Drug-Receptor Interactions

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 the word ‘drug’.

Answer 2

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

Question 3

State the four main target sites for drugs.

Answer 3

Receptors
Ion Channels
Transport Systems
Enzymes

Question 4

What are the two types of ion channels?

Answer 4

Voltage-Gated

Receptor Linked

Question 5

Give an examples of drugs that act on ion channels.

Answer 5

Local anaesthetics – they block the voltage gated sodium channels of nociceptor neurons to prevent the conduction of pain signals to the CNS
- Ca channel blockers (-dipine), block VGCC

Question 6

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

Answer 6

Tricyclic antidepressants
Cardiac glycosides – (cardiac stimulant drugs, eg Digoxin (give digoxin to heart failure patients)) it slows down the Na+/K+ pump thereby increasing the intracellular calcium ion concentration, which leads to an increased force of contraction

Question 7

What are the three ways in which drugs can interact with enzymes? and examples with mechanism of action

Answer 7

• Enzyme inhibitors (e.g. anticholinesterases, eg neostigmine, these increase Ach conc in synapse by decreasing its breakdown)
• False transmitter (e.g. methyldopa)
  methyl dopa is an antihypertensive, subverts normal NA pathway. It is taken up by NA terminal and takes place of DOPA in pathway, therefore reduces dopamine production and produces methyl noadrenaline, which is worse at vasocontriction than NA, therefore decreased TPR and BP
• Prodrugs e.g. chloral hydrate, chloral hydrate is used to treat insomnia, metabolised in the liver into trichloroethanol before effective. Therefore interacts with enzymes before useful

Question 8

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

Answer 8

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 9

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

Answer 9

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 10

Define agonist.

Answer 10

A molecule that binds to a receptor and generates a response

Question 11

Define antagonist.

Answer 11

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

Question 12

Define potency. What is it dependent on?

Answer 12

How powerful the drug is
It depends on affinity (how willingly the drug binds to the receptor) and efficacy (the ability of a drug to generate a response once bound)

Question 13

What is a full agonist?

Answer 13

An agonist that generates a maximum response

Question 14

What is a partial agonist?

Answer 14

An agonist that generates a less than maximum response

Question 15

What is selectivity?

Answer 15

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

Question 16

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

Answer 16

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

Question 17

Describe antagonists in terms of affinity and efficacy.

Answer 17

Antagonists have affinity but NO efficacy

Question 18

What are the two types of antagonist? And drug examples.

Answer 18

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

• atropine (muscarinic cholinoceptor antagonist)
• propanolol (comp b blocker)

Irreversible – could bind to the same site as the agonist but will bind more tightly with covalent forces so that they can’t be moved – some irreversible antagonists will bind to sites different to the site that the agonist binds to – insurmountable
- hexmethonium (irreversible nicotinic cholinoceptor antagonist, when ion channel is open it blocks it)

Question 19

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

Answer 19

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 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

Question 21

True or false: full agonists that are selective for a given receptor will have the same efficacy.

Answer 21

True

They are full agonists so they all elicit a maximum response hence they have the same efficacy