Block 4 Flashcards
What are the indication for digoxin?
Congestive HF (positive inotrope) + A. Fib (negative chronotrope)
Explain the absorption of digoxin
Absorbed in small intestines primarily
Eubacterium Lentum can inactive drug by reduction to 20R dihydrodigoxin
P-gp inhibitors have an interaction with digoxin
Explain the distribution of digoxin
Large Vd
Not highly protein bound
Stored mostly in skeletal muscle
Not affected by obesity (dose with IBW in obese patients)
Explain the metabolism of digoxin
Hepatically metabolized by non-CYP pathways
This is why digoxin is used as a P-gp substrate for drug interaction studies
Explain the elimination of digoxin
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
Explain the elimination of digoxin in heart failure patients
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
Overall, how do these conditions affect Digoxin PK?
Renal failure
HF
Hyperthyroidism
Electrolyte disturbance
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
Dosing of digoxin in A. Fib?
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
Dosing of digoxin in HF?
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
Digoxin monitoring for A. Fib and HF
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
What are some toxicity effects of digoxin?
GI, CNS, and Cardiac (2/3 degree heart block, bradycardia, etc)
When do you draw the metabolic panel levels for digoxin?
Prior to morning dose
What Rx interact w/ digoxin?
There a lot, but mainly amiodarone and verapamil
How does amiodarone inhibit digoxin?
Inhibits P-gp and decreases clearance, which increases digoxin concentration
Decrease digoxin dose by 50%
How does verapamil inhibit digoxin?
Inhibits renal clearance and increases digoxin concentration to 50-75%
Monitor digoxin levels
How do you reverse digoxin overdose?
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
If you dont know the serum digoxin levels, but pt is acutely or chronically overdosed on digoxin…what can you give them?
Acute - 20 vials of DigiFab
Chronic - 6 vials
F value of digoxin
Tabs
Elixir
Liq. Caps?
Tabs - 0.75
Elixir - 0.80
Liq. Caps - 0.95
Describe PK drug interactions
How body affects drug
Alters ADME
USUALLY mediated by P450
Describe PD drug interactions
How drug affects the body
Modulates effect of another drug through additive, synergistic, antagonistic effects, or idiosyncratic (unpredictable)
How does alterations in absorption affect GI motility?
Decreased GI motility due to methadone increases didanosine degradation and reduces its bioavailability
Increased GI motility due to metoclopramide reduces digoxin absorption
How does alterations in absorption affect chelation?
Tetracycline and quinolone ABx, iron, antacids, and dairy products have to be separated by at least 2 hrs can prevent this
How does alterations in absorption affect pH?
Some drugs like azoles and HIV meds require acidic environment
H2 inhibitors + PPIs raise pH and reduce their absorption
How does alterations in absorption affect anion exchange resins?
Cholestyramine can form insoluble complexes and decreases Rx absorption
Warfarin, digoxin, BB, NSAIDs
Also immunosuppressants
What affects OATP drug transport?
Fruit juices + Ketoconazole
Blocking OATP causes increased plasma concentration of statins because it is not taken into hepatocytes
What is the difference between non-restrictively and restrictively cleared drugs?
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
ABCB1 gene encodes for what transport protein?
P-gp
When does a P-gp limit absorption of P-gp substrate?
Slowly dissolving
Poorly water soluble
Large in size
