Inhalants and Solvents

Question 1

What are the forms of inhalants?

Answer 1

Solvents
Aerosols
Glue

Question 2

How can we administer by inhalation?

Answer 2

Huffing
Sniffing Bagging

Question 3

Where are inhalants distributed?

Answer 3

Brain and liver
Rapid and wide distribution because of small lipophilic molecules

Question 4

What happens to more volatile substances (gases)?

Answer 4

Mostly exhaled

Question 5

What are inhalants metabolized by?

Answer 5

Liver CYP2E1

Question 6

How long does an inhalant high last?

Answer 6

15-45 minutes

Question 7

What are inhalants absorbed?

Answer 7

Inhalation

Question 8

How are inhalants excreted?

Answer 8

Kidney
Breath

Question 9

What drug effects are inhalants similar to?

Answer 9

Alcohol, sedatives, hypnotics

Question 10

What are the two phases of an inhalant high?

Answer 10

1. Euphoria, disinhibition, dizziness, light-headedness, 15-45 minutes
2. Drowsiness, disorientation, headache, 1-2 hours

Question 11

What are the acute effects of inhalants?

Answer 11

Disinhibition of motor circuits at low doses
Slurred speech, inebriation
Hallucinations, anesthesia, coma, and death at high doses

Question 12

What are the physiological mechanisms of toluene?

Answer 12

Reward euphoria via VTA-NAc reward pathway, elevated DA levels

Question 13

What are motor effects via toluene use regulated by?

Answer 13

Regulated in part by GABA in the caudate putamen

Question 14

What are the cellular mechanisms of toluene action?

Answer 14

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

Question 15

What does toluene potentiate?

Answer 15

GABA and glycine NT action

Question 16

Which NMDA channels are most sensitive to toluene?

Answer 16

2B-containing channels

Question 17

What are cultured hippocampal neurons insensitive to in the presence of toluene

Answer 17

ACh

Question 18

What are the acute adverse effects of inhalant intoxication?

Answer 18

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

Question 19

What is aerosol-evoked cardiac arrest?

Answer 19

1. rapid chilling of the larynx
2. mucosal edema and laryngospasm cause hypoxia
3. irritate descending vagal nerve
4. elevated ACh release onto the heart
5. bradycardia and cardiac arrest

Question 20

What is sudden sniffing death syndrome?

Answer 20

Happens to 25% of new users
Cardiac arrhythmia, hypoxia, accidents, suicides

Question 21

How do mechanisms of inhalants relate to long-term abuse?

Answer 21

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

Question 22

What are the maladaptive hippocampal adaptations of inhalants?

Answer 22

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

Question 23

What are the long-term health risks of inhalant use?

Answer 23

Memory, cognitive, behavioural impairment
Damaged basal ganglia, cerebellum, thalamus, pons
Myelin loss which causes cognitive decline, slower processing, and cerebellar ataxia

Question 24

What does the long-term damage of inhalants target?

Answer 24

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

Question 25

What are the symptoms of myelin damage?

Answer 25

Tingling hands and feet
If muscle is denervated it atrophies