Cocaine Flashcards
What are the 3 consumable forms of cocaine?
Coca leves
Cocaine hydrochloride (powder)
Free-base cocaine = crack
How is cocaine powder absorbed?
Absorbed through mucous membranes
What is the bioavailability of cocaine powder?
70%
What does the dissolution of cocaine powder do?
Makes HCl which damages the nasal structures
What is the onset and duration of cocaine powder?
Onset = 3-5 minutes
Duration = 30-40 minutes
What is the onset and duration of crack?
Onset = 6-10 seconds
Duration = 5-30 minutes (intense)
Why can we smoke crack but not cocaine?
Cocaine pyrolyzes before it vaporizes while crack does not
What is the onset and duration of injecting crack?
Onset = 10-15 seconds
Duration = 10-20 minutes
Which enzyme primarily metabolizes cocaine?
Liver CYP3A4
Which major metabolite is produced by the hydrolysis of cocaine?
Benzoylecgonine (40%)
Spontaneously produced, non-enzymatic
What do liver/plasma esterases generate while breaking down cocaine?
Ecgonine methylester (30-50%)
What is the half-life of cocaine?
12 hours
How long is cocaine detectable in urine?
4 days
Where is cocaine distributed?
Brain
Spleen
Kidney
What are the psychological effects of cocaine?
Euphoria
Arousal
Increased energy
Takes longer to fall asleep
What are the effects of cocaine on the head?
Dry mouth
Headache
What are the effects of cocaine on the heart?
Increased heart rate and blood pressure
Constricted blood vessels
Promotes blood clot formation
What are the effects of cocaine on the skin?
Increased body temperature
Sweating
What are the effects of cocaine on the lungs?
Increased respiratory rate
Dilated bronchi
What are the effects of cocaine on the digestive system?
Decreased appetite
Increased fat breakdown
What are the effects of cocaine on the reproductive system?
Hyper-sexuality
What are the anesthetic properties of cocaine?
Blocks Na channels which block neurotransmission so there is no pain
What are the sympathomimetic effects of cocaine?
Increased heart rate, blood pressure
Anorexia, insomnia, agitation, hyperthermia
How does cocaine affect the basal ganglia?
Repetitive, compulsive movements
How does cocaine affect the PFC?
Influences planning, problem-solving, and social behaviours
How does cocaine affect the NAc?
It is extremely rewarding
How does cocaine affect the medulla?
High doses can cause respiratory and circulatory failure
What are the physiological mechanisms of cocaine?
Blocks transporter activity within synapses
Prolonged stimulation of post-synaptic nerves
The aromatic ring and amine group mimics NTs
Where does excess DA build up from cocaine use?
In the basal ganglia, PFC, VTA, and NAc
What does excess 5HT from cocaine use underlie?
Mood, sleep, appetite, and temperature
What does excess NE from cocaine use underlie?
Sympathomimetic effects
Enhances VTA sensitivity to Glu and reward
What are the adverse effects of acute cocaine use?
Irritability, hostility, anxiety, fear, depression
Formication = delusion of bugs crawling under skin
Depression, aggression, paranoia
Increased acute infections in GI tract
Nosebleeds
Allergic reactions at injection sites
What does the reinforcing mechanism of cocaine involve?
Block of DA reuptake
Where does cocaine bind in the brain?
To the same site as dopamine (dopamine transporter)
Locks the transporter in a stable conformation so dopamine cannot be reuptaken
Do exclusive DAT blockers mimic cocaine effects?
No, so not just DA is involved
What are the cocaine-induced mechanisms of tolerance?
Reduced euphoria caused by depleted DA and increased DAT efficiency
Internalization of D1 and D2 receptors via rapid mechanisms
Altered opioid-ergic signaling which induces striatal dynorphin expression
What are the symptoms of reverse tolerance?
Increased susceptibility to hyperthermia, convulsions, stereotyped movements
What is intermittent use of cocaine associated with?
Strong behavioural sensitization, increased locomotor activity
What are the symptoms of cocaine withdrawal?
Depression, anxiety, appetite changes
Strong drug cue-associated cravings
Long-term DAT efficiency increases so there is less dopamine in synapses causing episodes of depression
Cocaine and dependence
Mild physical symptoms
Intense psychological symptoms due to hijacked reward pathway and cue association
Do most cocaine users become addicted?
No, anxiety or loss of motor control is not fun
10-15% of users that snort become addicted
How do benzos treat acute cocaine intoxication?
Control agitation and overstimulation
Decrease BP, heart rate
How does nitroglycerine treat acute cocaine intoxication?
Evokes NO production to counteract vasoconstrictive effects
Useful to supply heart with oxygen
how does an ice bath treat acute cocaine intoxication?
Cooling body temperature
How does butyrylcholinesterase treat acute cocaine intoxication?
Causes rapid elimination of cocaine
How does topiramate help maintain cocaine abstinence?
The anti-seizure med that enhances GABAa receptor activity and inhibits Glu receptor activity
-reduce cravings
What are the long-term consequences of cocaine use?
Cardiovascular disease
-arrhythmias, arrest due to inhibited Na channels
Constricts vessels and organs can die if their blood supply is limited
Psychosis accelerated brain aging
Rhabdomyolysis breakdown of muscle tissue due to hyperthermia which releases myoglobinuria which causes kidney failure
Increased stroke risk
Brain shrinkage - enlarged ventricles and sulci
