Principles of Pharmacology

Question 1

Define a drug

Answer 1

any substance which interacts with a biology system and changes it

Question 2

what is pharmacology?

Answer 2

the study of the mechanism of drug action

Question 3

what are the characteristics of most drugs?

Answer 3

Their effects occur at very low concentrations –> Potency
Drugs can be very specific –> Biological/chemical specificity
Drugs can compete for their receptors

Question 4

What is an example of a pharmacological investigation?

Answer 4

The isolated ileum preparation

Question 5

what is the receptor concept?

Answer 5

Drugs produce their effects by combining with specific receptors sites in cells. The response is a function of the number of occupied receptors,

Question 6

What is an agonist in pharmacological terms?

Answer 6

Binds to a receptor and produces a response.

Therefore it poses both affinity and efficacy.

Question 7

What is an antagonist in pharmacological terms?

Answer 7

Binds to a receptor but do not produce a response. Competitive antagonists prevent agonists binding and so bloc the response to an agonist. Therefore it poses affinity but not efficacy.
Come in various different types (competetive, irreversible, other)

Question 8

What is affinity of a drug?

Answer 8

A measure of how well it binds to the receptor.

Question 9

What is the efficacy of a drug?

Answer 9

A measure of the degree to which an agonist produces a response when binding a given proportion of receptors.

Question 10

What is a Full Agonist?

Answer 10

A drug with an efficacy of 1

Question 11

What is a Partial Agonist?

Answer 11

A drug that cannot produce the cells maximal response, even when they have bound to all available receptors since they have low efficacy
A drug with an efficacy of less than 1 but >0

Question 12

What is an Inverse Agonist?

Answer 12

Bind to agonist receptors but produce an opposite response
A drug that can inhibit any intrinsic receptor activity (ie. prevents a protein from changing shape) that might exist in the absence of any ligand.
Has a negative efficacy ( one <0)

Question 13

what is quantitative pharmacology?

Answer 13

based on the assumption that drugs act by entering into a simple chemical reaction with certain receptors in cells and that there is a simple relation between the amoun of drug fixed by these receptors and the action produced.

Question 14

What is the law of mass action?

Answer 14

A + R <=> AR

point of equm (Kd) is the dissociation constant

Question 15

How can you work out Kd from the law of mass action equation?

Answer 15

Kd = [A][R] / [AR]

units mol/litre

Question 16

How can you calculate the fixed number of receptors?

Answer 16

Rt = [R] + [AR]

Question 17

How can you calculate the occupancy of a drug?

Answer 17

p = [AR] / [Rt] (p = occupancy) (Rt = fixed no of receptors; Rt = [R] + [AR])

Question 18

What is the Langmuir Isotherm equation and what is it used for?

Answer 18

p = [A] / (Kd + [A])

This equation can be theoretically used to determine the amount of drug bound to a receptor.

Question 19

what is the spare receptors concept?

Answer 19

The idea that some highly efficacious agonist can produce a maximal response from a cell without binding to all available receptors.

Question 20

Show how an agonist affects the path between the agonist and the receptor.

Answer 20

A + R AR AR* –3–> EFFECT

(1) - affinity governs binding
(2) - Through binding activates the drug
(3) - efficacy governs activation

Question 21

Show how an inverse agonist may affect the path of a reaction

Answer 21

A + {R} R AR AR —-> EFFECT

(1) - affinity governs binding
(2) - efficacy governs activation

Question 22

What are some drug targets (binding sites)?

Answer 22

Enzymes - cyclooxygenase (the aspirin receptor)

Ion channels - Nifedipine blocks Ca2+ ion channels

Transporters (pumps) - cocain blocks noradrenaline transporters

Physiological receptors - receptors for hormones or neurotransmitters

Question 23

How can you regulate cell function with drugs?

Answer 23

altered cell membrane potential
altered enzyme activity
altered gene expression

drugs can target these things directly to produce their effects
most drugs effect these cells via physiological receptors

Question 24

How are receptors classified?

Answer 24

Classified on the basis of the selective action of drugs

Named according to the neurotransmitter or hormone with which they interact

Most transmitters/hormones interact with more than one type of receptor - the differences in protein structure underlie the different subtypes

Question 25

How can transmitters act at more than one receptor?

Answer 25

Basic idea of multiple receptors per Nt (muscarinic and nicotinic ACh receptors)
The idea that ACh would induce relaxation of smooth muscle when 2ug were given,

Adding atropine blocks the mAChR receptors so no relaxation occurs

nAChR receptors activated stimulating muscle contraction

Adding atropine has no effect on nAChRs

Question 26

Give some receptor superfamilies

Answer 26

Integral Ion channels - nicotonic and glycine receptors

Integral tyrosine Kinases - insulin receptors
steroid receptors - oestrogen

GPCR - muscarinic and adrenoreceptors

Cytokine receptors - prolactin and growth hormone receptors.

Steroid receptors - Oestrogen

Question 27

What is the Isolated Ileum preparation?

Answer 27

Used a smooth muscle preparation of guinipig ileum

Added drugs to see if they caused contraction

Added drugs which produced no effects (antagonists)

Repeated experiment with drugs that did produce effects combined with antagonist to see if they worked by the same mechanisms (if they did then no effect would be seen as antagonist blocks receptors)

Question 28

What do agonists posses?

Answer 28

Affinity and efficacy

They BIND to a receptor and produce a RESPONSE

Question 29

What is the efficacy of an antagonist?

Answer 29

Antagonists have no efficacy

Question 30

How can we measure affinity of a drug?

Answer 30

The affinity can be measured using a drugs dissociation constant from its receptor. (Kd).

Question 31

What is Kd equal too?

Answer 31

This is equal to the concentration at which at eqm half the receptors will be bound with a drug.

Question 32

What do antagonists posses?

Answer 32

Affinity but no efficacy