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Do I Have IBS?
Published in Melissa G. Hunt, Aaron T. Beck, Reclaim Your Life From IBS, 2022
Melissa G. Hunt, Aaron T. Beck
The good news is that there is a very effective treatment for bile acid diarrhea. You take a medication called a bile acid sequestrant (cholestyramine, colestipol, or colesevelam). The medicine binds to the bile acid and keeps it from pulling so much water into the large intestine. A positive response to a bile acid sequestrant is usually a pretty good sign that excess bile acid was causing diarrhea, to begin with. Unfortunately, there are two downsides to the treatment. First, the medicine is a little hard to take. The medications come in two forms – resinous powder that needs to be mixed with food (like apple sauce or yogurt) or pills. The powder doesn’t taste great and it’s got a weird gritty texture that most people find pretty unappealing. The pills are quite large and hard to swallow, and you usually have to take at least 4 of them a day to get any benefit. (If you try them, be sure to ask the pharmacist to give you the brand name drug, not the generic. The generic pills are even harder to swallow.) The other downside is that the medications interfere with the absorption of lots of other medications, so you have to take it two hours after or four hours before you take anything else. That can make it hard to time them and hard to remember to take them. On the other hand, if your symptoms are really the result of bile acid diarrhea, and not IBS, then taking one of these medications may solve your symptoms completely.
Nanomedicine(s) under the Microscope *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
If the nanomedicine is biologically active in its own right (drug or a sequestrant), it is essential that the dose required to exhibit pharmacological activity is low enough to allow practical formulation for patient administration; e.g., tablet size and infusion volume have limits. Similarly, when the nanomedicine is transporting a drug or imaging agent, it must be able to carry a sufficiently high payload in relation to drug potency/imaging capacity. Acceptable minimum threshold values for carrying capacity are easy to estimate theoretically at the outset, especially if composition is expressed as weight % for all components. Unfortunately this information is rarely given. For example, the drug:lipid:polymer weight ratio of a PEGylated liposome is rarely stated, and it is more common to report % drug entrapment efficiency. Although useful to indicate manufacturing efficiency (impacts on cost and potential free drug content), this value gives no appreciation of overall composition by weight (i.e., the doses to be given). The latter better highlights practicality vis-a-vis final formulation design, and potential safety and efficacy of drug and carrier. It also guides the concentration or dose range of all components needed for meaningful preclinical in vitro and in vivo safety evaluation.
Management of Obesity-Associated Type 2 Diabetes
Published in Emmanuel C. Opara, Sam Dagogo-Jack, Nutrition and Diabetes, 2019
Wanda C. Lakey, Lillian F. Lien, Mark N. Feinglos
Other oral antidiabetic medications include the meglitinides (repaglinide, nateglinide) and alpha-glucosidase inhibitors (acarbose, miglitol). Although the potential for hypoglycemia in both classes is limited, their major role is in modifying postprandial hyperglycemia. Therefore, in patients with erratic food intake, there is no clear role for these agents. In that case, these agents should be discontinued in favor of a scheduled insulin regimen [147]. Colesevelam, a bile acid sequestrant, binds bile acids in the intestinal tract and prevents their reabsorption. The mechanism by which colesevelam improves hyperglycemia is not completely understood. Colesevelam is weight-neutral [149]. Bromocriptine (quick release), a dopamine-2 agonist, improves glycemic control by increasing insulin sensitivity and altering hypothalamic control of metabolism. Bromocriptine is weight-neutral [149].
Colesevelam – a bile acid sequestrant for treating hypercholesterolemia and improving hyperglycemia
Published in Expert Opinion on Pharmacotherapy, 2022
Oluwayemisi Esan, Adie Viljoen, Anthony S. Wierzbicki
Meta-regression studies show that lowering LDL-C seems to be beneficial irrespective of how it is achieved [8]. An initial analysis of 8 bile acid sequestrant (BAS), a surgical strategy (ileal bypass surgery) with an analogous action to BAS, but also including 13 statin trials and totaling 85,431 participants showed a 15–20% reduction in CVD events per 1 mmol/L LDL-C reduction [9]. Later analyses which included multiple statin trials, ezetimibe and now proprotein convertase subtilisin kexin-9 (PCSK-9) inhibitors confirmed and extended this relationship [8]. Data with non-statin interventions is scarcer or dated. Ezetimibe, a specific cholesterol absorption inhibitor blocking the duodenal Niemann-Pick C1-like 1 protein (NPC1L1) transporter lowers LDL-C by around 20% and has CVD outcome evidence in patients with acute coronary syndromes (ACS) which follows the predicted relationship [10]. Similarly, PCSK-9 inhibitors which reduce LDL-C by affecting LDL receptor (LDLR) expression by affecting receptor recycling follow the same relationship in patients with ACS [11].
Targeted agents for HER2-positive breast cancer in older adults: current and future perspectives
Published in Expert Opinion on Investigational Drugs, 2018
Enrique Soto-Perez-De-Celis, Kah Poh Loh, Capucine Baldini, Nicolò Matteo Luca Battisti, Yanin Chavarri-Guerra, Nienke A. De Glas, Tina Hsu, Arti Hurria
In summary, the evidence regarding the use of neratinib in older adults is very limited, and less than 15% of patients included in clinical trials were aged ≥65 [78,81]. Importantly, a meta-analysis found that the incidence of all-grade diarrhea in neratinib trials was 89% [82]. Therefore, antidiarrheal prophylaxis with loperamide is recommended starting with the first dose of neratinib and continuing for two cycles [81]. An ongoing phase II trial (NCT02673398) will help to estimate the safety and tolerability of neratinib in older adults with metastatic BC, and to understand if geriatric assessments can adequately identify patients who may better tolerate treatment. Additionally, at least two phase II studies are evaluating strategies to ameliorate neratinib-associated diarrhea, such as the use of the chloride channel-blocker crofelemer (NCT03094052), the bile acid sequestrant colestipol, and budesonide (NCT02400476).
PCSK9 inhibitors: a non-statin cholesterol-lowering treatment option
Published in Postgraduate Medicine, 2018
Finally, in addition to the simplified FH diagnosis criteria (as shown in Supplementary Table 1), the AHA provided a scientific statement on the treatment of patients with FH [7]. In this recent statement, the AHA recommended a drug formulary approach to treatment with an initial goal of reducing LDL-C by ≥50% (Table 3), usually with a high-intensity statin. If the LDL-C goal is not reached after 3 months of statin therapy, ezetimibe was recommended as an additional LMT. If the goal is not reached after 3 months of the two-drug combination, the addition of a third drug was recommended (PCSK9 inhibitor, colesevelam or other bile acid sequestrant, or niacin), taking into consideration multiple factors including disease severity, patient preference, cost, and outcomes data if available. If the goal is still not reached after 3 months of the three-drug combination, a four-drug combination (lomitapide or mipomersen in HoFH subjects) or LDL apheresis can be considered (Table 3) [7].