Amphetamines Flashcards
What are amphetamines?
is a potent central nervous system (CNS) stimulant of the phenethylamine class that is used in the treatment of attention deficit hyperactivity disorder(ADHD) and narcolepsy.
Ancient history of amphetamines:
- Cathinone, the active ingredient in khat (or gat) (Catha edulis), an evergreen shrub native to East Africa and Arabia
- Ephedrine, from the herb Ephedra vulgaris, used in Chinese medicine for thousands of years
- but unlike the others, amphetamines are not just purified fromt hese plants
What are some of the natural dangers of amphetamines?
- Ephedra-containing weight loss products became very popular in the 1990s
- But it also elevates blood pressure and increases risk of heart attack or stroke
- After many reports of adverse effects, including death of a baseball player, the FDA banned the sale of ephedra-containing dietary supplement in 2004
In terms of structure, what is amphetamine?
Amphetamine is the parent compund of family of synthetic psychostimulants that are structurally related to DA
Why were amphetamines created?
- In the 1920s, ephedra was found to be a valuable anti-asthmatic (bronchodilator).
- Because of limited supplies, search for a synthetic subtitue turned out to be amphetamine, frist synthesized in 1887
- An inhaler was introduced in 1932, then tablets were used to treat narcolepsy
In recent history, how were amphetmaines important?
- Amphetamine use bec ame popular for many ailments, as well as keeping soldiers awake and alert
- Used by Americans, Germans, and Japanese
- After WWII, usage soared
- In 50’s and 60’s very common for students and truck driversz
- By 1970 over 10% of the population in the US over 14 had used
- After 1970 use was largely replaced by cocaine, except for a recent surge in methamphetamine use
How is amphetamine taken? Streetnames?
- Amphetamine is taken orally or by IV or subcutaneous injectio (skin popping)
- Street names include
- uppers, bennies, dexies, black beauties, and diet pills
How are methamphetamines related to amphetamines?
- Methamphetamines are very similar to amphetamines (simply adding a methyl group to amphetamine)
- But one samll change can make a large difference in the system
- Methamphetamine has very strong effects on the CNS.
How can methamphetamine be introduced to the body? street names?
- Street names: meth, speed, crank, zip, and go
- It can be taken orally, snorted, injected IV, or smoked
- Smoking is doen with a glass pipe or by heating the drug on apiece of aluminum foil (“chasing the dragon”)
Give me a brief breakdown of meth’s history:
- Synthesized in 1919 by Akira Ogata
- Water-soluble, so it could be injected
- In 1950’s-> prescribed for everything from depression to obesity
- In 1960’s-> Beg. of making meth illegal (illegal in 1970)
- In 1978-1983-> “Golden years” of illicit methamphetamine manufacture (where “crank” comes from
- Cheaper than cocaine
- Controlled subtance act (1986)-> Federal Analong Act-> “any drug chemically similar to an illegal drug is illegal”
What is “ice”?
- Methamphetamine hydrochloride is a crystalline form particularly suitable for smoking (“ice” or “crystal”) began showing up in Hawaii in the 1980s
- Similar to difference between cocaine and crack
- “Ice” in inexpensive to make and is highly addictive
What are some stats on Meth for today?
- In 2011, 12 million
- 2000 DAWN (drug abuse warning network) reported a 30% (10,000- 13,000) increase of methamphetamine realted episode
- Today about 50% of the visits to ER caused by drugs are due to meth
- Dominant problem in San Francisco, San Diego and Hawaii
- Extended to Wst and Southwest and now South and Midwest
- Amphetamine and metamphetamine -> represent 12% of all Federal drug arrests
- Availability has increased in Boston, Chicago, Miami, New York
- There are 26 million users in the world (more than cocaine and heroin together)
What are some downsides to meth production?
hint: eco
- For each pound of methamphetamine produced in the traditional way there are 5 pounds of toxic waste and by-products
- Phosphine (toxic gas)
What are some behaviors displayed by meth abusers? “take the edge off”? “speedball”?
- Some users (“speed freaks”) go on binges, or “runs” of repeated IV injections to experience recurrent highs
- During a run, the drug is typically injected about every 2 hours for as long as 3 to 6 days, with little sleep or eating
- Barbiturates or other depressants are sometimes used to “take the edge off” during a run or to aid sleep afterward
- IV amphetamine or methamphetamine is sometimes combined with heroin to yield a so-called “speedball”
What about the pharmacology of amphetamine and methamphetamine?
- Amphetamine and methamphetamine are metabolized by theliver at a slow rate
- Because of long half-lives, users obtain a longer-lasting “high” from a single dose than from a dose of cocaine/
- Amphetamine and methamphetamine are indirect agonists of catecholaminergic systems
- Includes DA and NE
What are the mechanisms of action?
- There are two mechanisms of action
- Molecules enter DA nerve terminals through DA transporters (DAT) and cause vesicles with DA to open inside presynaptic cell
- Released DA is transported outside the cell by a reversal of DAT
- Skips exocytosis
- Results in high concentrations of DA outside cell
- NE-releasing effects of aphetamines occur in the brain and in the sympathetic nervous system
- Consequently, these compounds have potent sympathomiemetic actions, similar to those seen with cocaine
Pharmacokinetics of methamphetamine:
•Smoked, snorted, orally ingested or anally
•Smoked or injected
–“Flush” for a few minutes
•Snorted or orally ingested
–Euphoria in 3-5 min (snorted) or 15-20 min (ingested)
•Used in “binge and crash”
•Metabolismà Liver
•Excretion à urine
•Elimination half-life à 8 hours
–Much longer acting than cocaine
•Mechanism of action is the same as amphetamines
What are some of the behavioral effects of amphetamine:
•Physiological: Activates the sympathetic nervous system
–Decreased appetite
–Increased stamina and physical energy
–Faster breathing
–Increased heart rate
–Elevated blood pressure
–Involuntary bodily movements
–Increased perspiration
–Hyperactivity
–Jitteriness
–Nausea
–Itchy, blotchy or greasy skin,
–Increased heart rate,
–Irregular heart rate
–Headaches
What are some of the acute effects of amphetamines?
- •Psychological
- Rushes (when is injected IV)
- “Being lifted into the air with feelings of extreme happiness”
- “The heart starts beating at a terrible speed and his respiration is very rapid. Then, he feels as if he was ascending into the cosmos, every fiber of his body trembling with happiness.
- Euphoria
- Increased confidence
- Strong sexual component
- Increase in libido (sympathetic system is involved)
- Alertness
- Increased concentration
- Rapid talking
- Nystagmus (eye wiggles)
- Hallucinations
- Loss of REM sleep (dreaming) the night after use
- Rushes (when is injected IV)
Chronic physiological effects of amphetamines:
- Tremor
- Restlessness
- Changed sleep patterns
- Poor skin condition,
- Tachypnea
- Weakened immune system
- Fatigue and depression
- Erectile dysfunction
- Heart problems
- Stroke, and liver, kidney and lung damage can result from prolonged use.
Major Chronic physiological effects of amphetamines:
- Insomnia
- Mental states resembling schizophrenia
- Aggressiveness
- Dependence
- Withdrawal symptoms, irritability, confusion, and panic
- Amphetamine psychosis
- paranoia
- Engage in repetitive behavior and become fixated on trivial actions
Medical use of amphetamines:
- ADHD
- Narcolepsy
- Weight loss
- Supresses apetitie, but rarely used today for this purpose because of abuse potential
PFC and ADHD:
- Psychostimulatns in low doses produce a calming effect in more than half of children with ADHD
- Individuals with ADHD have many of the same symptoms as people with damage to the righ prefrontal cortex (PFC)
- Brain imaging studies have found abnormalities of the right PFC in ADHD patients
Inner workings of ADHD:
- The output neurons of the PFC are innervated by noradrenergic and dopaminergic systems. Key receptors are α2A for NE and D1 for DA
- NE activation of α2A receptors enhances the strength of relevant sensory input
- Increases ability to pay attention to what you want to pay attention to
- DA activation of D1 receptors weakens irrelevant sensory input
- Increases ability to ignore what you DON’T want to pay attention to