Dr. O kinetics Part 2
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SEE NOTE for EXAMPLE PROBLEM
Give the strengths that digoxin tablets come in
- 250mcg (0.25mg)
- 125mcg (.125mg)
Give the equation to convert from one dosage form to another...then be specific convert from IV to PO form
- dose of new= amount absd of oldF of new
Change IV to PO
If the dose equivalent of 2 dosage forms are found ex. old form is 200mcg IV and new form is 286mcg PO...how does the Css of the 2 dosage forms compare?
- the Css of the 2 dosage forms would be similar
- the Css of IV would be similar to Css of PO form
If an IV dose of 200mcg digioxin is given and the equivalent oral dosage is 286mcg, what must be done to the oral dosage, why? what effect does this have on the Css?
- the oral dosage form must be rounded down to 250mcg
- round down from 286mcg to 250mcg bc that is the closet dosage form available
- by rounding the dosage down this alters the Css, it is no longer equivalent
Give the equation to find the new Css after you have changed dosage forms or doses
Cssnew = Cssold ( Drounded/Dcomputed)
SEE notebook for example problem of finding the new Css after altering the dosage form/dose
What is the therapeutic range for some one with atrial fibrilation? Why?
0.8 to 1.5ng/dL bc digoxin is used for its chronotropic effect when someone has altrial fibirilation
What is the therapeutic range of digoxin for someone with HF? Why?
0.5 to 1ng/dL bc digoxin is used for its inotropic effect when the patient has HF
What is the volume of distribution of digoxin?
Give the equation to calculate the loading dose (LD)
Loading dose= (Vd *Css)/(S*F)
Give the equation to calculate the maintenance dose (MD)
MD = (Cl*Css*Int.)/(S*F)
Int = dosing interval
What is the dosing interval that should be used in the MD equation?
the dosing interval is 1 day so = 1
How should the loading dose of digoixin be administered?
- in divided doses
- 50% now
- 4-6 hrs later give 25%
- 46 hrs later give 25%
If a patient was given a dose and did not acheive the expected steady state, how can you find out what dose should be given to acheive the desired steady state?
set it up in a proportion
When would a booster dose be given?
- to increase serum conc. immediately in an acute situatin in patient with sub therapeutic level
- after giving the loading dose and the patient is still not controlled
Give the booster dose equation
BD = (Cdesired/Cactual)*Vd)/F
What is usually given along side the booster dose?
the maintenance dose
How does the booster dose effect the time to achieve Css?
giving the booster dose does not affect the time to acieve Css
How should the booster dose be administered?
split the booster dose into 2 seperated doses
NOTE: the LD is split by 50% then two 25% doses
What type of model does the distribution of digoxin follow?
a 2 compartment model
Why is serum level of digoxin taken bf complete distribution of digoxin misleading?
bc digoxin follows a 2 compartment model and the drug would not be completely distributed at that time to the heart
Describe compartment 1 of the 2 compartment model
digoxin distributes into plasma = a small Vd value
Describe compartment 2 of the compartment model
digoxin distributes large and slowly equilibrating tissues...the myocardium responds like it is in the slow tissue...Vd is large value
When should oral and IV levels of digoxin be drawn?
- 4 hrs after an IV dose
- 6 hrs after an oral dose
When can the clinical effect of digoxin be observed?
35 minutes after a dose is given
After 1 hr, what percent of an IV dose does the mycoadium experience the effects of
75% of an IV dose can affect the heart w/in 1 hr
What is the avg Vd for digoxin in patients w/out disease states?
*NOTE- means you need to mulitply 7 * the weight in kg to get the volume of distribution
How is the Vd effected in patients that have renal disease?
the Vd is DECREASED in patients with renal disease
How is the Vd of digoxin affected by hyperthyroid patients?
the Vd is INCREASED in hyperthyroidism
How is the Vd effected in obese subjects?
the Vd is not effected in obese patients
Name 5 factors that effect volume of distribution (Vd) and clearance of digoxin
What should be done if the patient has one of the factors that effects the Vd and Cl of digoxin?
- Calculate the Digoxin Clearance and then multiply the volume of distribution by:
- 0.7 for quinidine
- 0.7 for hypothyroidism
- 1.3 for hyperthyroidism
- 0.5 for amiodarone
- 0.75 for verapamil
What effect exactly do quinidine, hyperthyroidism and hyperthyroidism have on digoxin clearance?
- quinidine inhibits the metabolism of digoxin
- hyperthyroidism increases the clearance of digoxin
- hypothyroidism decreases the clearance of digoxin
What weight should be used to calculate the Vd? What is the exception?
- 1.if the patients acutal body weight is less than the IBW
- 2. if actual weight is <30% of the IBW then used the actual body weight
**if the patient is greater than 30% over IBW use IBW for calculation
1.Give equation for calculating the volume of distribution of digoxin if the patient has a CrCl < 30....
2.how is Vd calculated if the CrCl > 30??....
3. What wt should be used in this equation?
Vd = 226 + (298*CrCL/29.1+CrCL) * wt/70
- if normal CrCl use
- 7L/kg for Vd of digoxin
- IBW if the patients ABW is greater than 30% of the IBW
otherwise use the ABW
What is the metabolic clearance of digoxin in healthy people?
0.57 to 0.86 mL/kg/min
Effect of CHF on digoxin metabolic clearance?
reduces the metabolic clearance of digoxin by one-half its usual value
Effect of CHF on the renal clearance of digoxin?
reduces the renal clearance
Effect of decrease in hepatic blood flow on digoxin clearance
decreases digoxin clearance
Effect of hyperthyroidism on digoxin metabolism and clearance?
increases the metabolism and clearance of the drug thus a higher dose will be needed
Give the formula for digoxin clearance
Cldigoxin = 1.303(CrCl) + ClNR
What should be calculated before calculating the digoxin clearance?
the serum creatine clearance
When using the digoxin clearance formula give the ClNR values for patients with HF and those w/o HF
- w/o HF, ClNR = 40
- with HF, ClNR = 20
What does K stand for?
What is K equal to?
K = Cl/Vd
What is the half life (t 1/2) equal to?
- t 1/2 = 0.693/k
- t 1/2 = 0.693 (Vd)/Cl
- if K is unkown
What can t be equal to?
t = ln(C1/C2)/k
How are the t 1/2 and Vd related?
How are the t 1/2 and Cl related?
- the t 1/2 and Vd are directly related as Vd increases the t 1/2 increases
- the t 1/2 and Cl are inversely related as the Cl increased the t 1/2 decreases
SEE notebook for problem to calculate IV digoxin dose
True or False: Hypermetabolic states have higher renal and non-renal clearance?
All the following conditions will decrease reanl digoxin clearance except??
Decreased hepatic blood flow
Give the t 1/2 (half life) of digoxin
How does the half life of digoxin differ if the patient has renal failure? What does this mean?
- if the patient has renal failure then the t 1/2 of digoxin is about 5 days
- it means that it takes 3 more days for renal patients to reach 50% of the dose is gone than normal patients
- ** it takes 5 days to elminate 50% of the drug
- it takes 2 days w/o renal failure to eliminate 50% of the drug
Why is the increase in t 1/2 in renal patients shorter than what should be expected?
bc the digoxin Vd and the Cl are decreasing at the same time
Describe the half life of digoxin in infants, neonates, and children age (6months to 8 yrs old).
- neonates: 45hrs - 2.5 days
- infants: 60hrs -1.8 days
- children: 18hrs <1 day
What causes the majority of drug interactions with digoixn?
inhibiton of P glycoprotein
Where is the p glycoprotein efflux pump found in the body?
in the kidney, liver and intestines
What is found in 10% of patients that helps metabolize oral digoxin?
What drug class is the most potent inhibitor of digoxin?
Name drugs that inhibit digoxin clearance and lead to increase in Css of digoxin
Name drugs that decrease the metabolism of digoxin by killing Eubacterium
What is the first step when treating digoxin toxicity?
dicontinue its use
Give signs of digoxin toxicity
- sinus bradycardia
- SA arrest
- second or third degree AV block
- ventricular arrhythmias
What drug is used to treat sinus bradycardia, AV block, 2nd/3rd degree heart block?
atropine - antagonizes the acetylcholine receptor
What dose of atropine should be given to treat digoxin toxicity? max dose? length of time?
0.01mg/kg/dose and can be repeated up to 0.40mg/kg over 2 minutes
What drug is useful in treating digoxin induced ventricular arrhythmias?
What does lidocaine not improve?
AV nodal conduction
When is propanolol contraindicated?
when treating atrial tachycardia bc it will cause bradycardia by decreasing AV conduction
What drug is used to treat life threating episodes of digoxin toxicity?
How much drug is contained in 1 vial of digiFab?
How will the level of digoxin be affected by digibind?
if the level is drawn it will be falsely high
Does digibind have a greater affinity for Na/K ATPase pumps or for digoxin?
Give the formula to calculate how many vials of digibind will be needed for a digoxin overdose.
digibind vials = (digoxin conc. * body wt)/100
SEE powerpoint for EXAMPLE of digibind when the blood concentration is known
an overdose where the number of tablets is known
What does TBS stand for?
digoxin Total Body Store
What is the formula forTotal Body Stores (TBS)?
TBS = F * (#dosage units) * dosage form strength in mg
What is meant by # of dosage units?
this will be the number of tablets that the person took
What is meant by dosage form strength?
the stength of the tablets that were taken..ex. 0.125mcg
How should the dosage form stength be given for the TBS equation?
in mg NOT mcg
If the # of tablets is known how is the digibind dose calculated?
digbind dose = TBS/(0.5mg/vial)
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