Drug action mechanisms

Question 1

Define Pharmacokinetics and Pharmacodynamics.

Answer 1

Pharmacokinetics – the effect that the body has on the drug

Pharmacodynamics – the effect of the drug on the body

Question 2

Define a drug

Answer 2

A chemical substance that interacts with a biological system to produce a physiological response

Question 3

Define agonist.

Answer 3

A molecule that binds to a receptor and generates a response

Question 4

What is a full agonist?

Answer 4

An agonist that generates a maximum response (total efficacy)

Question 5

What is a partial agonist?

Answer 5

An agonist that generates a less than maximum response (some antagonistic response)

Question 6

What is the difference between full agonists with a high affinity and full agonists with a lower affinity?

Answer 6

Full agonists with a lower affinity can still generate a maximum response but requires a higher dose than the full agonist with lower affinity

Question 7

Define antagonist.

Answer 7

A molecule that binds to a receptor but do NOT generate a response

Question 8

What are the two types of antagonist?

Answer 8

Competitive Antagonist – bind to same site as agonist on the receptor, they are surmountable

Irreversible Antagonist - May bind to same site as agonist but bind tighter with covalent forces and can’t be moved (or bind to other site and change conformation), they are insurmountable

Question 9

What effect do these two types of antagonist have on dose-response curves?

Answer 9

Competitive – shifts the D-R curve to the RIGHT

Irreversible – shifts the D-R curve to the RIGHT and LOWERS the response elicited (it can no longer generate a full response)

Question 10

What is drug potency determined by?

Answer 10

Affinity (how willingly the drug binds to the receptor) and efficacy (the ability of a drug to generate a response once bound)

Question 11

Describe antagonists in terms of affinity and efficacy.

Answer 11

Antagonists have affinity but as they do not generate a response they have no efficacy.

Question 12

What is selectivity?

Answer 12

Drugs have a preference for binding to certain receptors (it is rarely specific – they normally bind to a few different receptors)

Question 13

State the four main target sites for drugs.

Answer 13

Receptors
Ion Channels
Transport Systems
Enzymes

Question 14

What are the two types of ion channels?

Answer 14

Voltage gated

Receptor linked

Question 15

Give an example of a group of drugs that act on ion channels.

Answer 15

Local anaesthetics – they block the voltage gated sodium channels of nociceptor neurons to prevent the conduction of pain signals to the CNS

Question 16

Give an example of a drug that acts on transport systems.

Answer 16

Cardiac glycosides – Slow down the Na+/K+ pump thereby increasing the intracellular calcium ion concentration, which leads to an increased force of contraction
Tricyclic antidepressants - (TCA is both a depressing cycle and an antidepressant)

Question 17

What are the three ways in which drugs can interact with enzymes?

Answer 17

Enzyme inhibitors (e.g. anticholinesterases) 
False transmitter (e.g. methyldopa) 
Prodrugs (e.g. chloral hydrate)

Question 18

What is a common example of the unwanted effects of drug interaction with enzymes?

Answer 18

Paracetamol overdose – this will saturate the microsomal enzymes in the liver so the paracetamol is then broken down by another set of enzymes (P450) which generates toxic metabolites

Question 19

Name three groups of drugs that are exceptions to the four target site rule.

Answer 19

General anaesthetics – reduce synaptic transmission without interacting with transport systems or receptors
Antacids – these are basic so they simply neutralize some of the stomach acid
Osmotic purgatives – draw water into the bowel due to its physicochemical properties

Question 20

What is receptor reserve?

Answer 20

In some tissues, not all the receptors need to be stimulated to generate a maximum response (sometimes as little as 1% of receptors may need to be activated)
This increases the sensitivity of the tissue to the agonist