Clinical Medicine. Therapeutics

The dopamine agonist pramipexole (PRA) ((S)-2-Amino-4,5,6,7-tetrahydro-6-(propylamino) benzothiazole dihydrochloride; molecular formula C 10 H 17 N 3 S-2(HCl), is a D 3 selective compound, approved in 1997 for the treatment of Parkinson disease and in 2006 for that of idiopathic restless legs syndrome (RLS). Because of its tolerability, safety and half-life, PRA is favored over levodopa and on the other ergot derivate dopamine agonists, and it is considered nowadays one of the first choices in the therapy of RLS. PRA is rapidly and completely absorbed after oral administration, its protein binding is around 15%, it is almost unaffected by hepatic metabolism and excreted by urine unchanged. PRA has a linear pharmacokinetics, with a half-life ranging between 8 and 14 hours. Double-blind, placebo-controlled studies demonstrated that PRA, even at low dosages and since the first nights of administration, is significantly effective on the typical sensitive symptoms of RLS, on the periodic leg movements during sleep, and in improving the quality of life of patients with RLS. A subjective improvement of sleep quality is usually also reported by the patients, but the polysomnographic assessment gave less solid results on objective sleep parameters. The most common PRA related side effects include headache, nausea and orthostatic hypotension. Data on the long-term therapy of PRA in RLS, and on the efficacy of PRA in symptomatic forms of RLS are warranted to better delineate the role of PRA in RLS treatment.

Mauro Manconi

Luigi Ferini-Strambi

Clinical Medicine Therapeutics

Pharmacotherapy of Restless Legs Syndrome with Pramipexole

普拉克索治疗不安腿综合征的药物疗法

Imiquimod (trade name Aldara™) is a small molecule of the imidazoquinoline family, a group of nucleoside analogs that were first synthesized as potential antiviral agents. It has since been discovered to activate both innate and adaptive immunity, as well as apoptosis. Clinically, it has been approved for three indications thus far: external genital warts, actinic keratosis, and superficial basal cell carcinoma. In addition to these applications, a number of off-label uses have been reported in the literature. In this review, we summarize and discuss the literature describing imiquimod's mechanism of action, its approved and off-label clinical uses, and its safety and tolerability.

Jubin Ryu

F. Clarissa Yang

A Review of Topical Imiquimod in the Management of Basal Cell Carcinoma, Actinic Keratoses, and Other Skin Lesions

局部咪喹莫特在基底细胞癌、光化性角化病及其他皮肤病变管理中的回顾

Three different classes of specific therapy exist for pulmonary arterial hypertension. Ambrisentan belongs to the endothelin receptor antagonist (ERA) class of drugs, which inhibit the action of Endothelin-1; a potent vasoconstrictor and mitogen. Unlike bosentan and sitaxentan, it has a propanoic-acid based structure and like sitaxentan it has selective affinity for type A Endothelin receptors. Two large randomized controlled trials (ARIES-1 and ARIES-2) have demonstrated clinical benefit with ambrisentan in pulmonary arterial hypertension by repeated measurement of 6-minute walk distance. The most common adverse effect associated with ambrisentan use is peripheral edema, the incidence of liver enzyme elevation seen is lower than for other ERAs. Ambrisentan is safe in combination with warfarin and sildenafil. It offers further flexibility in the treatment of PAH as monotherapy and in combination. Although encouraging, trial data do not exhibit improved efficacy compared with other ERAs or sildenafil and there are no direct comparison studies. Long-term outcome data, including subgroup analysis are awaited to see if there are particular benefits of this therapy in PAH.

Christopher J Valerio

Peter Kabunga

John G Coghlan

Safety and Efficacy of Ambrisentan in the Treatment of Pulmonary Arterial Hypertension

安立生坦治疗肺动脉高压的安全性与疗效

Bone loss and its associated risk of fracture is a serious long-term health issue for breast cancer and prostate cancer survivors. Hormone ablation therapy, in particular aromatase inhibitors (AIs) for breast cancer and androgen deprivation therapy (ADT) for prostate cancer, causes marked reduction in circulating estrogen or testosterone levels, resulting in increased bone resorption, decreased bone mineral density (BMD), and an increased risk of fragility fracture. In several clinical trials with small sample sizes and short follow-up periods, oral and intravenous bisphosphonates have been shown to improve BMD, but not actual fracture rates, in cancer patients on hormone ablation therapy. A number of professional organizations and expert panels recommend the use of bisphosphonates for selected patients at risk. Although bisphosphonates are generally well tolerated, physicians should be aware of safety concerns, including the risk of osteonecrosis of the jaw. With the growing number of older breast and prostate cancer survivors, additional research is needed to characterize patients who would benefit from pharmacotherapy and optimize strategies to prevent cancer treatment-induced bone loss.

Kouta Ito

Pharmacotherapy Options in Cancer Treatment-induced Bone Loss: Focus on Bisphosphonates

癌症治疗相关骨丢失的药物治疗选择：以双膦酸盐为重点

The first selective I f current inhibitor, ivabradine, lowers heart rate (HR) at rest and during exercise with no vasomotor, negative inotropic, or negative lusitropic effects. Given that elevated resting HR is a key factor in the onset of myocardial ischemia and a strong independent predictor of cardiovascular outcomes, ivabradine provides new therapeutic prospects in coronary artery disease (CAD). Its selective HR-lowering action has proven anti-ischemic and anti-anginal efficacy, and ivabradine is currently indicated for the symptomatic treatment of stable angina pectoris. Ivabradine can also be safely combined with other anti-anginal agents, and addition of ivabradine to beta-blocker therapy further improves anti-ischemic efficacy and exercise capacity of patients with stable angina. The recent BEAUTIFUL trial demonstrated that although the primary endpoint was not met in the overall population, addition of ivabradine on top of standard preventive treatments significantly reduced the risk of coronary events in stable CAD patients with left ventricular systolic dysfunction among the subgroup of patients with a resting HR ≥ 70 bpm. This is in accordance with pre-clinical data showing that long-term HR reduction improves endothelial function and reduces the progression of atherosclerosis. A significant proportion of patients with stable angina have elevated resting HR and ivabradine should therefore be considered as an important therapy in these cases. In combination with other standard treatments, ivabradine can improve angina and could potentially improve coronary outcomes. Ongoing and future clinical studies will evaluate the presence and magnitude of the cardioprotective benefits of HR lowering with ivabradine in patients with cardiovascular diseases.

Jean-Claude Tardif

Safety and Efficacy of Ivabradine in the Management of Stable Angina Pectoris

伊伐布雷定在稳定型心绞痛管理中的安全性和有效性

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Clinical Medicine. Therapeutics

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Pharmacotherapy of Restless Legs Syndrome with Pramipexole

A Review of Topical Imiquimod in the Management of Basal Cell Carcinoma, Actinic Keratoses, and Other Skin Lesions

Safety and Efficacy of Ambrisentan in the Treatment of Pulmonary Arterial Hypertension

Pharmacotherapy Options in Cancer Treatment-induced Bone Loss: Focus on Bisphosphonates

Safety and Efficacy of Ivabradine in the Management of Stable Angina Pectoris

Pharmacotherapy of Restless Legs Syndrome with Pramipexole

A Review of Topical Imiquimod in the Management of Basal Cell Carcinoma, Actinic Keratoses, and Other Skin Lesions

Safety and Efficacy of Ambrisentan in the Treatment of Pulmonary Arterial Hypertension

Pharmacotherapy Options in Cancer Treatment-induced Bone Loss: Focus on Bisphosphonates

Safety and Efficacy of Ivabradine in the Management of Stable Angina Pectoris