Neur 342 - Cocaine

drug that increases CNS activity

What is a stimulant?

low efficacy and high efficacy stimulants

What are two types of stimulant categories?

sympathetic nervous system

stimulants activated which part of the nervous system?

class II

Which schedule class is cocaine?

- ENT uses for eye surgery

- local anesthetic(lidocaine)

Name some instrumental uses of cocaine?

inhibits voltage gated Na+ channels

What is the mechanism of action for cocaine?

- cocaine hydrochloride(HCl)

- base cocaine(no HCL)

What are two forms of cocaine?

- nasal

- IV

- inhaled

- oral

In the pharmacokinetics of cocaine what are the different routes of administration?

slowly absorbed by mucous membrane

- 70% bioavailability

When cocaine HCl is snorted, how is it absorbed and what is the percentage of bioavailability?

false

True or false cocaine HCl can be absorbed through inhalation?

inhalation

What is the only way for absorption of freebase/crack cocaine?

lipophilic

- easily cross BBB and placental barrier

as cocaine is distributed around the body, is it lipophilic or lipophobic? What is the effect it has on different barriers?

butyrylcholinesterase(BChE)

What enzyme breaks down cocaine in the blood plasma level?

CYP3A4 enzyme

What enzymes breaks down cocaine in the liver?

- bezoylecgonine

- ecgonine methyl ester

What two inactive metabolites does the liver enzyme break cocaine down into?

norcocaine

What active metabolite does the liver enzyme break down cocaine to?

forms cocaethylene

What happens when alcohol and cocaine combine in the liver?

synergistic effect - more euphoria

What is the effect of cocaethylene?

urine

What is the route of elimination of cocaine?

~ 30 minutes

What is the half life of cocaine?

- dilated pupils

- red eyes

Which kind of eyes belong to a cocaine user?

- feelings of exhilaration

- great self confidence

- heightened energy

What are acute behavioral effects of cocaine?

- block reuptake transporters(DAT/NET)

What is cocaine's action at the synapse(acute)?

block DAT, NET, and SERT

What does cocaethylene block?

activation of alpha adrenergic receptors in the brain

The increase of NE after blocking NET leads to activation of which receptors in the brain?

- wakefulness, increased respiration

- decreased appetite

name some effects in the activation of alpha adrenergic receptors?

objective CNS effects

Is NE responsible for the objective or subjective CNS effects of cocaine?

activation of postsynaptic DA receptors

What does the build of DA in the synapses cause?

Subjective CNS effects

Is DA responsible for the objective or subjective CNS effects of cocaine?

- euphoria

- well being

- increased sense of confidence

name some effects in the activation of post synaptic dopamine receptors?

motivation/ pleasure effects

What is the mesolimbic DA pathway involved in?

motor stimulating effects

What is the nigrostriatal DA pathway involved in?

10-15%

What percentage of initial cocaine user become abusers of cocaine?

repeated cocaine use lasting hours to day w/ little sleep

What is "binging" in the context of cocaine use?

abstinence syndrome

What happens after a cocaine binge?

- crash

- withdrawal

- extinction

Abstinence syndrome consists of what three stages?

exhaustion and depressed mood

What are the symptoms of the "crash" phase after cocaine use?

- anhedonia

- anergia

- craving for cocaine

What are the symptoms of the "withdrawal" phase after cocaine use?

symptoms subside

What are the symptoms of the "extinction" phase after cocaine use?

- stimulating

- euphoric

- confidence enhancing effects

What are the reinforcers in the early stage of cocaine use?

pharmacodynamic tolerance

What type of tolerance develops with chronic cocaine use?

euphoric effects show the most significant tolerance.

Which effects of cocaine are most affected by tolerance?

nucleus accumbens

What brain region undergoes adaptations due to chronic cocaine use?

reduced DA levels and release at presynaptic neuron

How does chronic cocaine use affect presynaptic dopamine (DA) levels?

reduced rate of DA uptake

What happens to dopamine reuptake in chronic cocaine users?

reduced ability of cocaine to block DAT

How does chronic cocaine use affect cocaine's ability to block the dopamine transporter (DAT)?

- dysphoria/depression

- lethargy

- drug craving or suicidality

What are cocaine withdrawal symptoms?

gray matter in specific regions

cocaine use is linked to decreased _________?

- PFC

- ACC

- insula

- dorsal striatum,

- amygdala

- thalamus

Which areas of the brain have reduced gray matter?

- impulse control

- working memory

- decision making

What functional changes are seen with cocaine abuse and cognitive deficits?

- panic attacks

- paranoid psychosis

- formication syndrome

What are the long term behavioral effects of cocaine?

type of hallucination in which individuals believe there are bugs crawling on their skin

What is formication syndrome?

- malnutrition and weight loss

- septal necrosis or perforated septum from snorting

What are long term physiological effects of cocaine?

vasoconstriction in the brain leads to interrupted blood flow --> lead to stroke

how can cocaine kill you?