Drug action, standard mechanism

TCAs in more serious forms of depression such as melancholic or psychotic depression. Some studies have suggested that the SSRls do not work as well as the TCAs in melancholic depression (Roose et al. 1994]. Likewise, one study has suggested that venlafaxine, a drug with a mechanism of action similar to that of the TCAs, was superior to fluoxetine in the treatment of inpatients with melancholic depression (Clerc et al. 1994]. Still, other metaanalyses have failed to find a difference in the efficacy of SSRls versus TCAs in serious forms of depression [Nierenberg 1994]. Nonetheless, given that most studies have employed TCAs, and some debate exists about the utility of SSRls in severe subtypes, it may be prudent to start with a TCA in most patients until the debate is further resolved. For patients who present a significant suicide risk or who have not been able to tolerate TCAs, the SSRls in combination with a standard antipsychotic appears an effective option. 

This gigantic textbook is the standard in clinical pharmacology and contains an enormous amount of information of use to the clinician and researcher. It is strong in drug interactions and mechanism of action. It is updated every 5 years. Available on CD-ROM. 

The precise mechanism of SERM action is not well understood, but clearly, the ER is a primary target, as a signal transduction pathway, to modulate drug action in different tissues. Different concentrations of ER are present in breast cancers, which can be explained by heterogeneity in the tumor cell population. The more cells in the tumor that contain ERs, the higher the overall ER content, and the more likely the tumor will respond to antiestrogen therapy. Approximately 60% of ER-positive (receptor-rich) tumors are responsive to any form of additive or ablative endocrine therapy, whereas only 10% of ER-negative (receptor-poor) tumors respond to endocrine therapy (123). The current standard of care is to determine the ER status of the tumor in all patients with breast cancer. 

Our approach to each of these drug groups and related somatic therapies begins with a consideration of the possible mechanisms of action, followed by a comprehensive literature review on efficacy and adverse effects. These discussions then serve as the basis for the development of a clinical therapeutic strategy. Knowing that many patients fail standard treatment recommendations, because of either insufficient efficacy or intolerance to adverse effects, led us to emphasize the latter s importance. 

Isotretinoin (Accutane) is a synthetic retinoid currently restricted to the oral treatment of severe cystic acne that is recalcitrant to standard therapies. The precise mechanism of action of isotretinoin in cystic acne is not known, although it appears to act by inhibiting sebaceous gland size and function. The drug is well absorbed, extensively bound to plasma albumin, and has an elimination half-life of 10-20 hours. 

The discovery of the atypical antipsychotic clozapine opened a new era and set new standards in the drug treatment of schizophrenia. Modifications of the diben-zoazepine structure in clozapine resulted in olanzapine and quetiapine, which are among the most frequently used antipsychotic drugs. From a chemical viewpoint, clozapine, olanzapine and quetiapine can be considered as structural analogues. Although they share some common features in their molecular mechanism of action, the three compounds show significant differences in their clinical efficacy and adverse event profile. 

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