Anti-Arrhythmic agents week 3 Flashcards
Class IA anti-arrhythmics
Drugs in this class
MOA (channel it works on)
effects on AP
clinical use
CI
Disopyramide, Quinidine, Procainamide,
The Double Quarter Pounder
MOA: Sodium channel blockers
AP effects: Increase AP duration, increase effective refractory period (ERP), increase QT interval
Clinical use: Both atrial and ventricular arrhythmias, especially re-entrant and ectopic SVT and VT
Worsens mortality in post MI patients bc they have the substrate for for re-entry and these drugs may complete re-entry circuit
Procainamide
half life
toxicities
- Derivative of anesthetic procaine
- Effective in atrial & ventricular arrhythmias
- Short half-life (4 hrs) but sustained release preparation available (12 hrs half life)
Toxicity
- hypotension – when given IV
- lupus like syndrome – slow acetylators more likely to develop
- active metabolite N-acetylprocainamide (NAPA), has class III action very pro-arrhythmic, so not approved.
- thrombocytopenia, torsades de pointes due to prolonged QT interval
Quinidine
effect on PANS
toxicities
Drug-drug interaction
What two other drugs share the same drug-drug interaction?
Quinidine
- Chiral isomer in nature (other is quinine)
- Vagolytic action – decrease PANS effect
- Effects atrial & ventricular arrhythmias
Toxicity
- diarrhea
- Cinchonism – dizziness, vertigo, tinnitis
- thrombocytopenia
- torsade arrhythmia from QT prolongation
- digoxin interaction
Quinidine Digoxin Interaction(s)
Direct pharmacokinetic interaction:
- Quinidine displaces digoxin from binding sites, especially on striated muscle causing an increase in serum digoxin levels that can cause digoxin toxicity.
- Quinidine decreases the renal clearance of digoxin, this leads to increased digoxin levels and increased dig toxicity.
- Note that verapamil and amiodarone have the same drug drug interaction with digoxin
- a) Digoxin is often used to slow AV node conduction due to a direct effect on the AV node (slows conduction) and an indirect effect (increasing vagal tone) increasing AV node refractoriness.
b) Quinidine is vagolytic, so it reduces the digoxin slowing at AV node due to increased vagal tone.
* Quinidine can undo AV nodal block by digoxin
Disopyramide
toxicities
use (outside of atrial and ventricular arryhthmias)
- Effective in atrial & ventricular arrhythmias
Toxicities:
- thrombocytopenia, torsades de pointes due to prolonged QT interval
- Decrease LV function strongly
- Vasoconstriction – withdrawal parasympathetic dilation
-
Atropine like side effects
- urinary retention
- warmth
- dry mouth
- blurred vision
Used for hypertrophic cardiomyopathy patients since the drug decreases contractility and thus reduced outflow obstruction, the pathophysiologic disease problem in the cardiomyopathy.
Class IB anti-arrhythmics
Drugs in this class
MOA (channel it works on)
effects on AP
clinical use
toxicities
Lidocaine, Mexiletine
“I‘d Buy Liddy’s MexicanTacos”
Phenytoin can also fall into IB category
MOA: Na channel blocker, fast on fast off channel binding kinetics-weakly inhibits phase 0.
AP effects: decrease AP duration. Preferentially effect ischemic or depolarized Purkinje and ventricular tissue.
Clinical use: Acute ventricular arrhythmias (especially post MI), digitalis-induced arrhythmias. IB is Best post- MI
Toxicities: CNS stimulation/depression (tremors, delirium, coma), cardiovascular depression
Lidocaine
half life
form of administration
effects
toxicities
What binds to and inactivates lidocaine in MI pts?
Lidocaine
- Only IV-High first pass metabolism by liver so must be given IV
- Very short initial half-life
- CNS toxicity
- Only works on ventricular tissue – poor binding to atrial tissue.
- Does not suppress LV function
- α – acid glycoprotein, an acute phase reactant protein binds & inactivates lidocaine, the glycoprotein increased in MI, so less drug available in MI patients acutely.
- Used in MI pts, especially effective in binding to Na channels in ischemic tissue –very useful in MI patients to suppress ventricular automaticity.
Mexiletine
form of administration
use
Mexiletine
- Orally active congener of lidocaine
- Also used in certain types of genetic arrhythmias-SCN5a LQT syndrome
Class IC anti-arrhythmics
Drugs in this class
MOA (channel it works on)
effects on AP
clinical use
CI
Flecainide, Proafenone
“Can I have Fries Please”
MOA: Na channel blockers, slow binding and very slow release from Na channel
AP effects: Significantly prolongs ERP in AV node and accessory bypass tracts. No effect on ERP in Purkinje and ventricular tissue. Minimal effect on AP duration.
Use: SVTs, including A Fib. Only as a last resort in refractory VT
Toxicity: Proarrhythmic, especially post-MI-contraindicated. IC is Contrainidcated in structural and ischemic heart disease. Decreases LV function-why CI in structural heart disease
Flecainide: toxicities
Propafenone: toxicities
Flecainide
- Fluorinated version of procainamide
- Can be very proarrhythmic, used in atrial arrhythmias in people with normal left ventricles
- Suppresses LV function
- Increases mortality in low EF patients, increase conduction delay making re-entry more likely
Propafenone
- Weak ß blocker & calcium channel blocker with Ic action like flecainide
- Used for supraventricular arrhythmias in patients with good LV function
- Negatively inotropic
- Proarrhythmic in low EF patients
Class II antiarrhythmics
Drugs in this class
MOA
AP effects
Clinical use
Toxicities
How is B blocker OD treated?
Beta-Blocker – Class II (B is second letter in alphabet)
Propranolol
- Blocks ß receptor as well as some Class Ia action (membrane stabilizing)
- Nonselective ß blocker
Metoprolol
- Selective ß1
- Non polar – enters CNS, more CNS side effects
Atenolol
- Selective ß1
- Polar – less CNS side effects
Esmolol
- Short action – minutes. esmolol: effects end quickly
- Ester linkage disrupted by body esterase’s almost as fast as drug can be given
- Given IV
MOA: Decrease SA and AV nodal activity by decreases cAMP, decrease Ca2+ currents. Suppres abnormal pacemakers by decreasing slope of phase 4. AV node particularly sensitive–>increase PR interval.
Clinical use: SVT, ventricular rate control for a fib and a flutter
Toxicities:
Impotence, exacerbation of COPD and asthma, cardiovascular effects (bradycardia, AV block, HF), CNS effects (sedation, sleep alterations).
B blockers can cause unopposed a1 agonism if given alon for pheochromocytoma or cocaine toxicity.
Drug specific toxicities:
Metoprolol: dyslipidemia.
Propanolol: can exacerbate vasospasm in Prinzmetal angina (non-specific-blocks B2 receptors)
B blocker overdose: saline (increase preload), atropine (decrease parasympathetic tone), glucagon
Class III antiarrhythmics
Drugs in this class
MOA
effects on AP
Clinical use
Class III antiarrhythmics-K+ channel blockers
letter K: made of up 3 lines
Drugs in this class: AIDS: Amiodarone, Ibutilide, Dofetilide, Sotalol
also Dronedarone
MOA: : K channel blockers.
Effects on AP: Increase AP duration, increase ERP, increase QT interval
Clinical use: Atrial fibrillation, atrial flutter, ventricular tachycardia (amiodarone, sotalol)
Amiodarone
half life
active metabolite
toxicities
What must be monitored in patients after giving amiodarone?
What is the significance of amiodarone as it pertains to sudden cardiac arrest?
Amiodarone
- Most effective anti-arrhythmic drug
- Used for atrial & ventricular arrhythmias
- Has iodine (two) in molecule that contributes to thyroid toxicity can result in hypo- or hyper-thyroidism
- Weak sodium channel blocker, weak Ca blocker
- thyroid
- Meta analysis of multiple studies shows it to be only anti-arrhythmic that reduces sudden death recurrence post cardiac arrest
- Half-life is 55 days – very long acting
- Has an active metabolite also long acting (desethyl amiodarone)
Toxicities:
Pulmonary fibrosis, hepatotoxicity, hypo/hyperthyroidism (amiodarone is 40% iodine by weight), acts as hapten-corneal deposits, blue/gray skin depositis resulting in photodermatitis, neurologic effects (neuropathy, dizziness, lightheadedness, weakness), constipation, cardiovascular effects-bradycardia, heart block, HF
Dronedarone
clinical use
toxicities
CI
Dronedarone
- Amiodarone like chemical structure without iodine
- Used for SVT
- Pro-arrhythmic – much more than amiodarone, problem in lower EF pts
- Higher mortality in CHF & persistent AF pts – not recommended for these groups
- Not the amiodarone without toxicity it was advertised as
- Other toxicities: liver, GI, loss of taste
Sotalol
clinical use
toxicities
Sotalol
- Strong ß blocker
- Treats atrial arrhythmias with normal EF
- SVT, ventricular tachycardia
- Proarrhythmic (Torsade) – especially in low EF patients
- Chiral drug – d Sotalol no ß blocking action, only Class III activity
- Used for SVT, avoid in low EF patients due to proarrhythmia
Toxicity: Torsade de pointes, excessive B blockade-B blocker toxicities
Dofetilide
use
toxicities
how is it eliminated?
how is it dosed? (relatively)
Dofetilide
- Pure class III drug
- A fib, A flutter
- Proarrhythmia in low EF pts
- Renal clearance primarily elimination, adjust in renal disease by GFR.
- Very potent agent, administered in micrograms, not milligrams.
