HLSC 130

• Chemical name: Sodium chloride
• generic name: table salt
• brand name: Morton's

• Heroin - opioids, analgesics
• Cocaine-stimulants
• Alcohol-depressant
• LSD-hallucinogens
• Prozac-Antidepressant

Non-specific drug effects derive from the user's unique background and particular perception of the world.

Specific drug effects depend on the presence of the chemical at certain concentrations in the target tissue.

Dose-response relationship is the correlation between the response and the quantity of drug administered.

The dose of a drug that produces a meaningful effect in some percentage of test subjects

the dose of a drug that has a lethal effect in some percentage of test subjects

measured by the amount of a drug required to produce a given effect

Neither patient nor researcher know (about whether drug or placebo administered), but collect data on therapeutic and side effects.

The level at which an effect is first observed

• Drugs vary in the timing of the onset, duration and termination of effects
• -how the drug is administered
  
• -how rapidly is it absorbed
  
• -how it is eliminated from the body

• Fastest-inhalation
• Faster-injection
• Slowest-ingestion

• Advantages:
• From the lungs
  
• Through capillary walls
  
• Into the bloodstream
  
• To the brain
  
• Rapid effects in
  5 to 8 seconds
• liver metabolism avoided

• Disadvantages:
• increased risk for direct adverse effects
• potential for lung toxicity

• Advantages:
• Rapid effects
  
• High concentrations
  
• Subcutaneous-slow and sustained drug effect
• Intramuscular-more rapid than subcutaneous

• Disadvantages:
• Irritating material
  
• Can damage veins
  
• Infections
• necrosis
• Drug absorption unpredictable/unusual in very obese/emaciated individuals

Fastest-arm, medium-thigh, slowest-butt

• Advantages:
• Liver metabolism avoided
• rapid drug effects
• reliable and convenient
• faster absorption through mucous membranes

• Disadvantages:
• potential for nasal necrosis

Nonspecific factors would influence a psychoactive vs. an antibiotic because one is not expecting a "high" from an antibiotic. 

the LD₅₀ (te lethal dose in 50% of animals) should be greater than the ED₅₀ (effective dose in 50% of animals) because that is the level at which death occurs.

Tolerance caused by altered nervous system sensitivity (i.e. from overuse/abuse of psychoactive drugs)

Tolerance caused by learned adaptation to the drug.

because of the low dosage necessary for the effects (50 micrograms) to begin

the dosage between an acceptable level of effectiveness and the lowest toxic dose.

inhalation

CYP450 are liver enzymes which metabolize drugs; they wait in the liver to inactivate ingested chemicals. 

However, once the liver recognizes a foreign substance (drugs), the CYP450 enzyme tries to return the body to homeostasis - possibly rendering one drug inactive but with another develops a tolerance (competing drugs for metabolism).

this has to do with drug disposition tolerance, when increased CYP450 enzyme activity metabolizes the drug faster, requiring an increased dosage for the same effect.  But more drug activity causes increased metabolism...

the drug continues to have the same biochemical effect  but with a reduced effect on behavior (like someone who breaks their writing hand improves with the other)

A drug's reduced effectiveness and increased withdrawal reactions, most notably, the brain does not change, but neuron sensitivity to the drug does.

Five grams of crack was a minimum of 5 years, the same in powder was a maximum of one year. 

In addition, Blacks were disproportionately given harsher sentences, exaggerated crack's harmfulness (vs. "blow"), most often applied to low-level defenders, and quantity-based sentences overstated seriousness of crack

Anti-Drug Abuse Acts of 1986 and 1988
Penalties for sale of crack cocaine significantly moresevere than penalties associated with powder cocaine


Tougher penalties for first-time users of crack

• dopamine
• seratonin
• GABA
• glutamate

cocaine blocks the reuptake of dopamine, norepinephrine, and seratonin causing a prolonged effect on these neurotransmitters

Cocaine blocks reuptake of dopamine, serotonin, andnorepinephrine

Ingestion- (coca leaves) slow, steady and reduced absorption; release through mucous membranes

Inhalation-rapidly absorbed, reaches brain quickly

IV - very rapidly absorbed, rapid and brief effect

Smoking- same as IV but less invasive

Half life of one hour, drug screens half-life eight hours

Acute: small amounts not necessarily bad, but increased amounts causes CNS stimulation i.e. convulsions - respiratory or cardiac arrest.  Also, cocaine is "cut" with toxic substances, and combination with alcohol which can be more toxic.

Chronic: (binge) irritability, restlessness and paranoia, also paranoid psychosis with auditory hallucinations

causes largest proportion of admits into drug programs nationwide

can cause anxiety, irritability, depression, increased appetite, exhaustion, cocaine craving upon withdrawal (but psychological pull is strong)

Ephedrine - causes bronchial dilation, stimulates sympathetic branch of ANS, including elevated blood pressure

Patented into amphetamines, adderal is used to treat ADHD, and amphetamine for narcolepsy

Prevalent, as they were prescribed by MD's for postponing sleep, weight control and depression

in Haight-Asbury, next to established IV heroin users who were doing "speedballs" to intensify their high.  the hippies started doing that as well.

As the use of amphetamines were recognized as abuse, they were prescribed less and tightly controlled

associated with hippies and heroin, overprescribing as well

MDs prescribed less, manufactured less, cost went up, illicit manufacturing skyrocketed

HI, CA and midwest all hubs of meth manufacture and use, subculture in gay communities in urban areas

Causes increased activity of monoamine neurotransmitters by stimulating their release;

Chemical structure is similar to the catecholamine neurotransmitters


Methamphetamine structure allows it to moreeasily cross the blood-brain barrier

• Peak effects
   
• 1.5 hours after oral ingestion
  
• 5-20 min after intranasal administration
  
• 5-10 min following IV injection or smoking
  

Half-life
5-12 hours

Rapid tolerance (tachyphylaxis) can occurafter high doses

• Acute behavioral toxicity:
• 
  Increases in feelings of power, suspicion,paranoia
  

Potential risk of violent behavior


Very high doses may destroycatecholamine neurons


Contaminants formed during the manufacture of illicit methamphetamine may have toxic effects on brain cells

Paranoid psychosis


Two possible reasons for the psychosis
1. Heavy methamphetamine users have schizoid personalities.
2. Caused by sleep deprivation.


Higher risk among those who inject the drug

• Often no obvious withdrawal symptoms
  Produce psychological dependence
  
• Capable of producing dependence as defined by DSM criteria
  
• A potent reinforcer

at low dosages, can improve mental acuity and physical performance (because of disruption of sleep), simple tasks only

• Miami, FL is America’s "Cocaine Capital"
•  Two main forms of cocaine made is powder and crack cocaine
•  Crack cocaine is the cheaper alternative but more potent alternative to powder cocaine.
•  1984-crack cocaine first emerged in the US; 5.8 million crack cocaine users are addicted within the first year

• Powder cocaine is the preferred in London
•  1990’s use of cocaine sky rockets
•  42 tons of cocaine is used in the UK each year
•  Britain consumes more cocaine than any other nation in Europe.

•  2 million cocaine dealers around the world  1,000 tons of cocaine is manufactured/produced yearly
•  Fishing boats were used to smuggle drugs into the US through San Diego.
•  "Eddie" made $40,000 per month in trafficking cocaine from Mexico to New York.  Get $13 million for trafficking to LA and $18 million to NY = $5 million to get cocaine from San Diego to New York
•  Drivers had to pass a 30 second test, to determine if that person is worth interrogating when pulled over
•  Traffickers can make 25% of the retail price of cocaine. A worldwide total of $50 billion/year
•  "Blood in, blood out" means kill to get in and kill to get out.
•  Drug wars cost the lives of 20,000 people

 In 2006 Philippe Calderon is elected President of Mexico. The drug-related death rate went down and the cartel needed a new leader when the Mexican government took down the "Big Fish"/major

•  Over half of the world’s cocaine comes from Columbia
•  Cocaine farmers/growers make the least amount of money in the production chain, and traffickers make the most money.
•  Cocaine paste sells for $750/kilo and yucca plant sells for 40 cents/kilo
•  Coca paste is created from breaking down the coca leaves.
•  Only ½ of 1% of coca leaf is cocaine
•  Cement powder and liquid fertilizer are used to break down the leaves, then gas is used to extract the cocaine into a liquid cocaine, and then sodium crystals are added and the liquid is cooked off.
•  "The Producer" (farmer) has no intention to make people addicted to cocaine so he can make money, he’d rather grow local crops such as yucca.
•  Farmers make an average of $1 million pesos/$500 per year; 5 cents per gram.

•  Cocaine is snorted and smoked by 1.9 million Americans; 360,000 are hard core crack addicts
•  Euphoria from the first hit of crack cocaine is the highest. Never get the same high again and always chase the first high.
•  Crack cocaine is considered the "poor man’s drug".
•  Generally rich people use more powder cocaine and poor people use more crack cocaine.
•  Smoking crack cocaine is more addicting than snorting the powder form.

• 20 million cocaine users worldwide from United Nations World Drug Report; majority of the users snort
•  Cocaine creates intense feels of pleasure without a loss of control, falling into a stooper, or hallucinations
•  Dopamine is the neurotransmitter signaled in the brain when cocaine is snorted.
•  Cocaine use changes the structures in the brain

• 25% of users will develop a problem-prison or addiction
•  Animal research resulted in the animals compulsively taken cocaine and none survived, whereas the animals taking heroin were alive
•  Researchers believe people can get addicted to the lifestyle (environment, friends, and situations) of cocaine.
•  New research shows that cocaine can be so addictive that showing images of cocaine use can increase dopamine levels and lead a person into relapse. Relapse is due to effects on the memory system.
•  Law enforcement treats cocaine users as criminals, rather than people suffering from a disease
•  Over past 10 years government has repeated reduced funding for drug rehabilitation and increased funding for prisons. As a result, 1 million American are in prison in the US on drug related crimes costing tax payers $12.5 billion is spent on offenders in prison
•  40% of coke and 77% of crack offenders, reoffend

•  Cocaine eradication programs in Columbia have had an effect in the amount of cocaine produced in the country.
•  The amount of cocaine manufactured in Columbia today remains the same as a decade ago.

•  Austin, TX is the major "transit hub" for cocaine into the US
•  1.8 million people arrested on drug charges last year, that is one every 20 seconds.

• Supply and demand,
• addictive nature,
• quick euphoric feeling,
• and money made from distribution

• 
  Absorption
  
• Some: stomach;
• Most: small intestine
  
• Slower with food or water;
• Faster if carbonated
  

• Distribution
  Blood alcohol concentration (BAC)
  expressed as a percentage in terms of grams per 100 ml
  
• Throughout body fluids
  
• Less distributed in fatty tissues
  

• Metabolism
  Liver: about 0.25 oz of alcohol per hour
  
• If rate of intake = rate of metabolism, BAC is stable
  
• If rate of intake > rate of metabolism, BAC climbs
• Metabolism
  Liver: about 0.25 oz of alcohol per hour
  
• If rate of intake = rate of metabolism, BAC is stable
  
• If rate of intake > rate of metabolism, BAC climbs
  
• Blood Alcohol Concentration
  The relationship between blood alcohol concentration and alcohol intake

• 0.5 ounce of pure alcohol
  
• 12 ounces of beer
  
• 4 ounces of wine
  
• 1 ounce of 100-proof spirits

·“Buzzed driving is drunk driving”·        

.08 for over 21 years old is drunk driving

·.01 or above for under 21 years old is drunk driving – Zero tolerance policy·   

      DUI’so   Infraction – fineo   Misdemeanor – fine plus possible jail timeo   Felony-  possible prisono   1st time DUI’s include fees and court costs ranging from $15,000 to $20,000 if plea bargained. Add attorney fees if taken to court. Plus court ordered classes.

• ·        85-90 % of college rapes/sexual assaults involve alcohol (used by the victim, perpetrator, or both).·       
• A hangover is the most common negative consequence students report as a result of drinking alcohol.·       
• The prefrontal cortex does not fully develop until about age 24. Because of this, alcohol will affect cognition more in students under 24 when compared to those older than 24. (This was discussed within the context of impaired thinking the day after drinking.)·        Carbonated beverages mixed with alcohol speed up the absorption rate.·   
•      Alcohol interferes with the REM stage of sleep.·       
• High-risk drinking is defined as four drinks in one sitting for women, and five drinks in one sitting for men.·       
• The presence of food in the stomach will slow down how fast alcohol is absorbed.