Download Drugs

3/30/2015
CHM107
Chapter 10
Drugs
Good Presentation Topics
• Herbal medicines, supplements, vitamins
(section 10.11 is a good start)
• Pharmaceuticals in our drinking water
• Other drugs – legal or illegal
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For the equivalent of a quiz grade:
•
Class debate on legalizing marijuana
•
Prepare for both sides, be devil’s advocate, research and write down 1020 statements both PRO and CON on the legalization of marijuana
•
In ONE WEEK we will spend the class having a DEBATE.
•
You will be graded on how many times you speak, and the quality of your
arguments. You will say your name out loud each time you speak.
Remember other people may say the same stuff before you! Saying “I
agree with that” does not count as speaking!!!
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Consider health, economic, scientific, environmental, and political
aspects.
Your goal is to say something relevant to the discussion several times.
Speaking 5 times = 10 pts, 4 times =9 pts, 3 times =8 pts, 2 times =7 pts,
1 times =6 pts, 0 times =0
It is OK to argue BOTH sides.
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The Wonder Drug?
Drug History
• India, 4500 to 1600 BC, early reference to
using plants as drugs
• China, 3000 BC, refers to using a plant
that we now know has ephedrine
• 400 BC, Hippocrates (famous doctor)
made tea with willow bark. This lowered
fevers, helped with pain and inflammation.
A derivative is still in use today. What is
the wonder drug???
The wonder drug
• Salicylic acid is the original drug extracted from
willow bark. The problem is that is some
individuals experience stomach irritation.
• The derivative is Acetylsalicylic acid or aspirin.
It was synthesized by Felix Hoffman and
patented by the Bayer Company in 1893.
• Aspirin did not receive FDA approval. Why?
There was no approval process at that time! If
there had been, aspirin would most likely been
approved for prescriptions only, not over the
counter!
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The “Wonder Drug”?
Functional Groups
“The presence and properties of functional groups are
responsible for the action of all drugs” Look at the next
slide and identify aspirin’s functional groups.
O
Cl
amine
ketone
O
N
alkene
Aspirin
O
H
aldehyde
O
alkyne
O
H
O
O
ether
Cl
ester
H2N
O
OH
alcohol
OH
carboxylic
acid
SH
Carbon line drawings
• Carbon is so important the study of it is
called organic chemistry
• Organic chemists use line drawings to
represent carbon and hydrogens in
organic molecules
• 12 million of the 27 million known chemical
compounds are organic
• How many bonds does each 4
carbon atom have in
hexane?
• So how many electrons are
around each C atom in
hexane?
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• How many bonds does each
carbon atom have?
• How is a single bond
represented? Double?
• How many electrons are in a
single bond? Double?
• So how many electrons are
around each C atom?
4
One line
Two lines
2, 4
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Here is another organic molecule. What
generalizations can you make about the
number of bonds around carbon? About the
number of electrons around carbon?
Yes, carbon always has 4 bonds and 8 electrons around it.
Carbon follows the OCTET RULE. Note: 4 bonds can
mean 4 single bonds, 2 single + one double bond, 1 single
+ 1 triple bond, or 2 double bonds. Draw a carbon atom
with all these options.
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Draw this structure with the
carbon and hydrogen atoms
Draw this structure with the
carbon and hydrogen atoms
How many bonds and electrons
are around each C?
Draw this structure with the
carbon and hydrogen atoms
How many bonds and electrons
are around each C?
How many bonds and electrons
are around each C?
The Body’s Chemical Communication
• Electrical pulses that travel along nerves
triggers movement, breathing, heartbeats,
and reflexes.
• But most messages in the body are
chemical.
• Endocrine glands produce hormones.
Hormones are the body’s chemical
messengers.
– Thyroxine regulates metabolism
– Insulin regulates glucose use for energy
– Adrenaline (epinephrine) regulates “fight or flight”
How Aspirin Works
How Aspirin Works
•
Hormones regulate by altering
cell metabolism. These body
processes are regulated by
hormones:
• Body Metabolism
• Growth
• Puberty
• Tissue Function
• Body Temperature
• Attitude (mood)
Aspirin and other antiinflammatory drugs
(NSAIDs) block the action of
other molecules
• Aspirin blocks
cyclooxygenase (COX)
• COX produces
prostaglandins from
arachidonic acid
• Prostaglandins cause fever,
pain and swelling
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acetaminophen
• Acetaminophen (Tylenol) reduces fever, but does
not stop inflammation.
• Ibuprofen (Advil and Motrin) is a better pain reliever
and fever reducer than aspirin. Its anti-inflammatory
action is 5 to 50 times that of aspirin.
• However aspirin is the only one that inhibits blood
clotting. Which is why low doses are sometime
prescribed to prevent heart attacks and strokes. But
aspirin should not be given to those with ulcers or
undergoing surgery.
What is similar???
aspirin
ibuprofen
Penicillin
• Molds used for treating
infections for 2500 years.
• In 1928 Sir Alexander
Fleming accidentally saw
that in a petri dish of
bacteria, the area
contaminated by the mold
Penicillium was free of
bacteria. He correctly
concluded that this mold
inhibits bacterial growth.
The actual 1929
image by Fleming for
his publication. The
area at the top is the
penicillin, the smaller
white spots are
bacteria.
• Enzymes = proteins that speed up chemical
reactions in the body
• Substrate = substance whose reaction is
sped up by the enzyme
• The way some drugs work is by blocking the
substrate from the enzyme
Receptor Site
Receptor Site
Comparisons
• Mold spore from the next lab drifted in and
contaminated Fleming’s dish. Fleming was
on vacation and noticed this dish among
dirty glassware! It was his experience that
helped him recognize the importance.
• The development of other antibiotics
followed similar experiments.
• Today we have extreme overuse however.
We now have resistant bacteria.
• What can we do about overuse? What do
you think about antibacterial soap?
The Ideal Drug
1. Efficacy: The ability to produce some desirable
effect
2. Specificity: Should bind to its target receptor, but
not other receptors or biomolecules. This can lead
to the toxic effects of drugs
Receptor Site
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Let’s look at some common drugs
• Steroids
• Statins: Lovastatin, Lipitor, Zocor, etc.
• Opiates: Morphine, Demerol, Vicodin,
Percoset, Codeine, Darvocet
• Pseudoephedrine
• Anti-depressants
• Meth
Steroids
• All have 4 ring backbone
• Many uses: birth control, abortion, body
building, fighting asthma, allergies, rashes,
inflammation
• Some steroids you may recognize: cholesterol,
cortisone, corticosterone, prednisone,
estradiol, testosterone
• Anyone know what these do???
• Look at the pictures next – slight differences in
functional groups greatly change the steroid
• Estradiol - predominant sex hormone present
in females; present in males at lower levels,
produced in the ovaries and testes, the main
estrogen, promote female characteristics,
regulate menstrual cycle
• Testosterone – hormone secreted in testes /
ovaries, main sex hormone in males,
regulates male characteristics (hair, Adam’s
apple), anabolic steroid = builds up bone and
muscle mass, men have about 8-10 times as
much as females
Steroids
Cholesterol: Component of cell membranes
Steroid Backbone
Estradiol: Sex hormone present
in females; The major estrogen
Testosterone: Sex hormone present
in males; An anabolic steroid
Statins
• Used to lower cholesterol by
inhibiting the enzyme HMG-CoA
reductase, which controls the
speed of producing cholesterol in the liver.
• Lovastatin – first one developed. Occurs naturally in
oyster mushrooms. Pictures above.
• Mevastatin – next one. Occurs in red yeast rice.
• Lipitor - Sales top $10 billion a year.
• Other meds – Zocor, Crestor, Pravachol, Vytorin
• May help with Alzheimer’s, prostate cancer,
hypertension, preventing heart attack and stroke,
dementia, colon cancer
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Opiates
• Natural and semi-synthetic derivatives from opium
which is from poppy plants
• Natural: morphine, codeine (milder),
• Semi-synthetic: heroin, oxycodone (Purdue’s OxyContin, &
Percoset which is just oxycodone + acetaminophen), hydrocodone
(Vicodin = hydrocodone + acetaminophen)
• Fully Synthetic: Demerol, methadone, tramadol
• They are used as analgesics (painkillers), cough
suppressants, to stop diarrhea, and to stop anxiety
• The World Health Organization says opiates are
essential in the treatment of severe pain. However,
only six countries use 77% of them. Poor countries are
severely lacking.
• Morphine – for severe pain, very addictive
• Oxycodone – for moderate pain, often combined with
NSAIDs, “hillbilly heroin” or “oxy”
• Hydrocodone – intermediate pain reliever and strong cough
suppresant, possible addiction
• Methadone – treats chronic pain and used to get people off
heroin and morphine, “junkie juice”
• Codeine – treats mild to moderate pain, cough, diarrhea,
often with NSAIDS like Tylenol-3, not abused near as much
as other opiates
• Heroin – made from morphine, 90% comes from Afghanistan,
very addictive especially psychologically, aka diamorphine
which can be prescribed in the UK, Netherlands, Germany,
Switzerland
• Tramadol – treats moderate pain and restless leg syndrome,
atypical of opiates, has SSRI and SNRI qualities, withdrawal
is longer than most, lower risk of addiction
Morphine Derivatives
Morphine
Oxycodone
H3C
Hydrocodone
• Work directly on the central nervous system,
relieves pain by binding to the opioid receptors
which blocks the transmission of pain in the spinal
cord, creates higher levels of dopamine (feels
good) tolerance can develop
• Adverse reactions: vomiting, drowsiness, dry
mouth, constipation,
• Extremely unpleasant withdrawal symptoms:
confusion, sweating, depression, pain, vomiting,
nausea
• Often treat withdrawal with clonidine and
antidepressants
Morphine
Oxycodone
Hydrocodone
Can you find
functional groups?
Pseudoephedrine
H3C
Heroin
Opiates
Codeine
• Decongestant
• Was over the counter, now
behind the counter because it is a precursor of
methamphetamine
• Replaced by phenylephrine in over the counter
meds
• In the amphetamine class of drugs – can be a
stimulant. Reportedly abused by truck drivers
• Can be extracted from ephedra plant species
• Adverse effects: dizzy, nervous, anxiety,
sleeplessness, can trigger a manic episode in
bipolar patients
• Banned in Olympic sports
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Anti-depressants
• All inhibit the reuptake of neurotransmitters
• SSRI – selective serotonin reuptake inhibitors
(Zoloft, Prozac, Paxil)
• SNRI – selective serotonin norepinephrine reuptake
inhibitors (Effexor)
• NDRI – norepinephrine dopamine reuptake inhibitor
(Wellbutrin)
• SSRI used for treatment against social anxiety,
panic disorders, OCD, depression, posttraumatic
stress, premature ejaculation
• NRI and DRI used for stimulation, energy, focus,
alertness, desire, decrease appetite, used to treat
ADHD, narcolepsy, fatigue, obesity
Meth
• Methamphetamine – increases alertness, self-image,
energy, sexual pleasure
• Highly abused, increases levels of dopamine, serotonin, and
norepinephrine
• FDA approved in the US to treat morbid obeisity as Dexoyn
currently
• Was approved to treat narcolepsy, depression, and hay
fever but not anymore
• Made from ephedrine
• Used widely in WWII by German soldiers, suspected that
Hitler used it until he died in 1945
• Illegal use really picked up in the 1960’s and is still
increasing
• Part of the Patriot Act involves how much pseudoephedrine
and ephedrine one can buy legally in a given time period
Drug Development
(Testing and Approval)
Green Chemistry
• All chemical manufacturing is trying to go green =
less waste, less side-products
• Current way to make ibuprofen is green. Previous
method required 6 steps, used lots of solvent,
generated lots of waste. Now made in 3 steps with
hardly any solvent or waste. All starting material
recovered. BHC company awarded the 1997
Presidential Green Chemistry award.
• Codexis, winner of the 1996 award, created a way
to make Lipitor with increased yeild, less byproducts, less waste and less solvent which
increases worker safety.
Animal Testing
• Controversial topic these days – lots of legislation over the
world lately
• LD50 – lethal dose 50 – the dose size that will kill 50% of
animals
• Vioxx example – Merck made about 1 billion dollars a year
but in 2000 was seen to increase chance of heart attack,
withdrawn in 2004, thousands of law suits followed.
Scientists would like to prevent drug failures like this despite
the animal testing.
• In 2009 EU banned many animal tests and will use biochips
instead like Datachip and Metachip
• Frontier medicine – A new biochip holds hundreds of tiny
white dots loaded with human cell cultures and enzymes.
Scientists hope the chips can do away with the need to use
animals to test new blockbuster drugs or wrinkle creams.
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• Biochips are faster, cheaper, and use real human cells not
animal cells.
• “Testing chemicals on animals for human toxicity should be
greatly reduced and can potentially be eliminated in favor of
experiments using cells, cell lines, or cellular components,
says a National Research Council report released last
week.” (C&EN June 18, 2007)
• NIH, EPA, Berkeley, UCLA, and Rensalear Polytechnic U
are all working on these chips.
• It takes about $800 million and 14 years to develop a drug
and win FDA approval. The Hurel chip could save up to $200
million and years of time. (Forbes August 15, 2005)
Dangers of Prescription Drugs
• 1. Elvis Presley (42) Elvis had a long fight with prescription
drugs. Barbituates, Demoral, codeine, morphine, Valium. Vernon
Presley, Elvis' father, had the complete autopsy report sealed. It will
remain sealed until 2027, fifty years after The King's death.
• 2. John Belushi – Belushi was an actor, comedian, and
musician. He has starred in television shows such as Saturday Night
Live, The Blues Brothers, and programs put on by National
Lampoon. Eventually, he died of accidental drug overdose as a
result of taking 11 speedballs (a combination of cocaine and heroin).
• 3. Marilyn Monroe (36)– She is known as a famous actress,
model, and American sex symbol. She was born as Norma Jean
Mortenson and was married 3 times, all of which ended in divorce.
Today, Monroe is the only woman listed on Forbes list of top earning
dead celebrities. At the age of 36, Marilyn died in her sleep of
barbiturate poisoning (an overdose of sleeping pills). To this day, no
one knows for sure whether her death was a suicide or homicide.
Dangers of Prescription Drugs
Dangers of Prescription Drugs
• 4. Billie Holiday (44) – Billie was a famous female jazz singer. She
was originally named Eleanora Fagan. This singer used hard drugs
(primarily heroin) and was involved in unhealthy relationships where
abuse took place. Eventually she developed heart disease and liver
complications. She died at the age of 44 from cirrhosis of the liver, a
problem which arose from long-term drug and alcohol abuse.
• 5. River Phoenix (23)– This actor was the oldest of five children, one
of whom is actor Joaquin Phoenix. He acted in films such as Stand By
Me, Little Nikita, The Thing Called Love, and Running on Empty.
Throughout his life he was a proud supporter of animal rights and
refused to use animal products in the films he acted in. Phoenix died as
a result of speedballs (a combination of cocaine and heroin) outside of
the night club The Viper Room. He was 23 years old.
• 6. Anna Nicole Smith (39)– Smith was an actress and model. In fact,
she was named Playmate of the Year in 1993. She was married three
times during her lifetime, the most famous of which was to J. Howard
Marshall. This oil executive was a billionaire and 63 years older than
Smith. Anna Nicole Smith died at the age of 39 from accidental
overdose of chloral hydrate and other prescription drugs.
• 7. Jim Morrison (27)– He is most famous for being a singer, but he
also wrote a number of poems, directed films, and wrote his own songs.
Morrison was a lead singer for the famous band, The Doors. Throughout
his life, the singer struggled with both drug and alcohol abuse. He died
at the age of 27. Although several stories have circulated regarding his
death, the general consensus is that he died of a heart attack triggered
by accidental heroin overdose.
• 8. Chris Farley (33) - comedian, cocaine and heroin overdose
(speedball).
• 9. Sigmund Freud (83) - neurologist, long-term cocaine use,
physician assisted morphine overdose (euthanasia).
• 10. Judy Garland (47) - singer and actress, barbiturate (secobarbital)
overdose. Her death certificate states the overdose was "accidental"
however there is speculation it was intentional.
• 11. Jimi Hendrix (27) - rock and roll musician, respiratory arrest
caused by alcohol and barbiturate overdose and vomit inhalation.
Dangers of Prescription Drugs
• 12. Howard Hughes (70) - aviator, engineer, industrialist, movie
producer, liver failure - physician administered overdose of codeine at
"the highest clinical level ever recorded".
• 13. Michael Jackson (50) - musician, died June 25, 2009, lethal dose
of propofol along with two sedatives.
• 14. Janis Joplin (27) - rock and roll and blues musician, heroin
overdose.
• 15. Heath Ledger (28) - actor, accidental death Combined Drug
Intoxication of various prescription drugs, including oxycodone,
hydrocodone, temazepam, and others.
• 16. Bruce Lee (32) - actor, martial artist, died of acute cerebral edema
due to a reaction to compounds present in the prescription pain killing
drug Equagesic.
• 17. Sid Vicious (21) - musician, the Sex Pistols, heroin overdose
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