Toxicology of oral antidiabetic medications

Spiller, Henry A.

doi:10.2146/ajhp050500

Cited by 103 publications

(116 citation statements)

References 113 publications

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“…In the reported patient of ours, the initial discontinuing of tenofovir was appropriate not only because of potential role of this drug in causing a (rare) acute-onset kidney failure (similar to Fanconi's disease in its clinical features), but also because of the drug's prolonged half-life, which is expected during a potentially severe renal insufficiency [10,18,43,62,63,76,79,83]. In addition, it seemed essential to discontinue immediately the anti-hypertensive ACE-inhibitor drug [128], the loop diuretic furosemide, obviously the NSAIDs [10,18,19,43,60,76,93], and maybe metformin too [129,130], which may be associated with severe lactacidemia, regardless of its intrinsic renal safety profile [130]. The therapeutic approach is focused on providing a well "tailored" intravascular fluid intake and control, and to re-calibrate all fluid and electrolytes delivery on the basis of a continuous clinical and laboratory monitoring.…”

Section: Discussionmentioning

confidence: 99%

“…With regard to acute or chronicprogressive loss of renal function in persons living with HIV and taking cART, tenofovir was the only known "intrinsically" nephrotoxic anti-HIV agent taken by our patient before its episode of acute kidney failure, but it was carefully re-challenged and proved perfectly safe in our case (until a 16-month follow-up period after the acute episode), and played its key role in both prior and subsequent triple "classical" cART regimens, even after the acute kidney injury episode [5,8,10,18,19,36,[37][38][39][40][41][42][43][44]47,[57][58][59][60][61][62][63]85,86,110]. The described episode of acute-onset kidney failure might have been favored by a broad spectrum of causes acting concurrently with HIV itself, and all underlying and overwhelming diseases, to lead at some point to a somewhat "critically" impaired renal activity [111], which may be followed by a po-tentially life-threatening "cascade" of events, such as metabolic acidosis and lactic acidosis plus hypokalemia and other potentially severe electrolyte and acid-base status imbalances [110,112], which are already well known adverse events of many HIV-associated medications [10,18,32,54,62], and may be prompted by the concurrent (ab)use of very common drugs, including trivial diuretics and some anti-hypertensive compounds, as well as oral antidiabetics like metformin, and NSAIDs at least. Just these insuline-sensitizing drugs are of extremely frequent use in the metabolic syndrome and related issues [48,…”

Section: Lifetime Pharmacological Treatmentsmentioning

confidence: 99%

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Kidney failure during HIV disease treated with tenofovir, multiple concurrent diseases and drug therapies

Manfredi¹,

Calza

Colangeli

et al. 2012

RHC

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A significant case report of a HIV infected patient in his fifties who experienced an excellent virological and immunological response to antiretroviral therapy (which has been modified just to prevent or avoid some adverse events), but developed a severe, sudden acute kidney failure while under a polypharmacy due to some underlying and overwhelming disorders (i.e. arterial hypertension, non-insulin-dependent diabetes mellitus, a recent acute heart infarction with remarkable remnants, and finally an anecdotal muscle-joint pain with self-prescription of non-steroideal anti-inflammatory drugs), represents the key point for a debate around the increasing frequency of "polypharmacy" in the field of HIV infection, even when HIV resistance to antiretroviral is not a concern. The continuing increase of mean age of HIV-infected population, plus the existing, sometimes unmodifiable risk factors for cardiovascular, dysmetabolic, and renal disorders, plus the adjunct of anecdotal illnesses prompting the resort to different drugs and medications, either prescribed for HIV infection itself, or taken for concurrent or subsequent diseases, or self-prescribed occasionally due to an intercurrent, trivial disorders per se, may prompt a complicated scenario culminating with a lifethreatening acute renal failure of tubular origin. Our report gives us the opportunity to revise and discuss the expected interactions between antiretroviral therapy and the even growing exposure to multiple different drug and drug classes, which may be responsible for relevant drug interactions and direct or adjunctive end-organ impairment, up to life-threatening conditions, which may be avoided or prevented by considering carefully all comorbidites and co-treatments potentially administered to HIV infected patients, thirty years after the discovery of AIDS.

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Section: Discussionmentioning

confidence: 99%

Section: Lifetime Pharmacological Treatmentsmentioning

confidence: 99%

Kidney failure during HIV disease treated with tenofovir, multiple concurrent diseases and drug therapies

Manfredi¹,

Calza

Colangeli

et al. 2012

RHC

View full text Add to dashboard Cite

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“…Compared with chronic toxicity, acute overdose reportedly has higher mortality [1, 2]. Diagnosis of metformin overdose is difficult because of unreliable information and nonspecific symptoms such as tachycardia, hypotension, tachypnea, and altered mental status [3]. In addition, metformin concentration is not routinely measured in the clinical setting.…”

Section: Introductionmentioning

confidence: 99%

Early Initiation of Hemodialysis for Progressive Lactic Acidosis in a Diabetic Patient

Nyunoya¹,

Hayase²,

Doi³

et al. 2018

Case Rep Acute Med

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Metformin, a widely used medicine for diabetes mellitus, is well known to cause lactic acidosis, which may require intensive care, including hemodialysis, especially in severe cases because of the high mortality rate. Because metformin is effectively removed by renal replacement therapy, early initiation of hemodialysis is crucial for metformin overdose. We report a case of a 38-year-old male who was brought to our emergency department (ED) with altered mental status. He subsequently developed severe lactic acidosis with a peak lactate level of 33.4 mmol/L. No clear etiology was identified for these critical conditions at the ED. Although metformin intoxication could not be confirmed at this time, we decided to start hemodialysis immediately. Soon after hemodialysis, blood pH and lactate levels dramatically improved. The patient fully recovered after 9 days of intensive care unit (ICU) stay. Later on, his serum metformin concentration was revealed to be 146 μg/mL and 26 μg/mL at ICU admission and after dialysis at day 3, respectively (therapeutic range, 1–2 μg/mL). Early initiation of hemodialysis might be beneficial for diabetic patients with unexplained severe lactic acidosis despite uncertainties in history of overdose or serum concentration of metformin.

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“…Apart from having a number of side effects, the oral synthetic hypoglycemic agents have not been able to maintain euglycemia and to control long-term microvascular and macrovascular complications [3]. Due to toxicity and side effects of oral antidiabetic agents available, use of herbal medicines for the treatment of diabetes has gained importance throughout the world [4]. The World Health Organization also recommended and encouraged the practice of herbal medicine especially in countries where access to the conventional treatment of diabetes is not adequate [5].…”

Section: Introductionmentioning

confidence: 99%

In Vivo Anti-Diabetic Activity Evaluation of the Bark of Cascabela Thevetia L. In Streptozotocin Induced Diabetic Rats

Gogoi

Bhuyan

2017

Int J Pharm Pharm Sci

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Objective: In this study, the plant Cascabela thevetia L. was selected based on ethnomedicinal documentation reports for evaluation of the antidiabetic activity. The aim of this study was to carry out acute toxicity study and in vivo evaluation of antidiabetic activity in an animal model. Methods:Firstly direct extraction of the dried bark powder was done with methanol using soxhlet apparatus. After collecting the extract, acute toxicity study was performed according to OECD (Organization for Economic Cooperation and Development) guideline 425. For in vivo evaluation of antidiabetic activity, streptozotocin (STZ) and nicotinamide induced type 2 diabetic male rat model was used. Six groups containing six animals in each were taken for the in vivo study and marked as normal control, standard control, negative control and test controls. For all the animals body weight, body temperature, blood glucose levels were determined at an interval of 5 d. After 15 d of treatment different biochemical parameters like triglyceride, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), alkaline phosphatase level (ALP), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), total protein were determined and the results were evaluated by statistically using one-way analysis of variance (ANOVA). On the 15 th day, all the animals were sacrificed and histopathological study of pancreases tissue was done. Results:The effects of the test extracts in lowering the blood glucose level and maintaining other biochemical parameters in the test groups were compared with the effect of standard drug metformin hydrochloride, 10 mg/kg body weight treated group and negative control group. The data were statistically evaluated using one-way analysis of variance (ANOVA) followed by Dunnet comparison all vs control method and taking significant at p<0.01. By comparing different biochemical parameters and histoarchitecture of the different test groups of animals, it was found that group V treated with 200 mg/kg body weight shows a significant effect. Conclusion:After performing the experiment it was found that the bark of Cascabela thevetia L. has the potential for blood glucose lowering activity and able to control abnormal lipids and enzymes level in blood. Further isolation of the compounds can lead to finding out the exact compound responsible for the activity.

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Toxicology of oral antidiabetic medications

Abstract: The toxicity of oral antidiabetic agents differs widely in clinical manifestations, severity, and treatment.

Cited by 103 publications

References 113 publications

Kidney failure during HIV disease treated with tenofovir, multiple concurrent diseases and drug therapies

Kidney failure during HIV disease treated with tenofovir, multiple concurrent diseases and drug therapies

Early Initiation of Hemodialysis for Progressive Lactic Acidosis in a Diabetic Patient

In Vivo Anti-Diabetic Activity Evaluation of the Bark of Cascabela Thevetia L. In Streptozotocin Induced Diabetic Rats

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