Absorption and Distribution

Question 1

What is absorption?

Answer 1

A mass transfer process of unchanged molecules from the site of absorption into the bloodstream.

Question 2

Where is the site of absorption usually?

Answer 2

Usually the same as the site of administration but not always the case.

Question 3

Name some of the factors which may impact the drug reaching the plasma.

Answer 3

-Physiochemical properties of drug (molecular size, shape, how likely it is to ionise in certain environments, its lipophilicity, etc.)
-Dosage form

Question 4

What is the bioavailability of IV drugs?

Answer 4

100%

Question 5

In which type of medication do we not want any absorption?

Answer 5

Topical medication

Question 6

What is the intention of topical medication?

Answer 6

Drug not to make it into the systemic circulation, i.e. for it not to be absorbed.

Question 7

Why is topical medication useful?

Answer 7

By applying medication directly to the affected part, and ensuring that it isn’t systemically absorbed means that we can avoid “off-target” adverse effects by reducing overall exposure beyond the site of action.

Question 8

Give an example of a topical medicine.

Answer 8

Creams, eye drops, etc but also local anaesthetics,

Question 9

How do local anaesthetics bring about their
effect?

Answer 9

Pain signals rely on fast-acting voltage-gated sodium channels

Question 10

How can local anaesthetics be administrated?

Answer 10

Creams, numbing gels, injections

Question 11

Why do you not want local anaesthetics to be absorbed?

Answer 11

-If you take the drug away from the site of action, you terminate its effect.
-Fast-acting voltage-gated sodium channels are not confined to the peripheral pain-transmitting nerves.

Question 12

What are the effects of too much anaesthetic in the CNS?

Answer 12

Agitation, tinnitus, visual disturbance… seizures

->this is because paradoxically excitatory due to blockade of cortical inhibitory pathways

Question 13

What are the effects of too much anaesthetic in the heart and CVS?

Answer 13

Complex, but eventually bradycardia, hypotension and cardiac arrest (difficult to salvage)

Question 14

Suggest some steps that will minimise the chances of local anaesthetic getting into the circulation.

Answer 14

-Avoid injecting into circulation.
-Avoid injecting into highly vascular tissues.
-Co-administer the drug w adrenaline as will cause vasocontriction and reduce the chances of the drug being absorbed.

Question 15

Name two forms of administration you might choose when you want the drug to be absorbed systemically.

Answer 15

-Enteral administration
-Parental administration

->for your info-
enteral=oral; sublingual; rectal
parental=SC, IM ,pulmonary, nasal, IV

Question 16

What administrative group is the most desirable?
Why?

Answer 16

Oral
->cheapest, no equipment required, easiest, non-invasive

Question 17

What can solubility be affected by?

Answer 17

Gut contents

Question 18

Where are most drugs absorbed?

Answer 18

Small intestine as has larger surface area than stomach

Question 19

What is first class metabolsim?

Answer 19

Any metabolism that happens before the drug gets into the systemic circulation.

Question 20

What is phase 1 metabolism?

Answer 20

Phase I metabolism involves the additional of a functional group.

Question 21

What is phase 2 metabolism?

Answer 21

Phase 2 metabolism involves the addition of a conjugation.

Question 22

What is the first barrier for drugs administrated orally?

Answer 22

Involves surviving those pre-systemic chemical and biological changes.

Question 23

What is the main barrier to absorption?

Answer 23

Endothelium

Question 24

Define paracellular movement.

Answer 24

Drugs moving between cells.

Question 25

Define transcellular movement.

Answer 25

Drugs moving across the cells themselves.

Question 26

How do the majority of drugs get into the cell?

Answer 26

By dissolving in the lipid membrane and diffusing across.

Question 27

What prediction can Fick’s First Law allow us to make?

Answer 27

Predict how effively

Question 27

What prediction can Fick’s First Law allow us to make?

Answer 27

Predict how effectively the drug will be absorbed.

Question 28

What is the driving force for Fick’s First Law?

Answer 28

Driving force is the drug concentration

Question 29

Name one function of pericytes.

Answer 29

Regulating gene expression in endothelial cells.

Question 30

Name the two main drugs involved in drug binding,

Answer 30

Albumin
Alpha-1 acid glycoprotein.

Question 31

What is the lipid solubility of general anaesthetics

Answer 31

Highly lipid soluable.

Question 32

What types of drug are more likely to need transport mechanims?

Answer 32

Drugs that are less lipophilic and more polar.

Question 33

What is the real volume of distribution?

Answer 33

Physiological and is based on the total water in the body in which the drug could be dissolved.

Question 34

What is the apparent volume of distribution?

Answer 34

Theory
Proportionality constant between the total amount of drug in the body and the amount in the plasma at any one time

Question 35

What do drugs w high volume of distribution tend to do?

Answer 35

Tend to leave the plasma (more distribution)

Question 36

What do drugs w low volume of distribution tend to do?

Answer 36

Tend to remain in the plasma (less distribution)

Question 37

What drives the therapeutic effect?

Answer 37

Plasma conc.

Question 38

How does the level of distribution impact half life?

Answer 38

Drugs with a high volume of distribution tend to have a longer half life.

Question 39

What is the volume of distribution used to calculate?

Answer 39

Loading dose

Question 40

Gives pros and cons of oral administration.

Answer 40

P- cheaper, easier, no equipment
C-more factors which will affect absorbtion

Question 41

Gives pros and cons of IV.

Answer 41

P-speed
C-100% bioavailability means rapidly perfused compartments get rapid exposure; needs to be aqueous solution; acceptability

Question 42

Gives pros and cons of IM.

Answer 42

P-usually safer than IV; rapid absorption of aqueous drugs
C- Painful; clots, abscesses etc; dependence on blood flow

Question 43

Gives pros and cons of SC.

Answer 43

P- Similar to IM, but less painful etc
C- Irritation; impact on local tissue

Question 44

How can dosage form be manipulated to impact absorption?

Answer 44

By altering liberation of the drug from it’s dosage form.

Question 45

What are the only parts of the kinetic process that are under our control?

Answer 45

Liberation and absorption.