MODULE 1 Flashcards
the science that deals with the composition of matter and changes in composition it may undergo either spontaneously or because of intentionally established environmental conditions.
CHEMISTRY
that organic substances could only originate from living material
vital force theory
disabuse the vital force concept.
Friedrich Wohler
- converted soap (involved saponification process; uses acid & alkaline)
- first to discover fatty acid
Mitchel Eugene Chevreul
Faureroy and Vauquehin incorporate chemistry into pharmacy curriculum
1793
in 1793, they incorporated chemistry into pharmacy curriculum
Faureroy & Vauquehin
isolation of narcotine by Derosome
1803
in 1803, he isolated narcotine
Derosome
in 1803, Derosome isolated what
narcotine
C.R. Alder Wright synthesized diacetylmorphine
1874
in 1874, he synthesized diacetylmorphine
C.R. Alder Wright
in 1874, C.R. Alder Wright synthesized ____
diacetylmorphine
from party drugs to anesthetics.
ethyl ether, chloroform, nitrous oxide
1840’s
Adolphe Kolbe - ethanoic acid
1845
in 1845, he synthesized ethanoic acid
Adolphe Kolbe
in 1845, Adolphe Kolbe synthesized ____
ethanoic acid
Pierre Berthelot - methane
1856
in 1856, Pierre Berthelot syntehsized ____
methane
in 1856, he synthesized methane
Pierre Berthelot
Humphry Davy 1st use nitrous oxide called it as ____
laughing gas
he first used nitrous oxide and called it as laughing gas
Humphry Davy
ERA OF PURE COMPOUND
Friedrich Seturner - isolation of ____
morphine
ERA OF PURE COMPOUND
isolated morphine
Friedrich Seturner
ERA OF PURE COMPOUND
Pierre-Joseph Pelletier - isolation of ____, ____, ____ in 1816
strychnine
brucine
emetime
ERA OF PURE COMPOUND
Pierre-Joseph Pelletier - isolation of ____ in 1820
QUININE
ERA OF PURE COMPOUND
considered as the birth of pharmaceutical intestine
discovery of quinine, 1820
ERA OF PURE COMPOUND
he discovered strychnine, emetine, and brucine in 1816 and quinine in 1820
Pierre-Joseph Pelletier
ERA OF PURE COMPOUND
Pierre-Joseph Pelletier isolated strychnine, emetine, and brucine in what year
1816
ERA OF PURE COMPOUND
Pierre-Joseph Pelletier isolated quinine in what year
1820
- Friedrich Seturner isolated morphine
- Pierre-Joseph Pelletier isolated strychnine, emetine and brucine in 1816, and quinine in 1820
- Birth of Pharmaceutical Industry
- William Withering’s Digitalis
- Albert Niemann’s Cocaine (1860) and Physostigmine (1864)
ERA OF PURE COMPOUND
ERA OF PURE COMPOUND
birth of ____
pharmaceutical industry
ERA OF PURE COMPOUND
____’s digitalis
William Withering
ERA OF PURE COMPOUND
____’s cocaine (1860) and physostigmine (1864)
Albert Niemann
he uses phenol, also known as carbolic acid, an antiseptic
Joseph Lister
Joseph Lister used ____ as an antiseptic during surgeries
Phenol
phenol is also called as
carbolic acid
- a pinkish crystal
- protoplastic (highly corrosive)
phenol
to make the phenol milder, it is combined with ____
glycerin
Bucheim’s chloral hydrate (hypnotic)
1869
Bayer’s “sulphonal” hypnotic produced from ____
acetone
Bayer’s “____” hypnotic produced from acetone
sulphonal
____’s “sulphonal” hypnotic produced from acetone
Bayer’s
- suggest that a carbon with 2 ethyl group can be a good hypnotic agent – diethyl acetyl urea then diethyl barbituric acid.
- era of barbiturates/anticonvulsants
Von Mering
isolation of salicylic acid from Spirea ulmaria, started the era on analgesics
1875
in 1875, ____ is isolated from Spirea ulmaria
salicylic acid
in 1875, salicylic acid was isolated from
Spirea ulmaria
Salol (ester of salicylic acid and phenol); has poor solubility but better tolerated
1883
- era of paracetamol
- some people cannot synthesize salicylic acid because it leads to GI distress – discovery of aspirin
1875
- era of anilines, precursor to paracetamol (but they are hepatotoxic – extensively metabolized in the liver)
- Phenazone (Antipyrine)
- Phenacetin to paracetamol
1884
Dionin (ethyl ether morphine) cough sedative; safer alternative to morphine and called as “heroic drug” hence the term HEROIN
1898
____ (ethyl ether morphine) cough sedative; safer alternative to morphine and called as “heroic drug” hence the term HEROIN
dionin
Dionin (ethyl ether morphine) ____; safer alternative to morphine and called as “heroic drug” hence the term HEROIN
cough sedative
Dionin (ethyl ether morphine) cough sedative; safer alternative to morphine and called as “____” hence the term ____
heroic drug, heroin
Late 19th century:
* worked on antibacterial dyes and organoarsenicals;
* He coined the term chemotherapy, conceptualizes “magic bullet”.
* He coined the term receptor (receptive substance, Langley, 1878)
Paul Ehrlich
Father of modern chemotherapy
Paul Ehrlich
chemotherapeutic index
minimum curative dose / maximum tolerated dose
with Sacachiro Hata developed Salvarsan tx for syphilis
1910
in 1910, he developed Salvrsan tx for syphillis
Sacachiro Hata
used to tx sleeping sickness (anti-protozoal)
arsphenamine
Frederick Banting: discovery of insulin
1922
in 1922, he discovered of insulin
Frederick Banting
1922: Frederick Banting - discovery of ____
insulin
Alexander Fleming’s “Penicillin”
1929
1929: ____ - “Penicillin”
Alexander Fleming
1929: Alexander Fleming - ____
penicillin
Gerhard Domagk:
* Sulfonamidochrysoidine or “Prontosil” 2,4-diaminobenzene sulfonamide
* Prontosil - brilliant azo dye, parent for sulfonamides
* problem with sulfa drugs: crystalluria
1932
in 1932, he discovered Prontosil
Gerhard Domagk
- brilliant azo dye
- parent for sulfonamides
prontosil
problem with sulfa drugs
crystalluria
discovered sulphanilamide
Daniel Bovet
golden age of antibiotic
1940s-1960s
Howard Florey and Ernst Chain purification of penicillin
1941
____ and ____ purification of penicillin
Howard Florey & Ernst Chain
Howard Florey and Ernst Chain purification of ____
penicillin
Selman Waksman: Streptomycin,
first antibiotic used against TB
1944
in 1944, he discovered Streptomycin, first antibiotic used against TB
Selman Waksman
in 1944, Selman Waksman discovered ____, first antibiotic used against TB
streptomycin
streptomycin was the first antibiotic used against ____
tuberculosis
Guiseppe Brotzu:
* Cephalosporins;
* Chloramphenicol (Bartz);
* Tetracycline (Duggar)
1948
1948:
* Cephalosporins;
* Chloramphenicol (Bartz);
* Tetracycline (Duggar)
Guiseppe Brotzu
The birth of “sulfonamides”
1950’s
Hansch and Fujita devised QSAR
1960’s
- Cimetidine and Ranitidine
- H2 antagonists - targets histamine 2 receptor
- DRAWBACK: Cimetidine leads to man boobs
1970s
controlled clinical trials and placebo effects
Louis Lasagna
anesthetic agents
early 20th century
Development leading to various Medicinal Classes of Drugs Anticancer
discovery of anticancer drugs
1845
Development leading to various Medicinal Classes of Drugs Anticancer
Elucication by Alfred Werner
1893
Development leading to various Medicinal Classes of Drugs Anticancer
elucication by ___
Alfred Werner
Development leading to various Medicinal Classes of Drugs Anticancer
Barnett Rosenberg test on mice
1960s
Development leading to various Medicinal Classes of Drugs Anticancer
____ test on mice
Barnett Rosenberg
Development leading to various Medicinal Classes of Drugs Anticancer
clinical trials
1971
Development leading to various Medicinal Classes of Drugs Anticancer
1963: who discovered paclitaxel
Monroe Wall and Masakh Wani
Development leading to various Medicinal Classes of Drugs Anticancer
who discovered 6-Mercaptopurine
mustard gas, nitrogen mustard
George Hitchings
Gertrude Elion
Development leading to various Medicinal Classes of Drugs Anticancer
PACLITAXEL:
isolation
1967
Development leading to various Medicinal Classes of Drugs Anticancer
PACLITAXEL:
elucidation
year and by who
1971, Susan Horwitz
defined as the discipline of chemistry and biology that
is concerned with the identification, design, development and synthesis of chemical agents that have therapeutic use and evaluate properties of existing drugs.
medicinal chemistry
involves changes designed to transform a starting substance with a particular set of properties.
synthetic chemistry
New Field in Medicinal Chemistry
biotechnology
New Field in Medicinal Chemistry: Biotechnology
convenient dosing schedule
modified human insulin
New Field in Medicinal Chemistry: Biotechnology
dosing regimen for chemotherapy
cell - stimulating factors
New Field in Medicinal Chemistry: Biotechnology
target specific tissues
Humanized Monoclonal Antibodies
New Field in Medicinal Chemistry: Biotechnology
intercept immune cell-generated cytokinases
fused receptors
compounds that interact with a biological system to produce a biological response
drugs
chemical compound that is used to treat, mitigate, diagnose and prevent diseases both in humans and animals
drugs
a chemical compound that has pharmacological or biological activity and whose chemical structure is used as a starting point for chemical modifications in order to improve potency, selectivity, or pharmacokinetic parameters.
lead compound
a pharmaceutical agent that has been developed specifically to treat a rare medical condition
orphan drug
a rare medical condition is referred to as
orphan disease
chemical modification of a biologically active compound to form a new compound that, upon in vivo enzymatic attack, will liberate the parent compound
(Harper, 1959)
drug latentiation
- any compound that undergoes biotransformation prior to exhibiting its pharmacological effects (Albert, 1958)
- inactive form
prodrug
2 broad categories of PRODRUG
(Wermuth, 1984)
Carrier-linked prodrug
bio-precursors
compounds that already contain the embryo of the active species within their structure.
bioprecursor prodrug
consist of the attachment of a carrier group to the active drug to alter its physicochemical properties and then subsequent enzymatic or non enzymatic mechanisms to release the active drug moiety.
carrier-linked prodrug
only carried out by enzymatic conversion to prodrug is possible before the “pro-drug” release the active drug
Double prodrug/
pro-prodrug/
cascade latentiated prodrugs
PRODRUG
Heroin is deacetylated by esterase to the active ____
morphine
consists of two synergistic drugs chemically linked together, in order to improve the drug delivery properties of one or both drugs
Codrug/Mutual prodrug
PRODRUGS
Levodopa is bioactivated by ____ to the active ____
L-dopadecarboxylase, dopamine
PRODRUG
ester is used as an intravenous prodrug of chloramphenicol, because pure chloramphenicol is poorly soluble in water (2.5mg/mL) or palmitate ester to make a suspension (1.05 mg/mL).
chloramphenicol succinate
use macromolecules as carriers
Macromolecular prodrug
where carrier acts as transporter of the active drug to a specific targeted site.
Site-specific prodrugs
PRODRUGS
Valaciclovir is bioactivated by ____ to the active ____
esterase, aciclovir
PRODRUGS
Carisoprodol is metabolized into ____.
meprobamate
the only paracetamol in syrup form
Tempra
PRODRUGS
Enalapril is bioactivated by ____ to the active ____.
esterase, enalaprilat
PRODRUG
designed to prolong the drug activity of its active metabolite
azathioprine
PRODRUG
designed to mask the toxic side effects of the active metabolite
cyclophosphamide
A phenomenon when a patient receives a placebo treatment will have a perceived or actual improvement of medical condition.
placebo effect
PRODRUG
designed to increase the chemical stability of the active metabolite
hetacillin
the region of the molecule containing the** essential organic functional groups** that directly interact with the** receptor active site** and, therefore, confers the biologic activity of interest
pharmacophore
- as an antinuclear antibody test/drug
- study of the changes in antagonism of H2-histamine receptors induced by varying the physical properties of structure based on histamine.
cimetidine
- substance to which a drug needs to** interact with** to elicit pharmacologic response
- a relatively small region of a macromolecule which may be an/a: enzyme, structural or functional group/component of CM, specific intracellular substance such as proteins and nucleic acids.
receptors
enalapril is derived from
Bothrops jararaca
Discovery & Development of Organic Medicinal Chemicals:
-
opposite approach to high-volume screening using techniques like:
▫ X-ray crystallography
▫ Nuclear magnetic resonance
▫ Molecular graphics
▫ Computational chemistry - Leads to the development of drugs;
▫ HIV protease inhibitor
▫ ACE inhibitors
▫ H2 antagonists
rational drug design
bivalirudin is derived from
Haementeria officinalis
exenatide is derived from
Heloderma suspectum
Discovery & Development of Organic Medicinal Chemicals:
(with enzyme linked assays or receptors from gene cloning) of existing drugs lead to identification of new LEAD drug.
▫ e.g. Amantadine
random screening
Discovery & Development of Organic Medicinal Chemicals:
- refers to a process in which finding of new medication is based on knowledge of biological target is done
- involves design of small molecules that are complementary in shape and charge to the biomolecular target.
- Begins with hypothesis that modulation of a specific biological target may have therapeutic value.
rational drug design
Discovery & Development of Organic Medicinal Chemicals:
Categories of Rational Drug Design:
Development of small molecules with ____ properties for targets, biomolecule; has functional roles in cellular processes and 3D structural information
desired
Discovery & Development of Organic Medicinal Chemicals:
Categories of Rational Drug Design:
Development of small molecules with ____ properties for targets, whose cellular functions and their structural information maybe known or unknown.
predefined
CAPTOPRiL
Cough
Angioedema
Potassium increase (hyperlakemia)
Taste alteration
Orthostatic hypotension
Pregnancy (fetopathic)
Renal failure
iL - Leucopenia (granulocytopenia)
Strategies/Methods of Drug Discovery
▫ Penicillin
▫ 5-FU
▫ Minoxidil
▫ Sildenafil
▫ Levodopa
▫ Chlorpromazine
▫ LSD by Albert Hofmann “acid trip”
▫ “Mustine” = mustard gas
▫ Nitrous oxide
serendipity
Technique used to correct defective genes.
It is the process of inserting genes into cells to treat diseases.
It is used to correct a deficient phenotype.
gene therapy
- a prodrug
- antifungal (nucleoside inhibitor)
- antineoplastic
5-FU
- initially used in the management of hypertension
- currently used as hair grower
minoxidil
- the blue pill
- vasodilator
- used in erectile dysfunction
sildenafil
one i
ester
two i
amide
Approaches of Gene Therapy
- Sperm or egg cells are modified by introduction of functional genes 🡺 integrated into their genomes.
- The changes are HERITABLE and would be passed on the later generations.
Germline Gene Therapy
Approaches of Gene Therapy
- The therapeutic genes are transferred into the somatic cells of patients.
- Change is NOT INHERITED by the patient’s offspring or later generation.
Somatic Gene Therapy
Approaches of Gene Therapy
- Transfer of therapeutic genes in cultured cells which are then reintroduced into patients
- Therapy for ADA Deficiency
EX VIVO GENE THERAPY
Approaches of Gene Therapy
- Involves direct delivery of genes into the cells of a particular tissue.
- Therapy for Cystic fibrosis (no successful case yet)
in vivo gene therapy
Recent Developments
treatment of torpedo cancer
nanotechnology + gene therapy
Recent Developments
eye improvement (1st application of gene therapy)
inherited blindness at birth
Recent Developments
Newest method of gene therapy alters immune cells for the treatment of ____
advance melanoma
Recent Developments
suppresses lung cancer in pre-clinical test
dual gene therapy
a measure of a drug’s beneficial effect at a low dose versus its harmful effects at higher dose. A high therapeutic index indicates a large safety margin between beneficial and toxic doses.
therapeutic index
The principle of ____ means that useful drugs show toxicity against foreign or abnormal cells but not against normal host cells.
selective toxicity
Sources of Leads and Drugs
screening of local folk remedies
* Cinchona bark, Foxgloves,
* Indian snakeroot
ETHNOPHARMACEUTICAL SOURCES
Sources of Leads and Drugs
Random sampling of higher plants led to the discovery of crude plant drugs.
plant sources
Sources of Leads and Drugs
Glandular products from animals are used such as epinephrine (1901), thyroid (1914), (thyroxine), insulin (1921)
ANIMAL SOURCES
Sources of Leads and Drugs
Some drugs are prepared from minerals:
▫ e.g. KCl, and lithium carbonate (an antipsychotic).
MINERAL SOURCES
Sources of Leads and Drugs
- Laboratories duplicate natural processes.
- Frequently this can eliminate side effects and increase the potency of the drug.
▫ e.g. barbiturates, sulfonamides, ASA.
SYNTHETIC SOURCES
are the chief source of agents for the cure, mitigation or the prevention of disease.
PURE ORGANIC COMPOUNDS
Drug Classification
-
Agents acting on CNS:
(psychotropic and neurologic drugs) – like for pain and epilepsy - Chemotherapeutic agents: Those drugs which are used to fight pathogens (e.g. sulfonamides, antibiotics, anti –malarial agents, antiviral, anti-cancer etc.)
PHYSIOLOGICAL CLASSIFICATION
Drug Classification
Drugs that act on the various physiological functions of the body (e.g. general anesthetic, hypnotic and sedatives, vasodilators, antihistamines, analgesic etc.)
PHARMACODYNAMIC AGENTS
Drug Classification
hormones
miscellaneous agents
Born (transmitted) from person to person by outside agents, bacteria (pneumonia, salmonella), viruses (common cold, HIV), fungi (thrush, athletes foot), parasites (malaria).
infectious diseases
disorders of the human body caused by genetic malfunction, environmental factors, stress, old age etc. (e.g. diabetes, heart disease, cancer. Hemophilia, asthma, mental illness, stomach ulcers, arthritis).
non-infectious disease
alleviation of pain (analgesic), prevention of pregnancy (contraception), anesthesia.
non-diseases
Drug Name Types:
usually applied to compounds of known composition using the Chemical Abstract Services (CAS Registry Number)
Chemical Name
Drug Name Types:
substance of plant or animal origin that cannot be classified as pure chemical compounds.
biochemical, botanical or zoological name
Drug Name Types:
does not describe a compound in terms of the absolute structure embodied in the system.
trivial names
Drug Name Types:
assigned during development phase. It can be non-proprietary or a trademark.
code designations
Drug Name Types:
developed by the manufacturer; selected for their ease of recall but does not give a scientific information about the drug.
trademark name
Drug Name Types:
a single, simple, informative designation available for unrestricted public use. Specific for a given compound even though it may possess a stem common to a related group of drug
nonproprietary name / generic name
Drug Nomenclature
are standardized syllables that can emphasize a special chemical nucleus, pharmacological property, or combination of these attributes.
stems
a polypeptide antibiotic
gramicidin A
betalactam
benzylpenicillin
aminoglycoside
streptomycin
antibiotic but is used as antineoplastic
dactinomycin
antineoplastic
pentostatin
**Naming of Drugs | PHARMACOLOGICALLY DERIVED
STEM**
-stat-
enzyme inhibitors
**Naming of Drugs | PHARMACOLOGICALLY DERIVED
STEM**
-vir-
antivirals
**Naming of Drugs | PHARMACOLOGICALLY DERIVED
STEM**
-astine
antihistamines
Naming of Drugs | COMBINATION STEM
-olol
beta blockers
Naming of Drugs | COMBINATION STEM
-profen
anti-inflamm / analgesic
SPECIES SOURCE
-o-
mouse
SPECIES SOURCE
-a-
rat
SPECIES SOURCE
-u-
human
SPECIES SOURCE
-i-
primate
SPECIES SOURCE
-xi-
chimetric
SPECIES SOURCE
-zu-
humanized
The agency responsible for the selection of non-proprietary names for single-entity drugs marketed in the US.
USAN council
