Tolerance treatment

Though still the second leading cause of cancer death, mortality rates for colon cancer have declined over the last 30 years as a result of better and increasingly used screening programs and more effective and better tolerated treatments. 

SSRI structurally related to fluoxetine with a shorter half-life, was reported to be an effective and generally well-tolerated treatment for men with moderate-to-severe PE in clinical trial [13,14],... 

In Phase I clinical trials with stable renal transplant patients, FTY720 led to a transient reduction in the number of circulating lymphocytes whilst being well-tolerated. Treatment was associated with a mild reduction in heart rate that was maximal 6 h after the first dose and returned to baseline with continuous treatment [52,53]. The mild effect on heart rate is believed to arise from SlPj and/or SlP3-mediated activation of G-protein-gated inwardly rectifying potassium (GIRK) channels in atrial myocytes [54-56]. 

Anticonvulsants. Scattered case reports suggest that carbamazepine (Tegretol) and valproic acid (Depakote, Depakene) may be helpful in the treatment of panic disorder. This has yet to be verified in systematic studies. Furthermore, because these anticonvulsants are hindered by toxicity and side effect concerns (cf. Chapter 3), they should only be considered if other better studied and more tolerable treatment options have failed. 

Lithium is somewhat effective for the treatment of agitation however, elderly patients do not tolerate it well. In particular, demented patients are at risk for lithium toxicity, and this toxicity may not be easily detected in these patients. Despite its effectiveness, lithium has been abandoned in the treatment of agitation due to the availability of several effective and better-tolerated treatments, including the atypical antipsychotics described earlier. 

Renal function impairment For patients with severe renal insufficiency, do not start ezetimibe/simvastatin unless the patient has already tolerated treatment with simvastatin at a dose of 5 mg or higher. Exercise caution when ezetimibe/simvastatin is administered to these patients, and monitor them closely. Concomitant bile acid sequestrants Give ezetimibe/simvastatin either 2 hours or more before or 4 hours or more after administration of a bile acid sequestrant. Concomitant cyclosporine Exercise caution when initiating ezetimibe/simvastatin in the setting of cyclosporine. In patients taking cyclosporine, do not start ezetimibe/simvastatin unless the patient has already tolerated treatment with simvastatin at a dose of 5 mg or higher. Do not exceed 10 mg ezetimibe/10 mg simvastatin daily. 

As must be clear by now, drug development is a very dynamic activity with high interests at stake. For patients this is the availability of more effective or better tolerated treatments, for pharmaceutical companies it is the return on the huge investments that are needed to discover and develop new drugs. It is not difficult to predict that there will be continuous attempts to speed-up development times and to improve the quality and efficiency of the development... 

Orally administered sildenafil is an effective and well-tolerated treatment for men with ED, including those with diabetes mellitus. It has also been used for so-called salvage therapy in men who do not respond to intracorporeal injections of other agents. 

The risk of agranulocytosis and seizures limits use to patients who have failed to respond or were unable to tolerate treatment with appropriate courses of standard antipsychotics. 

Panic disorder is emerging from decades of comparative neglect as an apparently intractable and poorly understood condition to become the focus of intensive interest in epidemiological, pharmacological, and clinical research. Panic disorder is a chronic and distressing condition with a profound effect on the quality of life, similar to or even worse than the effect of major depression [Markowitz et al. 1989 Weissman 1991). Effective and well-tolerated treatment that can be used safely in the long term is badly needed. 

Aziridines have been prepared on insoluble supports by addition of primary amines to a-bromo acrylates and acrylamides (Entry 6, Table 15.1). These aziridines are sufficiently stable to tolerate treatment with TFA [6],... 

Famciclovir Famvir Tablet, oral—125 mg, 250 mg, 500 mg Oral famciclovir is an effective and well-tolerated treatment for suppressing recurrent genital ffSV infection. No studies have been done for ffSV ocular infections. 

No randomized controlled trials have evaluated the efficacy of femciclovir for the treatment of recurrent HSV keratitis. Randomized controlled trials have studied the efficacy and safety of femciclovir in the suppression of recurrent genital HSV infection, indicating that famciclovir is an effective and well-tolerated treatment for the suppression of genital HSV infection. 

Topical cyclosporine A is an effective, safe, well-tolerated treatment option for severe or intractable VKC. An immunosuppressant, it affects and inhibits cell-mediated and immediate hypersensitivity reactions. It inhibits the release of interleukins, and it may prevent mediator release from mast cells. Relief is often noted after the first month of cyclosporine treatment, with continued results for up to 2 years. Some, however, have found a return of signs and symptoms 1 to 2 months after discontinuance of treatment. 

An HIV-infected patient who developed an anaphylactic reaction to rifampicin tolerated treatment with rifabutin without any adverse event. 

Chancellor M, Freedman S, Mitcheson HD, et al. Tolterodine, an effective and well tolerated treatment for urge incontinence and other overactive bladder symptoms. Clin Drug Invest 2000 19 83-91. 

Exposure to low, non-freezing temperatures induces a process, known as cold acclimation, which makes the plant able to increase its fireezing tolerance. Treatment of wheat, rye and bromegrass cell cultures with ABA for four days at 20°C bypasses the requirement for exposure to low temperature for increased freezing tolerance suggesting that cold acclimation involves ABA. The Arabidopsis aba mutant is unable to cold acclimate by incubation at 4°C but the phenotype can be reverted by treatment with ABA. This shows that adaptation to freezing temperatures requires endogenous ABA. 

Docosanol is a long-chain saturated alcohol that is FDA approved as a 10% over-the-counter cream for the treatment of recurrent orolabial herpes. Topical treatment beginning within 12 hours of prodromal symptoms or lesion onset reduces healing time by 1 day and is well tolerated. Treatment initiation at papular or later stages provides no benefit. 

Schlumberger, E. Dulac, 0. (1994) Dev. Med. Child Neurol. 36, 863-872. A simple, effective and well-tolerated treatment regime for West syndrome. 

The time course of this adverse reaction is typically late. In one case there was rapid loss of visual field after 10 years of apparently well-tolerated treatment with vigabatrin [365 ]. 

These three reports suggested a strong anti-in ammatory activity of 1,8-cineole via both the cyclooxygenase and 5 lipooj genase pathways, and the possibility of a new, well-tolerated treatment of airway in ammation in obstructive airway disease. 

Sublingual buprenorphine has been proposed as an effective and well-tolerated treatment for neonatal abstinence syndrome. In a randomized trial, infants with neonatal abstinence syndrome, who had been born to mothers taking maintenance methadone, were randomized to either sublingual buprenorphine 13-39 micrograms/ kg per day ( = 13) or standard-of-care oral neonatal opium solution ( = 13) [29 ]. Buprenorphine administration was associated with a 31% reduction in length of treatment and a 29% reduction in the length of hospital stay. One infant had seizures after buprenorphine, but it was not clear whether buprenorphine was causal. 

---