Flashcards in Cardio - Pharm (Part 3: Cardiac glycosides & Antiarrhythmics) Deck (57)
What is a prominent example of a cardiac glycoside? What is its % bioavailability, % protein bound, and half-life?
Digoxin - 75% bioavailabiity, 20-40% protein bound, t1/2 = 40 hours
How is digoxin cleared from the body?
What is the mechanism by which cardiac glycosides/digoxin work? What are the 2 major effects that this has?
Direct inhibition of Na+/K+ ATPase leads to indirect inhibition of Na+/Ca2+ exchanger/antiport. (1) Increased intracellular [Ca2+] --> positive inotropy. (2) Stimulates vagus nerve --> decrease HR.
For what 2 conditions are cardiac glycosides/digoxin used clinically, and why?
(1) CHF (increase contractility) (2) Atrial fibrillation (Decrease conduction at AV node & depression of SA node)
What 3 major toxicities are associated with cardiac glycosides/digoxin? Describe each.
(1) Cholinergic- nausea, vomiting, diarrhea, blurry yellow vision (Think: "Van Gogh") (2) ECG - Increased PR, Decreased QT, ST scooping, T-wave inversion, arrhythmia, AV block (3) Can lead to hyperkalemia, a poor prognostic indicator
What findings can cardiac glycosides cause on an ECG?
Increased PR, Decreased QT, ST scooping, T-wave inversion, arrhythmia, AV block
What are 3 factors predisposing patients to cardiac glycoside/digoxin toxicity, and why?
(1) Renal failure (decreased excretion) (2) Hypokalemia (permissive for digoxin binding at K+-binding site on Na+/K+ ATPase) (3) Verapamil, Amiodarone, Quinidine (Decreases digoxin clearance, displaces digoxin from tissue-binding sites)
What is/are the antidote(s) for cardiac glycosides/digoxin?
Slowly normalize K+, lidocaine, cardiac pacer, anti-digoxin Fab fragments, Mg2+
What class are Antiarrhythmics that act as Na+ channel blockers? What are the subdivisions of this class? Give at least 2 examples of drugs that fall under each subdivision.
Class I; Class IA - Quinidine, Procainamide, Disopyramide; Class IB - Lidocaine, Mexiletine; Class IC - Flecainide, Propafenone
What 3 mechanistic effects do Class IA antiarrhythmics have?
(1) Increase AP duration, (2) Increase effective refractory period (ERP), (3) Increase QT interval.
For what kinds of arrhythmias do Class IA antiarrhythmics work?
Both atrial and ventricular arrhythmias, especially re-entrant and ectopic supraventricular (SVT) and ventricular (VT) tachycardia
Name 3 Class IA antiarrhythmics.
(1) Quinidine (2) Procainamide (3) Disopyramide
What are 5 toxicities are associated with Class IA antiarrhythmics? Specify which toxicities apply to only certain drugs in this class.
(1) Cinchonism (headache, tinnitus with quinidine) (2) Reversible SLE-like syndrome (procainamide) (3) Heart failure (disopyramide) (4) Thrombocytopenia (5) Torsades de pointes due to increased QT interval
Name 2 Class IB antiarrhythmics. What other drug can fall into this category?
(1) Lidocaine (2) Mexiletine; Phenytoin can also fall into the IB category.
What is the mechanism of Class IB antiarrhythmics? What do Class IB antiarrhythmics preferentially affect?
Decrease AP duration. Preferentially affect ischemic or depolarized Purkinje and ventricular tissue
For what kinds of arrhythmias are Class IB antiarrhythmics used?
Acute ventricular arrhythmias (especially post-MI), digitalis-induced arrhythmias. Think: "IB is Best post-MI"
What are 2 toxicities associated with Class IB antiarrhythmics?
(1) CNS stimulation/depression (2) Cardiovascular depression
Name 2 Class IC antiarrhythmics.
(1) Flecainide (2) Propafenone; Think: "class iC Flecainide Propafenone = Can I have Fries, Please."
What is the mechanism of Class IC antiarrhythmics? How does it differ from Class IA/IB antiarrhythmics?
Significantly prolongs refractory period in AV node. Minimal effect on AP duration.
For what kind of arrhythmias are Class IC antiarrhythmics used clinically?
SVTs, including atrial fibrillation. Only as a last resort in refractory VT.
What is a toxicity of Class IC antiarrhythmics? In what condition(s) are they contraindicated?
Proarrhythmic, especially post-MI (contraindicated). IC is Contraindicated in structural and ischemic heart disease.
What effect do Class I Antiarrhythmics (Na+ channel blockers) have on each of the following: (1) Conduction (2) Phase 0 depolarization (3) Threshold for firing in abnormal pacemaker cells.
(1) Slow or block (decrease) conduction (especially in depolarized cells) (2) Decrease slope of phase 0 depolarization and (3) Increase threshold for firing in abnormal pacemaker cells.
Are Class I antiarrhythmics (Na+ channel blockers) state dependent or independent? Why or why not?
Are state dependent (selectively depress tissue that is frequently depolarized [e.g., tachycardia])
What metabolic condition causes increased toxicity for all class I antiarrhythmics?
Hyperkalemia causes increased toxicity for all class I drugs.
Graph the Na current of ventricular depolarization, depicting changes in slope of phase 0 caused by each of the following Class I antiarrhythmics: (1) Class IA (2) Class IB (3) Class IC.
See p. 302 in First Aid 2014 for the 3 graphs on the right hand side. Note: Class IC decreases slope the most, then Class IA, then Class IB
What kind of drugs make up Class II antiarrhythmics? What are 6 examples of such drugs?
Antiarrhythmics - Beta blockers (Class II); (1) Metoprolol (2) Propanolol (3) Esmolol (4) Atenolol (5) Timolol (6) Carvedilol
What is the mechanism of Class II Antiarrhythmics (Beta-blockers)? What is particularly sensitive to their effects, and what results?
Decrease SA and AV nodal activity by decreasing cAMP, decreasing Ca2+ currents. Suppress abnormal pacemakers by decreasing slope of phase 4. Av node particularly sensitive - increase PR interval.
Which Class II antiarrhythmic (Beta-blocker) is very short acting?
Esmolol very short acting
What is/are the major clinical use(s) for Class II anti-arrhythmics (beta-blockers)?
SVT, slowing ventricular rate during atrial fibrillation and atrial flutter