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.
.