Inhalant Solvents

Question 1

How can inhalant solvents be classified?

Answer 1

There are many chemical and structural differences between solvents, but they tend to be hydrophobic. Anything with compressed gas can be abused

Question 2

What are their effects on behaviour?

Answer 2

Instant alcohol-like effects- euphoria, dizziness, disinhibition, impaired judgement… Eventually all act as a depressant

Question 3

How long do the effects last for?

Answer 3

Lasts about 15-45 mins followed by 1-2 hours of drowsiness

Question 4

What are the effects at low doses compared to higher doses?

Answer 4

Low levels: there is motor excitation (inhibition of inhibitory circuits–> excitation)
High doses: sedation or anesthetizes, can lead to hallucinations, coma and death

Question 5

What compounds are found in solvents?

Answer 5

Typically a mixture of compounds, aliphatic hydrocarbons (straight chain), aromatic hydrocarbons (ring structure), chlorinated hydrocarbons and ketones

Question 6

What is the typical route of administration?

Answer 6

Direct inhalation from container. Can soak a cloth and hold it over face, fill a bag, balloon and inhale, sniffing, bagging, huffing

Question 7

When inhaling from a bag, what problems could arise from this route of administration?

Answer 7

From inhaling from a bag, you aren’t getting any oxygen with it, which can cause asphyxiation, lung damage and hypoxia

Question 8

What is the demographic for this drug of abuse?

Answer 8

Usually kids in grade school, experimenting with different drugs.

Question 9

How quickly is the effect to the brain?

Answer 9

Delivered very fast to the brain, (highly lipophilic) but it leaves just as quickly. Needs constant re administration.

Question 10

How is the rate or absorption determined?

Answer 10

The drug enters the lungs down a concentration gradient (breathe it in, low in blood, and high in lungs–> so it diffuses into blood. When you stop breathing in the drug, theres more in the blood than the lungs, so it flows back into lungs and you breathe it out)

Question 11

Is all of the drug metabolized in the blood or is some excreted unchanged?

Answer 11

Volatile substances are typically eliminated unchanged via respiration, non volatile substances are metabolized in the body

Question 12

Where are solvents metabolized? And what are their metabolites?

Answer 12

Majority is metabolized in the liver to hydrophilic metabolites and excreted in urine.

Question 13

Toluene, a common solvent used in many compounds is metabolized into what?

Answer 13

Toluene is metabolized to benzoic acid and then ultimately to hippuric acid.

Question 14

What can hippuric acid lead to?

Answer 14

Acidosis

Question 15

Which receptors do solvents affect?

Answer 15

NR2B NMDA receptors, GABA-a and glycine receptors, and acetylcholine receptors

Question 16

Inhalants tend to produce effects similar to which drug of abuse?

Answer 16

Alcohol.

Question 17

Studies on individual receptor subtypes have been shown what?

Answer 17

There are very specific binding sites for different subunits, and changing the subtypes changes the response to inhalants

Question 18

Do inhalants and solvents increase dopaminergic neurones?

Answer 18

Yes, when there is an increase of toluene (and other solvents) in the Ventral Tegmental Area, there is an increase of firing in the dopamine pathways–> results in dopamine release at the Nucleus Accumbens

Question 19

What is sudden sniffing death?

Answer 19

For someone who sniffs for the first time (and they have cardiac arrhythmia) , and they get scared suddenly, the heart muscle isn’t working properly and the voltage activated sodium channels (cells beat out of sync) and the person die basically from inefficient heart pumping

Question 20

If released directly on the throat, what effect does compressed gas have?

Answer 20

It can freeze the vagal nerve, which results in excess acetylcholine release (leads to slowing heart, cardiac arrest)

Question 21

What are the immediate and long term effects of acute toluene exposure in the hippocampus of adolescents and adults after just one exposure?

Answer 21

Cell death occur immediately after exposure (don’t regenerate in adolescents–> long term effects too).
Adults are more resistant to the immediate effects, but they see the effects in the long term as well

Question 22

What are the effects with chronic exposure in the hippocampus? (4 days)

Answer 22

There is an increased response of NMDA receptors to agonists, decreased response of GABA-a receptors to GABA (decreased inhibition–> excitability), which leads to hyper excitability when drug is absent in the brain

Question 23

What are the effects on NMDA receptors when the presence of chronic exposure to toluene?

Answer 23

There is an increased density of the body and increased density of cluster size of NMDA receptors (toluene is a depressant, the brain produces more stimulating/excitable NMDA receptors to make up for the drug, when drug is taken away, lots of newly produced NMDA receptors activate and cause hyper excitability and even excitotoxicity

Question 24

What sort of brain damage occur with the use of inhalants?

Answer 24

Damage mostly in the white matter–> demyelination. Loss of neuronal mass (brain literally shrinks)

Question 25

What are some chronic damages to the body with the use of solvents or inhalants?

Answer 25

2-5 hexanedione (metabolite if hexane) causes axonal degeneration by altering protein structure. Happens especially in the periphery. Can results in tinging in hands and feet, and if no nerves reach the muscle it will eventually atrophy