Pharmacokinetics

Question 1

Pharmacokinetics

Answer 1

The quantitative study of drug movement in, through and out of the body

Question 2

ADME

Answer 2

• Absorption
• Distribution
• Metabolism
• Excretion

Question 3

Absorption

Answer 3

The process by which drugs enter systemic circulation.
The rate of absorption of a drug is determined by the properties of drugs & biological membranes of the body.

Question 4

Bioavailability

Answer 4

Bioavailability is the fraction of administered drug that reaches the systemic circulation in an unchanged form.

Question 5

Biological membranes

Answer 5

The outermost layer of the cell
Consisting of phospholipid bilayer along with membrane proteins & sugar molecules embedded within it.

Question 6

Passive diffusion

Answer 6

Hydrophobic drugs move across the lipid bilayer without protein assistance
Can occur over the entire membrane

Question 7

Facilitated Diffusion

Answer 7

SLC transporters in the membrane bind drugs and undergo conformational changes to move them across.
Uses specific protein channels

Question 8

Primary active transport

Answer 8

ABC transporters use ATP hydrolysis to move drugs against concentration gradients
Utilizes transmembrane domains

Question 9

Secondary Active Transport

Answer 9

SLC transporters move drugs against their concentration gradient using ion gradients
Employs specific protein channels.

Question 10

Endocytosis-mediated transport

Answer 10

Drugs bind to membrane proteins and are internalized though vesicle formation.
Involving the entire membrane structure

Question 11

Aquaglyceroporin-mediated transport

Answer 11

Proteins like TbAQP2 form wide conducting tunnels in the membrane for drug permeation, using specialised protein channels

Question 12

Lipid bilayer interaction with hydrophobic drugs

Answer 12

Hydrophobic drugs partition into the inner leaflet of the membrane before being transported by proteins like P-glycoprotein.

Question 13

Some factors of the drug that can affect absorption

Answer 13

• Lipid water solubility – lipid absorbed
• Molecular size
• Ionisation – not favoured
• Concentration – can be not favoured
• Formulation
• Bioavailability

Question 14

Some factors of the body that can affect absorption

Answer 14

• Vascularity
• pH
• Absorptive surface area
• Mobility of GI tract
• Patient conditions

Question 15

Fluid components

Answer 15

• Plasma
• Fats
• Interstitial fluid
• Transcellular fluid
• Intercellular fluid

Question 16

Vd =

Answer 16

Vd = total amount of drug absorbed / plasma concentration

Question 17

Distribution aims to …

Answer 17

Get an equal balance of substances across compartments

Question 18

Lipid-water partition coefficient of a drug

Answer 18

Affects volume of distribution
Log P positive values indicate higher lipophilicity

Question 19

Metabolism (Biotransformation)

Answer 19

Chemical alteration of a drug in the body to a less toxic form.

Question 20

A type I metabolism reaction…

Answer 20

Introduces a functional group such as OH, NH2 or SH.
Usually results in an increase of hydrophilicity.

Question 21

A type II metabolism reaction…

Answer 21

Usually results in more hydrophilic drugs.
Polar –> Phase II –> Hydrophilic

Question 22

Major excretion pathways

Answer 22

• Renal
• Biliary
• Intestinal, salivary, sweat etc

Question 23

Renal Excretion

Answer 23

Involves glomerular filtration, active tubular secretion, and passive reabsorption
Acidic urine increases excretion of weak bases and vice versa

Question 24

Biliary excretion

Answer 24

Important for drugs with molecular weight > 300 g/mol
Involves active secretion into bile

Question 25

Drug properties effecting secretion

Answer 25

• Lipophilic drugs require metabolic transformation before excretion
• Hydrophilic drugs can be directly excreted
• Protein Binding: Only unbound drugs are filtered by the glomerulus
• Active Transport: Some drugs are actively secreted in the proximal tubule