drug discovery and clinical trials Flashcards

1
Q

drug discovery initial identification

A
published research 
disease knowledge
pharmaceutical analysis generating hypotheses
traditional or herbal 
luck
metabolites of existing drugs
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2
Q

cellular drug targets

g protein coupled receptor

A

drugs as selective ligand

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3
Q

cellular drug targets

ion channels

A

challenging due to pore forming homology

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4
Q

cellular drug targets

transport proteins and enzymes

A

protein kinases, targets for oncology

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5
Q

genetic associations

A

GWAS sequencing of whole genomes allows for identification of subgroups requirements for new personalised medicines

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6
Q

high throughput screening target validation

A

large no. modulators against drug candidate to rapidly exclude those with poor response

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7
Q

bioinformatics

A

analyse data sets to show targets and understand disease processes to identify drug targets

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8
Q

Pre

pharmacodynamics PD

A

what drug does to the body

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9
Q

Pre

pharmacokinetics PK

A

what body does to the drug

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10
Q

Pre

basics of PRECLINICAL study

A
animal models no humans 
PK
PD
safety and toxicological investigations
pharmaceutical development-large scale feasibility
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11
Q

Pre

pharmacodynamics research

A

site/mechanism of action
influence of age sex and other factors
dose-response

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12
Q

Pre

pharmacokinetics research

A

absorption- rate and bioavailability
distribution in tissues
metabolisms - accumulation and interactions
excretion- clearance and organ

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13
Q

Pre

safety and toxicological

A
adverse effects
non toxic dose
therapeutic range
post mortem for tissue damage
intra and inter species variability
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14
Q

Pre

pharmaceutical development

A

formation and administration
large scale synthesis/purification feasibility
compound stability under different conditions

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15
Q

when can Pre go to clinical

A

once thorough and comprehensive preclinical satisfied a regulatory body for safety and efficacy can move on to human testing

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16
Q

basics CLINICAL TRIALS

A

human volunteers
expose more people collect more data
needs authorising by medicines and healthcare produce regulatory agency MHRA
good clinical practice

17
Q

phase 1 clinical trials

A

initial human administration
estimate safety and dose range
small n of health volunteers
use exhaustive pre clinical data to minimise risk
specialist units and trained investigators for consequences

18
Q

phase 1 clinical trial administration

A

slow infusion
SAD-single ascending dose, if no adverse effects increase dose in a new group until side effects or PK safety
MAD

19
Q

phase 1 clinical trial Pharmacokinetics PK

A

measure at freq. intervals for conc vs time
absorption, distribution, metabolism, excretion
monitor any variance from pre clinical animal models

20
Q

phase 1 clinical trial pharmacodynamics PD

A

consider mechanism of action, specificity and immune targets
body system disturbances
high potency

21
Q

phase 1 clinical trials drug dose

A

MABEL- minimum anticipated biological effect level(minimum dose to cause biological effect in human)
NOAEL- no observed adverse effect level(highest does no adverse effect)

22
Q

p1 clinical trial volunteers and objectives

A
small number less than 20 or 30 of healthy volunteers with no other medication with valid informed consent (or cancer patients)
determine MTD (max tolerated dose) and MEC (minimum effective conc)
23
Q

p1 ADME

A

absorption into systemic circulation
distribution of drug into tissues
metabolism and or metabolites
excretion of drug from body

24
Q

p2a basics

A

same as p1 but larger n 50-500
can look at differences in age
appropriate dosage in patients

25
Q

p2b basics

A

therapeutic range assessed for efficacy
pivotal trials-evidence for drug marketing approval
once shown effective against disease or condition can go to p3

26
Q

p3 basics

A

therapeutic confirmation using large n and RCT

large and long term assessment on safety

27
Q

p3a

A

before drug application submission
use on patient pop
info on labelling
modelling for drug drug interactions and differences in subgroups

28
Q

p3b

A

after application but before approval/marketing
supplements earlier trials
increased patient exposure

29
Q

p4

A

post registration and licensing
2000-10000
comparison against other drugs
continued pharmaco-economic evaluation

30
Q

RCT gold standard basics

A

intervention vs control
follow up and measure outcomes at time points
single or double blinded
randomisation

31
Q

PICO

A

population
intervention
control
outcome

32
Q

RCT problems

A
noncompliance
missing outcomes(loss follow up)
33
Q

NNT-number needed to treat

A

average no. patients receive treatment before ones positive outcome - ideally close to 1

34
Q

NNH-number needed to harm

A

chance of experiencing harm because of intervention

should be large

35
Q

types of RCT design

A

superiority- show more effective
equivalence - show same benefit, clinically unimportant difference
non inferiority - effect not weaker than current

36
Q

RCT advantages

A

comparable groups
valid stat tests
closely matched groups
gold standard

37
Q

RCT disadvantaged

A

cost and time
generalisability issues
recruitment
complex administration