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20 Cards in this Set
- Front
- Back
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Lead compound discovery
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a. Assays can be developed to screen for molecules that activate or inhibit a molecular target
b. Can be discovered in a variety of screening assays→ Libraries, assays |
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Libraries
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a. Large, diverse compound libraries are screened through high thoughput assays
b. Natural sources, extracts of metabolites from microorganisms or plants c. Chemical libraries from major pharmaceutical companies have been used for screening d. Combinatorial chemical libraries using degenerate synthetic methods |
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Assays
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a. Can be very specific→ screening for compounds that bind to the 5-HT2C receptor in search for a lead obesity drug compound using a competitive binding assay
b. High throughput screens can be functional, such as screening for compounds that kill cancer cells using an in vitro cell death assay |
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Drug targets
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a. Typically receptors or enzymes
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Medicinal chemistry
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a. Derivatives of a lead compound are synthesized to search for a compound with the required properties of a drug
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Affinity
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a. Lower or higher activity or more selectivity
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Stability
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a. Stability in vivo and bioavailability
b. Adsorption, distribution, metabolism, excretion (ADME) |
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Toxicity
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a. Toxicity and adverse effects
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Pre-clincial testing: in vitro
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a. Pharmacological profile of the compound can be determined using in vitro assays
b. The goal of these experiments is to determine the potency and selectivity of the compound c. Cell culture assays d. Tissue slices grown in culture |
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IACUC
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a. Institutional animal care and use committee
b. Approves protocols for care and use of vertebrate animals in research c. Animal care d. Minimize stress and pain e. Minimize animal numbers, but ensure that experiments are adequately powered |
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Animal studies
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a. Experiments in models are used to address→
b. → Efficacy of a drug candidate and other issues c. → Pharmacokinetic properties d. → Adverse effects and toxicity |
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Investigational New Drug Application
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i. If pre-clinical testing in vitro and in animals justifies, IND is filed
ii. Includes plan for human testing iii. FDA review determines reasonable safety in human testing iv. Approval of IRB is required→ approves clinical trail protocols |
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Phase 1 studies
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i. Emphasis on safety
ii. Pharmacokinetics iii. Small patient groups (20-80 volunteers) iv. Address dosage, metabolism, and excretion v. Use ascending dosage protocol→ maximum tolerated dose |
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Phase 2 studies
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i. Emphasis on effectiveness and safety
ii. Aim to obtain data on whether the drug works in patients who have certain disease or condition iii. Few dozen to 300 patients iv. At end of phase-2, FDA and sponsors need to work out an agreement on how the large-scale Phase-3 trials should be done |
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Phase 3 studies
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i. Larger trials powered to assess safety and effectiveness
ii. Broader scope→ hundreds to 3,000 iii. Confidence in any conclusions from the data correspondingly increases with subject number |
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New Drug Application
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i. Formal submission to FDA to consider approving a new drug for marketing in the US
ii. Includes all animal and human data and analyses of the data, as well as info about how drug behaves in body and how it is manufactured iii. FDA has 60 days to decide whether to review the NDA |
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Phase 4 studies
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i. Post-marketing studies are imposed upon a pharmaceutical firm as a condition for drug approval
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REMS
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e. Requiring risk evaluation and mitigation strategies programs
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Orphan drug status
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a. Developed specifically to treat a rare medical condition (orphan disease)
b. Seven-year market exclusivity c. Tax credits on development costs d. Fast-track approvals of drugs indicated for rare diseases |
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New Drugs with abuse potential and the DEA
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Schedules 1-5 based on probability of abuse
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