Pharmacokinetics (session 7) Flashcards Preview

Semester 1-ICPP > Pharmacokinetics (session 7) > Flashcards

Flashcards in Pharmacokinetics (session 7) Deck (51):
1

What are the enteral methods of drug delivery into the internal environment of the body?

Oral
Sublingual
Rectal

2

What are the parenteral methods of drug delivery into the internal environment of the body?

Intravenous
Subcutaneous
Intramuscular

3

What are the methods of drug absorption on a molecular level (that we need to know about)? (3)

Passive diffusion
Facilitated diffusion
Secondary active transport

4

Which method of drug absorption do lipophilic drugs use?

Passive diffusion

5

True or false: Molecules (or solutes) with net ionic positive or negative charge within the GI pH range can be carried across the GI epithelia

TRUE

6

Solute carriers (SLCs) can either be one of two types of transporters-what are these?

OAT=organic anion transporter
OCT=organic cation transporter

7

Which two things are SLCs pharmacokinetically important for?

Drug absorption and elimination

8

Where are SLCs highly expressed?

GI, hepatic and renal epithelia

9

True or false: SLCs can only enable drug transport in GI by facilitated diffusion

FALSE - also by secondary active transport

10

What do SLCs use instead of ATP in secondary active transport?

Transport is driven by pre-existing electrochemical gradient across GI epithelial membrane

11

Give two examples of SLCs that use secondary active transport?

1. Fluoxetine/Prozac - antidepressant co-transported with Na+ ion
2. B-lactam antibiotics/penicillin - co-transported with H+ ion

12

Name three physicochemical factors that affect drug absorption

GI length/SA
Drug lipophilicity/pKa
Density of SLC expression in GI

13

Name three GI physiology related factors that affect drug absorption

Blood flow
GI motility
Food IpH (low pH destroys some drugs)

14

What is 'first pass' metabolism?

Reduces availability of drug reaching systemic circulation (part of CV system that carries oxygenated blood away from heart to body and deoxygenated blood back to heart) and therefore affects therapeutic potential

15

What carries out first pass metabolism? (2)

GI and liver

16

Which two major enzyme groups are some drugs metabolised bY?

Cytochrome P450s - Phase I enzymes
Conjugating - Phase II enzymes

17

True or false: there is much larger expression of Phase I and II enzymes in the liver than in the GI

TRUE

18

Define bioavailability

Fraction of a defined dose which reaches its way into a specific body compartment

19

What is the bioavailability reference for the CV system?

IV bolus=100%

20

What does the first stage of drug distribution involve? (3)

1. Bulk flow - arteries to capillaries
2. Diffusion - capillaries to interstitial fluid to cell membranes to targets
3. Barriers to diffusion - interactions/local permeability/non-target binding

21

True or false: if a drug is largely lipophilic, it can freely move across membrane barriers

TRUE

22

If a drug is largely hydrophilic, its journey across membrane barriers is dependent on which factors? (3)

Capillary permeability
Drug pKa and local pH
Presence of OATs/OCTs

23

What does a smaller Vd (apparent volume of distribution) mean?

Less penetration of interstitial/intracellular fluid compartment

24

Where does drug metabolism largely occur?

In the liver via phase I and II enzymes

25

What do phase I and II enzymes do?

Metabolise drugs - increase ionic charge and enhance renal elimination
Lipophilic drugs diffuse out of renal tubules and back into plasma and once metabolised, drugs are usually inactivated

26

Which enzyme carries out phase I metabolism?

Cytochrome P450 enzymes (CYP450s)

27

What are the two options for drugs metabolised in phase I?

Eliminated directly or go onto phase II

28

Give an example of when prodrugs activated by phase I metabolism activate to active species

Codeine to morphine

29

What carries out phase II metabolism?

Hepatic enzymes

30

True or false: phase I enzymes are versatile generalists

TRUE

31

True or false: phase I and II metabolism decreases ionic charge

FALSE - increases ionic charge

32

What are the three superfamilies of cytochrome P450 enzymes?

1, 2 and 3

33

What is an isozyme?

Each of two or more enzymes with identical function but different structure

34

Complete the sentence:

If another drug in the body is metabolised by induced CYP450 isozyme then its rate of elimination will be ___________

Increased

35

What is an example of CYP450 induction and how does it work?

Carbamazepine (CBZ) = anti-epileptic metabolised by CYP3A4
CBZ induces CYP3A4-lowers its own levels, affecting control of epilepsy

36

What is an example of CYP450 inhibition and what does it inhibit?

Grapefruit juice inhibits CYP3A4
CYP3A4 metabolises Verapimil, used to treat high BP. The result of this inhibition can be reduced BP and fainting

37

What is the main route of drug elimination?

Kidney

38

What are the other routes of drug elimination?

Bile
Lung
Breast milk
Sweat
Tears
Genital secretions
Saliva

39

What are the three processes of renal excretion?

Glomerular filtration
Active tubular secretion
Passive tubular reabsorption

40

What is clearance?

Rate of elimination of a drug from the body

41

For most drugs, total body clearance is approximately equal to what?

Hepatic clearance + renal clearance

42

What are the units of clearance (CL)?

ml/min

43

What is the real plasma volume?

3L

44

True or false: Clearance (CL) and Vd provide an estimate of drug half-life or t1/2

TRUE

45

Define drug half-life

Amount of time over which the concentration of a drug in plasma decreases to a half of its original concentration

46

If CL stays the same and Vd increases, what happens to t1/2?

Increases

47

If CL increases and Vd stays the same, what happens to t1/2?

Decreases

48

True or false: the rate of metabolism or excretion is proportional to concentration of drug

TRUE

49

When is the rate of metabolism or excretion proportional to concentration of drug?

When there are:
Plenty of phase I/II enzyme sites
Plenty of OAT/OCT transporters

50

What happens when eliminated processes becomes saturated?

They become rate limited and elimination kinetics are referred to as saturated or zero order

51

True or false: most drugs exhibit zero order kinetics at lower doses

FALSE-at higher doses