consumable forms
- coca leaves
- cocaine hydrochloride
- free-form cocaine (crack)
insufflation
- 3-5 min on-set
- 30-40 min duration
- 70% bioavailability
- dissolution creates acid that is corrosive to nasal structures
inhalation of free-based cocaine
- 6-10 sec on-set
- 5-30 min duration
- inhaled before it degrades (crack vapourizes at 98C)
injection
- 10-15 sec on-set
- 10-20 min duration
CYP3A4
liver enzyme that metabolizes cocaine
benzoylecgonine
- metabolite
- 40% produced by hydrolysis (without enzyme) within 4 hours of use
ecgonine methylester
liver plasma generated from cocaine
cocaethylene
metabolite generated when cocaine is co-administered with alcohol
methylecgonidine
by-product of pyrolysis (smoking cocaine)
excretion
- detected in urine for up to 4 days
- detected in urine for up to 2 weeks in chronic users
- sweat
- saliva
- breast milk
half-life
12 hrs
effects of cocaine
sympathomimetic
physiological effects
- blocks sodium channels to prevent pain, therefore it’s anaesthetic BUT can cause dysrhythmias
- excess DA, 5-HT, NE, EP stimulates sympathomimetic effect
- excess DA in BG causes repetitive and compulsive movements
- PFC is affected as there is changes in planning, problem-solving, and social behaviours
- excess DA in NAc results in high euphoria
- high doses can affect medulla resulting in respiratory and circulatory failure
dysrhythmias
problems with heart rate/rhythym
physiological mechanisms
- block transporters in synapse
- longer stimulation of post-synaptic nerves
- aromatic rings and amine group mimics NTs resulting in excess DA, 5-HT, NE, EP
- enhances VTA sensitivity to Glu and reward
adverse effects
- irritability
- hostility
- anxiety/fear/paranoia
- restlessness
- fortification
- depression
- infections in GI tract
- nosebleeds
- allergic rxns at injection site
dopamine transporter (DAT)
- locks transporter in a conformation that inactivates it-
cardiovascular effects
NE and EP in synaptic cleft without reuptake results in hypertension and change in heart rate, respectively
tolerance
- decreased DA levels due to increased DAT efficiency and D1 and D2 receptors’ internalization results in decreased euphoria
- increased dynorphin in striatum to counter cocaine effects
- intermittent use causes sensitization
dynorphin
opioid released in striatum
withdrawl
- depression
- appetite changes
- anxiety
- cue-associated cravings
- DAT efficiency increases
dependance
- mild (most users do not become addicted)
- 10-15% of snorters become addicted
treating cocaine intoxication
- benzos decrease NT release
- nitroglycerine counteract vasoconstriction
- ice bath decreases body temp.
- butyrylcholinesterase through IV eliminates cocaine
consequences of cocaine
- 1/4 of heart attacks in 19-45 year olds
- organs will die due to vasoconstriction
- accelerated brain aging and psychosis
- breakdown of muscle tissue
- increased risk of stroke due to blood clots
