D1 - Drugs Intro Flashcards
pharmacology
Branch of science that studies the effects of drugs upon the functions of living systems
Drug
- A chemical substance given with the intention of preventing or curing disease or otherwise enhancing the medical or physical state of humans or animals
- A habit forming medicinal substance/narcotic - carries negative connotations
4 broad protein classes of receptors
- G protein coupled receptors GPCR
- Ion channels
- Kinases
- Nuclear receptors
Pharmacodynamics
- 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
Pharmacokinetics
- 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
Small molecule drugs are the domain of
Pharmacology
Biological drugs are the domain of
Biotechnology
Pros of small molecules
- easy to distribute / available at pharmacies
- easy and cheap to make / copy on patent expiry
- access to body readily - oral
Cons of small molecules
- 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
Pros of biotechnology
- specific for one receptor - few side effects
- rarely subject to DDIs - don’t compete for the same P450
- undergo minimal metabolism
Cons of biotechnology
- 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
Basic or experimental pharmacology
- medicinal chemistry and structural biology
- physiology and biochemistry
- genetics, systems biology and cellular biology
Clinical or human pharmacology
- clinical medicine
- optimising drug and regulation
- drug abuse and addiction
- legal, economic aspects, side effects
3 types of drug names
- Chemical
- Generic
- Brand
Bioprospecting
- medicines obtained from plants, microorganisms, animal venoms, marine organisms etc. - bioactive species
- systematic testing of naturally procured materials for pharmacological study
Bioprospecting example
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
Disease model screening
- 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
Disease model screening example
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
Me too drug optimisation
- competition between rival companies to make better and safer drugs
- better efficacy, less side effects, lower cost, less frequent doses
Me too drug optimisation example
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
Astute clinical observation
- 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
Astute clinical observation example
Sildenafil
- tested in angina pateints - was not found to have any efficacy
- used as viagra for patients with erectile dysfunction
rational drug design
- 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
rational drug design example
dorzolamide
- made using x ray analysis and rational drug design
- used in patients with glaucoma
irrational high-throughput discovery
- 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
irrational high-throughput discovery example
sorafenib
- kinase inhibitor that prevents tumour growth