drug development Flashcards
what are contract research organisations?
companies performing specific parts of the drug development process e.g. organising and running clinical trials
what is a lead compound?
molecule that acts specifically and selectively with protein target
what are some optical approaches used to determine receptor activity?
- measuring fluorescent emissions
- measuring light absorption
Lead finding
high frequency + automated screens against chemical libraries
screen = performing assay on cloned gene generating target
what is combinatorial chemistry?
synthesising multiple drugs that are derivatives of an initial molecule of interest
what does exploratory toxicology consist of?
- general toxicity –> in silico and in vitro
- preliminary genotoxicity - predict whether drug will cause dna mutations?
- preliminary toxicity -> in vivo
what does exploratory safety consist of?
- off target binding profile –> any unpredicted side effects?
- preliminary cvs safety
- preliminary cns safety - toxicity of small molecules that may enter cns?
describe the ames test
- isolate strains of salmonella that cannot grow on a medium missing histamine
- apply drug on medium
- bacteria grows? - may have acquired mutation reversing effect
so drug has potential to cause mutations
arrhythmia biomarker
drugs that can bind to hERG k+ channel give rise to long QT syndrome in patients = electrophysiology
so drug can give rise to cardiac arrhythmia
how long do preclinical studies for small molecules take?
4-4.5 years
how long do preclinical studies for biomolecules take?
2-2.5 years
what is exaggerated pharmacology
drug having a more extreme reaction than expected. relates to high specificity and effectiveness.
what is a cytokine storm?
massive immune reaction after injecting drug for 1st time
leads to massive organ failure
what is the irwin activity screen for rats?
- test if drug has entered cns and exerted any effects there
observing behaviour, respiratory rate, heart rate, muscle tone, motor coordination etc.
what is a major metabolite
metabolite accounting for >10% of parent compound - may have to synthesise and test separately
DEFINE: pharmacodynamics
study of the ability of a drug to exert its effect on intended target
phase I of clinical development
8-20 healthy volunteers minimal dose how safe is the drug? how well is the drug tolerated? - any side effects pharmacokinetics
phase II of clinical development
low 100s of patients/volunteers
test effectiveness
test concentration needed for effectiveness
phase III of clinical development
lasts for several years
1000+ patients
multi centre + multinational
broadening patient groups to which the drug is administered
toxic side effects, tolerance, pharmacokinetics?
compare to standard treatment
randomised and blind trials
what is hydromorphine?
narcotic painkiller
taking with alcohol -> respiratory depression -> overdose
what are the causes of drugs failing to be registered?
- not economically viable
- drug metabolism and pharmacokinetics - decreased strength of drug
- no improvement in efficacy in patients
