Aerosolized atropine

Berdy GJ, Berdy SS, Odin LS, Hirst LW. Angle closure glaucoma precipitated by aerosolized atropine. Arch Intern Med 1991 151(8) 1658-60. 

Atropine, epinephrine, and lidocaine can be administered through the tracheal tube before venous access is achieved at 2-2.5 times the recommended intravenous dose diluted with 10 mL of normal saline or sterile water. Stop CPR, administer beyond the tip of the endotracheal tube, follow with five quick insufflations to aerosolize the drug, and then resume CPR. 

Fenvalerate toxicity is antagonized by atropine sulfate or methocarbamol, which may be effective in treating severe cases of poisoning (Hiromori et al. 1986). Conversely, some compounds exacerbate the toxicity of fenvalerate and interfere with a desired use. Domestic cats (Felis domes-ticus) treated with Fendeet (an aerosol mixture of fenvalerate and A-A-diethyl-m-toluamide) to control fleas and ticks sometimes show signs of toxicosis, such as tremors, hypersalivation, ataxia, vomiting, depression, and seizures. Signs usually appeared within hours of topical application, and females and juveniles seem to be the most sensitive groups. The demonstrated ability of N-N-diethyl-m-toluamide to enhance the dermal absorption of fenvalerate is the probable cause of toxicosis (Dorman et al. 1990). 

Atropine methonitrate (BROVON INEIALANT) 2.5-10 mg/day oral/IM, 1-2 mg (aerosol)... 

Observation of the use of leaves from Datura stramonium for asthma treatment in India led to the discovery of atropine, a potent competitive inhibitor of acetylcholine at postganglionic muscarinic receptors, as a bronchodilator. Interest in the potential value of antimuscarinic agents increased with demonstration of the importance of the vagus nerves in bronchospastic responses of laboratory animals and by the development of a potent atropine analog that is poorly absorbed after aerosol administration and that is therefore relatively free of systemic atropine-like effects. 

The anticholinergic bronchodilators include ipratropium and tiotropium, which are muscarinic receptor blockers that are similar in structure and function to atropine. Although atropine is the prototypical muscarinic antagonist, its use in respiratory conditions is usually limited because it is readily absorbed into the systemic circulation and tends to produce many side effects even when administered by inhalation. Alternatively, ipratropium (Atrovent) is an anticholinergic agent that is poorly absorbed into the systemic circulation and can be administered by an aerosol inhaler.110 Thus, inhaled ipratropium is associated with substantially fewer systemic side effects. 

Lethality was prevented by treatment with nasal atropine (atropine methyl nitrate) and post-exposure treatment with atropine methyl bromide instillation in combination with pulmonary therapeutic surfactants or liquevents in guinea pigs exposed to approximate LC50 concentrations of VX aerosol (Nambiar et ah, 2007) this concept shows promise for operational application in emergency response. 

BZ (7.4 - 14.5 pg/kg) aerosol Inhalation, 2 subjects 3834 (2 0 mg) percutaneous, 1 subject Atropine (125 pg/kg) Intramuscular, 3 subjects Prolixin (15.0 - 23.0 pg/kg) Intramuscular, 6 subjects 302668 (10.0 pg/kg) Intravenous, 1 subject 302196 (75.6 Pg/kg) oral, 1 subject TAB (90 mg total) Intramuscular, 1 subject Pretreatment with methyl scopolamine (1.0 mg) 1 subject Only 2 subjects (AlOJ) and (AlOK) who received doses of BZ and were subsequently treated with physostlgmine, showed any prolonged central effects (hallucinations, disorientation, confusion) lasting 4 to 6 days post >exposure Both subjects were asymptomatic and appeared normal when discharged from test. One subject (AlCM)) was exposed to Prolixin (23.0 pg/kg) and then treated with multiple doses (1.0 mg X 7 doses) over a 2 ay period, intramuscularly At 27 hours post-exposure, the subject complained of blurred vision, and facial expression was mask-llke, tongue "thick" and jaws open. 

Andrews et al. (151) used nine subjects In a preliminary comparison of "the effects of atropine sulfate Injected Intramuscularly and subcutaneously In warm (35oc, 80Z relative humidity) and cool (16<>C, ambient relative humidity) environments and 24 subjects In a preliminary comparison of the effects of Inhalation of 2 mg of atropine sulfate as a dust and as an aerosolized solution In water. Finally, 10 subjects were used to repeat the coaq rlson of the effects of atropine sulfate administered by the two methods of injection In warn and cool environments and to compare the effects of 2 and 5 mg of atropine sulfate Inhaled as a dust and an aerosolized aqueous solution In the warm environment. The report did not state whether the sane subjects were used In more chan one part of this study. 

The mean increase in heart rate after injection of 2 ag of atropine sulfate in the warm environaent was k2 TX whereas that in the cool envlronaent was 31 3Z The aean increase in heart rate after inhalation of 2 ag of atropine sulfate as a dust or an aerosolized solution was 23.7% the aean increase after inhalation of 5 ag of the drug was 48 IX. The increases with the two types of dispersion of atropine sulfate were essentially Identical for the two doses used. It is apparent that inhalation of atropine sulfate is not as effective a aethod of delivery, with heart rate as the Indicator, as Intraauscular or subcutaneous injection. 

Bronchodilation is another property of belladonna alkaloids of potential usefulness. Due to relaxation of the smooth musculature of bronchial passageways, this effect has found applications in asthma and other pulmonary obstructive conditions. At one time the smoking of cigarettes made of stramonium leaves was popular. More recently, atropine, quater-nized with isopropyl bromide (Ipratropium, Fig. 8-13) has been introduced as an aerosol for inhalation. This renewed interest in antimuscarinics resulted in part from clarifications of the role of the parasympathetic system in bronchial obstructions. The availability of a potent agent such as atropine in a poorly absorbed form (i.e., quatemized) would minimize systemic effects following inhalation. Ipratropium bromide does not cross the BBB. It is longer acting and more bronchoselective than atropine methylbromide and exhibits no CNS effects. 

A. Prototypes and Pharmacokinetics Atropine and other naturally occurring belladonna alkaloids were used for many years in the treatment of asthma with only modest benefits. A quaternary antimuscarinic agent designed for aerosol use, ipratropium, has achieved much greater success. This drug is dehvered to the airways by pressurized tierosol. When absorbed, ipratropium is rapidly metabolized and has little systemic action. 

Impairment of breathing is an early effect of exposure to nerve agent vapor or aerosol. When the exposure is small, the casualty may have mild to severe dyspnea, with corresponding physical findings, and the impairment will be reversed by the administration of atropine. If the distress is severe and the casualty is elderly or has pulmonary or cardiac disease, the antidote may be supplemented by providing oxygen by inhalation. In most other circumstances, supplementation with oxygen is unnecessary. 

In asthmatics and chronic bronchitics atropine-like drugs are usually reserved for use when the patients become resistant to sympathomimetics. There is a risk of causing a drying effect and airways blocked with viscid secretions (39 ). Recent studies with atropine (40 ) and ipratropium (41 ) show them to be useful forms of treatment and the latter is as effective as salbutamol in chronic bronchitis. To produce toxic effects in animals relatively high doses of ipratropium are required (42) but when used in man in the doses recommended as a bronchodha-tor only jitteriness was reported (43 ). Slight transient disturbance of accommodation was observed in only 3 of 588 patients but it is recommended that direct contact of the aerosol with the eyes should be avoided (44 ). 

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