Pharmacokinetics

Question 1

Cmax

Answer 1

Maximum concentration of drug following administration

Question 2

Tmax

Answer 2

Time at which maximum concentration of drug occurs

Question 3

AUC

Answer 3

Area under the curve (of a concentration vs time curve)

Question 4

What measures total systemic exposure to a drug?

Answer 4

AUC

Question 5

Are the large majority of drugs eliminated by zero order or first order processes?

Answer 5

First order (concentration dependent)

Question 6

Semi-log plot

Answer 6

Plotting log(concentration) against time

Question 7

Relationship between half life and k

Answer 7

T1/2 = 0.693/k

Question 8

Formula to calculate the concentration at any given time for first order drug

Answer 8

Ln C = -kt + ln C0

Question 9

What percentage of a first order drug is eliminated by 4 half lives?

Answer 9

93.75%

Question 10

How do you calculate half life for a zero order drug?

Answer 10

T1/2 = 0.5 A0/k0 (A0 is initial drug in system, k0 is the zero order rate constant (mass/time))

Question 11

What effect does eating before taking an oral medication have on the pharmacokinetics of that drug?

Answer 11

Cmax is reduced and Tmax is delayed (because food inhibits gut housekeeper waves and thus slows absorption)

Question 12

Why is it recommended that penicillin be taken on an empty stomach?

Answer 12

Because penicillin is degraded in acidic environments, and food presence slows absorption (increasing amount of drug degraded while in stomach)

Question 13

Calculation for bioavailability

Answer 13

(Div * AUCoral) / (Doral * AUCiv)

Question 14

Factors affecting oral availability of a drug

Answer 14

Solubility, polarity, size, lumen alterations of drug, first pass metabolism, drug transporters, pH

Question 15

What type of drug best avoids being altered in the gut lumen when given orally?

Answer 15

Small, non-peptide molecules

Question 16

Two examples of multi-drug transporters in the gut

Answer 16

P-glycoprotein and ABC cassette binding proteins

Question 17

How do basic conditions in the stomach affect absorption of aspirin?

Answer 17

None will be absorbed in the stomach (requires acidic environment), but the small intestine will almost entirely make it for it

Question 18

What types of medications can be taken sublingually?

Answer 18

Lipid soluble molecules (nitroglycerin, buprenorphine)

Question 19

Why do rectally administered drugs have less first pass metabolism?

Answer 19

Venous drainage here is partially portal and partially systemic

Question 20

When drugs are administered IM or SubQ, how are they absorbed?

Answer 20

Large molecular weight drugs (100,000 and up) are drained by lymphatics, smaller are taken up by capillaries

Question 21

Is penicillin a good choice for treating meningitis? Why or why not?

Answer 21

No. Large and polar, does not cross BBB well

Question 22

Calculation for volume of distribution

Answer 22

(Amount of drug in body at equilibrium) / (Plasma drug concentration)

Question 23

Give the effects of tissue protein binding and plasma protein binding respectively on volume of distribution

Answer 23

Tissue protein binding - increases volume of distribution, plasma protein binding - decreases volume of distribution

Question 24

What are the two main plasma binding proteins and what type of molecule does each bind?

Answer 24

Albumin - binds acidic drugs, a1-acid glycoprotein - binds basic drugs

Question 25

Calculation for clearance

Answer 25

Elimination rate / (Plasma Concentration)

Question 26

Calculation for a loading dose

Answer 26

D = Vd*C (volume of distribution times desired concentration)

Question 27

The classic example of a drug that is freely filtered and not secreted

Answer 27

Inulin

Question 28

Which form of acids and bases tend to be reabsorbed from the kidney tubule, ionized or non-ionized?

Answer 28

Non-ionized (remember, lipophilic (i.e. non-polar non-ionized) substances can cross membranes easily

Question 29

When dosing drugs, what measurement do we use as a proxy for kidney function?

Answer 29

Creatinine clearance

Question 30

In two compartment models, what do the alpha and beta half lives represent respectively?

Answer 30

Alpha half life - distribution phase, beta half life - terminal elimination phase

Question 31

What effect does grapefruit juice have on the activity of p-glycoprotein?

Answer 31

Inhibits it (leading to an increase in drug levels)

Question 32

Give two examples of drugs with huge volumes of distribution and state whether this indicates greater distribution of drug in plasma or tissue

Answer 32

Greater in tissue. Nortriptyline (1300 L), Digoxin (440 L)

Question 33

Give two examples of drugs with small volumes of distribution and state whether this indicates greater distribution of drug in plasma or tissue

Answer 33

Greater in plasma (possibly only in plasma). Theophylline (35 L), Gentamicin (18 L)

Question 34

In two compartment models, what determines the elimination rate and biologic half-life

Answer 34

The beta (elimination) phase

Question 35

What two factors primarily determine elimination rate?

Answer 35

Blood flow to the eliminating organ and efficiency of the organ in eliminating the drug

Question 36

Relationship of clearance to volume of distribution

Answer 36

Cl = Vd*Ke (volume of distribution times elimination constant)

Question 37

Formula for estimating creatinine clearance

Answer 37

(140-age) * (Body weight in Kg) / (72 * Serum Creatinine) (applies to males, multiple by 0.85 for females)

Question 38

What system is used to classify patients with hepatic impairment?

Answer 38

Child-Pugh Score for Cirrhosis (takes into account serum bilirubin, albumin, ascites, INR)

Question 39

What effect does CHF have on drug pharmacokinetics

Answer 39

Decreases elimination (due to decreased blood flow to eliminating organs)

Question 40

What effects can pregnancy have on drug pharmacokinetics?

Answer 40

Decrease protein binding, increase renal excretion, variable effects on metabolism

Question 41

Approximately how many half lives are required to achieve steady state

Answer 41

4-5 half lives