W10 Drug metabolism and kinetics

Question 1

What makes a Good Drug?

Answer 1

Pharmacokinetics:
* Absorbed well by the body
* Reaches target easily
* Not modified, inactivated, or removed from the body
too quickly

Pharmacodynamics
* Effective at targeting the disease process
* Not toxic

Question 2

What is Potency vs Efficacy?

Answer 2

Potency:
oDose required to achieve the effect.
oMeasured as the 50% effective concentration (EC50

Efficacy:
oThe maximal effect.
oMeasured as “response.”
oUsually a percentage.

Question 3

What are the Factors Affecting Drug Absorption?

Answer 3

1.Solubility: Drugs need to be water-soluble to pass into the blood for distribution

2.Ionisation: Drugs need to be close to neutral to pass through membranes

3.Stability: Drugs need to be chemically stable until they reach their site of action

Question 4

What is omeprazole used for?

Answer 4

To treat heartburn and indigestion

Question 5

What are Factors Affecting Distribution (ADME)?

Answer 5

Plasma solubility: Including binding to plasma proteins (bind and release)
Lipophilicity: Balance between water and fat solubility. Influences drug levels in blood, muscles, adipose tissue, and organs
Perfusion: Level of blood flow to a tissue. Major organs (heart, liver . . .) well perfused, but brain is a special case – blood-brain barrier.

Question 6

What is elimination? (ADME)

Q. If the drug is removed without
metabolism.. it is called?

Answer 6

• After metabolism, organisms want
  to get metabolites and exogenous
  molecules out of their system.

A. the process is called
excretion

• Major routes: Urine (renal), faeces
  (biliary)
• Minor routes: Exhalation (lungs),
  sweat / other bodily fluids

Question 7

What is metabolism? (ADME)
What is it necessary for?

Answer 7

*Metabolic enzymes attack drug molecules forming metabolites
*Metabolites may be inactive, less active or even more active than parent
drug molecules
*They can also have a different activity – side effects and toxicity
*Metabolism of drugs is necessary for:
Designing new drugs which do not form unacceptable metabolites
Designing pro-drugs / understanding pre-drug strategy
Understanding half-lives and tailoring drug action

Question 8

What is Phase I Metabolism?
What reactions occur?

Answer 8

Chemically diverse small molecules transformed to more polar compounds

CYP- P450 Reactions (by CYP 450 enzymes)
Hydroxylation
Epoxidation
Dealkylation
Deamination
Oxidation
Dehalogenation

Non-CYP Reactions
Oxidation
Hydrolysis
Reduction
Deamination

Question 9

Which are more stable and have a longer half life?
Amides (N-R-C=O)
Esters (-O-)

Answer 9

Amides are more stable

Question 10

What does Methylation & Acetylation do?
What is a methyl and acetyl group?

Answer 10

Decreases the polarity of the drug
Methyl (-CH3)
Acetyl (-CH3C=O)

Question 11

Describe the First Pass Effect?

Answer 11

Drugs that are taken ORALLY pass DIRECTLY TO THE LIVER once they enter the blood supply. They are therefore exposed to metabolism before they are
distributed around the rest of the body

A certain percentage of the drug will be transformed before it reaches its target.

Drugs administered via a different route (e.g. injection, inhalation) avoid the first pass effect – they are distributed around the body before they reach the liver