Session 9 - Pharmacokinetics Flashcards Preview

Semester 2 - Membranes and Receptors > Session 9 - Pharmacokinetics > Flashcards

Flashcards in Session 9 - Pharmacokinetics Deck (62):
1

Define pharmacokinetics

What the body does to a drug

2

Define pharmacodynamics

What the drug does to the body

3

Give four questions which should be asked when administering a drug,

Is the drug getting into the patient?(pharmaceutical process)
Is the drug getting to the site of action? (pharmacokinetic process)
Is the drug producing the desired pharmacological effects? (pharacodynamic process)
Is the pharmacologic effect translated into a therapeutic effect? (therapeutic process)

4

What are the two methods of drug formulation?

What is another factor on the administration of a drug?

Solid, liquid

Compliance - simplified regime

5

If solid, what extra factors must be considered?

Solubility and acidic stability in stomach must be considered

6

Give two sites of administration?

Local (eye, skin, inhalation)
Systemic (enteral or parenteral)

7

Give three examples of enteral systemic administration

Sublingual
Oral
Rectal

8

Give five examples of parenteral systemic administration

Subcutaneous/intramuscular/intravenous injection, inhalation, transdermal

9

Define the term oral bioavailability

Oral Bioavailability is the proportion of a dose given orally (Or by any other route other than intravenous) that reaches the systemic circulation in an unchanged form.

10

What can bioavailability be measured by?

1) Amount (depends on GI absorption and first pass metabolism)
2) Rate of availability (depends on pharmaceutical factors and rate of gut absorption)

11

What are two factors which effect gut absorption?

Altered by food or disease

12

How is amount measured on graph?

Area under curve of blood drug level vs. time

13

How is rate measured on a graph?

peak height and rate of rise of drug level in blood

14

What is maximum tolerated dose?

Lethal Dose to 50% of people

15

What is minimum effective dose?

Effective Dose in 50% of people

16

What is the equation for measuring therapeutic ratio?

Maximum Tolerated Dose/Minimum Effective Dose

(LD50/ED50)

17

Advantage of local admin?

Less systemic side effects, more direct action

18

What is the first pass effect?

Substances absorbed from the lumen of the ileum enter the venous blood, which drains into the hepatic portal vein and is transported directly to the liver. Liver is main site of drug metabolism, so any drug which enters it may be extensively metabolised before it reaches systemic circulation - first pass effect

19

How can the first pass effect be avoided?

The parenteral, sublingual or rectal routes can avoid it.

Glyceryl trinitrate is a particular example

20

How much of an oral dose of paracetamol is metabolised via first pass effect?

90%

21

Define drug distribution

The theoretical volume into which a drug has distributed assuming that mixing occurs instantaneously

22

What is drug distribution calculated by?

mount Given / Plasma Concentration at Time 0

23

What happens to many drugs once they reach circulation?

Protein binding interaction - this is significant as it is the free concentration of drug which has an effect, not the total

24

What does rate of action depend on?

Dissolution

25

When is protein binding important? (3)

The drug is highly bound to albumin (>90%)
The drug has a small volume of distribution
The drug has a low therapeutic index

26

Give two examples of drugs where protein binding is important

Warfarin and tolbutamide

27

What is an object drug? (class 1)

Drug is used at a dose that is much lower than the number of albumin binding sites

28

What is a precipitant drug? (class 2)

Drug is used at a dose that is greater than the number of available binding sites.

29

What drug should you take now?

Caffeine, you look a little tired.
I mean, not tired drawn out, just fatigued? Go ahead scamp, it's going to be a couple of weeks of intense revision - you can afford to go make a coffee (or a tea, if you prefer!).

30

Name three object drugs and their precipitants

Warfarin - Sulphonamides, aspirin, phenytoin
Tolbutamide - Sulphonamides, aspiin
Phenytoin - Valproate

31

What happens if class 1 and class 2 drugs are given simultaneously?

When the drugs are administered simultaneously, Object (class1) drugs are displaced by precipitant drugs (Class II), raising the free levels of the object drug and therefore, higher risk of toxicity.

32

What law do enzymes which metabolise drugs follow?

Why are the effects of drugs transient?

Michaelis Mentin Kinetics
As free drug level rises, so to does rate of elimination

33

What is the standard equation for rate of metabolism?

V max x (concentration)/Km + (C)

34

In a situatioon where a drug is used at concentration lowerer than km, what is the equation?

Rate of metabolism = Vmax (C)/Km

35

What are first order kinetics?

metabolism is proportional to drug concentration
Constant fraction of drug broken down in unit time. Half life can be defined.

36

What do first order kinetics look like on a gaph?

straight line when a log scale is on the Y-axis versus time

37

Define first order kinetics

When the rate of decline of plasma drug level is proportional to drug level. Half life can be defined.

38

When are 0 order kinetics obeyed?

When drug is used at a concentration much greater than Km

39

What is the equation for 0 order kinetics?

Rate of metabolism = Vmax (c)/(C)
Rate of metabolism effectively = vmax and the enzyme is saturated

40

Define 0 order kinetics

When the rate of decline of plasma drug level is constant, regardless of concentration. Give a straight line when normal (not log) plasma conc plotted against time

41

How long until steady state of drug is reached after repeated doses? Irrespective of dose or frequencyof administration

Five half lives

42

What happens if an immediate effect of drug is needed?

A loading dose is given, which is determined by the volume of distribution

43

What is the advantage of 1st order kinetics?

Gives predictable therapeutic response from dose increases (most drugs behave this way)

44

What is the major effect of 0 order kinetics?

Gives a therapeutic response which can suddenly escalate as elimination mechanisms saturate (alcohol, yay!)

45

What are the two stages of drug elimination?

Metabolism (by liver)
Excretion (by kidney)

46

What is phase 1 of drug metabolism?

Most drug molecules are stable and relatively unreactive (a pro-drug) so in Phase I a reactive group is exposed on the parent molecule or added to the molecule.

47

Why are reactive groups added or exposed on parent molecule in phase 1 of drug metabolism?

Generates a reactive intermediate that can be conjugated (in Phase II) with a water-soluble molecule to form a water-soluble complex.

48

What are the three methods via which reactive groups added or exposed on parent molecule in phase 1 of drug metabolism?

Oxidation
Reduction
Hydrolysis

49

What enzymes are needed for phase one of drug metabolism?

Cytochrome P450 and high energy cofactor (NADPH). Enzymes are inducible and inhibitable.
Low substrate specificity
Affinity for lipid soluble molecules

50

When do drug interactions matter?

Low therapeutic ratio
Drug at minimum effective concentration

51

Name three enzyme inducers and the drugs the effect

Phenobarbitone - Warfarin, Phenytoin
Rifampicin - Oral contraceptive
Cigarette smoke - Theophylline

52

Name an enzyme inhibitor found in phase 1 and the drugs it effects

Cimetidine (stomach ulcer treatment) - Warfarin, Diazepam

53

Name a drug which can bypass phase 1 of drug metabolism

Morphine

54

What occurs in phase 2 of drug metabolism?

The reactive intermediate from Phase I is conjugated with a polar molecule to form a water-soluble complex. The process is also known as conjugation.

55

Name three conjugates involved in phase 2

Glucoronic acid
sulphate ions and glutathione

56

What high energy cofactor is required in phase 2 drug metabolism?

uridine diphosphate glucuronic acid (UDPGA)

57

Name three potentiators of warfarin, and how they have effect

Alcohol - inhibits metabolism
Aspririn, suplhonamides, phenytoin - displacement from plasma proteins
Broad spectrum antibiotics - reduced Vit K synthesis

58

Give two inhibitors of warfarin and their one effect

Barbiturates, rifampicin - Induces liver metabolizing enzymes

59

What state must a drug be to be excreted by the kidney? Give one method of excretion from tubule

Only the free unbound drug is filtered through glomerular tuft.
Drugs can be actively secreted by the tubule

60

What determines how much of a drug is excreted?

Urine pH

Pk of drug is pH at which half of it is ionised

61

What occurs for weak acids in terms of urine excretion?

For weak acids, e.g. aspirin, making the urine alkaline will make the drug ionised, so there will be less tubular absorption because the charged drugs stay in the tubule lumen.
Forced alkaline diuresis used in aspirin overdose

62

What occurs for weak bases in terms of urine excretion?

For weak bases, e.g. amphetamine, the opposite is true and acidic urine will increase excretion. Acid urine will ionise a weak base, making the charged drug stay in the tubule lumen.
Forced acidic diuresis to increase excretion.