Inhalants Solvents Flashcards
What are 4 types of inhalants and where are they commonly found? what do they have in common?
- solvents –> used to remove grease and oil
- fuels –> propane, gasoline
- propellants –> nitrious oxide, fluorinated hydrocarbon (computer duster)
- anesthetics –> chloroform and ehter, nitrous oxide (whippets)
- these are are legal things that are easily accessible especially by younger groups
- they all have different structures but their effects on the brain are the same
what are the effects of inhalants on behaviour?
- they have instant alcohol-like effects like euphoria, dizziness, disinhibition, impaired judgement, recklessness
- it lasts about 15-45 minutes followed by one to two hours of drowsiness
- motor excitation occurs at low levels due to inhibition of inhibitory circuits, sedates or anesthesizes at higher levels though
- at high levels can cause hallucinations, coma and death
this is a unique type of depresant cause it produces hallucinations at high amounts
what are solvents? what are 4 kinds and their properties and examples?
solvents contain a mixture of compounds
- aliphatic (straight chain) hydrocarbones: like isobutane, n-butane, hexane and PROPANE
- aromatic (ring structure) hydrocarbons: include toluene (in sniffing glue), xylene often found in gasoline
- chlorinated hydrocarbons: include tetrachloroethylene, trichloroehtylene (dry-cleaning supplies, fabric protectors)
- ketones: acetone
no common theme in strcuture but dangerous
what are 4 ways of administrating inhalants? what is a problem in this?
- direct inhalation form container
- soak a cloth and hold it over face
- fill a bag, balloon etc.. and inhale
- sniffing, bagging, and huffing
can cause asphyxiation, lung damage and hypoxia
How are inhalants absorbed?
they are delivered quickly to the brain because they are lipophilic but they leave the brain just as quickly and need constant administration
- the rate of absorption is determined by most volatile substances (substances that go from liquid to gas in the body), by diffusion down a concentration gradient (more in lungs, less in blood so it moves from lungs to blood)
- the rate at which volatile substances leave the lungs are also based on concentration gradient and evaporation rate (more in blood less in lungs so it moves out of lungs)
- fatty tissues with good blood flow get the highest amounts (like brain and liver)
- body fat gets little because poor blood flow
what are some ways that inhalants get metabolized in the body?
- if they are non-volitile (not exhaled out) they are metabolized in the liver
- toluene is not volatile only 20% is exhaled but the majority is metabolized in the liver to hydrophilic metabolites and excreted in the urine
- highly volitile substances tend to be elimated unchanged via respiration … so aliphatic hydrocarbons such as propane are like this … do not result in acidosis
what are the two metabolites of toluene in the liver? what do they cause?
toluene is metabolized to benzoic acid and then to hiippuric by mixing with a glycine..this can lead to acidosis (low blood pH)
how do inhalants act on NMDA receptors?
inhalants overall decrease NMDA activity (especially the ones for NR2B subunits)
-in frog egg experiment, they added NMDA and glycine to NMDA receptors and showed an activation in the receptor
but when benzene was added, there was less channel activty and more of a drop in NMDA receptor activation especially when added to NR2B subunit instead of the NR2A subunit
how do inhalants affect nicotinic acetylcholine receptors?
- again in the frog eggs, it showed that there is direct inhibition of acetylcholine in the presence of nicotine
- nicotine binds to acetylcholine receptors and when the toluene is exposed to acetylcholine receptors there is more inhibition of it and less nicotine binding depending on which receptor subunit is involved
alpha-a-4-beta-2 receptors had the most sensitivity to toulene but the receptors made of only alpha-7 subunits showed the least effects
how do inhalants affect GABA-A and glycine (both inhibitory) receptors?
- opposite effect of what happens when exposed to NMDA and nicotinic receptors
- theres direct enhancement of GABA-a receptor functionin in the presence of GABA
- there is direct enhancement of glycine receptor function in the presence of glycine
- the effects are similar to what happens when u drink ethanol
- all solvents potentiate the effects of gaba, and glycine but the effect is more profound in glycine
What do the studies on individual receptor subtypes tell us about the nature of how inhalants work?
it confirms the idea that toluene and other inhalants dont simply non-specifically disrupt neuronal membranes and proteins
receptors associated with neuronal excitability (glutamate NMDA, nicotinic acetylcholine) are inhibited. But those associated with neuronal inhibition (GABA, glycine) are more active
- we see that changing specific subunits within a single type of receptor changes the response to inhalants
- so there must be different specific i binding sites being formed by different subunits
What did the experiment on the effects of inhalants on dopamine and noradrenaline levels in the reward pathway show?
using in-vivo microdyalisis, and sampling areas of the pre-frontal cortex and nucleus accumbens simultaneously
they pump inhalants into a cage where the rat is being held at a constant level and then measure the individual neuronal firing within the prefrontal and nucleus accumbens
in nucleus accumbens: theres an increase in dopamine with long lasting effects even after the inhalant disappears in the body
in low doses of toluene, theres an increase in noradrenaline levels which could be responsible for excitatory effects
theres an increase in dopamine in the prefrontal cortex due to increase in dopamine in the VTA
what are the three big occurrences of acute damage and death when using inhalants?
- risks of burns and suffocation
- “sudden sniffing death” due to cardiac arrhythmia especially with toluene and butane
- toluene inhibits cardiac voltage-activated sodium channels
- it is also sensitize the heart to the effects of adrenaline - if its released directly into the throat, compressed gasses can freeze the vagal nerve, and freezing irritates the nerve and results in it releasing more acetylccholine than normal, acetylcholine interacts with acH receptors in the heart tissue, and leads to slowing down heart and to cardiac arrest
What happens with acute toluene exposure in the hippocampus? describe experiment
experiment treated adolesceent and adult rats with toluene and looked at immediate effects (day after treatment) and looked at persistent effect (40 days after treatment) and measured the loss of specific neuronal cell type in hippocampus
results: adults were resistant to immediate effects of toluene and showed less neuronal cell loss in the hippocampus compared to adolsecents but after 40 days they showed more loss of neurons than adolscents did.
The opposite for adolsecents was that they lost the most neurons immediately and then less neurons later
this correlates with memory loss presented in adolsecents and adults
What happens with chronic exposure of inhalants to the hippocampus? experiment
- as hippocampal neurons adapt to presence of toluene for 4 days … theres an increased response of NMDA receptors to agonists
- decreased response of GABA-A receptors to GABA
- This leads to hyperexcitability in the brain when toluene is not around
- this is why cessation of inhalant drugs can be dangerous and lead to seizures
the same doses administered during naive exposure have way more NMDA activity in chronic users because the brain has made more NMDA receptors and less GABA
