Chapter 17 Drugs and Medicine: Healing, Helping, and Hurting

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Chapter 17Drugs and Medicine Healing, Helping,
and Hurting
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Love and Depression

• Can feelings of love and depression have a
  molecular origin?
• Love
• Elevated phenylethylamine in the brain
• Depression
• Absence of serotonin (neurotransmitter)
• We are beginning to understand the connections
  between physical and psychological conditions and
  the molecules that cause them.

Serotonin
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Aspirin Relieving Pain, Reducing Fever,
andLowering Inflammation

• Aspirin is the most popular drug in the world.
• Analgesic (pain reliever)
• Antipyretic (fever reducer)
• Anti-inflammatory (lowers inflammation)
• Aspirin works on
• Prostaglandins to mediate pain and fever
• Histamines to reduce inflammation

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Aspirin Side Effects

• Stomach irritation
• Ulcer patients beware
• Blood thinning
• Lowers stroke and heart attack risk
• Reyes syndrome
• Children with chicken pox or flu should not take
  aspirin.
• Toxic in large doses
• More children are poisoned by aspirin than by any
  other drug.

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Concept Check 17.1

• What side effect of aspirin makes it unsuitable
  for use by children?

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Concept Check 17.1 Solution

• Aspirin has been linked to increased risk of
  Reyes syndrome.
• Aspirin is toxic in large doses. More children
  are poisoned by aspirin than by any other drug.

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Aspirin Substitutes

• Acetaminophen
• Tylenol, Anacin-3
• Does not reduce inflammation
• Ibuprofen
• Advil, Nuprin, Motrin IB
• Naproxen
• Long-lasting effect
• Aleve

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Concept Check 17.2

• Outline the structural similarities between
  naproxin and ibuprofen.

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Concept Check 17.2 Solution

• Structural similarities between naproxin and
  ibuprofen.

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Antibiotics

• Work by targeting the physiology of bacteria,
  selectively killing them
• Bacterial infections were top causes of death
• This is still the case in many underdeveloped
  countries.

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Common Antibiotic Categories

• Penicillins
• Cephalosporins
• Tetracyclines

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Penicillin

• Accidental contamination with a fungus destroyed
  bacteria
• Penicillins tried on humans by other researchers
• Effective in killing many pathogenic bacteria
• Almost no toxicity to humans
• MEDICAL MIRACLE
• BUT, resistant strains of bacteria discovered and
  others developed resistance over time

Alexander Fleming discovered penicillin.
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Penicillin Development and Use

• Oral administration or injection
• Multiple penicillin choices
• Chemically related cephalosporins active against
  penicillin-resistant strains
• Cephalosporins modified to meet specific purposes
• Penicillin and cephalosporins both prevent normal
  development of bacterial cell walls.
• Tetracyclines inhibit protein synthesis.
• A completely antibiotic-resistant TB strain has
  developed since the 1980s.

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Concept Check 17.3

• A childs dose of the antibiotic Amoxicillin is
  25 mg/kg per day. What is the correct Amoxicillin
  dose for a 35-pound child?

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Concept Check 17.3 Solution

• First, convert the mass of the child from pounds
  to kilograms
• Now, multiply the mass of the child (15.9 kg) by
  the conversion factor, which is the daily dose of
  the drug per kilogram body weight

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Antiviral Drugs and AIDS

• Viruses require a host cell for reproduction.
• Hard to attack them without also attacking
  healthy hosts
• Viruses do not respond to antibiotics.

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Vaccination

• Introduction of an inactive virus into the body
• Body develops antibodies that remain to fight off
  the virus should it occur
• Common cold
• No vaccine, too many strains of cold virus
• AIDS
• No vaccine, but research has led to the
  development of nucleoside analogs and protease
  inhibitors

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Nucleoside Analogs

• These are nucleotides without the phosphate
  groups.
• They work by fooling the enzymes that construct
  viral DNA.

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Concept Check 17.4

• AZT, the AIDS drug, is a replica of the
  nucleoside thymidine. How are AZT and thymidine
  similar and how are they different?

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Concept Check 17.4 Solution

• AZT and thymidine virtually identical except at
  C3, AZT has an N3 substituent where thymidine
  has an OH group.

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Integrase Inhibitors

• In 2007, the FDA approved the use of raltegravir,
  a new class of drugs called integrase inhibitors.
• Target HIV replication
• Work by suppressing the an enzyme that HIV uses
  to insert its RNA into host cells
• Can be used in combination with other drugs to
  lessen the chance of drug resistance
• Can be given to patients that have already
  developed a resistance to other drugs

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Protease Inhibitors

• Attack virus replication at the stage when viral
  protein is produced.
• Proteases act as molecular scissors to cut viral
  proteins properly.
• Protease inhibitors jam the cutting site and
  prevent the replication of the virus.

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Sex Hormones and the Pill

• Sexual characteristics are governed by hormones.
• Testosterone is the most important of the male
  sex hormones called androgens.
• In females estrogen and progesterone are secreted
  in cyclical patterns.
• The birth control pill contains analogs that
  regulate the menstrual cycle and establish a
  state of false pregnancy.

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Concept Check 17.5

• What structural features are common between the
  hormones progesterone and testosterone?

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Concept Check 17.5 Solution

• Progesterone and testosterone are almost exactly
  the same structurally except the hydroxyl group
  in testosterone is replaced with an acyl group in
  progesterone.

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New Developments

• Mini-pill
• Contains only progestin (a progesterone analog)
• Fewer side effects
• Slightly less effective than the normal pill
• Efficacy dependent on regular doses
• Mifepristone (RU-486 )
• Terminates pregnancy within five weeks of
  conception
• Blocks progesterone necessary to sustain
  pregnancy
• Controversial (when does life begin?)

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Steroids

• Sex hormones are part of this larger class of
  compounds.

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Adrenocortical Steroids

• Used primarily for potent anti-inflammatory
  effects
• Useful when inflammation causes pain
• Allergic reactions
• Rheumatoid arthritis
• Colitis
• Leaves the patient subject to infection
• Side effects include fluid retention, muscle
  loss, and osteoporosis.

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Anabolic Steroids

• Synthetic analogs of testosterone
• Used to increase muscle mass
• Serious side effects
• Males
• Lower sperm production and testicular atrophy
• Females
• Promotion of male secondary sex characteristics
• Both
• Liver damage, stroke, and heart attack

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Chemicals to Fight Cancer

• Cancer cells are similar to normal cells but with
  a faster division rate.
• Several methods of action of cancer drugs
• Alkylating agents
• Antimetabolites
• Topoisomerase inhibitors
• Hormone treatment
• Chemotherapy is the administration of these
  drugs.
• Alone and often combined with other treatments,
  like surgery and radiation
• Bone marrow, digestive tract, reproductive
  system, and hair follicles suffer most side
  effects

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Alkylating Agents

• Highly reactive compounds that add alkyl groups
  to other molecules
• Added to DNA, cell death results
• Cyclophosphamide is called a nitrogen mustard
  because its structure is similar to WWI-era
  mustard gases.

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Antimetabolites

• Methotrexate (chemical imposter)
• Mimic normal compounds but do not behave in a way
  that allows DNA synthesis

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Topoisomerase Inhibitors

• Topoisomerase inhibitors are more specific in
  their action.
• Modify the action of topoisomerase, which
  normally pulls DNA apart during replication
• Cells die whenever they initiate replication.

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Hormone Therapy

• Some cancers are fueled by hormones.
• Hormone therapy to specific tissues is available
  for cancers of the breasts or sex organs.
• Estrogen positive breast cancers are treated with
  estrogen agonists, which compete for estrogen
  receptor sites and block estrogen from
  initiating/supporting tumor growth.
• Fewest side effects of chemotherapies

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Concept Check 17.6

• Alkylating agents and topoisomerase inhibitors
  work by affecting how DNA operates in a cell.
  How are their activities different in their use
  to fight cancer?

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Concept Check 17.6 Solution

• Alkylating agents react with DNA in a
  non-specific way to destroy its function. At
  this point, cellular mechanisms detect DNA damage
  and will usually kill the damaged cell to prevent
  DNA mutations from propagating through cell
  division.
• Topoisomerase inhibitors are more specific in
  their action by modifying the action of
  topoisomerase, which normally pulls DNA apart
  during replication. Topoisomerase inhibitors
  result in DNA damage and therefore in cell death
  during the action of topoisomerase. Effectively,
  these compounds cause cells to die whenever they
  initiate replication.

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Depressants

• Called tranquilizers or downers
• Used medically to treat anxiety and insomnia, and
  as an anesthetic
• Abused widely as recreational drugs
• Alcohol
• Ethanol or grain alcohol
• Liver metabolizes at rate of one drink per hour
• Depresses the CNS
• Moderate consumption may increase lifespan
• Heavy consumption definitely decreases lifespan

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Depressants

• Barbiturates and benzodiazepines
• Barbiturates
• Depressant legally obtained through prescription
• From 19121960 used for anxiety and insomnia
  treatment
• Induce physical and psychological dependence
• Benzodiazepines
• Anxiety and insomnia treatment today
• Flumazil terminates the depressant effect of
  benzodiazepines.

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Concept Check 17.7

• What structural features are common in
  barbiturates?

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Concept Check 17.8 Solution

• Barbiturates differ by their substituents at the
  tetrahedral carbon on the six-membered ring.

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Inhalants

• Anesthetic
• Nitrous oxide Displacesair and hypoxia can
  result in brain damage and suffocation.
• Enflurane Used to anesthetize patients during
  major surgery.
• Abused
• Household chemicals Glue, pen solvents, and
  aerosol propellants. Brain damage, kidney and
  liver damage are common side effects.

Nitrous oxide
Enflurane
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Narcotics

• Drugs that act on the CNS to produce an analgesic
  and sedative effect bind to opioid receptors
• Greater ability to relieve pain and lower
  tendency to produce generalized sedation

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Opium

• Extracted from the opium poppy
• Has been used for thousands of years
• Produces euphoria, relieves pain, and induces
  sleep.
• Morphine is the primary component.
• Highly addictive

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Morphine

• Primary component of opium
• Drug of choice to treat severe pain
• Produces euphoria and feelings of well being, but
  user is left craving more
• 1914 Harrison Narcotic Act Banned nonmedical use

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Codeine

• Also found in opium, but only 1/10 as potent.
• Taken orally and administered with aspirin or
  ibuprofen to relieve moderate pain

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Heroin and Fentanyl

• Heroin
• Produced from morphine and reaches the brain
  faster
• Three times more potent than morphine
• Fentanyl
• Synthetic drug more potent than morphine
• China White

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Drugs that Fight Narcotic Overdose and Addiction

• Opioid antagonists
• Cancel the effect of the narcotic
• Naxalone
• Methadone

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Concept Check 17.8

• What structural features are common between
  morphine, codeine, and heroin?

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Concept Check 17.8

• Morphine, codeine, and heroin and the same
  skeleton of carbon, nitrogen, and oxygen atoms.
  The differences occur with the substituents off
  the oxygen atoms (-OR groups).

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Endorphins

• Why do opioid receptors in the brain exist?
• Body produces its own opioid compounds
  Endorphins
• Runners high

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Stimulants Cocaine and Amphetamines

• Uppers
• Increased alertness and energy
• Decreased appetite
• Fight or flight response
• Cocaine
• Plant derivative indigenous to Peru, Bolivia, and
  Ecuador
• Freud advocated use to treat depression
• Until 1903, Coca-Cola contained 60 mg per
  serving.
• Psychological dependence is intense
• Controlled under the Harrison Act
• Amphetamine
• Treatment of narcolepsy
• Methamphetamine is the most abused amphetamine.

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Caffeine The Legal Stimulant

• Blocks adenosine receptors, causing increases in
  dopamine and norepinephrine levels in the brain
• Effects felt at doses as low as 100 mg ingestion
  of 10 g or more is lethal
• Relatively harmless, but withdrawal symptoms
  develop even for modest consumers

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Nicotine

• Found in cigarette smoke and chewing tobacco
• Interacts with acetylcholine receptors in the CNS
• Powerful addictions well-documented negative
  health effects

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Concept Check 17.9

• What do nicotine, caffeine, and cocaine have in
  common?

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Concept Check 17.9 Solution

• Nicotine, caffeine, and cocaine are nitrogen
  based organic compounds extracted from plants
  which belong to a class of compounds known as
  alkaloids. All three also act as stimulants and
  are highly addictive.

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Hallucinogenic Drugs Mescaline

• Naturally occurring in the peyote cactus
• Inhibits the filtering of sensory stimuli on the
  nerves
• Used in sacramental and religious rites of the
  Aztec and Native American tribes

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Designer Drugs

• MDA, MMDA, MDMA (ecstasy)
• Mescaline-type action
• No physical addiction
• Psychological addiction is a concern.
• Potential brain damage
• Irreversible destruction

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Concept Check 17.10

• The designer drug MDMA has a structure similar to
  methamphetamine. Outline the structural
  similarities and predict one of MDMAs effects
  based on structural similarities.

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Concept Check 17.10 Solution

• MDMA and the stimulant methamphetamine have very
  similar structures. MDMA exerts the effect of a
  stimulant at small doses, with hallucinogenic
  effects at higher doses.

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LSD

• Dr. Albert Hoffman, 1938
• Personal experience with the effects of LSD
• Acoustic perceptions were transformed into
  optical illusions
• Believed to inhibit the filtering of sensory
  stimuli in the nerves.
• Exact effects are unpredictable flashbacks are
  possible long after drug use is terminated.
• Not physically addictive, but may cause
  psychologically addictive

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Marijuana

• When smoked, ?-9-tetrahydrocannabinol (THC) is
  absorbed into bloodstream through the lungs.
• Cannabinoid receptors bind THC sedative and
  mildly hallucinogenic effects
• Side effects are controversial.
• THC is metabolized very slowly long-term
  consequences

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Prozac and Zoloft

• Valium was the drug treatment of choice for
  anxiety.
• Now Prozac and Zoloft treat depression without
  sedation.

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Antidepressant Comparisons

• Depression is feeling of sadness. Extended or
  unremitting depression that interferes with
  normal activities can be a sign of an underlying
  mood disorder.
• First-generation antidepressants affected brain
  levels of neurotransmitters.
• New models are serotonin specific (SSRIs) and
  show minimal side effects.
• Fluoxetine (Prozac) inhibits re-uptake of
  serotonin.
• Action builds with repeated daily doses
• Sertraline (Zoloft)
• More selective for serotonin, shorter half-life
  in bloodstream

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Chapter Summary

• Molecular Concept
• Common drugs
• Sexual hormones and the ways drugs impact them
• Depressants
• Narcotics
• Stimulants

• Societal Impact
• The positive impact of drug therapy on society is
  obvious The average person today lives 20 years
  longer than the average person did in 1900.
• The easy access to drugs in our society also
  raises many issues regarding their use and abuse.