Inhalants Flashcards
What are inhalants?
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
Give a general discretion of inhalants including where most prevalent and why it’s so easy to access
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)
What are the effects of inhalants on behaviour
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
What are the properties of solvents
- 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
Describe toluene and gasoline
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)
What are the routes if administration of inhalants?
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
Explain the absorption of inhalants
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
Explain the significance of concentration difference
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
What is the excretion and metabolism mechanism?
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
Explain the difference between aromatic vs aliphatic hydrocarbon excretion
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)
What are the physiological effects of inhalants?
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
What is he effects of inhalants in the VTA and NA?
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
What are the effects f tolerance and withdrawal?
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
What are the short term effects?
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)
What are some of the acute damaging effects?
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
What are some dangers of inhalants to the airways
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
What are the effects if chronic damage?
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
What are the effects to the brain
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
Describe the effects of 2,5hexadione
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
Describe the effects of toluene
toluene strongly associated with kidney damage and renal failure along with hepatitis and hepatic failure
Describe the effects of benzene
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)
Describe fetal solvent syndrome
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)