Pharmacology

Question 1

Metabolism + Excretion =

Answer 1

Elimination

Question 2

What is a complication in terms of distribution of lipid soluble drugs?

Answer 2

While they can get into systemic circulation easily, it is harder for them to get back out.

Question 3

What are factors that affect drug absorption from the GIT?

Answer 3

GIT motility
Splanchnic blood flow
Particle size and formation
Physiochemical factors (interactions with other drugs and chemicals).

Question 4

How does the pKa of a substance influence its distribution?

Answer 4

PKa relates to the ionisation of a drug/substance. A higher pKa means that it is un-ionised up until that high pH (e.g. vitamin C has pKa 11). Therefore, for every pH under this, the substance will be able to travel in that environment (vitamin C can get everywhere with a pH <11).

Question 5

How does an enteric coating affect drug absorption?

Answer 5

An enteric coating means that drugs are more likely to be broken down in a pH > 5-6. This prevents drug breakdown in the stomach and thus protects the stomach from irritation.
It allows the drug to be presented to the appropriate sites in the ileum and colon.

Question 6

How does the lipophilicity of the drug affect its absorption?

Answer 6

Lipophilic drugs are more likely to be absorbed as they move more easily across the membrane.

Question 7

Where are hydrophilic and lipophilic drugs mostly excreted?

Answer 7

Hydrophilic drugs are mostly excreted by the kidneys.

Lipophilic drugs are converted to bile and excreted via the bile ducts.

Question 8

In a pH of 9, a weakly acidic drug (pKa 3) and a weakly basic drug (pKa 10) would be in what form?

Answer 8

Weakly acidic = ionised.

Weakly basic drug = ionised.

Question 9

What are the 4 ways that small molecules can pass the plasma membrane of a cell?

Answer 9

1. Diffusion through the membrane
2. Diffusion through aqueous pores which traverse the membrane.
3. Attached to solute carriers (SLCs) or other membrane transporters.
4. Pinocytosis: involves invagination of part of the cell membrane

Question 10

What is the permeability coefficient (P)?

Answer 10

This determines the number of molecules crossing the membrane / unit of area in unit time.

Question 11

What are the factors that contribute to the permeability coefficient?

Answer 11

• solubility in the membrane

- diffusivity (measure of the mobility of molecules within lipids).

Question 12

What drug, even in its ionised state struggles to cross the lipid membrane?

Answer 12

Aminoglycoside antibiotics.

Question 13

What are solute carrier transporters?

Answer 13

SLCs are transporters which mediate the passive movement fo solutes down their electrochemical gradient.

Question 14

What are ATP binding cassette transporters?

Answer 14

ABC transporters are active pumps fuelled by ATP.

Question 15

What are two important types of SLCs involved in the absorption of drugs?

Answer 15

Organic cation transporters (OCTs)

Organic anion transporters (OATs).

Question 16

What are the characteristics of OATs and OCTs?

Answer 16

They are transmembrane proteins that binds one or more molecules/ions, changes conformation and releases them on the other side of the membrane.

Question 17

Where are the main sites where SLCs work?

Answer 17

The BB
GIT
Renal tubule
Biliary tract
Placenta

Question 18

What family of transporters do P-glycoproteins belong to?

Answer 18

ABC transporters

Question 19

Where are P-glycoproteins located?

Answer 19

Renal tubular brush border.
Bile canaliculi
Astrocyte foot processes in the brain microvilli
GIT