Amphetamines Flashcards
1
Q
amphetamines
A
- type of drug but also used to describe a family of structurally similar drugs derived from amphetamines
- amphetamine (stimulant), methamphetamine (enters brain more rapidly), crystal meth (methamphetamine hydrochloride, smokable)
2
Q
Effects
A
- similar to cocaine (but magnified)
- sensations of well-being, euphoria, illusion of invincibility
- suppression of fatigue, increased alertness
3
Q
Source
A
- purely synthetic
- originally synthesized in hopes of new asthma medication but had stimulant properties
- used for weight loss, depression, asthma, stimulant, narcolepsy, ADHD
4
Q
Why is methamphetamine now the amphetamine of choice?
A
- extra methyl group makes easier to enter brain and more difficult to metabolize (profound euphoria), lipid soluble
- less peripheral more CNS effects compared to amphetamines (wont effect hr and bp as much)
- smokable in crystalline hydrochloride form
- > won’t need to use amphetamine IV to get same rush
5
Q
Methamphetamine synthesis
A
- mexico amphetamines
- smaller labs use pseudoephedrine from cold remedies as starting point of synthesis
- usually produces 5-7kg of dangerous waste for every kg (lithium batteries, sodium, phosphorous, ammonia), all done to get rid of hydroxyl group
- new shake and bake method requires less pseudoephedrine and done in 2L pop bottle, remaining waste discarded
- can cause explosions, flashfire if O2 enters bottle too quickly
6
Q
Pattern of use of methamphetamine
A
- orally (ADHD meds), snorted, smoked or injected (similar pattern as cociane)
- longer lasting effects (not as frequent admin as cocaine)
- high doses produce rapid tolerance (due to rapid NT depletion, have to take few days off for your brain to develop a supply and feel euphoria again)
7
Q
Meth vs Cocaine
A
- Meth: peak at approx 10 min (same as uptake), prolonged high b/c stays in brain longer (100 min still there)
- cocaine: peak at ~5min, self reported high decreases quickly, rapidly leaves brain (all gone before 40 min)
- AMPH 1100% DA release, Cocaine 350% basal release
8
Q
AMPH metabolism
A
- mostly in liver by CYP2D6
- major products are 4-hydroxyamphetamine (Oh is added so more soluble and can be excreted, also SNS stimulation) and norephedrine (causes SNS stimulation by release of adrenaline and noreadrenaline) for amphetamine
- methamphetamine products are amphetamine and 4-hydroxymethamphetamine followed by same metabolites as AMPH
- 10% caucasians are CYP2D6 deficient makes them highly sensitive to drug
9
Q
Mechanism AMPH vs Cocaine
A
- increase levels of NT in synapse like cocaine (blocks uptake of DA, NA and 5HT)
- cocaine needs NT release and depol for build up of DA, AMPH does not require NT release
- cocaine does not enter presynaptic terminal (blocks transporter from outside) AMPH enter the nerve ending through diffusion across membrane and transportation of DAT
10
Q
Mechanism for AMPH
A
- enter presynaptic terminal through diffusion or DAT
- AMPH transported by vesicular monoamine transporter into vesicles
- once inside they induce the vesicles to spew out their dopamine into the cytoplasm
- AMPH inhibits MAO so can’t break down dopamine
- AMPH results in reversal of DAT so that it pumps free dopamine into synapse also get DA leak across membrane
- get massive DA release don’t need stimulation of presynaptic cell to get activation of receptors
- also occurs in noradrenergic pathways and serotonergic pathways
11
Q
Why do AMPH have different effects on transporter compared to cocaine?
A
- methamphetamines bind to and activate the trace amine associated receptor (TAAR) inside presynaptic terminal
- results in activation of other enzymees (kinases) that phosphorylate other proteins
- results in reversal of DAT
- prevent AMPH from binding to TAAR loses rewarding ability
12
Q
Tolerance
A
- tyrosine hydroxylas (enzyme in synthesis pathways for DA and NA) is inhibited
- acutely: single high dose results in decreased DAT function (less cell surface expression), opposite cocaine
- too much DA pathways get activated to stop andy further synthesis of DA, TH inhibited
13
Q
Brain damage
A
- very damaging
- DA, NA and 5HT terminal reduced
- damage due to free dopamine forming ROS when metabolized by MAO, leads to damage of cells
- excessive glu release causes toxic environment that leads to neuronal death (too much Ca2+)
- brain damage similar to parkinsons disease (increased risk of getting disease)
14
Q
Psychological effects
A
- same as cocaine (euphoria, energy, alertness)
- at high doses: punding (too much DA in basal ganglia)
- unprovoked aggression, grandiosity, hallucinations, paranoia, delusions of parasitosis
15
Q
Physiological effects
A
- no local anesthetic actions
- SNS stimulation (same as cocaine) increased HR and bp, insomnia
- tremours, headache, profuse sweating
- meth mouth, skin disorders
- hyperthermia, renal and hepatic failure, strokes, seizures
