Lecture 5: Psychostimulants, Cocaine and Amphetamines Flashcards
Effects of coca plants/characteristics? where is cocaine from?
Helps with endurance, stamina, and appetite
90% Columbian
Plant is resistant to drought and disease, harvested several times a year, fied workers were given four breaks daily
Active ingredients first isolated in 1860 - cocaine is a crystalline tropane alkaloid (important to understand active component bcuz - BBB, lip soluble ect)
What are the metabolic stats of cocaine? what is the major metabolite of cocaine?
blocks presynaptic DA reuptake transproter
half-life of approx 50m (brain 8hrs, urine 12hrs)
Cocaethylene - can be detected for 2 weeks, more toxic than the cocaine
What are the different ways to administer cocaine? what does cocaine HCL do?
orally, intranasal, intravenous, smoking - dictates speed and duration of high
potent vasoconstrictor - closes veins
How does cocaine travel through the body when it is snorted? when it is smoked?
Snorted - lungs, 2 heart, 2 brain
Smoked - lungs, 2 heart, 2 brain
What are the pharmacological characteristics of cocaine? what neuroTs does cocaine potentiate the action of?
potent local anesthetic, vasoconstrictor, psychostimulant
Dopamine, norepinephrine, serotonin
When cocaine affects DA levels what are those changes associated with? when do these level changes occur?
Behavior reinforcing
Psychostimulant properties
Nucleus accumbens
Dopaminergic reward system (site for euphoric/addictive properties)
Blocks receptors - prolonged existence of dopamine in the synaptic cleft
What other changes can also be responsible for effects?
Changes in 5-HT are also responsible
Remove DA transporter experiments
Site for euphoric/addictive properties
What is the structure of cocaine in the brain?
VTA - nucleus accumbens - prefrontal cortex
What are the effects of coke in a short term low dose? moderate dose? long term high dose?
Short term low dose (25-75): Increased alertness, Hyperactivity, Euphoria, Enhanced self-consciousness, Poor appetite and sleep
Moderate-dose: Progressive loss of coordination, Rebound depression, Seizures
Cardiac complications, Nasal-septal perforations, C HCL deteriorates nose, Cerebral ischemia, vasoconstrictor/limits blood supply to brain
Long-term high dose: Anxiety, Paranoia, Hyperactivity, Aggressive Toxic paranoid psychosis (Formication), Cerebral ischemia
Gray matter reduces with chronic use
How can cocaine addiction be treated?
no generally accepted treatment
potential pharmacological intervention (aversive agents, dopaminergic agents (bupropion), anti craving agents (topiramate), drug-substitution, agents for comorbid disorders
What is a potential cocaine vaccine?
TA-CD
Must stimulate sufficient levels of antibody production
Sufficient duration of action
Prevents entry to BBB
Antibody must be well-tolerated (side effects)
What is the teratogenic potential of cocaine? - what can result from a coke baby?
higher concentration occurs in fetus
causes low birth weight, decreased head circumference
Early exposure can lead to spont abortion
withdrawal sympt are seen in 1/3 of babies
linked to neglect and poor lifestyle
What are amphetamines/what are their characteristics and what do they produce?
sympathomimetic agents - mimic the actions of adrenaline
Produces: vasoconstriction, hypertension, tachycardia (irregular heart beats)
What is the mechanism of amphetamines?
Increase pre-synaptic DA release
Interacts with vesicles, internal release
Block of DA reuptake transporter - causes more pre-synaptic dopamine release (more dopamine on the cleft - same as cocaine just different way)
High doses bind to MAO
increased dosage - more pronounced effects
What are the effects of amphetamines at a low-dose, moderate-dose and a chronic high-dose?
Low dose: Increased blood pressure, Increased heart rate, Relax bronchial muscle, Alertness, Euphoria, Useful in athletics
Moderate dose: simulation of respiration, tremors and restlessness, insomnia, agitation, euphoria, de novo anxiety disorders
Chronic high-dose: Repetitive acts, Outburst of aggression, Paranoid delusions, Severe anorexia
