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British Journal of Pharmacology Mar 2020The first clinically relevant reports of preparations of St. John's wort (SJW), a herbal medicine with anti-depressant effects, interacting with other drugs, altering... (Review)
Review
The first clinically relevant reports of preparations of St. John's wort (SJW), a herbal medicine with anti-depressant effects, interacting with other drugs, altering their bioavailability and efficacy, were published about 20 years ago. In 2000, a pharmacokinetic interaction between SJW and cyclosporine caused acute rejection in two heart transplant patients. Since then, subsequent research has shown that SJW altered the pharmacokinetics of drugs such as digoxin, tacrolimus, indinavir, warfarin, alprazolam, simvastatin, or oral contraceptives. These interactions were caused by pregnane-X-receptor (PXR) activation. Preparations of SJW are potent activators of PXR and hence inducers of cytochrome P450 enzymes (most importantly CYP3A4) and P-glycoprotein. The degree of CYP3A4 induction correlates significantly with the hyperforin content in the preparation. Twenty years after the first occurrence of clinically relevant pharmacokinetic drug interactions with SJW, this review revisits the current knowledge of the mechanisms of action and on how pharmacokinetic drug interactions with SJW could be avoided. LINKED ARTICLES: This article is part of a themed section on The Pharmacology of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.6/issuetoc.
Topics: Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Herb-Drug Interactions; Humans; Hypericum; Phytotherapy; Plant Preparations
PubMed: 31742659
DOI: 10.1111/bph.14936 -
Expert Opinion on Drug Safety Sep 2019: Efficient antiretroviral-treatment (ART) generally allows control of HIV infection. However, persons-living-with-HIV (PLWH), when aging, present a high prevalence of... (Review)
Review
: Efficient antiretroviral-treatment (ART) generally allows control of HIV infection. However, persons-living-with-HIV (PLWH), when aging, present a high prevalence of metabolic diseases. : Altered adiposity, dyslipidemias, insulin resistance, diabetes, and their consequences are prevalent in PLWH and could be partly related to ART. : At first, personal and lifestyle factors are involved in the onset of these complications. The persistence of HIV in tissue reservoirs could synergize with some ART and enhance metabolic disorders. Altered fat repartition, diagnosed as lipodystrophy, has been related to first-generation nucleoside-reverse-transcriptase-inhibitors (NRTIs) (stavudine zidovudine) and some protease inhibitors (PIs). Recently, use of some integrase-inhibitors (INSTI) resulted in weight/fat gain, which represents a worrisome unresolved situation. Lipid parameters were affected by some first-generation NRTIs, non-NRTIs (efavirenz) but also PIs boosted by ritonavir, with increased total and LDL-cholesterol and triglycerides. Insulin resistance is common associated with abdominal obesity. Diabetes incidence, high with first-generation-ART (zidovudine, stavudine, didanosine, indinavir) has declined with contemporary ART close to that of the general population. Metabolic syndrome, a dysmetabolic situation with central obesity and insulin resistance, and liver steatosis are common in PLWH and could indirectly result from ART-associated fat gain and insulin resistance. All these dysmetabolic situations increase the atherogenic cardiovascular risk.
Topics: Adipose Tissue; Anti-HIV Agents; Dyslipidemias; Glucose; HIV Infections; Humans; Life Style; Lipid Metabolism; Metabolic Diseases; Risk Factors
PubMed: 31304808
DOI: 10.1080/14740338.2019.1644317 -
Clinical Kidney Journal Apr 2014Drug-induced renal calculi represent 1-2% of all renal calculi. In the last decade, drugs used for the treatment of HIV-infected patients have become the most frequent... (Review)
Review
Drug-induced renal calculi represent 1-2% of all renal calculi. In the last decade, drugs used for the treatment of HIV-infected patients have become the most frequent cause of drug-containing urinary calculi. Among these agents, protease inhibitors (PIs) are well known to induce kidney stones, especially indinavir and atazanavir, and more recently darunavir. Urolithiasis attributable to other PIs has also been reported in clinical cases such as those during non-PI use. Antiretroviral drug-induced calculi deserve consideration because most of them are potentially preventable. This article summarizes the diagnosis, epidemiology, prevention and management of antiretroviral drug-induced urolithiasis.
PubMed: 25852859
DOI: 10.1093/ckj/sfu008 -
Journal of the American Society of... Mar 2015Crystalline nephropathy refers to renal parenchymal deposition of crystals leading to kidney damage. The most common forms of crystalline nephropathy encountered in...
Crystalline nephropathy refers to renal parenchymal deposition of crystals leading to kidney damage. The most common forms of crystalline nephropathy encountered in renal pathology are nephrocalcinosis and oxalate nephropathy. Less frequent types include urate nephropathy, cystinosis, dihydroxyadeninuria, and drug-induced crystalline nephropathy (e.g., caused by indinavir or triamterene). Monoclonal proteins can also deposit in the kidney as crystals and cause tissue damage. This occurs in conditions such as light chain proximal tubulopathy, crystal-storing histiocytosis, and crystalglobulinemia. The latter is a rare complication of multiple myeloma that results from crystallization of monoclonal proteins in the systemic vasculature, leading to vascular injury, thrombosis, and occlusion. In this report, we describe a case of crystalglobulin-induced nephropathy and discuss its pathophysiology and the differential diagnosis of paraprotein-induced crystalline nephropathy.
Topics: Biopsy; Crystallization; Female; Humans; Kidney; Kidney Diseases; Middle Aged; Multiple Myeloma; Serum Globulins
PubMed: 25190731
DOI: 10.1681/ASN.2014050509 -
The American Journal of Medicine Apr 1999Several medications--notably acyclovir, sulfonamides, methotrexate, indinavir, and triamterene--are associated with the production of crystals that are insoluble in... (Review)
Review
Several medications--notably acyclovir, sulfonamides, methotrexate, indinavir, and triamterene--are associated with the production of crystals that are insoluble in human urine. Intratubular precipitation of these crystals can lead to acute renal insufficiency. Many patients who require treatment with these medications have additional risk factors, such as true or effective intravascular volume depletion and underlying renal insufficiency, that increase the likelihood of drug-induced intrarenal crystal deposition. Acute renal failure in this setting may be preventable if it is anticipated by appropriate drug dosing, volume expansion with high urinary flow, and alkalinization of the urine when appropriate. Renal failure may be reversible if the drug is discontinued, and by volume repletion and alkalinization of the urine when appropriate. Management of established renal insufficiency includes volume repletion, dialytic support if necessary, adjustment of drug doses, and avoidance of further exposure to nephrotoxins.
Topics: Acute Kidney Injury; Acyclovir; Humans; Indinavir; Kidney; Methotrexate; Risk; Sulfonamides; Triamterene
PubMed: 10225250
DOI: 10.1016/s0002-9343(99)00041-8