MODULE 1 Flashcards
1
Q
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.
A
CHEMISTRY
2
Q
that organic substances could only originate from living material
A
vital force theory
3
Q
disabuse the vital force concept.
A
Friedrich Wohler
4
Q
- converted soap (involved saponification process; uses acid & alkaline)
- first to discover fatty acid
A
Mitchel Eugene Chevreul
5
Q
Faureroy and Vauquehin incorporate chemistry into pharmacy curriculum
A
1793
6
Q
in 1793, they incorporated chemistry into pharmacy curriculum
A
Faureroy & Vauquehin
7
Q
isolation of narcotine by Derosome
A
1803
8
Q
in 1803, he isolated narcotine
A
Derosome
9
Q
in 1803, Derosome isolated what
A
narcotine
10
Q
C.R. Alder Wright synthesized diacetylmorphine
A
1874
11
Q
A
12
Q
in 1874, he synthesized diacetylmorphine
A
C.R. Alder Wright
13
Q
in 1874, C.R. Alder Wright synthesized ____
A
diacetylmorphine
14
Q
from party drugs to anesthetics.
ethyl ether, chloroform, nitrous oxide
A
1840’s
15
Q
Adolphe Kolbe - ethanoic acid
A
1845
16
Q
in 1845, he synthesized ethanoic acid
A
Adolphe Kolbe
17
Q
in 1845, Adolphe Kolbe synthesized ____
A
ethanoic acid
18
Q
Pierre Berthelot - methane
A
1856
19
Q
in 1856, Pierre Berthelot syntehsized ____
A
methane
20
Q
in 1856, he synthesized methane
A
Pierre Berthelot
21
Q
Humphry Davy 1st use nitrous oxide called it as ____
A
laughing gas
22
Q
he first used nitrous oxide and called it as laughing gas
A
Humphry Davy
23
Q
ERA OF PURE COMPOUND
Friedrich Seturner - isolation of ____
A
morphine
24
Q
ERA OF PURE COMPOUND
isolated morphine
A
Friedrich Seturner
25
# **ERA OF PURE COMPOUND**
**Pierre-Joseph Pelletier** - isolation of ____, ____, ____ in **1816**
strychnine
brucine
emetime
26
# **ERA OF PURE COMPOUND**
**Pierre-Joseph Pelletier** - isolation of ____ in **1820**
QUININE
27
# **ERA OF PURE COMPOUND**
considered as the **birth** of **pharmaceutical intestine**
discovery of **quinine**, **1820**
28
# **ERA OF PURE COMPOUND**
he discovered **strychnine**, **emetine**, and **brucine** in **1816** and **quinine** in **1820**
Pierre-Joseph Pelletier
28
# **ERA OF PURE COMPOUND**
**Pierre-Joseph Pelletier** isolated **strychnine**, **emetine**, and **brucine** in what year
1816
29
# **ERA OF PURE COMPOUND**
**Pierre-Joseph Pelletier** isolated **quinine** in what year
1820
30
* **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
31
# **ERA OF PURE COMPOUND**
birth of ____
pharmaceutical industry
32
# **ERA OF PURE COMPOUND**
____'s ***digitalis***
William Withering
33
# **ERA OF PURE COMPOUND**
____'s ***cocaine (1860)*** and ***physostigmine (1864)***
Albert Niemann
34
he uses **phenol**, also known as **carbolic acid**, an **antiseptic**
Joseph Lister
35
**Joseph Lister** used ____ as an **antiseptic** during surgeries
Phenol
36
**phenol** is also called as
carbolic acid
37
* a **pinkish crystal**
* protoplastic (**highly corrosive**)
phenol
38
to make the phenol **milder**, it is combined with ____
glycerin
39
**Bucheim’s chloral hydrate** (hypnotic)
1869
40
**Bayer’s** “**sulphonal**” hypnotic produced from ____
acetone
41
**Bayer’s** “____” **hypnotic** produced from **acetone**
sulphonal
42
____’s **“sulphonal” hypnotic** produced from **acetone**
Bayer's
43
* 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
44
isolation of **salicylic acid** from ***Spirea ulmaria***, started the **era on analgesics**
1875
45
in **1875**, ____ is isolated from ***Spirea ulmaria***
salicylic acid
46
in **1875**, **salicylic acid** was isolated from
Spirea ulmaria
47
**Salol** (**ester** of **salicylic acid** and **phenol**); has **poor solubility** but **better tolerated**
1883
48
* era of **paracetamol**
* some people **cannot synthesize salicylic acid** because it leads to GI distress -- **discovery of aspirin**
1875
49
* era of **anilines**, precursor to paracetamol (but they are **hepatotoxic** -- extensively metabolized in the liver)
* **Phenazone (Antipyrine)**
* Phenacetin to paracetamol
1884
50
**Dionin** (ethyl ether morphine) **cough sedative**; **safer** alternative to **morphine** and called as “**heroic drug**” hence the term **HEROIN**
1898
51
____ (ethyl ether morphine) **cough sedative**; **safer** alternative to **morphine** and called as “**heroic drug**” hence the term **HEROIN**
dionin
52
**Dionin** (ethyl ether morphine) ____; **safer** alternative to **morphine** and called as “**heroic drug**” hence the term **HEROIN**
cough sedative
53
**Dionin** (ethyl ether morphine) **cough sedative**; **safer** alternative to **morphine** and called as “____” hence the term ____
heroic drug, **heroin**
54
**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
55
Father of **modern chemotherapy**
Paul Ehrlich
56
**chemotherapeutic index**
minimum **curative** dose / maximum **tolerated** dose
57
with **Sacachiro Hata** developed **Salvarsan tx** for **syphilis**
1910
58
in **1910**, he developed **Salvrsan tx** for **syphillis**
Sacachiro Hata
59
used to tx **sleeping sickness** (**anti-protozoal**)
arsphenamine
60
**Frederick Banting**: discovery of **insulin**
1922
61
in **1922**, he discovered of **insulin**
Frederick Banting
62
**1922**: **Frederick Banting** - discovery of ____
insulin
63
**Alexander Fleming’s** “**Penicillin**"
1929
64
1929: ____ - “**Penicillin**"
Alexander Fleming
65
**1929**: **Alexander Fleming** - ____
penicillin
66
**Gerhard Domagk**:
* Sulfonamidochrysoidine or “**Prontosil**” 2,4-diaminobenzene sulfonamide
* Prontosil - **brilliant azo dye**, **parent** for **sulfonamides**
* **problem** with sulfa drugs: **crystalluria**
1932
67
in **1932**, he discovered **Prontosil**
Gerhard Domagk
68
* **brilliant azo dye**
* **parent** for **sulfonamides**
prontosil
69
**problem** with **sulfa** drugs
crystalluria
70
discovered **sulphanilamide**
Daniel Bovet
71
**golden age** of **antibiotic**
1940s-1960s
72
**Howard Florey** and **Ernst Chain** **purification** of **penicillin**
1941
73
____ and ____ **purification** of **penicillin**
Howard Florey & Ernst Chain
74
**Howard Florey** and **Ernst Chain** **purification** of ____
penicillin
75
**Selman Waksman**: **Streptomycin**,
**first antibiotic** used against **TB**
1944
76
in **1944**, he discovered **Streptomycin**, **first antibiotic** used against **TB**
Selman Waksman
77
in **1944**, **Selman Waksman** discovered ____, **first antibiotic** used against **TB**
streptomycin
78
**streptomycin** was the **first antibiotic** used **against** ____
tuberculosis
79
**Guiseppe Brotzu**:
* **Cephalosporins**;
* **Chloramphenicol** (Bartz);
* **Tetracycline** (Duggar)
1948
80
**1948**:
* **Cephalosporins**;
* **Chloramphenicol** (Bartz);
* **Tetracycline** (Duggar)
Guiseppe Brotzu
81
The **birth** of “**sulfonamides**”
1950's
82
**Hansch** and **Fujita** devised **QSAR**
1960's
83
* **Cimetidine** and **Ranitidine**
* **H2 antagonists** - targets histamine 2 receptor
* DRAWBACK: Cimetidine leads to **man boobs**
1970s
84
**controlled** clinical trials and placebo effects
Louis Lasagna
85
**anesthetic** agents
early 20th century
86
# **Development leading to various Medicinal Classes of Drugs Anticancer**
**discovery** of **anticancer** drugs
1845
87
# **Development leading to various Medicinal Classes of Drugs Anticancer**
**Elucication** by **Alfred Werner**
1893
88
# **Development leading to various Medicinal Classes of Drugs Anticancer**
**elucication** by ___
Alfred Werner
89
# **Development leading to various Medicinal Classes of Drugs Anticancer**
**Barnett Rosenberg** test on **mice**
1960s
90
# **Development leading to various Medicinal Classes of Drugs Anticancer**
____ test on **mice**
Barnett Rosenberg
91
# **Development leading to various Medicinal Classes of Drugs Anticancer**
clinical trials
1971
92
# **Development leading to various Medicinal Classes of Drugs Anticancer**
**1963**: who discovered **paclitaxel**
Monroe Wall and Masakh Wani
93
# **Development leading to various Medicinal Classes of Drugs Anticancer**
who discovered **6-Mercaptopurine**
| mustard gas, nitrogen mustard
George Hitchings
Gertrude Elion
94
# **Development leading to various Medicinal Classes of Drugs Anticancer**
PACLITAXEL:
**isolation**
1967
95
# **Development leading to various Medicinal Classes of Drugs Anticancer**
PACLITAXEL:
**elucidation**
| **year** and by **who**
1971, Susan Horwitz
96
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
97
involves **changes** designed to **transform** a **starting substance** with a **particular set of properties**.
synthetic chemistry
98
New Field in Medicinal Chemistry
biotechnology
99
# **New Field in Medicinal Chemistry: Biotechnology**
convenient **dosing schedule**
modified human insulin
100
# **New Field in Medicinal Chemistry: Biotechnology**
dosing regimen for **chemotherapy**
cell - stimulating factors
101
# **New Field in Medicinal Chemistry: Biotechnology**
target **specific tissues**
Humanized Monoclonal Antibodies
102
# **New Field in Medicinal Chemistry: Biotechnology**
intercept **immune cell-generated cytokinases**
fused receptors
102
compounds that **interact** with a **biological system** to **produce a biological response**
drugs
102
chemical compound that is used to **treat**, **mitigate**, **diagnose** and **prevent diseases** both in humans and animals
drugs
103
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
103
a pharmaceutical agent that has been developed **specifically** to treat a **rare medical condition**
orphan drug
103
a **rare** medical condition is referred to as
orphan disease
103
**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
103
* any compound that undergoes **biotransformation** prior to exhibiting its pharmacological effects (**Albert, 1958**)
* **inactive** form
prodrug
103
2 broad categories of **PRODRUG**
| (Wermuth, 1984)
Carrier-linked prodrug
bio-precursors
103
compounds that **already contain the embryo** of the active species **within their structure**.
bioprecursor prodrug
103
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
104
**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
104
# **PRODRUG**
**Heroin** is **deacetylated** by **esterase** to the **active** ____
morphine
104
consists of **two synergistic drugs** chemically linked together, in order to **improve the drug delivery properties** of one or both drugs
Codrug/Mutual prodrug
104
# **PRODRUGS**
**Levodopa** is **bioactivated** by ____ to the **active** ____
L-dopadecarboxylase, dopamine
104
# **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
104
use **macromolecules** as **carriers**
Macromolecular prodrug
104
where **carrier acts as transporter** of the active drug to a **specific targeted site**.
Site-specific prodrugs
104
# **PRODRUGS**
**Valaciclovir** is **bioactivated** by ____ to the **active** ____
esterase, aciclovir
104
# **PRODRUGS**
**Carisoprodol** is **metabolized** into ____.
meprobamate
104
the **only paracetamol** in **syrup** form
Tempra
104
# **PRODRUGS**
**Enalapril** is **bioactivated** by ____ to the **active** ____.
esterase, enalaprilat
104
# **PRODRUG**
designed to **prolong** the **drug activity** of its **active metabolite**
azathioprine
104
# **PRODRUG**
designed to **mask** the **toxic side effects** of the **active metabolite**
cyclophosphamide
104
A phenomenon when a patient receives a **placebo treatment** will have a **perceived or actual improvement** of medical condition.
placebo effect
105
# **PRODRUG**
designed to **increase** the **chemical stability** of the **active metabolite**
hetacillin
105
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
105
* 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
105
* 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 substanc**e such as **proteins** and **nucleic acids**.
receptors
105
**enalapril** is derived from
Bothrops jararaca
105
# **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
105
**bivalirudin** is derived from
Haementeria officinalis
105
**exenatide** is derived from
Heloderma suspectum
105
# **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
105
# **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
106
# **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
107
# **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
108
CAPTOPRiL
**C**ough
**A**ngioedema
**P**otassium increase (**hyperlakemia**)
**T**aste alteration
**O**rthostatic hypotension
**P**regnancy (**fetopathic**)
**R**enal failure
**iL** - Leucopenia (**granulocytopenia**)
109
# **Strategies/Methods of Drug Discovery**
▫ Penicillin
▫ 5-FU
▫ Minoxidil
▫ Sildenafil
▫ Levodopa
▫ Chlorpromazine
▫ LSD by Albert Hofmann “acid trip”
▫ “Mustine” = mustard gas
▫ Nitrous oxide
serendipity
110
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
111
* a **prodrug**
* **antifungal** (nucleoside inhibitor)
* **antineoplastic**
5-FU
112
* **initially** used in the **management** of **hypertension**
* **currently** used as **hair grower**
minoxidil
113
* the **blue pill**
* **vasodilator**
* used in **erectile dysfunction**
sildenafil
114
one i
ester
115
two i
amide
116
# **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
117
# **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
118
# **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
119
# **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
120
# **Recent Developments**
treatment of **torpedo cancer**
nanotechnology + gene therapy
121
# **Recent Developments**
eye improvement (**1st application of gene therapy**)
inherited blindness at birth
122
# **Recent Developments**
Newest method of gene therapy **alters immune cells** for the treatment of ____
advance melanoma
123
# **Recent Developments**
**suppresses lung cancer** in pre-clinical test
dual gene therapy
124
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
125
The principle of ____ means that **useful drugs show toxicity** against **foreign** or **abnormal** cells but **not against normal** host cells.
selective toxicity
126
# **Sources of Leads and Drugs**
screening of **local folk remedies**
* Cinchona bark, Foxgloves,
* Indian snakeroot
ETHNOPHARMACEUTICAL SOURCES
127
# **Sources of Leads and Drugs**
**Random sampling of higher plants** led to the discovery of crude plant drugs.
plant sources
128
# **Sources of Leads and Drugs**
Glandular products from animals are used such as **epinephrine (1901)**, **thyroid (1914)**, **(thyroxine)**, **insulin (1921)**
ANIMAL SOURCES
129
# **Sources of Leads and Drugs**
Some drugs are prepared from minerals:
▫ e.g. **KCl**, and **lithium carbonate** (an antipsychotic).
MINERAL SOURCES
130
# **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
131
are the **chief source of agents for the cure**, **mitigation** or the **prevention** of disease.
PURE ORGANIC COMPOUNDS
132
# **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
133
# **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
134
# **Drug Classification**
hormones
miscellaneous agents
135
**Born** (transmitted) from **person to person** by outside agents, **bacteria** (pneumonia, salmonella), **viruses** (common cold, HIV), **fungi** (thrush, athletes foot), **parasites** (malaria).
infectious diseases
136
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
137
**alleviation of pain** (analgesic), **prevention of pregnancy** (contraception), **anesthesia**.
non-diseases
138
# **Drug Name Types:**
usually applied to compounds of **known composition** using the **Chemical Abstract Services (CAS Registry Number)**
Chemical Name
139
# **Drug Name Types:**
substance of **plant** or **animal origin** that **cannot be classified as pure chemical compounds**.
biochemical, botanical or zoological name
140
# **Drug Name Types:**
**does not describe a compound** in terms of the **absolute structure** embodied in the system.
trivial names
141
# **Drug Name Types:**
assigned **during development phase**. It can be non-proprietary or a trademark.
code designations
142
# **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
143
# **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
144
# **Drug Nomenclature**
are **standardized syllables** that can **emphasize** a **special chemical nucleus**, **pharmacological property**, or combination of these attributes.
stems
145
a **polypeptide antibiotic**
gramicidin A
146
betalactam
benzylpenicillin
147
aminoglycoside
streptomycin
148
antibiotic but is used as **antineoplastic**
dactinomycin
149
antineoplastic
pentostatin
150
# **Naming of Drugs | PHARMACOLOGICALLY DERIVED
STEM**
-stat-
enzyme inhibitors
151
# **Naming of Drugs | PHARMACOLOGICALLY DERIVED
STEM**
-vir-
antivirals
151
# **Naming of Drugs | PHARMACOLOGICALLY DERIVED
STEM**
-astine
antihistamines
152
# **Naming of Drugs | COMBINATION STEM**
-olol
beta blockers
153
# **Naming of Drugs | COMBINATION STEM**
-profen
anti-inflamm / analgesic
154
# **SPECIES SOURCE**
-o-
mouse
155
# **SPECIES SOURCE**
-a-
rat
156
# **SPECIES SOURCE**
-u-
human
157
# **SPECIES SOURCE**
-i-
primate
158
# **SPECIES SOURCE**
-xi-
chimetric
159
# **SPECIES SOURCE**
-zu-
humanized
160
The **agency** responsible for the **selection of non-proprietary names** for single-entity drugs marketed in the US.
USAN council
