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

Digoxin PPT Presentation Final

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Page 1: Digoxin PPT Presentation Final

Digoxin (Lanoxin/Lanoxicaps)

foxglove digitalis

Seth AdamsDuy CaoScott DavisCheryl HanslovanBryan IngKristin McKayVic PatelDan RackhamDarren SmithPhong Vuong

Page 2: Digoxin PPT Presentation Final

General Structure

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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.

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SR

ATP

ADP

Ca2+

Ca2+

3Na+

Contraction

NaCaX

ATPase

3Na+

ATPase

2K+

RyR

Digoxin(-)

Ca2+

Ca2+

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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.

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• Heart Failure– Increases cardiac output by positive inotropic actions– Therapeutic level of 0.5-1 mcg/L

• Atrial Fibrillation– Rate control by vagomimetic actions– Therapeutic level of 0.5-2 mcg/L

Main Clinical Indications

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Available Dosage Forms• Tablets ( F = 0.6 - 0.7)

– 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)

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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

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Drug Interactions• Amiodarone

– ↑[Digoxin] by 70%

• Verapamil– ↑[Digoxin] by 50-75%

• Propafenone– ↑[Digoxin] by 30%

• Quinidine– ↑[Digoxin] by 50-75%

• Erythromycin– ↑[Digoxin]

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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

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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

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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)

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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

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Problem Solutions - 1 • WB w/ Renal Dysfunction:

– IBW = 45.5 kg + 2.3 (4 in) = 54.7 kg

– CrCl = ((140-75) x 54.7 kg (.85)) / (3.4 x 72) = 12.35 mL/min

– Vd = (3.8 L/kg x 54.7 kg) + 3.1 (12.35 mL/min) = 246.15 L

– Cldig= (0.8 mL/min/kg x 54.7 kg) + 12.35 mL/min = 56.11 mL/min = 3.37 L/hr

– LD = (246.15 L x 1 mcg) / (0.7) = 351.64 mcg Use 375 mcg tabs once

– MD = Cpss = 1 mcg/L = (Xo(0.7)) / (3.37 L/hr x 24 hr) 0.7Xo = 80.88 mcg Xo = 115.54 mcg Use 125 mcg tabs qday

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Problem Solutions - 2• AS w/ Congestive Heart Failure:

– IBW = 50.0 kg + 2.3 (10 in) = 73 kg

– CrCl = ((140-78) x 73 kg) / (1.1 x 72) = 57.15 mL/min

– Vd = (7.3 L/kg x 73 kg) = 532.9 L

– Cldig= (0.33 mL/min/kg x 73 kg) + 0.9 (57.15 mL/min) = 75.52 mL/min = 4.53 L/hr

– LD = (532.9 L x 0.7 mcg) / (0.95) = 392.66 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 = 80.11 mcg Use 100 mcg caps qday

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References• 20th edition top 200 pharmacy drug cards. SFI Medical Publishing. 2004.

• Class lecture. Pharmacy 750. 11/3/2005. Connie Covington

• Tharp, R. (2006) Digoxin Dosing. Retrieved March 9, 2006 from the world wide web: http://www.rxkinetics.com/dig.html

• Medicinal Plants. (2006) Digoxin Image. Updated Aug 12, 2005. Retrieved March 8, 2006 from world wide web: http://www.science.siu.edu/plant-biology/PLB117/Nickrent.Lecs/Medicine.html

• Rx-List. (2006) Digoxin. Updated March 12, 2006. Retrieved March 8, 2006 from world wide web: http://www.rxlist.com/cgi/rxlist.cgi?drug=digoxin

• Digoxin Structure. Retrieved March 8, 2006 from world wide web: http://medpharm.chunma.ac.kr/Aldja/CVS/cardiac_glycoside/img/digoxin_structure.GIF