high efficacy stimulants - amphetamines Flashcards
what is amphetamine?
the parent compound of a family of synthetic psychostimulants that are structurally related to dopamine (DA).
what are the similar to amphetamine plant compounds ?
- cathinone
- ephedrine
what is true about amphetamines and methamphetamines in terms of formation?
they are synthetic (MADE IN LAB)
what are the different types of amphetamines?
- L-amphetamine (Benzedrine)
- D-amphetamine (Dexedrine)
a. More potent than L-amphetamine
Narcolepsy, ADHD (Adderall)- Adderall: 3:1 mixture of D-amphetamine to
L-amphetamine!
- Adderall: 3:1 mixture of D-amphetamine to
what type of drug is amphetamines and what is its accepted medical use
schedule 2
for…
- ADHD
- Narcolepsy (can’t stay awake)
what is the physical characteristics of methamphetamine?
commonly found as an odorless, white or off-white, bitter-tasting powder
also found in pills, capsules & larger crystals.
compare amphetamines to cocaine
- longer half life
a. cocaine = 30 min
b. amphetamines = 12 hours - longer drug actions
a. up to 30 minutes
b. 10 hours - pattern of drug use
a. cocaine = binges
b. amphetamines = use every few hours for
days
what is the route of administration of amphetamine and methamphetamine?
Amphetamine: oral, intranasal, injection (IV or SC)
Methamphetamine: orally, intranasal, IV injection, inhalation (smoked)
what is the absorption of amphetamine and methamphetamine?
- water soluble so well absorbed in blood
- GI tract absorption is slow
- amphetamines are weak bases
- high doses of vitamin C (ascorbic acid) can impair amphetamine absoption cuz it makes your GI more acidic and amphetamines are weak bases
- IV/smokes is very rapid
what is the disribution of amphetamine and methamphetamine?
- Highly lipophilic, readily crosses BBB
- ~20% of amphetamine gets trapped by plasma proteins (depot binding)
- Methamphetamine gets into the brain more quickly than d-amphetamine & l-amphetamine!
-D-amphetamine more potent than l-amphetamine
where are amphetamines and metamphetamines metabolized and what enzymes do the metabolism at those sites?
liver: CYP enzymes
brain: monoamine oxidases (MAO)
are amphetamines and metamphetamines completely broken down?
no
what is metamphetmaine metabolized into?
an active metabolite called amphetamine – so it re-enters your system and produces biological actions
what is amphetamine metabolized into?
an active metabolite 9k4-hydroxyamphetamine
what does the active metabolite of amphetamine cause?
4-hydroxyamphetamine dilates pupils, possibly causes hallucinations in animal models!
what is the half life of amphetamines and metamphetamines?
10-12 hours post administration , so much longer than cocaine
what is the rate of excretion influenced by?
pH of urine
acidic (low ph) urine – drug is removed more quickly
alkaline (high ph) urine – drug is removed less quickly
what is methamphetamine excreted as?
~50% excreted unchanged
~excreted as amphetamine!
what is amphetamine excreted as?
~40% excreted unchanged
what are the ways of excretion that we can detect levels of amphetamine?
- urine (MOST COMMON)
- blood
- saliva
- nails
- hair follicles
what neurotransmitter causes the objective effects of the drugs? what are these effects?
norepinephrine
- Blood pressure and heart rate increase
- Relaxation of the bronchioles
- Activation of fat breakdown
- Arousing effects
- Appetite effects
what happens when the drugs interact with our serotonin receptors?
- Body temperature increase
- Appetite effects
what neurotransmitter causes the subjective effects of the drugs? what are these effects?
dopamine
- Locomotor activation (tics)
- Euphoria
- Effects on attention
- Reinforcement
- Addiction
what are the behavioral symptoms that increase drug seeking behavior?
- heightened concentration
- increased self confidence
- reduced appetite
- increased alertness
what are the acute behavioral effects immediately after smoking or IV injection?
Intense “rush” sensation that is extremely pleasurable
what are the acute behavioral effects of oral or intranasal intake?
euphoria without the rush
what are acute behavioral effects that are not so good?
- nervousness, anxiety, panic
- punding (tweaking): teeth grinding, skin picking, nail bite
- insomnia
- reduced appetite
- stomach cramps (if ingested)
what are psychological issues after CHRONIC use?
- Hallucinations
- Formication syndrome (bugs crawling)
- Paranoia & delusions of persecution (someone’s out to get them) even if drug is out of system
what are physical issues after CHRONIC use?
- Tooth decay (meth mouth)
- Weight loss
- Cardiovascular & pulmonary dysfunction
- Heart attack, inflammation of heart tissue, stroke risk
what levels does methamphetamine use increase and what does that cause?
- increases ceramide levels
which speeds up cellular metabolism resulting in faster aging & earlier cell death
Permanent health problems!
what is the neurotoxicity of meth?
- chronic meth damages and depletes dopamine (DA) and serotonin (5-HT) neurons
- 10% loss of brain tissue in limbic structures causing depression, anxiety, memory deficits
- destroys nigrostriatal dopamine neurons which causes motor deficits and has trouble having behavioral flexibility (same symptoms as parkinson’s patients)
what are the possible mechanisms for methamphetamine induced neurotoxicity?
- Oxidative stress (toxic byproducts accumulate in brain)
- Excitotoxicity (too much positive stimulation in brain causes tissue death)
- Neuroinflammation (due to too much DA release)
- Mitochondrial dysfunction (constant use of energy to breakdown DA causes mitochondrial dysfunction)
what does chronic meth use lead to?
dependence and withdrawal symptom
how long does it take withdrawal symptoms to subside?
several weeks which is a time where the user is at high risk for relapse
what symptoms do you see when you start using the drug?
- CRASH
- exhaustion
- oversleeping
- overeating
what symptoms do you see after constant use of the drug?
- anhedonia
- lack of energy
- anxiety
- sleeplessness
- high cravings
what symptoms do you see when you try to reduce the drug use?
- flat mood
- emotional fragility
- episodic cravings to use
what are common withdrawal symptoms?
- Cravings
- mood changes (including depression & risk of suicidality)
-Exhaustion/ oversleeping - Hallucinations/ paranoid delusions
- Cognitive deficits (memory/ attention)
- Gi distress
