Fundamental principles of pharmacology 1

Question 1

Drug definition

Answer 1

-Chemical substance of known structure
-Which produces a biological effect when administered to a living organism
-Other than a nutrient or an essential dietary ingredient

Question 2

What 3 factors make a good medicinal drug?

Answer 2

-Can we deliver it to its site of action?
-Will it do anything once it gets there?
-Does it stay there?

Question 3

3 names of therapeutic drugs

Answer 3

-Chemical name
-Common name
-Trade name
-Drugs are grouped according to use or action it performs

Question 4

How do drugs produce their effects?

Answer 4

-The vast majority of drugs bind to receptors that are important proteins within the body
-Target proteins include
=>Receptors for neurotransmitters or hormones
=>Enzymes
=>Ion channels
=>Carrier or transporter molecules

Question 5

What are ligands?

Answer 5

-Small drug molecules that bind to large target proteins

Question 6

What affects drug binding?

Answer 6

-How well a drug fits into its binding site depends on its stearic factors (size and flexibility)
-How well it binds depends on the bonds
-Reversible binding occurs through hydrophobic and hydrogen bonds + weaker VDWs forces
-Irreversible binding occurs due to covalent interactions

Question 7

Specificity vs Selectivity

Answer 7

-One way of achieving specificity might be to design a drug that binds to only one molecular target
-However, if that molecular target is found in different systems, despite being specific it would be non-selective

Question 8

Pharmacodynamics vs Pharmacokinetics

Answer 8

Pharmacodynamics - what the drug does to the body
Pharmacokinetics - what the body does to the drug

Question 9

4 critical elements of pharmacokinetics

Answer 9

-Absorption
-Distribution
-Metabolism
-Excretion

Question 10

Outline of the drug discovery process

Answer 10

-Basic research
-Identification of potential drug targets
-Hypothesis generated

Question 11

Preclinical drug discovery

Answer 11

Question 12

Clinical trial timespan

Answer 12

Question 13

Phase I of clinical trial - Exploratory; first in human

Answer 13

-Before this, chronic toxicity of drug assessed in at least 2 mammalian species (1 non-rodent)
-Last 6 months - 1 year
-Checks for safety and tolerability (side effects)
-Small number of healthy volunteers exposed to increasing doses
-Randomised, double blind trial
-May involve selected groups (e.g. male/female)

Question 14

Phase II of clinical trial - Efficacy, proof of concept and safety

Answer 14

-To check for clinical effectiveness, safety and tolerability
-Phase IIA: exploratory
-Phase IIB: confirmatory (larger sample size)

Question 15

Phase III - Confirmatory

Answer 15

-Full scale evaluation of how effective and safe treatment is compared to standard/placebo
-Tested in multi-centres and different groups
-Drugs can be registered after success

Question 16

Phase IV clinical trials - Ongoing

Answer 16

-Continued after drug is licensed on the market
-To monitor consequences of increasing exposure in tens of thousands of patients
-Monitors drug’s efficacy in subgroups of the population