4. VOLATILE MOLECULES
The pulmonary elimination is inversely proportional to the blood
solubility of a molecule. Other chemical characteristics, such as vapour
pressure and molecular dimension, increase lung elimination via
exhalation: higher lipophilic properties, higher vapour pressure and
lower molecular weight contribute to easier elimination through
exhalation. The main classes of volatile organic compounds that are
exhalated by the lungs can be summarized as saturated (ethane, pentane
and aldehydes) and unsaturated hydrocarbons (isoprene), and oxygen-
(acetone), sulphur- (ethyl mercaptan and dimethyl sulphide) and
nitrogen- (dimethylamine, ammonia) containing compounds (Dent et al.,
2013).
The pharmacokinetic pathway of lung elimination is known, for example,
for chloral hydrate a highly lipophilic and small molecule used as
sedative. This drug is now used only in a few cases due to its narrow
therapeutic index, but it had been preferred in the paediatric
population for its easy oral administration and short half-life. Oral
administration represents a clear advantage, increasing patient
compliance. Another drug that stimulates indirect lung elimination is
disulfiram, used in the treatment of alcohol dependence. Its
metabolites, carbon disulphide (CS2) and acetone, are
transported from the blood into alveolar air and exhaled with the
breath. Disulfiram increases the acetaldehyde blood concentration by
aldehyde dehydrogenase inhibition of ethanol metabolism, with an
increase also in lung exhalation and acetaldehyde toxicity (Torsten et
al., 2017). The particular mechanisms of this drug cause many of the
unwanted effects of a hangover immediately after alcohol consumption to
break the ethanol addiction.
Curiously, disulfiram has been tested in vivo against the viruses that
cause severe acute respiratory syndrome (SARS) and Middle East
respiratory syndrome (MERS), but the studies did not provide adequate
clinical evidence (Lin et al., 2018).
Many volatile molecules come from natural sources. The most common
example of this, experienced by each of us, is the pulmonary excretion
of garlic diallyl-derivatives, such as diallyl disulphide, and other
organic sulphur compounds, such as allyl methyl sulphide and methyl
mercaptan, in expired air and how they affect social relations. A number
of molecules with typical volatile characteristics are the small
terpenoid class of monoterpenes consisting of two isoprene units that
can be linear (acyclic) or contain one or two rings.
Terpenoids represent the major component of essential oils, and the
large number of pharmacological properties of each compound have already
been discussed (Koziol et al., 2014). The most well-known are α-pinene,
limonene, γ-terpinene, terpinolene, arbanol, α-terpineol, linalool,
thymol, menthol and carveol. Common pharmacological effects of different
types of cyclic monoterpenes are antibacterial, antiviral and antifungal
effects (Dehsheikh et al., 2020).
In consideration of the chemical-physical properties of eucalyptol
(1,8-cineole), it is likely to think of significant levels of substance
in the lungs. In addition, taking note of its characterized kinetics of
pulmonary elimination and according to Fick’s law, the time of
persistence should also be sufficient for eucalyptol to perform a
considerable pharmacological action. Furthermore, due to the negligible
side effects, the risk/benefit ratio suggests that its pharmacological
effects are worth testing.
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