Download Chemistry for Changing Times 11th Edition Hill and Kolb

Chemistry for Changing Times
12th Edition
Hill and Kolb
Chapter 18
Drugs: Chemical Cures,
Comforts, and Cautions
John Singer
Jackson Community College, Jackson, MI
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Chemical Cures, Comforts, and
Cautions
Drugs are defined as any chemical substance
that affects the function of living things and is
used to relieve pain, treat illness, improve health
or well-being.
Drugs can be obtained from plant sources,
microorganisms, marine organisms, and
synthetic sources.
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Scientific Drug Design
Paul Ehrlich determined that certain drugs are
more toxic to disease organisms than to human
cells. He first coined the term chemotherapy and
was awarded the Nobel Prize in
medicine/physiology in 1908.
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Pain Relievers: Nonsteroidal
Anti-Inflammatory Drugs
(NSAIDs)
NSAIDs relieve pain and reduce inflammation by
blocking the production of prostaglandins. NSAIDs
include the over-the-counter aspirin, ibuprofen,
acetominophen, etc.
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Pain Relievers: Nonsteroidal
Anti-Inflammatory Drugs
(NSAIDs)
Aspirin for Heart Attack and Stroke
Prevention
NSAIDs block the production of prostaglandins,
some of which are responsible for blood clotting.
This is the source of their anticoagulant
properties. Many adults take daily small doses of
aspirin (81 mg) to help prevent heart attack and
stroke.
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Pain Relievers: Nonsteroidal
Anti-Inflammatory Drugs
(NSAIDs)
NSAIDs and Fever Reduction
Fevers are caused by compounds called
pyrogens that are released from leukocytes and
other circulatory cells. Pyrogens often use
prostaglandins as secondary messengers. Since
NSAIDs block the production of prostaglandins,
they help to reduce fever.
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Pain Relievers: Nonsteroidal
Anti-Inflammatory Drugs
(NSAIDs)
How NSAIDs Work
Cycloxygenase (COX) enzymes catalyze the production of
prostaglandins from arachidonic acid. Two COX enzymes
are known to exist: COX-1 found in the stomach and kidney
tissues and COX-2 found in tissues where inflammation
occurs.
Aspirin, ibuprofen, and naproxen block both COX enzymes.
Blocking COX-1 enzyme leads to the side effects of
excessive bleeding and stomach pain.
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Pain Relievers: Nonsteroidal AntiInflammatory Drugs (NSAIDs)
How NSAIDs Work
Newer NSAIDs only block the COX-2 enzyme
and do not experience the side effects of the
older NSAIDs. Unfortunately, some have side
effects of increased risks of heart attack and
stroke as well as allergic reactions and internal
bleeding.
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Pain Relievers: Nonsteroidal
Anti-Inflammatory Drugs
(NSAIDs)
Acetominophen
Acetominophen helps reduce pain and fever. It
is not anti-inflammatory and it is not an
anticoagulant. It appears to act by blocking the
COX-3 enzyme. Acetominophen can be taken
by those that are affected by aspirin side effects
and by children. However, when taken with
alcohol, it can cause liver and kidney damage.
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Pain Relievers: Nonsteroidal
Anti-Inflammatory Drugs
(NSAIDs)
Combination pain relievers can include a
number of different NSAIDs, as well as caffeine,
antihistamines, and other drugs. Excedrin and
Anacin are familiar brands.
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Chemistry, Allergies, and the
Common Cold
A variety of cold and allergy medications are
available over-the-counter. Colds are caused by
more than 200 different viruses. There are no
effective cures. Most cold medications treat only
the symptoms. Periodically, the FDA reviews
these medications for safety and effectiveness.
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Chemistry, Allergies, and the
Common Cold
Antihistamines relieve the symptoms of
allergies caused by the actions of histamine.
Histamines are released by certain cells when
an allergen binds to its surface. Histamines
cause redness, swelling, and itching.
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Chemistry, Allergies, and the
Common Cold
Cough suppressants (antitussives) include
two narcotics, codeine, and dextromethorphan.
In addition, the antihistamine diphenhydramine
has been found to be effective by the FDA.
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Chemistry, Allergies, and the
Common Cold
Expectorants help to bring up mucus from the
bronchial passages. Only one expectorant,
glyceryl guaiacolate (guaifenesin), has been
found to be marginally effective.
Decongestants are inhaled through the nasal
passage. They seem to be safe and effective for
occasional use. They include oxymetazoline,
xylometazoline, naphazoline, and
phenylephrine.
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Antibacterial Drugs
In 1900, infectious
disease was a leading
cause of death.
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Antibacterial Drugs
Sulfa drugs were the first antibacterial drug.
Sulfanilamide acts by replacing paraaminobenzoic acid that bacteria need to
manufacture folic acid.
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Antibacterial Drugs
Penicillins are antibiotic substances. Antibiotics
are soluble substances derived from molds or
bacteria that inhibit the growth of other
microorganisms. Penicillins work by inhibiting
the enzymes that bacteria use to make their cell
walls.
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Antibacterial Drugs
Cephalosporins
Bacteria have evolved
resistances to certain
antibiotics. Scientists
are working to develop
new and more potent
antibiotics to kill
resistant bacteria.
Penicillins have been
partially replaced by
cephalosporins, such
as cephalexin (Keflex).
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Antibacterial Drugs
Tetracyclines are broadspectrum antibiotics that act
by binding to bacterial
ribosomes, inhibiting protein
synthesis.
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Antibacterial Drugs
Fluoroquinolones are broad-spectrum
antibiotics first introduced in 1986. They act by
inhibiting DNA replication through the
interference with the enzyme DNA gyrase.
Ciprofloxacin (Cipro®) is the leading
fluoroquinolone.
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Viruses and Antiviral Drugs
Viruses are
composed of nucleic
acids and proteins.
Viral diseases cannot
be cured by
antibiotics.
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Viruses and Antiviral Drugs
The genetic material of viruses is either DNA or
RNA.
DNA viruses enter the host cell where DNA is
replicated and direct the production of viral proteins
forming new viruses that invade other host cells
and continue the process.
RNA viruses enter the host cell and induce the
synthesis of new proteins. Some RNA viruses are
retroviruses, which synthesize new DNA in the
host cell. HIV is one example of a retrovirus.
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Viruses and Antiviral Drugs
Antiviral drugs have
been developed,
which are effective
against some viruses,
but do not provide
cures.
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Viruses and Antiviral Drugs
Antiviral Drugs
Nucleoside analogs substitute an analog for
the nucleoside in the viral DNA effectively
crippling it.
Nonnucleoside reverse transcriptase
inhibitors stop the reverse transcriptase
enzyme from making more virus.
Protease inhibitors block the enzyme protease
so that new copies of the virus cannot infect new
cells.
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Chemicals Against Cancer
Cancer is a much dreaded disease. 1.3 million
new cases are diagnosed in the U.S. each year.
Some types of cancer have high cure rates,
while others have a very low survival rate.
Dozens of anticancer drugs are used. However,
drugs that kill cancer cells also damage normal
cells.
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Chemicals Against Cancer
Antimetabolites closely resemble a substance
used in normal metabolism and interfere with the
physiological reactions.
6-mercaptopurine (6-MP), 5-fluorouracil, and 5fluorodeoxyuridine are incorporated into
nucleotides and inhibit the formation of thymine
containing nucleotides during DNA synthesis.
This slows the division and growth of cancer
cells.
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Chemicals Against Cancer
Antimetabolites resemble substances essential
to metabolism and interfere with physiological
reactions.
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Chemicals Against Cancer
Nitrogen alkylating agents are relatives of the
mustard gases used during WWI. They act by
cross-linking DNA strands and hindering
replication. Cyclophosphamide (Cytoxan) is
used to treat Hodgkin’s disease, lymphomas,
leukemias, and other cancers.
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Chemicals Against Cancer
Miscellaneous Anticancer Reagents
There are many other anticancer agents
including plant derivatives, certain antibiotics,
such as actinomycin, etc.
Chemotherapy, surgery, and radiation therapy
are the major tools in treating cancers.
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Hormones: The Regulators
Hormones are
chemical messengers
produced in the
endocrine glands.
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Hormones: The Regulators
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Hormones: The Regulators
Prostaglandins are hormone-like lipids derived
from a fatty acid. They are similar to hormones
in that they react with target cells. However, they
differ from hormones in that they: act near where
they are produced, can produce different effects
in different tissues, and are rapidly metabolized.
Prostaglandins are mediators of hormone action.
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Hormones: The Regulators
Steroids are lipids with a
definite four-ring skeletal
structure. Many drugs
are based on steroids.
Some are illegally used
to enhance athletic
performance, some are
used to treat arthritis,
asthma, dermatitis, and
eye infections.
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Hormones: The Regulators
Sex hormones are
steroids.
Androgens stimulate or
control the development
of masculine
characteristics.
Estrogens are
compounds that control
female sexual functions.
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Chemistry and Social
Revolution: The Pill
Progestin is any
steroid hormone that
has the effect of
progesterone. They
are effective for
female birth control.
They “fool” the body
into acting as if it
were already
pregnant and blocking
ovulation.
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Chemistry and Social
Revolution: The Pill
Emergency contraceptives are used to prevent
pregnancy after unprotected intercourse:
• Emergency contraception pills (ECPs) can
contain both estrogen and progestin, or just
progestin only. They disrupt the hormone
patterns needed for pregnancy.
• Intrauterine devices (IUDs) interfere with sperm
transport and fertilization.
• Mifepristone (RU-486) is the so-called medical
abortion pill. It inhibits progesterone, preventing
the body from maintaining pregnancy.
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Drugs for the Heart
Drug treatments for the heart involve increasing
blood supply, normalizing heart rhythm, lowering
blood pressure, and prevention of lipid plaques.
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Drugs for the Heart
Normalizing Heart Rhythm
Arrhythmia is an abnormal heartbeat. Many
drugs can treat this through a variety of actions.
Fibrillation is a too-rapid heartbeat. It is treated
with defibrillator devices that are available in
many public places.
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Drugs for the Heart
Treating Coronary Artery Disease
Arteriosclerosis is blockage of the coronary
arteries by lipid-containing plaque. It leads to
angina pectoris (chest pain) and ultimately,
heart attack.
Nitroglycerin and amyl nitrite can be used to
treat angina pectoris. They act by releasing
nitric oxide (NO), which relaxes constricted
blood vessels.
Digitalis can be used to treat heart failure.
Digitalis is a mixture of glycosides that release
carbohydrates and steroids on hydrolysis.
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Drugs for the Mind
Psychotropic drugs affect the human mind.
They fall into three categories:
1. Stimulants, such as cocaine and
amphetamines, increase alertness, speed
mental processes, and elevate moods.
2. Depressants, such as alcohol, anesthetics,
opiates, barbiturates, and tranquilizers,
reduce consciousness and reaction to stimuli.
3. Hallucinogenic drugs, such as lysergic acid
diethylamide (LSD) and marijuana, alter the
way we perceive reality.
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Some Chemistry of the Nervous
System
The human nervous system is
made up of about 12 billion
neurons. The essential parts
of the neuron are the cell
body, axon, and dendrites.
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Some Chemistry of the Nervous
System
Messages are
transmitted across the
fluid-filled gaps called
synapses by
chemicals called
neurotransmitters.
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Some Chemistry of the Nervous
System
Neurotransmitters
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Brain Amines: Depression and
Mania
Epinephrine is secreted by the adrenal glands;
tiny amounts lead to an increase in blood
pressure and cause the fight-or-flight
syndrome. It has been implicated in some forms
of mental illness.
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Brain Amines: Depression and
Mania
Biochemical Theories of Mental Illness
Norepinephrine (NE) is a relative of
epinephrine. It causes feelings of elation and in
excess amounts leads to a manic state.
Deficiency can cause depression.
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Brain Amines: Depression and
Mania
Biochemical Theories of
Mental Illness
Serotonin is another
brain amine
neurotransmitter. It is
involved in the regulation
of body temperature,
sleep sensory perception,
and pleasure sensation.
Its metabolite is 5-HIAA.
Research suggests
reduced flow of serotonin
can cause depression.
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Brain Amines: Depression and
Mania
NE agonists are stimulants that mimic or enhance
the effects of NE. They can be used to treat
depression, anxiety, and obsessive-compulsive
disorder.
NE antagonists are drugs that block the effects of
NE. They can be used to treat hypertension, angina,
or cardiac arrhythmia.
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Anesthetics
Anesthetics are substances that cause lack of
feeling or awareness. General anesthetics
produce unconsciousness and block feelings of
pain. Local anesthetics block feelings of pain in
a specific part of the body.
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Anesthetics
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Anesthetics
Modern anesthetics can include a variety of
several drugs including:
• a tranquilizer
• an IV such as thiopental to cause
unconsciousness
• a narcotic painkiller like fentanyl
• an inhalant anesthetic to keep the person
unconscious and provide insensitivity to
pain
• a muscle relaxant like succinylcholine
chloride
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Anesthetics
Local Anesthetics
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Anesthetics
Local Anesthetics
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Anesthetics
Barbiturates are a family of related
depressants. They were once used as a mild
sedative. In larger doses, they induce sleep.
Barbiturates are very toxic.
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Anesthetics
Both alcohol and barbiturates are depressants.
Taken together, they cause a synergistic effect.
A synergistic effect is an effect greater than
each drug taken separately. For instance, the
depressant effect of barbiturates is enhanced up
to 200 times when taken with ethanol.
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Narcotics
Narcotics are drugs that produce narcosis
(stupor or general anesthesia) and are
analgesics (painkillers). In the United States,
such drugs that are addictive are legally
regulated and classified as narcotics.
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Narcotics
Opium and Morphine
Opium is the resinous juice of the unripe seeds
of the oriental poppy. It contains more than
twenty alkaloids, sugars, resins, and waxes.
Morphine is an alkaloid that makes up 20% of
the weight of opium.
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Narcotics
Codeine and Heroin
Codeine is a derivative of morphine.
Replacement of the phenolic hydroxyl (OH)
group with the methoxy (–OCH3) converts
morphine to codeine.
Heroin is made by converting both hydroxyl
groups of morphine to acetate esters. This
makes heroin less polar than morphine and
makes it more soluble in fatty brain tissue.
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Narcotics
Synthetic Narcotics
Much research has
been done to develop
a painkilling drug as
effective as morphine
but less addictive.
Methadone is one
such drug that is used
to treat heroin
addiction.
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Narcotics
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Narcotics
Morphine Agonists and Antagonists
Morphine agonists exhibit morphine-like activity
by binding to receptors in the brain.
Morphine antagonists inhibit the action of
morphine by blocking receptors.
Pentazocine acts as both. It is less addictive than
morphine and is effective at relieving pain.
Naloxone is a pure antagonist. It can be used to
treat opium addicts.
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Narcotics
Natural Opiates
Endorphins are morphine-like peptide chains
produced in response to pain. Morphine and
endorphins bind to the same receptors in the
brain. The result is pain relief and the “runner’s
high”.
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Antianxiety Agents
A variety of drugs have been used to relieve the
stress of modern living. One such class are the
benzodiazepines. They are thought to act on
the GABA receptor and are addictive.
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Antianxiety Agents
Antipsychotic Agents
In 1952, rauwolfia from the snakeroot plant was
used to treat hypertension. That same year,
reserpine (an active alkaloid) was isolated from
rauwolfia and found to be an effective sedative
as well as an antihypertensive agent. The
following year, it replaced electroshock therapy
for 90% of psychotic patients.
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Antianxiety Agents
Phenothiazines
Chlorpromazine (Thorazine®) was introduced
in 1952 as an effective tranquilizer for psychotic
patients in the U.S. Chlorpromazine is one of
several phenothiazines. They act as dopamine
antagonists by blocking the post synaptic
receptors for dopamine. They are effective at
treating the symptoms of schizophrenia.
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Antianxiety Agents
Antidepressant Drugs
Selective serotonin reuptake inhibitors
(SSRIs) are commonly used to treat depression.
They enhance the effect of serotonin by blocking
its reabsorption by nerve cells.
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Stimulant Drugs
Amphetamines have been used in treating
depression and narcolepsy. They increase pulse
rate and blood pressure. They induce excitability
and restlessness. At one time, they were used
as a diet drug. They are now used to treat ADD
in children.
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Stimulant Drugs
Cocaine is a powerful stimulant. It previously
arrived in the U.S. as cocaine hydrochloride. It is
now available as its free-base crack cocaine. It
acts by preventing the reabsorbtion of
dopamine. This leaves high levels of dopamine
to stimulate the pleasure centers of the brain.
The effect is short-lived and its use is quickly
followed by depression and craving for more.
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Stimulant Drugs
Caffeine: Coffee, Tea, or
Cola
Caffeine is a mild stimulant.
An effective dose is about
200 mg.
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Stimulant Drugs
Nicotine is another
common stimulant. It is
taken by smoking or
chewing tobacco. Its initial
stimulant response is
followed by depression.
Smokers are able to
maintain a near constant
level of nicotine in their
blood by regular smoking.
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Psychedelic Drugs
Lysergic acid diethylamide (LSD) is a
semisynthetic, powerful psychedelic drug. It is
synthesized by converting lysergic acid (from
ergot) to its diethylamide derivative.
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Psychedelic Drugs
Psilocybin is a
psychedelic alkaloid
found in several
mushrooms with effects
similar to LSD.
Mescaline is a
psychedelic drug found
in the peyote cactus. Its
effects last up to 12
hours.
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Psychedelic Drugs
Marijuana is
prepared from the
leaves, flowers,
seeds, and stems of
the Cannabis sativa
plant. One major
active ingredient is
tetrahydrocannabinol
(THC).
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Drug Problems
Drug abuse is the use of drugs for their
intoxicating effects. It causes major problems for
the abuser and society.
Drug misuse is the use of drugs for the wrong
purpose. An example is the use of antibiotics for
viral illness. Antibiotics have no effect on viruses
and such misuse contributes to antibioticresistant bacteria.
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The Placebo Effect
A placebo is an inactive substance administered
as a medication to a patient. Many patients
demonstrate positive results when administered
placebos. This demonstrates “mind-overmatter”.
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New Uses for Old Drugs
The development of new drugs is very
expensive. Many older drugs have been tested
and approved for new uses.
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