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Sedative/Hypnotics
Published in Frank A. Barile, Barile’s Clinical Toxicology, 2019
Frank A. Barile, Anirudh J. Chintalapati
Pharmacologically, GHB interacts with GABA-B and GHB receptors, as well as opioid receptors, resulting in a predominant CNS depression. It has a quick onset (15–30 min) and relatively short duration (3 h). Most users of GHB report that it induces a pleasant state of relaxation and tranquility. Frequent effects are a tranquil mental state, mild euphoria, emotional warmth, well-being, and a tendency to verbalize. Ingestion of GHB in an alcoholic drink by an unsuspecting victim, however, causes hallucinations and amnesia, as well as symptoms not unlike flunitrazepam. Alcohol potentiates the depressant and adverse reactions, including dizziness, nausea, vomiting, respiratory collapse, seizures, coma, and possibly death.
Current and future CFTR therapeutics
Published in Anthony J. Hickey, Heidi M. Mansour, Inhalation Aerosols, 2019
Marne C. Hagemeijer, Gimano D. Amatngalim, Jeffrey M. Beekman
The exact CFTR binding site of ivacaftor is still unknown but direct binding to the phosphorylated CFTR protein has been reported (105), with the transmembrane domains (TMDs) being suggested as possible binding site candidates (106). Ivacaftor stabilizes a posthydrolytic open state of CFTR and as a result stimulates decoupling of the gating and ATP hydrolysis cycle, resulting in an increased time period that the CFTR channel stays open (106). It is able to exert its function, as demonstrated in a reconstitution system with purified wild-type and mutant CFTR, via an ATP-independent mechanism (105). Indeed, it was reported that spontaneous opening of CFTR may occur without ATP and is coupled to NBD dimerization (107). In vitro studies, however, suggested that the effect of ivacaftor was due to an ATP-dependent increase of the opening rate and reduction of the closing rate of the channel (108). Clearly, more studies are required to elucidate ivacaftor’s mode of action in more detail, which would be beneficial for future development of novel potentiator compounds.
Social drugs
Published in Anne Lee, Sally Inch, David Finnigan, Therapeutics in Pregnancy and Lactation, 2019
Recent studies of the effects of caffeine upon birth weight have provided conflicting results, including: no adverse effects;37 no significant effect except in smokers with high caffeine intake;38 no adverse effects on fetal weight unless dose exceeds 70 mg daily;39 unless dose exceeds 300 mg daily;40 or a dose-related effect with some adverse effects at all levels of consumption.41 In the face of this conflicting data it would seem wise to suggest that pregnant women limit their caffeine intake until further studies provide a consensus view on the likelihood of any ill effects. During the second and third trimesters the ability to metabolise caffeine is reduced, and caffeine blood levels may rise even though intake remains stable. This could potentiate any adverse effects upon fetal development.
“That’s what we call the cocktail”: Non-Opioid medication and supplement misuse among opioid users
Published in Substance Abuse, 2021
Avik Chatterjee, Diego Lopez, Shankar Ramkellawan, Rory Brown, Kamala Smith, Jessie M. Gaeta, Travis P. Baggett
In addition to producing their own health effects, these “potentiator” substances—substances that may augment or alter the high from opioids—could increase the risk of opioid-related harms. According to the Centers for Disease Control, the herbal supplement kratom was listed as the cause of death in 91 individuals between July 2016 and December 2017, but in nearly all cases it was combined with another substance, most commonly fentanyl or heroin.19 For gabapentin, a recent large cohort study demonstrated increased inpatient hospitalizations and emergency department use among individuals prescribed opioids who also received high doses of gabapentin.20 Harms associated with gabapentin and opioid co-prescription are not limited to health care utilization, however. In a large case-control study in Ottawa between 1997 and 2013, gabapentin co-prescription with opioids was associated with 60% higher mortality.21 Additionally, combining multiple substances of any kind has also been shown to increase risk of complications such as thrombosis and injection with used needles22 and is associated more psychiatric symptoms and with heavier substance use even after addiction treatment.23
The use of ketamine to cope with depression and post-traumatic stress disorder: A qualitative analysis of the discourses posted on a popular online forum
Published in The American Journal of Drug and Alcohol Abuse, 2020
Tharcila V. Chaves, Bob Wilffert, Zila M. Sanchez
The recreational use of ketamine should not be confounded with the clinical use of it. First, using a drug in a medical setting prevents self-medication and allows extensive monitoring of the patients’ responses to it. Second, the doses used to treat depression (usually 0.5 mg/kg IV, so 35 mg for a person with 70 kg) are much lower than the doses used by heavy users (which can reach one gram of ketamine per day). It is very important to make this distinction because one of the main concerns surrounding the approval of ketamine as an antidepressant is due to its ability to develop dependence. Therefore, monitoring patients is an essential part of the treatment, especially when the patient takes the intranasal spray or oral tablet home; these two formulations present the risk of leading the patient to self-administer higher doses than prescribed and/or to use a different route of administration in order to potentiate the effect, as found in the analyzed reports. Bluelight members showed concern with the potential of ketamine to cause tolerance, addiction and adverse effects, hence several posts were dedicated to warnings about risks and harm reduction techniques.
How can we improve the safe use of herbal medicine and other natural products? A clinical pharmacologist mission
Published in Expert Review of Clinical Pharmacology, 2020
Elena Y. Enioutina, Kathleen M. Job, Lubov V. Krepkova, Michael D. Reed, Catherine M. Sherwin
Consumers haveused NPs for thousands of years and will continue to use them as alternatives to conventional drugs or in combination with conventional drugs. To improve DS safety, in our opinion, clinical pharmacologists need to make an alliance with DS companies and work out rules that will ensure the safety of DSs. We need to educate not only clinicians but also caregivers and consumers themselves about the risks associated with the use of alternative and complementary medicine. We should not stop people from trying these options, but they need to make informed decisions. It would be beneficial to have access to more clinical pharmacology/toxicology seminars/webinars. Also, experts on herbal medicines should be able to be consulted and answer FAQs for healthcare professionals. This includes options such as the presenting of webinars/information sessions and having pamphlets that describe the potential benefits and potential harm of NP. We need to gather knowledge of DSs that are widely available for distribution among patients/consumers interested in alternative and complementary medicine, especially in clinical areas where there is high use such as oncology. We need to expand the reporting of potential NP adverse reactions and improve the availability of such information, including when there is a positive outcome associated with NP use. The risk is real, and the consequences can be deadly, as we see with the increasing reported cases of DILI, nephrotoxicity, and potentiation of conventional drug toxicity associated with the herb-drug interactions.