Pharmokinetics

Question 1

What is absorption of a drug ?

2

Answer 1

Movement of drug from site of administration in the body to the site of measurement

Question 2

What’s distribution?

2

Answer 2

Reversible transfer of absorbed drug into and out various of variable tissues in the body from the bloodstream

Question 3

What is drug metabolism ?

2

Answer 3

Conversion of drug to a usually more water soluble compound

Question 4

What’s excretion ?

2

Answer 4

Loss of unchanged drug from the body in urine or faeces !!

Question 5

What’s the first pass effect ?

2

Answer 5

Metabolism with takes place before the drug reaches systemic circulation after oral administration.

Question 6

When is oral route not preferred ?

4

Answer 6

• low lipid solubility
• destroyed by acid / enzymes
• major gut adverse effects
• large 1st past effect ( low oral bioavailability)

Question 7

what’s elimination half life?(1)

Answer 7

time taken for the amount of drug in the PLASMA or BODY to decrease by a half .

Question 8

what’s bioavailability ? (1)

Answer 8

fraction of the drug which reaches the systemic circulation.

Question 9

what’s volume of distribution ?

how much is acc in the target tissue

Answer 9

• amount of drug In the body (g) / concentration of drug in the blood PLASMA .
  It is useful for predicting if drug will be concentrated in the blood or tissue .

Question 10

how can a drug be absorbed ?

4

Answer 10

1) passive diffusion
2) facilitated diffusion
3) Active transport
4) Endocytosis (larger drugs)

Question 11

what affects distribution of the drug ?

name 3 and explain their reasons …
6

Answer 11

1) chemical stability (PH of stomach )
2) stability after digestive enzymes = peptides are broken down by protease
3) solubility in aqueous solution ( they need dissolution before they can be absorbed )
4) lipid solubility will determine if they can go through the lipid bilayer
5) molecular weight - smaller molecules can diffuse through the bilayer more easily

Question 12

what chemical properties affect distribution of the drug ?

name 3 and explain their reasons …
6

Answer 12

1) chemical stability (PH of stomach )
2) stability after digestive enzymes = peptides are broken down by protease
3) solubility in aqueous solution ( they need dissolution before they can be absorbed )
4) lipid solubility will determine if they can go through the lipid bilayer
5) molecular weight - smaller molecules can diffuse through the bilayer more easily
6) Free drugs - drugs which don’t bind to the plasma proteins. (acidic drugs bind to plasma protein called Albumin = slows the distribution process).

Question 13

what physiological properties affect the distribution of a drug in stomach? (4)

Answer 13

1) Presence of a type of food
2) blood flow to GI tract and liver
3) Gastric motility - determines how long drug is exposed to absorption surface ( movement of digestive system)
4) pH of the stomach

Question 14

what’s first order kinetics ?

2

Answer 14

• half life remains constant because the rate of elimination is proportional to the concentration of drug in the body .
  ie : 16% Is always eliminated = curved graph

Question 15

What Zero order kinetics ? (2)

Answer 15

-half life increases as the rate of elimination is constant ie : always 200 mg decrease =straight line graph

Question 16

What is steady state concentration ? (2)

Answer 16

(When doses of a drug are repeatedly administered, the drug will accumulate in the body until the rate of administration is equal to the rate of elimination.)
-time at which the concentration of the drug stays constant , normally after 4-5 half lives.

Question 17

when would you use a high loading dose ? (1)

Answer 17

When rapid achievement of steady state concentration is needed, a large ( ie: IV ) loading dose could be applied .

Question 18

what’s a maintenance dose? (1)

Answer 18

calculated to achieve steady state concentration , replacing the drug that was eliminated .

Question 19

how does the liver metabolise lipid soluble drugs ?

6

Answer 19

1) PHASE 1 = redox and hydrolysis ( unmasking or addition of a polar functional group ). Catalysed by Cytochrome P450
2)PHASE 2=add another water soluble and less reactive group to the molecule.
ie:acylation , sulfanation, glutathione conjugation.
Poor conjugates which can not diffuse across membrane hence their easily eliminated from the body !

Question 20

where are most polar molecules excreted ? (1)

Answer 20

Kidney in urine

Question 21

what general factors affect drug metabolism? (5)

Answer 21

1) age
2) disease
3) genetic variation causing absence of enzymes
4) enzyme induction (making enzymes )
5) enzyme inhibition ( prohibiting the making of enzymes)

Question 22

How do you calculate the amount of drug in the body ?

2

Answer 22

Amount in body ( tissues etc) =VD x plasma concentration

>45L is good distribution !