Session 1 - Pharmacokinetics Flashcards Preview

Semester 5 - Farmocology > Session 1 - Pharmacokinetics > Flashcards

Flashcards in Session 1 - Pharmacokinetics Deck (39)
1

What does ADME stand for?

Absorption
Distribution
Metabolism
Elimination

2

What are two potential routes drugs can be administered?

Oral and parenteral

3

What is oral administration?

Enter via GI tract, sublingual or rectal

4

What is parenteral admin?

Any route that doesn't involve GI tract

5

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

Rate of uptake of a drug and first pass metabolism

6

Give four factors which can effect systemic entry of a drug

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

7

What is first pass metabolism?

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

8

How can the gut lumen effect drugs?

Gastric acid or proteolytic enzymes

9

How can gut wall effect drugs?

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

10

What is bioavailability?

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

11

How is bioavailability calculated?

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

12

What is the difference between oral bioavailability and bioavailability?

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

13

Why is bioavailabiity different between patients?

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

14

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

Lipophilicity/hydrophilicity
Protein binding

15

What is an object drug?

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

16

What is a prepicitant drug?

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

17

When can changes to protein binding happen physiologically?

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

18

When will physiological changes in protein binding be important?

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

19

What is volume of distribution?

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

20

What does a larger Vd mean?

The more drug distributes throughout the body

21

What facotr is Vd proportional to?

The half life of the drugs

22

What main factors in Vd affected by?

Protien binding

23

What causes acute changes in Vd?

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

24

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

CYP450

25

Give a few drugs which induce CYPs

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

26

Give a few drugs which inhibit CYPs

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

27

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

GFR, passive tubular reabsorption and active tubular secretion

28

What is clearance?

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

29

What are needed to excrete drugs into nephron lumen?

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

30

What three factors affect clearance?

HRH
Heart
Renal
Hepative

31

How does heart affect clearance?

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

32

How can you determine half life?

By using Vd and clearance levels
t1/2 = 0.693 x Vd/ Clearance

33

Define half life

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

34

What are 1st order kinetics?

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

35

What are 0 order kinetics?

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

36

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

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

37

How do you calculate CpSS?

CpSS = dose rate / clearance.

38

What is a loading dose?

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

39

How is loading dose calculated?

Loading Dose (DoseL) = Vd x CpSS