INTRODUCTION TO DRUGS/PHARMACY:
Trial/error -> drug therapy, in history evil spirits thought to cause illness (drugs not enough: gods, ceremonies, exorcism, healing intent); successes: coincidence/drug effect inconsequential/placebo effect; failures: inactive agents/under/overdosing/poisoning; research began in 1700s; USP in 1820 and later NF for drug stds/ingredients/dosage forms, morbidity: drug-induced disease; mortality: drug-induced death Food and Drug Act 1906: strength/purity/quality, Sherley: no false claims, declare misbranded Food drug cosmetic act: safe administration after sulfanilamide elixir toxicity from diethylene glycol solvent; new drugs tested for safety, marketing approval via NDA, direction Iabels, FDA unannounced inspections, preclinical pharmacology/toxicology DH amendments: OTC vs Rx, no refills w/o rx, KH amendments: spurred by thalidomide tragedy: morning sickness, phocomelia around the world; drugs must be efficacious by FDA, 1st GMP regulations/NDA Drug abuse prevention act: ffi schedules based on abuse potential Drug listing act: distributors register FDA, NDC 10-11 digits, manufacturer/drug/package FDA pregnancy categories: ABCDX for risk/benefit animal studies, black box Drug price competition: abbreviated NDA, less time/money for generic Rx drug marketing act: Dingell bill for sales/importing/purchasing Dietary supplement act: "not intended to cure/prevent disease", structure/fxn okay, truthful/not misleading FDA modernization act: streamline FDA, labeling, fast approval, recalls: class I serious/death, class ll reversible, class lll no consequence Code of ethics: AAPS: conflicts, misconduct, professionalism, ownership, discrimination
DRUG REGULATION/CONTROL:
Organic plant acids -> antipyrine made in test tube -> rapid advances (Fleming
penicillin, Watson/Crick DNA); morphine opium, quinine bark, digitalis foxglove, belladonna nightshade, problems w/purity/sufficiency/potency; early formulation studies: solubility, partition coeff, dissolution rate, physical form, stability (before animal preclinical); goal drug: oral compound w/desired effect, minimal dose/freq, eliminated efficiently w/o side effects; lead compound: closest to goal drug, modified to get closer; pharmacology: mxm/activity, metabolism: ADME; center for drug and evaluation research: benefit/risk, available quickly, clear stds, high priority; investigational NDA: before human admin, assigned to CDER official preclinical: animal testing/synthesis/characterization phase I: for safety, 20-100 pts, <1y, toxicology, metabolism, pharmacology, clinical trial material: extemporaneous quick/small/easy but unpleasant taste/compliance issue/dosing inconvenience; application: plan, structure, animal results, manufacturing info phase II: for effectiveness, 100-300 pts with disease, capsules/tablets, same as phase I except when strength/scale not feasible, large dose range, issues: high (dissolution/processability), low (uniformity/stability)
phase III: long-term safety/efficacy, 1000-3000 pts, years, controlled clinical research studies, at least 3 primary batches, stability 12mo 2ffi'c, same formulation/processing recommended; all 3: may take up to 1ffi years total, high-priority faster usual adult dose: starting dose; usual dosage range: safe range; dosage regimen: schedule; maintenance doses: clinical relevant blood levels; prophylactic dose: prevent pts from getting disease; therapeutic dose: once disease contracted; minimum effective conc: minimum required for effect; minimum toxic conc: above this level -> toxicity; median effective dose: desired intensity effect in ffio% tested; desired levels above MEC/below MTC
GMCP:
batch/batchwise control: quantity from one order during same cycle / test to prove process has accomplished its task; certification: authority says qualification acceptable; compliance: inspect if regulations/standards/practices followed; component: drug manufacture ingredients including those not in product; drug product/active ingredient/inactive ingredient: active drug and inactive ingredients/component for pharmacologic activity