Drug del

Chapter 1
Drug-an agent intended for use in the
diagnosis, mitigation, treatment, cure or
prevention of disease in humans
Mydriatic drugs-dilate the pupil of the eye
Miotics-constrict or diminish pupillary size
Emetics-induce vomiting
Antiemetic drugs-prevent vomiting
Diuretic drugs-increases the flow of urine
Expectorant drugs- increases the respiratory
tract fluid
Cathartics/ laxatives- evacuate the bowel
Basic pharmacology- nature and mechanism
of action of the drug on the biologic system
the only difference between a drug and a
poison is the dose
The pharmacist is entrusted with the legal
responsibility for the procurement, storage,
control, and distribution of effective
pharmaceutical products and for the
compounding and filling of the prescription
orders.
It was in the preparation of medicinal
materials that the art of apothecary
originated.
Pharmakon- where the word Pharmacy was
derived
- in Homeric epics, it connotes a
charm or a dug that can be
used for good or for evil
Placebo therapy- a substance or procedure
that is objectively without specific activity for
the condition being treated
Sumerian clay tablet- form 3rd millennium BC
-worlds oldest
prescription
Ebers papyrus- scroll 60ft. long and a foot
wide dating to 16th century BC
- now preserved at University of
Leipzig
- named after the German
Egyptologist Georg Ebers
discovered it in the tomb of a
mummy and partly translated it
during the last half of the 19th
century
- dominated by drug formulas, w/
more than 800 formulas or
prescriptions being described
and more than 700 drugs
mentioned
Hippocrates (460-377 BC)
- a greek physician
- credited with the introduction of
pharmacy and medicine
- rationalized medicine and put the
practice of medicine into a high ethical plane
- his works included description of
hundreds of drugs
-during this period the term
pharmakon came to mean a purifying
remedy only
-the Father of Medicine
Dioscorides (1st century AD)
- a greek physician and botanist

first to deal with botany as an

applied science of pharmacy
- his work De Materia Medica was
considered a milestone in the
development of pharmaceutical
botany and the study of
naturally occurring medicinal
materials. This area of study is
also know as natural product
chemistry or Pharmacognosy (in
greek Pharmakon, drug and
Gnosis, knowledge) (advanced
botany and drugs)
Claudius Galen (ca. 130-200 AD)
- greek pharmacist-physician
(attained roman citizenship)
- aimed to create a perfect
system of physiology, pathology
and treatment
- one of the prolific authors (500
treaties on medicine, 250 others
on philosophy, law and
grammar)
- his med writings include
description of numerous drugs
of natural origin with a
profusion of drug formulas and
methods of compounding
- he originated prescription of
vegetables drugs by mixing or
melting or melting of the
individual ingredients that the
field of pharmaceutical
preparation was commonly
referred to as Galenic
pharmacy (compounding)
- most famous of his formulas is
the cold cream called Galens
Cerate
*apothecary? Pharmacy
Emperor Frederick II of Germany
- pharmacy was officially
separated from medicine for the
first time (1240 AD) when he
regulated the practice f
pharmacy within his kingdom
called Two Sicilies.
Paracelsus (1493-1541)
- Aureolus Theophrastus
Bombastus von Hohenheim
- Swiss physician and chemist
- Calls himself Paracelsus
- Influenced the transformation of
pharmacy from a profession
based primarily on botanical
science to one based on
chemical science
- He specified and expanded
pharmacy
Swede Karl Wilhelm Scheele (1742-1786)
- perhaps the most famous of all
pharmacists
- his discoveries were lactic acid,
citric acid, oxalic acid, tartaric
acid and arsenic acid
- identified glycerin, invented
new methods of preparing
calomel and benzoic acid
- discovered oxygen a year
before priestly
Friedrich Serturner (1783-1841)
- isolation of morphine for opium

- German pharmacist
Joseph Canventou (1795-1877)
- with Pelletier isolated quinine (for
malaria) and cinchonine from cinchona and
strychnine and brucine from nux vomica
Joseph Pelletier (1788-1842)
- with Robiquet isolated caffeine
Pierre Robiquet (1780-1840)
- independently separated
codeine (for cough) from opium
Paclitaxel (taxol)- anti tumor activity derived
form the pacific yew tree (taxus baccata)
-employed in the treatment of
metastatic carcinoma of the ovary
Vincaleukoblastine- another antineoplastic
drug from vinca rosea
Digoxin- cardiac glycoside from digitalis
lanata
Pelletier and Serturner- prep of drug product
into the highest standards of uniformity and
efficacy as possible
Most drugs needed were imported from
Europe (19th century)
Philidelphia College of pharmacy
-the nations first school of pharmacy
United States of Pharmocopeia (USP)
- aids in establishing standards
for drugs in the U.S.
Pharmacopeias or formularies
- organized sets of monographs
or books of these standards
- greek word pharmakon (drug)
and poiein (make)
- any recipe or formula or other
standards required to make or
prepare a drug
- this term was first used on
Bergamo, Italy (1580)
In Great Britain three pharmacopeias
London, Edinburgh and Dublin were official
until 1864 when they were replaced by the
British pharmacopeia (BP)
Lititz Pharmacopeia- 1st American
pharmacopeia (1778), at Lititz Pennsylvania
- 32 page booklet 84 internal and
16 external drug and
preparations
Lyman Spalding- a physician from NYC
- father of the USP
- Jan 6 1817 submitted a plan
English and Latin language of medicine
Massachusetts Pharmacopeia- precursor of
USP
Barbiturates- sleep producing derivatives of
barbituric acids
Arsphenamine- a specific agent against
syphilis, this era was the start of
chemotherapy
Paul Ehrlich (German Bacteriologists) and
Sahachiro Hata (Japanese) discovered
arsphenamine
American Pharmaceutical Association APhA
National Formulary of Unofficial preparations
was changed into national formulary (specific
for other countries)
Phil. National Drug formulary
Pres. Theodore Roosevelt- signed into law of
the first federal food and drug act
designating USP and NF (the two is official
Compendia) to be legal standards

Products- generally used to refer to

manufactured drugs and preparations to
manufactured drugs and preparation to
compounded drugs
Homeopathic Pharmacopeia of the United
States (HPUS) and Pharmacopeia
Internationalis or international pharmacopeia
Homeopathy- coined by Samuel Hahnemann
(1755-1843)
- from the greek homoios
(similar) pathos (disease)
HPUS- is essential for pharmacists who
prepare drugs to be used in the practice of
homeopathy
IP- published by the WHO of the UN
- serves as a recommendation to
modify pharmacopeias
according to International
Standards
The Mexican Pharmacopeia (Farmacopea de
los Estados Unidos Mexicanos)
Comprehensive Drug Abuse Prevention and
Control Act of 1870- served to consolidate
and notify control authority over drugs of
abuse into a single statute
- established 5 schedules for the
classification and control of
drug substances subjected to
abuse
Schedule I: Drugs with no accepted medical
use, or other substances with a high
potential for abuse (ex. Heroin, marijuana,
Lysergic Acid Diethylamide (LSD))
Nonmedical substance that is being abused
can be placed in this category.
Schedule II: Drugs with accepted medical
uses and a high potential for abuse that if
abused may lead to severe psychologic or
physical dependence. (ex. morphine,
cocaine, methamphetamine)
Schedule III: Drugs with accepted medical
uses and a potential for abuse less than
those listed in Schedules I and II that if
abused may lead to moderate psychologic or
physical dependence (ex. Codeine,
hydrocodone)
Schedule IV: Drugs with accepted medical
uses and low potential for abuse relative to
those in Sched III that if abused may lead to
limited physical dependence or psychologic
dependence relative to drugs in Sched III (ex.
Diazepam, Oxazepam, Diphenoxin)
Schedule V: Drugs with accepted medical
uses and low potential for abuse relative to
those in Sched IV that if abused may lead to
limited physical dependence or psychologic
dependence relative to drugs in schedule IV
(ex. Diphenoxylate, dihydrocodeine)
In 1979, the united states FDA introduced
classification of fetal risks due to
pharmaceuticals
The pregnancy category X is the strongest
and states that if any data exists that a drug
may be implicated as a teratogen and risk

versus benefit ratio does not support the use

of the drug

or a formulation change a manufacturer is

required to submit for approval

The FDA assigned pregnancy categories:

Abbreviated new drug application- used to

gain approval to market a duplicate of a
product that is already approved
Sponsor of The ANDA- documentation of
chemistry, bioavailability of the proposed
product

Category A: Adequate and well-controlled

studies have failed to demonstrate a risk to
the fetus in the first trimester of pregnancy
(and there is no evidence of risk in later
trimesters)
Category B: Animal reproduction studies
have failed to demonstrate a risk to the
fetus, and there are no adequate and wellcontrolled studies in pregnant women.
Category C: Animal reproduction studies
have shown an adverse effect on the fetus
and there are no adequate and wellcontrolled studies in humans, but potential
benefits may warrant use of the drug in
pregnant women despite potential risks
Category D: There is a positive evidence of
human fetal risk based on adverse reaction
data from investigational or marketing
experience or studies in humans, but
potential benefits may warrant use of the
drug in pregnant women despite potential
risks
Category X: Studies in animals or humans
have demonstrated fetal abnormalities and/
or there is a positive evidence of human fetal
risk based on adverse reaction data from
investigational or marketing experience, and
the risks involved in use of the drug in
pregnant woman clearly outweigh potential
benefits.
Chapter 2 Drug del
The federal Food, Drug and Cosmetic act, as
regulated through title 21 of the US Code of
federal regulations, requires a new drug to
be approved by the FDA before it may be
legally introduced in the interstate
commerce
To gain approval for marketing, a drugs
sponsor must demonstrate, through
supporting scientific evidence, that the new
drug or drug product is safe and effective
Only when the preclinical studies
demonstrate adequate safety and the new
agent shows promise as a useful drug will
the drugs sponsor file an IND application w/
the FDA for initial testing on humans.
REFER TO fig. 2.1 ON THE BOOK
Treatment IND (investigational drug)protocols if there are no satisfactory
approved drugs or treatment alternatives fro
a serious medical condition
- often are sought for orphan
drugs
Orphan drugs- small no. of pt. with rare
disease or conditions for w/c there are no
satisfactory alternative treatments
Supplemental new drug application- certain
changes in previously approved NDA labeling

Alexander Fleming- penicillin 1944

Antibiotics- effectiveness against the range
of pathogens
International conference on Harmonization
Reserpine- atranquilizer and a hypotensive
agent from rauwolfia serpentina
Periwinkle or Vinca Rosea- treatment of
diabetes milletus
Vinca Rosea- yields vinblastine and
vincristine treatment of certain types of
cancer
Taxol- treatment for ovarian cancer
Semisynthetic drugs- have a slightly different
pharmacologic activity from that of a starting
substance
Dioscorea- Mexican Yams- where cortisone
and estrogens are chemically produced
The urine of pregnant mare is a rich source
of estrogens.
Edward Jenner- small pox vaccine, use of
animals as products
Poliomyelitis vaccine- prepared in cultures of
renal monkey tissues
Proteins- infinite source of drugs
- building blocks of the living
matter
Rocombinant DNA- involve the manipulation
of protein
- has the potential to produce
almost any proteins
Gene Splicing- induce the lower organisms to
make proteins it would not otherwise have
made
Monoclonal antibodies- used in home
pregnancy testing products
Human chorionic gonadotropin (HCG)- a
specific marker to pregnancy because in
healthy women the HCG is only synthesize
by the placenta
Human Gene therapy-used to prevent cure,
diagnose or mitigate human diseases caused
by genetic disorders
Adenine and Thymine (A and T respectively)
and Cytosine and Guanine (C and G
respectively)- constitutes the instructions on
a gene
Gene Therapy- is a medical intervention
based on the modification of the genetic
material of living cells
- entails the transfer of new genetic
material to the cells of a patient with a
genetic disease
Disabled retroviral gene transfer systemsthat integrate genetic material of living cells
Adenosine Deaminase (ADA) defieciency
- first human gene therapy used
- conditions that results in
abnormal functioning of the
immune system
Goal drug- 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
Bioassays- used to differentiate the effect
and potency of the test agent from those
controls of known actions and effect
Molecular Modification- chemical alteration of
a known and previously characterized
organic compound for the purpose of
enhancing the usefulness of drugs
Cimetidine- first commercial histamine
Ranitidine- an inhibitor of histamine
Lead compound- prototype chemical
compound that has fundamental desired
biologic or pharmacologic activity
Prodrug- a compound that requires metabolic
biotransformation after administration to
produce the desired pharmacologically active
compound
FDAs def. of a new drug
New drug- any drug that is not recognized as
being safe and effective in the conditions
recommended for its use in the labeling
among the experts who are qualified by
scientific training and experience
Page 49 2.1 and 2.2
Chapter 3
Amorphous powders- crystals of various
morphologic structure
- where pharm. Ingr. Occur in
solid state
Powders- intimate mixtures of dry, finely
divided drugs and chemicals that may be
intended for internal and external use
Granules- prepared agglomerates of the
powdered materials of powdered materials
Nonmedicated powders- serves as a carrier
for meds
Bulk- packaged in sets
Divided powder- already divided according to
dose
Powders- can be medicated or nonmedicated
In characterizing the particle size:
- very coarse, coarse, moderately coarse,
fine and very fine

Very Coarse (no. 8) All particles pass through

a no. 8 sieve and not more than 20% pass
through a No. 60 sieve
Coarse (no. 20) All particles pass through a
no. 20 sieve and not more than 40% pass
through a No. 60 sieve
Moderately coarse (no. 40) All particles pass
through a no. 40 sieve and not more than
40% pass through a No. 80 sieve
Fine (no. 60) All particles pass through a no.
60 sieve and not more than 40% pass
through a No. 100 sieve
Very fine (no. 80) All particles pass through a
no. 80 sieve. There is no limit to greater
fineness
How particle size can influence variety of
factors:
- Dissolution rate, drug
micronization can increase the
dissolution rate and its
bioavailability
- Suspendability of particles
- Uniform distribution
- Penetrability of particles
- Lack of grittiness
In determining the particle size
Sieving- particles pass by through
mechanical shaking
Microscopy- uses a calibrated grid
background or other measuring devices
Sedimentation rate- size is determined
by measuring the terminal settling velocity of
particles
Light energy diffraction or light
scattering- by reduction of light reaching the
sensor
- light pass through
Laser holography -fired through an
aerolized particle spray photographed 3D
with a holographic camera
Cascade impactionMicromeritics- science of small particles