Safe withdrawal

Gunpowder is best ignited by safety fuse. It burns very quickly and with a great deal of heat, so allow sufficient time delay for safe withdrawal from the vicinity. 

Drugs that have a radioactive isotope incorporated into their structures are invariably used in studies to establish safe withdrawal periods. The presence of the radioactive isotope is harmless to the animal, but offers a highly sensitive means of determining the biological half-life of the drug and the total residue concentrations in different tissues in different animals. 

Because of the withdrawal symptoms, it is often necessary to reduce neuroleptic drugs at a very slow rate. Sometimes withdrawal seems to become impossible. I describe the principles of safely withdrawing from psychiatric drugs in chapter 15. 

The new edition concludes with two entirely new chapters on treatment—one on how to safely withdraw from psychiatric drugs, and the other about psychosocial and educational approaches to very disturbed people, including 20 guidelines for therapy. I am pleased to include how-to treatment information in the book for the first time. 

The adverse effects and interactions of lithium have been reviewed (5,103-105,106). One review focused on lithium toxicity in elderly people (107). The adverse effects of lithium range widely in intensity and can be a major cause of nonadherence to therapy. However, with proper attention to the prevention and management of adverse effects, most patients can be treated effectively and safely. Withdrawal of lithium is almost always followed by resolution of adverse effects, although certain problems can sometimes persist (for example renal). 

Kountz DS, Clark CL. Safely withdrawing patients from chronic glucocorticoid therapy. Am Earn Physician 1997 55 521-552. 

Squifflet JP, Vanrenterghem Y, van Hooff JR et al. Safe withdrawal of corticosteroids or mycophenolate mofetil Results of a large, prospective, multicenter, randomized study. Transplant Proc 2002 34 1584-1586. 

Medications permit safe withdrawal and help prevent relapse. 

The two main purposes for prescribing medication for clients who are addicted to alcohol, sedative/hypnotics, and benzodiazepines are to permit safe withdrawal from the substance and to prevent relapse into addiction again. 

To ensure the safe withdrawal of a nonliquefied gas from a cylinder, the pressure must be reduced to a safe value. This pressure reduction is most commonly done with a pressure regulator like that shown in Fig. 5-2. Nonliquefied gas cylinders may be filled to pressures as high as 6000 psig (41 370 kPa), while the use pressure can be very low. 

For safe withdrawal and use of a gas, its pressure usually must be reduced below that in the cylinder. The dioice of a regulator to accomplish such reduction is influenced by several factors ... 

Issuing appropriate warnings at the correct time and ensuring the safe withdrawal of all persons on site to pre-arranged assembly points. 

If HjS is continuously present in the flare gas or if the flare seal drum also functions as a sour water disengaging drum, then the effluent seal water must be routed to a sour water stripper, desalter, or other safe means of disposal. Withdrawal from the drum is by pump in place of the normal loop seal arrangement. Two pumps are provided one motor driven for normal use, and the other having a steam turbine drive with low pressure cut-in. The seal drum level is controlled by LIC with high and low alarm lights plus an independent high level alarm. 

Produce from trial animals may not enter the food chain unless authorised by the CVM on the basis of data showing that residues will be either safe or not present in produce from animals treated at the maximum dosage with the minimum allowed withdrawal period. The CVM must be notified of the date and place of slaughter at least 10 days prior to each shipment for slaughter. The regulations also address the retention of records and the competence of study investigators. Records of drug shipments must be maintained for at least 2 years after the date of shipment. Data and results of trials must be retained for either 2 years after completion of the trial, or... 

Carroll KM, Ball SA, Nich C, et al Targeting behavioral therapies to enhance naltrexone treatment of opioid dependence. Arch Gen Psychiatry 38 755-761, 2001 Centers for Disease Control and Prevention Recommendation for prevention and control of hepatitis (virus (HCV) infection and HCV-related chronic disease. MMWR Recommendations and Reports 47(RR19) l-39, 1998 Charney DS, Steinberg DE, Kleber HD, et al The clinical use of clonidine in abrupt withdrawal from methadone. Arch Gen Psychiatry 38 1273-1277, 1981 Charney D S, Heninger OR, Kleber H D The combined use of clonidine and naltrexone as a rapid, safe, and effective treatment of abrupt withdrawal from methadone. Am J Psychiatry 143 831-837, 1986... 

My own practice was to refer to agents such as BZ or other related glycolates as similar to belladonna or atropine - belladonnoids if you will. Since the terms atropine and belladonna were also unfamiliar to many volunteers, I said that the effects would vary from person to person, but generally, they would include dryness of the mouth, sleepiness, difficulty in solving problems, and altered perceptions. I assured them that both the nursing staff and I would monitor them closely. I explained that extensive pre-clinical studies in several animal species had revealed no permanent ill effects. I told them we believed the drug to be safe, and would discuss the effects in detail after the test was over. Very few volunteers chose to withdraw after this orientation. 

To ensure compliance with the withdrawal period, an assay is needed to monitor total residues in the edible tissues. Because it is impractical to develop assays for each residue in each of the edible tissues, the concept of a marker residue and a target tissue is introduced. The marker residue is a selected analyte whose level in a particular tissue has a known relationship to the level of the total residue of toxicological concern in all edible tissues. Therefore, it can be taken as a measure of the total residue of interest in the target animal. The information obtained from studies of the depletion of the radiolabeled total residue can be used to calculate a level of the marker residue that must not be exceeded in a selected tissue (the target tissue) if the total residue of toxicological concern in the edible tissues of the target animal is not to exceed its safe concentration. 

Toxicity/symptoms high dose - agitation, tremors withdrawal - headache Regulatory facts GRAS (generally recognized as safe)... 

---