Digoxin (Lanoxin/Lanoxicaps)
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Transcript of Digoxin (Lanoxin/Lanoxicaps)
Digoxin (Lanoxin/Lanoxicaps)
foxglove digitalis
Seth AdamsDuy CaoScott DavisCheryl HanslovanBryan IngKristin McKayVic PatelDan RackhamDarren SmithPhong Vuong
General Structure
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.
SR
ATP
ADP
Ca2+
Ca2+
3Na+
Contraction
NaCaX
ATPase
3Na+
ATPase
2K+
RyR
Digoxin(-)
Ca2+
Ca2+
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.
• 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
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)
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
Drug Interactions• Amiodarone
– ↑[Digoxin] by 70%
• Verapamil– ↑[Digoxin] by 50-75%
• Propafenone– ↑[Digoxin] by 30%
• Quinidine– ↑[Digoxin] by 50-75%
• Erythromycin– ↑[Digoxin]
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
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
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)
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
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
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
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