eLFH - Antiarrhythmic agents Flashcards
Definition of bradycardia
HR < 60
Treated only if signs of compromise
Interim treatment options for Bradycardia (whilst awaiting trans-venous pacemaker insertion
Glycopyrrolate
Atropine
Isoprenaline
Adrenaline
Aminophylline
Dopamine
Glucagon
Transcutaneous pacing
Indication for Atropine use
Bradycardia due to increased vagal tone or to counter muscarinic effects of anticholinergics
Chemical composition of Atropine
Racemic mixture of D- and L-hyoscyamine
Only L- is active
Dose of Atropine and route of administration
20 micrograms / kg IV or IM
200 - 600 micrograms PO
3 mg needed for complete vagal blockade in adults (hence repeat boluses of 0.5 mg up to 3 mg max)
Pharmacokinetics of Atropine
Low bioavailability (10 to 20%)
Crosses placenta and blood brain barrier
Elimination half life 2.5 hours
Atropine mechanism of action
Competitive antagonist of acetylcholine at muscarinic receptors
Minimal nicotinic receptor action
CVS effects of atropine
Bezold-Jarisch reflex - low dose can initially produce bradycardia
Slows AV node conduction time
Dilation of cutaneous blood vessels at high doses
Respiratory effects of atropine
Bronchodilation - increases physiological dead space
Increased RR
CNS effects of atropine
Can cause central anticholinergic syndrome
GI and GU effects of atropine
Reduces gut motility
Reduces urinary tract tone
Other effects of atropine
Mydriasis
Increased intraocular pressure
Reduced ADH secretion
Has local anaesthetic properties
Chemical structure of Glycopyrrolate
Charge quaternary amine
Glycopyrrolate dose and route of administration
200 - 400 micrograms IV or IM for adults
4 - 10 microgram/kg for paediatrics
Glycopyrrolate mechanism of action
Competitive antagonist at peripheral muscarinic receptors
Glycopyrrolate pharmacokinetics
Poor bioavailability (5%)
Can cross placenta but NOT blood brain barrier
80% excreted unchanged
Elimination half life 0.6 to 1.1 hours
CVS effects of glycopyrrolate
Vagolytic effects last 2 to 3 hours
Tachycardia at high doses
Respiratory effects of glycopyrrolate
Bronchodilation - increases physiological dead space
Other effects of glycopyrrolate
5x more potent than atropine at drying secretion
Isoprenaline features
Mixed Beta 1 and Beta 2 agonist
SVR can drop due to B2 agonism
Usually IV, but can be inhaled or PO
Adrenaline features
Low dose has chronotropic beta agonist effects
Increasing dose increases the alpha action
Diastolic BP can fall due to beta 2 vasodilation
Aminophylline features
Non specific phosphodiesterase inhibitor - increases intracellular cAMP
Mild chronotropic effects
Dopamine features
Low dose infusion has beta 1 agonism
Higher doses increase alpha action
Increases atrio-ventricular conduction
Glucagon features
Glucagon receptors Gs protein coupled
Increase intracellular cAMP
Limited to second or third line management of beta blocker overdose
Classification of tachycardia
Supraventricular tachycardias
Ventricular tachycardias
Supraventricular tachycardia examples
Sinus tachycardia
Atrial fibrillation
Atrial flutter
AV nodal re-entry tachycardia (AVNRT)
AV re-entry tachycardia (AVRT) - e.g. Wolff-Parkinson-White syndrome
Note: An SVT with associated bundle branch block can mimic ventricular tachycardia
Ventricular tachycardia examples
Monomorphic VT
Polymorphic VT (Torsades de pointes)
VF
Vaughan-Williams classification of antiarrhythmics
(Less useful these days as doesn’t account for some more modern agents)
Don’t stress about side effects too much
Amiodarone mechanism of action
Mainly class III action - blocks K+ channels
Partial antagonist of alpha and beta adrenoreceptors
Higher doses can depress Na+ and Ca2+ channels
Slows rate of repolarisation and increases refractory period and phase III
Slows AV node automaticity and conduction
No effect on conduction through bundle of His and ventricles
Amiodarone IV dose
5 mg/kg IV loading over 1 hour (max 300 mg)
Then 15 mg/kg over 24 hours (usually max 900mg)
Amiodarone PO dose
200 mg TDS for 1 week
Then 200mg BD for 1 week
Then 200 mg OD
Amiodarone pharmacokinetics
Bioavailability 50 - 70%
Highly protein bound (>95%)
Elimination half life 4 hours to 52 days
Drugs which are potentiated by amiodarone (and why)
Can potentiate action of DOACs, digoxin, calcium antagonists and beta blockers as they are displaced from proteins
Side effects of chronic amiodarone use
Pneumonitis and fibrosis - reversible if stopped early enough
Corneal deposits
Peripheral neuropathy
Thyroid disease
Side effects of acute amiodarone use
Bradycardia
Hypotension
Prolonged QT interval
Adenosine mechanism of action
Acts of adenosine (A1) receptors in SA and AV node
Gi protein coupled receptors - cause hyperpolarisation and negative chronotropy
Transient heart block occurs
A2 receptors have anti-inflammatory actions
Adenosine onset and offset times
Onset 10s
Offset 10 - 20s
Contraindication to Adenosine use
Asthma - can cause bronchospasm
Adenosine dose in adults
6 mg, then 12 mg, then 18 mg
IV
Adenosine dose in paediatrics
0.0375 to 0.25 mg/kg
CVS effects of adenosine
Increases myocardial blood flow
Can induce AF or flutter as it decreases atrial refractory period
Decreases pulmonary vascular resistance in pulmonary HTN
Respiratory effects of adenosine
Causes bronchospasm in susceptible people
Increases RR and respiratory depth
Other effects of adenosine
Can induce neuropathic pain
Chest discomfort
Facial flushing
Digoxin mechanism of action
Directly blocks Na+/K+ ATPase - increases AV node refractory period
Indirectly increases ACh release - slows conduction and prolongs refractory period
Digoxin dose and route of administration
10 - 20 microgram/kg loading dose 6 hourly, then maintenance
Usually IV acutely followed by PO maintenance
Digoxin target serum levels
1 to 2 g/ml therapeutic range
Digoxin pharmacokinetics
50 - 70% excreted unchanged in urine - some active secretion
Dosing adjustments needed in renal failure
Side effects of digoxin
GI upset
Muscle weakness
Headache and convulsions
Arrhythmias - heart block, ventricular bigemini
Factors which increase risk of digoxin toxicity
Low K+
Low Mg2+
High Na+
High Ca2+
Hypoxaemia
Renal failure
Other drug use - amiodarone, verapamil, diazepam
Flecainide features
Amide local anaesthetic
Flecainide mechanism of action
Blocks fast sodium channels
Slows depolarisation
Flecainide indications
Supraventricular and ventricular tachycardias
Supresses ventricular ectopics
Flecainide doses and routes of administration
2 mg/kg IV bolus followed by infusion
100 to 200 mg PO 12 hourly
