Antiarrhythmics

Question 1

How does Atropine work?

Answer 1

• Competitive antagonist of acetylcholine at muscarinic receptors with minimal action on nicotinic receptors
  -Increases vagal tone
• Counters the muscarinic effects of anticholinergics

Question 2

What are the pharmacokinetics of Atropine?

Answer 2

• Low bioavalibility
• Crosses placenta & blood-brain barrier
• Half life 2.5hours

Question 3

How does Atropine work on the CV, Resp, CNS, GI and other systems?

Answer 3

CV: Slows AV node conduction time, high dose = vasoD
Resp: BronchoD, inc dead space, Inc RR
CNS: Central anticholinergic syndrome
GI: Reduces gut motility & urinary tone
Other: Mydriasis, inc IOP, Reduces ADH secretion, LA properties

Question 4

What type of drug is glycopyrrolate?

Answer 4

• Potent antisialogogue
• Charged Quaternary amine
• Competitive antagonist at peripheral muscarinic receptors

Question 5

What is the dosage of glyco?

Answer 5

200-400mcg in adults
4-10mcg/kg in paeds

Question 6

What are the pharmacokinetics of glyco?

Answer 6

Poor oral absorption (5%)
Can cross placenta
Can’t cross blood-brain barrier
Half life 0.6-1.1 hours

Question 7

What are the pharmacodynamics of Glyco?

Answer 7

CV: Tachy at high doses, vagoltic effects for 2-3hours
Resp: BronchoD, inc physiological dead space
Other: x5 more potent than atropine at drying secretions

Question 8

How do most agents work against bradycardia?

Answer 8

Direct/indirect beta agonist action causing positive chronotropy

Question 9

How does isoprenaline work?

Answer 9

B1 & B2 agonist
SVR drops due to B2 action

Question 10

How does aminophylline work?

Answer 10

Non-specific phosphodiesterase inhibitor
Inc intracellular cAMP

Question 11

How does glucagon work?

Answer 11

Gs-protein linked receptors
Increases intracellular cAMP

Question 12

How does Amiodarone work?

Answer 12

• Benzofuran derivative
• Class III action - blocks K+ Channels
• Partial antagoinst of alpha & Beta agonists
• High doses depress Na+ & Ca2+ channels
• Slows rate of repolarization & inc refractory period, prolonging phase 3
• Slows AVN automaticity & conduction

Question 13

What are the pharmacokinetics of amiodarone?

Answer 13

• 50-70% bioavailability
• Highly protein bound (>95%)
• Can potentiate action of oral anticoags, Digoxin, Ca antagonists, B-blockers - displace from proteins
• 1/2 life: 4hours - 52 days

Question 14

What are the pharmacodynamics of Amiodarone?

Answer 14

• CV: Bradycardia, hypoT, prolonged QT interval
• Resp: Penumonitis, fibrosis
• Opthalm: Corneal deposits, photosensitivity
  Met: Abnormal TFTs, peripheral neuropathy

Question 15

How does adenosine work?

Answer 15

Acts on A1 receptors in SA & AV node causing hyperpolarization & dramatic negative chronotropy
Transient heart block occurs
Cytoprotective properties in ischaemia
Causes direct smooth muscle relaxation in normal coronaries

Question 16

What is the structure of Adenosine?

Answer 16

Naturally occuring purine nucleoside of adenine & D-ribose

Question 17

What are the pharmacodynamics of Adenosine?

Answer 17

CV: Inc myocardial blood flow, dec PVR and therefore pulmonary HTN, induce AF as decreases atrial refractory period
Resp: Bronchospasm, Inc RR & depth
Other: Induce neuropathic pain, facial flushing, chest discomfort

Question 18

How does Digoxin work?

Answer 18

-Directly blocks Na/K+ ATPase pump
-Increases refractory period of AV node
-Reduces conductivity
-Indirectly acts by increasing ach release which prolongs refractory period & slows conduction

Question 19

What are the pharmacokinetics of Digoxin?

Answer 19

50-70% excreted unchanged in urine
Narrow therapeutic window

Question 20

What are the pharmacodynamics of Digoxin?

Answer 20

GI: Abdo pain, N&V
CV: Arrhythmia

Question 21

What factors increase the risk of Digoxin toxicity?

Answer 21

• HypoK
• HypoMg
• HyperNa
• HyperCa
• Renal failure
• Hypoxaemia
• Other drugs: Amiodarone, Verapamil, Diazepam

Question 22

What is Flecainide indicated for?

Answer 22

SVT
VT
Suppression of ventricular ectopics

Question 23

How does Flecainide work?

Answer 23

Blocks fast Na channels and slows depolarisation in conducting pathways
Amide of LA

Question 24

How are antiarrhythmics categorised?

Answer 24

• Cardiac tissue they affect
• Vaughan Williams classification based on electrophysiological action of isolated cardiac fibres

Question 25

What are the classes of antiarrhythmics?

Answer 25

1a: Block Na, prolong refractory
1b: Block Na, shorten refractory
1c: Block Na, no effect on refractory
2: b-adrenoreceptor blockade
3: K+ channel blocker
4: Ca2+ Channel blocker
5: Other (Mg, Digox, Adenosine)

Question 26

What is the main role of Class 1 antiarrhythmics?

Answer 26

• Local anaesthetic properties that stabilise membrane
• Affect conduction & refractory period & AP

Question 27

What do Nitrates do?

Answer 27

• Redistribute blood flow along collateral channels from epicardial to endocardial regions
• Dilate large coronary arteries
• Inc venous capacitance causing pooling in peripheral veins & reducing venous return & ventricular volume
• Reduces myocardial O2 demand

Question 28

What is the MOA for nitrates?

Answer 28

-Conversion of nitrates to nitrites
-Enzyme release of unstable NO
-NO stimulates enzyme granulate cyclase to produce cGMP
-Reduces Ca in vascular myocytes