Cocaine and Stimulants Flashcards by Beth Cocker

**Behavioral Stimulants

Cocaine
Amphetamines
Methylphenidate (ritalin)
Pemoline (Cylert)
Phenmetrazine (preludin)
MOA- Increased levels of NE and DA

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**Antidepressants

Imipramine and amitriptyline (MOA: block NE/5-HT reuptake)

Tranylcypromine (MOA: MAOi)

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**Legal Recreational Drug

Caffeine (blocks adenosine receptors)

Nicotine (stimulates ACh receptors)

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Cocaine Chemistry

Local anesthetic
Hydrochloride crystal or snow is inhaled (NOT suitable to be smoked because it decomposes at high temperatures)
Extracted in ether to make free base cocaine which can be smoked

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Cocaine Routes

Oral: Chewing Coca Leaves (~75% lost to first pass; 25% reach the brain)
Intranasal (snorting)
Inhalation (smoking or free basing)
Intravenous (mainlining)

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Cocaine Routes Onset

Oral: more than 1 hour
Intranasal: 30-60 minutes
Inhalation: Within seconds
IV: Delayed-onset about 30-60 seconds

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**Major Metabolite of Cocaine

Benzoylecgonine (in urine for 3 days and much longer in chronic user)

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3 Main Effects of Cocaine

Local anesthetic
Blood vessel constrictor
Psycho-stimulant (STRONG reinforcing qualities)

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Cocaine MOA

Block reuptake of DA, NE and 5HT

Increases DA in the VTA and NA (psycho-stimulant effects and behavior-reinforcing properties)

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Cocaine Psychological Changes

Mood elevation
Enhanced cognition, drive states (hunger, sex, thirst)
Talkative
Suppressed appetite
Delayed Sleep

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Cocaine Delayed Effects

60-90 minutes after administration: mild euphoria with anxiety followed by long-lasting anxiety (cravings)
High dose: loss of coordination, tremors and seizures

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Cocaine Toxic Symptoms

Anxiety, sleep deprivation, hyper-vigilance

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High dose, long-term use of Cocaine Symptoms

Dysphoria
Paranoia
Severe depressive
Schizo
CV/Neurovascular: strokes
Fetal: difficulty in unstructured play and easily frustrated, cognitive problems and ADHD is common

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Amphetamine was used to treat:

narcolepsy and then later 39 conditions like smoking, schizo, hypotension
WWII fight fatigue and enhance preformance

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Amphetamine MOA

Increase in the levels of monoamine (inhibit reuptake of NE and DA10 fold and is partly degraded into ROS which increase oxidative stress and neurotoxicity

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Low Dose Effects of Amphetamine

Behavioral and psychomotor stimulation
Appetite supressant effects
Agression in adults
Inhibits aggression and causes ADHD behavior in children
Increased BP followed by reflector bradycardia and bronchodilatio

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High Dose Effects of Amphetamine

Aggression and paranoid delusions
Severe anorexia
Amphetamine psychosis = acute schizophrenic attack

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Chronic Dose Effects of Amphetamine

Severe depletion of DA
Depletion of tyrosine hydroxylase
Less of DA receptors
Loss of responsiveness to natural reinforcers

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Amphetamine Tolerance

Develops rapidly with dysphoria, sedation, and lethargy

Caffeine Blackout in a Can

Energy drinks + Alcohol

Caffeine effects goes away faster than the alcohol, person would pass out due to the alcohol effects
Caffeine also covers the effects of alcohol so drink more but you don’t think you are

Caffeine MOA

Regular concentration: antagonist of adenosine receptor
High concentration: Increased intracellular Ca (increased strength and duration of contractions in skeletal and cardiac muscles)
Blocks both A1 and A2alpha receptors

A1 Receptors

Abundant in the brain

Decreased release of neurotransmitters which leads to decreased neuronal firing

A2alpha Receptors

DA rich regions of the brain
Increased GABA release
Decreased affinity of DA

Caffeine Halflife

2.5-4.5 hours but increases with decreased age

Smokers: 30-50% reduction due to CYP1A2

Caffeine Physiological Effects

Bronchodilation, increased gastric acid secretion and BP, and decreased RR (peripheral) Increased: alertness, cognitive performance and auditory vigilance (CNS)

Caffeine Symptoms of Intoxication (>250 mg)

``` Restlessness, nervousness, rambling Excitement, anxiety Flushed face Tachycardia, arrhythmia GI Insomnia Psychomotor, agitation, low seizure threshold ```

Cigarette Chemicals

>4000 compounds in cigarette smokes (43 known cancer-causing agents) Nicotine is the main compound with regards to addiction

Nictonine PK

Readily crosses plasma membrane Readily absorbed through skin, lungs, mucous membrane High first pass metabolism

Smoking + Nicotine

Sharp increase leading to lots of DA release to the NA

**Nicotine Metabolite

Cotinine (80%) | Excreted in the urine and has a 24 hour plasma half-life

Nicotine + Reward System

``` Nicotine causes DA release in the NA by binding alpha4beta2 in the VTA (post) Nicotine binds to alpha 7 in the VTA (pre) which causes dopamine release in the NA Desensitize alpha4beta2 (post) on GABA interneurons in the VTA ```

What does GABA do?

Reduced GABA disinhibits mesolimbic dopamine neurons and thus enhances dopamine release in NA

Nicotine + CNS Stimulation

Activates brain nicotinic ACh receptors

Low Dose Nicotine + CNS Stimulation

```  Increased alertness and cognitive functioning  Feelings of pleasure and relaxation  Reduced depression, anxiety and hunger  Stimulated respiration  Induced vomiting ```

High Dose Nicotine + CNS Stimulation

Induces tremors and convulsions followed by depression and death

Nicotine + Cardiovascular

Increased HR, cardiac output, oxygen consumption and BP

Nicotine + GI Tract

Increased bowl activity and tone | Causes N/V/D (through PS/S)

Nicotine + Exocrine Glands

Initial stimulation and then inhibition

Nicotine Patch and Gum

Nicotine levels increase sharply to pleasurable reinforcing levels Between puffs, this level falls As nicotine levels fall, receptors begin to re-sensitize and cause craving

Nicotinic Partial Agonists

Varenicline

Varenicline MOA

Stabilize nicotinic receptors in an intermediate state

Smoking while on Varenicline

If they smoke while on NPA, it will still compete with nicotine for the receptor and cause a drop in the DA which blocks the euphoria and brings DA back down

Transdermal Delivery of nicotine

Steady level of nicotine which can desensitize some receptors and relieve some craving Does NOT induce euphoria NOR does is it sufficient to eliminate all cravings

Buproprion MOA

Increased amounts of DA through the synaptic cleft, it will only be enough to cover the craving not causing euphoria

ACh and Nicotine

ACh is a full agonist of alpha4beta2 nicotinic receptors but it is short acting due to AChE (short pulses of DA release) Nictonine is a full agonists of alpha4beta2 nicotinic receptor (prolong opening of these channels until they desensitize - prolong burst of DA release)

NPA (Nicotinic Partial Agonists) MOA

Causes sustained small increases in frequency of opening of alpha4beta2 nicotinic receptors in the VTA leading to small sustained increases in DA release

NPA vs Bupropion

NPA is more effective than bupropion