmias.
Special populations for flecainide
Cap the dose in elderly and those with renal/hepatic impairment
Important side effects of flecainide x2
Proarrhythmic, HF exacerbation
Action of sotalol (+ class)
Indications
B blocker and blocks potassium channels (Class II and III)
Indications: rhythm control but NOT used for rate control
Important side effects fo sotalol
When to avoid sotalol
Drug interactions with sotalol:
Side effects: proarrythmia
Avoid in: HF and severe renal impairment, asthma
Drug interactions: cardiodepressant CCBs
What is the main fact about PK for sotalol?
Requires dose adjustment in renal disease as it is excreted unchanged by kidneys
Examples of drugs that cause or exacerbate arrhythmias (non-exhaustive list, but x5)
Anti-arrythmics Macrolides Some quinolones Antipsychotics Hydroxychloroquine
