Svensson Lectures Flashcards
Psychostimulants use & effects
- activate CNS resulting in alertness, excitation, and elevated mood
- stimulants play a major role in drug abuse crisis
Stimulants historical & medical use
- Cocaine: reduce hunger & fatigue; anesthetic
- ephedrine widely used for asthma & overall stimulant properties
- nicotine smoking to treat asthma
- amphetamines for various uses
Nicotine - MOA
- activates nicotinic acetylcholinergic receptor
- Na enters cell, K exits, which creates an action potential.
- heterogeneity of subunits determines how many molecules of Ach bind to receptor
- variation in receptor composition at different sites may influence physiological response
ACh vs Nicotine
- both have charged amino groups and H bond acceptor groups
- nicotine is membrane penetrable at physiological pH
- nicotine is not degraded by acetylcholinesterase
partial agonist therapy
- causes release of dopamine
- highly addictive
- nicotine replacement therapy relatively ineffective alone
- varenicline partial agonist increases quit rate success
Cocaine MOA
- antagonist of amine transporters: DAT, SERT, NET
- DAT>= SERT > NET
- prevents DA reuptake and increases DA concentration
- also increases duration of dopamine action
Methamphetamine, Ecstasy, & Bath Salts – MOA
- amphetamines/XTC/bath salts compete for reuptake (resemble endogenous DA, NE; they block DA reuptake and push out DA from vesicles)
- increase extra-vesicular DA, reverse transport gradient
- amphetamines are MAOi’s
- activate Trace amine-associated receptor (TAAR1) which phosphorylates DAT and induces reverse transport function
Mesolimbic Dopamine System
key dopaminergic pathway that transports dopamine from the ventral tegmental area to the nucleus accumbens and amygdala
addiction liability
- likelihood that a person using the drug will become addicted
sympathomimetic toxidrome
a constellation of signs/symptoms indicative of ingestion of psychostimulant
cocaine
a psychostimulant first isolated from cocoa leaves in 1857. primarily an inhibitor of dopamine transporter, preventing reuptake of DA released into synaptic cleft
Nicotine
most addictive substance in current use; activates nicotinic acetylcholinergic receptors
- (other psychostimulants directly enhance dopamine release and inhibit reuptake)
methamphetamine, ecstacy, MDMA
psychostimulants that primarily release endogenous DA
cathinones
derivatives of Khat plant (bath salts) that display similat activity to methamphetamine
dose-effect of psychostimulants
low dose - enhance wakefulness and vigilance
higher doses - increase agression, euphoria, and psychosis
chronic psychostimulant use effects
- produce tremors, anxiety, paranoia, delusions, repetitive behavior, profuse dental decay, dilated cardiomyopathy
- results in downregulation of DA receptors (return to baseline after period of abstinence)
Hallmarks of Sympathomimetic Syndrome
MATHS:
- mydriasis
- aggitation/arrhythmia/angina
- tachycardia
- hypertension/hyperthermia
- seizures/sweating
Hemp
a strain of cannabis that is grown for agricultural products and contains less than 0.3% THC
Marijuana
a strain of cannabis sativa that commonly contains 15-20% THC content for its psychoactive effects
Synthetic Marijuana
Illicit synthetic compounds that are analogs of THC and bind to CB1 receptor as full agonists producing similar psychoactive effects as THC
Endocannabinoid System
an endogenous system comprised of four components
1 cannabinoid receptors
2 ligands
3 endocannabinoid membrane transporters
4 synthetic and degradative enzymes
this system regulates immunity, memory, mood, pain, and perception
THC
tetrahydrocannabinol is the primary euphoric component in marijuana is an agonist of CB1 and CB2 receptors of ECS
CBD
cannabidoil is a non-euphoric natural cannabinoid widely marketed for variety of uses that is not an agonist for CB receptors
Δ8-THC:
A euphoric componene in cannabis sativa that is increasingly present in the unregulated market
Dronabinol/Marinol
schedule III FDA approved synthetic Δ9-THC in sesame oil indicated for AIDS-associated anorexia and refractory chemotherapy-related nausea and vomiting
Nabilone/Cesamet
A schedule II FDA approved THC mimetic for chemotherapy induced N/V
Cannabidoil/Epidolex
FDA approved form of CBD indicated for 2 rare seizure disorders, Dravet Syndrome and Lennox-Gastaut Syndrome
Endocannabinoids and phytocannabinoids
primarly serve as retrograde regulators of neurotransmission
- inhibit release of GABA and glutamine
Psychadelics
agents that produce non-ordinary and variable forms of conscious experiences.
- ex: changes in mood, thoughts, distorted perceptual sensations generally only experienced in dreams
delusion
- fixed, false belief unresponsive to logic
- despite contrary evidence, a person in a delusional state cant let go of these convictions
- paranoia is a common manifestation
hallucination
- a false perception arising from internal stimuli
- creates a false reality
illusion
- a misperception of external stimuli
- special perceptual experiences in which information arising from “real” stimuli leads to incorrect perception
- distorts reality
- misperceiving something that’s true
visionary restructuralization
sensory illusions
oceanic boundlessness
highly pleasurable state of self-dissolution
anxious ego-dissolution
thought disorder leading to unpleasant state of anxiety and sense of loss of control
LSD
lysergic acid is the most widely recognized classical psychedelic and is a derivative of tryptamine
DMT
dimethyltryptamine is a naturally occuring psychedelic found in Ayahuasca Vine, haarvested in peruvian amazon
Psilocybin
prodrug of psychedelic psilocin and found in over 200 types of mushrooms
mescaline
phenethylamine psychedelic found in Peyote cactus and other plants that has amphetamine-like activity
Ketamine
dissociative psychedelic that is an NMDA receptor antagonist and induces anesthesia and analgesia
Dextromethorphan
antagonist of NMDA receptor, and SERT inhibitor
- commonly found in OTC cough syrups
Phencyclidine
NMDA antagonist that is more potent than ketamine and sometimes used to lace tobacco or marijuana cigarettes
Muscimol
agonist of GABAa found in Amanita muscaria
- dissociative psychedelic
Alkyl nitrites
commonly known as ‘poppers’
- release nitric oxide
- AE arise from the production of methemoglobinemia
Volatile solvents
compounds that are liquid at room temp but readily evaporate when exposed to air
- psychoactive volatile solvents affect numerous ion channels in CNS through GABAa potentiation.
– predominantly used by adolescents
At common doses psychedelics induce ___
illusions rather than hallucinations
classical psychedelics
- derived from phenethylamine or tryptamine
- act as agonist of 5HT2A receptor
- ingestion results in increased global integration in the brain
Primary adverse effects of classical psychedelics
acute dysphoric reaction or prolonged psychotic reactions
dissociative anaesthetics
NMDA antagonists that induce anesthesia and analgesia
Sudden Sniffing Death Syndrome
a lethal arrhythmia developed after inhilation of volitale solvent (toluene)
Long-term volatile solvent inhalation
- neurotoxic in both individuals who inhale them recreationally and via occupational exposure
