Respiratory system absorption

When kaolin or aluminum is administered widi die lincosamides, die absorption of the lincosamide is decreased. When the lincosamides are administered with the neuromuscular blocking drag (drag diat are used as adjuncts to anesthetic drag diat cause paralysis of the respiratory system) die action of die neuromuscular blocking drug is enhanced, possibly leading to severe and profound respiratory depression. 

White, granular, or crystalline deliquescent solid that is odorless when dry but has a faint odor like almond when wet. This material is hazardous through inhalation, skin absorption, penetration through broken skin, and ingestion, and produces local skin/eye impacts. It causes irritation of the eyes, skin, and upper respiratory system, asphyxia, lassitude, headache, confusion, nausea, vomiting, increased respiratory rate or slow gasping respiration, as well as thyroid and blood changes. 

The three targets that are the first point of contact between environmental chemicals and the body will be discussed first the gastrointestinal tract, the respiratory system, and the skin. Recall from Chapter 2 that chemicals enter the blood after absorption, so this fluid is the next target (see Figure 2.1). Then come the liver, the kidneys, and the nervous system. The chapter concludes with a discussion of some chemicals that can damage the reproductive system and some that can cause birth defects, the so-called teratogens, and other forms of developmental toxicity. Brief discussions of immune system, cardiovascular system, muscle, and endocrine system toxicities are also offered. 

Ribavirin can be administered as an aerosol using a small-particle aerosol generator. When administered by this route, the drug has only minimal systemic absorption, with drug concentrations in respiratory tract secretions approximately 100 times as high as those found in plasma. Oral absorption is rapid, and first-pass metabolism is extensive ribavirin s oral bioavailability is 64% and can be increased by administration with a high-fat meal. Steady-state levels are reached after 4 weeks. 

Geriatric Considerations - Summary Systemic absorption of ophthalmic drugs may occur and cause adverse effects in older adults. Since betaxolol is beta-selective, cardiovascular, respiratory and CNS adverse effects occur less frequently than with beta-nonselective topical opthalmics. These effects may still occur therefore close monitoring for systemic side effects is warranted. Betaxolol maybe less effective than the nonselective topical beta-blockers with an average lOP reduction of 18%-26%. Tachyphylaxis may occur after long-term therapy. 

Larger particles (several micrometers in size) are deposited in the ciliated portion and are cleared from the respiratory system by muco-ciliary action into the gastronomical tract, but may produce systemic toxic effects by absorption in body fluids. Finer particles reach the lower non-ciliated portion of the lungs, are cleared very slowly, and are responsible for diseases such as pneumoconiosis and lung cancer. Metallic lead (Pb), tellurium ( ), selenium (Se), and platinum (Pt) are known to cause both systemic and respiratory toxicity in laboratory animals and several cases of acute and chronic poisoning among metal workers have also been documented. 

In addition to oral administration for hepatitis C infection in combination with interferon alfa, aerosolized ribavirin is administered by nebulizer (20 mg/mL for 12-18 hours per day) to children and infants with severe respiratory syncytial virus (RSV) bronchiolitis or pneumonia to reduce the severity and duration of illness. Aerosolized ribavirin has also been used to treat influenza A and infections but has not gained widespread use. Systemic absorption is low (< 1%). Aerosolized ribavirin is generally well tolerated but may cause conjunctival or bronchial irritation. Health care workers should be protected against extended inhalation exposure. The aerosolized drug may precipitate on contact lenses. 

Figure 3.10 The structure of the mammalian respiratory system (A) trachea, (B) bronchiole, (C) alveolar sac with blood supply, (D) arrangement of blood vessels around alveoli, (E) arrangement of cells and airspaces in alveoli showing the large surface area available for absorption, (F) cellular structure of alveolus showing the close association between (G) the endothelial cell of the capillary (H) with erythrocytes and (I) the epithelial cell of the alveolar sac. The luminal side of the epithelial cell is bathed in fluid, which also facilitates absorption and gaseous exchange. Source From Ref. 1.

In addition, size reduction can also enhance delivery of poorly water-soluble APIs to the respiratory tract. SpeciLcally, aerosolized particles should have aerodynamic diameters in the range of 1-5(xm. With larger particles, deposition occurs primarily on the back of the throat, which can lead to systemic absorption and undesired side effects. 

Suspensions contain micronized drug for proper delivery to and absorption in the respiratory system. Typical particle size of the micronized drug is from 2 to 5 microns [5], Aerodynamic mean particle size as measured by cascade impactor or direct method of microscopic analysis is usually from 0.5 to 4 microns [5], Additional particle-sizing techniques such as light scattering can be used [6],... 

Inhalation Rapid onset direct application for respiratory disorders large surface area for systemic absorption Chance of tissue irritation patient compliance sometimes a problem General anesthetics antiasthmatic agents... 

More qualitative indicators are also useful absorption through healthy skin, irritation to skin, eyes, and respiratory system, together with sensitization with the following indicators carcinogenic, mutagenic, teratogenic, reprotoxic, and so on. These properties can be summarized by indication of a toxicity class. 

It is possible that systemic absorption of airborne aluminum occurs via the lungs, gastrointestinal tract after mucociliary clearance from the respiratory tract (ICRP 1994), or via the olfactory tract. Gitelman et al. (1995) found a better correlation between respirable aluminum air concentrations and urinary... 

The vapor irritates all parts of the respiratory system and may cause unconsciousness. Short exposure may cause pain to the nose and eyes in addition to intense irritation. Poisoning can occur by absorption of acrolein through the skin. Swallowing would cause severe poisoning.4 Avoid breathing vapor. Prevent contact with eyes and skin. TLV-STEL-C 0.1 ppm (0.23 mg/m3).5 LD50 (rat, oral) 0.046 g/kg.1... 

The vapor irritates the respiratory system and eyes. Liquid irritates the eyes and skin. Swallowing or skin absorption results in nausea, vomiting, and liver and kidney damage.3 Avoid breathing vapor. Avoid contact with skin and eyes.3 Animal carcinogen reasonably anticipated to be a human carcinogen.4 TLV, no exposure permitted.5... 

Red phosphorus is not considered to be harmful physiologically. White phosphorus burns the skin and eyes and causes severe internal damage if swallowed. The vapor from burning phosphorus irritates the respiratory system and eyes. Prolonged absorption of small quantities results in anemia, intestinal weakness, and bone and liver damage. Avoid contact with skin and eyes.3 TLV-TWA (yellow phosphorus) 0.1 mg/m3.30... 

Hydrogen selenide irritates the nose, eyes, and lung tissue, and disturbs the digestive and nervous systems. Solutions of selenium compounds may burn the skin and cause severe pain by skin absorption. Selenium dioxide dust irritates the respiratory system, eyes, and... 

Vapor irritates the eyes and respiratory system high concentrations have a narcotic effect. Liver damage may result from skin absorption or ingestion. Avoid breathing vapor. Avoid contact with eyes.3 TLV-TWA 200 ppm (590 mg/m3) TLV-STEL 250 ppm (737 mg/m3).10... 

Avoid breathing vapor. Prevent contact with skin and eyes. Destructive to tissues of respiratory system causes burns. Harmful by inhalation, ingestion, or absorption through the skin.9 TLV-STEL-C 1 ppm (4.9 mg/m3).10... 

Bioavailability from Environmental Media. No studies were located regarding the bioavailability of acrolein from environmental media. Since acrolein has been detected in ambient air and in food and beverages (ppb levels), it is important to determine if acrolein can be absorbed by humans from environmental samples. However, the chemical structure of acrolein makes it a highly reactive molecule, which presumably is why its effects are, for the most part, restricted to the area of exposure (i.e., respiratory system for inhalation exposure or localized skin damage for dermal exposure). The limited information available regarding absorption parameters of acrolein in experimental animals indicates that acrolein is easily retained in the respiratory airways however, virtually no information is available regarding absorption by the gastrointestinal tract or skin. Therefore, based on the data available, it is likely that inhalation of contaminated air will result in irritation of the eyes and respiratory tract. 

---