WEEK 4 (CHAPTER 2)

Question 1

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.

Answer 1

Federal Food, Drug, and Cosmetic Act

Question 2

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.

Answer 2

Food and Drug Administration
(Philippines)

Question 3

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.

Answer 3

Republic Act No. 3720 “Foods, Drugs,
Devices and Cosmetics Act” as amended by E.O. 175

Question 4

• 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)

Answer 4

Special Regulations

Question 5

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

Answer 5

Treatment Investigational New Drug

Question 6

a pharmaceutical that remains
commercially undeveloped owing to
limited potential for profitibility

Answer 6

ORPHAN DRUG

Question 7

• (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

Answer 7

Doxorubicin HCL liposome

Question 8

• (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).

Answer 8

Hydroxyurea

Question 9

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

Answer 9

Abbreviated New Drug Application
(ANDA)

Question 10

such as human blood products and vaccines, which require approval of
a biologics licensing application (BLA) for distribution

Answer 10

Biologics

Question 11

• which may require an investigational new animal drug application
  (INADA)
• a new animal drug application (NADA)
• or a supplemental new animal drug application (SNADA)

Answer 11

Animal drugs

Question 12

cumulative body of scientific and
biomedical information generated
worldwide in research institutes, academic
centers, and industry

Answer 12

DRUG DISCOVERY and
DRUG DESIGN

Question 13

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.

Answer 13

Penicillin

Question 14

• 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

Answer 14

Biologic Drugs

Question 15

• plant drug
• chemical reserpine
• a tranquilizer
• hypotensive agent

Answer 15

Rauwolfia serpentina

Question 16

• 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

Answer 16

Periwinkle (Vinca rosea)

Question 17

• prepared from an
  extract of the Pacific
  yew tree (Taxus brevifolia)
• treatment of ovarian cancer.

Answer 17

Paclitaxel (Taxol)

Question 18

• 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.

Answer 18

Semisynthetic Drugs

Question 19

have served humans in their search for drugs in a number of ways

Answer 19

ANIMALS

Question 20

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.

Answer 20

HORMONAL SUBSTANCES

Question 21

• is a rich source of estrogens (urine)
• used as oral contraceptives

Answer 21

PREGNANT MARES

Question 22

________________ 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.

Answer 22

BIOLOGIC PRODUCTS

Question 23

• prepared in cultures of renal monkey tissue

Answer 23

Poliomyelitis Vaccine

Question 24

• in fluids of chick embryo

Answer 24

Mumps and Influenza vaccines

Question 25

* in duck embryo

Answer 25

Rubella (German measles) vaccine

Question 26

* from the skin of bovine calves inoculated with vaccinia virus.

Answer 26

Smallpox vaccine

Question 27

* recombinant DNA * Monoclonal antibody (mAb) production * BOTH influence cells’ ability to produce proteins.

Answer 27

BIOTECHNOLOGY

Question 28

* 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.**

Answer 28

recombinant DNA

Question 29

* 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.

Answer 29

mAb Production

Question 30

The first FDA- approved therapeutic mAb was ____________________, a transplant rejection drug, approved in 1986.

Answer 30

muromonab

Question 31

* 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**

Answer 31

Human Gene Therapy

Question 32

* 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

Answer 32

adenosine deaminase (ADA)

Question 33

* 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.

Answer 33

Goal Drug

Question 34

What are the methods of Drug Discovery?

Answer 34

* research programs of screening * molecular modification * mechanism-based drug design

Question 35

* 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.

Answer 35

Random or untargeted screening

Question 36

* 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

Answer 36

Molecular modification

Question 37

–also known as beta-adrenergic blocking agents, are medications that reduce your blood pressure.

Answer 37

Beta blockers

Question 38

– 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.

Answer 38

H2 blockers

Question 39

* 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

Answer 39

Mechanism-based drug design

Question 40

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**

Answer 40

enalaprilat

Question 41

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.

Answer 41

ranitidine (Zantac)

Question 42

inhibits the central nervous system’s neuronal uptake of serotonin, making the drug useful in the **treatment of depression.**

Answer 42

sertraline (Zoloft)

Question 43

* 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.

Answer 43

LEAD COMPOUND

Question 44

is a term **used to describe a compound that requires metabolic biotransformation** after administration to produce the desired pharmacologically active compound.

Answer 44

Prodrug

Question 45

* which, after oral administration, is bioactivated by hydrolysis to enalaprilat, an ACE inhibitor used in the treatment of hypertension.

Answer 45

enalapril maleate (Vasotec)

Question 46

* is defined by the FDA as an active ingredient that has never before been marketed

Answer 46

New Molecular Entity (NME)

Question 47

what phase of clinical testing has **20-100 patients**, has a length of **several months**, mainly safety, and has a **67%** of successfully completing?

Answer 47

Phase 1

Question 48

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?

Answer 48

Phase 2

Question 49

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?

Answer 49

Phase 3

Question 50

* 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

Answer 50

International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use

Question 51

**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

Answer 51

DRUG STANDARDS

Question 52

in ____ United States Pharmacopeia (USP) was created ➢ to aid in establishing standards for drugs in the United States.

Answer 52

1820

Question 53

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.

Answer 53

Lititz Pharmacopeia

Question 53

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

Answer 53

Lyman Spalding