Chronic obstructive pulmonary disease patients with severe

The AEGL-1 concentration was based on a 1-hour (h) no-effect concentration of 8,000 parts per million (ppm) in healthy human subjects (Emmen et al. 2000). This concentration was without effects on pulmonary function, respiratory parameters, the eyes (irritation), or the cardiovascular system. Because this concentration is considerably below that causing any adverse effect in animal studies, an intraspecies uncertainty factor (UF) of 1 was applied. The intraspecies UF of 1 is supported by the absence of adverse effects in therapy tests with patients with severe chronic obstructive pulmonary disease and adult and pediatric asthmatics who were tested with metered-dose inhalers containing HFC-134a as the propellant. Because blood concentrations in this study approached equilibrium following 55 minutes (min) of exposure and effects are determined by blood concentrations, the value of 8,000 ppm was made equivalent across all time periods. The AEGL-1 of 8,000 ppm is supported by the absence of adverse effects in experimental animals that inhaled considerably higher concentrations. No adverse effects were observed in rats exposed at 81,000 ppm for 4 h (Silber and Kennedy 1979) or in rats exposed... 

Q66 Hypnotic doses of diazepam may cause hyperventilation in patients with severe chronic obstructive pulmonary disease. Diazepam causes central nervous system depression. 

Iloprost has not been evaluated in patients with chronic obstructive pulmonary disease (CORD), severe asthma, or acute pulmonary infections. 

Propranolol, nadolol, timolol, penbutolol, carteolol, sotalol, and pindolol Bronchial asthma or bronchospasm, including severe chronic obstructive pulmonary disease. Metoprolol Treatment of Ml in patients with a heart rate less than 45 beats/min significant heart block greater than first degree (PR interval 0.24 seconds or more) systolic blood pressure less than 100 mm Hg moderate to severe cardiac failure. Sotalol Congenital or acquired long QT syndromes. 

Epidural/Intrathecal administration Limit epidural or intrathecal administration of preservative-free morphine and sufentanil to the lumbar area. Intrathecal use has been associated with a higher incidence of respiratory depression than epidural use. Asthma and other respiratory conditions The use of bisulfites is contraindicated in asthmatic patients. Bisulfites and morphine may potentiate each other, preventing use by causing severe adverse reactions. Use with extreme caution in patients having an acute asthmatic attack, bronchial asthma, chronic obstructive pulmonary disease or cor pulmonale, a substantially decreased respiratory reserve, and preexisting respiratory depression, hypoxia, or hypercapnia. Even usual therapeutic doses of narcotics may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea. Reserve use for those whose conditions require endotracheal intubation and respiratory support or control of ventilation. In these patients, consider alternative nonopioid analgesics, and employ only under careful medical supervision at the lowest effective dose. 

Ramelteon is available in 8-mg tablets for oral administration. The current maximum dosage is 8 mg administered at night however, during trials, up to 16 mg was studied. Ramelteon should be used with caution in elderly patients because plasma levels were twice those in healthy adults in clinical trials. Ramelteon should not be used by patients with severe hepatic impairment. This medication has been evaluated in moderate sleep apnea and chronic obstructive pulmonary disease and appeared to be safe to administer in this population. Ramelteon was not studied in subjects with severe sleep... 

Nonselective beta blockers affect beta-2 receptors on the lungs as well as beta-1 receptors on the heart, and these nonselective agents can increase bronchocon-striction in patients with asthma and chronic obstructive pulmonary disease. Hence, a drug that is more specific for beta-1 receptors is preferred in these patients. Beta blockers can also produce excessive slowing of cardiac conduction in some patients, resulting in an increase in arrhythmias. Severe adverse reactions are rare, however, and beta blockers are well-tolerated by most patients when used appropriately to treat arrhythmias. 

Cachexia is loss of weight, muscle atrophy, fatigue, weakness and significant loss of appetite. It is seen in patients with cancer, acquired immunodeficiency syndrome (AIDS), chronic obstructive pulmonary disease and congestive heart failure. Underlying causes are poorly understood, but there is an involvement of inflammatory cytokines, such as TNF-a, IFN-y, IL-6 and tumour-secreted proteolysis-inducing factor. Related syndromes are kwashiorkor and marasmus, although these are most often symptomatic of severe malnutrition. 

Continuous long-term domiciliary oxygen therapy (LTOT) is given to patients with severe persistent hypoxaemia and cor pulmonale due to chronic obstructive pulmonary disease (see later). Patients are provided with an oxygen... 

Almitrine is a respiratory stimulant that improves hypoxemia in about 80% of patients with severe chronic obstructive pulmonary disease (SEDA-17, 212). Oral almitrine bimesilate (100 mg/day) increased Pa02 in patients with severe chronic obstructive pulmonary disease without altering mean pulmonary artery pressure (1). Adverse effects were rarely observed and it was concluded that long-term treatment was safe. In other studies, respiratory, digestive, and neurological symptoms have been noted but were often pre-existent (2,3). 

The practicability of dipyridamole A-ammonia myocardial positron emission tomography for perioperative risk assessment of coronary artery disease in patients with severe chronic obstructive pulmonary disease undergoing lung volume reduction surgery has been studied in 13 men and 7 women (mean age 57 years) without symptoms of coronary artery disease (12). Nine patients had intolerable dyspnea due to bronchoconstriction and required intravenous aminophylline. Dipyridamole cannot be recommended as a pharmacological stress in this setting. 

Thurnheer R, Laube 1, Kaufmann PA, Stumpe KD, Stammberger U, Bloch KE, Weder W, Russi EW. Practicability and safety of dipyridamole cardiac imaging in patients with severe chronic obstructive pulmonary disease. Eur J Nucl Med 1999 26(8) 812-17. 

In a randomized, double-blind, placebo-controlled, crossover study of the use of nitric oxide in chronic obstructive pulmonary disease (COPD) 11 patients with documented severe COPD received 25 ppm of nitric oxide combined with supplementary oxygen at a flow rate of 2 1/minute via nasal cannulae (8). Four of the patients reported an increase in cough and a feeling of retrosternal rawness after breathing nitric oxide for 24 hours two had an increase in dyspnea, and one developed... 

The safety of perflenapent has been evaluated in multicenter phase II studies in 146 patients with congestive heart failure (NYHA class III or IV, mean age 68 years), of whom 99 received perflenapent and 47 received isotonic saline, and in 134 patients with severe chronic obstructive pulmonary disease (FEVi no more than 60% of predicted, mean age 65 years), of whom 91 received perflenapent and 43 received isotonic saline (13). Blood pressure, heart rate, respiratory rate, oxygen saturation, the electrocardiogram, FEVi, complete serum biochemistry, hematology, and mental state were assessed. Adverse events were mild and required no treatment. There was no significant difference in the incidence of adverse reactions between those given perflenapent (15%) and those given placebo (11%). The most frequent adverse events with perflenapent were vasodilatation (n = 8), taste disturbance (n = 6), nausea (n = 5), and headache (n = 3). 

Burge PS, Calverley PM, Jones PW, et al. Randomised, double-blind, placebo-controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease The ISOLDE trial. Br Med J 2000 320 1297-1303. 

Patients with a history of chronic respiratory acidosis (e.g., those with chronic obstructive pulmonary disease) may experience an acute worsening of their respiratory acidosis. This may result in severe life-threatening hypoxemia. As with acute respiratory acidosis, the goals... 

Patients receiving radiation therapy may experience complications including severe esophagitis, fatigue, radiation pneumonitis, and cardiac toxicity. These toxicities are usually more common and severe when radiation is combined with chemotherapy. The patient s baseline performance status and the degree of pulmonary dysfunction (e.g., chronic obstructive pulmonary disease from years of tobacco use) must be considered in the decision of radiation dosage and fractionation. 

Fenoterol (200 to 400 meg by inhalation), a beta2-adrenergic receptor agonist, is being used in patients with moderate to severe asthma, with chronic obstructive pulmonary disease, in protection against exercise-induced asthma, and for acute treatment of asthma attack. However, no apparent advantage of fenoterol over equipotent doses of albuterol or terbutaline has been demonstrated in clinical trials (see also Figure 94). 

The drugs generally are administered as eye drops and have onset in approximately 30 minutes with a dmation of 12 to 24 hours. While topically administered P-blockers usually are well tolerated, systemic absorption can lead to adverse cardiovascular and pulmonary effects in susceptible patients. They therefore should be used with great caution in glaucoma patients at risk of adverse systemic effects of p-receptor antagonists (e.g., patients with bronchial asthma, severe chronic obstructive pulmonary disease [COPD], or those with bradyarrhythmias). Recently three P-blockers... 

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