Withdrawal syndrome therapeutic drugs

Flutamide was the first drug used in prostate cancer therapy for which the withdrawal syndrome was reported. In that study, 40% of patients showed a decline in prostate specific antigen (PSA) levels after cessation of flutamide from the therapeutic protocol. The decline in PSA levels was associated with an improvement of the clinical symptoms. Based on these paradoxical observations, the concept of sequenced androgen ablation was proposed [217]. Several phase II clinical studies were performed, demonstrating safety and tolerability, however, a direct comparison in randomised phase III trials is necessary [218]. 

Dependence on benzodiazepines, as evidenced by a withdrawal syndrome, can develop to large doses of drugs. Mild dependence is produced at therapeutic doses. 

Naltrexone is generally taken once a day in an oral dose of 50 mg for treatment of alcoholism. An extended-release formulation administered as an IM injection once every 4 weeks is also effective. The drug can cause dose-dependent hepatotoxicity and should be used with caution in patients with evidence of mild abnormalities in serum aminotransferase activity. The combination of naltrexone plus disulfiram should be avoided, since both drugs are potential hepatotoxins. Administration of naltrexone to patients who are physically dependent on opioids precipitates an acute withdrawal syndrome, so patients must be opioid-free before initiating naltrexone therapy. Naltrexone also blocks the therapeutic effects of usual doses of opioids. 

C. It may be used therapeutically or diagnostically for patients with suspected alcohol or sedative-hypnotic drug withdrawal syndrome. 

The fact that P(3HB-co-4HB) and P(4HB) are also polymers with potential therapeutic applications has been pointed out in a review [6]. The 4HB units are pharmacologically active compounds, which have been used in the treatment of alcohol withdrawal syndrome [239,240] and narcolepsy [241]. Other potential applications include the treatment of patients with chronic schizophrenia, catatonic schizophrenia, atypical psychoses, chronic brain syndrome, neurosis, drug addiction and withdrawal, Parkinson s disease and other neuropharmacological illnesses, hypertension, ischaemia, circulatory collapse, radiation exposure, cancer and myocardial infarction [242]. 

With frequently repeated therapeutic doses of morphine or its surrogates, there is a gradual loss in effectiveness this loss of effectiveness is denoted tolerance. To reproduce the original response, a larger dose must be administered. Along with tolerance, physical dependence develops. Physical dependence is defined as a characteristic withdrawal or abstinence syndrome when a drug is stopped or an antagonist is administered (see also Chapter 32). 

Pancreatitis due to azathioprine or mercaptopurine has usually been reported as part of the hypersensitivity syndrome (SEDA-16,520) (SEDA-20,341). It has mostly been observed in patients with inflammatory bowel disease, and required withdrawal of treatment in 1.3% of patients with Crohn s disease (3). Pancreatitis was not dose-related within the therapeutic range of doses and often recurred in patients who were rechallenged with either drug (SEDA-20, 341) (35). Fatal hemorrhagic pancreatitis occurred in one patient, but a role of concomitant drugs was also possible (SEDA-20, 341). Pancreatitis or hyperamylasemia were not significantly different in renal transplant patients randomly assigned to receive azathioprine or ciclosporin, and other causative factors were found in most patients with pancreatitis (36). 

Dantrolene is life-saving in mahgnant hyperthermia associated with volatile anesthetics and suxamethonium and is also the drug of choice for the treatment of neuroleptic mahgnant syndrome. Dantrolene has therefore been suggested as an additional therapeutic option in baclofen withdrawal (18), but there is only limited experience (24). In one case of baclofen withdrawal, dantrolene was given with success (24). 

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