antidsrhythmia drugs Flashcards
what are dysrhythmias caused by
disruption of normal electrical conduction of the heart:
SAN-atria-AVN-purkinje fibres-ventricles
4 main factors: delayed after depolarisation, disordered conduction pattern, abnormal pacemaker activity, heart block
what is the ventricular resting membrane potential
just higher than -90mV
ventricles have stable resting potential due to high potassium permeability due to leak potassium channels and inward rectifier potassium channels which are open at rest
what is the plateau in the ventricular AP caused by
caused by delayed rectifier potassium channels and voltage gated calcium channels opening, which balance out depolarisation and hyperpolarisation
plateau persists for 100-200ms, which causes the long duration of ventricular APs
describe the APs of the SAN and AVN
APs of SAN and AVN: slower rising phase than ventricles and lower peak due to no sodium current, relies of slower calcium current
what affect does symapthetic stimulation have on SAN and AVN
causes slow depolarisation of the resting potential
via NA on beta 1 receptors; causes sodium and calcium to enter cell which causes depolarisation and shortens interval between APs
what affect does parasympathetic stimulation have on SAN and AVN
stimulates via Ach on M2 receptors
parasympathetic stimulation via vagus nerve
causes increase in potassium conductance, decreases depolarisation, increasing interval between APs
what is delayed after depolarisation
occurs when intracellular calcium conc is above normal
activates transient inward current due to stimulation of caclium sodium exchanger, which promotes net charge entry as 3 Na+ in for every Ca++ out
may cause an early (ectopic) beat
what is disordered conduction
damaged atrial muscle can lead to a unidirectional block
instead of atrial AP finishing as it converges on AVN one side continues to circulate
this means that the activation wavefront interacts with repolarisation phase of the succeeding wave
this allows slowly moving APs to re-excite tissue that is no longer refractory which leads to a re-entrant dysrhythmia with an impulse circulating indefinitely
what may cause abnormal pacemaker activity
can happen due to damage, which induces ectopic foci in atra or ventricles
what does failure of impulse generation in SAN or failure of propagation through AVN lead to
can lead to heart block, in dysrhythmias ventricular beating is maintained by abnormal pacemaker which is usually slow and unreliable
how do antidysrhythmic drugs work
they alter:
the max diastolic (most negative) potential in pacemaker cells or the resting potential of ventricular cells
the rate of conduction via sodium channel blockers
rate of phase 4 depolarisation (beta blockers)
the AP threshold ( sodium and calcium blockers)
the AP duration and the refractory period ( potassium channel blockers)
the excitability of the SAN and AVN conduction (calcium channel blockers)
how are anti-dysrhythmic drugs classified in vaughan williams classification
1a: sodium channel block (intermediate block) e.g disopyrimide, causes slow rise of AP and slows depolarisations, causes prolongation of AP
1b sodium channel block (fast dissociation, within a single beat): e.g lidocaine, causes small slowing of AP rise, channels are blocked following peak so premature beat is aborted, bind preferentially to inactivated sodium channels so selective block occurs in depolarised regions
1c: sodium channel block: slow dissociation, level of block is constant throughout cardiac cycle, e.g flecainide, have little effect on AP duration, slows AP rise, show marginal selectivity for inactivated channels
class 2: beta blockers, e.g propranolol, block excitatory sympahtetic effects by blocking beta 1 receptors, reduce inward calcium current, reducing SAN pacemaker activity and slowing AVN conduction
class 3: potassium channel block: e.g sotalol, prolongs cardiac AP and increases refractory period, reduces time window in cardiac cycle when dysrhythmias can occur
class 4: calcium channel block, e.g verapamil, slows inward calcium current which indirectly reduces transient inward current, decreases SAN excitability and AVN conduction
in addition to drugs in vaughan williams classification what other treatment can be used to treat dysrhythmias
cardiac glycosides: tend to cause dysrhythmias by increasing intracellular calcium, however also cause partial AV block which is useful in reducing ventricular rate in atrial fibrilation or flutter
adenosine: potent blocker of AVN conduction, receptor is linked to potassium channels, used treat AV nodal re-entrant tachycardias
electrical defibrillation; often used in conjunction with drug treatment
implanted electrical pacemakers: only reliable way to treat heart block, although beta agonists may be useful
what are 4 main antidysrhythmic drugs used
quinidine: optical isomer of quinine, orally active so is used prophylactically
side affects: hypotension due to cardiac depressant action
