Introduction to Pharmacology

Question 1

define pharmacology

Answer 1

the study of the mechanism of drug action

Question 2

what is a drug?

Answer 2

the active ingredient of a medicine
any substance which interacts with the biological system and changes it

Question 3

drugs can be subdivided into..?

Answer 3

Chemical: smaller in size
Biologics: e.g., proteins - greater in size and complex

Question 4

how are drugs named?

Answer 4

they have:
chemical names
generic names
trade names (brand names)
e.g
chemical name: acetylsalicylic
generic name: aspirin
trade name: Aspro, Disprin, Anadin

Question 5

why can’t you use the chemical name when naming drugs?

Answer 5

some drugs have very long complicated names that need to be simplified

Question 6

how do drugs produce their effects?

Answer 6

• By binding to a receptor e.g. agonists/antagonists
• Drugs can also produce their effects due to their physicochemical properties (not by binding to a receptor).

Question 7

why do you need high conc of a drug?

Answer 7

Effects are rather non-specific so you tend to need rather high concentrations to see an effect

Question 8

what are examples of drugs that produce their effects due to their physicochemical properties?

Answer 8

Antacids (stomach)
Laxatives
Heavy metal antidotes
Osmotic diuretics
General anaesthetics
Alcohol

Question 9

what are antacids and what do they do?

Answer 9

Contain sodium bicarbonate (buffer)
neutralise stomach acid

Question 10

what are laxatives and what do they do?

Answer 10

Methylcellulose:
- is a bulk-forming laxative that increases the amount of water in your stools to help make them softer and easier to pass

Magnesium sulfate (osmotic):
- cause water to be retained in the intestinal lumen making stool easier to pass

Question 11

what are heavy metal antidotes and what do they do?

Answer 11

EDTA:
removing heavy metals, such as mercury or lead, from blood to stop metal poisoning.

Question 12

what are osmotic diuretics and what do they do?

Answer 12

Mannitol:
Given by IV
filtered in kidneys into the urine drawing water with it causing increased urine production

Question 13

what is an example of a general anaesthetic?

Answer 13

Halothane

Question 14

what affect does alcohol have on the body?

Answer 14

doesn’t have a direct receptor in the body that it binds to
however it influences membrane fluidity
has an effect on the reward systems in the brain

Question 15

define potency

Answer 15

amount of drug needed to produce a given response
- High potency drugs requires a low dosage
- Low potency drugs need a high dosage

Question 16

define efficacy in relation to drugs

Answer 16

refers to the ability of a drug-receptor complex to produce a maximum functional response

Question 17

what are the two specificities that drugs attain to?

Answer 17

Biological specificity - The molecule and the receptor are the same however, the receptors are located on different tissues leading to different effects.
Chemical specificity - Drugs are specific and complimentary to their receptor. This is illustrated by the lock and key model and allows for the altering of cell function.

Question 18

what is stereoselectivity?

Answer 18

if a drug has a chiral centre it would have 2 versions of the drug (racemates)
one of the isomers is the active form e.g. thalidomide

Question 19

what is dangerous about the thalidomide drug?

Answer 19

pain relief medication that is only active in one racemic version
S isomer is the active form
R isomer is a potent teratogen (agent that causes an abnormality following fetal exposure during pregnancy)

even if you synthesis the thalidomide so that its racemically pure (only S) the chiral centre isn’t a C but a N, so over time it will equibrilate with the R version - turning toxic

Question 20

what is the lock and key hypothesis?

Answer 20

Drugs produce their effects by combining with receptor sites in cells
Lock and Key hypothesis: The shape of the drugs complements the shape of the receptor (chemical specificity)

Question 21

what models can you use to test for drugs?

Answer 21

Cells-
Example Cultured Cardiomyocytes are taken from rats
Then with this model you can test drugs for blood pressure, arrhythmia (problems with heart beat rhythm) and cardiotoxicity.
Organoids –
small and simplified versions of organs. They can be used for two things:
Monitoring the development of a disease
Drug testing

Question 22

define affinity in relation to drugs

Answer 22

the strength of the drug receptor interaction or the ‘likelihood’ of binding. A potent drug has high affinity

Question 23

define recombinant

Answer 23

a cell or organism whose genetic material is produced from segments of DNA from different sources joined together - recombinant DNA.

Question 24

define transgenic

Answer 24

genes transferred from one species to another e.g. a human gene into a mouse

Question 25

what are agonists and what do they possess?

Answer 25

Bind to a receptor and produce a response
Possesses both affinity and efficacy

Question 26

what are the 2 types of agonists?

Answer 26

Exogenous
Endogenous

Question 27

what is an endogenous agonist?

Answer 27

is a compound naturally produced by the body which binds to and activates that receptor.

Question 28

what is an exogenous agonist?

Answer 28

is a synthesised drug, such as synthetic dopamine, which binds to the dopamine receptor and elicits a response similar to endogenous dopamine signalling.

Question 29

what are antagonists and what do they possess?

Answer 29

Bind to a receptor but do not produce a response
Prevent the agonist binding and so prevent (block) the response to an agonist.
Possess affinity but no efficacy.

Question 30

what are the types of antagonists?
give examples

Answer 30

Competitive
Irreversible/Reversible

Examples:
Atropine
Mepyramine (anti histamine)
Etanercept - a decoy receptor that binds to TNF agonist. (Usually the antagonist is a ligand but this is the actual receptor which causes the TNF agonist to bind to it and no response occurs)

Question 31

define quantitative pharmacology

Answer 31

direct relationship between amount of drug bound to a receptor and the size of the response

Question 32

define Emax

Answer 32

maximal response
read on the y- axis

Question 33

define EC50

Answer 33

concentration of agonist which produces half the maximal effect
read on the x- axis

Question 34

define threshold

Answer 34

Required concentration of agonist needed for an initial response (Can only be seen on log scale)

Question 35

why does the graph need to be converted to a sigmoid graph?

Answer 35

most of the data collected is at the beginning of the graph
in order to present it better you can log the conc of agonist (x- axis)
this produces a sigmoidal curve which is the same data - just stretched

Question 36

what are the 2 assumptions you need to make for a graph?

Answer 36

Assumption one: Reponses scales with concentration of drug receptor complexes (receptors occupied with a drug)
Assumption two: Fixed number of receptors

Question 37

what is this equation and what does it calculate?

Answer 37

LAW OF MASS ACTION
describes the binding event
you can calculate drug action quantitatively and plot a graph
it follows that KD is the conc of agonist at which the receptor is half- maximally saturated

• P is the proportion of receptors with a agonist bound i.e. RA/(R total)
• The units of KD are Mol/Litre or M

Question 38

what is the difference between KD and EC50?

Answer 38

EC50 is the model free equivalent of KD value
can be used interchangeably…
HOWEVER,
KD is not the same as EC50. As the point where half the receptors are full does not coincide with the point where the drugs effect is at 50%.