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Flashcards in MR 9 Pharmacokinetics Deck (41):
1

What is pharmacokinetics?

What the body does to a drug

2

What 4 questions should be asked when prescribing drugs?

Is drug getting into patient? (pharmaceutical process)
Is drug getting to site of action?(pharmacokinetic process)
Is drug producing desired effect? (pharmacodynamic process)
Is it translated to a therapeutic effect? (therapeutic process)

3

What formulations of drugs are there?

solid
liquid

4

What sites of administration can there be for a drug?

Local (eye, skin, inhalation etc)
Systemic:
Enteral (sublingual, oral, rectal)
Parenteral (subcutaneous/intramuscualar/intravenous injection, inhalation, transdermal

5

What is oral bioavailability?

The proportion of a dose given orally (or by any other route than intravenous) that reaches systemic circulation in an unchanged form

6

How is bioavailability expressed?

Amount -measured by area under curve of blood drug level vs time. depends on 1st pass metabolism and gut absorption
Rate- measured by peak height and rate of rise of drug level in blood. Depends on pharmaceutical factors, gut absorption

7

What is the therapeutic ratio?

Max tolerated dose/minimum effective dose
(lethal dose to 50% of people) LD50/ED50 (effective dose in 50% of people)

8

Describe the first pass effect

Substances absorbed from lumen of ileum enter venous blood which drains to hepatic portal vein and is transported directly to liver which is main site of drug metabolism as contains all necessary enzyme systems. This means the drug may be extensively metabolised during first pass through the liver.

9

What routes of administration can avoid first pass effect?

parenteral, sublingual, rectal

10

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

90%

11

What is drug distribution?

The theoretical volume into which a drug has distributed assuming occurred instantaneously

12

How is drug distribution calculated?

Amount given/ Plasma concentration at time 0

13

Does free or total drug exert an effect?

free

14

When are protein binding interactions important?

When drug highly bound to albumin (>90%)
Drug has small volume of distribution
Drug has low therapeutic index
e.g warfarin, tolbutamide

15

What dose is an object drug (class I drug) used at?

dose much lower than number of albumin binding sites

16

What dose is a Precipitant Drug (class II drug) used at?

dose greater than number of available albumin binding sites

17

What happens when object and precipitant drugs are administered simultaneously?

Object drugs displaced at albumin binding sites by precipitant drugs, raising free levels of object drug.
This gives higher risk of toxicity

18

What are precipitant drugs to warfarin?

sulphonamides, aspirin, phenytoin

19

What are precipitant drugs to tolbutamide?

sulphonamides, aspirin

20

What is a precipitant drug to phenytoin?

Valproate

21

What is 1st order kinetics?

When drug elimination is proportional to drug level.
Constant fraction of drug eliminated in unit time
Half life can be defined

22

What is 0 order kinetics

When rate of elimination is a constant

23

Is 1st order kinetics linear?

No but when plotted log y axis against time yes

24

What does a graph of 0 order kinetics look like?

linear downward diagonal

25

During repeated drug administration how long does it take to achieve a new steady state?

5 half lives

26

Which rule of kinetics do most drugs follow?

1st order

27

Compare 1st and 0 order drugs

1st order- give predictable therapeutic response from dose increades
0 order- give therapeutic response that can suddenly escalate as elimination mechanisms saturate (rare examples e.g alcohol)

28

What happens in phase 1 drug metabolism?

Most drugs stable and unreactive so in phase 1 a reactive molecule is exposed on parent molecule or added to the molecule

29

What are the most common reaction types in phase I?

oxidation, reduction, hydrolysis

30

What enzyme system is used in phase I?

Cytochrome P450 (CYP) system

31

What qualities do the enzymes in CYP system have?

inducible
inhibitable

32

What high energy co-factor is used in phase I drug metabolism?

NADPH

33

What are some enzyme inducers of phase I and what drugs do they affect?

Phenobarbitone- warfarin
Rifampicin- oral contraceptive
Cigarettes- theophylline

34

What is an example of an enzyme inhibitor of phase I and what drugs does it affect

Cimetidine, diazepam

35

Give an example of a drug that can bypass phase 1?

morphine

36

What happens in phase II of drug metabolism?

The reactive intermediate from phase I is conjugated with a polar molecule to form a water soluble complex

37

What is the most common conjugate?What else can drugs conjugate with?

Glucoronic acid
sulphate ions, glutathione

38

What does phase II of drug metabolism requuire?

Specific enzymes and high energy co-factor uridine diphosphate glucuronic phosphate UDPGA

39

In what state is the drug when its filtered through the glomerular tuft in the kidney?

Free

40

When are weak acid drugs most excreted?

When urine is alkaline as this will ionise the drug and ionised drugs arent reabsorbed by the tubule
e.g aspirin

41

When are weak base drugs most excreted?

When urine is acidic as this will ionise drug and ionised drug stays in lumen and isnt reabsorbed by lumen
e.g amphetamine