Transcript Chapter 19

Chemistry for Changing Times
11th Edition
Hill and Kolb
Chapter 19
Drugs
John Singer
Jackson Community College, Jackson, MI
© 2007 Prentice Hall
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, or improve health or wellbeing.
Drugs can be obtained from plant sources,
microorganisms, marine organisms, and
synthetic sources.
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.
Pain Relievers: Nonsteroidal AntiInflammatory Drugs (NSAIDS)
NSAIDS relieve pain and reduce inflammation by
blocking the production of prostaglandins. NSAIDS
include aspirin, ibuprofen, acetominophen, etc.
Pain Relievers: Nonsteroidal AntiInflammatory 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.
Pain Relievers: Nonsteroidal AntiInflammatory 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.
Pain Relievers: Nonsteroidal AntiInflammatory 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 naproxin block both COX
enzymes. Blocking COX-1 enzyme leads to the side
effects of excessive bleeding and stomach pain.
Pain Relievers: Nonsteroidal Anti-Inflammatory
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 risk
of heart attack and stroke as well as allergic reactions
and internal bleeding.
Pain Relievers: Nonsteroidal AntiInflammatory 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. Acetominphen can be taken by
those affected by aspirin side effects and
children. However, when taken with alcohol it
can cause liver and kidney damage.
Pain Relievers: Nonsteroidal AntiInflammatory 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.
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.
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.
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.
Chemistry, Allergies, and the
Common Cold
Expectorants help to bring up mucus from the
bronchial passages. Only one expectorant,
glyceryl guaiacolate (guaifensin), 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 oxymetaxoline,
xylometaxoline, naphaxoline, and
phenylephrine.
Antibacterial Drugs
In 1900, infectious
disease was a leading
cause of death.
Antibacterial Drugs
Sulfa drugs were the first antibacterial
drug. Sulfanilamide acts by replacing
para-aminobenzoic acid that bacteria need
to manufacture folic acid.
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.
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).
Antibacterial Drugs
Tetracyclines are broadspectrum antibiotics that act
by binding to bacterial
ribosomes inhibiting protein
synthesis.
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.
Viruses and Antiviral Drugs
Viruses are
composed of nucleic
acids and proteins.
Viral diseases cannot
be cured by
antibiotics.
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 which 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.
Viruses and Antiviral Drugs
Antiviral drugs have
been developed
which are effective
against some viruses
but do not provide
cures.
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.
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.
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 5-fluorodeoxyuridine are incorporated
into nucleotides and inhibit the formation
of thymine-containing nucleotides during
DNA synthesis. This slows the division
and growth of cancer cells.
Chemicals Against Cancer
Antimetabolites resemble substances essential to
metabolism and interfere with physiological reactions.
Chemicals Against Cancer
Nitrogen alkylating agents are relatives
of the mustard gases used during WWI.
They act by crosslinking DNA strands
and hindering replication.
Cyclophosphamide (Cytoxan) is used to
treat Hodgkin’s disease, lymphomas,
leukemias, and other cancers.
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.
Hormones: The Regulators
Hormones are
chemical messengers
produced in the
endocrine glands.
Hormones: The Regulators
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.
Hormones: The Regulators
Steroids are lipids with a
definite 4-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.
Hormones: The Regulators
Sex hormones are
steroids. Androgens
stimulate or control the
development of
masculine characteristics.
Estrogens are
compounds that control
female sexual functions.
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.
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.
Drugs for the Heart
Drug treatments for the heart involve
increasing blood supply, normalizing heart
rhythm, lowering blood pressure, and
prevention of lipid plaques.
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.
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.
Drugs for the Mind
Psychotropic drugs affect the human mind.
They fall into three catagories:
Stimulants such as cocaine and amphetamines
which increase alertness, speed mental
processes, and elevate mood.
Depressants such as alcohol, anesthetics,
opiates, barbiturates, and tranquilizers which
reduce consciousness and reaction to stimuli.
Hallucinogenic drugs such as LSD and
marijuana which alter the way we perceive
reality.
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.
Some Chemistry of the Nervous
System
Messages are
transmitted across the
fluid-filled gaps called
synapses by
chemicals called
neurotransmitters.
Some Chemistry of the Nervous
System
Neurotransmitters
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-orflight syndrome. It has been implicated
in some forms of mental illness.
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.
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.
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.
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.
Anesthetics
Anesthetics
Modern anesthetics can include a variety of
several drugs including:
- a tranquilizer
- an IV such as thiopental to cause
unconsciousness
- a narcotic pain killer, such as fentanyl
- an inhalant anesthetic to keep the person
unconsciousness and provide insensitivity to
pain
- a muscle relaxant like succinylcholine
chloride
Anesthetics
Local Anesthetics
Anesthetics
Local Anesthetics
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.
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.
Narcotics
Narcotics are drugs that produce narcosis
(stupor or general anesthesia) and are
analgesics (pain killers). In the United
States, such drugs that are addictive are
legally regulated and classified as
narcotics.
Narcotics
Opium and Morphine
Opium is the resinous juice of the unripe seeds of the
oriental poppy. It contains more than 20 alkaloids,
sugars, resins, and waxes.
Morphine is an alkaloid that makes up 20% of the
weight of opium.
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.
Narcotics
Synthetic Narcotics
Much research has been
done to develop a pain
killing drug as effective as
morphine but less
addictive. Methadone is
one such drug that is
used to treat heroin
addiction.
Narcotics
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.
Narcotics
Natural Opiates
Endorphins are morphine-like peptide
chains produced in response to pain that
bind to the receptors in the brain that
morphine reacts with. It causes natural
pain relief and the “runner’s high.”
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.
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.
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.
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.
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 used
to treat ADD in children.
Stimulant Drugs
Cocaine is a powerful stimulant. It used
to arrive in the U.S. as cocaine
hydrochloride. It is now available as freebase crack cocaine. It acts by preventing
the reabsorption 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.
Stimulant Drugs
Caffeine: Coffee, Tea, or
Cola
Caffeine is a mild
stimulant. An effective
dose is about 200 mg.
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.
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.
Psychedelic Drugs
Psilocybin and Mescaline
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.
Psychedelic Drugs
Marijuana is
prepared from the
leaves, flowers,
seeds, and stems of
the Cannibis sativa
plant. One major
active ingredient is
tetrahydrocannabinol
(THC).
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 antibiotic-resistant bacteria.
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-over-matter.”
New Uses for Old Drugs
The development of new drugs is very
expensive. Many older drugs have been
tested and approved for new uses.