WEEK 4 (CHAPTER 2) Flashcards
as regulated through Title 21 of the U.S. Code of Federal Regulations
requires a new drug to be approved by the Food and Drug Administration (FDA) before it may be legally introduced in the interstate commerce
- ## the regulations apply to the drug products manufactured domestically and those imported into the United States.
Federal Food, Drug, and Cosmetic Act
formerly the Bureau of Food and Drugs or
(BFAD)
- was created under the Department of
Health to license, monitor, and regulate
the flow of food, drugs, cosmetics, medical
devices, and household hazardous waste
in the Philippines
- main goal is to ensure the health and
safety of food and drugs made available
to the public.
Food and Drug Administration
(Philippines)
AN ACT TO ENSURE THE SAFETY AND
PURITY OF FOODS AND COSMETICS, AND THE PURITY, SAFETY, EFFICACY AND QUALITY OF DRUGS AND DEVICES BEING MADE AVAILABLE TO THE PUBLIC, VESTING THE BUREAU OF FOOD AND DRUGS WITH AUTHORITY TO ADMINISTER AND ENFORCE THE LAWS PERTAINING THRETO, AND FOR
OTHER PURPOSES.
Republic Act No. 3720 “Foods, Drugs,
Devices and Cosmetics Act” as amended by E.O. 175
- product’s approved labeling
- summary of the entire drug development
process - it contains the essential chemistry, pharmacology, toxicology, indications and contraindications for use, adverse effects, formulation composition, dosage, and storage requirements
- as ascertained during the research and
development (R&D)
Special Regulations
a special protocol that may be issued permitting the use of an investigational drug to treat some patients prior to approval of the NDA
if there are no satisfactory approved drugs or treatment
alternatives for a serious medical condition often are sought for orphan drugs, which are targeted for small numbers of patients who have rare conditions or diseases for which there are no satisfactory alternative treatments
Treatment Investigational New Drug
a pharmaceutical that remains
commercially undeveloped owing to
limited potential for profitibility
ORPHAN DRUG
- (Brand name: Doxil®)
- Manufactured by Ortho Biotech
- FDA-approved indication: Treatment of metastatic carcinoma of the ovary in patients with disease that is refractory to both paclitaxel- and platinium-based chemotherapy regimens. Refractory disease is defined as disease that has progressed while on treatment, or within 6 months
Doxorubicin HCL liposome
- (Brand name: Droxia®) - Manufactured by Bristol-Myers Squibb Pharmaceutical
Research Institute - FDA-approved indication: To reduce the frequency of painful crises and to reduce the need for blood transfusions in adult patients with sickle cell anemia with recurrent moderate to severe painful crises (generally at least 3 during the
preceding 12 months).
Hydroxyurea
is used to gain approval to market a
generic equivalent of a product that is
already approved and being marketed by
the pioneer, or the original sponsor, of the
drug
Abbreviated New Drug Application
(ANDA)
such as human blood products and vaccines, which require approval of
a biologics licensing application (BLA) for distribution
Biologics
- which may require an investigational new animal drug application
(INADA) - a new animal drug application (NADA)
- or a supplemental new animal drug application (SNADA)
Animal drugs
cumulative body of scientific and
biomedical information generated
worldwide in research institutes, academic
centers, and industry
DRUG DISCOVERY and
DRUG DESIGN
the antibiotic that became commercially
available in 1944, 15 years after its
discovery in England by Sir Alexander
Fleming and 1 year before the end of the
war.
Penicillin
- Presently it is the fastest growing segment
within the new prescription drug market - advance development which
transforms the treatment of many
diseases - including monoclonal antibodies
- therapeutic proteins
- immunotherapies
- vaccines
Biologic Drugs
- plant drug
- chemical reserpine
- a tranquilizer
- hypotensive agent
Rauwolfia serpentina
- plant drug
- was first scientifically investigated as an
agent useful in the treatment of diabetes mellitus - extracted two potent drugs that
exhibited antitumor capabilities
» vinblastine and vincristine
» used successfully in the treatment of certain types of cancer, including acute
leukemia, Hodgkin disease, lymphocytic lymphoma, and other malignancies
Periwinkle (Vinca rosea)
- prepared from an
extract of the Pacific
yew tree (Taxus brevifolia) - treatment of ovarian cancer.
Paclitaxel (Taxol)
- may have a slightly or vastly different pharmacologic activity from that of the starting substance, depending on the nature and extent of chemical alteration.
- Other plant constituents that in
themselves may be inactive or rather
unimportant therapeutically may be
chemically modified to yield important
drugs with profound pharmacologic
activity. - For example, the various species of
Dioscorea, popularly
known as Mexican yams, are rich in the chemical steroid structure from which cortisone and estrogens are semisynthetically produced.
Semisynthetic Drugs
have served humans in their search for drugs in a number of ways
ANIMALS
such as thyroid extract, insulin,
and pituitary hormone
obtained from the endocrine glands of
cattle, sheep, and swine
lifesaving drugs used daily as replacement therapy in the human
body.
HORMONAL SUBSTANCES
- is a rich source of estrogens (urine)
- used as oral contraceptives
PREGNANT MARES
________________ including serums, antitoxins, and vaccines, has had lifesaving significance ever since the pioneering work of Edward Jenner on the smallpox vaccine in England in 1796.
BIOLOGIC PRODUCTS
- prepared in cultures of renal monkey tissue
Poliomyelitis Vaccine
- in fluids of chick embryo
Mumps and Influenza vaccines
- in duck embryo
Rubella (German measles) vaccine
- from the skin of bovine calves inoculated with vaccinia virus.
Smallpox vaccine
- recombinant DNA
- Monoclonal antibody (mAb) production
- BOTH influence cells’ ability to produce proteins.
BIOTECHNOLOGY
- has the potential to produce almost any protein
- Genetic material can be transplanted from higher species to lowly bacterium (gene splicing)
- Such drug products
- human insulin, human growth hormone, hepatitis B vaccine, epoetin alfa, and interferon
- Human insulin was the first recombinant biopharmaceutical approved in the United States,
in 1982.
recombinant DNA
- the technique exploits the ability of cells with the potential to produce a desired antibody and stimulates an unending stream of pure antibody production
- These antibodies have the capacity to
combat the specific target.
mAb Production
The first FDA- approved therapeutic
mAb was ____________________, a
transplant rejection drug, approved in
1986.
muromonab
- is an experimental technique that uses genes to treat or prevent disease
- used to prevent, treat, cure, diagnose, or
mitigate human diseases caused by genetic disorders - is another promising new technology
Human Gene Therapy
- The first human gene therapy used a condition that results in abnormal functioning of the immune system
- Therapy consisted of the administration of genetically modified cells capable of
producing ADA
adenosine deaminase (ADA)
- would produce the specifically desired effect
– be administered by the most desired route (generally orally)
at minimal dosage and dosing frequency
– have optimal onset and duration of activity
– exhibit no side effects
– and following its desired effect would be eliminated from the
body efficiently, completely, and without residual effect. - It would also be easily produced at low cost, pharmaceutically elegant, and physically and chemically stable in various conditions of use and storage.
- Although not completely attainable in practice, these qualities and features are sought in drug and dosage
form design.
Goal Drug
What are the methods of Drug Discovery?
- research programs of screening
- molecular modification
- mechanism-based drug design
- involves the testing of large numbers of synthetic organic compounds or substances of natural origin for biologic activity
- may be used initially to detect an unknown activity of the test compound or substance or to identify the most promising compounds to be studied by more sophisticated nonrandom or targeted screens to
determine a specific activity.
Random or untargeted screening
- is a chemical alteration of a known andpreviously characterized organic compound (frequently a lead compound) for the purpose of enhancing its usefulness as a drug.
-
enhancing its specificity for a particular body target site, increasing its potency, improving its
rate and extent of absorption, modifying to advantage its time course in the body, reducing its toxicity, or changing its physical or chemical properties (e.g., solubility) to provide desired features
Molecular modification
–also known as beta-adrenergic blocking
agents, are medications that reduce
your blood pressure.
Beta blockers
– reduce the amount of acid produced by the cells in the lining of the stomach
– also called ‘histamine H2-receptor antagonists’ but are commonly called H2 blockers.
H2 blockers
- is molecular modification to design a drug that interferes specifically with the known or suspected biochemical pathway or mechanism of a disease process
- is the interaction of the drug with specific
cell receptors, enzyme systems, or the
metabolic processes of pathogens or
tumor cells, resulting in a blocking,
disruption, or reversal of the disease
process
Mechanism-based drug design
the active metabolite of enalapril (Vasotec), which inhibits the angiotensin-converting enzyme (ACE) that catalyzes the
conversion of angiotensin I to the vasoconstrictor substance angiotensin II. Inhibition of the enzyme results in decreased plasma angiotensin II, leading to decreased vasopressor effects and lower blood pressure
enalaprilat
an inhibitor of histamine at
the histamine H2-receptors, including receptors on the gastric cells.
This inhibits gastric acid secretion, making the drug effective in the treatment of gastric ulcers and other gastrointestinal conditions related to the production of gastric acid.
ranitidine (Zantac)
inhibits the central nervous system’s neuronal uptake of serotonin, making the drug useful in the treatment of depression.
sertraline (Zoloft)
- is a prototype chemical compound that has a fundamental desired biologic or pharmacologic activity
- Although active, may not possess all of the features desired, such as potency, absorbability, solubility, low toxicity, and so forth.
LEAD COMPOUND
is a term used to describe a compound
that requires metabolic biotransformation after administration to produce the desired pharmacologically active compound.
Prodrug
- which, after oral administration, is bioactivated by hydrolysis to enalaprilat, an ACE inhibitor used in the treatment of hypertension.
enalapril maleate (Vasotec)
- is defined by the FDA as an active ingredient that has never before been marketed
New Molecular Entity (NME)
what phase of clinical testing has 20-100 patients, has a length of several months, mainly safety, and has a 67% of successfully completing?
Phase 1
what phase of clinical testing has up to several hundred patients, has a length of several months to 2 years, short term but mainly effective, and has a 45% of successfully completing?
Phase 2
what phase of clinical testing has up to several hundred and several thousand patients, has a length of 1-4 years, safety effectiveness dosage, and has a 5-10% of successfully completing?
Phase 3
- An organization that has worked toward
harmonizing, or bringing together, the
regulatory requirements with the long-
range goal of establishing a uniform set of
standards for drug registration
International Conference on Harmonization of Technical
Requirements for Registration of Pharmaceuticals for Human Use
scientific basis for drugs and drug
products developed
➢ uniform standards to ensure quality
➢ used by those involved in the
production of drugs and
pharmaceutical products
➢ pharmacopeias or formularies
DRUG STANDARDS
in ____ United States Pharmacopeia (USP)
was created
➢ to aid in establishing standards for
drugs in the United States.
1820
first American pharmacopeia
➢ published in 1778 at Lititz, Pennsylvania
➢ use by the Military Hospital of the
United States Army
➢ a 32-page booklet containing
information on 84 internal and 16
external drugs and preparations.
Lititz Pharmacopeia
January 6, 1817
➢ a physician from New York City,
submitted a plan to the Medical
Society of the County of New York for
the creation of a national
pharmacopeia
➢ Father of the United States
Pharmacopeia
➢ He proposed dividing the United
States as then known into four
geographic districts— northern,
middle, southern, and western
Lyman Spalding
