2 - PKPD of cardiac medications (Digoxin, Amiodarone)

Question 1

Indications of digoxin

Answer 1

1. For congestive HF

2. rate control for atrial fibrillation (slows down HR in this scenario)

Question 2

Therapeutic range of digoxin

Answer 2

1-2mcg/L

Question 3

Does digoxin have a salt form?

Answer 3

No!

Question 4

Digoxin is dosed based on body weight: T/F

Answer 4

false, has a huge Vd of 6-7L, so differences in pt body weight don’t make much of a difference

Question 5

Do we adjust digoxin dose in renal failure?

Answer 5

NO! Give the same dose no matter the renal function

Question 6

Which formula is good for predicting plasma digoxin levels?

Answer 6

Formula of Dobb’s => predicts plasma levels at steady state

Question 7

Digoxin bioavailability

Answer 7

> = 75%

Question 8

Why don’t we administer digoxin as one big loading dose?

Answer 8

• Myocardium actually senses the digoxin concentration in the tissues, rather than in the blood. Our goal is to build up the digoxin load in the tissues throughout the day with a loading dose.
• If we give 1000mcg (for ex) all at once, the myocardium will sense a huge dose coming into the tissues at once, so potentially greater incidence of toxicity after the first dose.

Question 9

Digoxin is a 2-comp drug. Where does the myocardium sense the drug? (ie which compartment)

Answer 9

within the 2nd compartment (ie tissues) and not in the blood (1st compartment)

Question 10

What are the important clinical implications of digoxin being a 2-comp drug?

Answer 10

transiently high concentrations are achieved after every dose, however they do NOT result in an immediate cardiac effect! Digoxin has to get into the tissues first.

Question 11

Classify amiodarone

Answer 11

Class III antiarrhythmic

Question 12

Amiodarone indications

Answer 12

1- tx of ventricular tachycardia/fib
2- conversion to normal sinus rhythm from atrial flutter or fibrillation
3- rate control for a. fib

Question 13

Describe the importance of desethylamiodarone, the active metabolite of amiodarone

Answer 13

• metabolite has a lot of K+-blocking effects
• we see this if amiodarone is given orally, b/c then it goes to the liver to be metabolized. This is why we like to give it orally, to optimize cardiac tx.
• if given IV, it won’t get metabolized like this and will have more beta-blocking effects

Question 14

What compartment model is amiodarone? Discuss

Answer 14

Multi-compartmental (up to 4 compartments!). This means it can have a variable t 1/2: 12 mins, 6h, 24h, 53 days!

Question 15

Amiodarone AE’s

Answer 15

• CNS: ataxia, dizziness, fatigue, tremor, h/a
• Pulmonary: pneumonitis (LIFE-threatening!) STOP drug immediately
• CV: hypotension and bradycardia with the IV drug, QT-prolongation, heart block
• GI: N&V, constipation
• Ocular: corneal microdeposits, visual disturbances
• Endocrine: hypothyroidism, hyperthyroidism
• Dermatologic: slate blue discolouration of the skin

Question 16

Describe pneumonitis, a life-threatening AE of amiodarone

Answer 16

Can look like pneumonia, but without productive cough or fever.
- if pt on amiodarone gets an Rx for an AB, be suspicious!

Question 17

When is a case where amiodarone is CI’d?

Answer 17

If patient already has QT-prolongation

Question 18

Amiodarone recommended dosing for atrial tachydysarrhythmias (ie A. flutter or A. fib)

Answer 18

DL for prevention or tx of artrial arrhythmias: 600-800mg/day (usually in divided doses) for a total of 10 grams

• then a maintenance dose of 200mg per day

Question 19

Amiodarone dosing regime (DL and MD) for atrial tachyarrhythmias

Answer 19

Amiodarone 200mg TID for 14 days (8.4g)
Amiodarone 200mg BID for 4 days (1.6g)
=> total 10g DL achieved over 18 days

Now, MD of amiodarone 200-300mg once daily long term

Question 20

Amiodarone dosing regime (DL and MD) for ventricular dysrhythmias

Answer 20

DL: amiodarone 400mg TID x 5 days (6g)
amiodarone 400mg BID x 5 days (4g)
=> total 10g DL achieved over 10 days

Now, MD of amiodarone 200-300mg once daily