Download Digoxin - Dr Ted Williams

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
General Structure
Mechanism of Action
• Digoxin inhibits membrane bound sodiumpotassium 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 reninangiotensin system.
Digoxin
Ca
(-)
2+
2K
3Na+
+
NaCaX
ATPase
3Na +
Ca2+
RyR
ATP
Ca
SR
Contraction
2+
ATPase
Ca2+
ADP
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 reninangiotensin system.
• Slowing of the heart rate
and decreased conduction
velocity through the AV
node.
Main Clinical Indications
• 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
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/plantbiology/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.GI
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