Cocaine (First Stimulant) Flashcards
Where do cocaine originates?
The Eyrhtoxy coca plant
(A.K.A. E. Coca)
Who made cocaine popular in late 1800-1900?
This person thought cocaine can be used for both theoretical setting and recreation.
Sigmund Freud
Psuchotherapist
What are the two different forms of cocaine?
HCl salt –> powder form
and
Free Base –> crack cocaine
What are the routes of administration for the Powder form of cocaine (HCl salt)?
Which route is the fastest activate?
What tends to be the dosages?
What route of administration can not occur for the HCl salt version of cocaine?
snorting (the drug intake the nasal mucous and absorb by vascular mucous)
IV injection
IV injection is the fastest to obtain peak conc in blood. Snorting takes about 15 to 20 minutes to obtain peak conc in blood.
Dosage tend to be in 50-100mg
HCl salt can not be smoke, if you heat to vapor form the active indgredient is destroyed
What is the route of administration for crack cocaine?
What tend to be the dosage?
Normally Smoke
Dosages tend to be higher around 150mg per dose.
What is the half-life of cocaine (both versions)?
(Recall: Half-life is the time required for the drug conc in the blood to drop by half.)
30-90min
True or False
Cocaine rapidly and completely metabolized in plasma and liver. When metabolizing in the liver, the liver enzyme, cyctcome 450, lack specificity and performs the metabolism.
True
What is the byproduct of cocaine’s metabolize?
Is this metabolite active or inactive?
How long can it be detected in your body?
Benzoylecgonine
Inactive
For roughly 48 hours to 2 weeks depending on the drug usage
What would be the new metabolite when cocaine is taken with another drug? For instance, cocaine with alcohol.
Is it an active or inactive byproduct?
If active what is the effective half-life?
Cocaethylene
Active
effective half-life: 150 minutes
This is 3 to 5 times more effective than taking cocaine by itself.
What are the 3 important pharmacological effects of cocaine?
Local anesthetic (not used frequency)
Vasocontrictior
Psychostimulant (stimulate reward and reinforcement which can lead to compulsive use and to addiction)
Now that you know the three important Pharmalocial effects of cocaine, what is the mechanism of action that source these effects?
Potentiates synaptic action of monoamines (DA, NE, 5-HT)
How does cocaine act as a local anesthetic?
Inhibits sodium voltage-gated channels in some cells that block the transmission of signal in our small thyrsus which contain the pain pathways.
What are the three categories (in this case they are categorized based on how they act) that explain the acute effects of cocaine( the immediate effects)?
Physiological (sympathomimetic)
the primary effect that includes: vasoconstriction which increases blood pressure and increases heart rate
Brondchioldilation
Increase temp
Pupil dilation
Anorectic (lessen the appetite)
increase plasma glucose by breaking down fat
Attention (a stimulant)
Includes
high alertness
high ability to concentrate (that is a belief)
and lessen fatigue
Movement( psychomotor)
activates motor pathways (nigrostriatal pathways)
In low doses
Your movement, talking fidgeting, and pace increase
In high doses
repetitive movements
How do the effects change as user progress from brief use to more repeated use?
The toxic effects of cocaine
The user will have cardiovascular problems (more numerous)
and
seize problem
What is considered a “toxic” dose?
How does overdose occur?
1-2 mg per kg and multiple it by the user weight and you will find the toxic dose of the user.
An overdose occurs when a person creates a significant amount of tolerance.
check the image of the two-dose curves to explain overdose.
Now that we know about one of the toxic effects of cocaine is more numerous cardiovascular problems, what is cocaine acting on in the cardiovascular system?
The drug is acting on Vasculator (blood vessel)
Performing vasoconstriction and prothrombotic state (likelihood a blood clot will occur)
Increased platelet coagulation
Endothelial dysfunction and thrombosis
Decrease myocardial 02 supply
Sympathetic N.S.
Increased myocardial oxygen demand due to the decrease of O2 supply from the vasculature
Increase heart rate. blood pressure, contractility
Inhibition of catecholamine (DA or NE) reuptake and increase sensitivity to NE which increase the NT tone in the synaptic cleft
Cardiomyocytes
block of Na and K channels which depresses cardiovascular parameter
Interference with calsequestrin mediated Ca2+ storage and release which disrupts excitation-contraction coupling and progressive oxidative stress cause mitochondrial damage and cell death
What are the short and long-term Cardiovascular consequences of cocaine?
Short Term consequences
Chest pains
Myocardial ischemia or infraction that leads to a heart attack due to lack of 02 in the heart
Hemorrhagic or ischemic stroke leads to cell death
arrhythmias
Long Term Consequences
Atherosclerosis and increased sensitivity to insult
Cardiomyopathy and heart failure
Aortic dissection which is swelling of the heart and muscle
Endocarditis – inflammation of endothelial cells
When users have continued using cocaine we ask them, Why do you take the drug?
What are the progression effects with continuous use?
For recreation –> euphoria
for alertness
reduce anxiety
After the user repeatedly take the drug the
increase fatigue
increase anxiety levels
less of a euphoria
some will experience paranoia or sensory hallucinations
What do we know about the psychomotor effects of cocaine?
Psychomotor stimulants
at low/moderate dose it will increase normal motor activity
at high dose, it will display stereotypes movements
Also, cocaine activates nigrostriatal and mesolimbic Da pathways
What do we know about the neuroadaptations induced by repeated exposure?
Cocaine causes the production of dendritic spines that were associated with condition Pefromance Placement (associative learning (the adminstarion of the drug + the environment))
How are self-administration and place conditioning paradigm studies used in the investigation of drug effects?
The researchers knew that the increase in dendrites’ spine was not associated with the locomotion effect of cocaine.
The researchers used the Place Conditioning Paradigm to ask if the animal shows any resembles towards the drug?
A subject is a place in a training phase in where it is given a drug, in a closed environment, and then place in a test phase in where the environment is open and if the subject enjoyed the drug it will remain in the same environment and if it didn’t it will move to the other side. If the animal liked the drug it will demonstrate preference which resembles associate learning.
Also, the researchers used the Self-Administration experiment to look at Reinformcnent and Reward. Ask these questions during these studies,
Is the drug reinforcing
What is the natural pattern of use?
How hard will subject work for a drug
Do stimulants include tolerance, sensitization, and/or dependence?
Cocaine can induce tolerance and sensitization and it depends on the pattern of administration.
Does cocaine act as teratogens?
Yes
