Pharacokinetics I/II - Patel

Question 0

Vd

Answer 0

Volume of distribution - the “apparent” volume that relates the amount of the drug in the body to the concentration in the blood. The “imaginary container” that is required to account for the total amount of drug in the body. DOES NOT relate to physiological volumes, only conceptual.
Amount of drug in the body/initial drug concentration
=Ab/Co
=F*dose/Co
Units: L or ml

Question 1

Pharmacokinetics

Answer 1

The study of the disposition of a drug and/or its metabolites in the body based on time. Pharmacokinetics is an attempt to model how the body acts upon a drug in a systematic manner, by utilizing mathematical correlates adapted to the graphical representation of variables such as time and serum or plasma concentration.

Question 2

Obese patient alterations

Answer 2

T1/2 increases for lipophilic drugs
Vd: increases for lipophilic drugs, decreases for hydrophilic drugs, CL (clearance) is increased in patients with normal renal fxn
Albumin bound medications are unlikely to be altered in obese patients
CO (cardiac output) increases
Normal W patient - 5% CO goes to adipose tissue
Obese patient - 2% CO goes to adipose tissue

Question 3

Determinants: Protein Binding

Answer 3

Drug properties: pKa, concentration
Protein: Albumin, alpha1-glycoprotein (higher acidic or basic drugs bind more frequently
Protein affinity: Highly protein bound drugs have a lower CL(hepatic), amount of free drug determines clinical effect. Higher protein binding drugs may require more amount to create clinical effect.
Drug interactions: high protein binding, Uremia

Question 4

Protein Binding

Answer 4

Most bind to blood protein (albumin), bound drugs stay in plasma, free drugs cross capillary wall = tissues, unbound and unionized drugs can cross placenta and BBB

Question 5

Bioavailability (F)

Answer 5

Fraction of drug absorbed from a given dose.
Does not consider rate of absorption
Ab (amount absorbed) = F * dose
F is usually given as a percent, which needs to be converted to a decimal.
IV administration is always F=1 (direct)

Question 6

First-Pass Elimination

Answer 6

Consists of the amount of drug transported to the liver after being absorbed by the gut wall, prior to being transported to into circulation
**IV , inhalation, and sublingual administration bypass 1st pass elimination
Concentrates amount of drug at action site

Question 7

Phase I metabolism

Answer 7

Hydrolyses
Oxidation - CYP450 reactions
Reduction
**Patients with liver disease have trouble metabolizing phase I drugs.

Question 8

Phase II Metabolism

Answer 8

Methylation
Acetylation 
Glucuronidation
Glutathione conjugation
Glycine conjugation
Sulfation

Question 9

CYP450 Induction

Answer 9

Certain drugs when administered concomitantly can increase the activity of an CYP450 enzyme

Question 10

CYP450 Inhibition

Answer 10

Certain drugs when administered concomitantly can decrease the activity of an CYP450 enzyme

Question 11

Elimination

Answer 11

Metabolism - EX transformation from lipophilic to hydrophilic
Excretion - elimination of the parent drug/metabolite from the body
Clearance - Removal of drug from a given volume in specific time frame (ml/min)

Question 12

Factors effecting CL

Answer 12

Impaired hepatic/renal fxn
Protein binding/ionizing
Blood flow to kidney/liver
Smoking
Concurrent medications (interactions)

Question 13

Clearance (CL)

Answer 13

Renal CL = 100 ml/min
CON = 5 mg/ml so, 500 mg in 100 ml or in 1 min, 500 mg of drug will be eliminated.
=Vd * Ke

Question 14

Zero Order Elimination Rate

Answer 14

Amount of drug eliminated at a constant rate
K is constant that relates amount in body/time
Units=mg/hr
A=Ao-(rate of elimination) * t

Question 15

First Order Elimination Rate

Answer 15

Amount of drug eliminated at a rate proportional to the amount of drug remaining
K is a constant that relates the rate of drug elimination to the amount in the body at any time (t)
k=rate of elimination/amount in the body
Units = mg/min
C=Co * e^-kt

Question 16

Rate of elimination

Answer 16

= CL (ml/min) * Concentration (mg/ml)

= CL/Vd

Question 17

Zero Order Absorption Rate

Answer 17

Constant, independent of amount administered
Ko
Ex: IV administration

Question 18

First Order Absorption Rate

Answer 18

Absorption rate is proportional to the amount of drug present (Ka)
Fraction of drug absorbed per unit of time
Larger Ka = faster the drug is absorbed

Question 19

Elimination 1/2 life (T1/2)

Answer 19

Time it takes for 50% drug in the body to be eliminated. Dependent on V and Cl in the same way k is
T1/2= 0.693/Ke
= 0.693 * Vd/Cl

Question 20

Steady State [Css]f

Answer 20

state of equilibrium where the rate of administration = the rate of elimination

• *Usually take 5 1/2 life’s to reach steady state
• • Time to reach Css is independent of dose!! Dependent on T1/2.
• • Css value is dependent on dose as well as dosing frequency

Question 21

Maintenance Dosing (MD)

Answer 21

Administration at constant time intervals
time between dosing is denoted with T
MD = (Cl * Css * T) / F

Question 22

Loading Dose (LD)

Answer 22

A higher starting dose used to quickly up concentration of drug in the plasma to a specific target quickly
= Vd * Css , where Css it the target concentration
Since reaching 1/2 life takes time, immediate drug response requires loading doses

Question 23

Creatinine Clearance (CrCl)

Answer 23

Used as a marker for renal function (glomerular filtration rate). Normal CrCl for 70 Kg patient is 120 ml/min
= [(140/age) * IBW] / (72 * Scr)
Multiply this formula by 0.85 for females (smaller CrCl than males).

Question 24

Factors effecting Creatinine

Answer 24

Muscle mass - lower in the elderly
Severe liver disease - interferes with conversion from creatine to creatinine
Directly proportional to BM