Gender differences drug responses

Jackson A, Stephens D, Duka T. Gender differences in response to lorazepam in a human drug discrimination study. J Psychopharmacol 2005 19(6) 614—9. 

Becker IB, Beer ME, et al (1984) Striatal dopamine release stimulated by amphetamine or potassium influence of ovarian hormones and the light-dark cycle. Brain Res 311(1) 157-160 Becker IB, Molenda H, et al (2001) Gender differences in the behavioral responses to cocaine and amphetamine. Implications for mechanisms mediating gender differences in drug abuse. Ann N Y Acad Sci 937 172-187... 

If most dmgs had been developed in mixed gender populations, then the extent to which these issues contribute to gender-related variability in drug response would be clearer. However, women were systematically excluded from many clinical trials until relatively recently, and gender-related differences in drug response have only been sporadically reported. [Berg et al. NIH Publication No. 99-4386 1999. p. 151 (1)]... 

Franconi F, Brunelleschi S, Steardo L, Cuomo V (2007) Gender differences in drug responses. Pharmacol Res 55 81-95... 

The steroids are a remarkable family of molecules. They are essential for health, responsible for the characteristics of our genders, useful medicinal agents, and drugs of abuse. Modest structural variations on the central theme of steroid structure profoundly alter the physiological response to the action of these molecules. Small differences in structure can create big differences in function. 

The reasons why individuals differ in their responsiveness to drugs in medical products are manifold, and include age, gender, genetics, disease, and drugs given concomitantly. 

In general, the between-gender variations did not result in obvious pharmacodynamic dose-response differences, but care must be exercised in drugs having a steep dose-response curve and/or... 

An integrated summary and analysis is to be provided on all data that pertain to dose-response or drug candidate plasma concentration-response relationships of effectiveness and thus to contribute to dose selection, dosing interval, and dosage duration. Relevant data from nonclinical and clinical studies should be referenced and, where appropriate, summarized to illustrate further and describe these relationships. Any identified deviations (e.g., nonlinearity of pharmacokinetics, delayed effects, tolerance, enzyme induction) from relatively simple relationships should be discussed. Also, any evidence of differences in the relationships that result from the age, gender, race, disease status, or other factors of the patients should be described. How the potential for these deviations and differences were evaluated, even if no differences were found, should be described. 

Patients may include psychopaths who express habitual aggression and are responsible for much crime, some of which is violent. Impulsivity, aggression and lack of empathy are often observed in some patients following head trauma or encephalitis, which supports an organic cause. Drugs that block serotonin transporters and increase synaptic serotonin levels help these people. Hormonal effects also are involved, because of gender-related differences in the incidence of violence and aggressiveness. More than... 

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