Introduction to Drug Discovery

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  • Created by: LBCW0502
  • Created on: 02-10-19 11:42
Why are drugs important?
Health of the nation, economy and international prestige
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How can drugs enhance the health of the nation?
Decrease morbidity, improve quality of life, reduce hospitalisation, help patients to avoid surgery, reduce mortality (can also benefit economy e.g. fewer loss of working days due to illness, less long-term cost to the NHS)
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Describe features of life expectancy
From Victorian to Edwardian to 1940s to present, increase in life expectancy from 41 M/43 F to 73 M/79 F. Ageing society (likely to live beyond 100, has far reaching consequences and provides new opportunities and challenges)
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How many drugs are there?
Between 1000-1500 individual drug substances approved world-wide for medical use. Most are custom-designed synthetic compounds or discrete natural products. 20-30 compounds approved every year in the UK
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Describe the trend in the number of new drugs per year
General increase then decrease (due to incidents with thalidomide and sulphonamide)
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What are biopharmaceuticals? (1)
Small molecules, 500 in MW e.g. antibodies, cell based therapies (CAR T-cell therapy). Market share of biopharmaceuticals is growing but is only controlled by a few key companies. Biosimilars and bioequivalents
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What are biopharmaceuticals? (2)
Usually difficult to make generic version (e.g. antibody, synthesis and purity). More generic biopharmaceuticals being made
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What are the three main phases of creation of a new drug? (1)
Discovery (therapeutic concept, target selection, target validation, lead finding/lead compound, lead optimisation/candidate drug), development (preclinical development, clinical development, regulatory approval)
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What are the three main phases of creation of a new drug? (2)
Commercialisation (registration, product). Enter process with many possible compounds and then have very few compounds near the end of the process (e.g. toxicity). Risky/time consuming
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Like any other consumer item, drugs are subject to what?
Market forces, legislation, designer syndromes, trends (life-style drugs), hype
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What is the public's perception of drugs? (1)
They are sophisticated hi-tech products but the public perception of value of 'pills' versus latest mobile phone/tablet/computer is poor. Members of public often fail to see why drugs are so expensive
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What is the public's perception of drugs? (2)
E.g. US - payment for healthcare, receive best medicines/treatment, healthcare viewed with high value. UK - NHS, may not get best treatment, healthcare not valued as highly as in the US
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Give an example of 'hype'
Extravagant or intensive publicity/promotion
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Describe features of drug discovery in different therapeutic areas
Drug discovery depends on the therapeutic area. Most research done in oncology. Large drive for new antibiotics (but they won't make a lot of money/use for acute conditions)
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What is a lead molecule?
First type of molecule (prototype) which expresses a pharmacological effect
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What is precision medicine?
Select drug for the patient in order to have the most beneficial effect. Future - precision medicine and pharmacogenomics
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Describe the general approach to drug therapy
Usually a 'one size fits all' approach to drug therapy. A patient may not receive optimal drug/dosing for disease. Drug prescribed may lead to ADRs which can be life threatening. Drug may not work at all wasting time, further distress to patient
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Describe features of Vemurafenib (Zelboraf) (1)
Discovered by Plexxikon. A kinase inhibitor used to treat melanoma (condition which causes metastases, secondary tumours/growths). Vemurafenib targets BRAF V600E mutation
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Describe features of Vemurafenib (Zelboraf) (2)
Requires pharmacogenic assay to determine if the mutation is present in the patient. Select patients using biopsy. Don't waste money/resources, benefits most relevant patients
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Outline the history of drug discovery
In ancient times it was thought that disease resulted from demonic possession or from the wrath of God. Primitive medicine associated with magic/religion. Priesthood entrusted with discovering new treatments
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What is the doctrine of signatures? (1)
Idea that resemblance between an animal part, shape of a plant (or one of its parts) or habits and that of a human organ or disease would effect a cure. Shape association - outer shell walnut (skull diseases), kernel of walnut (brain diseases)
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What is the doctrine of signatures? (2)
Snake root (snake bites), rhino horn (sexual dysfunctions). Environmental association - willow/swamps (arthritis/damp)
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Which drugs originated in the late 1700s/early 1800s?
Morphine, colchicine, quinine, codeine, atropine, cocaine (landmark drug discoveries)
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Where can the list of essential medicines be found?
On the WHO website (important drugs)
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State features of economics (1)
Drug discovery is the most successful industry. Requires very high investment in R&D. 25% of total UK R&D budget (greater than any other industrial sector). Very high cost and high risk industry. (Issue of NHS not able to afford cost of new drugs)
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State features of economics (2)
E.g. use of eculizumab costs £340,200 per patient per year, rise in patients forced to pay for cancer drugs. Generics and biosimilars can help the NHS e.g. rituximab, etanercept
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Successful discovery and development of new drugs depends on what?
Large pharmaceutical companies (and universities may partner with large pharma company for development). Pharmaceutical companies have the resources and infrastructure required but need to recover costs of research, make profit for shareholders
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Give examples of pharmaceutical companies
Johnson & Johnson. Pfizer. Merck & Co.
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What are the three major reasons for high costs of drugs?
Expensive of investment and research. Relatively short period of exclusivity (patents for 20 years). High risk (attrition rate, litigation, e.g. thalidomide)
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Which factors are involved in the expense of investment and research?
Discovery cost, development cost, extensive testing, highly skilled workforce, expensive plant/equipment, cost of - licensing, marketing, distribution, legal fees, compensation, associated with use of animals, develop companion diagnostic
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What is the time period for evaluating new drugs for approval?
10 to 12 years (FDA). Two opposing risks - risk of approving a drug with ADRs vs risk of not approving a life saving drug
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Give examples of relatively recent examples additional studies required for approval
Imaging (animals/humans), stereochemistry, pharmacogenomics/biomarkers, circadian rhythms, ability to degrade in environment, new types of studies required for humans cells (e.g. CAR-T)
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How are pharmacogenetics, biomarkers and metabonomics used?
To predict disease occurrence/re-occurrence, discover safer/effective therapeutic agents, indicate best drug therapy for individual patients, monitor/optimise drug therapy for maximum efficacy/reduce S/E
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Describe features of trastuzumab (Herceptin)
Monoclonal antibody used to treat breast cancer. Her2 Status - diagnostic test to check if the patient in Her2 receptor positive
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What is the role of the regulatory body?
Must protect the public at all costs but without denying life-saving drugs to worthy patients (having the right balance)
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Describe features of patent life
Lasts for 20 years. Development time increases due to increased sophistication of research/requirement for more sophisticated evaluation. Effective Patent Life is reducing. Patents are important for protection (own intellectual property)
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What is the onion approach to patent protection?
Starting with an invention, get a patent, another patent would be required for another idea (number of patents required is increased)
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How does relatively short patent lives lead to pressures on drug companies?
Explosive marketing (dangerous for patients). Competition from 'me too' products where original patent is broken. Companies need to strategise to extend patents (may not benefit patients in NHS)
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Which approach is used to make 'me too' drugs to break the patents of other drug companies?
Bioisostere approach e.g. ranitidine and cimetidine
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Give an example of a chemical approach to increase patent life
Omeprazole modified to form esomeprazole
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What is explosive marketing?
Pressures caused by patenting issues have led to practice of rapid promotion of drugs to get the market saturated as quickly as possible
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Describe the risks of drug development
Attrition, rick of delayed toxicity and legal action, late stage clinical failures, post-marketing failures and litigation (e.g. thalidomide), financial risks
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What are strategic intents?
Companies try to minimise risks by staying in research areas in which they have built up an expertise
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What are orphan drugs?
Because of the massive development costs, drugs for rare diseases are neglected e.g. MS, psoriasis, muscular dystrophy, certain types of rare cancers
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Give an example of an orphan drug
Dinutuximab used in neuroblastoma immunotherapy
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Give examples of lifestyle drugs
Hair loss (minoxidil), erectile dysfunction (sildenafil), female version of sildenafil, (flibanserin), memory loss, improved exam performance, shyness, weight loss
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Give examples of future drugs
Monoclonal antibodies for migraine, immuno-oncology agents, CAR-T cell therapy, RNAi therapies, role of artificial intelligence in drug discovery
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Other cards in this set

Card 2

Front

How can drugs enhance the health of the nation?

Back

Decrease morbidity, improve quality of life, reduce hospitalisation, help patients to avoid surgery, reduce mortality (can also benefit economy e.g. fewer loss of working days due to illness, less long-term cost to the NHS)

Card 3

Front

Describe features of life expectancy

Back

Preview of the front of card 3

Card 4

Front

How many drugs are there?

Back

Preview of the front of card 4

Card 5

Front

Describe the trend in the number of new drugs per year

Back

Preview of the front of card 5
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