Farmacología de las drogas antiarrítmicas: Clases Ia y efectos

Notas del editor

1. Entre las taquiarritmias las mas frecuentes son las supraventriculares: - ---- fibrilacion auricular (FA) en la cual el latido cardiaco es totalmente irregular - la taquicardia paroxistica supraventricular (TSV)en el que el latido es rapido pero regular. Las taquicardias ventriculares son mucho menos habituales, pero mucho mas grave:comprenden la taquicardia ventricular y la fibrilacion ventricular y los sindromes.................
2. ACTIVIDA MARCAPASOS ECTÓPICA:aunque el marcapasos fisiológico se situa en el nodo SA, otros tejidos cardíacos pueden ejercer la actividad de marcapasos. Esto representa un mecanismo de seguridad por si fallase el nodo SA, aunque también puede originar taquiarritmias. Esta actividad marcapasos ectópica es favorecida por la activida simpatica y por la despolarizacion parcial que puede aparecer durante la isquemia. POSDEPOLARIZACION TARDIA: la principal causa de despolarizacion tardia en el musculo ventricular es el aumento anormal de Ca2+ intracelular, que desencadena una corriente de entrada, y por tanto, una serie de potenciales de accion anormales (taquicardia ventricular) REENTRADA:En condiciones normales, un impulso generado en el nodo SA estimula una sola vez el miocardio. Sin embargo en condiciones patologicas (bloqueo parcial de la conducción )un impulso puede reexcitar 2 o mas veces el miocardio despues de finalizar el periodo refractario; se hable entonces de REENTRADA DEL IMPULSO CARDÍACO,pudiendo dar lugar a una circulacion continua del impulso. Este es el principal mecanismo responsable de la aparición de las taquiarritmias clínicas. BLOQUEO CARDIACO: consecuencia de una fibrosis o lesion isquémica del sist de conduccion generalmente del nodoAV. Se produce un enlentecimiento de la conduccion o un bloqueo completo, en el cual laten de forma independiente las aurículas y los ventriculos: se trata mediante la implantacion de un marcapasos artificial
3. Clasificación de las DAA por Vaughan Williams según el efecto predominante.
4. Clasificación de las DAA por Vaughan Williams según el efecto predominante.
5. The Vaughn-Williams classification as I stated before divides antiarrhythmics based on certain ion channels they affect. Class I antiarrhythmics are sodium channel blockers and have direct membrane action upon the sodium channel. Class II antiarrhythmics are the beta-blockers and affect the heart by sympatholysis (beta blocking). Class III antiarrhythmics prolong repolarization by affecting the potassium channels and Class IV antiarrhythmics are calcium channel blockers. In addition to these classes other antiarrhythmics would include purinergic agonists and the digitalis glycosides, which do not fall in any of the above classifications.
6. The sodium channel blockers affect Phase 0 of depolarization-the rapid inflow of sodium through the sodium channels. They are divided into 3 subclasses. 1A includes quinidine, procainamide, and disopyramide. Class 1B includes lidocaine, mexiletine, and phenytoin. Finally, Class IC would include flecainide as well as the others listed on the slide.
7. As I said, Class I antiarrhythmics are sodium channel blockers. More specifically, Class IA depresses conduction and prolongs refractoriness of the atrial his-purkinje and ventricular tissue. There is also an affect of peripheral alpha blockade. These antiarrhythmics are vagolytic in nature and most are negative inotropes. EKG changes that occur with this class of antiarrhythmics include an increase in the PR interval and an increase in the QRS duration. Toxicity occurs as the corrected QT interval increases-this can be as much as 30% increase. There is also some calcium channel blockade making disopyramide a potent anticholinergic.
8. As I said, Class I antiarrhythmics are sodium channel blockers. More specifically, Class IA depresses conduction and prolongs refractoriness of the atrial his-purkinje and ventricular tissue. There is also an affect of peripheral alpha blockade. These antiarrhythmics are vagolytic in nature and most are negative inotropes. EKG changes that occur with this class of antiarrhythmics include an increase in the PR interval and an increase in the QRS duration. Toxicity occurs as the corrected QT interval increases-this can be as much as 30% increase. There is also some calcium channel blockade making disopyramide a potent anticholinergic.
9. As I said, Class I antiarrhythmics are sodium channel blockers. More specifically, Class IA depresses conduction and prolongs refractoriness of the atrial his-purkinje and ventricular tissue. There is also an affect of peripheral alpha blockade. These antiarrhythmics are vagolytic in nature and most are negative inotropes. EKG changes that occur with this class of antiarrhythmics include an increase in the PR interval and an increase in the QRS duration. Toxicity occurs as the corrected QT interval increases-this can be as much as 30% increase. There is also some calcium channel blockade making disopyramide a potent anticholinergic.
10. As I said, Class I antiarrhythmics are sodium channel blockers. More specifically, Class IA depresses conduction and prolongs refractoriness of the atrial his-purkinje and ventricular tissue. There is also an affect of peripheral alpha blockade. These antiarrhythmics are vagolytic in nature and most are negative inotropes. EKG changes that occur with this class of antiarrhythmics include an increase in the PR interval and an increase in the QRS duration. Toxicity occurs as the corrected QT interval increases-this can be as much as 30% increase. There is also some calcium channel blockade making disopyramide a potent anticholinergic.
11. As I said, Class I antiarrhythmics are sodium channel blockers. More specifically, Class IA depresses conduction and prolongs refractoriness of the atrial his-purkinje and ventricular tissue. There is also an affect of peripheral alpha blockade. These antiarrhythmics are vagolytic in nature and most are negative inotropes. EKG changes that occur with this class of antiarrhythmics include an increase in the PR interval and an increase in the QRS duration. Toxicity occurs as the corrected QT interval increases-this can be as much as 30% increase. There is also some calcium channel blockade making disopyramide a potent anticholinergic.
12. Uses of Class I antiarrhythmics at your level of training will include primarily procainamide. This medicine is a good medicine for the treatment of refractory reentry supraventricular tachycardia (we will discuss better agents to use initially), and ventricular tachycardia (again there are other agents which would be the first choice). It is also a good medicine for the treatment of atrial fibrillation and atrial flutter with patients on Digoxin especially. This medication does decrease the metabolism of other antiarrhythmics including amiodarone. We have outlined the doses on the slide as shown. These are much like the doses included in Harriet Lane. One thing to remember is that procainamide has an active metabolite-NAPA. I will discuss this in brief later, however, its mechanism of action is in the lines of a potassium channel blocker (Class III affects). In long-term use there are some side affects as listed above including a Lupus-like syndrome.
13. Lidocaine, mexiletine and phenytoin all fall into the Class IB antiarrhythmics. This is a nice group of medications to use as antiarrhythmics. They have little effect on normal tissues but decrease the effective refractory period and the purkinje cells. This decreases automoticity. Resultantly there is an increase in ventricular fibrillation threshold. Phenytoin in particular is useful in suppressing Digoxin-induced dysrhythmias and mexiletine is useful in depressing conduction times especially at higher heart rates. There is actually a slight decrease in the corrected QT interval with both Lidocaine and phenytoin, and mexiletine is quite useful in the treatment of patients with prolonged QT syndrome secondary to sodium channel abnormalities.
14. Lidocaine is one of the Class 1B antiarrhythmics that you should feel very comfortable using. As you know, its main use is in the acute treatment of ventricular tachycardia. It acts rapidly and there is no depression of contractility or AV conduction. Its half-life is extremely short-5-10 minutes in its first phase, then 80-110 minutes during its second phase. Therefore, a bolus must be followed relatively closely with a maintenance infusion. You must remember that there is decreased metabolism with congestive heart failure and hepatic failure as well as the certain medications including beta-blockers like propranolol and H2 blockers like cimetidine. There is increased metabolism with medications like Dilantin, Phenobarbital, isuprel.
15. Lidocaine is one of the Class 1B antiarrhythmics that you should feel very comfortable using. As you know, its main use is in the acute treatment of ventricular tachycardia. It acts rapidly and there is no depression of contractility or AV conduction. Its half-life is extremely short-5-10 minutes in its first phase, then 80-110 minutes during its second phase. Therefore, a bolus must be followed relatively closely with a maintenance infusion. You must remember that there is decreased metabolism with congestive heart failure and hepatic failure as well as the certain medications including beta-blockers like propranolol and H2 blockers like cimetidine. There is increased metabolism with medications like Dilantin, Phenobarbital, isuprel.
16. The dose is well described in your Harriet Lane manual but basically includes a 1mg/kg bolus followed by a 20-50 microgram/kp/min. infusion.
17. Mexiletine, a second 1B antiarrhythmic has good use in postoperative ventricular tachycardia (on the long-term, not acute basis). Its main side affects are gastrointestinal intolerance with a few patients developing some central nervous system complaints.
18. Phenytoin or Dilantin is also a useful medicine in postoperative ventricular tachycardia however, its use to remember primarily is that in Digoxin-induced arrhythmias. There are many medications which it affects including coumadin and verapamil. Remember the intravenous form of phenytoin can cause hypotension (secondary to the carrier, fos phenytoin is as effective as an antiarrhythmic without the hypotensive effects).
19. I have outlined the dose of flecainide, one of the more common antiarrhythmics that you may see, solely for your reference. Again, I would stress hesitancy in using these medications without the guidance of a Pediatric Cardiologist. The Class 1C antiarrhythmics have very little use in adults currently after a particular 1C-encainide was actually shown to have an increased mortality rate in a large adult study of antiarrhythmias. Based on this study, these medications have absolutely no utility in the postoperative patient.
20. I have outlined the dose of flecainide, one of the more common antiarrhythmics that you may see, solely for your reference. Again, I would stress hesitancy in using these medications without the guidance of a Pediatric Cardiologist. The Class 1C antiarrhythmics have very little use in adults currently after a particular 1C-encainide was actually shown to have an increased mortality rate in a large adult study of antiarrhythmias. Based on this study, these medications have absolutely no utility in the postoperative patient.
21. The Class IC antiarrhythmics are rarely used in the acute setting. They have many affects on the conduction of the heart and propofenone is a relatively profound negative inotrope. These medications should be used under the guidance of a Pediatric Cardiologist primarily for long-term treatment of dysrhythmias. One of the most important things to remember is that all of these medications (propofenone more than the other 2) can prolong the QT interval. This, in combination with other medications, which prolong the QT interval, can become very serious.
22. The Class II agents are commonly referred to as the beta- blockers. The first 5 listed here are the primarily beta-blocker medications you will be exposed to. Sotalol is an interesting beta-blocker designer drug with properties both related to its beta-blocker roots as well as properties of potassium channel blocker like the Class III antiarrhythmics.
23. Propranolol is probably the most common beta-blocker you will see in pediatric practice. This is because of its availability as a syrup as well as because of its properties as an antiarrhythmic. It is an excellent medicine for reentry as well as ectopic supraventricular tachycardias. Likewise, its beta-blocker properties make it a good choice for patients with sinus tachycardia secondary to thyrotoxicosis. Finally, it does have a fairly good profile in the treatment of exercised-induced ventricular tachycardia (although arguably Atenolol would be a preferred medication). Its half-life is approximately 3 hours requiring a 6 hour dosing schedule (although many cardiologists have been able to “get away with” every 8 hour dosing.
24. Propranolol is probably the most common beta-blocker you will see in pediatric practice. This is because of its availability as a syrup as well as because of its properties as an antiarrhythmic. It is an excellent medicine for reentry as well as ectopic supraventricular tachycardias. Likewise, its beta-blocker properties make it a good choice for patients with sinus tachycardia secondary to thyrotoxicosis. Finally, it does have a fairly good profile in the treatment of exercised-induced ventricular tachycardia (although arguably Atenolol would be a preferred medication). Its half-life is approximately 3 hours requiring a 6 hour dosing schedule (although many cardiologists have been able to “get away with” every 8 hour dosing.
25. The doses are outlined in this slide and are very similar to those in many reference manuals. One particular comment about propranolol is that it does cross the blood brain barrier and has been associated with changes affect of patients. In the teenagers this can be relatively profound, and Atenolol appears to have less profound of an affect. However, patients “adjust” to this within a couple of weeks of therapy in most cases. Beta-blockers are a negative inotrope and they also can cause decreased blood pressure by suppressing the renin aldosterone, angiotensin axis.
26. Class III antiarrhythmics are the potassium channel blockers. These medications prolong repolarization therefore prolonging the action potential duration. They do not affect contractility in most cases. Class III agents include amiodarone, Sotalol, bretylium, as well as the metabolite of procainamide-NAPA. Most of these medications do not solely function as a potassium channel blocker and have beta-blocker as well as calcium channel blocker activity. For the function of this discussion, I will de-emphasize these antiarrhythmics in that most should be administered under the guidance of a Pediatric Cardiologist and have little or not use in the acute treatment of dysrhythmias.
27. Class III antiarrhythmics are the potassium channel blockers. These medications prolong repolarization therefore prolonging the action potential duration. They do not affect contractility in most cases. Class III agents include amiodarone, Sotalol, bretylium, as well as the metabolite of procainamide-NAPA. Most of these medications do not solely function as a potassium channel blocker and have beta-blocker as well as calcium channel blocker activity. For the function of this discussion, I will de-emphasize these antiarrhythmics in that most should be administered under the guidance of a Pediatric Cardiologist and have little or not use in the acute treatment of dysrhythmias.
28. Class III antiarrhythmics are the potassium channel blockers. These medications prolong repolarization therefore prolonging the action potential duration. They do not affect contractility in most cases. Class III agents include amiodarone, Sotalol, bretylium, as well as the metabolite of procainamide-NAPA. Most of these medications do not solely function as a potassium channel blocker and have beta-blocker as well as calcium channel blocker activity. For the function of this discussion, I will de-emphasize these antiarrhythmics in that most should be administered under the guidance of a Pediatric Cardiologist and have little or not use in the acute treatment of dysrhythmias.
29. Class III antiarrhythmics are the potassium channel blockers. These medications prolong repolarization therefore prolonging the action potential duration. They do not affect contractility in most cases. Class III agents include amiodarone, Sotalol, bretylium, as well as the metabolite of procainamide-NAPA. Most of these medications do not solely function as a potassium channel blocker and have beta-blocker as well as calcium channel blocker activity. For the function of this discussion, I will de-emphasize these antiarrhythmics in that most should be administered under the guidance of a Pediatric Cardiologist and have little or not use in the acute treatment of dysrhythmias.
30. Class III antiarrhythmics are the potassium channel blockers. These medications prolong repolarization therefore prolonging the action potential duration. They do not affect contractility in most cases. Class III agents include amiodarone, Sotalol, bretylium, as well as the metabolite of procainamide-NAPA. Most of these medications do not solely function as a potassium channel blocker and have beta-blocker as well as calcium channel blocker activity. For the function of this discussion, I will de-emphasize these antiarrhythmics in that most should be administered under the guidance of a Pediatric Cardiologist and have little or not use in the acute treatment of dysrhythmias.
31. Class III antiarrhythmics are the potassium channel blockers. These medications prolong repolarization therefore prolonging the action potential duration. They do not affect contractility in most cases. Class III agents include amiodarone, Sotalol, bretylium, as well as the metabolite of procainamide-NAPA. Most of these medications do not solely function as a potassium channel blocker and have beta-blocker as well as calcium channel blocker activity. For the function of this discussion, I will de-emphasize these antiarrhythmics in that most should be administered under the guidance of a Pediatric Cardiologist and have little or not use in the acute treatment of dysrhythmias.
32. Class III antiarrhythmics are the potassium channel blockers. These medications prolong repolarization therefore prolonging the action potential duration. They do not affect contractility in most cases. Class III agents include amiodarone, Sotalol, bretylium, as well as the metabolite of procainamide-NAPA. Most of these medications do not solely function as a potassium channel blocker and have beta-blocker as well as calcium channel blocker activity. For the function of this discussion, I will de-emphasize these antiarrhythmics in that most should be administered under the guidance of a Pediatric Cardiologist and have little or not use in the acute treatment of dysrhythmias.
33. Class III antiarrhythmics are the potassium channel blockers. These medications prolong repolarization therefore prolonging the action potential duration. They do not affect contractility in most cases. Class III agents include amiodarone, Sotalol, bretylium, as well as the metabolite of procainamide-NAPA. Most of these medications do not solely function as a potassium channel blocker and have beta-blocker as well as calcium channel blocker activity. For the function of this discussion, I will de-emphasize these antiarrhythmics in that most should be administered under the guidance of a Pediatric Cardiologist and have little or not use in the acute treatment of dysrhythmias.
34. Class III antiarrhythmics are the potassium channel blockers. These medications prolong repolarization therefore prolonging the action potential duration. They do not affect contractility in most cases. Class III agents include amiodarone, Sotalol, bretylium, as well as the metabolite of procainamide-NAPA. Most of these medications do not solely function as a potassium channel blocker and have beta-blocker as well as calcium channel blocker activity. For the function of this discussion, I will de-emphasize these antiarrhythmics in that most should be administered under the guidance of a Pediatric Cardiologist and have little or not use in the acute treatment of dysrhythmias.
35. Class III antiarrhythmics are the potassium channel blockers. These medications prolong repolarization therefore prolonging the action potential duration. They do not affect contractility in most cases. Class III agents include amiodarone, Sotalol, bretylium, as well as the metabolite of procainamide-NAPA. Most of these medications do not solely function as a potassium channel blocker and have beta-blocker as well as calcium channel blocker activity. For the function of this discussion, I will de-emphasize these antiarrhythmics in that most should be administered under the guidance of a Pediatric Cardiologist and have little or not use in the acute treatment of dysrhythmias.
36. Class III antiarrhythmics are the potassium channel blockers. These medications prolong repolarization therefore prolonging the action potential duration. They do not affect contractility in most cases. Class III agents include amiodarone, Sotalol, bretylium, as well as the metabolite of procainamide-NAPA. Most of these medications do not solely function as a potassium channel blocker and have beta-blocker as well as calcium channel blocker activity. For the function of this discussion, I will de-emphasize these antiarrhythmics in that most should be administered under the guidance of a Pediatric Cardiologist and have little or not use in the acute treatment of dysrhythmias.
37. Purinergic agonists is a fancy way to describe adenosine. Currently, it is the only medication in this class (although different attempts at varying the molecule have been made in an attempt to capture patents and increase profits at different drug companies). Its mode of action includes a direct affect on the slow inward calcium current and increasing potassium conductance therefore hyperpolarizing the cell. It also is a potent vagotonic and antiadrenergic medication. When evaluated by electrophysiology study, it increases the length of time between an atrio-electrocardiogram and a His-electrocardiogram (it increases time of conduction through the AV node).
38. Purinergic agonists is a fancy way to describe adenosine. Currently, it is the only medication in this class (although different attempts at varying the molecule have been made in an attempt to capture patents and increase profits at different drug companies). Its mode of action includes a direct affect on the slow inward calcium current and increasing potassium conductance therefore hyperpolarizing the cell. It also is a potent vagotonic and antiadrenergic medication. When evaluated by electrophysiology study, it increases the length of time between an atrio-electrocardiogram and a His-electrocardiogram (it increases time of conduction through the AV node).
39. Adenosine’s main treatment use is in the termination of reentry tachycardias. It also can be used in other atrial tachycardias to provide atrio-ventricular block for diagnosis. It is metabolized rapidly by red blood cells and vascular endothelial cells and therefore is a short-acting medication. Its half-life is less than 10 seconds.
40. Adenosine’s main treatment use is in the termination of reentry tachycardias. It also can be used in other atrial tachycardias to provide atrio-ventricular block for diagnosis. It is metabolized rapidly by red blood cells and vascular endothelial cells and therefore is a short-acting medication. Its half-life is less than 10 seconds.