HMG-CoA Reductase Inhibitors (Statins) and their Drug Interactions Involving CYP Enzymes, P-glycoprotein and OATP Transporters-An Overview.

BACKGROUND: Hydroxymethyl glutaryl-CoA (HMG-CoA) reductase inhibitors (Statins) are used to treat dyslipidemia. Generally, the statins are the substrates of CYP enzymes, P-glycoprotein (P-gp), and organic anion transporting polypeptides transporters (OATP1B1). OBJECTIVE: This review article focuses on the clinical significance of statins, and their interactions in real practice. METHODS: The databases like Medline/PubMed Central/PubMed, Google Scholar, Science Direct, Cochrane Library, Directory of open access journals (DOAJ), and reference lists were searched to identify relevant articles. RESULTS: Most of the drug interactions of statins result in elevated plasma concentrations and toxicity of statins due to the inhibition of CYP3A4, P-gp and/or OATP1B1 transporters. The toxicity of statins includes myopathy, rhabdomyolysis, elevated liver enzymes, acute kidney injury, and diabetes. The statins like simvastatin, lovastatin, and atorvastatin are substrates of CYP3A4 enzyme and P-glycoprotein and their concomitant use with the drugs inhibiting or inducing them would result in changes in plasma concentrations and toxicity/efficacy. However, the statins like pravastatin, rosuvastatin and pitavastatin are not substrates of CYP enzymes and hence the concomitant use of CYP inhibitors or inducers does not affect them. Almost all the statins are the substrates of OATP1B1 transporter, and the co-prescription of inhibitors of OATP1B1 elevates the plasma concentrations and muscle toxicity of statins. CONCLUSION: Understanding the interacting potential of each statin will enable the prescribers, pharmacists, and other health care professionals to use statins effectively without compromising patient safety.

Nigella Sativa (Black Seeds), A Potential Herb for the Pharmacotherapeutic Management of Hypertension - A Review.

Hypertension is one of the leading risk factors for stroke, myocardial infarction and untimely death. The prevalence of hypertension is extremely high among the global population, and many of them depend on modern medicines to manage their blood pressure. The modern antihypertensive medications include angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), diuretics, beta-adrenergic blockers, direct renin inhibitors, direct-acting vasodilators, alpha-adrenergic blockers and centrally acting drugs that are associated with many harmful and undesirable effects. The patients may consider traditional herbal medicines as a good strategy to manage chronic conditions due to the reasons such as perceived failure of allopathic medicines, relatively high cost of allopathic medicines, social-cultural practices and/or herbal knowledge, poor access to medical facilities and safety concerns about modern medicines. Nigella sativa (Black seeds) has been used to treat various conditions, including hypertension, obesity, diabetes, cancer, etc. Hence, the antihypertensive potential of N. sativa is analyzed in this review. The literature was searched in databases including Medline/PMC/PubMed, Google Scholar, ScienceDirect, Directory of Open Access Journals (DOAJ) and reference lists to identify articles associated with antihypertensive properties of N.sativa. Numerous randomized controlled trials and animal studies reported that N.sativa has potential antihypertensive effects. Hence, N. sativa could be used effectively to manage patients with stage 1 hypertension, and the patients using modern antihypertensive medications could reduce their doses by adding N. sativa into their regimen as adjuvant therapy.

Pharmacokinetic Approach of Clinically Important Drug Interactions of Hormonal Contraceptives - A Review.

Hormonal contraceptives contain an Estrogen and/or a Progestin, which are the substrates of the CYP3A4 enzyme and the drugs inducing the CYP3A4 enzyme can decrease the plasma concentrations and thereby therapeutic efficacy of Hormonal contraceptives resulting in unintended pregnancy. Moreover, the hormonal contraceptives associated risk of thrombotic events are further exacerbated by the simultaneous administration of drugs like Tranexamic acid and tobacco smoke. Therefore, while prescribing hormonal contraception and other drugs to women, drug interactions should always be considered because there could be a possible contraceptive failure or other adverse drug effects. This article provides a summary of guidance to healthcare professionals such as prescribers and pharmacists on pharmacokinetic based interactions between hormonal contraception and other drugs.