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
How can stimulatns help ADHD?
- Arnsten et al. argue that PFC functioning is an inverted U-shaped function of the activity of both catecholaminergic systems and that the action of stimulants and nonstimulants is to enhance catecholaminergic activity in the PFC.
- DA activity in the PFC may be deficient in ADHD patients.
What does dopamine have to do with reward(s)?
- Dopamine Pathways: In the brain, dopamine plays an important role in the regulation of reward and movement. As part of the reward pathway, dopamine is manufactured in nerve cell bodies located within the ventral tegmental area (VTA) and is released in the nucleus accumbens and the prefrontal cortex. Its motor functions are linked to a separate pathway, with cell bodies in the substantia nigra that manufacture and release dopamine into the striatum.
- Source: NIDA: The Science of Drug Addiction
Dopamine: cocaine vs methamphetamine
•Animal studies conducted at UCLA show that cocaine releases 350 units of dopamine, while methamphetamine releases almost four times as much – about 1,200 units. Similarly, smoking meth produces a high that lasts from six to 24 hours, while smoking cocaine produces a high that lasts only 20 to 30 minutes. And it takes the human body about 12 hours to remove about 50 percent of methamphetamine, compared to only one hour for cocaine.
Effects of meth:
- Similar to amphetamines, but more intense
- The “Rush” lasts up to 35 min. increase in heart rate, blood pressure, high pleasure
- The “High” lasts 4-16 hours
- The person feels very confidentà Aggressively smarter
- Argumentative
- Focused on insignificant behaviors
- The “Binge”
- Uncontrolled use of drug (3-15 days). Eventually no high, no rush.
- Tweaking
- After days of taking drug the person can’t get the high or rush.
- Person feels empty
- Looses sense of identity
- Psychotic episodes
What is tweaking?
- The most dangerous stage of methamphetamine abuse occurs when an abuser has not slept in 3-15 days and is irritable and paranoid. This behavior is referred to as “tweaking,” and the user is known as the “tweaker.” The tweaker craves more methamphetamine, but it is difficult to achieve the original high, causing frustration and unstable behavior in the user. Because of the tweaker’s unpredictability, there have been reports that they can react violently, which can lead to involvement in domestic disputes, spur-of-the-moment crimes, or motor vehicle accidents.
- A tweaker can appear normal - eyes clear, speech concise, and movements brisk; however, a closer look will reveal that the person’s eyes are moving ten times faster than normal, the voice has a slight quiver, and movements are quick and jerky. These physical signs are more difficult to identify if the tweaker has been using a depressant such as alcohol; however, if the tweaker has been using a depressant, his or her negative feelings - including paranoia and frustration - can increase substantially. A person should use extreme caution when dealing with an individual on methamphetamine.
Acute effects of meth:
- CNS stimulant
- Increased attention
- Great motivation
- Increased thinking and brain activity
- Decreased fatigue
- Decreased appetite
- Euphoria and rush
- Increased respiration
- Inhibits pain and increased activity
- Hyperthermia
- Toxic effectsà Animals damage nerve terminal
- Jaw clenching or teeth grinding
- Sexually compulsive behavior
- Stimulates motor activity à Stereotypical behaviorsà Twitching or picking the skin
- Tweaking
Chronic effects of meth:
- Violent behavior
- Anxiety, depression
- Confusion
- Insomnia
- Psychosis à homicidal or suicidal thoughts
- Paranoia
- Hallucinations
- Mood disturbances
- Repetitive motor activity
- Weight loss
- Erectile dysfunction
- Long-term cognitive impairment due to neurotoxicity
- Tooth decay
- Caused by the grinding
- Decrease in saliva secretion
- Damage to the immune system
- Damage to the brain
Complications of meth abuse:
- Cardiovascular problems
- Tachycardia (fast heart rate)
- Irregular heartbeat
- Increased blood-pressure
- Irreversible stroke-producing damage
- Hyperthermia
- Convulsions
- Fetal exposure leads to prenatal complications
- Increased risk for HIV
Long term effect of meth on the brain:
Brain imaging shows reduction in striatal DAT binding with chronic methamphetamine and methcathinone use, and also in a Parkinson’s disease patient, where the DA innervation of the striatum is known to be severely compromised.
Legal status of meth:
- Schedule II drug, can be used for medical purposes (Desoxyn)
- Manufacturing methamphetamine now has 10 years mandatory prison sentence
- In 2004,
- Oklahomaà Forbid the OTC sale of non-prescription medicines with components used in meth production
- Iowaà Non-prescriptions drugs containing pseudoephedrine à behind pharmacist counterà max of 330 mg/day/person
- Oregonà Require prescription to obtain drugs containing pseudoephedrine
- DC you can’t buy pseudoephedrine over the counter
Treatment for meth abuse:
- Cognitive behavioral therapy
- No pharmacological treatments
- Antidepressants
- In the ER:
- treatment for hyperthermiaà ice baths
- convulsions
