drug design 2 Flashcards

Question

What has an effect on outcome of phase 3

Answer 1

Patient compliance - must monitor that ppl actually take drug Hospitalization rates lower in ppl who following the regime and took drug all the time = fully adherent

Answer 2

Help Prevent cardiovascular catastrophe drug With >80% compliance = took meds every day and mortality the same for drug and placebo = not effective

Answer 3

Drug to prevent heart failure and heart attacks, drugs much better than placebo but couldn’t see difference for first years = gradually protects person

Answer 4

2 drugs heal ulcers But down road = ulcer came back more for one of drugs

Answer 5

Drugs can cause sedation, if sedation wore off= said more pain, if sedation continued = less pain Side effects can bias patient reaction, both pos and neg Sedation provides some pain relief, not really analgesic just sedation so react less to pain

Answer 6

Psychology of use r Social factors Need to control pychosocial context

Answer 7

Report of pain relief Iv vs actual Human Medication administered by person = friendly, so effect greater when person there, placebo effect added to effect of drug

Answer 8

Condition ppls response

Answer 9

Not as intense as effect of drug but simailrties between response in brian

Answer 10

Everywhere = Mood, pain, gi, immune, cvs, respirator

Answer 11

Highest in kids = children v repsonsive to enrviemnt, placebo response greater As get older = less but still significant

Answer 12

Pl given placebo report side effects = generates feeling of side effects

Answer 13

Many clincial trials focus on cancer Tumours not homogenous = start as one cancer cell that divides, the more it divides = can accumulate more mutations= sub clones of cancer cells within us our Tumour —> chemo —> apparent remission with low symptoms —> bit if resistance tumour = cells stilll there nad can lead to patient death since hard to kill

Answer 14

Resistant Tumor cells continue uncontrolled growth despite treatment with chemotherapeutic drug Even a slight increase in tumour cell resistance to anti cancer drugs leads to resistance tumours

Answer 15

Should be able to get enough exercise to no get this Measure bone density as age, if any risk = given meds 3 year study = will one injection/year work=. Yes Very successful, works, approved Zoledronic acid

Answer 16

Lumbar spine Injections 1-2 times per years Bone strength increases Continual inclrease in one strength Decided it was not fair to keep ppl on placebo bc ppl getting actual drug had little side effects 21.7% increase at 10 years and 16.5% increase at 10 years Monitor with time, need to treat for life 10 years, not blinded, open label

Answer 17

Review by gov Phase 3 Evaluate data on safety and effigy

Answer 18

All info = characterize exposure database Identify drugs elated adverse events Estimate risk or rate of those adverse events Identify risk factors for those adverse events

Answer 19

Takes 14-17 years and investment up to 4 billon with 95% risk failure If approved = scale up production and get it onto market Preclinical = 3-6 years Clincial = 6-7 years Scale up to manufacture/regulatory review =0.5-2 years Post marketing surveillance = idnefine

Answer 20

Major issue = pathogens is still unclear Do not understand much

Answer 21

Ideally pill bit sometimes need to be Injected

Answer 22

Based on pharmacokinetics and pharmacodynamics that were worked out during clincial trials Ideally = oral, soluble, economical, accessible chemistry, stable =

Answer 23

New generic and bio similar drugs approved After patent expires —> patent ensures they get back the money they spent reasearching drug

Answer 24

Effort for strategies of administration Pills that slowly release content in gi tract

Answer 25

Every pill and vial have same dose concentration,everything os perfect and sterile

Answer 26

Thousands of ppl 1+ year Monitor long term safety and efficacy of a therapy after its approval 70-90% success rate Some are taken off = discover issue or drug withdrawn since something better comes out Want to see drug in therapeutic window where see vey few side effects

Answer 27

Identify end points in advance = know what we want Hypothesis testing Focus on individual studies

Answer 28

Don’t know endpoints in advance - use broad screening and careful observation Exploration and estimation Focus on pools of studies Rare side effective

Answer 29

For an adverse drug interact that occurs once in 1000 cases, one would have to study 3000 cases to have a 95% chance of observing event Neeed to have many ppl to see effect

Answer 30

Most drugs approved by fda with average of 1500 patient exposures Some drugs have rare toxicity profiles - bromefenac hepatotoxicty in 1 in 20 000 patients For drugs with rare toxicity, more than 100,000 patients must be exposed to generation a signal - after drug is marketeted

Answer 31

Keep tack = ask if any any Sid effects

Answer 32

V old and young= kids can get into meds, old ppl = may have risk of interactions, variability = Lowe p450s so metabolize slower = greater chance side effect + Interactions

Answer 33

Affects drug metabolizes enzymes = blocks 3A4 Interactions between drugs and food

Answer 34

Need to take certain precautions Valuable in a limited range of patients Does it indicate drug is too dangerous just that maximum precaution must be taken Way of flagging important safety info Most serious medication warning required by fda Used when meds can cause serious undesirable effects compared to potential benefit from drug Indicates needs for extra precautions

Answer 35

Safety warnings have even increasing Phase 4 v improatnt = somethings only occurs after prolonged time

Answer 36

May be promising for cance therapy = bc now drug is safe and can look at sides effects = can be used for sometime else Mostly happens in paste 4 sometimes phase.3 Mutleiple advanatges = do not hav to redo lab work bc already done

Answer 37

Fast track Condense trials Or for fatal disease = request faster testing

Answer 38

Funding and recognition - give ha made special provisions Not worth time an money For uncommon disease Styludies more often now

Answer 39

Cns infectious disease Oncology

Answer 40

Pdl1 ligand interacts with T cell Cancer = develop ability to inhibit te cell - blocks reocogniotn Either or both = antibodies block inhibition = interrupt recognizing Anti pd1, or anti ctla4 Removes brakes on T cells = tumor reocgnziiotn and detach, can kill cancer cells now = Use antibody to block a built of cancer cell to inhibit T cells = T cell attack cancer Works well

Answer 41

Non small cell lung cancer = used to kill a lot Most common category Drug saved 40% of ppl with this therapy = antibodies block

Answer 42

Skin cancer Combine 3 = antibodies and pd1 blockage = almost everyone survives

Answer 43

Therapy developed by understanding pathoegneiss Looked at what went wrong = btk = enzyme involved in controlling proliferation of B cells

Answer 44

Selective inhibitor btk, blocks tangent for particular type of cancer

Answer 45

Forms specific bond with cysteine 481 in btk Highly potent btk inhibit Orally administers with once daily dosing resulting in 24 hr target inhibition Not cytotoxic effect on T cells or nk cells In clll cells promotes apoptosis and inhibits cll cell migration and adhesion Phase 1/2 data of single agent ibrutinib in 61 relapsed/refractory cll patients demonstrated high frequency durable response

Answer 46

Enzyme blocker superior to chemo Oral administration works better tahan if antibod- do not need it injections, minimal side effects if detected early = everyone survives

Answer 47

Administered as a single agent to patients > or equal to 65 years with treatment naive cll = understanding pathogenesis important Overall survival = better if treated from day 1

Answer 48

Monocoloncal antibodies Murine - Momab - mouse Chimeric - ximab Humanize = Zumab Human = umab

Answer 49

Anti cancer drug linked to monoclonal antibody = Have antibody target something specific on cancer cell and deliver drug = proper effect it far less side effects than Iv admin

Answer 50

Onto monoclonal antibody = deliver to cancer cell Fewer sides effects than a big area of tissue radiated

Answer 51

Antibody against growth factor Herceptin blocks receptor Breast cancer cell = has great increase in growth factors Growth slows = decrease replication rate and will kill tumour cells

Answer 52

Allow rig to be taken into cancer cell and release cytosine agent in cell

Answer 53

See how prostate cancer spread Better diagnosis It radicalize compound on monoclonal antibodies = target prostate cancer cells Actinium

Answer 54

Target and destroy cancer cell

Answer 55

Take blood from patient In lab = extract tumour cells, antigen linked to a cytokine, tumour cells circulate in blood Create dendritic cell - matrices and infused back into patient Triggers = T cell attacks cancer cell

Answer 56

3 ways to block CGRP - know to be part of pathognesis of migraines 3 diff antibodies to blocks it Result of clinical trial = ajovy All 3 antibodies effective and approved = on market

Answer 57

Ways to limit amount of cholesterol floating in blood Receptor internalizes and gets rid of cholesterol

Answer 58

Pcsk9 inhibitors = more cholesterol, taken up by receptors and then broken down in liver,increase breakdown Statins - decrease synthesis

Answer 59

Natriuretic and other vasoactove peptides = lower bp and promote sodium excretion Natural peptides that lower bp Neprilysin drug Block metabolism so increase natural peptide Survival doubled, quality of life improved

Answer 60

Used to kill everyone = now curvale Sofosbuvir - sovaldi blocks rna rep of hep c

Answer 61

Better Against rsv = beyfortus = infant protection against rsv, v good immunization for it, serious in young kids

Answer 62

Avoid injection Want oral drugs mostly Targets in cns - need to understand Parkinson’s and Alzheimer’s, major site of challenge

Answer 63

Intracellualr targets for bio pharmaceutical drugs

Answer 64

Anti viral drugs Prevent of cancer and treat Gene therapy Proteomics - individual therapy Prevention of dementia - not just treat Extend health span and lifespan

Answer 65

If shown to work in humans = tested and often benefits animals= cats, dogs, birds Many benefits extend to other species