Cardio - Pharm (Part 3: Cardiac glycosides & Antiarrhythmics) Flashcards
Pg. 301-304 in First Aid 2014 Pg. 282-284 in First Aid 2013 Sections include: -Cardiac glycosides -Antiarrythmics - Na+ channel blockers (class I) -Antiarrythmics - Beta-blockers (class II) -Antiarrythmics - K+ channel blockers (class III) -Antiarrythmics - Ca2+ channel blockers (class IV) -Other antiarrythmics
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?
Urinary excretion
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
What are 4 toxicities associated with all Class II Antiarrhythmics (beta-blockers)?
(1) Impotence, (2) Exacerbation of COPD and asthma, (3) Cardiovascular effects (bradycardia, AV block, CHF), (4) CNS effects (sedation, sleep alterations).
What condition may Class II antiarrhythmic (beta-blocker) drugs mask?
May mask the signs of hypoglycemia.
What class of antiarrhythmic is Metoprolol? What particular toxicity does it cause?
Class II antiarrhythmics (Beta-blockers); Metoprolol can cause dyslipidemia
What class of antiarrhythmic is Propanolol? What particular toxicity does it cause?
Class II antiarrhythmics (Beta-blockers); Propanolol can exacerbate vasospasm in Prinzmetal angina.
In what patient population are Class II (Beta-blocker) antiarrhythmics contraindicated, and why?
Contraindicated in cocaine users (risk of unopposed alpha-adrenergic receptor agonist activity)
What is used to treat an overdose of Class II (Beta-blocker) antiarrhythmics?
Treat overdose with glucagon.
Graph pacemaker cell potential (x) versus membrane potential (y), indicating the effect of Class II (beta-blocker) antiarrhythmics on slope of phase 4 depolarization and AV node.
See p. 303 in First Aid 2014 for visual near top/middle of page
What are 4 examples of Class III (K+ channel blockers) antiarrhythmics?
(1) Amiodarone (2) Ibutilide (3) Dofetilide (4) Sotalol; Think: “AIDS”
What is the mechanism of Class III (K+ channel blockers) antiarrhythmics? In what context are they used?
Increase AP duration, Increase ERP. Used when other antiarrhythmics fail. Increase QT interval.
What are 3 conditions for which Class III (K+ channel blocker) antiarrhythmics are used clinically? Which of these conditions is only treated by 2 particular drugs, and what are those 2 drugs?
(1) Atrial fibrillation, (2) Atril flutter; (3) Ventricular tachycardia (amiodarone, sotalol)
What class of antiarrhythmics is Sotalol? What are 2 toxicities associated with it?
Class III (K+ channel blocker) antiarrhythmic; (1) Torsades de pointes (2) Excessive Beta blockade
What class of antiarrhythmics is Ibutilide? What toxicity is associated with it?
Class III (K+ channel blocker) antiarrhythmic; Torsades de pointes
What class of antiarrhythmics is Amiodarone? What are 8 toxicities associated with it?
Class III (K+ channel blocker) antiarrhthmic; (1) Pulmonary fibrosis (2) Hepatotoxicity (3) Hypothyroidism/Hyperthyroidism (amiodarone is 40% iodine by weight) (4) Corneal deposits (5) Skin deposits (blue/gray) resulting in photodermatitis (6) Neurologic effects (7) Constipation (8) Cardiovascular effects (bradycardia, heart block, CHF)
What are 3 things that should be checked for clinically when giving a patient amiodarone?
Remember to check PFTs, LFTs, and TFTs when using amiodarone
Although Amiodarone is technically a Class III (K+ channel blocker) antiarrhythmic, what is important to know about its actual effects?
Amiodarone has class I, II, III, and IV effects and alters the lipid membrane.
Graph the effect of Class III antiarrhythmics on cell action potential, labeling their effect on K+ current.
See p. 303 in First Aid 2014 for graph at bottom of page
What type of drugs are Class IV (Ca2+ channel blocker) antiarrhythmics? Give 2 examples.
Class IV (Ca2+ channel blocker) antiarrhythmics; (1) Verapamil (2) Diltiazem
What is the mechanism of Class IV (Ca2+ channel blocker) antiarrhythmics?
Decrease conduction velocity, Increase ERP, Increase PR interval.
What are 2 clinical uses for Class IV (Ca2+ channel blocker) antiarrhythmics?
(1) Prevention of nodal arrhythmias (e.g., SVT) (2) Rate control in atrial fibrillation
What are 4 toxicities associated with Class IV (Ca2+ channel blocker) antiarrhythmics?
(1) Constipation (2) Flushing (3) Edema (4) CV effects (CHF, AV block, sinus node depression)
Graph the effects of Class IV (Ca2+ channel blocker) on membrane potential, indicating its effects on action potential and AV node.
See p. 304 in First Aid 2014 for graph at top of page
What are 2 examples of antiarrhythmics other than Class I-IV antiarrhythmics?
(1) Adenosine (2) Mg2+
What is the mechanism of Adenosine as an antiarrhythmic?
Increase K+ out of cells => hyperpolarizing the cell and decrease Ca current.
For what clinical use is Adenosine the drug of choice?
Drug of choice in diagnosing/abolishing supraventricular tachycardia.
Describe the length of action of Adenosine.
Very short acting (~15 sec).
What are 3 adverse effects of Adenosine?
Adverse effects include (1) flushing, (2) hypotension, (3) chest pain.
What 2 drugs/substances block the effects of adenosine?
Effects blocked by theophylline and caffeine.
In what 2 conditions is Mg2+ effective?
Effective in Torsades de pointes and Digoxin toxicity.
