Drug-Receptor Interactions

Question 1

Define Pharmacokinetics

Answer 1

the effect that the body has on the drug

Question 2

Define the word ‘drug’.

Answer 2

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

Question 3

State the 4 main target sites for drugs.

Answer 3

Receptors
Ion Channels
Transport Systems
Enzymes

Question 4

What are the 2 types of ion channels?

Answer 4

Voltage-Gated: respond to change in membrane potential e.g. VGCC
Receptor Linked: respond to stimulation of receptor that changes conformation and opens ion channel e.g. nAChR

Question 5

Give 2 examples of groups of drugs that act on ion channels.

Answer 5

Local anaesthetics
Block the VGSCs of nociceptor neurons to prevent conduction of pain signals to the CNS
Calcium channel blockers
Block Ca2+ channel, block influx of Ca2+, allow relaxation of vasculature, lead to dilation of vessels + drop in BP

Question 6

Give 2 examples of drugs that act on transport systems.

Answer 6

Tricyclic antidepressants: bind to uptake 1 system so less NA taken up, prolongs action of NA in cleft
Cardiac glycosides: it slows the Na+/K+ ATPase, thereby increasing the intracellular Ca2+ concentration, which improves contractility

Question 7

What are the 3 ways in which drugs can interact with enzymes?

Answer 7

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

Question 8

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

Answer 8

Paracetamol OD saturates the enzymes in the liver so the paracetamol is then broken down by another set of enzymes which generates toxic metabolites

Question 9

Name 2 groups of drugs that are exceptions to the 4 target site rule.

Answer 9

Antacids: these are basic so they simply neutralise 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 e.g. ACh

Question 11

Define antagonist.

Answer 11

A molecule that binds to a receptor but do NOT generate a response e.g. Atropine

Question 12

Define potency. What is it dependent on?

Answer 12

Power of the drug
Depends on affinity (avidity of which drug binds to receptors) + efficacy (the ability of a drug to generate a response once bound, often involves conformational change)

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 2 types of antagonist?

Answer 18

Competitive: bind to the same site as the agonist on the receptor – surmountable
Irreversible: bind to a different site to the agonist or the same site but more tightly with covalent forces so that they can’t be moved – insurmountable

Question 19

What effect do the 2 types of antagonist have on dose-response curves?

Answer 19

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

Question 20

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

Answer 20

True

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

Question 21

Define Pharmacodynamics

Answer 21

the effect of the drug on the body

Question 22

What type of drug is atropine?

Answer 22

Competitive selective muscarinic cholinoceptor antagonist

Question 23

What are ion channels?

Answer 23

Selective pores

Allow transfer of ions down electrochemical gradients

Question 24

What are transport systems?

Answer 24

Proteins that transport substances against their concentration gradient e.g. glucose

Question 25

What is chloral hydrate converted to?

Answer 25

Trichloroethanol

mediated by an enzyme in the liver

Question 26

What is the activity of plasma protein bound drugs?

Answer 26

No physiological response

PPB provides a reservoir of inactive drug

Question 27

What happens when a partial agonist is administered with a full agonist?

Answer 27

The partial agonist has a degree of antagonist activity

Question 28

Structure- activity relationship

Answer 28

Activity of a drug is strongly dependent on its chemical structure
Small changes in structure of a drug can produce large changes in activity + metabolism

Question 29

Describe the dose-response curve of a full agonist and partial agonist

Answer 29

Full: Hyperbola- increase dose = increased response
Partial: Increase to a lower maximum

Question 30

Describe the log dose-response curve of a full agonist

Answer 30

Sigmoidal curve

Question 31

Give examples of each of the types of antagonist

Answer 31

Competitive: Atropine, Propranolol
Irreversible: Hexamethonium