Drug-induced liver injury (DILI) is complicated and difficult to predict. It has been observed that drugs with extensive hepatic metabolism have a higher likelihood of causing DILI. Cytochrome P450 (P450) enzymes are primarily involved in hepatic metabolism. Identifying the associations of DILI with drugs that are P450 substrates, inhibitors, or inducers will be extremely helpful to clinicians during the decision-making process of caring for a patient suspected of having DILI. We collected metabolism data on P450 enzymes for 254 orally administered drugs in the Liver Toxicity Knowledge Base Benchmark Dataset with a known daily dose, and applied logistic regression to identify these associations. We revealed that drugs that are substrates of P450 enzymes have a higher likelihood of causing DILI [odds ratio (OR), 3.99; 95% confidence interval (95% CI), 2.07-7.67; P < 0.0001], which is dose-independent, and drugs that are P450 inhibitors have a higher likelihood of generating DILI only when they are administered at high daily doses (OR, 6.03; 95% CI, 1.32-27.5; P = 0.0098). However, drugs that are P450 inducers are not observed to be associated with DILI (OR, 1.55; 95% CI, 0.65-3.68; P = 0.3246). Our findings will be useful in identifying the suspected medication as a cause of liver injury in clinical settings.
Osteoporosis and hypertension are two frequent diseases among the aging population that share a similar etiopathology and often coexist. Moreover, treatment of hypertension affects bone mineral density and, therefore, can worsen osteoporosis. This narrative review considers the influence of the main etiologic factors that contribute to the development of hypertension and osteoporosis and examines the effect of the most often used antihypertensives on bones. A computerized literature search of relevant English publications regarding the etiology of hypertension and osteoporosis as well as the impact of antihypertensives on osteoporosis from 1996 to 2011 was completed in October 2011. The latest update in the search was performed from May to June 2012. The most relevant nongenetic factors in the etiology of osteoporosis and hypertension are low calcium intake, vitamin D and vitamin K deficiency, high consumption of sodium salt, and the effects of different forms of nitric oxide. Thiazide diuretics are the only antihypertensives that have a positive influence on bone mineral density. For other antihypertensive drugs, the data are conflicting, indicating that they may have a potentially negative or positive influence on bone mineral density and fracture risk reduction. Some studies did not find a correlation between the use of antihypertensives and bone mineral density. Due to the frequent coexistence of hypertension and osteoporosis, when selecting long-term antihypertensive therapy the potential effects of antihypertensive drugs on development, worsening, or improvement of osteoporosis should also be considered.
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