Pharm 11- Antiarrhythmics Flashcards
Arrythmia
abnormalities in the electrical impulse generation of conduction through the heart
What percent of anesthetized patients have arrythmias?
> 50%
What percent of patinets with MIs have arrhythmias?
80%
How do virutally all antiarrythmics work?
Altering the ionic transmembrnae balance (Na+ Ca++, K+) or the sympathetic tone to the heart; which alters the shape of the action potential
What is the name of the classification system that classifies 4 types of antiarrhythmics?
The Vaughan Williams Classification
What classes are Na+ channel blockers?
1A, 1B, 1C
What class is B-Blockers?
2
WHat class is K+ blocker?
3
What class is Ca++ channel blocker?
4
How does class IA work on the action potential?
Slows phase 0 depolarization in ventricular muscle fibers
How does class IB work on the action potential?
Shortens Phase 3 repolarization in ventricular muscle fibers
How does class IC work on the action potential?
Markely slows phase 0 depolarization in ventricular muscle fibers
How does class II work on the action potnetial?
Inhibits phase 4 depolarization in SA and AV nodes
How does class III work on the action potential?
Prolongs phase 3 repolarization in ventricular muscle fibers
How does class IV work on the action potential?
Inhibits action potential in SA and AV nodes
How do Class I: Na+ Channel Blockers work?
Preferentially bind to open Na+ channels rather than to fully repolarization Na+ channels; preferentially block conduction in tssues that are depolarizing more frequently (use-dependence blockade)
Use-Dependence Blockade
preferentially blocking conduction in tissues that are depolarizing more frequently; used in Class I: Na + channel blockers
How are the 3 subclasses of Class I antiarrythmics differentiated?
Ia: Shorten the AP and affect QRS
Ib: Shortern the AP w/o affecting QRS
Ic: Does not shorten the AP
Which Class is nicknamed “Membrane stabilizers?”
Class Ia: Na+ Channel Blockers
How do Class Ia: Na+ Channel Blockers shift the action potential?
Shift to the right by slowing Phase 0 depolarization; hence their nickname “membrane stabilizers”; also inhibits some K+ channels (class III activitY) which widens the AP causing prolonged QT intervals
How do Class Ia: Na+ Channel Blockers widen the AP causing prolonged QT intervals?
They inhibit some K+ channels (class III activitY)
What is the pneumonia to remember Ia drugs?
Double Quarter Pounder
What are the three Class Ia drugs?
Double Quarter Pounder
Disopyramide (Norpace)
Quinidine (Quinidex)
Procainamide (Pronestryl, Procan)
Quinidine (Quinidex)
Administered Orally
Various tachyarrhythmias, but rarely used due to toxic side effects: Cinchonism/Torsades de Pointes
Cinchonism
poisoning due to excessive ingestion of cinchona alkaloids; unclear vision red skin vomiting vertigo diarrhea
Torsades de Pointes
Polymorphic Ventricular Tachycardia
usually resolves spontaneously; may devolve in to V-fib
Dispyramide (Norpace)
More negative inotropic effects and increase SVR than Quinidine (Quinidex); could precipitate HF
3-4th line antiarrythmic
What is the most widely used Ia: Na+ channel blocker?
Procainamide (Pronestryl, Procan)
Procainamide (Pronestryl, Procan)
most widely used Ia
Derived from procaine (anesthetic)
Given orally IV, IM
Adverse effects similar to Quinidine (although less severe) but may cause reversible lupus erythematosus
Reversible Lupus Erythematosus
Autoimmune disease; Neurologic manifestations are among the features of systemic lupus erythematosus (SLE), a multisystem autoimmune connective tissue disorder with various clinical presentations. SLE affects many organ systems, including the central and peripheral nervous systems and muscles
How do Class Ib: Na+ Channel Blockers shift the action potential?
Shift the AP to the left by shortening Phase 3 repolarization.
Where do class Ib : Na+ Channel Blockers have their greatest effect?
Heart cells with long action potentials like Purkinje fibers and ventricular myocytes
What is the pneumonic for remember Class Ib: Na+ channel blockers?
Lettuce, Mayo and Tomato
What are some examples of Class Ib: Na+ Channel Blockers
Lidocaine (Xylocaine)
Mexiletine (Mextil)
Tocainide (Tonocard)
Lidocaine (Xylocaine)
Local anesthetic
Only given parenterally
Wide therapeutic index
Extends refractory period further into diastole in depressed cardiomyocytes than healthy ones (sick heart cells have a longer refractory period so they cant fire as fast)
What is the major toxic side effect of Lidocaine (Xylocaine) at high doses?
Cardiac depression
What is the drug of choice for ventricular arrhythmias particularly those associated with “sick hearts’ with arrhythmias like post MI?
Lidocaine (Xylocaine)
*or post XC removal
Why is Lidocaine (Xylocaine) a common component of cardioplegia?
To stop arrhythmias; minimizes instances of ventricular arrhythmias Ex. used for PVCs
If choosing between EKGs which patient should receive lidocaine (xylocaine) what do you look for?
Ventricular anomalies such as PVCs; ventricular arrhythmias
Mexiletine (Mextil)
Like an oral lidocaine (xylocaine)
used in the treatment of ventricular tachyarrythmias
Tocainide (Tonocard)
Like lidocaine (xylocaine) Given orally used in patients resistance to and or sensitive to lidocaine (xylocaine) /mexiletine (mextil)
What is Tocainide (Tonocard) a second or third line treatment and not a first?
Pulmonary toxicity fairly common; can cause pulmonary fibrosis rendering i a 2nd or 3rd line treatment; can be as fatal as ventricular arrhythmias
What are the effects of giving Class Ic: Na+ Channel Blockers?
Does not shift the action potential.
Ic’s even have profound effects on normal hearts. Recent studies indicate some are very dangerous and are not used when better/safer alternatives are available (being phased out)
What is the pneumonic for remember Class Ic: Na+ Channel Blockers?
Fries Please
What are the two Class Ic: Na+ Channel Blockers? (fries please)
Flecainide (Tambocor)
Propafenone (Rhythmol)
What is the effect of giving Flecainide (Tambocor)?
Given orally
Suppresses Phase 0 upstroke in Purkinje fibers and cardiomyocytes
Dramatically slows conduction and automaticitiy is decreased via an increase in the threshold potential
(more harm than good)
What is Flecainide (Tambocor) used for?
Refractory ventricular arrhythmias (particularly PVCs)
What effects of Flecainide (Tambocor) worsen CHF?
Negative inotropic effects
Propafenone (Rhythmol)
Similar uses as quinidine; given orally
Considered to be a “broad spectrum” antiarrythmic but used mostly for supraventricular tachyarrhythmias
How do Class II: B-Adrenoceptor Blockers work?
Work by diminishing Phase 4 depolarization= decreased automaticity, prolonged AV conduction, negative chronotrope, negative inotrope
B1-blockers are selective for what?
Cardioselective, but many/most have other adrenergic blocker activity; some have partial adrenergic agonist activity
What arrhythmias are B-Adrenoceptor Blockers used for?
Atrial tachyarrhythmias Includes AV nodal re-entrant tachyarrythmias (most common type, particularly in women) Ventricular arrhythmias (post MI)
AV Nodal Re-entrant Tachyarrhythmias
Ectopic dischange during refractory period; cycle of circulating current is conducted
two tracts depolarizing at a different rate; two conducting tissues with different electrical properties; no abnormality on the EKG at rest
What are some B-blockers used as antiarrhythmics?
Propranolol (inderal)
Metoprolol (Lopressor, Toprol- XL)
Esmolol (Brevibloc)
Propranolol (Inderal)
Extenstively used for decades
Has been proven to decrease incidence of mortality within the first year of an MI
The most commonly used B-blocker for treating cardiac arrythmias (less B2 than Inderal)
Metoprolol (Lopressor, Toprol-XL)
Esmolol (Brevibloc)
Very short acting IV B-blocker commonly used during surgery and during emergencies
How do Class III: K+ Channel Blockers work?
Block K+ channels with little effect on Na+ channels
Blocking the outward flow of K+ during repolarization they prolong the action potential without affecting Phase 0 (depolarization)
Increases refractory period and refractoriness; makes them less sensitive to arrhythmias
How do Class III: K+ block re-entrant arrhythmias?
Prolonged AP with normal conduction velocity
What are the negative side effects of Class III: K+ Channel Blockers?
Reverse use-dependence blockade; which can contribute to arrhythmias; generally prolong the QT
What are the Class III: K+ Channel Blockers
Amiodarone (Cordarone) Drondarone (Multaq) Sotalol (Betapace, Sorine) Dofetilide (Tikosyn) Ibutilide (Corvert)
Amiodarone (Cordarone)
Iodinated Benzofuran, which means it looks a little like thyroxine; effects all cardiac tissues so it has a broad-spectrum of antiarrhythmic acitivty
2nd Line Rx for lots of refractory arrhythmias
What is the drug of choice for A-fib?
Amiodarone (Cordarone)
What is the half-life of amiodarone?
Very long half-life (20-100 days) combined with high ability to interact with other drugs and a boat-load of side-effects (particularly with long-term use) limits its use
At what dosages do you get less toxicity?
100-200 mg/ day; but it takes weeks to months to get therapeutic levels because of the long half-life
What high loading doses of amiodarone must you give?
800-1600 mg/day
What are some side effects of amiodarone?
Sinus Bradycardia
Hypotension
ARDS and Pulmonary Fibrosis
and “a lot of other nasties”
Dronedarone (Multaq)
Like amiodarone but w/o iodine (no thyroid dysfunction or blue skin)
Much shorter half-life (24 hours) than amiodarone
less effective than amiodarone for a-fib but has fewer of those side effects except risk of stroke and death
Sotalol (Betapace, Sorine)
Non-selective B-blocker
Reduces post Mi mortality
Class III activity (lengthens the refractory period)
Reduces myocardial o2 consumption and acts as a powerful antiarrhthmic
Prevents fibrillation and makes defibrillating patients easier to its idea for post-MI patients
What is the drug of choice for a-fib patients with HF or low ejection fractions?
Dofetilide (Tikosyn)
What is the drug of choice for a fib?
Ibutilide (Corvert)
Ibutilide (Corvert)
Class III and Ia antiarrhythmic properties
What class if antiarrhtyhmics are more prone than others to cause arrhythmias?
Class III: K+ Channel blockers
What is the effect of Class IV: Ca++ Channel Blockers?
Decrease the rate of Phase 4 spontaneous depolarization
Preferentially slow the rate of conduction in tissues dependent on calcium currents for depolarization
What are examples of some Ca++ Channel Blockers?
Verapamil (calan, isoptin)
Cardizem (diltiazem)
Nifedipine (procardia)
What is the order of preference of Ca++ Channel Blockers to use?
Verapamil > Cardizem > Nifedipine
Verapamil/Cardizem for Arrhythmias
Interchangably for arrhtyhmias
Preferentially block the voltage sensitive channels
use-dependent (preferring to block channels on tissues depolarizing too fast) and block Ca++ channels most effectively on the AV and SA nodes
Tx Hypertension, angina, a flt
Since Verapamil and Cardizem are both negative inotropes, so they should be avoided….
Patients with depressed EF, pateints with HF
What are the classless antiarrhythmis?
Digoxin
Adenosine (Adenocard)
Magnesium Sulfate
Digoxin
Shortens the refractory period in atrial and ventricular tissue while slowing conduction through the AV node; used to control ventricular response rates in a-fib and a-flut
What is the drug of choice for abolishing SVT?
Adenosine (Adenocard)
Adenosine
fast IV push on bypass; decresaes av node automaticity and cardiac conduction velocity and automaticity
Short half-life 10-15 sec
Adenosine Dose
First dose: 6 mg fast IV push
If that doesn’t convert the SVT give 12 mg fast IV push
What is the drug of choice for digoxin-induced arrhythmias?
Magnesium Sulfate
Magnesium Sulfate
Slows rate of SA node impulse formation and the rate at which the impulse travels through myocardium
must be given iv to be effective as an antiarrhtyhmic
