Antiarrhythmics Flashcards
How does Atropine work?
- Competitive antagonist of acetylcholine at muscarinic receptors with minimal action on nicotinic receptors
-Increases vagal tone - Counters the muscarinic effects of anticholinergics
What are the pharmacokinetics of Atropine?
- Low bioavalibility
- Crosses placenta & blood-brain barrier
- Half life 2.5hours
How does Atropine work on the CV, Resp, CNS, GI and other systems?
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
What type of drug is glycopyrrolate?
- Potent antisialogogue
- Charged Quaternary amine
- Competitive antagonist at peripheral muscarinic receptors
What is the dosage of glyco?
200-400mcg in adults
4-10mcg/kg in paeds
What are the pharmacokinetics of glyco?
Poor oral absorption (5%)
Can cross placenta
Can’t cross blood-brain barrier
Half life 0.6-1.1 hours
What are the pharmacodynamics of Glyco?
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
How do most agents work against bradycardia?
Direct/indirect beta agonist action causing positive chronotropy
How does isoprenaline work?
B1 & B2 agonist
SVR drops due to B2 action
How does aminophylline work?
Non-specific phosphodiesterase inhibitor
Inc intracellular cAMP
How does glucagon work?
Gs-protein linked receptors
Increases intracellular cAMP
How does Amiodarone work?
- 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
What are the pharmacokinetics of amiodarone?
- 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
What are the pharmacodynamics of Amiodarone?
- CV: Bradycardia, hypoT, prolonged QT interval
- Resp: Penumonitis, fibrosis
- Opthalm: Corneal deposits, photosensitivity
Met: Abnormal TFTs, peripheral neuropathy
How does adenosine work?
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
What is the structure of Adenosine?
Naturally occuring purine nucleoside of adenine & D-ribose
What are the pharmacodynamics of Adenosine?
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
How does Digoxin work?
-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
What are the pharmacokinetics of Digoxin?
50-70% excreted unchanged in urine
Narrow therapeutic window
What are the pharmacodynamics of Digoxin?
GI: Abdo pain, N&V
CV: Arrhythmia
What factors increase the risk of Digoxin toxicity?
- HypoK
- HypoMg
- HyperNa
- HyperCa
- Renal failure
- Hypoxaemia
- Other drugs: Amiodarone, Verapamil, Diazepam
What is Flecainide indicated for?
SVT
VT
Suppression of ventricular ectopics
How does Flecainide work?
Blocks fast Na channels and slows depolarisation in conducting pathways
Amide of LA
How are antiarrhythmics categorised?
- Cardiac tissue they affect
- Vaughan Williams classification based on electrophysiological action of isolated cardiac fibres
What are the classes of antiarrhythmics?
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)
What is the main role of Class 1 antiarrhythmics?
- Local anaesthetic properties that stabilise membrane
- Affect conduction & refractory period & AP
What do Nitrates do?
- 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
What is the MOA for nitrates?
-Conversion of nitrates to nitrites
-Enzyme release of unstable NO
-NO stimulates enzyme granulate cyclase to produce cGMP
-Reduces Ca in vascular myocytes
