1. Digoxin (Lanoxin/Lanoxicaps)
Seth Adams
Duy Cao
Scott Davis
Cheryl Hanslovan
Bryan Ing
Kristin McKay
Vic Patel
Dan Rackham
Darren Smith
Phong Vuong
foxglove digitalis

2. General Structure

3. Mechanism of Action
Digoxin inhibits membrane bound sodium-potassium ATPase resulting in an increased intracellular [Na+] and thus an increase in the intracellular [Ca2+] by stimulation of Na+ and Ca2+ exchange.
Digoxin has an indirect effect on the sinoatrial and atrioventricular nodes (vagomimetic actions).
Baroreceptor sensitization also results from digoxin. This leads to increased afferent inhibitory activity and reduced activity of the sympathetic nervous system and renin-angiotensin system.

4. Ca Digoxin (-) SR 2 + Ca2+ Ca2+ 3Na 2K 3Na Contraction Ca RyR ATP ADP
NaCaX
ATPase
3Na +
Ca2+
RyR
ATP
Ca2+ Ca 2 +
ATPase SR
ADP
Contraction

5. Net Effect
Positive inotropic action (an increase in the force and velocity of myocardial systolic contraction).
A decrease in the degree of activation of the sympathetic nervous system and renin-angiotensin system.
Slowing of the heart rate and decreased conduction velocity through the AV node.

6. Main Clinical Indications
Heart Failure
Increases cardiac output by positive inotropic actions
Therapeutic level of mcg/L
Atrial Fibrillation
Rate control by vagomimetic actions
Therapeutic level of mcg/L

7. Available Dosage Forms
Tablets ( F = )
125 mcg ( yellow, # Y3B ) or 250 mcg ( white, # X3A )
Capsules (Lanoxicaps) ( F = 0.9 – 0.95)
50 mcg ( red, # A2C ) , 100 mcg ( yellow, # B2C ), and 200 mcg ( green, # C2C)
Pediatric Elixer ( F = 0.75 – 0.85)
50 mcg per 1 ml (10% alcohol)
Injection ( F = 1.0 )
250 mcg per 1 ml (1 ml ampule)
Pediatric Injection ( F = 1.0 )
100 mcg per 1 ml (1 ml ampule)

8. Side Effects & Toxicities
Yellow/green visual changes, halos around light
N&V and diarrhea (50-75% of patients)
Bradycardia (75-90% of patients)
Fatigue, malaise, confusion, headache, etc.
Anorexia

9. Drug Interactions Amiodarone Verapamil Propafenone Quinidine
↑[Digoxin] by 70%
Verapamil
↑[Digoxin] by 50-75%
Propafenone
↑[Digoxin] by 30%
Quinidine
Erythromycin
↑[Digoxin]

10. Pharmacokinetic Parameters
Absorption
After oral dosing:
Onset of action in 0.5 – 2 hours
Peak effect reached in 2 – 6 hours
Distribution
Skeletal and heart muscle, but not into adipose tissue
Up to 25-30% is bound to plasma proteins
Metabolism
Follows first-order kinetics
Limited metabolism via sugar hydrolysis and lactone ring reduction
Half-life = 1-2 days
Excretion
60-80% excreted unchanged in urine
Undergoes ACTIVE tubular secretion in the kidneys

11. Clinical Considerations
Doses must be individualized and depends on the type & severity of the disease, age & weight of the patient, renal function, and concomitant disease states
Normal dosage range is 125 – 500 mcg (50 – 200 mcg capsules) a day in a single dose
Contraindications: Patients w/ ventricular fibrillation, renal impairment, hypokalemia, hypomagnesemia, hypercalcemia, and pulmonary disease
Patient must be advised not to take nonprescription cough or cold medications, antacids, laxatives, or antidiarrheals without consulting the pharmacist or physician
Pregnancy category C

12. Digoxin Equations IBW = 50 (or 45.5) + 2.3 x (inches over 60)
CrCl = ((140 - Age) x IBW) / (72 x SCr) ( x 0.85 for females)
Clearance Digoxin: Cldig = (0.8 ml/min/kg x IBW) + CrCl
w/ CHF: Cl = (0.33 ml/min/kg x IBW) + (0.9 x CrCl) (these values were multiplied by 0.06 to convert them from mL/min to L/hr)
w/ co-administration of amiodarone: Cl = 0.5 x Cl (without amiodarone)
Vd = 7.3 L/kg x IBW
w/ renal dysfunction: Vd = (3.8 L/kg x IBW) + (3.1 x CrCl)
LD = (Cp (desired level) x Vd) / (F)
MD = (Cp (desired level) x Cldig x Xo) / (F)

13. Sample Problems
WB is a 75-year-old female with PMH including atrial fibrillation, type II diabetes, hypertension, and renal insufficiency. She is 5’4” and weighs 75 kg. Her SCr is 3.4 mg/dL. Calculate a loading and maintenance dose for Lanoxin tablets for Mrs. B.
Target Cpss = 1.0 mcg/L for atrial fibrillation
AS is a 78-year-old male with CHF. He is 5’10” and weighs 73kg. His SCr is 1.1 mg/dL. Calculate a dosing regimen using Lanoxicaps.
Target Cpss = 0.7 mcg/L for CHF

14. Problem Solutions - 1 WB w/ Renal Dysfunction:
IBW = 45.5 kg (4 in) = 54.7 kg
CrCl = ((140-75) x 54.7 kg (.85)) / (3.4 x 72) = mL/min
Vd = (3.8 L/kg x 54.7 kg) (12.35 mL/min) = L
Cldig= (0.8 mL/min/kg x 54.7 kg) mL/min = mL/min = 3.37 L/hr
LD = ( L x 1 mcg) / (0.7) = mcg  Use 375 mcg tabs once
MD = Cpss = 1 mcg/L = (Xo(0.7)) / (3.37 L/hr x 24 hr)  0.7Xo = mcg  Xo = mcg  Use 125 mcg tabs qday

15. Problem Solutions - 2 AS w/ Congestive Heart Failure:
IBW = 50.0 kg (10 in) = 73 kg
CrCl = ((140-78) x 73 kg) / (1.1 x 72) = mL/min
Vd = (7.3 L/kg x 73 kg) = L
Cldig= (0.33 mL/min/kg x 73 kg) (57.15 mL/min) = mL/min = 4.53 L/hr
LD = (532.9 L x 0.7 mcg) / (0.95) = mcg  Use 400 mcg caps once
MD = Cpss = 0.7 mcg/L = (Xo(0.95)) / (4.53 L/hr x 24 hr)  0.95Xo = 76.1 mcg  Xo = mcg  Use 100 mcg caps qday

16. References
20th edition top 200 pharmacy drug cards. SFI Medical Publishing
Class lecture. Pharmacy /3/2005. Connie Covington
Tharp, R. (2006) Digoxin Dosing. Retrieved March 9, 2006 from the world wide web:
Medicinal Plants. (2006) Digoxin Image. Updated Aug 12, Retrieved March 8, 2006 from world wide web:
Rx-List. (2006) Digoxin. Updated March 12, Retrieved March 8, 2006 from world wide web:
Digoxin Structure. Retrieved March 8, 2006 from world wide web: