Cocaine

Question 0

What region of the world predominantly produce cocaine and what are the issues with smuggling

Answer 0

 Major sources in order of amounts are:
 Columbia, Peru and Bolivia
 Columbia major source of Canadian supply
mostly transported in bricks of the powder form
 “mules” may swallow mul&ple bags - either &ed-off condoms or the fingers of latex gloves
 An increasing trend has been smuggling liquid cocaine in carry-on
 this form most frequently caught in Pearson Airport in Toronto

Question 1

Why was cocaine first created

Answer 1

 was used as anesthetic- still is in rare instances, usually eye surgeries
 Freud recommended it to treat depression and addic&on
 used to be part of OTC remedies and drinks (coca- cola)

Question 2

What’s the source of cocaine

Answer 2

 a natural product of the coca plant
 grows in highlands of south america
 locals chew the leaves mixed with very basic substances (lime -to increase extrac&on)
 cocaine = benzoylmethylecgonine

Question 3

Explain cocaine production

Answer 3

 leaves are dumped in makeshift trench
 500 kg of leaves for 1 kg of paste
 kerosene or gasoline is added to extract active ingredients
 after drying, obtain cocaine paste
 about 75% cocaine but heavily contaminated with solvent

Question 4

What is cocaine hydrochloride?

Answer 4

 refinement of paste can result in a salt
 this is cocaine hydrochloride
 more easily transported
 this is polar and soluble in water
often cut (diluted) with other white powders to maximize profit
 powdered milk, baby laxative or other numbing anesthe&cs like lidocaine or benzocaine (to produce a similar “freeze” as cocaine)

Question 5

What are the consequences of cutting with levamisole?

Answer 5

 in these cases, cocaine was cut with levamisole
 an anti- helminthic drug given to cattle but shown to mildly increase dopamine release
 purpura (purple discolouration) leading to necrosis of &ssue due to vasculitis (inflammation of vasculature)
DEA es&mates 70% of cocaine in US is contaminated

Question 6

Explain administration by insufflation

Answer 6

 insuffla&on (snorting)
 cocaine hydrochloride
 onsetin3-5min.
 effects last 30 - 40 min.
 absorption through mucous membranes
 90% of American and Canadian bills are contaminated with trace amounts
chronic snorters can lose cartilage separating nostrils
- mix of vasoconstriction and acidic erosion from hydrochloric acid of cocaine hydrochloride

Question 7

Explain administration by IV

Answer 7

 intravenous injection
 onset in 15 - 30 seconds
 effects may last only 10 - 20 minutes
 severe vasoconstric&on and necrosis is a danger if the needle goes into an artery
 vasoconstriction due to prevention of noradrenaline uptake and decreased nitric oxide production
 can result in gangrene, amputation

Question 8

What happens if you try to smoke cocaine hydrochloride?

Answer 8

 if try to smoke cocaine hydrochloride
 cocaine hydrochloride will burn before it
produces vapours
 therefore it is destroyed in the process of smoking
 pyrolysis (degrada&on by heat) and vapours from cocaine HCl occur at approx. same temp. of 195° C
 so must convert to a different form to smoke it - the freebase form

Question 9

What is freebase cocaine and how is the purest form prepared

Answer 9

freebase cocaine vaporizes at 98oC - it vaporizes before it burns
 to make high quality freebase:
 dissolve cocaine hydrochloride in water
 add a base (usually ammonia)
 extract with ether (highly explosive, flammable)
 evaporate to dryness

Question 10

Describe crack cocaine and its preparation

Answer 10

 named after the crackling sound it makes when smoked
 dissolve low-purity cocaine in water
 add sodium bicarbonate (baking soda) to neutralize the hydrochloride
 heat
 freebase will precipitate and can be purified
 will be less pure than true freebase

Question 11

Explain the effects of smoking cocaine

Answer 11

  smoking
  freebase and crack cocaine
  onset of effect in 6 - 10 seconds
  intense but short duration, only minutes
  usually requires repeated doses

Question 12

Explain the metabolism of cocaine

Answer 12

 metabolized by carboxylesterase enzymes in blood and liver
 metabolites can be detected in urine up to four days after use

Question 13

What is benzoylecgonine

Answer 13

 benzoylecgonine is a major metabolite - appears within 4 hours of using cocaine - found in sewage of major cites - in Italy, one city found to be snorting equivalent of 200,000 lines per day with a pop’n of 5 million

Question 14

What is cocaethylene

Answer 14

 cocaethylene if taken with alcohol - damaging to heart &ssue - may enhance euphoria

Question 15

What does the prescience of methylecgonidine indicate?

Answer 15

 presence of methylecgonidine indicates cocaine was smoked

Question 16

What is the half life of cocaine

Answer 16

1hr

Question 17

What is the half life of benzoylecgonine

Answer 17

6hrs

Question 18

What are the psychological effects of cocaine

Answer 18

 feeling of extreme euphoria, energy
 hyperactivity, hypersexuality
 confidence
 makes the mundane more pleasurable
 can develop psychosis - can be dangerous
It is very reinforcing and helps some people maintain a busy schedule

Question 19

What are the physiological effects

Answer 19

local anaesthetic actions:
 blocks sodium channels
 prevents nerve conduction (no pain signals)

sympathetic system is simulated:
 due to excess neurotransmitter in synapses
 heart rate and blood pressure increase
 anorexia, insomnia

some report enhancement of sense
Can lead to cardiovascular issues

Question 20

What is the action mechanism of cocaine

Answer 20

 blocks the action of transporter proteins that normally remove neurotransmitters
 get prolonged and greater stimulation of post-synaptic receptors
 results in large dopamine accumulation at the nucleus accumbens
 aromatic and nitrogen important - may mimic the same groups found in dopamine and other neurotransmitters
 still not clear if it binds to same site as dopamine or to a different part of the transporter

Question 21

What are the effects if dopamine at the synapse?

Answer 21

1. Depolarization results in dopamine release from presynaptic
2. Activation of dopamine receptors
3. DAT inhibited
4. Presynaptic uptake blocked
5. Dopamine remains in the synapse thus prolonging signal
6. Can’t reuse dopamine as efficiently

Question 22

What are the effects at the NA

Answer 22

 cocaine inhibits transporters at dopamine-releasing nerve terminals
 cocaine therefore increases the amount of dopamine at the nucleus accumbens

Question 23

What are the effects of cocaine on other transporters

Answer 23

 although most research has focused on DAT, similar effects are observed with noradrenaline and serotonin transport
 if try to mimic cocaine effects with drugs developed to exclusively block DAT, do not get the same effects in animals
 therefore, dopamine is not entirely responsible for the effects

Question 24

Explain the evidence for increase in DAT activity with chronic use

Answer 24

 expose animals to cocaine for several days
 isolate nerve endings from specific brain regions
 add radioac&ve dopamine to the prepara&on
 measure how much gets transported into the nerve endings
 compare uptake to animals exposed to saline for same amount of &me
 in absence of cocaine, may explain depressed state of users between doses
Saw increased activity of DAT thus when not taking cocaine, dopamine sucked out of synapse (over active transporter)

Question 25

What are some of the damages from cocaine?

Answer 25

 expose animals to cocaine for several days
 isolate nerve endings from specific brain regions
 add radioactive dopamine to the prepara&on
 measure how much gets transported into the nerve endings
 compare uptake to animals exposed to saline for same amount of time
 in absence of cocaine, may explain depressed state of users between doses

Question 26

What are the effects on psychosis

Answer 26

 usually only in heavy users
 usually indistinguishable from paranoid schizophrenia
 hostility, violence, bugs under skin
 usually clears in several days with no long-lasting effects, but can last much longer, long after drug has stopped being used

Question 27

What happens with withdrawal

Answer 27

 withdrawal symptoms are usually fairly mild compared to alcohol, sedatives
 depression is most prominent characteristic
 acutely, a “let down” occurs within 30 minutes of
cocaine use
 the “let down” severity is related to dose and duration of use

Question 28

What does vigabatrin do?

Answer 28

 gamma-vinyl-gaba (vigabatrin) inhibits GABA-transferase, the enzyme that degrades GABA
 reduces dopamine release in reward pathways
 add a radioactive compound that binds to the dopamine receptors- it competes with dopamine released by cocaine
 the more dopamine that is released, the less radioactive compound binds useful for heroin and alcohol also

Question 29

What are the effects of topiramate?

Answer 29

 drugs that increase GABAergic activity are efficacious in decreasing the reward of cocaine
 topiramate, an antiseizure drug that enhances GABA-A receptor activity and inhibits glutamate receptor activity
 reported to reduce craving

Question 30

What are the effects of modafinil?

Answer 30

 modafinil is a stimulant used to treat narcolepsy
 it increases the release of norepinephrine, dopamine and
glutamate
 it also increases serotonin levels

may counteract depression of these systems in long- term users