ADME One

Question 1

What does ADME stand for?

Answer 1

Absorption
Distribution
Metabolism
Excretion

Question 2

What are the physico-chemical properties of drugs?

Answer 2

• Solubility in lipids(non-polar-good) and water (ionized-good)
• Chemical structure

Question 3

What is the solubility of a drug important for?In regards to ADME

Answer 3

Absorption, distribution and excretion

Question 4

What is the chemical structure of a drug important for IN regards to ADME?

Answer 4

Susceptibility to metabolism

Question 5

What are the major organs involved in absorption?

Answer 5

GI tract

Question 6

WWhat are the major organs involved in metabolism?

Answer 6

Liver

Question 7

What are the major organs involved in excretion?

Answer 7

kidney

Question 8

What are the lungs important in with regards to ADME?

Answer 8

Absorption and excretion of volatile anesthetic gases

Question 9

What does ADME affect?

Answer 9

Onset of drug action and duration + intensity of drug effect.

Question 10

What sort of molecules are distributed faster?

Answer 10

Small, uncharged and lipid soluble drugs will distribute faster and more widely than bulky, ionized, water soluble drugs.

(most drugs most dissolve through the lipid bilayer and lipid soluble = nonpolar

Question 11

What are the four main mechanisms of transport across the biological membranes?

Answer 11

Transcellular passive diffusion (90%)
Facilitated diffusion
Active transport
Endocytosis

Question 12

What are the key features of Passive diffusion?

Answer 12

• Most important mechanism (90%) do this.
• Applies to non-polar drugs (i.e lipid soluble)
• Concentration gradient is the driving force
• No energy required

Question 13

What are the key features of facilitated diffusion?

Answer 13

-Some drugs move faster than predicted, this appears to depend on an OSCILLATING carrier protein
- Depends on concentration gradient
- No energy required
- Sugars and AA are the usual substrates
(not so important for drugs)
i.e tetracyclines diffusion into bacteria

Question 14

What are the specifics for active transport?

Answer 14

• Can proceed against a concentration gradient
• Requires energy (ATP)
• Can become saturated
• Specific organs i.e Liver, BBB, Kidney, Gut epithelium

Question 15

What does active transport allow cells to do?

Answer 15

1) Accumulate compounds essential for growth
2) remove waste products
3) Protects against toxins

Question 16

What are the principles of endocytosis?

Answer 16

Endocytosis = pinocytosis

• Internalization of large molecules and nano particles by cell
• Mainly for drugs with MW above 1000 i.e cytokines, hormones, growth factors etc

Question 17

What are the three steps of endocytosis?

Answer 17

1) Substrate binds to receptors
2) Invagination of receptor-substrate complex
3) Budding off and delivery of vesicle into cell.

Question 18

What is the last mechanism of drug movement?

Answer 18

Filtration

Question 19

What are the important steps of filtration?

Answer 19

Most drugs pass through cells except in:

Blood capillaries - Contain fenestrations that allows rapid interchange between blood and interstitial fluid

Glomerular capillaries - Extremely porous allowing the passage of all plasma constituents except macromolecules MW 30k+