Consequences of Gastrointestinal Surgery on Drug Absorption

Titus, R.; Kastenmeier, Andrew; Otterson, Mary F.

doi:10.1177/0884533613490740

Cited by 37 publications

(36 citation statements)

References 53 publications

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“…This strongly suggests that the regional drug metabolism capacity is differently regulated within one human being. Furthermore, pharmacokinetics and bioavailability of drugs are greatly affected in patients with a short small bowel following gastrointestinal surgery, and the changes will vastly differ between patients (Severijnen et al, 2004;Titus et al, 2013). Studies with matched hPCIS can aid in the identification of suitable therapies for this patient population.…”

Section: Downloaded Frommentioning

confidence: 99%

Regional Differences in Human Intestinal Drug Metabolism

et al. 2018

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The intestines are key for the absorption of nutrients and water as well as drug metabolism, and it is well known that there are clear differences in the expression profile of drug metabolism enzymes along the intestinal tract. Yet only a few studies have thoroughly investigated regional differences in human intestinal drug metabolism. In this study, we evaluated phase I and phase II metabolism in matched human ileum and colon precision-cut intestinal slices (PCIS). To this end, human PCIS were incubated for 3 hours with testosterone and 7-hydroxycoumarin (7-HC) to examine phase I and phase II metabolism, respectively. Metabolite formation was assessed by high-performance liquid chromatography analysis.Our results demonstrated that androstenedione, 6b-hydroxytestosterone, 2b-hydroxytestosterone, and 7-HC sulfate were predominantly formed in the ileum, while 15a-hydroxytestosterone and 7-HC glucuronide were mainly produced in the colon. Moreover, we also observed sex differences in phase II metabolite formation, which appeared to be higher in men compared with women. Taken together, we demonstrated that phase I metabolism predominantly occurs in ileum PCIS, while phase II metabolism mostly takes place in colon PCIS. Moreover, we revealed that human PCIS can be used to study both regional and sex differences in intestinal metabolism. This work was supported by De Nederlandse organisatie voor gezondheidsonderzoek en zorginnovatie (ZonMW)-The Netherlands [Grant 114025003]. https://doi.org/10.1124/dmd.118.083428.s This article has supplemental material available at dmd.aspetjournals.org.

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Section: Downloaded Frommentioning

confidence: 99%

Regional Differences in Human Intestinal Drug Metabolism

et al. 2018

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“…As with all oral drugs, initial doses are predicated on normal gastrointestinal absorption. The replacement dose may need to be increased if the patient has gastrointestinal disease or surgery resulting in malabsorption (154, 257). …”

Section: Adrenal Insufficiencymentioning

confidence: 99%

Physiological Basis for the Etiology, Diagnosis, and Treatment of Adrenal Disorders: Cushing's Syndrome, Adrenal Insufficiency, and Congenital Adrenal Hyperplasia

Raff

Sharma

Nieman

2014

Comprehensive Physiology

127

105

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The hypothalamic-pituitary-adrenal (HPA) axis is a classic neuroendocrine system. One of the best ways to understand the HPA axis is to appreciate its dynamics in the variety of diseases and syndromes that affect it. Excess glucocorticoid activity can be due to endogenous cortisol overproduction (spontaneous Cushing’s syndrome) or exogenous glucocorticoid therapy (iatrogenic Cushing’s syndrome). Endogenous Cushing’s syndrome can be subdivided into ACTH-dependent and ACTH-independent, the latter of which is usually due to autonomous adrenal overproduction. The former can be due to a pituitary corticotroph tumor (usually benign) or ectopic ACTH production from tumors outside the pituitary; both of these tumor types overexpress the proopiomelanocortin gene. The converse of Cushing’s syndrome is the lack of normal cortisol secretion and is usually due to adrenal destruction (primary adrenal insufficiency) or hypopituitarism (secondary adrenal insufficiency). Secondary adrenal insufficiency can also result from a rapid discontinuation of long-term, pharmacological glucocorticoid therapy because of HPA axis suppression and adrenal atrophy. Finally, mutations in the steroidogenic enzymes of the adrenal cortex can lead to congenital adrenal hyperplasia and an increase in precursor steroids, particularly androgens. When present in utero, this can lead to masculinization of a female fetus. An understanding of the dynamics of the HPA axis is necessary to master the diagnosis and differential diagnosis of pituitary-adrenal diseases. Furthermore, understanding the pathophysiology of the HPA axis gives great insight into its normal control.

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“…NSAIDs should be avoided in patients with restrictive type procedures due to potential direct irritation of the gastric lining. [17]…”

Section: Bariatric Surgery Outcomesmentioning

confidence: 99%

Bariatric Surgery and the Neuro-Ophthalmologist

Moss

2016

Journal of Neuro-Ophthalmology

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Background As the prevalence of obesity increases, so are the prevalences of weight related diseases and the incidence of surgical procedures to promote weight loss. It is important for neuro-ophthalmologists to be familiar with these procedures and possible downstream effects on afferent and efferent visual function. Evidence acquisition Review of ophthalmology, neurology, general surgery, obesity, endocrinology, nutrition, psychiatry and neurosurgery literature. Results Bariatric surgery is a safe and effective treatment for weight loss in obese individuals. There is level IV evidence that it is associated with improvement in idiopathic intracranial hypertension(IIH). Laboratory nutrient deficiencies are common following some types of bariatric procedures. Symptomatic deficiencies are less common but can be devastating. Thiamine deficiency can cause nystagmus and other symptoms in weeks to months following surgery, B12 or copper deficiency can cause optic neuropathy in the years to decades following bariatric surgery. Conclusions Bariatric surgery may be a treatment for IIH. Postoperative vitamin deficiencies may present with nystagmus, optic neuropathy, nyctalopia and/or ophthalmoparesis weeks to years after surgery.

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Consequences of Gastrointestinal Surgery on Drug Absorption

Cited by 37 publications

References 53 publications

Regional Differences in Human Intestinal Drug Metabolism

Regional Differences in Human Intestinal Drug Metabolism

Physiological Basis for the Etiology, Diagnosis, and Treatment of Adrenal Disorders: Cushing's Syndrome, Adrenal Insufficiency, and Congenital Adrenal Hyperplasia

Bariatric Surgery and the Neuro-Ophthalmologist

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