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Flashcards in 3 Medical Mathematics: Pharmacokinetics (not done) Deck (50):
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What is Pharmacokinetics?

Is the mathematical description of the plasma concentration-time course

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Dosage regimen

Dosage
Route of administration
Frequency
Duration of administration

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Optimum dosage regimen

Effective
Nontoxic
Without prolonged drug residues in tissues of food animals

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Rate of absorption Measured by what?

Time

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Extent of absorption Measured by what?

systemic bioavailability (F%)

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Rate of absorption
Is the time to peak plasma concentration

.

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What is Systemic bioavailability?

is the fraction of the dose which reaches the systemic circulation intact

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Systemic bioavailability formula

Systemic bioavailability (F%) = AUC extravascular X 100 / AUC IV

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What is AUC?

Area under the plasma concentration-time curve

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Compartment refers to what?

to those tissues and organs for which the rates of uptake and subsequent clearance of a drug are similar.
One-compartment model
All tissues and organs which the drug penetrates behave as if they were in ready equilibrium with the blood.

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Rate of distribution is Estimated by what?

the distribution phase half-time (t1/2) in the two-compartment model

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Extent of distribution is Measured by what?

the apparent volume of distribution (Vd)

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What is Apparent volume of distribution (Vd)?

the volume of fluid which would be required to contain the amount of the drug in the body if it were uniformly distributed, and the concentration in that fluid was equal to the concentration in the plasma

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Apparent volume of distribution (Vd) formula

Vd (L/kg) = amount of drug in the body (D) / plasma drug concentration (Cp)

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The amount of drug in the body = the dose IV

For IV the Vd (L/kg) = Dose (D) (mg/kg) / Cp (mg/L)

.

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For extravascular the Vd (L/kg) = D (mg/kg) X F% / Cp (mg/L)

.

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Clinically when:
Vd < 1L/kg

The drug has a limited distribution (tends to stay in plasma)

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Clinically when:
Vd = 1L/kg

The drug has a wide distribution

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Clinically when:
Vd > 1L/kg

The drug has a very wide distribution

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Elimination is measure by what?

Measured by half-life (t1/2) or total body clearance (CLB)

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What is Half-life (t1/2)?

is the time required for the body to eliminate one-half of the drug it contains

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What is First-order kinetics?

Elimination of most drugs follows first-order kinetics.
First-order kinetics means that the rate of removal of drug from the plasma is proportional to the concentration present at a given time (a constant percent of drug is eliminated per unit time).

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Few drugs such as aspirin in cats and phenylbutazone in dogs and horses follow what?

zero-order kinetics

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What is zero-order kinetics?

the rate of elimination remains constant regardless of the amount of drug in the body (a constant amount of drug is eliminated per unit time)

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The half-life determines what?

the rate at which plasma concentration of a drug rises during constant IV infusion to attain a steady-state concentration

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What is Steady-state plasma concentration or plateau (Cp (SS))?

Is the plasma concentration of drug when the maintenance rate of drug administration is equal to the rate of elimination

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After four half-lives, the plasma concentration is what?

93.75% of the eventual steady-state plasma concentration (or 90% of the steady-state concentration is achieved in 3.3 t1/2)

27

Acceptable residue of a pesticide in cow’s milk is 5 ppb. Average concentration of this pesticide in milk from a herd inadvertently exposed to this pesticide is 80 ppb. The half-life of elimination in milk is 5 days. How long would you recommend the milk from this herd to be withheld assuming that elimination follows first-order kinetics?
a. 10 days
b. 15 days
c. 20 days
d. 25 days
e. 30 days

c. 20 days

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What is Total body clearance (ClB)?

is the rate of drug elimination from the body, by all routes, relative to the concentration of drug in plasma.
CLB = CLr + CLnr

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What is Plasma clearance (CLp)?

the volume of plasma cleared of the drug per unit time (mL/min.).

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Plasma clearance (CLp) formula

Plasma clearance (CLp) = rate of elimination (mg/min) / plasma drug concentration (mg/mL)
The rate of elimination (mg/min) = urine flow (mL/min) X
concentration of drug in urine (mg/mL)

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Calculation of half-life

CLB = Vd X (k) / T1/2
CLB = 0.693 X Vd / T1/2
T1/2 = 0.693 X Vd / CLB

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What is the Extraction ratio?

Is the fraction of the drug removed from the perfusing blood by an organ
Extraction ratio (E) = CA - CV / CA
CA = the concentration of drug in arterial blood entering the organ
CV = the concentration of drug in venous blood leaving the organ
Clorgan = Q X E
Q = blood flow to the organ
E = Extraction ratio

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examples of drugs that have high hepatic extraction ratio

Lidocaine, propranolol, diazepam and nitroglycerin

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Calculating Dosage Regimen

Maintenance dose
Loading dose

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Maintenance dose
(Best to see notes for all formulas) (pgs ~152)

Dosing rate = Clearance X desired steady-state concentration
The daily dosing intervaldose = dose/min X 60 min per hour X 24 hours
Dose X F / dosing interval = CLB X Cp (ss)
CLB = total body clearance
Cp(ss)= steady-state plasma concentration

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The ClB of an antibiotic in a dog is 80 mL/min and Vd is 40 L. What maintenance dose must be administered intravenously every 6 hours to eventually obtain average steady-state plasma concentrations of 4 mg/L?
a. 0.32 mg
b. 115 mg
c. 160 mg
d. 230 mg
e. none of the above

b. 115 mg

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Loading dose

Loading dose = Vd X desired serum drug concentration

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If you wish to give this dog a loading dose to achieve the therapeutic plasma concentration of 4 mg/L rapidly, how much should be given?
a. 0.1 mg
b. 10mg
c. 115.2 mg
d. 160 mg
e. none of the above

d. 160 mg

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Dosage adjustment in renal disease

For drugs that depend on renal clearance
Adjustment of either the dose or the dose interval relative to renal function

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Dosage adjustment in renal disease formulas

Adjusted dose = Normal dose X Patient’s renal clearance / Normal renal clearance
Adjusted dose interval = Normal dose interval X Normal renal clearance / Patient’s renal clearance
Renal clearance is usually estimated by creatinine clearance

41

Soon after the IV injection of 2 grams of a drug, the concentration in the plasma is 10 mg/100 mL. The calculated apparent volume of distribution would be
a. 0.50 liters
b. 2.00 liters
c. 5.00 liters
d. 20.00 liters
e. 200.00 liters

d. 20.00 liters

42

Following the IV injection of 100 mg of a drug and before a significant amount is metabolized or excreted, the plasma concentration reaches the constant level. The apparent volume of distribution is found to be 20 liters. The plasma concentration therefore is found to be:
a. 1 mg/liter
b. 2 mg/liter
c. 3 mg/liter
d. 4 mg/liter
e. 5 mg/liter

e. 5 mg/liter

43

If the apparent volume of distribution of a drug in an animal were 7 liters, what would be the predicted initial plasma concentration of the drug following IV injection of 70 mg?
a. 7 mg/mL
b. 0.7 mg/mL
c. 10.0 mg/mL
d. 0.01 mg/mL
e. 0.001 mg/mlL

d. 0.01 mg/mL

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5. The concentration of a drug in urine is 100 mg/mL and in plasma 10 mg/mL, the urine flow is 10 mL/min. What is the renal clearance of the drug?
a. 100 mL/min
b. 30 mL/min
c. 10 mL/min
d. 3 mL/min
e. 1 mL/min

a. 100 mL/min

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6. The concentration of drug X “free” in plasma is 1 mg/mL and in urine is 5 mg/mL. Urine
flow is 10 mL/min. What is the plasma clearance of drug X?
a. 5 mL/min
b. 50 mL/min
c. 100 mL/min
d. 150 mL/min
e. 500 mL/min

b. 50 mL/min

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7. The concentration of a drug in urine is 10 mg/mL and in plasma is 1 mg/mL. The urine
flow is 10 mL/min. What is the renal clearance of the drug?
a. 100 mL/min
b. 30 mL/min
c. 10 mL/min
d. 3 mL/min
e. 1 mL/min

a. 100 mL/min

47

The ClB of an antibiotic in a dog is 80 mL/min and Vd is 40 L. What maintenance dose must be administered intravenously every 6 hours to eventually obtain average steady- state plasma concentrations of 4 mg/L?
a. 0.32 mg
b. 115 mg
c. 160 mg
d. 230 mg
e. none of the above

b. 115 mg

48

If you wish to give this dog a loading dose to achieve the therapeutic plasma
concentration of 4 mg/L rapidly, how much should be given?
a. 0.1 mg
b. 10mg
c. 115.2 mg
d. 160 mg
e. none of the above

d. 160 mg

49

Which of the following MOST closely describes the clearance rate of a drug that is infused at a rate of 4 mg/min and produces a steady-state concentration of 6 mg/L in the plasma?
a. 67 mL/min
b. 132 mL/min
c. 300 mL/min
d. 667 mL/min
e. 1,200 mL/min

d. 667 mL/min

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