Exam 1 - Lecture 1 & 2 Flashcards
(170 cards)
Describe the drug development process
Steps involved in the marketing of drugs are:
- preclinical testing (animal models),
- Clinical testing phases
- I (Safety),
- II (Efficacy- does it work) &
- III (Double-blind studies) [all phases drug metabolism],
- NDA (FDA New Drug Application) and
- Phase IV or post-marketing surveillance.
To be approved for marketing by the Food and Drug Administration (FDA), a drug must be shown by studies to be “safe and effective”, terms that are relative to each particular drug.
Results from post-marketing surveillance have revealed rare but serious adverse reactions to drugs not reported during the investigational stages.
This may result in a “warning” added to the drug literature (e.g., torsade’s de pointes with thioridazine) or even withdrawal of the drug from the market (such as seen with Seldane, Vioxx, Redux, etc.
When a new drug is approved for marketing in the USA its conditions for use are detailed in the package insert the compilation of scientific data submitted by the manufacturer for FDA review and approval “indications.”
However, many drugs, once marketed, often find therapeutic utility for different purposes or in populations other than those described in the package insert.
Such drugs are used for “unlabeled” purposes.
What does phase I clinical testing test?
I (Safety),
Phase I clinical evaluation is the first testing of a new compound in subjects, for the purpose of establishing the tolerance of healthy human subjects at different doses; defining its pharmacological effects at anticipated therapeutic levels; and studying its absorption, distribution, metabolism, and excretion patterns in humans.
What does phase II clinical testing look for?
II (Efficacy- does it work)
Phase II clinical evaluation is controlled studies performed on patients with the target disease or disorder to determine a compound’s potential usefulness and short-term risks.
A relatively small number of patients, usually no more than several hundred subjects, are enrolled in phase II studies.
What does phase III clinical testing look for?
III (Double-blind studies) [all phases drug metabolism]
Phase III trials are controlled and uncontrolled clinical trials of a drug’s safety and efficacy in hospital and outpatient settings.
Phase III studies gather precise information on the drug’s efficacy for specific indications, determine whether the drug produces a broader range of adverse effects than those exhibited in the small study populations of phases I and II studies, and identify the best way of administering and using the drug for the purpose intended.
Woo, Teri Moser; Robinson, Marylou V (2015-08-03). Pharmacotherapeutics For Advanced Practice Nurse Prescribers (Page 39). F.A. Davis Company. Kindle Edition.
What is an IND?
An investigational new drug (IND) application is filed with the FDA prior to human testing.
What is an NDA?
New Drug Application
Regulatory Review: New Drug Application To market a new drug for human use, a manufacturer must have a new drug application (NDA) approved by the FDA. All information about the drug gathered during the drug discovery and development process is assembled in the NDA. During the review period, the FDA may ask the company for additional information about the product or seek clarification of the data contained in the application.
The FDA has 60 days to determine whether the NDA will be filed for review. Once the FDA files the NDA, a team is assigned to review the drug sponsor’s research on the safety and effectiveness of the drug.
Usually, the FDA requests additional information, and the manufacturer needs from 1 to 5 years to complete any additional well-controlled trials necessary to support the claimed indications or prove the drug’s safety.
What is a phase IV clinical trial?
Clinical trials conducted after a drug is marketed (referred to as phase IV studies in the United States) are an important source of information on as-yet undetected adverse outcomes, especially in populations not included in the premarketing trials (e.g., children, the elderly, pregnant women), and the drug’s long-term morbidity and mortality profile.
Regulatory authorities can require companies to conduct phase IV studies as a condition of market approval.
Clinical experience with a new drug may include no more than 1,000 to 2,000 patients. The detection of rare (less than 1 in 1,000) adverse drug reactions is not reliable until hundreds of thousands of patients have taken the drug.
Woo, Teri Moser; Robinson, Marylou V (2015-08-03). Pharmacotherapeutics For Advanced Practice Nurse Prescribers (Page 40). F.A. Davis Company. Kindle Edition.
What is bioavailability?
Bioavailability is the percentage of the dose of the drug administered by any route reaches the systemic circulation.
What is bioequivalence?
Bioequivalence is “equivalent release of the same drug substance from 2 or more drug products or formulations.”
Two different dosage forms of the same drug are considered to be bioequivalent when they produce AUC, Cmax and Tmax values that are neither clinically nor statistically different.
Levothyroxine and certain brands of phenytoin sodium are examples of drugs where the bioequivalence of various brands of the drug are questionable.
Sustained-release dosage forms may not be bioequivalent because of differences in the sustained-release formulation (e.g., niacin).
What is a drug indication?
Drugs condition for use.
What is drug use for unlabeled purpose?
Unlabeled Purpose: the therapeutic utility for different purposes or in populations other than those described in the package insert (discovered after marketing).
What are orphan drugs?
The Orphan Drug Act of 1983 provides incentives for the development of drugs for treatment of diseases affecting fewer than 200,000 patients in the US, or for research using commonly available (nonpatentable) chemicals for treatment of specific diseases.
The incentives (usually tax breaks) are to encourage companies to do research for which they are unlikely to recoup their costs.
Generic vs. Trade Drugs
Must prove equivalence “bioavailability” or equivalence
Controls required for Scheduled I drugs:
- No accepted medical use
- No legal use permitted
- For registered research facilities only
Examples:
Heroin, LSD, mescaline, peyote, marijuana
Controls required for Scheduled II drugs:
- No refills permitted
- Written prescriptions only (no telephone orders)
- Prescription expires in 72 h if not filled
Examples:
Narcotics (morphine, codeine, meperidine, opium, hydromorphone, oxycodone, oxymorphone, methadone)
Stimulants (cocaine, amphetamine, methylphenidate), hydrocodone,
Depressants (pentobarbital, secobarbital)
Controls required for Scheduled III drugs:
- Prescription must be rewritten after 6 mo or 5 refills
- Telephone prescription okay
Examples:
Stimulants (benzphetamine, chlorpheniramine, diethylpropion)
Depressants (butabarbital),
Testosterone
Controls required for Class IV drugs:
- Same as schedule III
- Penalties for illegal possession are different
- Prescription must be rewritten after 6 mo or 5 refills
- Telephone prescription okay
Examples:
Pentazocine, propoxyphene, phentermine, benzodiazepines, meprobamate
Controls required for Class V drugs:
- Same as all prescription drugs
- May be dispensed without a prescription unless regulated by the state.
Example:
Loperamide, diphenoxylate
Describe Schedule I Drugs:
Schedule I: Addictive substances with no approved medical use, no legal use, and only used in medical research facilities (e.g., heroin)
Describe Schedule II Drugs:
Schedule II:
No refills permitted,
No telephone orders
Unless emergency and written order to be provided within 7 days,
Electronic prescribing permitted with certain software
(Woo & Robinson, 2016). (e.g., morphine)
Describe Schedule III Drugs:
Schedule III: Prescription must be rewritten after 6 months or 5 refills, and a telephone or fax prescription is acceptable.
Describe Schedule IV drugs:
Schedule IV: Has same control requirements as schedule III, but penalties for illegal possession are different (e.g., Benzodiazepines)
Describe Schedule V drugs:
Schedule V: Same as all prescription drugs, and may be dispensed without a prescription unless state regulated. Texas law requires a prescription for Schedule V drugs so essentially, in Texas, there is no difference in prescribing or how schedules III, IV, & V are handled. (e.g., Loperamide)
Pharmacology
•The total knowledge of drugs including history, chemistry, source, biochemical & physical effects, pharmacodynamics (what the drug does to the body), pharmacokinetics (what the body does to the drug), therapeutics, site of action, interactions, distinctive features, etc.
