Know Your Nose Candy Crack or Cocaine

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Know Your Nose CandyCrack or Cocaine

• Legal and Illicit Compounds
• And
• How They Work

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Outline

• Axons (the hardware)
• Neurotransmitters (the software)
• Drugs (the virus)

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Axons The Hardware

• Dendrites at one end receive stimuli.
• Depolarize and allow charges to cross the cell
  membrane starting an action potential.
• Release stored chemical messengers into the
  synaptic gap.

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The Synapse

• At the presynaptic axon, neurotransmitters are
  made and stored.
• When released, they diffuse across a gap, and
  bind at a specific receptor (protein).
• The receptor changes shape and allows for
  depolarization.

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The Synapse

• Binding is reversible.
• The neurotransmitter lets go
• Metabolized or taken back into the original axon.
• Can happen more than 400 times per second.

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Two Basic States

• Excitement
• Axons in this state release neurotransmitters
  that stimulate other neurons.

• Inhibition
• Axons in this state release neurotransmitters
  that inhibit other neurons.

Therefore the chemical messengers often occur in
pairs to both stimulate and inhibit various
functions. A sample pair would be GABA and
Glutamate
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Important Point 1

• Neurotransmitters are small molecules, whose
  presence in the synaptic gap stimulates a
  response in other axons, tissues, etc.
• Neurotransmitters are removed from the synaptic
  gap to end transmission of the signal.
• They can either excite or inhibit activity.

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Modes of Action

• Agonism
• A compound that produces more of a compound, or
  does the job of a natural substance.
• Does not effect the rate of an enzyme catalyzed
  reaction.

• Antagonism
• A compound inhibits an enzyme from doing its job.
• Slows down an enzymatically catalyzed reaction.
• May chemically appear like a normal analate.

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Important Point 2

• Agonists drugs that create an artificial
  stimulus and trick the body into doing
  something that it would normally do in the
  presence of the actual stimulus.
• Antagonists drugs that keep something in the
  body from doing its normal job. Generally this
  inhibits the reuptake of neurotransmitters.

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Drug Philosophy

• Act as either an agonist or an antagonist for
  something in the body.
• Any psychoactive drug that is administered plays
  on the use of neurotransmitters to do its job.
• The drug is not always necessary.
• A coach isnt always necessary either, but it
  helps.

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Enzyme Action

• Protein based catalyst that binds to a substrate
  molecule.
• Chemical activity happens at the active site.
• The rest of the molecule stabilizes the active
  site.

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Enzyme Specificity

• The reaction is specific to one substrate.
• pH and Temperature disrupt local forces.
• Distorts the shape of the active site.
• Enzyme activity drops off.
• Same with pH.

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Enzyme Kinetics

• The overall rate of an enzyme catalyzed reaction
  depends on the concentration of the substrate and
  the enzyme.
• Usually this is shown for a constant enzyme
  concentration.

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Enzyme Kinetics - Inhibition

• Inhibitor molecules can alter the rate through an
  inhibition scheme.
• Competitive inhibition inhibitor molecule
  competes for the active site through reversible
  binding.

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Enzyme Kinetics - Inhibition

• Inhibition can take more than one form.
• Non competitive inhibition blocks an allosteric
  site, changes the shape of an enzyme, and
  inactivates it.

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Enzyme Kinetics Drug Design

• Drugs (medicinal and otherwise) are designed to
  interact with active or allosteric sites on
  enzymes.
• They are eventually metabolized or degrade and
  the enzymes continue to function normally.
• Drug design requires intimate knowledge of the
  active site for the enzyme to be targeted, and
  the process to be effected.

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The Legal Stuff

• According to the US, there are classes
  (schedules) of controlled substances.
• Five schedules assigned by the Comprehensive Drug
  Abuse Prevention and Control Act.

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Schedules I-III

• Schedule I Very high abuse potential and no
  accepted medicinal use (marijuana, heroin, LSD)
• Schedule II Very high abuse potential and an
  accepted medical use (cocaine, morphine,
  amphetamines). Requires DEA permit for
  prescription.
• Schedule III High abuse potential and an
  accepted medical use. Commonly prescribed.
  (Barbituates, opiates)

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Schedules IV-V

• Schedule IV Moderate abuse potential and an
  accepted medical use. (Valium and
  antidepressants)
• Schedule V Low, but significant abuse
  potential, and an accepted medical use. May be
  purchased without a prescription.

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Who Knows?

• The decision as to abuse potential is handled by
• The Secretary of the department of Health and
  Human Services (HHS)
• The Food and Drug Administration.

• The decision as to how to schedule the drug is
  handled by
• Administrator of the Drug Enforcement Agency.
• The DEA cannot recommend a tighter control than
  the HHS. (Temp. Emerg. Order)

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Birth Control Medication

• Agonist
• Basic steroid structure.
• Progesterone naturally released after
  fertilization of an egg to limit further
  ovulation events.
• Original use of progesterone analogs pregnancy
  promoters.
• Enovid approved for sale in 1960. GD Searle.

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Birth Control Medication

• This progesterone analogs mimics the natural
  steroid that is produced during pregnancy.
• The pill tricks the body into thinking it is
  pregnant to stop ovulation events.
• Male version of the pill developed and tested in
  2000.

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Plan B

• Levonorgestrel
• High hormone dose (0.75mg)
• Agonist
• Intended to inhibit ovulation and/or
  implantation.
• Recommended for use within 72 of intercourse with
  a second pill 12 hours later.
• 8 chance with no contraception. 1 with Plan B.

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Birth Control - Variation

• RU-486 (Mifeprestone). Antagonism.
• Blocks progesterone receptors which produce
  proteins.
• These proteins are needed to maintain a healthy
  uterine lining.
• Alt. treatment replaced by methotrexate which
  blocks folic acid uptake, misoprostol used to
  remove the fetus. Off-label prescription.

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Alcohol

• Long history of use.
• Tied to success of some societies. (Alcohol
  kills germs)
• Grain alcohol is ethanol.
• Marketed to a near ludicrous degree.

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Alcohol - Adsorption

• The movement of alcohol into the system happens
  as it leaves the stomach and enters the small
  intestine.
• Equilibration effects.
• Food effects.
• Concentration effects.
• Metabolized into acetaldehyde in the liver with
  an enzyme.
• Acetaldehyde is toxic to the body, accumulation
  leads to nausea.

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Alcohol effects on the brain

• Depressant inhibits brain activity.
• Interacts with GABA and glutamate receptors.
• Alcohol increases stimulation of GABA receptors,
  slowing brain activity.
• Inhibits the ability to form new memories.

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Alcohol (antabuse disulfiram)

• Inhibits the activity of the enzyme that
  catalyzes aldehyde oxidation.
• The legal limit is 0.08g alcohol per 100mL blood.
• With antabuse this would equate to a full-blown
  violent hangover.
• Antabuse does not change the rate of alcohol to
  aldehyde oxidation.
• Whatever alcohol one consumes, you are stuck with
  it.

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Caffeine

• Basic Information
• The most widely used and abused legal stimulant
  in the world.
• Coffee Beans were originally chewed
• Hot extract drinks (coffee) were produced around
  1000 A.D.
• Currently present in soda and coffee beverages.

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Caffeine

• Caffeine blocks adenosine receptors.
• There is enough caffeine in 2-3 cups of coffee to
  block 50 of the adenosine receptors.
• Effects
• Heart stimulation
• Diuresis (excess urination or urine volume)

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Caffeine Function

• Caffeine blocks adenosine receptors.
• Adenosine acts as a neural inhibitor for CNS
  activity.
• Adenosine is not a neurotransmitter, it is a
  neuromodulator.
• As caffeine blocks the receptors it acts as a
  stimulant.

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Caffeine in Excess

• Too much caffeine (6 cups or more/day) increases
  the number of adenosine receptors on axons.
• Sluggishness in the absence of caffeine.
• Physiological and Psychological addiction.

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Where to go to get your fix.
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Nicotine

• Second to caffeine in terms of use (abuse).
• Comes from smoked Nicotania tabacum leaves
• Water and lipid soluble
• Absorbed through the skin
• Dopamine agonist

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Nicotine Addiction

• Each puff of a cigarette produces a spike in
  blood levels and adds to the total background
  level.
• Increasing use and tolerance establishes a
  pattern that allows smokers to maintain a level
  without withdrawal effects. Deeper drags, more
  drags.
• The desire to smoke comes when nicotine levels
  drop, or with behavioral cues.

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Nicotine Mode of Action

• Resembles acetylcholine, and binds with those
  receptors.
• Stimulates Ca channels to increase positive
  charge inside neurons and release
  neurotransmitters.
• Blocks other channels.

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Nicotine Effects on Brain

• Stimulates a nicotine acetylcholine receptor.
• Receptors are all over the brain, so nicotine
  affects many sites.
• Stimulates receptors and production of
  acetylcholine.

• Staves off hunger in the absence of smoking.
• Acts as anti-anxiety agent.
• Has been shown to increase memory in Alzheimers
  Patients.

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The Illegal Stuff

• So lets look at less than legal stuff.
• Agonists, antagonists
• Effects on other parts of the body.
• Mode of action.
• Ways in which they are used.

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Cocaine

• Schedule II compound. Used for pain relief for
  some procedures.
• Cocaine hydrochloride
• Quaternary amine, charged, white powder.

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Crack

• Tertiary amine
• No formal charge
• Fat soluble
• Must be smoked

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Cocaine - Origins

• Found in leaves of various plants.
• Sold in tonics.
• Part of the original Coca-Cola recipe.
• Coca leaves chewed by indigenous peoples to
  increase alertness.

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Taking Cocaine

• Smoking (Crack) Gets to the brain the fastest
  (Peak in 1-2 minutes)
• Snorting Cocaine (Peak in 30 minutes)
• Ingestion (Tonic, Leaf chewing) Low levels
  maintained over long time.

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Cocaine Effects

• Cocaine is an antagonist for the dopamine
  reuptake enzyme.
• Quickly metabolized. Half of the original dose
  gone in an hour.
• Blocks reuptake of norepinephrine, serotonin, and
  dopamine.

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Dopamine - Rewards

• Since dopamine deals with rewards, excess levels
  leads to stimulus addiction.
• Cocaine is a quick high so people will take
  enough cocaine to kill themselves, whereas they
  would not choose that with alcohol.

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Amphetamines / Methylamphetamines

• Amphetamines are chiral compounds.
• Levoamphetamine affects nasal passages.
• Dextroamphetamine enters the brain.
• Once given to soldiers in WWII to promote
  alertness and delay sleep, hunger, etc.

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Methylamphetamines

• These cause a rapid release of stored serotonin
  and dopamine.
• Are not easily metabolized by the body.
• Readsorbed by axons.
• Very long effectiveness 8-10 hours.

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Full body effects of amphetamines

• Simulates the fight or flight response.
• Basically makes you ready for a fast response for
  several hours.
• Your heart rate increases, brain function speeds
  up.
• You are in constant motion.
• Other portions of the nervous system get
  sensitive to invisible stimuli. Picking

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MDMA - Ecstasy

• Never produced by a drug company, all stores are
  illegal.
• Amphetamine
• Causes a dump of neurotransmitters, specifically
  serotonin, dopamine, and norepinephrine.
• Takes a long time to build up serotonin, so there
  is chance for long term mood and appetite
  problems .

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Marijuana

• Schedule I controlled compound. It is illegal to
  possess/transport/sell.
• Marijuana Tax Act in 1937 made interstate trade
  illegal.
• Decriminalized since the 1970s.
• California (Prop 205) allows patients to possess
  or grow marijuana with a prescription.

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Chemical Characteristics

• Active component is d-9-tetrahydrocannabinol
  (THC).
• Fat soluble, must be smoked or eaten.
• Immediate effects, peak in 15-45min, wear off
  after 2 hours.
• Digested THC must be heated first, otherwise, it
  is ineffective as a psychoactive drug.

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Detection

• THC is metabolized to another compound.
• Detection of 15ng/mL is legal limit for proof of
  exposure to significant amount. (More than being
  passively surrounded.)
• Single use detectable for up to 3 days. 10 days
  in a simple urine analysis.
• Continual use detectable for 28 days or more.

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SSRI

• Selective Serotonin Reuptake Inhibitors
• Serotonin effects mood and appetite in the brain.
• Blocks the enzymes that take them up.
• Artificially elevates serotonin levels.
• Prozac, Celexa, Zoloft, Paxil

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Prescription

• Since 1986 more than 50 million people have taken
  Prozac for treatment for anything from anorexia
  to panic disorder.
• Zoloft is prescribed for SAD, PTSD, OCD, PMDD
  (all entries to the DSM)

• Diagnostic and Statistical Manual of Mental
  Disorders
• Arbitrary entries, like homosexuality.
• Easier to obtain an entry than make a new drug.
• Easier to make a disease than a cure.

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Fin

• Vote well.
• Be well informed in all of your choices.
• These substances have effect while you take them,
  and after.
• Especially for drugs, the laws are very
  confusing.
• For prescription medication, know the rules of
  how you can be marketed to.
• Mark it 8 dude.