Anti arrhythmics Flashcards
(19 cards)
Mechanism of action of Adenosine
Adenosine binds to A1 receptors in the heart, leading to:
Increased outward K⁺ current (via GIRK channels)
(Potassium leaves the cell)
Inhibition of adenylate cyclase → ↓ cAMP
(Suppression of Ca²⁺ influx)
✅ Hyperpolarizes the AV node
✅ Temporarily blocks AV nodal conduction
Pharmacodynamics of Adenosine
As a bolus dose blocks AV nodal conduction and increases AV nodal refractory period due to:
> Opens K⁺ channels (GIRK) ↑ K⁺ efflux → hyperpolarization
> enhanced potassium conductance
> Inhibition of Ca current
> Results in hyperpolarisation and suppression of calcium-dependent action potentials
This interrupts re-entry pathway through AV node
Pharmacokinetics of Adenosine
Very rapid metabolism by adenosine deaminase in red cells and endothelial wall
Half-life < 10 seconds
Duration of action ~ 30 seconds
What does potassium enhanced conductance mean
Enhanced potassium conductance means more K⁺ channels are open, allowing K⁺ to leave the cell more easily.
Clinical used of Adenosine
Conversion of paroxysmal SVT to sinus rhythm:
Given via rapid IV bolus, proximal IV site
If initial dose ineffective, subsequent doses should be increased (no accumulation occurs)
An uncommon variant of VT is adenosine-sensitive
Will not be effective for SVT caused by adenosine-blockers such as theophylline
Adverse effects of Adenosine
Short-lived
Flushing 20%
SOB or chest burning (likely bronchospasm-related) 10%
Short-lived induction of high grade AV block
AF
Sense of impending doom
Anti arrhythmic calssifcation
I - Na blockers
II - B blockers
III - K blockers
IV - Ca blockers
others - Adenosine, Digoxin
Class Ia antiarrhythmics
Quinidine, Procainamide, Disopyramide
Class Ia antiarrhythmic effects on Action Potential duration and kinetics of Na blockade
Prolong APD
dissociate (from channel) with intermediate kinetics
Class Ib antiarrhytmics
Lignocaine
Class Ib (Lignocaine) effects on Action Potential duration and kinetics of Na blockade
Shorten APD
dissociate with rapid kinetics
Class 1c antiarrhythmics
Flecainide, Propafenone
Class 1c effects in action potential duration and kinetics of Na blockade
Minimal effects on APD
dissociated with slow kinetics
Examples of class III antiarrhythmics
Amiodarone, sotolol
Pharmacodynamics of amiodarone
Class III antiarrhythmic. Also has class I, II and IV effects
Prolongs action potential duration (and QT interval) due to blockade of rapid component of delayed K current
Chronic use also blocks slow K rectifier
Other effects:
Blocks inactivated Na channels. AP prolonging action reinforces this effect
Weak adrenergic and Ca channel blocking actions. Causes slowing of HR and AV nodal conduction.
Peripheral vasodilation (after intravenous administration)
pharmacokinetics of amiodarone
Variable absorption with bioavailability 35-65%
Bimodal half-life:
Rapid component 3-10 days (50% of drug)
Slower component of several weeks
After cessation, drug effects are maintained for 1-3 months
CYP inhibitor
clinical uses of amiodarone
Treatment of atrial and ventricular tachyarrhythmias (SVT, AF, VT, VF)
Used both to revert VT and prevent recurrence
ALS algorithm after 3rd cycle of shockable rhythm
chronic adverse effects of amiodarone
Pulmonary fibrosis
Deranged LFTs and hepatitis
Hypothyroidism (blocks peripheral conversion of T4 to T3) or hyperthyroidism (source of large amounts of inorganic iodine)
Skin deposits: photodermatitis and grey-blue discolouration in sun-exposed areas
Asymptomatic corneal microdeposits
Optic neuritis (rare)
Drug interactions of amiodarone
Administration in conjunction with other CYP substrates:
Increases INR in co-administration with warfarin
Increases effect of digoxin
Increases concentration of statins
