PHRM845-FINAL EXAM Flashcards
Pharmacology of psychedelics and psychoactive inhalants
What are psychedelics?
Produce non-ordinary and variable forms of conscious experiences. These include changes in mood, thoughts, and distorted perceptual sensations gradually only experienced in dreams.
What are hallucinogens?
-It has fallen into disfavor b/c these drugs rarely produce frank hallucinations at doses commonly used.
What are delusions?
-Fixed, false belief unresponsive to logic (logic will NOT take them out of it)
-Paranoia is a common manifestation
(ex: shooting their way into building to get breakfast)
What are hallucinations?
False perception arising from internal stimuli
-Creates a false reality (auditory or visual)
(ex: bears having tea party on roof)
What are illusions?
-Misperception of external stimuli
-Distorts reality (something is actually there)
(ex: bear is sitting in a chair–it is really a person)
What are the two classical psychedelics?
-Derivatives of phenethylamine
-Derivatives of tyramine
What are examples of dissociative psychedelics?
-Phencyclidine
-Ketamine
-Muscimol
Dimethyltryptamine (DMT)
-Naturally occurring classical psychedelic drug
-From Amazonian
-Aaron Rodgers popularized this
5-MeODMT
-Naturally occurring classical psychedelic drug
- 5-6x more potent than DMT
-Derivative of DMT
-Colorado River Toad has this
Psilocybin (psilocin)
-Naturally occurring classical psychedelic drug
-Magic mushrooms
-Psilocybin is a pro-drug of psilocin (via rapid dephosphorylation)
Mescaline combines MOA of ___ and ___
-LSD and MDMA
Phenethylamine
-Amphetamine-like (stimulant and psychedelic activity)
~MDMA and bath salts
-Increases release of 5-HT> DA, NE
-Empathogens/Entactogens (more hallucinogenic than stimulatory)
-Lowest potency (~500 mg)
-Long lasting (10-12h)
-Cross tolerance to LSD due to similar MOA
~Suspected interaction with serotonin system
Most classical psychedelics are agonists of ____.
We want to pretreat with ___ antagonists to block psychedelic effects.
**Exception ____ stimulates 5-HT release
5-HT2A
5-HT2A
MDMA
Psychedelic drugs markedly increase ____ integration in the CNS.
-Global
**shows connectivity across regions of the brain
Effects on the dimensions and subscales of the 5-dimension altered states of consciousness (5D-ASC) scale.
-What are the 3 main sections?
-Visionary restructuralization (sensory illusions)
-Oceanic boundlessness (highly pleasurable state of self dissolution)
-Thought disorder leading to unpleasant state (bad trip)–> anxious ego dissolution
What is audio-visual synsthesiae?
-Hear something and see colors
-Enhanced visual perception
-Falls under visionary restructuralization (sensory illusions)
What is spiritual experience?
-Can happen to pts even without a religious background
-Connected with world like never had before
-Falls under oceanic boundlessness (highly pleasurable state of self dissolution)
What is blissful state?
-Lost all cares/concerns
-Falls under oceanic boundlessness (highly pleasurable state of self dissolution)
What is disembodiment?
-Pt feels they are outside of their body
-Falls under thought disorder leading to unpleasant state (bad trip)
What is impaired control and cognition?
-Pt cannot control themselves
-Falls under thought disorder leading to unpleasant state (bad trip)
Psychedelic drug use adverse effects:
Short term:_____
Physiological
-Tachycardia
-HTN
-Tremors
-Dry mouth
-Nausea
-Hyperthermia
**NOT life-threatening; bigger issue is how people respond
Psychedelic drug use adverse effects:
Acute dysphoric:_____
Reaction
-Terrifying thoughts (impeding doom; separating from body and won’t get back in)
-Fear of insanity
-Fear of losing control
-Fear of death
**Likely have 2 therapists
Psychedelic drug use adverse effects:
3rd phase:____
Psychotic reaction
-Flashbacks (hallucinogen persisting perception disorder; can last for years and they are usually negative)
-Enduring changes in personality (whole world view might change; how do you get consent for that?)
-Exacerbate underlying psychotic disorder
-Instigate prolonged psychotic disorder
-Rate of psychosis after LSD is 1-5%
Psychedelic drug use can lead to rapid development of ___ on the ____ consecutive day; marked attenuation of effect
tolerance; 3rd
-Frequent use can lead to mood changes
-No evidence of addictive potential
Potential therapeutic uses of psychedelics
-Cancer related psychological distress
-PTSD
-Depression
-SUD (alcohol)
Shortcomings of clinical trials for psychedelics
-Small sample size
-Lack of or inadequate controls (private companies providing $$ with little/no oversight)
-Many investigators/patients know which medication they received
-What is the proper control group?–controlled sensory input?
-Selection bias (those experienced with or comfortable with psychedelic drug use)
Over ____ % of volunteers are excluded from psilocybin trials because of previous experience/family hx.
-How is the average person going to respond to them?
90%
-We don’t know
MOA of dissociative psychedelics
-NMDA receptor antagonists
1. Inhibit GABA release
2. Disinhibition of glutamate release (increases glu levels)–>excitatory
Overview of glutamate receptors
-(competitive/noncompetitive) antagonist that enters when channel is open
-NMDA receptors are primarily (presynaptic/postsynaptic)
-NMDA receptors can also bind ____
-Noncompetitive
-Post-synaptic
-Glycine
Ionotropic glutamate receptors
-NMDA receptor antagonist
-Induces anesthesia AND analgesia
-Taken at high enough doses, don’t feel pain so pt can injure themselves and not know it
Ketamine (‘Special K’)
-Prominent NMDA receptor antagonist
-Racemic mixture (S+ is more active)
-Fast and short acting (10-60 min)
-Esketamine recently FDA approved for tx resistant depression
-Used in opioid tolerant pts for chronic pain
Dextromethorphan (DXM)
-Prominent NMDA receptor antagonist
-In cough syrup
-Also serotonin reuptake inhibitor
-Abused by ~4% of high schoolers
-Doses for cough suppression are <60 mg, while 100-600 mg are used to induce “high”
Phencyclidine (PCP)
-NMDA antagonist
~More potent than ketamine
~Also DA D2 receptor agonist
-Cigarette dipped in liquid PCP (more severe interaction with ketamine)
~Nicotine or marijuana cigarette
~Effect is 4-6h
-Pts often unaware of cannabis laced with PCP
-Severe dissociation and analgesia
~Self-mutilation without recognition (dissociation)
-Provokes psychotic rxn
-Misuse associated with violence and suicide
Muscimol
-Different from ‘magic mushrooms’
-GABA-A agonist–>can induce dissociative psychedelic effects
-In contrast, benzos and alcohol of allosteric modulators
Psychoactive inhalants
-Often 1st substance of abuse with kids (easily accessible)
Liquid psychoactive inhalant examples
-Paint thinner
-Paint remover
-Dry-cleaning fluids
-Gasoline
-Glue
-Correction, fluids
-Felt-tip markers
Aerosol psychoactive inhalant examples
-Spray pain
-Deodorant
-Hair spray
-Vegetable oil spray
-Fabric protector spray
Gases psychoactive inhalant examples
-Chloroform
-Nitrous oxide
-Whipped cream cans
-Butane lighters
-Propane tanks
-Refrigerants
Nitrites psychoactive inhalant examples
-Leather cleaner
-Room deodorizer
-Food preservatives
Inhalants can be misused in many ways. Provide ways of routes of administration
-Sniffing
-Huffing (gives highest concentration)–soak cloth and hold over face
-Bagging (spray into paper bag and breathe in)
-Dusting (put dust remover spray nozzle into mouth)
Alkyl nitrites
-Commonly sold as “poppers”
-Marketed as cleaning solutions and room deodorizers
-Nitric oxide release results in smooth muscle relaxation, platelet inhibition, and change in gene expression
-Relaxes anal sphincter, enhances erections, and gives pt euphoria
-Highest abuse among gay men (25x)
-Methemoglobinemia is greatest risk
Pharmacology of volatile solvents
-Widely used!
-Volatile solvents are liquid at room temp and evaporate readily when exposed to air
Toluene
-Volatile solvent
-Model glues, correction fluids, lacquer thinners, plastic cements, spray paints
Acetone
-Volatile solvent
-Nail polish remover
-Model glue
-Rubber cements
Benzene
-Volatile solvent
-Cleaning fluids, rubber cements, tire tube repair kits
Butane
-Volatile solvent
-Cigarette lighters, hair spray, spray paint
Highest volatile solvent use is among ___
Adolescents, especially in isolated communities (access driven?)
____ is the most characterized of the volatile solvents. Not a lot of research on it, but alters activity of a wide range of ion channels.
-Toluene
**GABA-A is the strongest channel that is potentiated
Acute effects (min) of volatile solvents
-Locomotor stimulation
-Euphoria, exhilaration
Effects of high dose (>3000 ppm) of volatile solvents
-CNS depression
-Slurred speech
-Disorientation
-Weakness
-Sedation
Repeated exposure to toluene causes ___
Lipid accumulation
Risks of inhalant abuse
-Asphyxiation: from repeated inhalations that lead to high concentrations of inhaled fumes, which displace available O2 in lungs
-Suffocation: from blocking air entering lungs when inhaling fumes from a plastic bag placed over the head
-Convulsions/seizures: from abnormal electrical discharges in the brain
-Coma: from brain shutting down all but most vital functions
-Choking: from inhaling vomit after inhalant use
-Fatal injury: from accidents including motor vehicle fatalities suffered while intoxicated
Based on independent studies performed over a 10-year period in 3 different states, the number of inhalant-related fatalities in the US is approximately ____ per year.
100-200
**Not clear how frequently it causes fatality
Sudden sniffing death syndrome
-Most concerning response
-Development of fatal arrhythmias within minutes of inhalation
-Compulsive use (some use it chronically)
-Neurotoxicity
~Brain is smaller and fills less of the space inside the skull
