Basics of Drug Pharmacology

Question 1

What is a drug?

Answer 1

Any substance intended for use in diagnosis, cure, mitigation, treatment or prevention of disease

Question 2

What is a drug substance?

Answer 2

Material exerting pharmacological action with excipients used to formulate medicinal product

Question 3

What is a drug product?

Answer 3

One or more drug substances that contains excipients

Question 4

What are the general properties of drugs?

Answer 4

Therapeutic effect
Side effects
Drug interaction with other drugs

Question 5

What is therapeutic effect?

Answer 5

Desirable drug action

Question 6

What are side effects?

Answer 6

Undesirable or harmful drug actions

Question 7

What can drug interactions with other drugs produce?

Answer 7

Unpredictable effects

Question 8

What is the sequence of drug discovery?

Answer 8

Target selection
Lead discovery 
Medicinal chemistry
In vitro studies
In vivo studies
Clinical trials

Question 9

What is hit identification?

Answer 9

Once you have a target, you need to synthesise compound

Molecules identified have affinity for target

Question 10

What test systems are required for hit identification?

Answer 10

Recombinant protein expressed artificially in cells grown in lab
Isolated enzyme assay
Biochemical assay

Question 11

How to identify suitable bioassay?

Answer 11

Test should be simple, quick + relevant

Question 12

Describe in vitro identification of suitable bioassay

Answer 12

Cheap
Easier
Less controversial

Question 13

Describe in vivo identification of suitable bioassay

Answer 13

Needed to check drug interaction with target

Question 14

What are in vitro pharmacology assays?

Answer 14

Isolated tissues, cells or enzymes

Question 15

What are enzyme inhibitors tested on?

In vitro pharmacology assays

Answer 15

Pure enzyme in solution

Question 16

What are receptor agonist/antagonists tested on?

In vitro pharmacology assays

Answer 16

Isolated tissue/cells

Question 17

How are antibacterial drugs tested?

Answer 17

By measuring how effectively they kill in culture

Question 18

What is affinity?

Answer 18

Strength of chemical interactions responsible for drug-target interaction

Question 19

What is potency?

Answer 19

Degree of functional change imported to receptor upon binding of drug

Question 20

What if efficacy?

Answer 20

Extent of biological effect as result of drug-induced modulation of receptor activity

Question 21

Describe lead identification

Answer 21

Validated hits would be tested to determine factors such as:
Selectivity vs panel of other receptors
Physiochemical characteristics
Drug-like properties
Metabolic properties (half life)

Question 22

Describe optimisation

Answer 22

Molecules fulfilling lead identification criteria can go on to molecular finishing school

Question 23

What happens in optimisation?

Answer 23

Extensive SARs to improve potency + selectivity

Question 24

What is optimisation an opportunity for?

Answer 24

To improve physiochemical + drug-like properties

Question 25

What happens in preclinical studies?

Answer 25

``` Identify pharmacological properties PD (mode of action) PK (metabolism) Toxicology Safe initial dose ```

Question 26

What are the 3 R's strategy?

Answer 26

Reduce no. of animals to min Refine way experiment carried out = animals suffer as little as possible Replace animal experiments with non-animal techniques

Question 27

How long does regulatory affairs take?

Answer 27

8-15 years

Question 28

What do regulatory affairs look at?

Answer 28

Attention to early development = reduce no. of development failures

Question 29

What happens if there is compliance to regulatory affairs?

Answer 29

Development success

Question 30

What is a hazard?

Answer 30

Potential for damaging effect

Question 31

What is a risk?

Answer 31

Includes likelihood that hazard would occur

Question 32

How can risks be reduced?

Answer 32

Patient evaluation prior to use for "once a day" Restrict patient population to those with greatest need Lower dose Develop safer analogues

Question 33

When is a drug considered safe?

Answer 33

Expected therapeutic gain justifies risk

Question 34

What is pharmacovigilance?

Answer 34

Science + activities relating to detection assessment, understand + prevention of adverse effects

Question 35

What is an adverse event?

Answer 35

Any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product, which does not necessarily have casual link with treatment

Question 36

What is an adverse reaction?

Answer 36

Any untoward + unintended response to an investigational medicinal product related to any drug administered

Question 37

What is an unexpected adverse reaction?

Answer 37

An adverse reaction, the nature or severity of which is not consistent with the product info

Question 38

What is a serious adverse event/reaction?

Answer 38

``` Any AE/AR/UAR that results in: Death Life threatening Hospitalisation Persistent disability Birth defect ```