Drug Testing and Development - Vocabulary Flashcards

Vocabulary flashcards covering key terms from the lecture notes on drug testing and development.

Designer drugs

Drugs created by minor modification of an existing chemical structure to produce a new substance with similar effects, often to avoid classification or testing.

MPTP

A neurotoxin that caused rapid Parkinson-like degeneration by destroying dopaminergic neurons; historically used to create animal models of Parkinson's disease.

Nigrostriatal pathway

Dopaminergic tract from the substantia nigra to the striatum (caudate and putamen) involved in movement control; degeneration leads to Parkinsonian symptoms.

SNpc (Substantia nigra pars compacta)

A brain region that contains dopamine-producing neurons crucial for movement; affected in MPTP-induced Parkinsonism.

Disulfiram (Antabuse)

A drug given to deter alcohol use by causing sickness when alcohol is consumed.

Iproniazid

An early monoamine oxidase inhibitor (MAOI) antidepressant originally developed to treat tuberculosis; increased monoamine levels.

Bromides

Historically used sedatives/anticonvulsants; later phased out due to adverse effects and safety concerns.

Lithium

A mood stabilizer used to treat bipolar disorder; effective for mania but has a narrow therapeutic window and potential toxicity.

Bupropion

An antidepressant that also reduces nicotine cravings; atypical mechanism compared with SSRIs.

Thalidomide

A sedative initially marketed for morning sickness; teratogenic causing birth defects; later reintroduced for other uses after regulatory caution.

Ephedrine

A stimulant commonly used in decongestants and weight loss products; safety concerns have led to restrictions.

Over-the-counter (OTC) drugs

Medications available without a prescription; regulated differently from prescription drugs.

Prescription drugs

Medications that require a licensed healthcare provider's authorization due to safety and monitoring needs.

Dietary supplements

Herbal drugs and other supplements marketed to support health; regulated less strictly than conventional drugs.

Preclinical testing

Laboratory and animal studies conducted before human trials to assess safety, toxicity, pharmacokinetics (PK), and pharmacodynamics (PD).

IND (Investigational New Drug)

FDA permission to begin clinical trials in humans after preclinical testing.

Phase 1 clinical trials

Initial human trials in a small group (often healthy volunteers) to assess safety, dosing, PK/PD.

Phase 2 clinical trials

Mid-sized trials assessing efficacy and side effects in patients with the target condition.

Phase 3 clinical trials

Large-scale trials to confirm efficacy and monitor adverse reactions, often thousands of participants.

NDA (New Drug Application)

FDA submission seeking formal approval to market a drug after successful clinical trials.

Phase 0

Exploratory microdosing studies to assess target engagement and PK in a very small number of participants.

Postmarketing surveillance

Phase IV monitoring of a drug after approval to identify rare or long-term adverse effects.

MedWatch

FDA safety reporting system for adverse events and product problems.

Orphan Drug Act (1983)

US legislation providing incentives (e.g., tax credits, market exclusivity) to develop drugs for rare diseases.

Orphan drug

A drug developed to treat a rare disease, typically receiving incentives to encourage development.

Accelerated approval

FDA pathway to speed approval for serious conditions using surrogate endpoints, with confirmatory trials required later.

BPCA (Best Pharmaceuticals for Children Act)

US act encouraging pediatric testing of drugs by offering incentives and extensions for studies in children.

PREA (Pediatric Research Equity Act)

US law requiring drug sponsors to study the safety and efficacy of drugs in pediatric populations.

Off-label use

Prescribing a drug for an indication, dose, or population not approved by the FDA.

Pediatric drug testing

Clinical testing focused on safety and dosing in children, addressing historical underrepresentation.

FDA Modernization Act 2.0

2022 Act proposing to reduce mandatory animal testing for new drugs and accelerate research with alternatives.

CDER (Center for Drug Evaluation and Research)

FDA center responsible for evaluating and approving new drugs and ensuring safety.

ClinicalTrials.gov

Public registry of clinical trials; required registration and reporting of results for many trials.

Designer drugs

Drugs created by minor modification of an existing chemical structure to produce a new substance with similar effects, often to avoid classification or testing.

MPTP

A neurotoxin that caused rapid Parkinson-like degeneration by destroying dopaminergic neurons; historically used to create animal models of Parkinson's disease.

Nigrostriatal pathway

Dopaminergic tract from the substantia nigra to the striatum (caudate and putamen) involved in movement control; degeneration leads to Parkinsonian symptoms.

SNpc (Substantia nigra pars compacta)

A brain region that contains dopamine-producing neurons crucial for movement; affected in MPTP-induced Parkinsonism.

Disulfiram (Antabuse)

A drug given to deter alcohol use by causing sickness when alcohol is consumed.

Iproniazid

An early monoamine oxidase inhibitor (MAOI) antidepressant originally developed to treat tuberculosis; increased monoamine levels.

Bromides

Historically used sedatives/anticonvulsants; later phased out due to adverse effects and safety concerns.

Lithium

A mood stabilizer used to treat bipolar disorder; effective for mania but has a narrow therapeutic window and potential toxicity.

Bupropion

An antidepressant that also reduces nicotine cravings; atypical mechanism compared with SSRIs.

Thalidomide

A sedative initially marketed for morning sickness; teratogenic causing birth defects; later reintroduced for other uses after regulatory caution.

Ephedrine

A stimulant commonly used in decongestants and weight loss products; safety concerns have led to restrictions.

Over-the-counter (OTC) drugs

Medications available without a prescription; regulated differently from prescription drugs.

Prescription drugs

Medications that require a licensed healthcare provider's authorization due to safety and monitoring needs.

Dietary supplements

Herbal drugs and other supplements marketed to support health; regulated less strictly than conventional drugs.

Preclinical testing

Laboratory and animal studies conducted before human trials to assess safety, toxicity, pharmacokinetics (PK), and pharmacodynamics (PD).

IND (Investigational New Drug)

FDA permission to begin clinical trials in humans after preclinical testing.

Phase 1 clinical trials

Initial human trials in a small group (often healthy volunteers) to assess safety, dosing, PK/PD.

Phase 2 clinical trials

Mid-sized trials assessing efficacy and side effects in patients with the target condition.

Phase 3 clinical trials

Large-scale trials to confirm efficacy and monitor adverse reactions, often thousands of participants.

NDA (New Drug Application)

FDA submission seeking formal approval to market a drug after successful clinical trials.

Phase 0

Exploratory microdosing studies to assess target engagement and PK in a very small number of participants.

Postmarketing surveillance

Phase IV monitoring of a drug after approval to identify rare or long-term adverse effects.

MedWatch

FDA safety reporting system for adverse events and product problems.

Orphan Drug Act (1983)

US legislation providing incentives (e.g., tax credits, market exclusivity) to develop drugs for rare diseases.

Orphan drug

A drug developed to treat a rare disease, typically receiving incentives to encourage development.

Accelerated approval

FDA pathway to speed approval for serious conditions using surrogate endpoints, with confirmatory trials required later.

BPCA (Best Pharmaceuticals for Children Act)

US act encouraging pediatric testing of drugs by offering incentives and extensions for studies in children.

PREA (Pediatric Research Equity Act)

US law requiring drug sponsors to study the safety and efficacy of drugs in pediatric populations.

Off-label use

Prescribing a drug for an indication, dose, or population not approved by the FDA.

Pediatric drug testing

Clinical testing focused on safety and dosing in children, addressing historical underrepresentation.

FDA Modernization Act 2.0

2022 Act proposing to reduce mandatory animal testing for new drugs and accelerate research with alternatives.

CDER (Center for Drug Evaluation and Research)

FDA center responsible for evaluating and approving new drugs and ensuring safety.

ClinicalTrials.gov

Public registry of clinical trials; required registration and reporting of results for many trials.

Describe the primary difference in regulatory approval between prescription drugs and dietary supplements.

Prescription drugs undergo rigorous FDA testing for safety and efficacy before approval, while dietary supplements are regulated more as food, with manufacturers responsible for safety claims before marketing, and the FDA acting mostly post-market.

Why are 'pharmacokinetics' (PK) and 'pharmacodynamics' (PD) studied in preclinical and Phase 1 trials?

PK studies examine how the body affects a drug (absorption, distribution, metabolism, excretion), while PD studies look at how the drug affects the body (mechanisms and effects). Both are crucial for determining appropriate human dosing, safety, and efficacy before broader trials.

Therapeutic Window/Index

The range of drug dosages that can treat disease effectively without causing toxic side effects; a narrow therapeutic window indicates a drug with a small difference between effective and toxic doses, requiring careful monitoring (e.g., Lithium).

Agonist

A drug that binds to a receptor and activates it, producing a pharmacological response similar to an endogenous ligand.

Antagonist

A drug that binds to a receptor but does not activate it, thereby blocking the action of an agonist or endogenous ligand and preventing a response.

Placebo effect

A psychological or physiological response to a 'fake' treatment, often observed in clinical trials, highlighting the importance of blinded, controlled studies to distinguish drug effects from patient expectation.