eLFH - Antiarrhythmic agents

Question 1

Definition of bradycardia

Answer 1

HR < 60

Treated only if signs of compromise

Question 2

Interim treatment options for Bradycardia (whilst awaiting trans-venous pacemaker insertion

Answer 2

Glycopyrrolate
Atropine
Isoprenaline
Adrenaline
Aminophylline
Dopamine
Glucagon

Transcutaneous pacing

Question 3

Indication for Atropine use

Answer 3

Bradycardia due to increased vagal tone or to counter muscarinic effects of anticholinergics

Question 4

Chemical composition of Atropine

Answer 4

Racemic mixture of D- and L-hyoscyamine

Only L- is active

Question 5

Dose of Atropine and route of administration

Answer 5

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)

Question 6

Pharmacokinetics of Atropine

Answer 6

Low bioavailability (10 to 20%)

Crosses placenta and blood brain barrier

Elimination half life 2.5 hours

Question 7

Atropine mechanism of action

Answer 7

Competitive antagonist of acetylcholine at muscarinic receptors

Minimal nicotinic receptor action

Question 8

CVS effects of atropine

Answer 8

Bezold-Jarisch reflex - low dose can initially produce bradycardia

Slows AV node conduction time

Dilation of cutaneous blood vessels at high doses

Question 9

Respiratory effects of atropine

Answer 9

Bronchodilation - increases physiological dead space

Increased RR

Question 10

CNS effects of atropine

Answer 10

Can cause central anticholinergic syndrome

Question 11

GI and GU effects of atropine

Answer 11

Reduces gut motility

Reduces urinary tract tone

Question 12

Other effects of atropine

Answer 12

Mydriasis

Increased intraocular pressure

Reduced ADH secretion

Has local anaesthetic properties

Question 13

Chemical structure of Glycopyrrolate

Answer 13

Charge quaternary amine

Question 14

Glycopyrrolate dose and route of administration

Answer 14

200 - 400 micrograms IV or IM for adults

4 - 10 microgram/kg for paediatrics

Question 15

Glycopyrrolate mechanism of action

Answer 15

Competitive antagonist at peripheral muscarinic receptors

Question 16

Glycopyrrolate pharmacokinetics

Answer 16

Poor bioavailability (5%)

Can cross placenta but NOT blood brain barrier

80% excreted unchanged

Elimination half life 0.6 to 1.1 hours

Question 17

CVS effects of glycopyrrolate

Answer 17

Vagolytic effects last 2 to 3 hours

Tachycardia at high doses

Question 18

Respiratory effects of glycopyrrolate

Answer 18

Bronchodilation - increases physiological dead space

Question 19

Other effects of glycopyrrolate

Answer 19

5x more potent than atropine at drying secretion

Question 20

Isoprenaline features

Answer 20

Mixed Beta 1 and Beta 2 agonist

SVR can drop due to B2 agonism

Usually IV, but can be inhaled or PO

Question 21

Adrenaline features

Answer 21

Low dose has chronotropic beta agonist effects
Increasing dose increases the alpha action

Diastolic BP can fall due to beta 2 vasodilation

Question 22

Aminophylline features

Answer 22

Non specific phosphodiesterase inhibitor - increases intracellular cAMP

Mild chronotropic effects

Question 23

Dopamine features

Answer 23

Low dose infusion has beta 1 agonism
Higher doses increase alpha action

Increases atrio-ventricular conduction

Question 24

Glucagon features

Answer 24

Glucagon receptors Gs protein coupled
Increase intracellular cAMP

Limited to second or third line management of beta blocker overdose

Question 25

Classification of tachycardia

Answer 25

Supraventricular tachycardias Ventricular tachycardias

Question 26

Supraventricular tachycardia examples

Answer 26

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

Question 27

Ventricular tachycardia examples

Answer 27

Monomorphic VT Polymorphic VT (Torsades de pointes) VF

Question 28

Vaughan-Williams classification of antiarrhythmics (Less useful these days as doesn't account for some more modern agents)

Answer 28

Don't stress about side effects too much

Question 29

Amiodarone mechanism of action

Answer 29

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

Question 30

Amiodarone IV dose

Answer 30

5 mg/kg IV loading over 1 hour (max 300 mg) Then 15 mg/kg over 24 hours (usually max 900mg)

Question 31

Amiodarone PO dose

Answer 31

200 mg TDS for 1 week Then 200mg BD for 1 week Then 200 mg OD

Question 32

Amiodarone pharmacokinetics

Answer 32

Bioavailability 50 - 70% Highly protein bound (>95%) Elimination half life 4 hours to 52 days

Question 33

Drugs which are potentiated by amiodarone (and why)

Answer 33

Can potentiate action of DOACs, digoxin, calcium antagonists and beta blockers as they are displaced from proteins

Question 34

Side effects of chronic amiodarone use

Answer 34

Pneumonitis and fibrosis - reversible if stopped early enough Corneal deposits Peripheral neuropathy Thyroid disease

Question 35

Side effects of acute amiodarone use

Answer 35

Bradycardia Hypotension Prolonged QT interval

Question 36

Adenosine mechanism of action

Answer 36

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

Question 37

Adenosine onset and offset times

Answer 37

Onset 10s Offset 10 - 20s

Question 38

Contraindication to Adenosine use

Answer 38

Asthma - can cause bronchospasm

Question 39

Adenosine dose in adults

Answer 39

6 mg, then 12 mg, then 18 mg IV

Question 40

Adenosine dose in paediatrics

Answer 40

0.0375 to 0.25 mg/kg

Question 41

CVS effects of adenosine

Answer 41

Increases myocardial blood flow Can induce AF or flutter as it decreases atrial refractory period Decreases pulmonary vascular resistance in pulmonary HTN

Question 42

Respiratory effects of adenosine

Answer 42

Causes bronchospasm in susceptible people Increases RR and respiratory depth

Question 43

Other effects of adenosine

Answer 43

Can induce neuropathic pain Chest discomfort Facial flushing

Question 44

Digoxin mechanism of action

Answer 44

Directly blocks Na+/K+ ATPase - increases AV node refractory period Indirectly increases ACh release - slows conduction and prolongs refractory period

Question 45

Digoxin dose and route of administration

Answer 45

10 - 20 microgram/kg loading dose 6 hourly, then maintenance Usually IV acutely followed by PO maintenance

Question 46

Digoxin target serum levels

Answer 46

1 to 2 g/ml therapeutic range

Question 47

Digoxin pharmacokinetics

Answer 47

50 - 70% excreted unchanged in urine - some active secretion Dosing adjustments needed in renal failure

Question 48

Side effects of digoxin

Answer 48

GI upset Muscle weakness Headache and convulsions Arrhythmias - heart block, ventricular bigemini

Question 49

Factors which increase risk of digoxin toxicity

Answer 49

Low K+ Low Mg2+ High Na+ High Ca2+ Hypoxaemia Renal failure Other drug use - amiodarone, verapamil, diazepam

Question 50

Flecainide features

Answer 50

Amide local anaesthetic

Question 51

Flecainide mechanism of action

Answer 51

Blocks fast sodium channels Slows depolarisation

Question 52

Flecainide indications

Answer 52

Supraventricular and ventricular tachycardias Supresses ventricular ectopics

Question 53

Flecainide doses and routes of administration

Answer 53

2 mg/kg IV bolus followed by infusion 100 to 200 mg PO 12 hourly