D1 - Drugs Intro

Question 1

pharmacology

Answer 1

Branch of science that studies the effects of drugs upon the functions of living systems

Question 2

Drug

Answer 2

1. A chemical substance given with the intention of preventing or curing disease or otherwise enhancing the medical or physical state of humans or animals
2. A habit forming medicinal substance/narcotic - carries negative connotations

Question 3

4 broad protein classes of receptors

Answer 3

1. G protein coupled receptors GPCR
2. Ion channels
3. Kinases
4. Nuclear receptors

Question 4

Pharmacodynamics

Answer 4

• what the drug does to the body
• a scientific description of the mechanisms underlying the effects of the drug on the body, extending from the interactions of drugs with target receptors, effects on cell signalling pathways, cell and tissue responses, and changes in the functions of whole organs and body systems

Question 5

Pharmacokinetics

Answer 5

• what the body does to the drug
• a scientific description of the fate of the drug once it enters the body, extending from its absorption from the site of administration, distribution through the blood stream to body tissues, metabolism within the liver, and eventual excretion by the kidneys
• readiness of absorption, distribution, metabolism, excretion

Question 6

Small molecule drugs are the domain of

Answer 6

Pharmacology

Question 7

Biological drugs are the domain of

Answer 7

Biotechnology

Question 8

Pros of small molecules

Answer 8

• easy to distribute / available at pharmacies
• easy and cheap to make / copy on patent expiry
• access to body readily - oral

Question 9

Cons of small molecules

Answer 9

• can hit multiple receptors / side effects
• subject to DDIs - competing for the same P450 molecules
• problems with toxicity - P450 processes to form toxic metabolites
• undergo extensive metabolism in the liver

Question 10

Pros of biotechnology

Answer 10

• specific for one receptor - few side effects
• rarely subject to DDIs - don’t compete for the same P450
• undergo minimal metabolism

Question 11

Cons of biotechnology

Answer 11

• hard to copy upon patent expiry
• expensive to make - make with cell bio reactors, complex structure and hard to confirm purity - expensive for patients
• hard to get into the body - ie. infusion/infection - needs a trained person to administer

Question 12

Basic or experimental pharmacology

Answer 12

• medicinal chemistry and structural biology
• physiology and biochemistry
• genetics, systems biology and cellular biology

Question 13

Clinical or human pharmacology

Answer 13

• clinical medicine
• optimising drug and regulation
• drug abuse and addiction
• legal, economic aspects, side effects

Question 14

3 types of drug names

Answer 14

1. Chemical
2. Generic
3. Brand

Question 15

Bioprospecting

Answer 15

• medicines obtained from plants, microorganisms, animal venoms, marine organisms etc. - bioactive species
• systematic testing of naturally procured materials for pharmacological study

Question 16

Bioprospecting example

Answer 16

Lexisenatide

• use in diabetic patients who respond poorly to conventional sugar lowering drugs
• naturally occurring peptide discovered in a salivary glands of a toxic lizard
• boost insulin release after meals

Question 17

Disease model screening

Answer 17

• microbiologists isolate infective pathogens and reproduce them in animal models and test with synthetic libraries
• transgenic technology allows animal modelling of gene based diseases
• routine for most drugs

Question 18

Disease model screening example

Answer 18

Prontosil

• identified as working against streptococcus in mice
• antibacterial
• lead to sulphonamide class of antibacterial drugs - “sons of sulphonamide”
• group gets cleaved in the body and liberates sulphonamide which has pharmacological effects

Question 19

Me too drug optimisation

Answer 19

• competition between rival companies to make better and safer drugs
• better efficacy, less side effects, lower cost, less frequent doses

Question 20

Me too drug optimisation example

Answer 20

Captopril

• ACE inhibitor - blood pressure lowering drug, a small molecule version of a biological that can be taken orally
• has issues with side effects, has now been replaced by enalapril

Question 21

Astute clinical observation

Answer 21

• unexpected effects can occur when testing drugs in humans
• sometimes these effects can be negative eg. thalidomide
• serendipitous observations of new drugs can lead to new uses

Question 22

Astute clinical observation example

Answer 22

Sildenafil

• tested in angina pateints - was not found to have any efficacy
• used as viagra for patients with erectile dysfunction

Question 23

rational drug design

Answer 23

• due to advances in X-ray crystallography - detailed knowledge of drug receptors is available
• using computer aided software virtual screening of compound libraries is possible

Question 24

rational drug design example

Answer 24

dorzolamide

• made using x ray analysis and rational drug design
• used in patients with glaucoma

Question 25

irrational high-throughput discovery

Answer 25

• technological advancement allows mechanisation of lab process
• quicker screening of compounds for pharmacological activity
• expectation that massive libraries of compounds will contain
• less often used - too many false positives

Question 26

irrational high-throughput discovery example

Answer 26

sorafenib

- kinase inhibitor that prevents tumour growth