17. CPK OF DIGOXIN

Question 1

Describe DIG toxicity

Answer 1

Non-cardiac & Cardiac

Question 2

What units are used to dose DIG?

Answer 2

MICROgrams

Question 3

How is DIG absorbed?

Answer 3

Small intestine, Pgp

Question 4

Does DIG experience significant first-pass metabolism?

Answer 4

no

Question 5

Describe DIG protein binding

Answer 5

mainly bound to albumin

Question 6

What is the main route of elimination for DIG?

Answer 6

renal (66-76% of total Cl is renal Cl)

Question 7

What is one of the main causes of DIG drug interactions?

Answer 7

P-gp

Question 8

When should DIG concentrations be measured?

Answer 8

Ideal - 12-24 hours after dose
MUST be after 6-8 hours

Question 9

Why does DIG concentration have to be measured AFTER 6-8 hours?

Answer 9

Over the first 6-8 hours, there is no relationship between plasma digoxin concentration & inotropic response

Question 10

Where is the site of action of DIG and how does it affect the concentration vs. response relationship?

Answer 10

• NOT the central compartment (plasma) - heart
• Counterclockwise hysteresis → effect lags

Question 11

Are loading doses of DIG typically given clinically?

Answer 11

no

Question 12

What patient factors affect DIG dosing?

Answer 12

• alterations in renal function (diseases, drugs)
• drug interactions

Question 13

What ClCr should be used when estimating DIG dosing?

Answer 13

DIG CrCl (coops or dobs method)

Question 14

How do most clinicians dose DIG?

Answer 14

• empirically
  0.125 - 0.25 mg daily

Question 15

When are lower doses of DIG typically considered necessary?

Answer 15

> 70 yrs
impaired renal function
low weight

Question 16

When do we see increased DIG bioavailability?

Answer 16

Inhibition of P-glycoprotein

Question 17

When do we see decreased DIG bioavailability?

Answer 17

Reduced absorption
Reduced intestinal metabolism
Induction of P-glycoprotein

Question 18

When do we see decreased DIG clearance?

Answer 18

Inhibition of P-glycoprotein

Question 19

When do we see altered DIG distribution?

Answer 19

changes in P-glycoprotein

Question 20

How does Amiodarone affect DIG concentrations?

Answer 20

increased Digoxin conc (~70-100%)

need to decrease DIG dose

Question 21

How does Itra/Ketoconazole affect DIG concentrations?

Answer 21

increased Digoxin conc (~50-100%)

need to decrease DIG dose

Question 22

How does Quinine affect DIG concentrations?

Answer 22

increased Digoxin conc (~70%)

need to decrease DIG dose

Question 23

How does Verapamil affect DIG concentrations?

Answer 23

increased Digoxin conc (~70%)

need to decrease DIG dose

Question 24

What 4 specific drugs necessitate DIG dosing adjustment when taken co-currently with DIG?

Answer 24

Amiodarone
Itra/Ketoconazole
Quinine
Verapamil