Americans with Disabilities Act. Considerations for the practice of occupational medicine.

The Americans with Disabilities Act (ADA), although developed in the context of civil rights legislation, is likely to have notable impact on the practice of occupational medicine. The ADA contains provisions limiting the use of preplacement examinations to determinations of the capability to perform the essential functions of the job and of direct threat to the health and safety of the job applicant or others. The Title I employment provisions of the ADA establish definitions and requirements similar to those found in section 504 of the Rehabilitation Act of 1973, as amended; leading cases that have been litigated under the Rehabilitation Act, as amended, are described. The limitations of available scientific and medical information related to determinations of job capability and direct threat and ramifications of the ADA on the practice of occupational medicine are discussed.

Drug testing in the workplace--are methods legally defensible? A survey of experts, arbitrators, and testing laboratories.

Urinalysis results are increasingly being used by employers to detect use of prohibited substances in the workplace. Actions taken on the basis of positive urinalysis results can have a significant effect on employees' lives and careers, and may face legal challenge. Important aspects of urinalysis are choice of analytical methods and their legal defensibility. Medical directors are frequently required to select testing laboratories, but have had few data correlating analytical methods with legal defensibility. To evaluate the legal defensibility of the methods used for drug testing, we conducted a survey of technical experts, testing laboratories, and arbitrators. Experts reported wide differences in the legal defensibility of methods rated. Arbitrators had considerable experience in drug use cases and understood the critical role of urinalysis results, but were unable to distinguish legal defensibility of analytical methods. Commercial laboratory practice in urinalysis varies widely among laboratories. An objective of this article is to provide company medical directors with information that will enable them to make informed decisions when choosing urinalysis laboratories and methods.

Variable-interval responding in the horse: a sensitive method of quantitating effects of centrally acting drugs.

An operant conditioning apparatus for studies in equine pharmacology was constructed. Horses interacted with this apparatus by breaking a light beam and were rewarded with 30 ml of oats. Horses readily learned to use this apparatus and were trained to respond on a variable-interval-60 schedule. With this schedule, there was no direct relationship between the rate of light beam breaking and the reward. Horses thus developed their own individual response rates (ie, light-beam breaking rates), and these rates remained stable at between 5 and 35 responses/min for each horse over a period of months. The effects of 2 drugs on this paradigm were tested. Reserpine (5 mg/horse, IV) depressed the response rate in all horses tested. This depression was maximal between 3 and 5 days after treatment and lasted for up to 10 days. After small doses of cocaine (0.01 mg/kg of body weight IV), the response rate of 1 horse was stimulated, whereas 1 mg of cocaine/kg was required for maximal stimulation of response rate in another horse. Larger doses of cocaine inhibited response. Variable-interval response was a sensitive method of measuring drug effects in the horse and allowed accurate quantitation of drug effects that were not detectable by clinical observation.

The pharmacokinetics, pharmacological responses and behavioral effects of acepromazine in the horse.

After intravenous (i.v.) injection, acepromazine was distributed widely in the horse (Vd = 6.6 litres/kg) and bound extensively (greater than 99%) plasma proteins. Plasma levels of drug declined with an alpha half-life of 4.2 min, while the beta phase or elimination half-life was 184.8 min. At a dosage level of 0.3 mg/kg acepromazine was detectable in the plasma for 8 h post dosing. The whole blood partitioning of acepromazine was 46% in the plasma phase and 54% in the erythrocyte phase. Penile prolapse was clearly evident at doses from 0.01 mg/kg to 0.4 mg/kg i.v., and the duration and extent of protrusion were dose related. Hematocrit levels were significantly lowered by administration of 0.002 mg/kg i.v. (about 1 mg to a 500 kg horse) and increasing dosages resulted in greater than 20% lowering of the hematocrit from control levels. Pretreatment of horses with acepromazine also reduced the variable interval (VI 60) responding rate in all horses tested. These data show that hematocrit changes are the most sensitive pharmacological responses to acepromazine, followed by changes in penile extension, respiratory rate, VI responding and locomotor responses. Acepromazine is difficult to detect in plasma at normal clinical doses. However, because of its large volume of distribution, its urinary elimination is likely prolonged, and further work on its elimination in equine urine is required.

Pharmacology of narcotic analgesics in the horse: selective blockade of narcotic-induced locomotor activity.

The locomotor responses of horses given morphine and fentanyl were blocked or lessened by administration of naloxone or acepromazine. Naloxone given at the dosage of 0.015 mg/kg completely blocked the locomotor activity induced in horses given fentanyl (0.020 mg/kg of body weight). The locomotor stimulation produced by morphine given at the dosage of 2.4 mg/kg was reduced by 75% of naloxone (0.020 mg/kg). Acepromazine partially blocked the locomotor responses to fentanyl and morphine. This blockade activity reached its peak about 30 minutes after acepromazine was given (IV) and lasted more than 6 hours. Simultaneous administration of acepromazine and morphine was associated with substantial respiratory depression for more than 4 hours after administration of both drugs. In other experiments, fentanyl did not add to the partial locomotor response observed after large doses of pentazocine were given--this being consistent with the concept that pentazocine possesses both antagonist and agonist actions at the narcotic receptor. Furosemide and phenylbutazone, given at usually used clinical doses, had no effect on the locomotor response to fentanyl, indicating that the usual clinical dosages of neither drug exerted stimulant or depressant actions.

Pharmacokinetics and behavioral effects of methylphenidate in Thoroughbred horses.

In horses given (rapid IV) methylphenidate (Ritalin, alpha-phenyl-2-piperidinacetic acid methyl ester; 0.70 mg/kg), plasma concentrations of the drug decreased rapidly at first, with an apparent alpha half-life of about 19 minutes, and then more slowly, with an apparent beta half-life of about 2.4 hours. These data were well fitted by a 2-compartment open model. In blood, about 40% of the methylphenidate present was in the plasma fraction, and of this, about 80% was plasma-protein bound. If given by subcutaneous or IM injection, plasma concentrations of methylphenidate peaked in about 1 hour and were no longer detectable (cleared) from plasma by 6 hours. Urinary clearance time, however, was longer, and between 12 and 24 hours should be allowed for a dose of methylphenidate to "clear" from urine. Using a variable-interval responding apparatus, methylphenidate was shown to stimulate the responding rate of horses up to 6 times above base line, making it the most potent central stimulant tested in this responding apparatus to date. Peak central stimulation at 30 minutes after IV dosing was seen in horses given 0.4 to 1.0 mg of methylphenidate/kg.