ELM 15: Dysrhythmias - VW drug classification Flashcards
Risk factors for dysrhythmias
- Too much alcohol
- Smoking
- Genetics
- Obesity
- Congenital abnormalities
What is an arrhythmia?
Absence of rhythm
What is a dysrhythmia?
Disturbance in rhythm
What are the 3 main effects of Sympathetic Autonomic Nervous System on the Heart
- Increase slope of pacemaker potential in SA node (Inc HR)
- Increased force of contraction due to Inc intracellular Ca2+
- Increased conduction velocity through AV node
What do the different components of an ECG trace represent?
P wave = Atrial activation
QRS complex = Ventricular activation
T wave = Recovery wave
What is wolff-parkinson-white syndrome
- Congenital abnormality with an accessory AV pathway
- Global re-entry circuit
- No rate limiter in kent bundle so causes atrial and ventricular fibrillation
What is heart block?
- Form of bradycardia
- Damage to AV node impairs atrial to ventricular conduction
3 degrees:
1 = slow conduction, PQ increased and QRS for every P wave
2 = miss QRS complexes
3 = impulses dont get from atria to ventricles
What is paroxysmal supraventricular tachycardia?
- Re-entry circuit through AV node
- Starts at teens-40s
- Ventricular rate of 250bpm
What is the Singh-Vaughan Williams system for antidysrhythmic drugs?
Divides antidysrhythmic drugs according to mechanism of action
What is the target and examples of Class I antidysrhythmic drugs?
- Sodium channels
1a = Disopyramide
1b = Lidocaine
1c = Flecainide
What is the target and examples of Class II antidysrhythmic drugs?
Beta 1 adrenoceptor
- Atenolol
- Bisoprolol
- Propranolol
What is the target and examples of Class III antidysthrythmic drugs?
Potassium channels
- Amiodarone
- Sotalol
- Dronedarone
What is the target and examples of Class IV antidysrhythmic drugs?
Calcium channels
- Verapamil
- Diltiazem
What is the target and examples of unclassified antidysrhythmic drugs?
Various targets
- Adenosine
- Atropine
- Digoxin
What are some weaknesses of the Vaughan Williams classification system?
- Some drugs have multiple action sites
- Action sites can be different in healthy and diseased tissue
- Doesn’t include lots of useful drugs
- Some dysrhythmias can be treated with drugs form more than one class
What is a more modern alternative system for the Vaughan Williams system?
Lei et al system
Has 7 classes
How do Class IA dysrhythmic drugs work?
EG Disopyramide
- Moderate Na+ channel block
- Blocks K+ efflux
- Increased effective refractory period
- Increase action potential duration
How do Class IB antidysrhythmic drugs work?
EG Lidocaine
- Weak Na+ channel block
- Promotes K+ efflux
- Decreased effective refractory period
- Decreased action potential duration
How do Class IC antidysrhythmic drugs work?
EG Flecainide
- Strong Na+ channel block
- No effect on K+ efflux
- No change in effective refractory period
- No change in action potential duration
What are the characteristics of the Class IA drug disopyramide?
- Intermediate dissociation rate
- Prevent ventricular and supraventricular dysrhythmias
- Used after heart attack or defibrillation
What are the side effects of Class Ia drug disopyramide?
- GI tract problems
- Arrhythmias
- Cognitive problems
- Visual problems
- Urinary disorders
- Hypotension
- Contraindicated in heart block and severe heart failure
What are the characteristics of the class Ib drug licodaine?
- Binds to inactivated sodium channels
- Fast dissociation
- Also used as local anaesthetic
- Given intravenously to suppress ventricular dysrhythmias
- Used after defibrillation
What are some side effects of the class Ib drug lidocaine?
- CNS excitation
- CNS depression at high doses
- Bradycardia, hypotension and dysrhythmias
- Contraindicated in Wolf-Parkinson-White, severe heart block
What are some characteristics of class Ic drug flecainide?
- Slow dissociation
- Used for supraventricular and ventricular arrhythmias under specialist supervision
What are some side effects of class Ic drug flecainide?
- Dysrhythmias
- Oedema
- Visual disturbances
- Contraindicated after heart attack as it increases risk of sudden death
What are the characteristics of class II drug atenolol?
- Reduces automaticity, slows SA and AV node conduction
- Useful in dysrhythmias triggered by SNS activation like atrial fibrillation and supraventricular tachycardias
- Prevents dysrhythmias after heart attack
- Used for thyrotoxicosis
What are the side effects of Class II drug atenolol?
- Bronchoconstriction
- Precipitation of heart attack failure, block
- Masks sympathetic signs of hypoglycaemia in T1 diabetes
- Decreased mobilisation of glucose from glycogen in diabetes
- Decreased insulin sensitivity in T2 diabetes
- Can cause cold extremities and raynauds
What is the mechanism of the Class III drug amiodarone?
- In class III as a K+ channel blocker but also inhibits beta adrenoceptors and sodium channels and blocks calcium channels
- Blocks potassium channels to delay repolarisation
- Increased action potential duration and refractory period
- Decreased AV node conduction velocity and re-entry tendency
What are the indications for class III drug amiodarobe?
- Used in range of dysrhythmias
- Given orally or IV
What are some side effects of class III drug amiodarone
- Worsen bradycardias or AV node block
- Cause TdP
- Analogue of thyroxine and can interfere with thyroid function
- Cause lung fibrosis
- Deposited in eye and causes visual problems
- Liver toxicity
- Deposited in skin and causes blue gray colour when exposed to UV
- Long 100 day plasma half life
- Long time to reach steady state
What are the indications for Class IV drug verapamil?
- Oral, IV formulations
- Prevents or terminates PSVT
- Controls ventricular rate in AF
- Angina, hypertension, cluster headaches
What are some side effects of Class IV drug verapamil?
- Headache constipation flushing and hypotension
- Contraindicated in Wolf-parkinson-white, bradycardia, heartblock
- Broken down by CYP3A4 in body
What is CYP3A4?
- Cyt P450 enzyme expressed in liver and intestines that metabolises drugs
- Irreversibly inhibited by furanocoumarins found in fruit
- Inhibition can cause overdose on prescription drugs
Examples of drugs broken down by CYP3AR
Ritonavir
Diazepam
Sertraline
Verapamil
What is the mechanism of the unclassified drug adenosine?
- Can bind to 4 GPCR subtypes
- A1 A2A A2B A3
Which pathways are used by the 4 GPCR subtypes adenosine can bind to?
A1 = Gi via GIRK KACh
A2a A2b = Gs
A3 = Gi/Gq
What are the indications of the unclassified drug adenosine?
- Short 10 second plasma half life
- Rapid uptake by RBC and metabolism
- Suppresses PSVT, ventricular tachycardia with WPW syndrome, supraventricular tachycardias in surgery
What is the mechanism of the unclassified drug digoxin
- Directly blocks sodium pump
- Indirectly blocks sodium/calcium exchange
- Increases calcium in stores which causes more contraction force
- Stimulates PNS
- Increases AV node refractory period but decreases it in myocytes
- Increases force of contraction, slows ventricles for better filling
What are the indications for unclassified drug digoxin?
- Heart failure
- Persistent atrial fibrillation
What is the mechanism of unclassified drug atropine?
- Competitive antagonist at M2 receptor
- M2 receptor slows heart rate so inhibition will increase heart rate
What are the indications of unclassified drug atropine?
- IV in bradycardia and heart block
