308 Drugs used in arrhythmias Flashcards
What are the 2 types of cardiac cells?
contractile cells - which make up most of the walls of the atria and ventricles - when stimulated they generate force for contraction of the heart (myocyte)
conducting cells - initiate the electrical impulse which controls those contractions (automaticity). Found in SA node, AV node, His bundles and purkinje fibres
Why is the SA node the natural pacemaker of the heart?
It reaches membrane potential the fastest
Describe normal cardiac conduction
SA node action potential triggers atrial depolarisation
- AV node is the only pathway for AP to enter the ventricles
- The bundle of His and its branches conduct the impulse to the Apex of the heart
What are the areas of fast and slow conduction within the heart?
- Slow conduction: complete atrial systole before ventricular systole starts (SA/AV node)
- Fast conduction: His bundles and Purkinje fibres (ventricular depolarisation and contraction)
What causes arrhythmias?
-Changes in automaticity of the natural pacemaker
- Etopic foci causing abnormal APs
-excitable groups of cells that cause premature heart beats
-hypoxic/ischaemic tissue can undergo spontaneous depolarisation and can become an ectopic pacemaker
-the normal conduction pathway is interrupted
-abnormal conduction pathways
-electrolyte disturbances and drugs
What are the mechanisms of tachycardias?
Abnormal automaticity
- when membrane becomes abnormally permeable to sodium
- this can cause other cells to accelerate
automaticity thus generating impulses faster than the SA node
Triggered activity
- Anormal leakage of positive ions into cardiac cell leading to bump on action
potential called after depolarisation
- if sufficient magnitude can trigger premature AP, can lead to TdP
Re-entry
-Where an extra/accessory pathway exists
between upper and lower chambers of the heart
Eg. Wolf-parkinson-white syndrome
- AVNRT
- cardiac re-entry is responsible for the majority of clinically important arrhythmias
How can drugs cause arrhythmias?
- Suppressing enhanced automaticity
- Decreasing conduction velocity
- Changing the effective refractory period to suppress re-entry
What is the Vaughan Williams Classification?
Classifies antiarrhythmic drugs
agents by their ability to directly or indirectly block flux of one or more of these ions across the membranes of excitable cardiac
muscle cells
What are some class 1A agents in the Vaughan Williams Classification?
Disopyramide, quinidine (not licensed in
the UK), procainamide
Block fast sodium and potassium channels infast APs and depress phase 0, prolong repolarisation. Can prolong QRS duration and QT interval on the ECG: can be pro-arrhythmic
- Useful for supraventricular arrhythmias, and
ventricular arrhythmias
Only in patients with good ventricular function because of their negative inotropic effects
What are some class 1B agents in the Vaughan Williams Classification?
Lidocaine: causes weak blockade of fast sodium channels, shorten repolarisation and
therefore action potential
-Only used to treat ventricular arrhythmias (does not work on atrial tissues
or on normal cardiac tissues)
-Given by intravenous bolus followed by a continuous intravenous
infusion (high first pass metabolism)
Mexiletine: lidocaine’s orally active sister
-Do not prolong QT interval
-The most frequent side effects are CNS:
including tinnitus and seizures, and occasionally hallucinations, drowsiness,
and coma, nausea/vomiting with mexiletine
What are some class 1C agents in the Vaughan Williams Classification?
Propafenone, flecainide
Potent fast Na channel blockade
depress phase 0 depolarisation markedly and inhibits His/purkinje conduction system, with
limited effect on repolarisation period
- No effect on AP duration
- No effect on QRS length
- treatment of refractory ventricular arrhythmias
Flecainide: A potent fast inward sodium channel blocker used to treat symptomatic supraventricular arrhythmias
-Lowers ventricular function in most patients
-It also raises the threshold of pacing and cardiac defibrillators and should be used with caution in patients with
pacemakers or ICDs
What are some class 2 agents in the Vaughan Williams Classification?
Beta blockers
Competitive beta1 receptor blockade preventing action of catecholamines on the heart
-Depress sinus node automaticity, slows conduction in AV node which
causes reduction in heart rate and contractility
-Prolonged repolarisation phase, which helps reduce incidence of re-entry
-Increases diastolic filling time (chronotropy), reduces the force of
contraction (inotropy)
-Improves coronary perfusion
-Prolongs PR interval which may lead to 1st degree AV block
Give examples of class 2 Vaughan Williams Classification edications
-Propranolol
-Labetalol
-Atenolol
-Metoprolol
-Bisoprolol
-Nebivolol
-Carvedilol
-Esmolol
What are some side effects of beta blockers?
Side effects:
o Bronchospasm – Asthma and COPD
o Hypotension
o Bradycardia
o Cardiac failure
o Impotence
o Exacerbation of PVD
Overdose:
o Glucagon
o Temporary pacing
o Inotropic support
No proarrhythmic effects
What are some class 3 agents in the Vaughan Williams Classification?
Potassium channel blockers
Eg. Amiodarone, Dronaderone, Sotalo
Prolong repolarization phase by blocking outward potassium flux in phase 3 causing
prolonged refractory period
- leads to increase in duration of AP and decreases incidence
of re-entry - Anti-fibrillatory agents
- Useful in re-entry tachyarrhythmias (supraventricular)
What is amiodarone good for?
The “demestos” of anti-arrhythmics – kills all known arrhythmias
Also blocks, Na channels, calcium and even alpha and beta receptors (hence ++ SE’s)
What is the drug Sotalol good for?
has both Class II and Class III effects
= Beta-blocking effects and effects on prolonging the action potential
The combination of effects makes the drug effective in atrial and ventricular arrhythmias
When in sotalol contraindicated?
In patients with QT prolongation,
bradycardia, torsades, hypomagnesemia, hypokalemia, bronchospasm, pulmonary oedema, heart failure, or AV block
Drug combinations that enhance the pharmacological effects of sotalol (beta-blockade, QT prolongation, AV
blockade) should be used with caution
How does amiodarone work?
Structurally related to thyroid hormone, contains iodine
It has multiple function so is considered a ‘broad spectrum antiarrhythmic’
Used IV, amiodarone is superior to lidocaine (Lignocaine) and other agents for the treatment of ventricular arrhythmias
++ Drug-drug interactions
What are the side effects of Amiodarone?
-Pulmonary fibrosis / interstitial pneumonitis (2-15%)
-Hepatotoxicity
-Hyperthyroidism and hypothyroidism (2-24%; amiodarone is structurally similar to thyroid hormone and contains large
quantities of iodine) - need baseline TFTs and at 3-6 months, earlier if already have thyroid dysfunction
-Peripheral neuropathy (20-40%, but reversible by lowering
dose)
-Skin reactions (15-20%) including photosensitivity (10%), which can result in blue-grey skin colour, and various visual
disturbances (10%)
-Corneal microdeposits - virtually all patients on drug for more than 6 months develop these which can eventually interfere
with vision
What are some class 4 agents in the Vaughan Williams Classification?
Calcium channel blockers
More effective than Digoxin in controlling ventricular rate in patients with AC
- Relatively contraindicated in heart failure, impaired LV function, sick sinus
syndrome, heart block - ++CYP450 liver enzyme inhibitors therefore increased toxicity of many drugs
What is the drug adenosine used for?
For paroxysmal SVT
IV only, extremely short half-life
Used to terminate arrhythmias (blocks
re-entrant pathway)
How does the drug adenosine work?
stimulates A1 adenosine receptors on atrium, SA node and AV node
Decreased automaticity, decreased conduction velocity and prolonged refractory period
What are some side-effects of adenosine?
Facial flushing
Dyspnoea
Chest pressure
How does Digoxin work?
Digoxin is a cardiac glycoside that acts by inhibiting the sodium/potassium ATPase.
Used to control ventricular rate in patients with atrial tachycardias(AF), improves filling and efficiency
It increases vagal tone, thus slowing AV conduction
How can Digoxin exacerbate AF?
It can cause calcium overload (and increased contractility which man help in HF) → but
should only be used in patients with sedentary lifestyles (any added
sympathetic drive can worsen)
What is the drug magnesium sulphate used for?
To treat convulsions during pregnancy, nephritis in children, magnesium deficiency, and tetany
In arrhythmias, mechanism is unknown
What is torsades de pointes?
A type of polymorphic ventricular tachycardia characterized on electrocardiogram by oscillatory changes in amplitude of the QRS complexes around the isoelectric line
It’s associated with QTc prolongation, which is the heart rate adjusted lengthening of the QT interval
What is the drug magnesium sulphate used for?
Given IV in torsades de pointes and digoxin induced arrhythmias
What are the side effects of magnesium sulphate?
bradycardia
respiratory paralysis
flushing
headache
What are some examples of tachyarrhythmias?
- Supraventricular tachycardia
- Atrial fibrillation
- Atrial flutter
- Ventricular tachycardia
- Monomorphic
- Polymorphic (Torsades de pointe)
- Ventricular fibrillation
What is meant by narrow vs broad tachycardia?
Relates to the QRS internal
What is a Supraventricular Tachycardia?
Any tachyarrhythmia arising from above the level of the Bundle of His
What is a Sinus Tachycardia?
An increase in HR to >100bpm
Normal sinus rhythm on ECG
What is Wolff-Parkinson-White syndrome?
A condition that makes the heart suddenly beat abnormally fast, in an abnormal heart rhythm called supraventricular tachycardia (SVT)
Because WPW has both normal conduction through the AV node and accessory pathway conduction that bypasses the AV node, AF can happen via the accessory pathway
Inhibition of the AV node will end up in worsening the AF because none of the signals are slowed down by the AV node before hitting the ventricle
What is the normal range for a QT interval?
adult men </=440 msec
adult women </=460 msec
What is the management for a prolonged QT interval?
Acute: Remove offending medication. Shorten the QT interval with magnesium, lidocaine, or temporary overdrive pacing (if available)
Chronic: may need Pacemaker, ICD, amiodarone, or beta-blockers
What are some common drugs that prolong QT interval?
antidepressants
antipsychotics
anticholinergic agents
methadone
loperamide
quinine
antibiotics like clarithromycin, ciprofloxacin
What is ventricular fibrillation?
Chaotic irregular deflections without identifiable P-QRS-T waves
-This rapid and irregular electrical activity renders the
ventricles unable to contract in a synchronised manner,
resulting in immediate loss of cardiac output
The most important shockable cardiac arrest rhythm
It is invariably fatal unless advanced
life support is rapidly instituted
