Medicines Pathway Flashcards
What are stages bringing a drug to market?
- Drug discovery
- pre-clinical trials
- Clinical trials
- pharmacoviliglance/post marketing surveillance
What is the aim of each stage of bringing a drug to market?
- discovery- understanding disease or ailement and taget + identify the drug needed
- pre-CTs- assess the PK profile
- CTs: phase I- assess the ADME profile, safety + side effects
phase II- efficacy, side effects
phase III- comparison of drug to current interventions/placebo - Pharmocovigilance-monitor the new med in practice.
How are drug candidates chosen for pregression to pre-clinical stage?
- around 10,000 of known or NCEs are tested
- around 250 ‘hit’
- around 10-50 ‘lead’ compounds are identified
- ‘lead’ compounds are optimised through QSARs -usually 3-5
What are SARs and QSARs?
- Structure activity relationships and quantitative structure activity relationships
SARs= changes in structure of a molecule and how they relate to the effects on the molecular target
QSARs= a process of modelling mathematically the relationship between structure and activity
What are the advantages of testing compounds from natural sources?
- lots of potential for variety of new compounds
What are the sources of compounds for drug development?
- Natural materials
- compound libraries
- computerised simulations
Disadvantages of natural compounds for drug development
- time consuming
- complex doesn’t tend to cross GI tract
- if can’t cross GI then need to be administered via injection
- injections aren’t appealing to public so poor selling point
- complex and hard to synthesis
Describe how compound libraries work?
- An array of compounds (previously used or NCEs)
How are new compounds synthesised?
via combinatory chemistry:
-in a larger reactor are substrates and common molecules found in most drugs.
-lots of different combinations are made
-isolated and purified
What are the disadvantages of ONLY using compund librabries?
- time consuming
- some/most may not interact, so wasted materials
Compound libraries are used in combination with….
Computerised simulations
What are computerised simulations and why are they used in drug discovery?
- they model interaction using virtual compounds and virtual targets
- they are used so the best virtual compounds are chosen for synthesising
Pre-clinical trials: advantages of In vitro
- HTS (high throughput screening) is possible
- Cost effective
- human models can be used
- mechanisms can be studied
Disadvantages of In Vitro
- models are simplified
- often different fron In Vivo tissue
- No interconnections between different biological systems
How are animal studies conducted?
- PK profile: ADME
- Toxicity- increasing doses to determin max effective dose
- determine therapeutic window
CTA is split into 3 parts, which are ….
- Chem + formulation data
- In Vitro and animal studies data
- Clinical trials protocols
Explain phase I trials
- on healthy volunteers except unethical then only performed on one type of patient
- clinical setting-clinical research unit- CRU
- drug is administed i formulation
- monitoring
What is monitored during phase I trials?
- record side effects
- physical examinations
- blood/urine samples for AMDE profile
how does phase I trials conducted?
- randomised groups -computer generated
- Double blind and placebo trials
- doses are increases when PK profile is expected and ni adverese effects
- max dose stop when pre-determined max therapeutic conc is reached
- does frequency is tested
- cross-over of groups
- effect with food is tested- with high fat meal
How are phase 2 tials conducted?
- 100-300 patients with disease
- patients of high homogeneity chosen
- different doses and dose frequencies are tested
- side effecs are monitored
- efficacy is determined
describe how phase III trials are conducted?
- current intervention/placebo is compared with drug
- broad patient population-involving 2-3 hospitals
- expensive
- cross over and double blind trials
Describe pharmacovigilance
- monitoring of medicine to population + in practice
- adverse effects? and in some more than others
- improve quality of life
- better value than other treatments
What license of drugs cannot be marketed or promoted during pharmacovigilance?
POMs
why is marketing and promotion done during the pharmacovigilance stage?
- Cover costs in the development and re-invest in other discoveries
- promote use in healthcare practices
- inform scientific and medical community of a new drug in market
What are the different applications needed to be made for a drug to go into market?
- CTA
- MA
state and describe the first application needed to be made after drug discovery?
- CTA- allows for manufacture for sale/supply for trial, use, import to UK for trials
- EAMS- allows for people with life threatening/debilitating conditions to use unlicensed meds when there are no alternatives
What is still needed for EAMSs ?
Pharmacovigilance- if harmful then it is stopped
state and describe the types of applications can be made follwing CTs?
- MA- data is scrutinised for evidence of safety and efficacy, if MHRA are satifised then MA is granted
- Abridged application- for generic medicines, a shorter MA application, still results in an MA
What does MA grant?
- med classification- type of license, who and what for
- sale/ supply, import/export, manufacture and assemble for wholesalers and pharmacies
Before market launch of med, describe what must happen?
- ML-manufacturing license
- Manufaturing facility inspection by NHRA
- GMP ( good manufacturing practice) is tested by QP
