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Pharmacology I
Arrhythmias & Antiarrythmic Drugs

Learning Objectives:

Understand the basic mechanisms associated with abnormal automaticity and abnormal conduction.

  1. Abnormal Automaticity: SA node sets pace of conduction. Abnormal when other sites (other than SA node) generate competing stimuli therefore causing arrhythmias. Can come from damaged muscle cells.
    DAD’s intracellular Ca+2, EAD’s – the Na/Ca+2 exchanger doesn’t work correctly. Normally for every one Ca +2 out = 3 Na+ in.
  2. Re-entry loops (circus): 

    The impulse travels in retrograde direction and re-enters the conduction pathway causing an extra beat. This is the most common cause of arrhythmias.
  3. ¯ Conduction Velocity: Rate of depolarization is slower (¯ Vmax). The action potential is longer in duration ( APD). There is an inactivation of Na+ channels that makes the channels open in an uncoordinated way, which causes arrhythmias. If a discrepancy exist btw damaged regions and normal heart, you can get arrhythmias btw the two regions.
  4. Abnormal Pacemaker activity
    Catecholamines (epi and NE) will HR – this rate of depol of nodal cells in phase 4. A ¯ Catecholamines or an in Ach will ¯ HR and you’ll see a slower rate of rise of phase 4. Ectopic pacemaker activity can take over with low HR.

Know the therapeutic uses for each class of antiarrhythmic drugs.

Why do most antiarrhythmic drugs have the potential to be proarrhythmic?

They function to alter the AP or Vmax thru the phases of the cardiac cycle and depending on whether the channels are open or closed or inactivated and which drugs are used can have reverse effects. IE. If you block the K+ efflux the membrane potential stays higher longer and you increase the incidence of DAD’s and EAD’s. While the cell is depol, the Ca+2 channels are staying open and don’t inactivate quickly which can lead to triggered activity. Another example is quinidine which activates a receptors and is vagolytic so you could VSM contraction, and TPR and potentially HR and if vagal tone is decreased then that could HR and potentiate the arrhythmia.

Understand the mechanism by which digitalis glycosides and antiarrhythmic drugs can potentiate each other’s toxicity.

Digoxin inhibits the Na/K/ATPase pump which intracellular Na+ and Ca+2 exchange which leads to intracellular Ca+2 which leads to an in contractility. Digoxin also causes suppression of the AV node, an refractory period causes enhanced vagal tone and a ¯ ventricular rate.

Lidocaine blocks Na+ ions thus inhibits depolarization and blocks conduction, (¯ action potential specific for vent muscle cells with digoxin and lidocaine together you will ¯ conduction with digoxin at the AV node and ¯ conduction with lidocaine in the ventricular fibers by decreasing conduction in general.

How would the use of certain diuretics (loop and thiazides) potentiate the toxicity of antiarrhythmic drugs?

Loop diuretics inhibit reabsorption in the ascending loop of Henle of Na+/K+/Cl-, which causes water, Na, Cl, K, and Ca+2 to be excreted. Antiarrhythmic drugs function as Na+ channel blockers or Ca+2 blockers, or K+ blockers. The massive excretion by a potent diuretic and the blocking of channels can cause electrolyte imbalances and arrhythmias and frequency dependent block. where the drug gets in when the channel is open.

Last updated 04/10/00 12:26 PM
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