Definition of Pharmacology and the Related Subjects. Drug development

Question 1

Definition and Goals of Pharmacology

Answer 1

Study of effects of drugs on the function of living systems

Goal
To understand what drugs do to living organisms and how their effects can be applied to therapeutics

Question 2

Subcategories: Pharmacology

Answer 2

Neuro
CV
GI
Immuno
Respiratory

Question 3

Definition of Pharmacokinetics

Answer 3

Effect of body on the drug
Absorption (sit of admin-> systemic)
Distribution
Metabolism (biotransformation, liver, plasma, gut wall)
Excretion (urine, stool, sweat, resp tract, mothers milk)

Question 4

Definition of Pharmacodynamics

Answer 4

Effect of drug on body
Activation
Inhibition
Stimulation

Question 5

Definition of Toxicology

Answer 5

Non desired effects
drug–> effects of overdose
Poisons not drugs; rare exceptions

Question 6

Definition of Pharmacy

Answer 6

Formation and development of drugs as chemical compounds

Question 7

Definition of Homeopathy

Answer 7

Ailments treated by minute doses of natural substances that in larger amounts would produce symptoms of the ailment.

Question 8

Definition of Pharmacoeconomics

Answer 8

‘Cost-benefit’ of therapy

Example
Rituximab is expensive

Question 9

Definition of Pharmacogenesis

Answer 9

Genetic influences on response to substance

Question 10

Steps in the Development of Drugs

Answer 10

Choose a disease
Choose a drug target
Identify a 'bioassay'
Find a lead component
Synthesis analogues of the lead
Identify Structure Activity Relationships (SARs)
Detemine toxicity and efficacy in animal models 
Determine pharmacokinetics and dynamics
Design a manufacturing process
Carry out clinical trials
Market the drug

Question 11

Choosing a Disease

Answer 11

Tendency towards avoidance of products with small markets

Most research on diseases of ‘first world countries’

Question 12

Identifying a Drug Target

Answer 12

Specific macromolecule, biological system with which the drug will interact with

Importance of selectivity; not present in mammals or significant structural differences

Question 13

Combinatorial Chemistry

Answer 13

Process in which large amounts of compounds can be prepped at one time

Question 14

Computer Assisted Drug Design

Answer 14

Use of computer to design a perfectly fitting ligand to known molecular structure of target

Drawbacks
Ligands id designed and/or docked into active site–> Most programs don’t allow conformational movement in target

Question 15

Choosing a Bioassay

Answer 15

Bioassay= test to determine biological activity

In Vitro: artificial environment, Test tube or culture media
In Vivo: within living body
Ex Vivo: Test on tissue taken from living organism

Question 16

In Vitro Testing

Answer 16

Advantages
Speed
Req relatively small amounts of compound

High throughput screening (HTS)
Increase in speed to point where can analyse several
100s compounds per day

REM: results may to translate to living animals

Question 17

In Vivo Testing

Answer 17

More expensive
Moral debate- animals

Disadvantage
Possible clouding of results by interference with other
biological systems

Question 18

Finding the Lead

Answer 18

Screen Natural Products
plants, microbes, marine world, animals..
Req quick assay for desired biological activity
Req to be able to separate bioactive component from
other inactive substances

Screen Synthetic Banks
Stored in freezer
Catagorisation and screening of new targets as these
are being identified

Question 19

Structure- Activity - Relationship (SARs)

Answer 19

Identifying which structural features are resp for a leads biological activity = pharmacophore

Example
Longer chains decrease the effect

Question 20

Xenobiotics

Answer 20

Foreign substances which are not produced naturally

Goal of body is to remove these

Question 21

Toxicity: With Thalidomide as Example

Answer 21

Sold 1957-61 mainly as antiemetics for morning sickness

Lead to severe malformations in offspring; incl phocomelia

New Studies, now used in ex: erythema nodosum leprosum

Question 22

Clinical Trial: Phases

Answer 22

I: Test drug on healthy volunteers
Det: toxicity relative to dose
screen for unexpected SE

II: Test on small group of patients
See if drug has beneficial effect
Determine dose level required for this effect

III: Test on larger group of people
Compare with existing treatments and placebo

IV: Drug is placed on market
Patients monitored for SE

Takes approximately 12 years for the drug to be approved from Phase I-Beg. Phase IV