Gastrointestinal drugs case study

A review of case reports, clinical trials, post-marketing surveillance, and drug monitoring studies concurrently showed that the most common side effects were gastrointestinal, dizziness/confusion, and sedation (Ernst et al. 1998). Importantly, the side effects of hypericum in this study were comparable to placebo levels. A pharmacokinetic study showed that plasma levels of up to 300 ng/ml were well tolerated. Headache occured in one subject who was taking 1200 mg extract (59 mg hyperforin, plasma cone. >400 ng/ml) (Biber et al. 1998). 

Gastrointestinal complaints (eg, nausea, diarrhea, vomiting, flatulence) are the most common adverse effects but rarely require discontinuation of therapy. Other potential adverse effects include headache and asthenia. Tenofbvir-associated proximal renal tubulopathy causes excessive renal phosphate and calcium losses and 1-hydroxylation defects of vitamin D, and preclinical studies in several animal species have demonstrated bone toxicity (eg, osteomalacia). Monitoring of bone mineral density should be considered with long-term use in those with risk factors for or with known osteoporosis, as well as in children. Reduction of renal function over time, as well as cases of acute renal failure and Fanconi s syndrome, have been reported in patients receiving tenofovir alone or in combination with emtricitabine. For this reason, tenofovir should be used with caution in patients at risk for renal dysfunction. Tenofovir may compete with other drugs that are actively secreted by the kidneys, such as cidofovir, acyclovir, and ganciclovir. 

Numerous cases exist in the pharmaceutical field in which pH control of drug delivery may be beneficial. For example, the ability to store a drug molecule in the dry state in a polymer, to be released when the polymer reaches a region in the gastrointestinal tract that is characterized by a certain pH range (acidic in stomach, alkaline in the small intestine) has prompted a number of researchers to study pH-sensitive polymer gels as potential drug carriers for oral delivery [1-4]. 

If the drug is insoluble in water, suspensions have to be administered. In such cases vehicles like sesame oil, hydroxy-methyl-cellulose or hydroxy-ethyl-cellulose can be used. The selection of the vehicle is a critical issue because of inherent toxicity of the vehicle used frequently for kinetic and metabolism studies (e.g. vehicles which form metabolically oxalic acid). Natural oils such as sesame or com oil can be used. However, it should be checked whether the use of oily vehicles alters the gastrointestinal absorption due to their laxative properties and whether oily vehicles can cause oil granulomas (reaction to oily vehicles in the reticulo-endothelial system) in case of parenteral administration. 

The anticholinergic effects of imipramine and other tricyclic antidepressants can delay gastrointestinal motility enough to interfere with the absorption of various other drugs. Such was the case in an experimental study of the absorption of levodopa in four healthy subjects (177). It is likely that this effect may interfere with absorption of other drugs, especially those, such as chlorpromazine, that are extensively metabolized in the gut. 

Whether elderly patients taking lithium received proper monitoring was questioned in a case note audit of 91 patients, over 40% of whom had deviations from practice standards. These included absence of pretreatment laboratory tests, infrequent monitoring of serum lithium concentrations, lack of adequate adverse effects documentation, and the use of risky concomitant drugs (403). In a placebo-controlled study, there was poor tolerance of hthium augmentation of antidepressants in 76% (13/17) of elderly (mean age 70 years) patients at a mean serum concentration of 0.63 mmol/1, due to tremor and muscle twitches, cognitive disturbance, tiredness and sedation, and gastrointestinal upsets (404). 

Evans JM, McMahon AD, McGilchrist MM, White G, Murray FE, McDevitt DG, MacDonald TM. Topical nonsteroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation a record linkage case-control study. BMJ 1995 311(6996) 22-6. 

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