Absorption

Question 1

Define

Pharmacokinetics

(2)

Answer 1

Study and characterization of drug: ADME, with the aid of mathematical models which allow data to be interpreted.

Question 2

What is the difference between

pharmacokinetics and Pharmacodyanmics?

(2)

Answer 2

Pharmacokinetics: Effect of body on drug
Pharmacodynamics: Effect of drug on body

Question 3

Explain

Clinical pharmacokinetics

(1)

Answer 3

The application of pharmacokientics in the safe and effective therepeutic managment of the patient.

Question 4

Summarise

Pharmacokinetics, Pharmacodynamics, Pharmacotherapeutics

(3)

Answer 4

1. Pharmacokientics: ADME
2. Pharmacodynamics: drug/receptor interaction
3. Pharmacotherapeutics: Drug effect/response

Question 5

State how we can use

The pharmacokientic properties of a drug

(3)

Answer 5

Dose and frequency of drug
How to change dose in certain medical conditions
How some drug interactions occur

Question 6

Define

Abosrption

(1)

Answer 6

Movement of drug from site pf administration, across membranes and into the bloodstream

Question 7

Note the factors

Which affect the rate of absorption

Red doors like working

(4)

Answer 7

1. Route of administration
2. Dose (concentration)
3. Lipid-solubility of the drug
4. Weak organic acid/base drugs

Question 8

Draw a table

with routes of administration and their site of absorption

(10)

Answer 8

Draw table

Question 9

Most drugs are weak organic acids/bases, what does this tell us?

Answer 9

1. Most drugs are hydrocarbon molecules, sucg as aspirin, vitamins.
2. They undergo ionisaiton/dissociation
3. The pH of the solution as well as the pKa of the drug will tell us if the drug is in an ionised or non-ionised state.

Question 10

Henderson - Hasselbach equation

(5)

Answer 10

pH = pKa + log (A- / HA)

• pH = -log(H+)
• pKa - dissociation constant for the acid
• A- -concentration of the conjugate base
• HA - concentration of the acid

Question 11

Define

Passive diffusion

Answer 11

Movement of molecules from a higher concentration to a lower concentration, down a concentration gradient not requiring energy

Question 12

Requirements of

passive diffusion

Answer 12

1. Water solubility - almost all drugs are sufficiently water soluble
2. Lipid solubility - some drugs lack the necessary lipid solubility
3. In practice, passive diffusion depends mainly on lipid solubility

Question 13

Draw a table with

Which molecules are effieicnet/ineffieicent in passive diffusion?

5|3

Answer 13

draw a table

Question 14

Define

facilitated diffusion

(1)

Answer 14

Selective gateway allows entry of one group of molecules, but excludes all others.

Question 15

What is

active transport

(3)

Answer 15

1. Structurally selective
2. Requires energy
3. Can operate against the concentration gradient

Question 16

Specifity of modes of transport?

(2)

Answer 16

• Pasive diffusion - non specific, anything lipid soluble
• Faciliated diffusion & Active transport - structurally specific group of molecules

Question 17

What are

p-glycoproteins?

(4)

Answer 17

Proteins with carbohydrates attached

1. found in the apical cell membrane (facing gut contents)
2. Substances are absorbed, but then actively pumped back into the gut contents (efflux).
3. ATP dependent

Question 18

Draw a table showing

Location of P-glycoproteins

(4)

Answer 18

draw a table

Question 19

State the purpose of

P-glycoproteins?

(1)

Answer 19

Gnereally a defense mechanism against foreign substances

Question 20

What is

p-glycoprotein mediated efflux

(1)

Answer 20

This is when substances are absorbed, but then activley pumped out into gut contents, decreasing their absorption

Question 21

Examples of substances where intestinal absorption is opposed by p-glycoprotein mediated efflux

(6)

Answer 21

Celiprolol - Beta blocker
Cyclosporin - immunosuppresant
dexamethasone - glucocorticoid
ivermectin - anthelmintic
verapamil antihypersensative
vincristine - cytotoxic

Question 22

What is

Induction of p-gp

answer with example

(2)

Answer 22

example Rifampicin increase the amount of P-gp in the instestinal epithelium. this reduces absorption of other substances

Question 23

What is

inhibition of p-gp

answer with example

(2)

Answer 23

example: Large enough doses of verapamil will saturate the p-gp. Other substances then absorbed more easily. Has been suggested as a means to increase absorption of problem molecules

Question 24

What is

bioavailability (F)

(2)

Answer 24

The fraction of a dose that reaches the systematic circulation in a chemically unaltered form
1. as percentage or decimal
2. has no units

Question 25

# Causes of Incomplete bioavailability ## Footnote (4)

Answer 25

1. Failure of disintegration or dissolution 2. Chemical, enzymatic, or bacterial attack 3. Failure of absorption and pGp efflux 4. First pass metabolism in the gut wall/liver

Question 26

# Causes of failure in absorption ## Footnote (3)

Answer 26

1. Binding to other molecules in the gut content 2. Too polar to udnergo passive diffusion 3. p-gp efflux

Question 27

# Explain the Ionisation of weak acids ## Footnote (1)

Answer 27

will ionise more as the pH of the solution increases (the solution becomes less acidic) and vice versa

Question 28

# Explain the Ionisation of weak bases ## Footnote (1)

Answer 28

Will ionise less as the pH increases and vice versa

Question 29

# Explain the effect of ionisation on drug absorption | membranes ## Footnote (1)

Answer 29

Ionised drugs become too polar to cross the lipophilic layer across membranes

Question 30

# In practice Acidic drugs absorption | where in the body ## Footnote (3)

Answer 30

In practice, acidic drugs will be absorbed mostly in the small intestine, this is because the surface fo the small instestine has villi and microvilli which greatly increasse the surface area of absorption.

Question 31

# In practice, Talk about the absorption of basic drugs and where absorption occurs ## Footnote (3)

Answer 31

A basic drug will not be absorbed in the stomach all since pH is too low. so all of the drug will be abosrbed in the small intestine where the drug is unionised and the surface area is large.