Cardio - Pharm (Part 3: Cardiac glycosides & Antiarrhythmics)

Question 1

What is a prominent example of a cardiac glycoside? What is its % bioavailability, % protein bound, and half-life?

Answer 1

Digoxin - 75% bioavailabiity, 20-40% protein bound, t1/2 = 40 hours

Question 2

How is digoxin cleared from the body?

Answer 2

Urinary excretion

Question 3

What is the mechanism by which cardiac glycosides/digoxin work? What are the 2 major effects that this has?

Answer 3

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.

Question 4

For what 2 conditions are cardiac glycosides/digoxin used clinically, and why?

Answer 4

(1) CHF (increase contractility) (2) Atrial fibrillation (Decrease conduction at AV node & depression of SA node)

Question 5

What 3 major toxicities are associated with cardiac glycosides/digoxin? Describe each.

Answer 5

(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

Question 6

What findings can cardiac glycosides cause on an ECG?

Answer 6

Increased PR, Decreased QT, ST scooping, T-wave inversion, arrhythmia, AV block

Question 7

What are 3 factors predisposing patients to cardiac glycoside/digoxin toxicity, and why?

Answer 7

(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)

Question 8

What is/are the antidote(s) for cardiac glycosides/digoxin?

Answer 8

Slowly normalize K+, lidocaine, cardiac pacer, anti-digoxin Fab fragments, Mg2+

Question 9

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.

Answer 9

Class I; Class IA - Quinidine, Procainamide, Disopyramide; Class IB - Lidocaine, Mexiletine; Class IC - Flecainide, Propafenone

Question 10

What 3 mechanistic effects do Class IA antiarrhythmics have?

Answer 10

(1) Increase AP duration, (2) Increase effective refractory period (ERP), (3) Increase QT interval.

Question 11

For what kinds of arrhythmias do Class IA antiarrhythmics work?

Answer 11

Both atrial and ventricular arrhythmias, especially re-entrant and ectopic supraventricular (SVT) and ventricular (VT) tachycardia

Question 12

Name 3 Class IA antiarrhythmics.

Answer 12

(1) Quinidine (2) Procainamide (3) Disopyramide

Question 13

What are 5 toxicities are associated with Class IA antiarrhythmics? Specify which toxicities apply to only certain drugs in this class.

Answer 13

(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

Question 14

Name 2 Class IB antiarrhythmics. What other drug can fall into this category?

Answer 14

(1) Lidocaine (2) Mexiletine; Phenytoin can also fall into the IB category.

Question 15

What is the mechanism of Class IB antiarrhythmics? What do Class IB antiarrhythmics preferentially affect?

Answer 15

Decrease AP duration. Preferentially affect ischemic or depolarized Purkinje and ventricular tissue

Question 16

For what kinds of arrhythmias are Class IB antiarrhythmics used?

Answer 16

Acute ventricular arrhythmias (especially post-MI), digitalis-induced arrhythmias. Think: “IB is Best post-MI”

Question 17

What are 2 toxicities associated with Class IB antiarrhythmics?

Answer 17

(1) CNS stimulation/depression (2) Cardiovascular depression

Question 18

Name 2 Class IC antiarrhythmics.

Answer 18

(1) Flecainide (2) Propafenone; Think: “class iC Flecainide Propafenone = Can I have Fries, Please.”

Question 19

What is the mechanism of Class IC antiarrhythmics? How does it differ from Class IA/IB antiarrhythmics?

Answer 19

Significantly prolongs refractory period in AV node. Minimal effect on AP duration.

Question 20

For what kind of arrhythmias are Class IC antiarrhythmics used clinically?

Answer 20

SVTs, including atrial fibrillation. Only as a last resort in refractory VT.

Question 21

What is a toxicity of Class IC antiarrhythmics? In what condition(s) are they contraindicated?

Answer 21

Proarrhythmic, especially post-MI (contraindicated). IC is Contraindicated in structural and ischemic heart disease.

Question 22

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.

Answer 22

(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.

Question 23

Are Class I antiarrhythmics (Na+ channel blockers) state dependent or independent? Why or why not?

Answer 23

Are state dependent (selectively depress tissue that is frequently depolarized [e.g., tachycardia])

Question 24

What metabolic condition causes increased toxicity for all class I antiarrhythmics?

Answer 24

Hyperkalemia causes increased toxicity for all class I drugs.

Question 25

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.

Answer 25

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

Question 26

What kind of drugs make up Class II antiarrhythmics? What are 6 examples of such drugs?

Answer 26

Antiarrhythmics - Beta blockers (Class II); (1) Metoprolol (2) Propanolol (3) Esmolol (4) Atenolol (5) Timolol (6) Carvedilol

Question 27

What is the mechanism of Class II Antiarrhythmics (Beta-blockers)? What is particularly sensitive to their effects, and what results?

Answer 27

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.

Question 28

Which Class II antiarrhythmic (Beta-blocker) is very short acting?

Answer 28

Esmolol very short acting

Question 29

What is/are the major clinical use(s) for Class II anti-arrhythmics (beta-blockers)?

Answer 29

SVT, slowing ventricular rate during atrial fibrillation and atrial flutter

Question 30

What are 4 toxicities associated with all Class II Antiarrhythmics (beta-blockers)?

Answer 30

(1) Impotence, (2) Exacerbation of COPD and asthma, (3) Cardiovascular effects (bradycardia, AV block, CHF), (4) CNS effects (sedation, sleep alterations).

Question 31

What condition may Class II antiarrhythmic (beta-blocker) drugs mask?

Answer 31

May mask the signs of hypoglycemia.

Question 32

What class of antiarrhythmic is Metoprolol? What particular toxicity does it cause?

Answer 32

Class II antiarrhythmics (Beta-blockers); Metoprolol can cause dyslipidemia

Question 33

What class of antiarrhythmic is Propanolol? What particular toxicity does it cause?

Answer 33

Class II antiarrhythmics (Beta-blockers); Propanolol can exacerbate vasospasm in Prinzmetal angina.

Question 34

In what patient population are Class II (Beta-blocker) antiarrhythmics contraindicated, and why?

Answer 34

Contraindicated in cocaine users (risk of unopposed alpha-adrenergic receptor agonist activity)

Question 35

What is used to treat an overdose of Class II (Beta-blocker) antiarrhythmics?

Answer 35

Treat overdose with glucagon.

Question 36

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.

Answer 36

See p. 303 in First Aid 2014 for visual near top/middle of page

Question 37

What are 4 examples of Class III (K+ channel blockers) antiarrhythmics?

Answer 37

(1) Amiodarone (2) Ibutilide (3) Dofetilide (4) Sotalol; Think: "AIDS"

Question 38

What is the mechanism of Class III (K+ channel blockers) antiarrhythmics? In what context are they used?

Answer 38

Increase AP duration, Increase ERP. Used when other antiarrhythmics fail. Increase QT interval.

Question 39

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?

Answer 39

(1) Atrial fibrillation, (2) Atril flutter; (3) Ventricular tachycardia (amiodarone, sotalol)

Question 40

What class of antiarrhythmics is Sotalol? What are 2 toxicities associated with it?

Answer 40

Class III (K+ channel blocker) antiarrhythmic; (1) Torsades de pointes (2) Excessive Beta blockade

Question 41

What class of antiarrhythmics is Ibutilide? What toxicity is associated with it?

Answer 41

Class III (K+ channel blocker) antiarrhythmic; Torsades de pointes

Question 42

What class of antiarrhythmics is Amiodarone? What are 8 toxicities associated with it?

Answer 42

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)

Question 43

What are 3 things that should be checked for clinically when giving a patient amiodarone?

Answer 43

Remember to check PFTs, LFTs, and TFTs when using amiodarone

Question 44

Although Amiodarone is technically a Class III (K+ channel blocker) antiarrhythmic, what is important to know about its actual effects?

Answer 44

Amiodarone has class I, II, III, and IV effects and alters the lipid membrane.

Question 45

Graph the effect of Class III antiarrhythmics on cell action potential, labeling their effect on K+ current.

Answer 45

See p. 303 in First Aid 2014 for graph at bottom of page

Question 46

What type of drugs are Class IV (Ca2+ channel blocker) antiarrhythmics? Give 2 examples.

Answer 46

Class IV (Ca2+ channel blocker) antiarrhythmics; (1) Verapamil (2) Diltiazem

Question 47

What is the mechanism of Class IV (Ca2+ channel blocker) antiarrhythmics?

Answer 47

Decrease conduction velocity, Increase ERP, Increase PR interval.

Question 48

What are 2 clinical uses for Class IV (Ca2+ channel blocker) antiarrhythmics?

Answer 48

(1) Prevention of nodal arrhythmias (e.g., SVT) (2) Rate control in atrial fibrillation

Question 49

What are 4 toxicities associated with Class IV (Ca2+ channel blocker) antiarrhythmics?

Answer 49

(1) Constipation (2) Flushing (3) Edema (4) CV effects (CHF, AV block, sinus node depression)

Question 50

Graph the effects of Class IV (Ca2+ channel blocker) on membrane potential, indicating its effects on action potential and AV node.

Answer 50

See p. 304 in First Aid 2014 for graph at top of page

Question 51

What are 2 examples of antiarrhythmics other than Class I-IV antiarrhythmics?

Answer 51

(1) Adenosine (2) Mg2+

Question 52

What is the mechanism of Adenosine as an antiarrhythmic?

Answer 52

Increase K+ out of cells => hyperpolarizing the cell and decrease Ca current.

Question 53

For what clinical use is Adenosine the drug of choice?

Answer 53

Drug of choice in diagnosing/abolishing supraventricular tachycardia.

Question 54

Describe the length of action of Adenosine.

Answer 54

Very short acting (~15 sec).

Question 55

What are 3 adverse effects of Adenosine?

Answer 55

Adverse effects include (1) flushing, (2) hypotension, (3) chest pain.

Question 56

What 2 drugs/substances block the effects of adenosine?

Answer 56

Effects blocked by theophylline and caffeine.

Question 57

In what 2 conditions is Mg2+ effective?

Answer 57

Effective in Torsades de pointes and Digoxin toxicity.