PHCHEM212R: DOSAGE  AI + etc.

 It provides
CHAPTER 1: Introduction to Drugs and Pharmacy  Protect

What is Drug? Why are pharmacists vital in the industry?

- A Drug is defined as an agent intended for use in the - accessibility/ patient counseling
diagnosis, mitigation, treatment, cure, or prevention of - Advisor on drugs
disease in humans or in other animals (Food, Drug, and - they can dispense medicine
Cosmetics Act, 1938).
- the component which produce pharmacologic activity
HERITAGE OF PHARMACY
DRUG MEDICINE  The primary methods of removing spirits were
Harmful through:
Effect (+)
(+) (-)  The use of spiritual incantations
Dose Fixed dose  Application of noisome materials
Dosage form AI AI + Excipients  Administrations of specific herbs or plant
materials
Important notes: Not all drugs are medicine
The First Apothecary
Excipients - no therapeutic effect  Factors needed
- anything other than the drug substance in the dosage 1. Compassion of a God
form. 2. Observance of ceremonies
 Should be harmeless 3. Absence of evil spirit
 Does not exceed the minimum request for the 4. Hiding intent of disperse
intended effect
 Could not impair the therapeutic effect
 Does note interfere the assays Early Drugs
 Eberes Papyrus - most famous surviving artifacts
Classifications  George Ebers - a German Egyptologist, who
1) Based on stability (e.g. preservatives) discovered it in the tomb of a mummy and partly
2) Based on In-vivo Absorption - usually added to translated it during the last half of the 19th century.
increase absorption (increase absorption of drugs)
3) Based on Manufacturing Abilities (diluent, Introduction of the Scientific Viewpoint
emulsifiers, plasticizer, solubilizer)  Hippocrates - Father of Medicine
4) Based on Acceptability (sweetening agent, flavorants)  Dioscorides
- enhance the taste colorants  Claudius Galen - Father of Pharmaceutical compound
 Aureolus Theophrastus - Paracelsus
Drug Product
- finished dosage form that contains the active Hippocrates
ingredients, generally, but NOT necessarily in association  A greek physician
with 1 or more other ingredients  Credited with the introduction of scientific pharmacy
- or the dosage form in the final immediate packaging and medicine
intended for marketing.  He rationalized medicine, systematized medical
- ex. Paracetamol + Diluents + Binded + Tablet knowledge, and put the practice of medicine on a
high ethical plane.
Why not the plain active ingredient?  His works included the descriptions of hundreds of
1. Chemically unstable/ degrade easily drugs, and it was during this period that the term
2. After tastes or bitterness of the drug / unacceptable pharmakon came to mean a purifying remedy for
taste good only, transcending the previous connotation of
3. Dosage accuracy a charm or drug for good or for evil purposes.
4. High contamination
5. Low efficacy Dioscorides
6. Local irritation  A Greek physician and botanist
 Was the first to deal with botany as n applied science
Drug Substance of pharmacy.
- the unformulated drug substance that may subsequently  De Materia Medica - is conidered a milestone in the
be formulated with excipients to produce the dosage development of pharmaceutical botany and in the
form. study of naturally occurring medicinal materials.
- Dosage Form
 Pharmacognosy/ Natural products of chemistry - a
term formed from to Greek words, pharmakon, drug,
and gnosis, knowledge.
 Some of the drugs Dioscorides described, including
opium, ergot, and hyoscyamus
Claudius Galen
 A Greek pharmacist-physician
 Who attained Roman citizenship, aimed to create a
perfect system of physiology, pathology, and
treatment
 “Galenic Pharmacy”
 Galens’s Cerate - cold cream
Aureolus Theophrastus Bombastus von Hohenheim
 A Swiss physician and chemist
 Paracelsus
 He influenced the transformation of pharmacy from a
profession based primarily on botanical science to
one based on chemical science.
Early Research
 Swede Karl Willheim Scheele (1742-1786)
 The most famous of all pharmacists because of his
scientific genius and dramatic discoveries
 Among his discoveries were the chemical lactic acid,
citric acid, oxalic acid, tartaric acid, and arsenic acid.
 He identified glycerin, invented new methods of
preparing calomel and benzoic acid, and discovered
oxygen a year before Priestley.
 Friedrich Serturner (1783-1841)
 German pharmacist
 Isolated morphine from opium
 Joseph Caventou (1795-1877) and Joseph Pelletier
(1788-1842)
 Isolated quinine and cinchonine from cinchona and
strychnine and brucine from nux vomica.
 Pelletier and Pierre Robiquet (1780-1840)
 Isolated caffeine
 Pierre Robiquet
 Independently separated codiene from opium
 Comtemporary examples of drugs isolated from a
natural source include:
 Paclitaxel (Taxol) - an agent with antitumor activity
derived from the Pacific yew tree (Taxcus baccata)
and employed the treatment of metastatic carcinoma
of the ovary;
 Vincaleukoblastine - another antineoplastic drug,
from Vinca rosea;
 Digoxin - a cardiac glycoside, from Digitalis lanata.
_______________________________________________
DRUG STANDARDS
Why is USP in the drug standard?
 Culture
 Geographic heritage
 Language
 Availability
The United States Pharmacopeia and the National
Formulary
 the term pharmacopeia comes from the Greek
pharmakon, meaning drug, and poiein, meaning
make, and the combination indicates any recipe or
formula or other standards required to make or
prepare a drug.
 Drug standards were first provided on a national
basis in 1820, when the first USP was published.
 Lititz Pharmacopeia - The first American
pharmacopeia, published in 1778 at Lititz
Pennsylvania, for use by the Military Hospital of the
United States Army.
 In 1808, the Massachussets Medical Society
published a 272-page pharmacopeia containing
information or monographs on 536 drugs and
pharmaceutical preparations.
 January 1, 1820, the first United States
Pharmacopeial Convention, in Washingtion, DC.
 January 6, 1817, Lyman Spalding, a physician from
New York City, submitted a plan to the Medical
Society of the Country of New York for the creation of
a national pharmacopeia. His being recognized as the
Father of the USP.
 December 15, 1820, The first USP was published, in
English and Latin, then the international language of
medicine, to render the book more intelligible to
physicians and pharmacists of any nationality
 Before 1940, the NF, like the USP, was revised every
10 years. After the date, new editions appeared every
5 years, with supplements issued periodically as
necessary.
 In 1975, the United States Pharmacopeial
Convention, Inc., purchased the NF, unifying the
official compendia and providing the mechanism for a
single national compendium.
 Today, the United States PharmacopeIa-National
Formulary (USP/NF) is continuously revisedrevisions
are available annually in hard copy and as online
editions, including twice-yearly supplements and
update notices on the USP web site.
 Monographs for drug substances, dietary
supplements, dosage forms, and compounded
preparations are contained in the USP sections of the
combined compendium whereas monographs for
pharmaceutical excipients are contained in the NF
section.
Other Pharmacopeias
 In addition to the USP and the NF, other references
to drug standards, such as the Homeopathic
Pharmacopeia of the United States (HPUS) and the
 Pharmacopeia International, or International
Pharmacopeia (IP), provide additional guidelines for
drug quality required by certain practitioners and
agencies.
 HPUS is used by pharmacists and homeopathists as
well as by law enforcement agencies that must
ensure the quality of homeopathic drugs.
 The term homeopathy was coined by Samuel
Hannemann (1755-1843) from the Greek homoios,
meaning similar, and pathos, meaning disease.
 Embodied in the homeopathic approach are:
a) The testing of drug on healthy persons to find
the drug’s effect so that it may be employed
against the same symptoms manifesting a
disease in an ill person;
b) The use of only minute doses of drug in therapy,
employed in dilutions expressed as “1x” (a 1:10
dilution), “2x” (a 1:100 dilution), and so on;
c) The administration of not more than one drug at
a time; and
d) The treatment of entire symptom complex of
the patient, not just one symptom (4-6).
 Over the years, a number of countries have published
their own pharmacopeias, including the United
Kingdom, France, Italy, Japan, India, Mexico, Norway,
and the People’s Republic of China. These
pharmacopeias and the European Pharmacopeia (EP
or Ph Eur) are used within their legal juridictions and
by multinational pharmaceutical companies that
develop and market products internationally.
Standards Set Forth in FDA-Approved Neew Drug
Applications
 In the US, in addition to the official compendia, some
initial drug and drug product standards and assay
methods are established as set forth in new drug
applications approved by the FDA.
 The manufacturer must rigidly adhere to these initial
stnadards to maintain product quality and continued
FDA approval for marketing.
 Ultimately, these or subsequently developed
standards are adopted as new monographs by the
USP/NR.
International Organization for Standardization
 The International Organization for Standardization
(ISO) is an international consortium of representative
bodies constituted to develop and promote uniform
or harmonized international standards.
 Among the various ISO standards used in the
pharmaceutical industry are those in the series ISO
9000 to ISO 9004.
DRUG REGULATION AND CONTROL
 The first federal law in the United States designed to
regulate drug products manufactured domestically
was the Food and Drug Act of 1906.
 The law required drugs marketed interstate to
comply with their claimed standards for strength,
purity, and quality.
_______________________________________________
___
THE FEDERAL FOOD, DRUG, AND COSMETIC ACT OF 1938
 The need for additional drug standards was tragically
demonstrated in 1938.
 The then-new wonder drug sulfanilamide, which was
not soluble in most common pharmaceutical solvents
of the day, was prepared an distributed by an
otherwise reputable manufacturer as an elixir using
as the solvent diethylene glycol, a highly toxic agent
used in antifreeze solutions.
 Before the product could be removed from the
market, more than 100 persons died of diethylene
glycol poisoning.
 Congress responded with the passage of the Federal
Food, Drug, and Cosmetic Act of 1938 and the
creation of the FDA to administer and enforce it.
 The 1938 Act prohibits the distribution and use of any
new drug or drug product without the prior filing of a
New Drug Application (NDA) and approval of the FDA.
Durnham-Humphrey Amendment of 1952
 The Durham-Humphrey Amendment of the Federal
Food Drug and Cosmetic Act established a legal
distinction between prescription and over-the-
counter (OTC) or non-prescription drugs.
 Prescription drugs must bear thee symbol “Rx Only”
or the legend “Caution: Federal Law Prohibit
Dispensing Without Prescription.”
 New drug substances are limited to prescription-only
dispensing.
Kefauver-Harris Amendments of 1962
 A tragedy in 1960 led to the passage of the Kefauver-
Harris Amendments to the Federal Food Drug and
Cosmetic Act of 1938.
 A new synthetic drug, thalinodomide (barbiturates),
recommended as sedatives and tranquilizer, was
being sold OTC in Europe. It was a drug of special
interest because of its apparent lack of toxicity even
at extreme dosage levels.
 Thalinodomide given to women during pregnancy
produced birth defects, most notably phocomelia, an
arrested development of the limbs of the affected
newborn.\
 Interestingly, WHO now considers thalinodomide to
be the standard treatment for the fever and painful
skin lesions associated with erythema nodosum
leprosum (ENL) in patients with leprosy and the FDA
has approved its use for this purpose.
Comprehensive Drug Abuse Prevention and Control Act
of 1970
 Now referred to as the Controlled Substances Act
(CSA) served to consolidate and codify control
authority over drug of abuse into a single statute.
 Under its provisions, the Drug Abuse Control  Codiene
Amendments of 1965, the Harrison Narcotic Act of  Hydrocodone
1914, and other related laws governing stimulants,  Oxacodone
depresssants, narcotics, and halucinogens were  Ketamine
repealed and replaced by regulatory framework now III
 Butabarbital
administered by the Drug Enforcement  Dronabinol
Administration (DEA) in the DOJ.  Phendimetrazine
 Established five “schedules” for the classification and  Buprenorphine
control of drug substances that are subjected to
 Difenoxin
abuse. These schedules provide for decreasing levels
 Diazepam
of control, from schedule I to V.
 Oxazepam
 The drugs in the five schedules may be described as
 Zolpidem
follows:
 Alprazdam
 Schedule I: Drugs with no accepted medical use, or IV
 Tramadol
other substances with a high potential for abuse. Any
 Clonazepam
nonmedical substance that is being abused can be
 Sentraline
replaced in this category.
 Lorazepam
 Schedule II: Drugs with accepted medical uses and a
 Enflurane
high potential for abuse that if abused may lead to
severe psychologic or physical dependence.  Dihydrocodeine
 Schedule III: Drugs with accepted medical uses and a  Diphenoxylate
potential for abuse less than those listed in schedules  Pregabilin
I and II that if abused may lead to moderate  Locosamide
V
psychologic or physical dependence.  Brompheniramine/
 Schedule IV: Drugs with accepted medical uses and codeine
low potential for abuse relative to those in schedule  Atropine/
III that if abused may lead to limited physical diphenoxylate
dependence relative to drugs in schedule III.
 Schedule V: Drugs with accepted medical uses and
low potential for abuse relative to those in schedule FDA Pregnancy and Lactation Labeling
IV that if abused may lead to physical dependence or  The FDA has amended its regulations governing the
psychologic dependence relative to drugs in schedule content and format of the “Pregnancy,” “Labor and
IV. delivery,” and “Nursing mothers” subsections of the
“use in Specific Populations” section of the labeling
SCHEDULES AGENTS for human prescription drug and biological products.
 Heroin
Pregnant Animals
 Lysergic acid
women
 Diethylamide (LSD)
I  Mescaline Category A Safe
 Peyote Category B Safe Unsafe Paracetamol
 Methaqualone No studies Safe Amoxicillin
 Marijuana Category C No studies Unsafe Rifampicin
 Morhpine Theophyllins
 Cocaine Category D Unsafe Thalidomide
 Methamphetamine Isotretinoin
 Amorbarbital Category Unsafe C/I -
 Fentanyl E/X contraindication
 Nabilone
II
 Aspirin
 Pethidine Black Box Warning
 Oxycodone  A black box warning in prescription drug labeling is
 Hydrocodone used to call attention to one of the following
 Dextroamphetamine situations:
 Dexmethylphenidate a) There is an adverse reaction so serious in
proportion to the potential benefit that it be
considered in assessing the risks and benefits of
using the drug,
b) The risk of a serious adverse reaction can be
prevented or reduced in severity by careful use
 of the drug (e.g. patient selection, special
monitoring, certain concomitant therapy), or
c) The FDA has approved the drug with restriction
to prescribing/dispensing tribution to ensure its
safe use.

Drug Listing Act of 1972

 Was enacted to provide the FDA with the legistative
authority to compile a list of marketed drugs to assist
in the enforcement of federal laws requiring that
drugs be safe and effective and not adulterated or
misbranded.
 Each firm that manufactures or repackages drugs for
ultimate sale or distribution to patients or consumers
must register with FDA and submit appropriate
information for listing.
 Exempt from the registration and listing
requirements are hospitals, clinics, and the various
health practitioners who compound pharmaceutical
preparations for use in their respective institutions
and practices.

Important notes:
> adulterated - mixed w/ something that will lower the
quality of the product
> misbranded - (e.g. softdrinks) the label and content are
not match. Not sugar but another sweetening agent is
used
- another example is counterfeit product

Drug Price Competition and Patent Term Restoration Act

of 1984
 Changes to speed FDA approval genetic drugs and the
extension of patient life for innovative new drugs
were the major components of the Drug Price
Competition and Patent Restoration Act of 1984.
 Under the provisions of the legislation, applications
for generic copies of an originally approved new drug
can be filed through an abbreviated new drug
application (ANDA), and the extensive animal and
human studies of an NDA are not required.
 This reduces considerably the time and expense of
bringing a generic version of the drug to market.