Block 4

Question 1

What are the indication for digoxin?

Answer 1

Congestive HF (positive inotrope) + A. Fib (negative chronotrope)

Question 2

Explain the absorption of digoxin

Answer 2

Absorbed in small intestines primarily

Eubacterium Lentum can inactive drug by reduction to 20R dihydrodigoxin

P-gp inhibitors have an interaction with digoxin

Question 3

Explain the distribution of digoxin

Answer 3

Large Vd

Not highly protein bound

Stored mostly in skeletal muscle

Not affected by obesity (dose with IBW in obese patients)

Question 4

Explain the metabolism of digoxin

Answer 4

Hepatically metabolized by non-CYP pathways

This is why digoxin is used as a P-gp substrate for drug interaction studies

Question 5

Explain the elimination of digoxin

Answer 5

75% is eliminated as unchanged digoxin by glomerular filtration and/or active tubular secretion

15-25% is removed by biliary excretion

Clearance is proportional to CrCl

Question 6

Explain the elimination of digoxin in heart failure patients

Answer 6

Non-renal clearance is lower for those patients

HF causes less delivery of digoxin to liver however wont nearly change drastically compared to a decline in renal failure

Question 7

Overall, how do these conditions affect Digoxin PK?

Renal failure
HF
Hyperthyroidism
Electrolyte disturbance

Answer 7

Renal failure, decreased clearance and longer half life, decreased Vd

HF, decreased cardiac output, decreased hepatic clearance

Hyperthyroidism, higher renal and non-renal clearance

Electrolyte disturbance, higher digoxin response if low K, low magnesium, high Ca

Question 8

Dosing of digoxin in A. Fib?

Answer 8

Loading dose = PO, 500mcg, then 250mcg 6 hrs later, and then 250mcg again (total 1mg)

IV, 250mcg with repeated dosing to max of 1.5mg in 24hrs

MD = 0.125 to 0.25mg daily

Question 9

Dosing of digoxin in HF?

Answer 9

No LD

MD = 0.125 to 0.25mg daily

or just 0.125mg daily/every other day if pt is >70, has crap kidneys or low body mass

Question 10

Digoxin monitoring for A. Fib and HF

Answer 10

A. Fib = 0.8-1.5 (ventricular rate <100bpm)

HF = 0.5 - 1.0 (look to see if any symptoms of HF like dyspnea, tachypnea, cough, etc)

> 2.5 is associated with digoxin toxicity

Question 11

What are some toxicity effects of digoxin?

Answer 11

GI, CNS, and Cardiac (2/3 degree heart block, bradycardia, etc)

Question 12

When do you draw the metabolic panel levels for digoxin?

Answer 12

Prior to morning dose

Question 13

What Rx interact w/ digoxin?

Answer 13

There a lot, but mainly amiodarone and verapamil

Question 14

How does amiodarone inhibit digoxin?

Answer 14

Inhibits P-gp and decreases clearance, which increases digoxin concentration

Decrease digoxin dose by 50%

Question 15

How does verapamil inhibit digoxin?

Answer 15

Inhibits renal clearance and increases digoxin concentration to 50-75%

Monitor digoxin levels

Question 16

How do you reverse digoxin overdose?

Answer 16

DigiFab

Antigen binding fragment of the IgG anti digoxin antibody

Each vial = 40mg

Improvement in 30min

Serum digoxin is NOT useful after DigiFab is given

Question 17

If you dont know the serum digoxin levels, but pt is acutely or chronically overdosed on digoxin…what can you give them?

Answer 17

Acute - 20 vials of DigiFab

Chronic - 6 vials

Question 18

F value of digoxin

Tabs
Elixir
Liq. Caps?

Answer 18

Tabs - 0.75

Elixir - 0.80

Liq. Caps - 0.95

Question 19

Describe PK drug interactions

Answer 19

How body affects drug

Alters ADME

USUALLY mediated by P450

Question 20

Describe PD drug interactions

Answer 20

How drug affects the body

Modulates effect of another drug through additive, synergistic, antagonistic effects, or idiosyncratic (unpredictable)

Question 21

How does alterations in absorption affect GI motility?

Answer 21

Decreased GI motility due to methadone increases didanosine degradation and reduces its bioavailability

Increased GI motility due to metoclopramide reduces digoxin absorption

Question 22

How does alterations in absorption affect chelation?

Answer 22

Tetracycline and quinolone ABx, iron, antacids, and dairy products have to be separated by at least 2 hrs can prevent this

Question 23

How does alterations in absorption affect pH?

Answer 23

Some drugs like azoles and HIV meds require acidic environment

H2 inhibitors + PPIs raise pH and reduce their absorption

Question 24

How does alterations in absorption affect anion exchange resins?

Answer 24

Cholestyramine can form insoluble complexes and decreases Rx absorption

Warfarin, digoxin, BB, NSAIDs

Also immunosuppressants

Question 25

What affects OATP drug transport?

Answer 25

Fruit juices + Ketoconazole

Blocking OATP causes increased plasma concentration of statins because it is not taken into hepatocytes

Question 26

What is the difference between non-restrictively and restrictively cleared drugs?

Answer 26

Non-restrictively = removes both bound and unbound drug, no examples given, increase in fu will NOT increase CL proportionally

Restrictively = only unbound is cleared, increase in fu WILL increase CL proportionally, significant in drugs with long half-life and small Vd, and narrow therapeutic range like warfarin

Question 27

ABCB1 gene encodes for what transport protein?

Answer 27

P-gp

Question 28

When does a P-gp limit absorption of P-gp substrate?

Answer 28

Slowly dissolving

Poorly water soluble

Large in size