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Chem-127 – Impact of Chemistry – H. D. Roth
Chapter 10: Drugs, Manipulating Molecules
Everyday drugs – are we dependent?
Prescrip0on drugs – are we dependent? How harmful are illicit drugs? Are “natural” herbal remedies safer than synthe0c ones? How are effec0ve drugs designed? We begin with some everyday stimulants and
drugs HDR-F-2012
Azo dyes were the first commercially produced
chemicals. They effectively dyed wool fibers
(animal protein). Over 10,000 dyes were
screened in vitro in antibacterial tests, but none
showed any antibiotic activity. Scientists then
turned to in vivo studies with mice that had been
infected with a bacterial culture. Several dyes
were found to counteract gram-positive bacterial
infections.
NH2
O
H2 N
N
N
S
O
Prontosil
NH2
Gerhard Domagk was a research scientist at
Gerhard Domagk was a research scientist at
I. G. Farbenindustrie, a German
I. G. Farbenindustrie, a German
manufacturer of dyes and other chemicals.
manufacturer
of dyes
other chemicals.
manufacturer
dyes and
and
chemicals.
He carried outofstudies
thatother
showed
Prontosil
He
carried
out
studies
that
showed
Prontosil
He
out studies
that showed
wascarried
an effective
antibacterial
agent.Prontosil
was an effective antibacterial agent.
was an effective antibacterial agent.
His daughter, who was dying of a streptococcal
His daughter, who was dying of a streptococcal
infection
as a result
of cutting
her streptococcal
finger, was the
His
daughter,
who was
dying of
infection
as a result
of cutting
hera finger,
was the
first
patient
to
receive
the
drug
and
be
cured
by
infection
as to
a result
ofthe
cutting
wasby
the
first
patient
receive
drugher
andfinger,
be cured
it (1935).
(1935).
Prontosil
received
wider
fame
when
patientProntosil
to receive
the drug
and fame
be
cured
byitit
itfirst
received
wider
when
used to
to save
save the
the life
life of
of Franklin
Franklin D.
D.
was
used
itwas
(1935).
Prontosil
received
wider fame
when it
Roosevelt,
Jr.,
son
of
the
US
president.
Roosevelt,
sonthe
oflife
the of
USFranklin
president.
was used toJr.,
save
D.
Roosevelt,
son of thethat
USProntosil
president.was
Later it wasJr.,
discovered
Later it was discovered that Prontosil was
converted to
to sulfanilamide
sulfanilamide in
in living
living organisms
organisms
converted
Later
it was
thatactive
Prontosil
was
and that
that
thisdiscovered
was the
the actual
actual
active
compound.
and
this
was
compound.
Sulfanilamide
inhibits the
the synthesis
synthesis
of folic
folic acid,
acid,
converted
to sulfanilamide
in living of
organisms
Sulfanilamide
inhibits
an essential
essential
chemical
compound
for
bacterial
and
that thischemical
was the actual
activefor
compound.
an
compound
bacterial
growth.
Sulfanilamide
inhibits the synthesis of folic acid,
growth.
were found to counteract gram-positive bacterial
infections.
NH2
O
H2 N
N
N
S
O
Prontosil
NH2
first used for war casualties in Sicily and Tunsia.
H
N
R
O
S
N
CH3
CH3
O
Penicillin
O
O
Penicillins act
act by
by modifying
modifying an
an enzyme
enzyme involved
involved
Penicillins
in the
the synthesis
synthesis of
of aa bacterium’s
bacterium’s cell
cell wall.
wall.
in
Actively growing
growing bacteria
bacteria die
die because
because they
they are
are
Actively
unable to
to produce
produce aa functional
functional cell
cell wall.
wall.
unable
Penicillins have
have no
no effect
effect on
on mammalian
mammalian cells
cells
Penicillins
because they
they are
are not
not enclosed
enclosed by
by cell
cell walls.
walls.
because
The first
first penicillin
penicillin was
was isolated
isolated in
in 1938
1938 and
and
The
found to
to cure
cure bacterial
bacterial infections
infections in
in mice.
mice. ItIt was
was
found
used successfully
successfully in
in nine
nine cases
cases of
of human
human
used
bacterial infections
infections in
in 1941.
1941. By
By 1943,
1943, penicillin
penicillin
bacterial
was being
being produced
produced for
for the
the military
military and
and was
was
was
first used
used for
for war
war casualties
casualties in
in Sicily
Sicily and
and Tunsia.
Tunsia.
first
Hormones are chemical messengers – organic compounds synthesized in glands and delivered by the bloodstream to target 8ssues in order to s8mulate or inhibit some biochemical process. Many hormones are steroids. Remember: All steroids contain a tetracyclic ring system. The most abundant member of the steroid family in animals is cholesterol, the precursor of all other steroids. HDR-F-2012
Cortison
Cor8sone, used extensively in the treatment of rheumatoid inflamma8ons, is one of the adrenocor8cal hormones produced in the outer part of the adrenal gland. These hormones par8cipate in regula8ng the electrolyte and water balance in the body, as well as in protein and carbohydrate metabolism. HDR-F-2012
Steroids
CH3
R
H
H
CH3
H
C
H
H
C
H
R
H
Steroids perform many functions in the body:
Function
Regulation of secondary
sexual characteristics
Reproduction and control of
the reproductive cycle
Regulation of metabolism
Examples
Estradiol (an estrogen); testosterone
(an androgen)
Progesterone and the gestagens
Digestion of fat
Cell membrane component
Cholic acid; bile salts
Cholesterol
C
A
B
Cortisol; cortisone derivatives
D
This is the basic carbon
skeleton for all steroids.
10.7
The sex hormones are divided into three groups:
(1) the male sex hormones, or androgens; (2)
the female sex hormones, or estrogens; and (3)
the pregnancy hormones, or progestins.
Testosterone is the principal male sex hormone
and is responsible for the development of the
male secondary sex characteristics. Synthetic
testosterone analogs (anabolic steroids) are
used in medicine to promote muscle and tissue
growth, for example, in patients with muscular
atrophy. Unfortunately, such steroids are also
abused and consumed illegally, most
commonly by “body builders” and athletes,
even though the health risks are numerous,
including liver cancer, coronary hear disease,
and sterility.
Estradiol is the principal female sex hormone. It
is responsible for the development of the
female secondary sex characteristics and
participates in the control of the menstrual
cycle. An example of a progestin is
progesterone, responsible for preparing the
uterus for the implantation of a fertilized egg.
Synthetic analogs of estradiol and progesterone
are the active agents in the birth control pill,
allowing for control of the menstrual cycle and
ovulation. It is estimated that 50 to 60 million
women worldwide use the pill as the primary
form of contraception.
RU-486, The Abortion Pill
RU-486 acts as an antagonist – a drug that fits into a receptor
site, but does not have the customary effect as does another drug;
in this case the other drug is progesterone.
Antagonist – a drug that binds to a receptor site,
but does not– have
thethat
biological
of thesite,
binds toeffect
a receptor
Antagonist
a drug
Methotrexate
is biological
a prescription
drug used in
natural
substrate
but
does
not have the
effect of the
the
treatment
natural
substrate of breast cancer. It can be used
to block the action of folic acid, which is
Methotrexate is a prescription drug used in
required
for normal cell division and growth
theMethotrexate
treatment ofisbreast
cancer. Itdrug
can used
be used
a prescription
in
of
an
embryo.
Like
RU-486,
itisbe
can
be used to
to
block
the action
of folic
acid, which
the
treatment
of breast
cancer.
It can
used
induce
the
firstwhich
seven
required
for
cell
division
and
growth
to block abortion
the normal
action ofin
folic
acid,
is weeks of
of
an embryo.
Like
RU-486,
it can
be used
to by the
required
for normal
cell
division
growth
pregnancy.
Once
a drug
isand
approved
of an embryo.
it can
be used
induce
abortionLike
in theRU-486,
first seven
weeks
of to
FDA,
a physician
can
prescribe
itof for
pregnancy.
Onceina the
drug
is approved
by the
induce abortion
first
seven weeks
purposes
not
originally
intended
by the drug
pregnancy.
Once
a drug
is approved
FDA,
a physician
can
prescribe
it for by the
FDA, a physician
can prescribe
purposes
not originally
intended it
byfor
the drug
manufacturer.
purposes not originally intended by the drug
manufacturer.
manufacturer.
Should
such
“off-label”
prescriptions
Should
such
“off-label”
prescriptions
be
Should such “off-label” prescriptions be
allowed?
allowed?
allowed?
be
Medicines
Prescription,
Generic,
andand
Over-the-Counter
Generic,
APrescription,
generic drug is
chemically
equivalent
to Over-the-Counter
the pioneer drug, but cannot be
marketed until the patent
protection on the pioneer drug has run out after 20
Medicines
Medicines
years.
A generic
drug drug
is chemically
equivalent
to the
drug,
butbut
cannot
bebe
A generic
is chemically
equivalent
to pioneer
the pioneer
drug,
cannot
The lower
drug commonly
marketed
under drug
its generic
name,
in
this20
marketed
untilpriced
the
patent
protection
on the
hashas
run
outout
after
marketed
until
the patent
protection
on pioneer
the pioneer
drug
run
after 20
case alprazolam instead of Xanax.
years. years.
The lower
drug commonly
marketed
under
its generic
name,
this
The lower
pricedpriced
drug commonly
marketed
under
its generic
name,
in in
this
case alprazolam
instead
of Xanax.
case alprazolam
instead
of Xanax.
Prescription, Generic, and Over-the-Counter
Medicines
A generic drug is chemically equivalent to the pioneer drug, but cannot be
marketed until the patent protection on the pioneer drug has run out after 20
years.
10.10
The lower priced drug commonly marketed under its generic name, in this
case alprazolam instead of Xanax.
10.1
Herbal Remedies
10.11
Ephedra – used safely for thousands of years as herbal remedy
known as Ma Huang.
In 2003, several deaths related to the ingredients led the FDA
(in 2004) to ban ephedra products. At this time, there are
ongoing discussions to make the product available again.
Ephedra
The herb contains the amphetamine-like
alkaloids – ephedrine and the less active
pseudoephedrine.
Pseudoephedrene is used as a decongestant
Ephedrine is a bronchodilator (opens the airways), and a stimulant
Ephedra
The herb contains the amphetamine-like
alkaloids – ephedrine and the less active
pseudoephedrine.
Pseudoephedrene is used as a decongestant
Ephedrine is a bronchodilator (opens the airways), and a stimulant
Ephreda was responsible for the deaths of over 80 people.
An ephreda manufacturer challenged the FDA ban in court,
claiming that the FDA had failed to prove that ephreda was not
safe at low doses. In 2006, the US Court of Appeals for the Tenth
Circuit upheld the FDA’s ban on ephreda.
Drugs of Abuse
Drugs of Abuse
OxyContin contains oxycodone
Oxycodone has been used
safely for many years.
But this formulation includes a time-released mechanism for long-lasting
treatment of chronic pain.
Drug abusers quickly determined how to get around the time-release and
were able to rapidly ingest large amounts of oxycodone. The effects were
said to be similar to heroin.
Over-prescribed in the Appalachian areas in late 1990s and early 2000s.
Many became addicted.
10.12
Marijuana – Cannabis sativa
THC, or delta-9-tetrahydrocannabinol is the active drug in
marijuana.
Medical uses continue to be argued, the Federal Government is
opposed.
MDMA
–
Ecstacy
MDMA or Ecstasy
CH3
CH3
3,4-methylenedioxy-n-methylamphetamine
Schedule I drug, yet clinical therapists are continuing to argue
its potential benefits as a therapeutic agent.