Inhalants and Solvents Flashcards
What are the forms of inhalants?
Solvents
Aerosols
Glue
How can we administer by inhalation?
Huffing
Sniffing Bagging
Where are inhalants distributed?
Brain and liver
Rapid and wide distribution because of small lipophilic molecules
What happens to more volatile substances (gases)?
Mostly exhaled
What are inhalants metabolized by?
Liver CYP2E1
How long does an inhalant high last?
15-45 minutes
What are inhalants absorbed?
Inhalation
How are inhalants excreted?
Kidney
Breath
What drug effects are inhalants similar to?
Alcohol, sedatives, hypnotics
What are the two phases of an inhalant high?
- Euphoria, disinhibition, dizziness, light-headedness, 15-45 minutes
- Drowsiness, disorientation, headache, 1-2 hours
What are the acute effects of inhalants?
Disinhibition of motor circuits at low doses
Slurred speech, inebriation
Hallucinations, anesthesia, coma, and death at high doses
What are the physiological mechanisms of toluene?
Reward euphoria via VTA-NAc reward pathway, elevated DA levels
What are motor effects via toluene use regulated by?
Regulated in part by GABA in the caudate putamen
What are the cellular mechanisms of toluene action?
DA-mediated reinforcement
Potentiates GABA and glycine neurotransmitters
Inhibits NMDA Glu receptors and nAChRs
Sum of actions on several ionotropic channels, Ca2+ signaling, G-proteins
What does toluene potentiate?
GABA and glycine NT action
Which NMDA channels are most sensitive to toluene?
2B-containing channels
What are cultured hippocampal neurons insensitive to in the presence of toluene
ACh
What are the acute adverse effects of inhalant intoxication?
Sensitize the heart to epinephrine
Cardiac dysrhythmias caused by inhibited activation of voltage-gated Na+ and Ca2+ channels - QTc prolonged
Lighters are common causes of ER visits
Mechanical asphyxiation
Aspiration of vomit
Trauma - especially with glue
Unconsciousness, respiratory suppression, coma
What is aerosol-evoked cardiac arrest?
- rapid chilling of the larynx
- mucosal edema and laryngospasm cause hypoxia
- irritate descending vagal nerve
- elevated ACh release onto the heart
- bradycardia and cardiac arrest
What is sudden sniffing death syndrome?
Happens to 25% of new users
Cardiac arrhythmia, hypoxia, accidents, suicides
How do mechanisms of inhalants relate to long-term abuse?
Heavily inhibitory - NMDA/AChR inhibited, GABA/glycine potentiated
Subunit composition may change, neuroadaptation = altered sensitivity of channels to drug binding
ACh attenuation initially, but excitotoxicity occurs after each withdrawal period
What are the maladaptive hippocampal adaptations of inhalants?
Structural changes (can take 4 days)
NMDA receptor subunit composition changes (more B,C)
40 day 200 ppm toluene cycle causes neuronal death in hippocampal CA1 and CA3, memory loss
What are the long-term health risks of inhalant use?
Memory, cognitive, behavioural impairment
Damaged basal ganglia, cerebellum, thalamus, pons
Myelin loss which causes cognitive decline, slower processing, and cerebellar ataxia
What does the long-term damage of inhalants target?
Myelinated neurons, and inhalants accumulate here
Metabolites of inhalants cross-link neuron cytoskeletal components and long peripheral neurons like motoneurons contain more of these components
