Inhaled drugs

Despite the paucity of systematic studies in humans, the available evidence suggests that, like drugs such as alcohol, sedatives, and stimulants, inhalant drugs (i.e., solvents, general anesthetics, and nitrites) exert reinforcing effects and increase motor activity. Furthermore, with continuous use, these drugs appear to induce both tolerance and symptoms of withdrawal. 

There are similarities between the biological actions of inhalants and those of alcohol and barbiturates (Bowen et al. 1996b). For example, acute administration of inhalants affects motor coordination (Moser and Balster 1981) and induces anxiolysis, whereas chronic administration is associated with physical dependence and withdrawal (Bowen et al. 1996a Evans and Balster 1991, 1993). In addition, some inhalant drugs have anticonvulsant properties (Wood et al. 1984). Like other CNS-depressant agents, inhalants have biphasic effects on spontaneous locomotor activity in rodents, with increased activity seen at lower doses and diminished locomotion seen at higher doses (Cause et al. 1985 Kjellstrand et al. 1985). 

Beckstead MJ, Weiner JL, Eger El 2nd, et al Glycine and gamma-aminobutyricacid(A) receptor function is enhanced by inhaled drugs of abuse. Mol Pharmacol 57 1199—... 

Relenza ) in 1999. The polar nature of Relenza precluded significant oral absorption, and therefore an infraoral inhalation drug delivery method was developed that delivered the drug to the primary site of infection. 

Educate patients on the use of inhaled drug delivery devices, peak flow monitors, and asthma education plans. 

All patients on inhaled drugs should have their inhalation technique evaluated monthly initially and then every 3 to 6 months. 

Paracelsus stated over 400 years ago that All substances are poison. The right dose differentiates a poison and a remedy. Thus, in safety assessments of inhaled drugs, the dose, or magnitude of inhalation exposure, in relation to the physiological,... 

Two different circulatory systems, the bronchial and the pulmonary, supply the lungs with blood [133], The bronchial circulation is a part of the systemic circulation and is under high pressure. It receives about 1% of the cardiac output and supplies the conducting airways, pulmonary blood vessels and lymph nodes [133], It is important for the distribution of systemically administered drugs to the airways and to the absorption of inhaled drugs from the airways [18]. The pulmonary circulation comprises an extensive low-pressure vascular bed, which receives the entire cardiac output. It perfuses the alveolar capillaries to secure efficient gas exchange and supplies nutrients to the alveolar walls. Anastomoses between bronchial and pulmonary arterial circulations have been found in the walls of medium-sized bronchi and bronchioles [18, 65, 67],... 

Figure 6.2 Schematic illustration of the fate of an inhaled drug. (Modified from Tronde [139]).

Figure 6.3 Simple schematic to illustrate the hierarchy of complexity of systems used for preclinical absorption and disposition investigations of inhaled drug products. Interspecies variation should be considered. In silico modelling based on human data and use of the human perfused lungs can provide complex information regarding human absorption and disposition data.

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