Inhalants

Question 0

What are inhalants?

Answer 0

 solvents - used to remove grease and oil
 fuels - propane, gasoline
 propellants - nitrous oxide, fluorinated hydrocarbon (computer “Duster”)
 anaesthetics - chloroform and ether, nitrous oxide (Whippets)
 liOle or no structural similarities between types of inhalants

Question 1

Give a general discretion of inhalants including where most prevalent and why it’s so easy to access

Answer 1

 solvent inhalation most prevalent in younger popula&ons (grade school - up to 26% of 12 year olds)
 easy to obtain, not illegal to possess
 cheaper than alcohol (gasoline very cheap)
 esp. in low-income, fractured or abusive homes
 high rate of use associated with poverty, isolation, marginalized groups (50 - 60% life&me)

Question 2

What are the effects of inhalants on behaviour

Answer 2

 instant alcohol-like effects - euphoria, dizziness, disinhibi&on, impaired judgement, recklessness
 lasts 15 - 45 minutes followed by one to two hours of drowsiness
 motor excitation at low levels (inhibition of inhibitory circuits (stimulatory effects)), sedates or anesthetize at high levels
 high levels can lead to hallucinations, coma and death

Question 3

What are the properties of solvents

Answer 3

• typically contain a mixture of compounds
• aliphatic (straight chain) hydrocarbons
• chlorinated hydrocarbons ketones (acetone)
  (isobutane, n-butane, hexane and propane)
• aromatic (ring structure) hydrocarbons (toluene and xylene)
  (tetrachloroethylene, trichloroethylene) - dry cleaning supplies, fabric protectors
• ketones

All these solvent s produce same effect although structurally different

Question 4

Describe toluene and gasoline

Answer 4

toluene also known as methylbenzene:
 clear, colourless, flammable
 solvent used in manufacture of paint, chemicals, pharmaceuticals, rubber
 highest potential for abuse

gasoline contains toluene, benzene, n- hexane and in some countries, lead (lead will destroy neurons)

Question 5

What are the routes if administration of inhalants?

Answer 5

  direct inhala&on from container
  soak a cloth and hold it over face
  fill a bag, balloon etc and inhale
  sniffing, bagging, huffing
  can cause asphyxiation (decrease oxygen), lung damage

Question 6

Explain the absorption of inhalants

Answer 6

 delivered quickly to the brain - highly lipophilic - but leave just as quickly - need constant administration
 rate determined for most of the volatile substances by diffusion down a concentration gradient
 fatty tissue with good blood flow get highest amounts (brain, liver)
 body fat gets little because of poor blood flow

Have highest absorption at the beginning of the day

Question 7

Explain the significance of concentration difference

Answer 7

 concentration in blood can drop quickly once inhalation stops
 rate at which volatile substances leave the lungs based on concentration gradient and evaporation rate
 any drug that gets into body fat stays in body fat longer because of less blood flow

Question 8

What is the excretion and metabolism mechanism?

Answer 8

 if not exhaled, metabolized in liver
 if highly volatile, metabolism contributes liOle to
elimination
 toluene is not particularly volatile - only 20% is exhaled
 majority is metabolized in liver
 some metabolites can be very toxic

Question 9

Explain the difference between aromatic vs aliphatic hydrocarbon excretion

Answer 9

 aromatic hydrocarbons tend to be converted to hydrophilic metabolites in the liver and then excreted in urine (e.g. toluene)
 aliphatic hydrocarbons tend to be eliminated unchanged via respiration (e.g. propane)

Question 10

What are the physiological effects of inhalants?

Answer 10

inhalants seem to produce similar effects as alcohols:

GABAA and glycine receptor activity increases
 NMDA (esp. those containing NR1 and NR2B subunits) and nicotinic acetylcholine receptors (esp. alpha4 beta2) activity decreases
 also shown to disrupt activity of many voltage- gated ion channels important for neuronal excitability.

Overall the effects are inhibitory

Question 11

What is he effects of inhalants in the VTA and NA?

Answer 11

 measure firing rate of neurons in ventral tegmental area
 toluene shows concentration-dependent increase in firing in dopamine and non- dopamine neurons
 results in increased dopamine release at nucleus accumbens
 thus they are reinforcing

Question 12

What are the effects f tolerance and withdrawal?

Answer 12

with chronic use: (similar to ethanol)
 NMDA receptor expression increases
 GABA-A receptor subunit levels increase or decrease depending on brain region
 seizures can occur upon withdrawal because brain has shi[ed to a hyperexcitable state - it has more NMDA receptors

Question 13

What are the short term effects?

Answer 13

in the short term, use leads to:
  dizziness, slurred speech, sleepiness, blurred vision and
headache
  confusion and ataxia
  hallucinations - auditory and visual

In short term person displays symptoms f being drunk and have a general mental fog (confusion)

Question 14

What are some of the acute damaging effects?

Answer 14

 risk of burns and suffocation - most are heavier than air and tend to “pool”
 “sudden sniffing death” due to cardiac arrhythmia especially with toluene, butane
 toluene inhibits cardiac voltage-activated sodium channels
 also sensitize the heart to the effects of adrenaline
 UK data - 39% of deaths had no previous experience

Question 15

What are some dangers of inhalants to the airways

Answer 15

 if released directly into throat, compressed gasses can freeze the vagal nerve
 leads to slowing of heart, cardiac arrest
 also if larynx freezes, asphyxia&on
 burns, explosion can be lethal

Question 16

What are the effects if chronic damage?

Answer 16

 n-hexane (petrol and glues) and methyl n-butyl ketone (paints) associated with peripheral neuropathy
 toluene is associated with neuronal death/disease states and dementia
 memory loss via hippocampal atrophy
 length of exposure and damage is highly correlated
 severity lessened or reversed with abstinence

Question 17

What are the effects to the brain

Answer 17

 brain imaging shows inhalant abuse causes more structural damage than most other drugs
 damage mostly in white matter - demylienation
 white matter defects - memory, language, processing speed
 amotivational state linked to decreased blood flow to prefrontal cortex

Question 18

Describe the effects of 2,5hexadione

Answer 18

2-5 hexanedione is a metabolite of hexane and n-butyl ketone
 causes axonal degeneration by altering protein structure (cross-linking certain amino acids in neuronal cytoskeletal proteins)
- causes the cytoskeleton to form abnormally by sticking together

Causes chronic damage

Question 19

Describe the effects of toluene

Answer 19

 toluene strongly associated with kidney damage and renal failure along with hepatitis and hepatic failure

Question 20

Describe the effects of benzene

Answer 20

 benzene strongly associated with blood disorders
 bone marrow suppression, leukemia, aplas&c anemia (malformed red and white blood cells and platelets), lymphoma (cancer of lymph cells)

Question 21

Describe fetal solvent syndrome

Answer 21

 similar symptoms as fetal alcohol syndrome
 similar craniofacial abnormali&es
 pre- and postnatal development delayed
 spontaneous and induced locomotor ac&vity significantly reduced in newborns
 in animal models, prenatal exposure linked to decreases in NMDA receptor subunit NR2
 humans are o[en taking many other drugs as well

• leads to floppy infant syndrome (decrease in spontaneous movement and motor action)