Amphetamines

Question 0

Explain the difference between methamphetamine vs crystal meth

Answer 0

• methamphetamine - amphetamine derivative that
  enters the brain more rapidly
• crystal meth - methamphetamine hydrochloride crystals - smokable

Question 1

What are amphetamines?

Answer 1

amphetamine is a type of drug but is also used to describe a family of structurally similar drugs derived from amphetamine
- amphetamine - stimulant
- methamphetamine - amphetamine derivative that
enters the brain more rapidly

Question 2

What are some other names for amphetamine

Answer 2

• speed,bennies,uppers,crystal,glass,crank

Question 3

What is Benzedrine?

Answer 3

Another name for amphetamine

Used to be given in planes as inhaler to expand airways

Question 4

What are the effects of amphetamines?

Answer 4

 similar to cocaine
 sensations of well-being, sometimes profound
euphoria, illusion of invincibility
 also suppression of fatigue, increased alertness

Question 5

What is the source of amphetamine?

Answer 5

 amphetamines are purely synthetic
 originally synthesized in hopes of a new asthma medication
 but had stimulant properties
 has been used for weight loss, depression, asthma, stimulant (pilots and soldiers), narcolepsy, ADHD (Adderall for attention deficit/hyperac&vity disorder)

Question 6

Explaine the structure if amphetamine in relation to methamphetamine, noradrenaline and dopamine

Answer 6

• Ampeth: benzyl with attached ethane region and nitrogenous group
  Met- Ampeth: benzyl with attached ethane region and nitrogenous group and additional methyl
  NA: benzyl, ethane, nitrogen and 3 OH
  Dopamine:benzyl, ethane, nitrogen and 2 OH

Question 7

What are the implications of ampthetamines structure?

Answer 7

• amphetamines interact with the same transporters as dopamine and other neurotransmitters because of close structural similarity
• small structural differences between amphetamines and neurotransmitters lead to dramatic effects at transporters

Question 8

Why is methamphetamine becoming more popular choice?

Answer 8

 extra methyl group makes it easier to enter the brain and more difficult to metabolize - profound euphoria
 less peripheral effects, more CNS with meth compared to amphetamine
 it is smokable in its crystalline hydrochloride form
 would need to use amphetamine IV to get the same rush, and this is associated with too many problems - needles etc

Question 9

Explain methamphetamine synthesis

Answer 9

 majority of amphetamines entering US and Canada come from Mexico
 smaller labs use pseudoephedrine from cold remedies as starting point of synthesis
 typically produce 5 - 7 kg of dangerous waste (lithium (batteries), sodium, phosphorous (match heads), ammonia) for every kg of product

Question 10

What are the implications of the new shake and bake method?

Answer 10

 new shake and bake method (one-pot method) requires less pseudoephedrine and is usually done in a two-litre pop bottle
 remaining waste discarded
 can cause explosions, flash fire if oxygen enters the bottle too quickly

Question 11

What are the patterns of use of methamphetamine

Answer 11

 orally, snorted, smoked or injected
 use pattern similar to cocaine
 longer lasting effects means that it is not administered as frequently as cocaine
 high doses produce rapid tolerance
 seems to be due to rapid neurotransmitter depletion

Question 12

What are the main comparisons between meth and cocaine

Answer 12

• High of cocaine drops of quicker whereas amphetamine sustained
• cocaine peaks earlier but lasts shorter
• similar dose of amphetamine release much more dopamine than cocaine
• some metabolizes of amphetamine have stimulatory effect

Question 13

Explain the metabolism of amphetamine

Answer 13

 amphetamine metabolism mostly in the liver by CYP2D6
 major products are 4-hydroxyamphetamine and
norephedrine for amphetamine

Question 14

What are the effects of norephedriene?

Answer 14

norephedrine causes release of adrenaline and noradrenaline resulting in sympathetic stimulation

Question 15

What are the effects of 4-hydroxyamphetamine

Answer 15

 4-hydroxyamphetamine can also cause sympathetic stimulation

Question 16

How is methamphetamine metabolized?

Answer 16

 with methamphetamine, products are amphetamine and 4- hydroxymethamphetamine followed by the same metabolites as for amphetamine

Question 17

What is the implication of CYP2D6 for Caucasians

Answer 17

 10% of caucasians are deficient in CYP2D6 which makes them highly sensitive to the amphetamine
- amphetamine stays in their body longer

Question 18

What is the difference in mechanism between cocaine and amphetamine

Answer 18

like cocaine, amphetamines increase the levels of neurotransmiCers in synapses:
 blocks uptake of dopamine, noradrenaline and serotonin

but has important differences to cocaine:
 cocaine will cause dopamine build up with
depolarization - need neurotransmitter release
 amphetamines do not require release of neurotransmitter

Question 19

What are the effects if cocaine vs amphetamine on the presynaptic neuron

Answer 19

cocaine does not enter the presynaptic terminal
 it blocks the transporter from outside

amphetamines do enter in two ways:
 diffusion across the membrane
 transportation by DAT (dopamine transporter)

Question 20

What are the effects of AMPHETAMINE on the synapse?

Answer 20

1. Enters presynaptic by diffusion or DAT
2. Transported by vesicular monomania transporter into dopamine vesicles
3. Once inside, induce vesicle to spew out their dopamine into cytoplasm
4. Additional amphetamine inhibits MAO
5. Presynaptic amphetamine results in reversal of DAT so it pumps free dopamine into synapse (also leaks across membrane)
6. Massive dopamine release

Don’t been stimulation of presynaptic to activate post synaptic receptor

Question 21

What is the summary of the overall mechanism of amphetamine

Answer 21

these types of effects:
 reversal of neurotransmitter transporters
 release of neurotransmitter into cytoplasm and then into synapse

are thought to occur in primarily in dopaminergic pathways, but also in:
 noradrenergic pathways
 serotonergic pathways

Question 22

Explain amphetamine tolerance

Answer 22

 tyrosine hydroxylase (enzyme in synthesis pathway for dopamine and noradrenaline) is inhibited
 acutely - a single high dose of amphetamine results in DAT function decrease
 DAT function decreases, less cell-surface expression (opposite of cocaine)
 also see decrease in levels of other transporters such as the one for noradrenaline

Question 23

What are the effects of amphetamine on brain damage?

Answer 23

 very damaging to the brain - studies show profound changes in brain structure
 dopaminergic, noradrenergic and serotonergic terminals are reduced - likely permanently
 damage seems to be due to free dopamine forming reac&ve oxygen species when metabolized by monoamine oxidase (even though the enzyme is inhibited by the drug) - leads to damage of cell membranes and proteins, mitochondria
 also excessive glutamate release causes toxic environment that leads to neuronal cell death (excitotoxicity)

Question 24

What is the implication of amphetamine in links to Parkinson’s disease

Answer 24

 long-las&ng changes suggest that dopaminergic neurons die
 this is what happens in Parkinson’s Disease
 many animals models support idea of dopaminergic neuron death
 evidence not as strong in post- mortem human studies but s&ll significant
76% increased risk of developing parkinsonism in meth users, but not in cocaine users
• study showing that post-mortem, some meth users had dopamine levels as low as Parkinson’s patients
• caudate and putamen form the ventral striatum
• Nucleus accumbens is part of the ventral striatum

Question 25

What are the psychological effect of amphetamine

Answer 25

 same as cocaine - euphoria, energy, alertness
 at high doses
 punding - repetitive meaningless behaviours
 via too much dopamine in basal ganglia
 basal ganglia involved in voluntary motor control and action
selection - which of several behaviours to engage
 striatum is major component of basal ganglia
 punding is also seen in Parkinson’s patients if medicine drastically increases dopamine levels

Question 26

What are the implications of amphetamine on aggression and hallucination?

Answer 26

 unprovoked aggression - amphetamines are strongly associated with violence especially in the intoxication stage
 in one study, 43% of users had engaged in violent behaviour, 27% had attempted suicide
 grandiosity
 hallucina&ons and paranoia
 delusions of parasitosis
 these get worse with prolonged use and may also include homicidal and suicidal thoughts coupled with violent behaviour and extreme anxiety

Question 27

What are the physiological effects of amphetamine

Answer 27

 no local anaesthetic actions
 same type of sympathetic stimulation as cocaine - increased
heart rate, BP, insomnia etc
 tremours, headache, profuse sweating
 meth mouth, skin disorders from picking (meth mites)
 hyperthermia, renal and hepatic failure, strokes and seizures

Question 28

What are the effects of withdrawal on amphetamine

Answer 28

 anhedonia, extreme fatigue, mood volatility, vegetative state, intense craving
 very long lasting often at least 12 months - link with degree of brain damage/dysfunction caused by use
 If dopaminergic neurons were destroyed, unlikely to recover completely

Question 29

What is meth mouth

Answer 29

 meth mouth - profound dental decay
 from contaminants in meth?
 many meth components are highly corrosive
 lack of saliva?
 vasoconstriction in gums?
 Effects on saliva production and vasoconstriction may be mediated through:
 excess noradrenaline activating adrenergic alpha1 receptors on blood vessels
 activation of inhibitory alpha2 presynaptic receptors in salivary gland neurons