Lecture 9-Pharmacology

Question 1

What is the ultimate outcome of drug metabolism?

Answer 1

• The metabolite no longer has the same action as the drug usually
• The metabolite is more likely to be excreted by the kidneys

Question 2

Metabolites may be…

Answer 2

• inactive
• Active- and may even be as active as the original chemical, known as the parent compound

Question 3

Steps in the sequence of elimination and breakdown

Answer 3

1. blood
2. hepatic artery
3. liver, metabolized to by-products
4. returned to bloodstream
5. to the kidney

Question 4

What might be the effect of chronic exposure to a drug on the total amount of enzymes in the liver? What would the impact of that be on metabolism?
What would be necessary to maintain the same amount of drug in the body?

Answer 4

• 1. Enzyme levels would increase
• 2. Metabolism would increase
• 3. Drug intake would have to increase

Metabolic tolerance!

Question 5

Major routes of drug elimination:

Answer 5

• kidneys/urine
• lungs-exhaling
• skin-sweating
• fecal matter

Question 6

Elimination 2 laws of kinetics

Zero order (linear)

Answer 6

• A constant amount of drug is eliminated per unit time, and that is independent of the concentration in the blood
• Ex. alcohol will be metabolized and eliminated at a constant rate no matter how much has been ingested

Question 7

Elimination 2 laws of kinetics

First-order (exponential)

Answer 7

• Refers to the process whereby the rate of elimination is proportional to amount of drug in the body, I.e. the larger the quantity of a drug- the faster the body tried to get rid of it

the majority of drugs are eliminated this way

Question 8

Half-lives

Answer 8

• Zero-order kinetics is related to half-life (the time it takes for the distribution, or the initial bood level, to be reduced by half or 50% in the body

Question 9

Why are half-lives important?

Answer 9

• knowledge of when more drug is needed (i.e. antibiotics, pain killers)
• reduces chances of over-dosing
• used to determining window for drug testing

Question 10

Caveats to Admet

Answer 10

• Weight
• Gender- body composition (fat-ratio/water proportion) and hormones
• Pharmacogenetics/pharmacogenomics

Question 11

PD

Dose effect/response curve

Answer 11

• Effect “X” as dose increases (dose is displayed in log form)
• Examples of effects are: mood, behavior, NS function

Question 12

Dose-response/dose-effect curve

Answer 12

• Efficacy (y-axis), the peak level for a given effect
• Potency (x-axis) the minimum amount needed for a drug to yield its’ efficacy
• Potency is usually based on EC50 (effective concentration) or ED50 (effective dose)
• The smaller the amount, the more potent the drug

Question 13

Lethal Dose (LD) 50

Answer 13

50% of subjects (always based on animal studies) die

Question 14

Therapeutic window

Answer 14

• dose with the highest efficacy for beneficial effects, but lowest efficacy for negative effects

Question 15

Where do drugs act?

Answer 15

• drugs act as ligands “key”
• Ligands act on receptors “lock”

Question 16

Agonist

Answer 16

• An agonist drug activates/stimulates a specific receptor in the body (protein) and triggers a response which can mimic or enhance the effects of naturally occuring substances in the body

Question 17

Partial agonist

Answer 17

• Produces a submaximal response from a system
• drug will pull receptor to the active state but not as much as a full agonist
• agonist which is unable to induce maximal activation of a receptor population, regardless of the amount of drug appliedg

Question 18

Competitive antagonist

Answer 18

• binds to the same site as the agonist but does not activate it, thius blocking the agonist’s action

Question 19

Noncompetitive Antagonist

Answer 19

• prevents the biological response of an agonist without competing with the agonist on the same binding site on the receptor
• prevents the action of an agonist without any effect on the binding of the agonist to the receptor

Question 20

Inverse Agonist

Answer 20

• produces an effect opposite to that of a normal agonist
• ex. if agonist drug is supposed to decrease anxiety, the inverse agonist would increase anxiety

Question 21

Positive Allosteric Modulators (PAMs)

Answer 21

• increase agonist affinity and/or efficacy
• modulation occurs when the binding of one ligand enhances the attraction between substrate molecules and other binding sites