Pharmacology - Therapy of Arrhythmias I (Dr. T) PDF

Preview

Summary

Lecture Notes...

Description

Pharmacology: Therapy of Arrhythmias I (Dr. T) Arrhythmia: disturbance in rate, rhythm, or pattern of cardiac contraction; can be caused by acute ischemia, chronic heart disease, imbalance of electrolytes or hormones, or drugs affecting ion channels or autonomic function Anti-Arrhythmics Most have multiple complex effects and are not easily classified Since arrhythmias have many causes, there are many different types of drugs Drugs selected to target most relevant underlying mechanism: Suppression of mech initiating triggered activity or enhanced automaticity Alteration of reentrant circuits Proarrhythmic Effect: can promote new arrhythmias Mechanisms of Arrhythmias 1) Altered Impulse Formation (Automaticity) Enhanced Automaticity Normal: acceleration of intrinsic pacemaker activity in nodal tissue or specialized conducting pathways – can lead to faster conduction that SA node and take over HR Escape Beat: impulse initiated by latent pacemaker in specialized conduction pathway in absence of SA nodal suppression (1 extra beat) Escape Rhythm: cont series of escape beats – may help maintain cardiac output if SA node impaired or there is high degrees of AV block Latent Pacemakers: parts of specialized conducting system (Purkinje fibers, etc.) that will take over if SA node stops functioning or there is AV block – may cause escape beats/rhythms; these cells can spontaneously depolarize w/o stimulation Ectopic Beat/Rhythms: enhanced automaticity of latent pacemakers  faster firing that SA node; can be caused by high [catecholamines], hypoxemia, ischemia, electrolyte disturbances, and drug toxicities Abnormal: induction of pacemaker activity in normally non-automatic tissue (ex: myocardial cells) – job is usually to contract, but can develop automaticity after cardiac injury and spontaneously depolarize Mech: hypoxia  resting membrane potential shifted upward to -50 mV  fast NA+ channel inactivated & inward currents carried by Ca2+  spontan. phase 4 depolarization & AP firing – myocardial cells move away from Na+ AP and into Ca2+ AP (much slower) Triggered Activity: oscillatory depol that may follow AP Early Afterdepolarization (EADs): occur BEFORE AP has fully depolarized; interrupt repol during phase 2 or 3 Promoted by: (longer phase 3 = more likely EAD)

-

prolonged AP bradycardia bc plateau lengths as HR slows  in outward repol. Current (longer repol.) from hypokalemia, drugs, long QT syndrome Delayed Afterdepolarizations (DADs): occur AFTER full repolarization; arises from resting potential If they don’t reach threshold, they don’t cause arrhythmias; increase in stimulatus rate may cause amplitude of DADs to increase until they reach threshold and cause self-sustained firing Promoted by: conditions with increased [Ca2+] Tachycardia B-adrenergic stimulation Digitalis glycosides 2) Altered Impulse Conduction Reentrant Excitation (Reentry): can occur with slow conduction causes majority of clinically significant arrhythmias (early atrial/ventric beats, nonsustained/sustained tachycardia) requirements: propagating impulse must cont encounter excitable tissue; requires the time around loop to be greater than time required for recovery (refractory period) 2 critical conditions for reentry: Unidirectional Block Slowed Conduction through reentry path Reentry occurs in regions with fibrosis (infarction scars) Circus Movement Reentry: activate wave propagates around anatomical/functional obstacle to re-excite site of origin; can also occur at branching junctions between Purkinje fibers and ventricular muscle AV Nodal Reentrant Tachycardia (AVNRT): Normal: impulse travels down fast pathway, can’t go up slow pathway bc still in refractory period, so it travels out and goes where it is need; AVNRT: if there is a premature atrial impulse, it cannot travel down fast pathway bc still refractory from previous impulse  travels down slow pathway  travels back up fast pathway bc refractory period over  continue in cycle

-

Reentry at Ventricular Muscle/Purkinje Fiber Junction: Normal: when an AP reaches a branch, it travels down both sides with same conduction velocity; Unidirectional Block: at branch point, 1 side of branch is blocked (B), impulse can only travel down unblocked side (a)  impulse reaches branch point (y) and can

-

-

do retrograde travel and enter the previously blocked branch  when entry point branch reached again (x), a is still repolarizing and can’t conduct  impulse stops; HOWEVER, if conduction through retrograde pathway is slow enough, it reaches x after a pathway has recovered  impulse can excite again  loop Disruption of this Circuit: STOP circuit Increased refractory period in a pathway – cause impulse to stop at x, despite slow retrograde conduction through B pathway Increased conduction velocity in B pathway  reach a before completely recovered Transmural Dispersion of Repolarization: AP duration is different between different myocardial layers Increases after taking QT-prolonging drugs in genetically predisposed patients – lengthens AP, but not equally Middle cells have longest recovery period  can cause arrhythmias bc impulse comes down the layers, finds refractory periods in middle cells and find alternate route  current cycles that can cause arrhythmias Torsade de pointes (TdP): polymorphic ventricular tachycardia  twisting of QRS complex around baseline occurs following prolongation of AP duration (dec HR) or EAD during prolonged repolarization phase – if EAD reaches threshold and generates premature ventricular complexes during period of dispersed repolarization, TdP can be initiated- can’t get reentry bc of change in refractoriness...