lecture 22a: amphetamines, cocaine, PCP, LSD, inhalants

ventral tegmental area--> nucleus accumbens via medial forebrain bundle ---> prefrontal cortex

pathway of dopamine in the reward pathway

concominant use of benzos and opioid

•FDA added a black box warning for the concomitant use of this combination due to the result of profound sedation, respiratory depression, coma, and death.

•Reserve concomitant use for those patients whom treating options are inadequate

•Limit dosages and durations to the minimum required

•Follow patients for signs/symptoms of respiratory depression and sedation

•***DOCUMENT IN THE RECORD THAT YOU ARE AWARE OF THE CO-PRESCRIBING AND THAT YOU HAVE DISCUSSED THE RISKS NOTED ABOVE WITH THE PATIENT AND RATIONALE FOR THE CHOICE**

concominant use of benzos and opioids should be reserved for

fentanyl

•potent opioid (50 X more potent than heroin and 100 x more potent than morphine)

•cheaper to produce than heroin and can be "pill pressed" as counterfeits that say "oxycodone" or other agent. The buyer/user may not be aware that they are really using fentanyl.

•Can be injected, snorted, smoked, taken orally, and spiked onto blotter paper.

heroin

-processed from morphine

-usually a white or brown powder or a black sticky substance

-most are cut with other substances

bacterial endocarditis, affects the inner lining andd valves of the heart

IV usage of heroin is associated with

dopamine and norepinephrine

-causes an adrenaline rush-more blood to muscles, focus, feelings of power, and activates the DA reward pathway which causes the brain to associate the reward with the drug.

use of stimulants causes buildup of these neurotransmitters

1. ADHD

2. Narcolepsy

3. Binge-eating disorder

4. Shift-work sleep disorder

stimulants are FDA approved for use in

1. severe major depressive disorder that requires augmentation therapy to alleviate severe, and possibly life-threatening neuro-vegetative signs that are resistant to treatment with approved medications.

2. disorders of diminished attention and motivation (an investigational category of psychiatric syndromes that could be due to medical conditions that are not alleviated by other therapies). Think Long COVID, Post-stroke, etc.

off label (but not illegal) uses of stimulants

amphetamine

adderall is aka

-stimulates the release of NE and other biologic amines

-higher doses cause release of dopamine, even higher does 5-HT

MOA of amphetamine

schedule II

amphetamines are what schedule?

Frequently misused for weight loss

Performance Enhancement

Toxic Euphoria (Pills are crushed and snorted or mixed with water and injected) - drug delivery methods can influence the addictive potential of the drug.

stimulants are often misused for

-tachy or brady

-pupillary dilation

-elevated or lower BP

-sweating, nausea, weight loss, muscular weakness, chest pain, arrythmias, confusion, seizures

signs of stimulant intoxication

Atomoxetine

-selective NE reuptake inhibitor approved for ADHD

-NOT a controlled drug

clonidine and guanfacine

alpha 2 agonists used in treatment for ADHD

-reduce locus coeruleus activity

Armodafinil

schedule IV drug approved for Narcolepsy, OSA, and

Shift-Work Sleep Disorder

Modafinil

schedule IV drug approved for Approved for Narcolepsy, OSA, Shift-Work

Sleep Disorder, and Fatigue related to MS

activating glutamatergic circuits and inhibiting GABA; indirectly activates orexin

MOA of modafinil

Cocaethylene

-more cardiotoxic than cocaine!!

cocaine + alcohol yields

cocaine plus heroin

-called speed balling when adding these two drugs together

-side effects of each are attenuated but it is a deadly comob

-binds to dopamine reuptake transporters on the pre-synaptic membranes of dopaminergic neurons

-this binding inhibits the removal of dopamine from the synaptic cleft and its subsequent degradation by Monoamine oxidase

MOA of cocaine

•Cocaine therefore increases DA, Epinephrine, Norepinephrine, And Serotonin via transporter proteins.

•Immediately this increases DA/5HT in the nucleus accumbens.

cocaine increases concentrations of these neurotransmitters

Benzoylecgonine

primary metabolite of cocaine

•Actions on the cardiac system are from alpha and beta-1 adrenoceptor stimulation resulting in increased heart rate, systemic arterial pressure, and myocardial contractility.

•

Cocaine induces platelet activation and thrombus formation

affects of cocaine on the CV system

amphetamine

the short term effects of cocaine use are virtually identical to effects of

cocaine

short term effects of _______

Vasoconstriction

Tachycardia

Chest pain

Pupillary dilation

Hyperthermia

Tremors

Rhabdomyolysis/myoglobinuria/renal failure

Teeth grinding

resp failure, HTN, ischemic bowel, parkinsonism issues, malnourishment, degradation of nasal cartilage

long term effects of cocaine use

-ABC, IV access

-avoid restraints (rhabdo)

-monitor for hyperthermia

treatment for cocaine toxicity

craving, exhaustion, mental confusion, insomnia, extreme hunger, anxiety

withdrawal effects from stimulants

There is currently no FDA approved medication for this purpose :(

Psychotherapy-Contingency management, supportive recovering communities, cognitive behavioral therapy

Pharmacological treatment for depression

treatment for cocaine/stimulant users

-stimulate release of DA and NE form terminals

-inhibits Monamine oxidase

-can directly activate catecholamine receptors

how do amphetamines work?

methamphetamine

Common names include chalk, crank, crystal, ice, meth, and speed

Modes of abuse: inhalation/smoking, swallowing (pill), snorting, and injection of the powder that has been dissolved in water or alcohol

The “high” fades quickly; form of binging called a “run” in which the person will give up food and sleep while continuing to take the drug every few hours for up to several days.

meth mouth

enamel eroded away due to corrosive chemicals in product

LSD

discovered in 1938 from lysergic acid which is found in ergot, a fungus that grows on rye and other grains

peyote

(a small spineless cactus with mescaline (psychoactive ingredient as well as can be produced from chemical synthesis)-originally used by natives of Mexico as part of religious rites.

LSD

Tablets, capsules, liquid form or decorated pieces

“trips” last 12 hours-delusions, hallucinations, hearing colors and seeing sounds-synesthesia; DELUSIONS OF FLYING

Mydriasis, tachycardia, htn, hyperthermia, diaphoresis

peyote

Buttons from the top are cut and dried which are later chewed or soaked in water. Lasts 12 hours of hallucinations, altered perception of time. Effects can vary depending on potency. Can have flashbacks (hallucinogen persisting perception disorder) with reoccurrences of hallucinations long after ingesting the drug

psilocybin

Can be brewed as a tea to mask the bitter flavor. Initial effects may present with nausea and emesis before the psychological effects which appear within 20 mins. And last 6 hours. Can be taken from the mushroom or made synthetically. Other physical effects are hyperthermia, tremors, sweating, htn, tachycardia, loss of appetite and insomnia

psilocybin

aka magic mushrooms/shrooms

ACID; BLOTTER BOOMERS, DAFFY DUCK; GOLDEN DRAGON; LOONY TOONS, LUCY IN THE SKY

LSD is aka

LSD, peyote, psilocybin, PCP

list the hallucinogens

PCP (phencyclidine)

was discontinued in 1965 from medical anesthesia due to the problems patients had in recovery-lability, psychosis, confusion, and aggression.

NMDA receptor antagonist in the glutamate inputs of d-1 in nucleus accumbens

MOA of PCP

RED DANES

rage, erythema, dilated pupils, delusions, amnesia, nystagmus, excitation, and skin dryness

mneomonic for the effects of PCP

PCP

what hallucinogen?

Feelings of strength, super-human power, and immortality

Loss of balance, blurred vision, drooling

Hallucinations, delirium, seizures, coma

Long-term use leads to memory loss, speech difficulties, and depression

Unpredictable cardiac abnormalities

One of the most dangerous drugs of abuse

PCP

Treatment involves placement in a quiet room with little sensory stimulation but should not be left alone/unattended

Fry

the slang for marijuana that has been dipped in PCP and then dried

inhibits NMDA glutamate receptors

moa of MDMA (ecstasy)

Ecstasy (MDMA)

EFFECTS IN 45 MINS OF ENHANCED SENSE OF WELL-BEING

INCREASED EXTROVERSION, EMOTIONAL WARMTH, EMPATHY

TOWARD OTHERS (ALSO KNOWN AS AN EMPATHOGEN); HEIGHTENED SEXUAL SENSORY EXPERIENCE (OFTEN CALLED THE LOVE PILL) AND WILLINGNESS TO DISCUSS EMOTIONALLY CHARGED MEMORIES

molly is a form of pure MDMA, while ecstasy is MDMA combined with other ingredients such as caffeine, dextromethorphan, ephedrine, ketamine, or methamphetamine

what is the difference between ecstasy and molly?

yes, may cause severe hyperthermia

can ecstasy act as a stimulant

ecstasy

CAN DAMAGE SEROTONIN PATHWAYS

PERMANENTLY AND LEAD TO SEIZURES AND LOC.

ecstasy

-lots of serotonin!!!!

CHEMICAL STRUCTURE SIMILAR TO METHAMPHETAMINES

AND HALLUCINOGENS, BUT WITH A SEROTONIN TO DA STIMULATION OF 10:1 COMPARED TO METH WITH IS 1:10

ecstasy

considered the club drug for "raves"

dextromethorphan

1.Primary active ingredient in most cough syrup preparations.

2.NMDA receptor blockade and mild increases of dopamine.

3.Altered perceptions (hallucinations) as well as present with nystagmus, ataxia, slurred speech, diaphoresis, htn, and possibly hyperexcitability vs. lethargy

4.Can lead to liver failure and toxic psychosis with long-lasting effects

Rohypnol

-known as roofies

-a benzo not approved in US but sold OTC in mexico and india

Gamma-hydroxybutyrate (GHB)

known as the date rape drug

ketamine

known as special K, a date rape drug

1. destroys bone marrow

2. destroys myelin sheath

3. multi-organ damage (Cardiac/liver)

4. eventual cerebral anoxia

long term effects of inalants

Tetrahydrocannabinol (THC)

-principle psychoactive contituent of cannabis

ananda

an endogenous cannabinoid that influences pleasure, memory, concentration, movement, coordination, and sensory input with time/perception; also found in chocolate, black truffles, black pepper, echinacea.

-THCs structure is similar, allows body to recognize THHC instead of ANA

THC-COOH (carboxy-THC)

-longer half life of 5-6 days and can indicate exposure to THC for up to 30 days

-fat soluble, makes it harder to eliminate

what is the metabolite of THC and what is its half-life?