Despite increased access to contraception over the last 60 years, unplanned pregnancies continue to contribute to economic disparities and overpopulation. Additionally, the burden of family planning falls primarily on women, as a reliable pharmaceutical male contraceptive has yet to be developed. The objective of this literature-based systematic review was to identify compounds for future study from natural sources with potential nonhormonal male contraceptive activity. After the exclusion of extracts and compounds with known hormonal mechanisms, 26 unique compounds were identified from natural species. The plant source, compound class, structure, target, mechanism of action, safety/toxicity profile, and in vitro, in vivo, and human studies for each compound were evaluated and discussed. β-Caryophyllene, embelin, oleanolic acid, triptonide, and N-butyldeoxynojirimycin (NB-DNJ) were selected as the five most promising compounds for future study using prespecified criteria such as number of studies, efficacy and safety profile, reversibility, and previous use in humans for any indication. In order to move forward with development of a male contraceptive from a natural source, additional studies are needed to determine the predicted safety and efficacy for in vivo and human clinical trials.
Background Achieving therapeutic doses of sedation and analgesia are necessary for the safety and comfort of mechanically ventilated patients. Patients with complicated psychiatric histories, are neurocritical, and have acute respiratory distress syndrome usually require maximum sedation, making sedation weaning an arduous task. Case Presentation A 42-year-old female presented with a chief complaint of headache, hypertensive crisis, confusion, and nausea. Her past medical history is notable for hypertension, attention deficit hyperactivity disorder, bipolar II disorder, manic depression, agoraphobia, anxiety, and prior suicide attempts. Noncompliance with anti-hypertensive and psychiatric medications and prior substance abuse history was reported. A head computerized tomography scan revealed multifocal intraparenchymal hemorrhages and multifocal subarachnoid hemorrhages throughout the cerebrum. Within two hours, the patient became obtunded and required intubation. The patient’s severe agitation, likely due to metabolic encephalopathy, was difficult to control. Despite being on maximum dexmedetomidine, fentanyl, and quetiapine doses, the patient’s agitation remained. Due to her substance abuse and psychiatric history, a methadone and clonidine taper was initiated to attempt sedation weaning. Conclusion Sedation and analgesia weaning protocols for patients with psychiatric or substance abuse histories may aid in decreasing time on mechanical ventilation and/or in the ICU. The successful clonidine and methadone taper utilized in this patient has potential to be utilized in patients with similar histories. Future trials and approved sedation and analgesia weaning protocols for patients with a profound psychiatric and substance abuse history are urgently needed.
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