Pharmacodynamics

Question 1

Difference between pharmacodynamics and pharmacokinetics

Answer 1

DYNAMICS - what the drugs do to the body

KINETICS - what the body does to the drug

Question 2

Explain the difference between intracellular and extracellular drug targets

Answer 2

cellular receptor on the cell membrane

intracellular receptor exerting an effect on the nucleus, an enzyme, transport proteins or even a specific nucleic acid sequence.

Question 3

Name the 4 types of cellular drug target

Answer 3

Ion channel
G-protein coupled receptor (GPCR)
Tyrosine Kinase Receptors
Nuclear Receptor

Question 4

Explain how drugs act on ion channels

Answer 4

• Drug binds to receptor
• Channel is either opened or closed dependent upon the action of the drug (agonist or antagonist)

Question 5

Local anaesthetics (e.g. lidocaine) work on which ion channel?

Answer 5

voltage-gated sodium (Na+) channels.

Question 6

Explain how drugs act on GPCRs

Answer 6

• drug binds to the target
• causes a sequence of events within the G-protein subunits
• leads to production of secondary messenger such as cyclic AMP or a protein phosphorylation cascade

These second messengers are actually responsible for causing the effect.

Question 7

Give an example of G-protein coupled receptors

Answer 7

Adrenoreceptors

Question 8

Explain how drugs act on Tyrosine Kinase receptors

Answer 8

• Drug binds
• series of steps within the cell, involving phosphorylation of targets
• affects cell growth/differentiation

Question 9

Give an example of a drug which acts on Tyrosine kinase receptors

Answer 9

Insulin

Question 10

Explain how drugs act on nuclear receptors

Answer 10

• located within nucleus of the cell
• activation/inhibition typically causes increased or decreased gene transcription

Question 11

Why must drugs working on nuclear receptors be lipid soluble?

Answer 11

To penetrate the cell membrane

(after which it forms a complex with a receptor protein before exerting an effect)

Question 12

Give examples of drugs which work on nuclear receptors

Answer 12

steroids e.g. prednisolone

other hormone replacements e.g. levothyroxine.

Question 13

Describe the difference between Agonists and Antagonists

Answer 13

Agonists - activates the receptor.

Antagonists - block a receptor and PREVENT activation
**they do not deactivate a receptor

Question 14

Describe the difference between a competitive and non-competitive antagonist

Answer 14

Competitive - binds to same site as agonist and blocks activation

Non-competitive - binds to alternative site which changes shape of original site, and therefore agonist cannot bind

Question 15

Binding affinity

Answer 15

how readily a drug will bind to the specific receptor.

> More receptors occupied by a drug = greater effect produced.

Question 16

efficacy

Answer 16

how effective an agonist is at producing a response
once it has bound to the receptor

Question 17

therapeutic index

Answer 17

Ratio of the drug dose which causes an undesired effect compared to that at which it produces the desired effect.

e.g. Gentamicin has a narrow therapeutic index => monitoring

Question 18

potency

Answer 18

concentration at which a drug is effective

Question 19

Most drugs exhibit ‘first-order’ elimination kinetics. What does this mean?

Answer 19

the rate of drug elimination is proportional to drug concentration

i.e. more drug ingested = more drug excreted

Question 20

Explain ‘zero-order’ kinetics

Answer 20

rate of excretion is constant despite changes in plasma concentration (graph plateaus)

*due to saturation of the metabolic process

Question 21

Give examples of drugs which exhibit zero-order elimination kinetics

Answer 21

phenytoin
salicylates (e.g. aspirin)

Question 22

Drug metabolism usually involves phase I and phase II reactions. Describe what happens in each

Answer 22

Phase I reactions:
- oxidation, reduction, hydrolysis
- usually P450 enzymes (some exceptions)

Phase II reactions:
- conjugation
- Glucuronyl, acetyl, methyl, sulphate and other groups are typically involved

Question 23

Where do most Phase I + II metabolism reactions take place?

Answer 23

Liver

Question 24

Are products of Phase I or Phase II metabolic reactions usually active and potentially toxic?

Answer 24

Phase I

In Phase II the products are often inactive and excreted in urine/bile

Question 25

What is meant by First Pass Metabolism?

Answer 25

concentration of a drug is greatly reduced before it reaches the systemic circulation due to hepatic metabolism

=> larger oral doses needed than if given by other routes

Question 26

Give examples of drugs which exhibit first pass metabolism.

Answer 26

aspirin
isosorbide dinitrate
glyceryl trinitrate
lignocaine
propranolol
verapamil
isoprenaline
testosterone
hydrocortisone

Question 27

Describe zero-order kinetics

Answer 27

Metabolism not proportional to concentration of drug. I.e. graph plateaus once metabolic process to eliminate that drug is saturated

Therefore constant amount of drug eliminated per unit time

Question 28

Give examples of drugs which exhibit “zero-order” kinetics

Answer 28

phenytoin
salicylates (e.g. high-dose aspirin)
heparin
ethanol

Question 29

50% of the UK population are deficient in hepatic N-acetyltransferase.

What drugs are affected by acetylator status?

Answer 29

isoniazid
procainamide
hydralazine
dapsone
sulfasalazine