VAPING/INHALANTS

vaping/e-cigs

• produce an aerosol by heating a liquid - usually nicotine and flavorings

• inhale aerosol, bystanders can also breath aerosol

• note: no vapors actually involved in e-cigs

• vapor - gas phase of a substance

• aerosol - suspension of particles of a liquid, solid or both within a gas

e-liquids

• typically a mixture of H2O, food grade flavorings, nicotine, cannabis (THC, CBD), propylene glycol (PG) or vegetable glycerin (VG)

• PG and VG used as humectants (to create smoke cloud)

• effects of nicotine well known

• toxic effects of aerosol flavoring chemicals, solvents and other products largely unknown

• nicotine: newer mods use nicotine salts

  • lower pH tan free base nicotine

  • allow for high levels to be inhaled more easily w/ less irritation on throat

e-cigs vs regular cigs

• not approved as a ‘quit’ smoking aid but may assist (toxicity from burning and smoke you inhale - heating up components but no filter)

• generally have fewer toxic chemicals (regular ~7000 chemicals)

• e-cig aerosols contain many harmful substances

  • nicotine

  • cannabinoids (THC, CBD)

  • volatile organics

  • ultrafine particles

  • heavy metals such as Cr, Ni, Pb, Sn

  • carcinogenic substances (formaldehyde, acetaldehyde)

  • flavoring - diacetyl (e.g. ‘popcorn’ lung)

• unintended injuries (exploding)

• synthetic cannabinoids - K2, Spice, Black Mamba, Kronic

aerosol composition

• over 250 e-cig brands and >8000 flavorings (note: besides methanol all flavoring banned in cigs)

• full evidence of impact on heating substances is unknown

• formation is linked to device characteristics (e.g. coil temp, metals used)

• vaping req used to puff both harder/longer than regular cigs (bringing aerosols deeper into lungs increasing exposure and damage)

• carbonyl compounds:

  • thermal degradation of 1,2-propylene glycol and glycerin produces

    • acetaldehyde, acrolein, formaldehyde

• diacetyl and 2,3-pentanedione

  • found in majority of e-cigs

  • flavoring agent (“butter-flavored” popcorn - not actually butter you smell), but can create a variety of flavors

  • previously linked to bronchiolitis obliterans (‘popcorn’ lung)

  • evidence they impair production and fxn of cilia in human airway

• volatile organic compounds

  • benzene, toluene, ethylbenzene, xylene

• metals

  • many types predominant include Al, Fe, Cr, Ni, tin, Cu, Pb

vaping assoc pulmonary injury (VAPI) [EVALI - e-cig or vaping assoc lung injury]

• ‘new’ disease assoc w/ vaping

• an acute or subacute chemical pneumonitis

• predominantly young males (<35 in 80% cases) and healthy individuals

• pts cough, dyspnea, chest pain

• common nausea, ab pain, diarrhea

• happens in most ppl that start vaping w/i last 3mo

• pulmonary infiltrates on chest radiography (atypical pneumonia)

• many pts req ICU and ventilator support

• some developed acute resp distress syndrome (ARDS)

• pathogenesis largely unknown

• products that contained THC and/or vitE acetate were assoc w/ disease (used to thicken or dilute the THC in vaping liquids)

• not found in nicotine products (too viscous - nicotine doesn’t work as well w/ vitE acetate)

• MOA for pulmonary tox not known

  • interfere w/ membrane fxn

  • heating may produce ketenes (reactive compound)

bronchiolitis obliterans (popcorn lung)

• an inflammation of bronchioles, the lung’s smallest airways

• toxic substances assoc w/ developing popcorn lung

  • acetaldehyde

  • ammonia

  • chlorine

  • diacetyl

  • formaldehyde

  • fumes from metal oxides

  • HCl

  • mustard gas or sulfur mustard

  • nitrogen oxides

  • sulfur dioxide

nicotine poisoning

• binds to nicotinic cholinergic receptors (mimics acetylcholine)

• absorbed rapidly by all routes, enters brain quickly, volume of distribution, rapidly. metabolized (CYP2A6 and CYP2D6)

• urinary excretion, t1/2 120min

• increased incident in children (<5y.o) ~1000x more than adults (lethal dose <50mg), severe toxicity ~6mg

• 2.6x odds severe outcomes, highly concentrated e-liquid

• dose and time dependent effects (biphasic response)

• early (0.25-1h)

  • GI: N/V, salivation, ab pain

  • resp: bronchorrhea, hyperpnea

  • CV: HTN, tachy, pallor

  • neuro: agitation, anxiety, dizziness, blurred vision, headache, hyperactivity, confusion tremors, fasciculations, seizures

• late (0.5-4h)

  • GI: diarrhea

  • resp: hypoventilation, apnea

  • CV: brady, hypotension, dysrhythmias, shock

  • neuro: lethargy, weakness, paralysis

cannabinoids

• key constituents of cannabis: THC (primary psychoactive compound) vs CBD

• key receptors: CB1R vs CB2R

• CB1 and CB2 receptors found throughout body but brain has stimulant, sedative or hallucinogenic actions

• trigger both catecholamine release and inhibition of sympathetic reflexes

• acute effects - decreased coordination, muscle strength, lethargy, decrease [ ], psychomotor activity

• non-classical effects (agitation and seizures) - synthetic or’spice’ blends ‘incense’ packaging (Zombie)

‘Tree-in-Bloom’ Severe Acute Lung Injury example case (vaping cannabis oil)

1. developed dyspnea, rapid and shallow breathing 6h post vaping and next day

2. expectorate blood-tinged sputum - pure blood

3. ED - O2 sat 82%

4. chest CT scan extensive airspace opacification

5. histopathology of alveolar tissue - pneumonia, urine cannabinoids only, lavage fluid neutrophil dominant

6. chest CT 2wks complete resolution following cessation of exposure

bagging/huffing/sniffing/spraying

• inhalants

  • refers to various substances that individuals typically take only by inhaling (e.g. volatile substances)

• abuse

  • common among teenagers

  • legal and easy to obtain, cheap

• effects

  • intoxicating effects - immediately

  • plethora of chemicals readily absorbed through the lungs and distribute rapidly

  • initially stimulating, then less inhibited and less in control

  • chemicals prevent/limit breathing in O2 (one of main effects is limiting O2 content**)

  • a lot of long-term tox

inhalants

• MeOH - toxicity

• DFE - sudden sniffing death sydrome

• toluene - hypokalemia, metabolic acidosis, leukoencephalopathy, renal injury, rhabdomyolysis

• methylene chloride - metabolized to CO

• ‘poppers’ - methemoglobinemia, hemolysis

inhalant AEs

short term effects

• headaches, N/V

• loss of balance

• dizziness

• slurred and slow speech

• mood changes

• hallucinations

long term effects

• cardiotox (e.g. inflamm, CHF, sudden cardiac death)

• resp damage

• anoxic brain damage

• liver and kidney damage

• progressive neuro injury (e.g. hearing loss, muscle spasms, loss of coordination)

• loss of [ ], short term memory loss

sudden sniffing death syndrome

• abrupt CV collapse due to an irregular heartbeat

• 1,1 difluoroethane (DFE)

  • organic hydrocarbon, colorless, odorless gas used as refrigerant chemical component of canned air

  • can cause sx of inebriation, frostbite or blisters

  • CNS depression (drowsiness, N, headache, fatigue, weakness)

  • asphyxiant (displaces O2), heavier than air

  • flammable

• pathophys DFE

  • cardiac dysrhythmias

  • sensitization of myocardium to catecholamines

  • blocking K and Ca channels and Na current → prolong repolarization or increase QT dispersion

  • effects are often unpredictable and occur in first-time users

  • startled by being caught (e.g. parents) sudden release of catecholamines

• Management

  • CPR, defibrillation

  • avoid E, use BBs