Drug Elimination I

Question 1

Other than plasma, what compartments can drugs distribute to

Answer 1

Interstitial fluid

Fat store

Intracellular fluid

Trans cellular fluid

Question 2

Why isn’t drug distribution equal

Answer 2

Blood perfusion to organs /tissues

Ability to cross membranes (lipid solubility,ionisation)

Plasma protein binding (if bound can’t pass)

Question 3

What is another barrier apart from the GI tract

Answer 3

Blood brain barrier

Drugs can’t enter the brain from blood unless psychotic

Question 4

What does albumin bind to

Answer 4

Acidic drugs

Question 5

Which protein can bind to neutral drugs

Answer 5

a1 acid glycoprotein

Question 6

What happens if drugs are bound to eg A1 acid glycoproteins

Answer 6

They can’t pass membranes into other fluid compartments

Question 7

How do you work out volume of distribution of drug (Vd)

Answer 7

Total amount of drug administered (Q)
/
Plasma concentration of drug (Cp)

Question 8

Why does chloroquine drug have high volume of distribution

Answer 8

Because it’s lipiphillic

Question 9

Why do drugs like heparin and warfarin have a low Vd

Answer 9

Because they are bound to proteins so more in the plasma

Question 10

Which types of drugs need to be metabolised first before elimination and why

Answer 10

Lipophillic drugs

Need to be converted to water soluble products before elimination eg via kidney

Question 11

What are the major sites of metabolism

Answer 11

Liver , enterocytes , kidney, lungs

Question 12

What kind of reactions are phase 1

Answer 12

Catabolic

Question 13

What are drugs introduced to in phase 1 to become reactive/ soluble

Answer 13

OH, amino NH2, COOH(carboxylic)

Question 14

What are the 3 oxidation reactions which occur in phase 1 (loss of e/h)

Answer 14

1- hydroxylation : H —-> OH

2- deamination: NH2 —-> C=O

3- dehydrogenation: OH ——> C=O

Question 15

Where do oxidation reactions occur and name some enzymes

Answer 15

Liver
(Monooxygenases)
Cytochrome p450
Alcohol dehydrogenase

Question 16

Which kind of reaction occurs in reduction (gain of H/e)

Answer 16

Hydrogenation

C=O —-> OH

Question 17

Which enzymes are involved in reduction in phase 1 (hydrogenation)

Answer 17

Reductases

Question 18

What is the 3rd reaction type in phase 1 and where does it occur

Answer 18

Hydrolysis (addition of HOH)

Usually in plasma (not often in liver)

Question 19

What are the enzymes involved in hydrolysis usually in plasma

Answer 19

Esterases eg cholinesterase, peptidase

Question 20

What do cytochrome p450s require in oxidation

Answer 20

Oxygen, NADPH, NADPH reductase

Question 21

Why do P450 vary

Answer 21

Species differences
Environmental factors which can induce them
Genetic polymorphism
Other drug interference

Question 22

What does aspirin esterase do

Answer 22

Hydrolyses aspirin into salicylate

Question 23

WhAt does butrylcholine esterase do

Answer 23

Hydrolyses SUXAMETHONIUM drug which usually binds to cholinergic receptors and causes muscle paralysis

Question 24

Where do phase 2 reactions occur

Answer 24

Usually in liver but can happen in kidney or lung too

Question 25

What happens in phase 2

Answer 25

Donors add a group to the drugs to make them less reactive than in phase 1 = form a conjugate

Question 26

Give an example of a donor in phase 2

Answer 26

Acetyl coA which forms an acetyl conjugate out of the drug

Question 27

What are prodrugs

Answer 27

Drugs which become active only within metabolism

Question 28

Give 3 examples of drugs which become active after metabolism (prodrugs)

Answer 28

Diacetylmorphine—-> morphine L dopa —-> dopamine Valaciclovir —-> acyclovir

Question 29

Where are most drugs which aren’t absorbed excreted

Answer 29

In the gut as faeces

Question 30

Which kind of drugs are excreted through the kidney as tribe

Answer 30

Water soluble via metabolism

Question 31

Give 3 other excretion sites other than gut and kidney

Answer 31

Liver in bile which is emptied to small intestine Gases —> exhaled Secretion in glands —> breast milk or sweat

Question 32

When can saturation of elimination route happen and what happens in result

Answer 32

If organ is failed eg kidney failure Causes build up in plasma which is toxic

Question 33

What is CLtot

Answer 33

Total clearance Volume of plasma which has been cleared of the drug per unit of time

Question 34

How do you work out total clearance cltot

Answer 34

Dose / total exposure (AUC)

Question 35

How do you work out clTOT for administration with little bioavailability

Answer 35

Dose x bioavailability/ AUC (exposure)

Question 36

What is first order kinetics in elimination

Answer 36

Rate of elimination is related to Cp (plasma conc) How much of the drug given affects Kel

Question 37

What is Kel

Answer 37

Elimination constant rate

Question 38

How do you work out Kel

Answer 38

CLtot/ volume of distribution

Question 39

How do you work out Kel from a slope on a graph

Answer 39

Plot conc and time and then take 2 readings under curve Do log concA/conc B / time difference between A and B

Question 40

What is elimination half life

Answer 40

Time taken for plasma drug conc Cp to decrease by 1/2

Question 41

How do you work out half life elimination off the same slope a and b

Answer 41

Log2 / Kel

Question 42

How many half life’s do drugs have

Answer 42

6

Question 43

When can someone’s half life increase

Answer 43

If they have lower conc of enzymes in metabolism eg via age,genetics or taken inhibitors for eg CYP enzymes Means they have lower rates of metabolism and elimination

Question 44

What is zero order kinetics

Answer 44

Dosage of the drug given isn’t related to plasma conc and Kel Elimination is limited due to other factors such as number of enzymes rather than dosage/conc of drug