ADME

Question 1

Passive diffusion

Answer 1

Most important mechanism
Applies to non-polar drugs
Conc gradient is the driving force
No energy required

Question 2

Facilitated diffusion

Answer 2

Appears to depend on a oscillating carrier protein
Depends on the conc gard
No energy required
Sugars/amino acids

Question 3

Active Transport

Answer 3

Can proceed against a conc grad
requires energy
can become saturated
allows accumulation of specific compounds
removes waste product

Question 4

Endocytosis

Answer 4

internalisation of large molecule by cell

mainly for drugs with a molecular weight higher than 1000

Question 5

Drug absorption

Answer 5

The passage or a drug form the site of administration into the general circulation

Question 6

Rate of absorption

Answer 6

how rapidly does the drug get from its site of administration to the general circulation?

Question 7

Extent of absorption

Answer 7

how much of the administered does enters the general circulation

Question 8

What is bioavailability

Answer 8

F - the area under the concentration time curve

the patients exposure to the drug

Question 9

What is the minimum therapeutic level?

Answer 9

The level above which a drug needs to reach in order to produce a response

Question 10

What are the enteral routes of drug administration?

Answer 10

per Ossa
Sublingual
Rectal

Question 11

What are the parenteral routes of drug administration

Answer 11

Intravenous
Sub cut
Intradermal
IM
lungs

Question 12

What is the rate and extent of IV administration

Answer 12

Immediate absorption

100% aborption

Question 13

What is the rate and extent of oral administration

Answer 13

Rate is gradual

extent is incomplete

Question 14

What are the advantages of IV administration?

Answer 14

very rapid
precise control (100% F)
avoids problems of absorption
Good for irritating drugs

Question 15

What are the disadvantages of IV?

Answer 15

skill required
Careful preparation of injected material (sterile)
no recall so is hazardous

Question 16

What are the advantages of po administration?

Answer 16

Safe

convenient

Question 17

What are the disadvantages of po administration?

Answer 17

slow

unpredictable with regard to rate, extent and reproducibility

Question 18

What are the factors influencing the bioavaliability of oral drugs

Answer 18

Decomposition ir gastric acid
decompositon by gut enzymes
Degradation by gut microorganisms
Food in gut may alter absorption rate
Metabolism by gut wall enzymes
Metabolism by liver enzymes

Question 19

What is the rate limiting step of oral drugs?

Answer 19

The gastric emptying determines how quickly it is let into the small intestine to be absorbed.

Intestinal motility and interactions with food are also important

Question 20

What are the sites of drug metabolism?

Answer 20

Liver
GI bacteria and proteases
Intestinal wall enzymes
Plasma (esterases)
Specialised tissue

Question 21

What is a prodrug?

Answer 21

A drug that has it’s activity promoted by metabolism

Question 22

What is an example of a drug that produces toxic metabolites when metabolised?

Answer 22

Paracetamol

Question 23

What is an example of a drug that has no change in activity when metabolised?

Answer 23

Valium (diazepam)

Question 24

What is phase 1 of a drug metabolism reaction?

Answer 24

The point is to make the drug more susceptible to phase 2 reactions

Oxidation
Reduction
Hydrolysis

Question 25

What is phase 2 of a drug metabolism reaction?

Answer 25

The point is to make the molecule more polar so that it's an ideal substrates for active transport and excretion Glucuronide Sulphate Amino acids GSH Acetlyation.methylation

Question 26

What is the most important reaction for phase 1 metabolism of drugs?

Answer 26

Oxidation

Question 27

What happens during oxidation?

Answer 27

``` The most important class of enzymes are the cytochrome P450 dependent mixed function oxidase system located in the smooth ER. Requires oxygen, NADPH and cytochrome P450 reductase ```

Question 28

Describe the metabolism of Phenytoin

Answer 28

Phase 1 - hydroxylated to become slightly more soluble in water and inactive Phase 2 - Becomes very soluble in water and highly lipophillic after conjungation by UDP transferase compound is removed from liver and then 90% of it is excreted in urine

Question 29

What is the effect of age on drug metabolism?

Answer 29

It decreases it

Question 30

Which group has a higher metabolism and so requires a higher maintenance dose

Answer 30

Neonates

Question 31

Why do smokers have a higher metabolism?

Answer 31

Because there is a compound in cigarettes that can induce synthesis of metabolizing proteins in the liver

Question 32

How is drug metabolism inducted?

Answer 32

Enzyme synthesis is initiated wihtin 24h of exposure but the effect decreases over 1-3 weeks. ``` Cigarette smoking BBQ meat Cruciferous veges High protein diet Insecticides PCBs Barbituates Pheytoin Rifampcin St johns wort ```

Question 33

How is drug metabolism inhibited?

Answer 33

rapid onset within 1 day Exaggerated response with a risk of toxicity(no breakdown of drug) ``` Reversible inhinibtors Cimetidine Ketoconazole quinolones HIV protease inhibitors Grapefruit juice ``` Heavy metals Lead Cadium Mercury

Question 34

What is the outcome of the standard does of most drugs in a patient population?

Answer 34

20% will have no response 20% will get adverse effects 50-60% will get some therapeutic benefit

Question 35

What is excretion?

Answer 35

The process whereby compounds are removed from the body to the external environment

Question 36

What are the sites of drug excretion?

Answer 36

Kidney Biliary excretion - important for drugs with a Mw >400 and ionized Lungs

Question 37

What are the three main mechanisms of excretion by the kidney?

Answer 37

1. Glomerluar filtration of the unbound drug (130ml/min) 2. Active secretion of both free and protein bound drug by transporters. (Anions or cations) 3. Filtrate 100fold concenrated in tubules for a favourable conc grad for reabsorption by passive diffusion (lipid soluble will pass back into body)

Question 38

What are the factors influencing renal drug excretion?

Answer 38

Gender (males higher) Age (decreases with age) Pregnancy (increases) Disease

Question 39

How can you alter the renal excretion of drugs?

Answer 39

Competitive inhibition of tubular secretion (there is a second drug that has a higher affinity so decreases the excretion of the first drug) e.g. penicillin decreased by probenecid Influence of pH (sodium bicarbonate > increased excretion by stopping the reabsorption by ionising weak acids)(Ammonium chloride > increased excretion of amphetamines etc) Urinary flow rate (dilutes drug conc in tubule > decreased conc grad > increased excretion)

Question 40

The effect of urinary flow rate on drug clearance is......?

Answer 40

Linear

Question 41

If someone overdoses on amphetamine what can you give them?

Answer 41

Ammonium cholride as this will increase the excretion of the drug from teh kidney