Session 1 - Pharmacokinetics

Question 1

What does ADME stand for?

Answer 1

Absorption
Distribution
Metabolism
Elimination

Question 2

What are two potential routes drugs can be administered?

Answer 2

Oral and parenteral

Question 3

What is oral administration?

Answer 3

Enter via GI tract, sublingual or rectal

Question 4

What is parenteral admin?

Answer 4

Any route that doesn’t involve GI tract

Question 5

What are two overarching factors which effect peak plasma concentration of a drug?

Answer 5

Rate of uptake of a drug and first pass metabolism

Question 6

Give four factors which can effect systemic entry of a drug

Answer 6

Gastrointenstinal motility, splanchnic blood flow, molecular size, pH levels

Question 7

What is first pass metabolism?

Answer 7

Any metabolism drug undergoes before reaching systemic circulation. This occurs via liver, gut lumen or gut wall.

Question 8

How can the gut lumen effect drugs?

Answer 8

Gastric acid or proteolytic enzymes

Question 9

How can gut wall effect drugs?

Answer 9

Glycoprotein efflux pumps drugs out of intenstinal enterocyte back into the lumen

Question 10

What is bioavailability?

Answer 10

The amount of drug which reaches the systemic circulation in an unchanged form relative to that if administered via IV.

Question 11

How is bioavailability calculated?

Answer 11

Amount of drug reaching systemic circulation/total amount of drug adminstered

Question 12

What is the difference between oral bioavailability and bioavailability?

Answer 12

Oral bioavailability is normally synonymous with bioavailability, yet specifically refers to when drug is administered orally. It can be calculated by AUCoral / AUCintravenous.

Question 13

Why is bioavailabiity different between patients?

Answer 13

Affected by intestinal motility, food, age and first pass metabolism

Question 14

What are the main factors which determine drug distribution? (ability to “dissolve” in the body)

Answer 14

Lipophilicity/hydrophilicity

Protein binding

Question 15

What is an object drug?

Answer 15

Amount of drug administered lower than the binding site numbers (warfarin)

Question 16

What is a prepicitant drug?

Answer 16

Number of molecules administered higher than the number of binding sites (aspirin/phenytoin)

Question 17

When can changes to protein binding happen physiologically?

Answer 17

From factors such as hypoalbuminaemia, pregnancy, renal failure, or displacement by other drugs

Question 18

When will physiological changes in protein binding be important?

Answer 18

• High protein binding
• Low Vd
• Drug has a narrow therapeutic ratio

Question 19

What is volume of distribution?

Answer 19

Vd (l/kg) = total amount of drug in the body/plasma conc of drug (at time =0)

Question 20

What does a larger Vd mean?

Answer 20

The more drug distributes throughout the body

Question 21

What facotr is Vd proportional to?

Answer 21

The half life of the drugs

Question 22

What main factors in Vd affected by?

Answer 22

Protien binding

Question 23

What causes acute changes in Vd?

Answer 23

Sepsis (increased vascular permeability), concurrent drugs (binding site taken up, lower Vd), hypoalbuminaemia

Question 24

What is the family of enzymes necessary for phase 1 reactions?

Answer 24

CYP450

Question 25

Give a few drugs which induce CYPs

Answer 25

Phenytoin, Carbamazapine, Barbiturates, Rifampicin, Alcohol, and Sulphonylureas (PCBRAS)

Question 26

Give a few drugs which inhibit CYPs

Answer 26

Omeprazole, Disulfiram, Erythromycin, Valproic acid, Isoniazid, Cimetidine, Ethanol (acute) and Sulphonamides (O-DEVICES)

Question 27

What three factors determine the rate of renal excretion of drugs?

Answer 27

GFR, passive tubular reabsorption and active tubular secretion

Question 28

What is clearance?

Answer 28

a measure of both hepatic clearance and renal clearance; any reduction in GFR will reduce renal clearance so increase a drugs t1/2.

Question 29

What are needed to excrete drugs into nephron lumen?

Answer 29

Organic Anion and Cation Transporters (OAT and OCT) act as renal transporters (via active transporter.
defined as the rate of elimination of a drug from the body

Question 30

What three factors affect clearance?

Answer 30

HRH
Heart
Renal
Hepative

Question 31

How does heart affect clearance?

Answer 31

Cardiovascular system factors affect blood flow to the main organs of elimination

Question 32

How can you determine half life?

Answer 32

By using Vd and clearance levels

t1/2 = 0.693 x Vd/ Clearance

Question 33

Define half life

Answer 33

‘the amount of time over which the concentration a drug in plasma decreases to once half of the concentration value it had when measured

Question 34

What are 1st order kinetics?

Answer 34

rate of elimination is proportional to drug level. Constant fraction of drug eliminated in unit time and a half life can be defined.

Question 35

What are 0 order kinetics?

Answer 35

rate of elimination is constant and no half life can be defined. Drug monitoring is essential.

Question 36

How can drugs administration be tailored to maintain a steady state?

Answer 36

During repeated drug administration, a new steady state (Steady State Concentration in Plasma (CpSS)) can be achieved allowing levels to stay within a therapeutic window

Question 37

How do you calculate CpSS?

Answer 37

CpSS = dose rate / clearance.

Question 38

What is a loading dose?

Answer 38

When a clinician wants to achieve a CpSS within the therapeutic window quickly (i.e. without waiting for 4-5 half lives), a loading dose (DoseL) can be used

Question 39

How is loading dose calculated?

Answer 39

Loading Dose (DoseL) = Vd x CpSS