2 - PKPD of cardiac medications (Digoxin, Amiodarone) Flashcards
Indications of digoxin
- For congestive HF
2. rate control for atrial fibrillation (slows down HR in this scenario)
Therapeutic range of digoxin
1-2mcg/L
Does digoxin have a salt form?
No!
Digoxin is dosed based on body weight: T/F
false, has a huge Vd of 6-7L, so differences in pt body weight don’t make much of a difference
Do we adjust digoxin dose in renal failure?
NO! Give the same dose no matter the renal function
Which formula is good for predicting plasma digoxin levels?
Formula of Dobb’s => predicts plasma levels at steady state
Digoxin bioavailability
> = 75%
Why don’t we administer digoxin as one big loading dose?
- 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.
Digoxin is a 2-comp drug. Where does the myocardium sense the drug? (ie which compartment)
within the 2nd compartment (ie tissues) and not in the blood (1st compartment)
What are the important clinical implications of digoxin being a 2-comp drug?
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.
Classify amiodarone
Class III antiarrhythmic
Amiodarone indications
1- tx of ventricular tachycardia/fib
2- conversion to normal sinus rhythm from atrial flutter or fibrillation
3- rate control for a. fib
Describe the importance of desethylamiodarone, the active metabolite of amiodarone
- 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
What compartment model is amiodarone? Discuss
Multi-compartmental (up to 4 compartments!). This means it can have a variable t 1/2: 12 mins, 6h, 24h, 53 days!
Amiodarone AE’s
- 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
Describe pneumonitis, a life-threatening AE of amiodarone
Can look like pneumonia, but without productive cough or fever.
- if pt on amiodarone gets an Rx for an AB, be suspicious!
When is a case where amiodarone is CI’d?
If patient already has QT-prolongation
Amiodarone recommended dosing for atrial tachydysarrhythmias (ie A. flutter or A. fib)
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
Amiodarone dosing regime (DL and MD) for atrial tachyarrhythmias
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
Amiodarone dosing regime (DL and MD) for ventricular dysrhythmias
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
