Human aspects of cardiovascular and renal pharmacology: Dysrhythmias Flashcards
Quinidine
VW class IA
Procainamide
VW class IA
Lidocaine
VW class IB Local anaesthetic
Flecainide
VW class IC Pro-dysrhythmic
Propranolol
D and L- propranolol have Class I actions L-propranolol is a β-blocker (class II)
Atenolol
β1 antagonist (Class II actions)
Amiodarone
VW Class III
Inhibits both inward (Na and Ca) and outward (K) currents- AP duration would be shortened if inhibitory action was greater on inward than outward current, and vice versa.
Inhibition of inwards Na+ and Ca2+ currents show use-dependence (greater in tissues stimulated at higher frequencies), & also depends on voltage at which channels become de-inactivated (greater inhibition in tissues with less negative resting membrane potentials)
-> suppression of excitability & conductivity in both I[Na] and I[Ca] dependent cardiac tissues.
Various outward K+ channels also inhibited, but exactly which depends on [ ] of amiodarone present.
Verapamil
VW class IV
Nifedipine
Ca2+ channel blocker
Not effective as an antidysrhythmic
May be useful in myocardial salvage by decreasing Ca++ loading of damaged tissue.
Vasodilator effects reduce myocardial oxygen demand.
Adenosine
Antidysrhythmic, does not fit in VW classification
Acts on A1 receptors in AV node -> reduces cAMP levels via Gi.
Results in activation of I[K-ACh] current -> hyperpolarization of cardiac pacemaker & conductive tissue.
Used for certain supraventricular tachycardias, short half-life can have some advantages under these circumstances.
Cardiac glycosides
Antidysrhythmic, does not fit in VW classification
Increase vagal activity through an action in the CNS
Leads to inhibition at the AV node (slowing AV conduction)
Also affects arterial refractory period
Myocardial salvage
Ca2+ channel blockers e.g nifedepine may be useful by decreasing Ca++ loading of damaged tissue.
Beta-blockers will also decrease Ca2+ influx.
VW Class I
Block voltage gated Na+ channels- useful for suppression of inappropriate APs in cells that depend on VGNaC to generate the AP.
Subdivided into IA, IB, IC on basis of kinetics of association & dissociation with the channel, and effect on AP duration.
VW Class IA
Increased action potential duration
Intermediate rate of association/ dissociation
Affinity for open (activated) state > inactivated. Thus AP duration has no effect on drug action.
Show use-dependence at normal resting potentials
Work against atrial & ventricular dysrhythmias, but not commonly used.
VW Class IB
Decreased action potential duration
V fast association & dissociation
Affinity for inactivated > activated states. Thus influenced by length of AP.
Rate of dissociation during diastole decreases if MP is depolarised. As membrane repolarises & drug dissociates, effect removed.
Due to kinetics, most effective:
- at high rates of firing
- when diastolic (i.e resting membrane potential) is depolarised
- in parts of the heart where AP is longest.