Drug Absorption and Distribution

Question 1

What are some factors affecting drug absorption?

Answer 1

solubility
chemical stability
lipid to water partition coefficient
degree of ionisation

Question 2

How does lipid water partition coefficient affect drug absorption?

Answer 2

a large partition coefficient shows that the drug is readily absorbed in a lipid membrane

Question 3

What form of drug readily diffuse across the lipid bilayer?

Answer 3

unionised forms of a drug

Question 4

What does the degree of ionisation depend upon?

Answer 4

the pKa of the drug and local pH

Question 5

What is the equation used to calculate the proportion of ionised and unionised drug?

Answer 5

Henderson-Hasselbach

pKa - pH = log(HA/A)

Question 6

Where does the majority of drug absorption occur?

Answer 6

the intestine - even for weak acids

Question 7

What types of drug are poorly absorbed?

Answer 7

strong acids and bases

Question 8

When are acidic drugs less ionised?

Answer 8

in an acidic environment

Question 9

When are basic drugs less ionised?

Answer 9

in a basic environment

Question 10

What are the gastrointestinal factors that affect absorption?

Answer 10

the GI motility
pH at the absorption site
blood flow to the stomach and intestines
the way the tablet is manufactured
physiochemical interactions - i.e. rate of absorption is modified by calcium rich foods

Question 11

What is the oral availability?

Answer 11

the amount in the systemic circulation/amount administered

Question 12

What is systemic availability?

Answer 12

the amount in the systemic circulation/amount absorbed

Question 13

What affects systemic availability?

Answer 13

first-pass metabolism

Question 14

What are the possible routes of drug administration?

Answer 14

oral
inhalational
sublingual
transdermal
IV
rectal
Intramuscular

Question 15

What are the advantages and disadvantages of oral administration?

Answer 15

\+convenient
\+good absorption
-inactivation through first pass
-absorption variable
-GI irritation

Question 16

What are the advantages and disadvantages of sublingual administration?

Answer 16

+bypasses portal system
+ avoids gastric acid
- infrequent route
- few preparations available

Question 17

What are the advantages and disadvantages of rectal administration?

Answer 17

+ by passes portal system
+ avoids gastric acid
- infrequent route
- people are squeamish

Question 18

What are the advantages and disadvantages of IV administration?

Answer 18

\+ rapid onset
\+ continuous infusion
\+ complete availability
\+ route for drugs that cause local tissue damage
- sterile preparation
- risk of sepsis
- high levels of drug at heart

Question 19

What are the advantages and disadvantages of intramuscular administration?

Answer 19

\+ rapid onset of lipid soluble
\+ slow prolonged release
- painful
- tissue damage
- absorption variable

Question 20

What are the advantages and disadvantages of inhalational administration?

Answer 20

+ suited to lungs
+ good for volatile agents
+ good for local effect

Question 21

What are the advantages and disadvantages of topical administration?

Answer 21

+ ideal for local effect

Question 22

What form of drug can pass between interstitial, intracellular and plasma water?

Answer 22

unbound and unionised

Question 23

What form of drug can pass between transcellular water and fat?

Answer 23

unionised

Question 24

What is the equation for the volume of distribution?

Answer 24

Vd=dose/plasma conc.

Question 25

What does a Vd less than 5L imply?

Answer 25

drug is retained in the vascular compartment or too large to cross capillary wall i.e. haparin

Question 26

What does a Vd less than 15L imply?

Answer 26

the drug is restricted to the extracellular water - i.e. permanently charged compounds - tubocurarine

Question 27

What does a Vd greater than 15L imply?

Answer 27

distribution throughout total body water or concentration in certain tissues i.e. ethanol - lipid soluble drugs