drug design 1 Flashcards by Lucie Netscher

why do we need new drugs

New ones with less side effects
Beuase of drug reisstnce and tolerance
To improve treatment of an existing disease
To treat new diseases
To give specific action on new targets for treating disease

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what needs testing preclinical safety testing

carcinogenesis
not tetragenic
-non toxic
-optimal route of administration

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how is toxicity measured

by the LD50 value

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what is the therapuetic index

amount causes toxic vs non toxic effect

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what is pharmacogentic

what does the body do to the drug

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what are genotoxic effects tested on

yeast

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what does stage 4 of clinical phases do

To compare a drug with other driugs already on the market
To monitor a drugs long term effects and impact the patients quality of life
To determine the cost effectiveness f a drug therpay relative to to other traditional and new therapaies

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how many drugs tested in clinical trails make it

1 in 5

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reasons for drug failure

Drug simply doenst work
Drugs too toxic
Drug comoany issues – loss of interest or finical problems
Markert too small for cost of development – rare tumour and orphan indication

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what are analgoues

druhgs which share simialr properties can be structural or fucntional

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what is chirality

potential of a molecule to occur in two assymteric forms that are non-superimposable mirror images of eachother with out chnaing the atmoic composition, atom-atom connections or binds order

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what types of drug action is tehre

stimaultion or depressuion of fucntional activity
-replacement of an essentiasl compound (e.g. under active thyroid)
-killing forgein organism
-changinga physiochemical enviroment

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classification of drugs

phychopharamaceutical agents acting on CNS
-pharmacodynamic agents
-chemotherapuetic agents
-metabolic agents

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what are primary affects and secondary affects

primary - desired therpauetic effects
secondary - side affects

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what is the mechanims of drug action

involve interaction between the chemical and parts of the organims

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what is an agonist

a drug that mimics and reproduces a reponse simalr to taht of naturally occuring biological molecule

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what is an anatagnosist

a drug that supresses a naturally occuring event

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what is a lead structure

molecular structure which gives some desired biological activity in an assay

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what is optimasation

modification for example making teh drug more soluble

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what was the first medicinal drug and where was it from

asprin from willow leaves

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how long does it take to initial docovery to a marketable medidicne

12-15

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what is toxoty of drug measured by

LD50

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what saftey is needed with drugs

not teratogenic
-carcinogenic
non toxic
optimal route of admisitartion

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what is looked for at preclincial level

-proof of prinicple
-safe potent and efficacous
-evaluates aspects of PD/PK and toxicology
-ideal preclinical model mimics himan disease
-PD establiushes the therpautoc index of a drug
-PK descibles chnages in plasmsa conc as a consequcen of ADME

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what is the advanatge of in vitro preclinical studies

fast simple and effctive

what are genotoxic affectes tested on

yeast based systems

what are the advnatge of cell lines for invitro preclincial

can easily test proliferation against apoptosis

what is main advnatges of invivo precloinical studies

ADME suitable can also gentically engeneer mice

what are the disadvantge of animal testing

doesnt always highlight potentail properties they have a differnet affect

what are the disadvatnages of making a too lipidphilic drug

would accumalet in liver and kidneys and cause toxic damage

what is done at phase 1 clinical trail

monitor drug in healthy ppl for about a year

what is done at phase 2 clinical trail

what does drug do and the dose needed, done in a small amount of patinets (still looking at saftey)

what is done at phase 3 clinical trail

an increased amount of ppl used

what is done at phase 4 clinical trail

approval and long term results

what are the aims of drug deisgn

- good selectivity - good level of activity - minimal side affectrs -easily synthesised -chemically stable -acceptible pharmacokinetc properties -non toxic

what is the funnel affect

drug discover compounds screened preclincial clinical approval

what is a new molecular entitiy

a drug that has never been approved by FDA or marketed in any form or deriviative

what are the advantages of small molecules over macromolecules

greater dverity, cheaper, easier to make and manipulate, more scaleable and rapidly diffuse into cells.

what are the sources if kead structure

- from obserevd clincial and pharmacological side affect - from traditional medecine - random screening and high throughpout screening -combinational chemistry

what is ligand based drug design

biologcial affect no idea with mode reaction

what is target based drug design

serial tetsing of substances with an isolated biological target to indentify an agent that induces a desired biochemical outcoem

how are the drugs classified

- molecular target - biochemical process - pharmacological affect - chemical structure

how are the drugs classified

- molecular target - biochemical process - pharmacological affect - chemical structure

what are the actions of drugs

the way the drug excerts teh desired affect

what are teh affects of a drug

the observed consequences

what is mechainims of drug action interactions

interaction betwene chemical and parts of organism

what are the 9 satges of drug design

- indentify targets - extract compound - check acticity - detrmine molecular structure -synthesise analgoges - deduce molecular features - syntyhesise new compounds with increased acticity - test -select lead

what is a selecetive drug

many actions one effect

what is a specific drugs

1 target many affects

what are the aims of preclinical saftey testing

to be able to give the patient a dose of the drug that achieves the desired affect with causing harmful side affects

in preclincial what does PK describe

the changes in the plasma conc as a consequnce of ADME

in preclincial what does PD establish

the theraputic index

what is an example of a ligand based drug

penecilin

what is an exammpleof a speciific drug

atrapine - binds to acetylcholine receptors and affects heart rate and dilution of pupils

what is an example of a selective drug

heparin, high target numbers but is only an anticoagualnt

what type of ddrug do you normal get from targetted drug design

specific drugs

what type of drug is produced from ligand based drug disovery and give an exmaple

selective drugs asprin (tends to be older drugs)

what drug is an example of nieither speicific or selective

antihisatmine

what is an exmaple of a drug with a very narrow theraputic window

warafron - small window between anticogualnt and bleeding out

what is an exmaple of antagonoist

chemotherpay on cell pathway

what types of drugs can be people easily become reistant

targetted drugs

what is a lead

minium structure that is needed to get the desired biological acticity

what is a lead

minium structure that is needed to get the desired biological acticity

what does invivo preclinical trails

genticically modified mice humna tumour xenografts

what is invivo

in animal studies or people

what is in inivtro

in petri dish

what are advantges if invivo

can look at toxicity, PD and pk

what is the disadvantage of animals models

doesn't always highlight potentail issues and the main issue is because the drug is too lipophillic and goes to kidneys and livers

what is the translational phase

bench to bedside

what is a new molecular entitiy

a whole new drig taht has never been approved by the FDA

what are the sources of lead structure and give examples for 3

- side affects of compounds - from traditional medicine using natural sources- asprin - random and high throughput screening - combination chemistry and inital screening - me better - captoprill

what is an example of a me better drugger

captopril

how was asprin developed

salicin was fouond in willow bark and found to give pain relief, the mechinims was invetsigated, analgoues were found which got rid of mouth irratation and bad taste

what is an orphan receptor

a nuclear recpetotr taht hasn't doesnt have a ligand or there is lack of information on it