cns depressants: inhalants Flashcards
how do CNS depressants affect brain activity?
they reduce brain activity which is why their called downers
what is another name for depressants and explain the function?
sedative-hypnotics
sedatives: calm anxiety
hypnotics: induce sleep
what is the main target of depressants?
GABA receptors
what are the 2 GABA receptors and what are their functions?
GABAa: inhibitory, ionotropic
- Cl- into the cell
- Many depressants are positive allosteric modulators of GABA-A receptor - they change confirmation so it is more responsive to GABA binding
GABAb: inhibitory, metabotropic
- K+ out of the cell
what are the types of CNS depressants?
- inhalants
- alcohol
- sedative hypnotics
a. Barbiturates
b. Benzodiazepines
c. γ-hydroxybutyrate (GHB)
what is an inhalant?
Any breathable chemical that alters cognitive function or level of consciousness
what are characteristics of inhalant?
- Inhalants are volatile substances
- Legal status
they are NOT regulated by DEA because they are misused household products that have a intended use
what are types of inhalants?
- volatile solvents: gas, paint thinner
- gases: butane, propane
- aerosols: hair sprays
- nitrites: amyl nitrite
who uses inhalants the most?
teens and pre teens due to lack of access
why is inhalants a 1st abused substance?
it is abused early in life before tobacco, alcohol, marijuana
how are inhalants administered?
- sniffing - direct inhalation of vapors
- spraying - dispensing from a spray can directly into the mouth
- huffing - breathing vapors from solvent-soaked rag
a. cuffing - soaking cuffs/ other clothing with
solvent & breathing vapors - bagging - placing compounds in a bag (paper/ plastic) & breathing the fumes
- inhaling - filling balloon with nitrous oxide and breathing it in
what is the absorption of inhalants?
incredibly rapid
what is the distribution of inhalants?
there is variable distribution - some leave the body quickly while others are stored in fat
what is the metabolism of inhalants?
mostly by enzymes in liver (some not at all)
what is the elimination of inhalants?
very rapid
what are the general inhalant pharmacodynamics?
- inhibit action potentials
- pos GABAa receptor modulator (increases inhibitory signals)
- NMDA receptor antagonist (blocks glutamate- so shuts down excitatory signals)
- produce short term effects similar to
anesthetics
what does inhalants generally do to the brain?
they cause white matter atrophy which is myelin breakdown
how do inhalants effect specific parts of the brain? what parts? what do they do?
- Cerebral cortex
Hallucinations, learning & memory impairment, permanent personality changes - Cerebellum
Loss of coordination & speech - Optic nerve
Degradation leading to visual impairment
why is it that inhalants can kill you during first time use?
they cause…
- asphyxiation
- suffocation
- seizures
- choking
what is sudden sniffing death?
where the user goes into sudden, unexpected cardiac arrest.1 out of every 4people who fall victim to SSDS were first-time users.
what are the stages of inhalant toxication?
stage 1: excitation, disinhibition, anxiolysis (reduced anxiety), euphoria
stage 2 (when depressant symptoms begin): early CNS depression, slow reaction time, slurred speech, visual problems
stage 3: medium CNS depression, psychomotor impairment, motor incoordination, confusion and delirium
stage 4: late CNS depression, confusion and stupor, seizures, coma and death
what are the 2 types of inhalants we will be discussing?
- volatile solvents
- anesthetics
what is the most commonly abused solvent? in what items is it found in? why is it most commonly abused?
toluene
found: paint thinner, nail polish, spray paint, glues
it is most commonly abused because it produces psychoactive effects
what is the route of admin of toluene?
huffing and bagging are most common
what is the absorption of toluene?
primarily by respiratory tract (lungs) - pretty quick
what is the distribution of toluene?
- highly fat soluble
- readily crossed BBB and placental barrier
if mom was exposed to toluene, it causes fetal solvent syndrome: smaller head, lower ears, thin upper lip, lower ears
what is the metabolism of toluene?
- broken down in liver
- enzymes: CYP450s
- toxic metabolite formed: benzyl alcohol
what happens when benzyl alcohol breaks down?
it is broken into hippuric acid (removes K+ & Na+ from body leading to weakness, muscle spasticity, metabolic acidosis - confusion, rapid breathing, shock, death)
what is the elimination of toluene? what is the half life?
~70-75% excreted in urine as hippuric acid within 12 hrs after exposure
~20-30% exhaled unchanged via the lungs
Elimination half-life in breath = 25 min Elimination half-life from fat tissue = 0.5 – 3 days
what are the reinforcing effects of toluene?
- Anxiolytic-like properties - calms people down
- Anticonvulsant effects - relieve seizures
- Antidepressant-like actions - mild euphoria
- Biphasic locomotor responses -
(increases activity at low concentrations; decreases activity at high concentrations)
what are the detrimental effects of toluene?
- Impaired learning
- Impaired short-term & long-term memory
what does toluene do after acute exposure?
- affects GABA and glutamate system
- causes firing of dopamine in VTA
- indirectly affects dopamine dorsal striatum, nucleus acumens, prefrontal cortex
what does toluene do after chronic exposure?
- tolerance
- downregulation of GABAa receptors
- less sensitivity to GABAa receptors
- upregulation of NMDA receptors
- more sensitivity to NMDA receptors
in chronic users, if we find cerebral, cerebellar, and brainstem atrophy, what symptoms should we see?
apathy and inattention
in chronic users, if we find lateral, third, and fourth ventricle enlargement what symptoms should we see?
memory impairment
in chronic users, if we find loss of gray-white matter differentiation, what symptoms should we see?
visuospatial dysfunctions
what are some acute effects of toulene vs chronic effects?
acute:
- euphoria
- mood changes
- slurred speech
chronic:
- memory loss
- loss of muscle tone
- hearing lose
- nystagmus: rapid movement of eyes
what type of anesthetics are abused as inhalants?
- nitrous oxide (what we are focusing on)
- methoxyflurane
- ether
- chloroform
what are the effects of anesthetic drugs?
- rapid but short lived (matter of minutes_
- repeated use extends experience
what are recreational and instrumental uses of anesthetics?
recreational uses:
- temporarily causes loss of motor control
- dissociative psychological effect (dream state)
instrumental uses:
- anxiolytics
- mild analgesics
- amnestic effects
what is nitrous oxide known as?
whippets
what is the administration of nitrous oxide?
inhalation by sniffing or spraying
what is the absorption of nitrous oxide?
-by your respiratory system (lungs)
- low blood and tissue solubility
- rapid onset within seconds
what is the distribution of nitrous oxide?
- travels through blood
- not stored in tissue
- BBB permeable
what is the metabolism of nitrous oxide?
none
what is the elimination of nitrous oxide? what is the half life?
Rapidly eliminated unchanged from the body primarily via the lungs
Elimination half-life ~ 5 minutes!
what are the anxiolytic actions of nitrous oxide?
- activates GABAa receptors
- NMBA receptor antagonist
what are the analgesic actions of nitrous oxide?
Activates neurons containing opioid receptors in pain areas of the brain - turns of pain signals by activating descending pain pathway
what are acute vs chronic effects of nitrous oxide?
acute:
-euphoria
-relaxation
-hallucinations
-drowsiness
- headaches
chronic:
- vitamin B12 deficiency: nerve damage
- paresthesia : tingling and numbness in fingers and toes
- bone marrow damage
- heart, liver, lung damage
- hypoxia
