Exercise testing adverse effects

The AEGL-1 value was based on the observation that exercising healthy human subjects could tolerate exposure to concentrations of 500 or 1,000 ppm for 4 h with no adverse effects on lung function, respiratory symptoms, sensory irritation, or cardiac symptoms (Utell et al. 1997). The exercise, which tripled the subjects minute ventilation, simulates an emergency situation and accelerates pulmonary uptake. Results of the exposure of two subjects for an additional 2 h to the 500-ppm concentration and the exposure of one subject to the 1,000-ppm concentration for an additional 2 h failed to elicit any clear alterations in neurobehavioral parameters. The 4- or 6-h 1,000-ppm concentration is a NOAEL in exercising individuals, there were no indications of response differences among tested subjects, and animal studies indicate that adverse effects occur only at considerably higher concentrations, so the 1,000-ppm value was adjusted by an uncertainty factor (UF) of 1. The intraspecies UF of 1 is supported by the lack of adverse effects in patients with severe... 

The precise testing required to diagnose GH deficiency is controversial. Treatment of GH-deficient adults can cause increased lean body mass and bone density, decreased fat mass, increased exercise tolerance, and an improved sense of well-being. Adverse effects often include arthralgias and fluid retention. 

The incidence of major adverse reactions to dipyridamole was determined in a multicenter retrospective study, involving 73 806 patients who underwent intravenous dipjridamole stress imaging in 59 hospitals and 19 countries (4). The main conclusion was that the risk of serious dipjridamole-induced adverse effects is very low, a conclusion that is in line with other reports (5), and comparable to that reported for exercise testing in a similar patient population. Combined major adverse events among the entire patient population included 7 cardiac deaths (0.95 per 10000), 13 non-fatal myocardial infarctions (1.76 per 10000), 6 non-fatal sustained ventricular dysrhythmias (0.81 per 10000) (ventricular tachycardia in 2 and ventricular fibrillation in 4), 9 transient cerebral ischemic attacks (1.22 per 10000), 1 stroke, and 9 severe cases of bronch-ospasm (1.22 per 10000). Minor non-cardiac adverse effects were less frequent among the elderly and more frequent in women and patients taking maintenance aspirin. 

The manufacturers have on record in the USA several pulmonary adverse effects during isotretinoin therapy, including worsening of asthma (SEDA-21,162), recurrent pneumothorax, pleural effusion, interstitial fibrosis, pulmonary granuloma, and deterioration in lung function tests. Exercise-induced asthma (35) may be caused by a significant reduction in the forced expiratory flow rate (36) and a drying effect of isotretinoin on the mucous membranes of the respiratory tract (37). 

The major adverse effect of PBZ is postural hypotension, often accompanied by reflex tachycardia and other arrhythmias. Hypotension can be particularly severe in hypovolemic patients or under conditions that promote vasodilation (administration of vasodilator drugs, exercise, ingestion of alcohol or large quantities of food). Reversible inhibition of ejaculation may occur because of impaired smooth muscle contraction in the vas deferens and ejaculatory ducts. PBZ is mutagenic in the Ames test the clinical significance of this finding is unknown. 

In this study, central nervous system function was evaluated in multiple tests including perceptual speed, simple reaction time, short-term memory, numerical ability, and manual dexterity. A lowest-observed- adverse-effect level (LOAEL) was seen in the same study when humans were exposed to 4,000 mg/m for 50 minutes. The subjects had a prolonged simple reaction time compared to control results in the same volunteers during a non-exposure period. It should be noted that because of practical constraints, these tests were conducted on volunteers at rest and that parallel pharmacokinetic studies have demonstrated greater uptake during exercise (Astrand et al. 1975). 

In contrast, the effect on performance of carbohydrate feeding 30 to 60 min before exercise is unclear. Although blood glucose concentrations increased after ingestion of carbohydrate, one study reported improved and othCTS - showed no effects on performance compared to controls. There was consensus of no adverse effects on performance. Sherman et al. reported a 15% improvement in cycling performance when cyclists consumed 300 g of carbohydrate 4 h before the performance test. Thus, exogenous carbohydrate fed before exercise may be beneficial to individuals who have low glycogen stores. 

The safety and tolerability of once-daily oral metrifonate has been evaluated in patients with probable mild to moderate Alzheimer s disease in a randomized, doubleblind, placebo-controlled, parallel-group study (9). Metrifonate was given to 29 patients as a loading dose (2.5 mg/kg) for 2 weeks, followed by maintenance dose (1 mg/kg) for 4 weeks 10 patients received placebo. The proportion of patients who had at least one adverse event was comparable in the two groups metrifonate 76%, placebo 80%. Selected adverse events, defined as those for which the incidence in the metrifonate and placebo group differed by at least 10%, were diarrhea, nausea, leg cramps, and accidental injury. The adverse events were predominantly mild and transient. Those who took metrifonate had a significantly lower heart rate. Metrifonate had no clinically important effect on laboratory tests, such as liver function tests, and did not affect exercise tolerance or pulmonary function. 

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