Anti-arrhythmics Flashcards
What causes arrhythmias?
Tachyarrhythmias:
enhanced automaticity: before the SA node
Ischaemia: after potentials
Re-entry
Bradyarrhythmias:
failure of conduction to SA node
Treatment
SVT:
digoxin, adenosine, verapamil, B blockers, quinidine
VT:
Lidocaine, mexiletine
SVT/VT:
amiodarone, flecanide, procainamide, disopramide, propafenone, sotalol
Digoxin toxicity:
phenytoin
Tell me about Digoxin
Glycoside
extracted from the leaves of the foxglove
Oral tabets (62.5-250Ug) IV (100-250Ug)
Uses:
AF and Atrial Flutter
Loading dose
Mechanism:
Direct:
binds to and inhibits Na/K ATPase: increased intracellular Na and decreased intracellular K
Raised intracellular Na leads to increased exchange for extracellular Ca. Increased intracellular Ca = increased force contraction, refractory period AV node and bundle His increased, conductivity reduced
Indirect:
release Ach at cardiac muscarinic receptors enhanced. Slows conduction and further prolongs the refractory period in the AV node and bundle of His
AF: slow conduction through AV node, longer diastole therefore longer vent filling = increase CO
Side effects:
Cardiac: arrhythmias. Hypo K, Hyper Ca, altered pH precipitate effects. prolonged PR, ST depression, T wave flattening, shortened QT
Non cardiac: anorexia, N&V, diarrhoea, lethargy, colour disturbance, headache, eosinophilia
Interactions
Kinetics: Oral bio >70% 25% plasma VoD 5-10L.kg secreted mainly unchanged at glomerulus active tubular secretion elimination half life 35hrs
Toxicity:
>2.5Ug/L
serious problems unusual below 10
Treatment toxicity: High K atropine for brady Fab indicated if arrhythmias uncontrolled IgG: binds. renal excretion
Tell me about Adenosine
Naturally occuring purine nucleoside consisting of adenine (purine base) and D-Ribose (pentose sugar)
Presentation:
Colourless solution
Vials 3mg/ml
Uses:
SVT due to re-entry circuits that involve AV node may go sinus
AF/flutter not changed
Mechanism:
Acts on adenosine A1 receptors found in heart. K channels opened.
Membrane hyperpolarisation
Gi proteins reduction in cAMP
negative chronotropic effect within AV node
Side effects:
Cardiac: May induce AF/flutter as it decreases atrial refractory period. Contra in 2nd/3rd heart block or with sick sinus
Non-cardiac: chest discomfort, sob, bronchospasm, facial flushing
Kinetics:
rapidly de-aminated in the plasma and taken up by rbc. half life
Describe Vaughan- Williams classification
I:
a: Na channel blocker-prolonged refractory cardiac muscle-
quinidine, procainamide, disopyramide
b: Na channel blocker. Shortens refractory period.
Lidocaine, mexiletine, phenytoin
c: Na channel blocker- no affect on RP
Flecanide, propafenone
II:
B adrenoreceptor blocker
Propranolol, atenolol, esmolol
III:
K channel blockade
Amiodarone, bretylium, sotalol
IV:
Ca channel blockade
Verapamil, diltiazem
Tell me about verapamil
Competitive Ca antagonist
Presented as film coated or MR tablets or as a solution of 2.5mg/ml
Uses:
SVT, AF or flutter
Prophylaxis angina
Tx of HTN
Mechanism:
Prevents influx Ca through voltage-sensitive slow L channels in SA and AV node
Reduced automaticity
Does reduce Ca influx during plateau phase 2
Coronary artery dilatation
side effects:
Cardiac- avoid in WPW- VT (condition along accessory pathway). Precipitate cardiac failure. Bradycardia/AV block exacerbated
Hypotension
Cerebral artery vasodilatation
Kinetics: 90% absorbed high first pass metabolism Oral bio 25% 90% bound plasma proteins Metabolised in liver to 12 inactive metabolites- excreted in urine VoD 3-5l.kg Elimination half life 3-7hrs
Tell me about esmolol
Relatively cardioselective b blocker with rapid offset/onset
Presentation:
Clear liquid 2.5g or 100mg in 10ml
Uses:
Short term mx of tachycardia/HTN
No intrinsic sympathomimetic activity or membrane stabilising properties
Side effects:
Use in caution in asthmatics
Vein irritant
Kinetics: 60% plasma protein bound VoD 3.5L.kg Rapidly metabolised rbc esterases to inactive acid metabolite and methyl alcohol Rapid metabolism half life 10min
Tell me about quinidine
Rarely used
SVT, AF, flutter, vent ectopics
Mechanism
Class Ia- reduce rise of phase 0 by blocking Na channels
Raises threshold potential and prolongs refractory period
No affect on duration of AP
Antagonises vagal tone
side effects:
Unacceptable in 30% pts
Cardiac: arrhythmias (heart block, sinus tachy (vagolytic action), ventricular arrhythmias)
ECG: prolonged PR, widened QRS and prolonged QT
Non cardiac: CNS toxicity- cinchonism
Drug interactions:
Digoxin increased (displaced from binding sites)
Phenytoin reduce (enzyme induction)
Cimetidine increase (enzyme inhib)
Depolarising and non depolarising increased
Kinetics: Well absorbed Oral bio availability 75% Highly protein bound 90% Liver- inactive met abilities Elim half life 5-9hrs
Tell me about lidocaine
Class Ib anti-arrhythmic
Presentation:
1-2% (10-20mg/ml)
Uses:
sustained VT esp when associated with ischaemia or re-entry arrhythmias
Initial IV dose 1mg/kg followed by infusion of 1-3mg/min
reduce rate if decreased hepatic blood flow
Mechanism:
Reduces rate of rise of phase 0 by blocking inactivated Na channels raising the threshold potential
Duration of AP and refractory period decreased as depolarisation phase 3 is shortened
Side effects:
Cardiac: CVS toxicity plasma levels >10g/ml. AV block, hypotension due to myocardial depression
Non-cardiac: >4ug/ml. LA toxicity
Kinetics:
33% unionised and 70% protein bound
metabolised by hepatic amides: urine excretion
elimination half life 90min
Tell me about mexiletine
Analogue of lidocaine
Presented as colourless solution.
Uses:
Similar to lidocaine: VT
Mechanism:
reduces the rate of rise of phase 0 by blocking Na channels and raising threshold potential
Side effects:
low therapeutic ratio:
cardiac: sinus brady, supraventricular/ventricular tachyarrhythmias
non-cardiac: N&V, altered bowel habit, tremor, ataxia, thrombocytopenia
Kinetics:
oral bio 90%. 65% plasma protein bound and VoD 6-13kg/L
hepatic metabolism inactive metabolities
20% excreted unchanged in urine
Tell me about amiodarone
Benzofuran derivative
Presented as tablets 100-200mg
Uses:
SVT, VT and WFW
loading 5mg/kg 1hr then 15mg/kg 24hours
Mechanism of action: class III anti arrhythmic I, II, IV activity
Side effects:
Pulmonary: pneumonitis, fibrosis, pleuritis.
Thyroid: Hypo/hyper. Prevents peripheral conversion of T4 to T3
Hepatic: cirrhosis, hepatic, jaundice
Cardiac: brady/hypo. Low arrhythmic potential. QT prolonged
Ophthalmic: corenal microdeposits
GI: metallic taste
Neuro: peripheral neuropathy
Derm: photosensitivity, slate-grey
Interactions: highly protein bound drugs
Kinetics:
Poorly absorbed from gut. Bio availability 50-70%. Plasma highly protein bound (>95%)
VoD 2-70L.kg
hepatic metabolism: desmethylamiodarone :antiarrhythmix
excreted by lachrymal glands, skin and biliary tract
