Cocaine (First Stimulant)

Question 1

Where do cocaine originates?

Answer 1

The Eyrhtoxy coca plant

(A.K.A. E. Coca)

Question 2

Who made cocaine popular in late 1800-1900?

This person thought cocaine can be used for both theoretical setting and recreation.

Answer 2

Sigmund Freud

Psuchotherapist

Question 3

What are the two different forms of cocaine?

Answer 3

HCl salt –> powder form

and

Free Base –> crack cocaine

Question 4

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?

Answer 4

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

Question 5

What is the route of administration for crack cocaine?

What tend to be the dosage?

Answer 5

Normally Smoke

Dosages tend to be higher around 150mg per dose.

Question 6

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.)

Answer 6

30-90min

Question 7

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.

Answer 7

True

Question 8

What is the byproduct of cocaine’s metabolize?

Is this metabolite active or inactive?

How long can it be detected in your body?

Answer 8

Benzoylecgonine

Inactive

For roughly 48 hours to 2 weeks depending on the drug usage

Question 9

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?

Answer 9

Cocaethylene

Active

effective half-life: 150 minutes

This is 3 to 5 times more effective than taking cocaine by itself.

Question 10

What are the 3 important pharmacological effects of cocaine?

Answer 10

Local anesthetic (not used frequency)

Vasocontrictior

Psychostimulant (stimulate reward and reinforcement which can lead to compulsive use and to addiction)

Question 11

Now that you know the three important Pharmalocial effects of cocaine, what is the mechanism of action that source these effects?

Answer 11

Potentiates synaptic action of monoamines (DA, NE, 5-HT)

Question 12

How does cocaine act as a local anesthetic?

Answer 12

Inhibits sodium voltage-gated channels in some cells that block the transmission of signal in our small thyrsus which contain the pain pathways.

Question 13

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)?

Answer 13

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

Question 14

How do the effects change as user progress from brief use to more repeated use?

The toxic effects of cocaine

Answer 14

The user will have cardiovascular problems (more numerous)

and

seize problem

Question 15

What is considered a “toxic” dose?

How does overdose occur?

Answer 15

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.

Question 16

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?

Answer 16

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

Question 17

What are the short and long-term Cardiovascular consequences of cocaine?

Answer 17

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

Question 18

When users have continued using cocaine we ask them, Why do you take the drug?

What are the progression effects with continuous use?

Answer 18

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

Question 19

What do we know about the psychomotor effects of cocaine?

Answer 19

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

Question 20

What do we know about the neuroadaptations induced by repeated exposure?

Answer 20

Cocaine causes the production of dendritic spines that were associated with condition Pefromance Placement (associative learning (the adminstarion of the drug + the environment))

Question 21

How are self-administration and place conditioning paradigm studies used in the investigation of drug effects?

Answer 21

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

Question 22

Do stimulants include tolerance, sensitization, and/or dependence?

Answer 22

Cocaine can induce tolerance and sensitization and it depends on the pattern of administration.

Question 23

Does cocaine act as teratogens?

Answer 23

Yes