他汀类药物对动脉粥样硬化斑块的影响

他汀类药物是一种新型降血脂药，通过竞争性抑制HMG-COA还原酶，阻断甲羟戊酸代谢的中间产物及最终产物-胆固醇的合成，降低血浆总胆固醇和LDL胆固醇，对动脉粥样硬化斑块有稳定和逆转作用。     

他汀类药物非降脂作用研究进展

他汀类药物属于羟甲基二酰辅酶A(HMG-CoA)还原酶抑制剂,其作用是通过抑制肝脏内胆固醇合成的限速酶HMG-CoA还原酶而达到减少胆固醇合成,降低胆固醇水平.目前被认为是治疗高胆固醇血症的首选药物.大剂量使用也可显著降低血清甘油三酯水平,升高高密度脂蛋白.随着研究的深入,他汀类药物的非降脂作用日益受到重视.本文对其非降脂作用的进展综述如下.     

他汀类药物临床研究进展

他汀类药物为3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶抑制药。HMG-CoA还原酶是催化胆固醇合成的限速酶,还参与如Ras蛋白的合成,以及引导原始生殖细胞的转移。他汀类药物主要作用为降低血浆低密度脂蛋白(LDL)胆固醇水平。自1987年美国FDA批准洛伐他汀上     

他汀类药物的研究进展及用药安全性

他汀类药物为羟甲基戊二酰辅酶A（HMGCoA）还原酶抑制剂，是目前临床上应用最为广泛的血脂调节药物。其主要机制是抑制胆固醇合成途径的HMG-CoA还原酶，可有效地降低血液中的低密度脂蛋白胆固醇（LDL—C）水平，且对各种类型的高脂血症均有一定疗效。     

浅谈他汀类药物治疗动脉粥样硬化

动脉粥样硬化(atherosclerosis)是一组称为动脉硬化的血管病中常见且最重要的一种,常累及各组织器官,引起严重的并发症。因此,抗动脉粥样硬化药(antiatherosclerotic drugs)的研究日益受到重视。羟甲基戊二酸单酰辅酶A(CHMG-CoA)抑制剂(他汀类药物)是目前公认的有效降低胆同醇和低密度脂蛋白胆固醇的药物,对动脉粥样硬化的治疗作用也越来越受到大家的关注。     

他汀类药物的合理应用

<正>动脉粥样硬化与脂质代谢异常密切相关,而低密度脂蛋白胆固醇(LDL-C)在其中起着重要作用。他汀类药物问世20年来,经历了大量的循证检验,不但确立作为调脂治疗的首选用药,而且也充分显示在冠心病防治方面的巨大意义,现已成为冠心病治疗不可或缺的药物。     

他汀类药物防治动脉粥样硬化机制研究进展

动脉粥样硬化 (AS)的发生与多种危险因素有关 ,血脂异常是其中最主要的一个环节。低密度脂蛋白胆固醇(LDL C)作为AS发展的关键因素已被普遍接受。以此为基础 ,以调节血清总胆固醇 (TC)和LDL C为主要目标的干预方法取得了一定成效 ,并开发和研制出他汀类药物 ,由于能有效控制TC和LDL C水平 ,在临床上得到广泛应用 ,成为有效防治血脂异常和AS的重要手段。1　他汀类药物的作用机制及调脂作用他汀类药物有共同的调节胆固醇的作用机制 ,由于这类化合物的分子结构中的部分侧链 β、δ 二羟基戊酸与HMG CoA还原酶 (胆固醇合成过程中限速…     

他汀类药物抗动脉粥样硬化研究进展

近年来,随着人们生活水平的提高和工作节奏的加快,心脑血管病的发病率和病死率都呈明显的上升态势.动脉粥样硬化是心脑血管病的主要病理基础,引起动脉粥样硬化的危险因素很多,其中脂质代谢紊乱甚为重要.3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制药（他汀类）是目前临床上应用最为广泛的调血脂药物，其降低血浆总胆固醇和低密度脂蛋白的作用已为大量临床研究所证实。目前研究认为，他汀类对心脑血管病的治疗作用还得益于多种非调脂作用，包括改善血管内皮功能、抑制血栓形成、抗炎作用、抗氧化和稳定动脉粥样硬化斑块等，他汀类的非调脂作用可能在动脉粥样硬化的防治中占有重要地位。     

他汀类药物的临床应用及不良反应

他汀类药物是治疗动脉粥样硬化的传统常规药物,不仅能够降低血脂,还具有抗炎、改善血管内皮功能、减少缺血再灌注损伤、抗氧化应激、调节神经内分泌等作用。然而长期使用他汀类药物也会出现一些不良反应。笔者对他汀类药物的临床应用及不良反应进行综述。     

他汀类药物在动脉粥样硬化治疗中的研究进展

动脉粥样硬化是心血管疾病的重要基本病变,血脂异常是导致动脉粥样硬化的主要因素.他汀类药物是临床常用的调脂药物,除此之外,他汀类药物还有改善血管内皮功能.抗血栓.抑制炎症反映.稳定斑块等作用.     

Buserelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical profile

The gonadotrophin releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH); gonadorelin] agonist buserelin is a promising new agent in the treatment of a variety of disorders in gynaecology and andrology, paediatrics and oncology. While a single dose of buserelin stimulates the release of pituitary gonadotrophins, multiple doses produce reversible pituitary desensitisation, and this specific blockade of gonadotrophin support to the gonads provides the basis for the drug's efficacy in conditions dependent on sex hormone secretion. Thus, buserelin provides comparable efficacy to orchidectomy or high dose estrogens in the treatment of hormone-sensitive prostate cancer and exhibits a lower incidence of adverse effects. During the early phase of treatment it may be particularly useful in combination with antiandrogens. Buserelin also appears promising in hormone-sensitive premenopausal breast cancer. Extensive studies have proven the value of buserelin in endometriosis, where it produces a transient remission with gradual recurrence of the disease on cessation of treatment. Surgical intervention is necessary in severe disease after buserelin-induced involution of the lesions. In patients with uterine leiomyoma, preliminary data suggest that buserelin may be beneficial in rendering surgery more conservative by reducing fibroid size, although it appears unlikely to preclude surgical intervention. The use of buserelin to induce a state of reversible hypogonadotrophism before administration of exogenous gonadotrophins is a promising strategy in the treatment of infertility associated with polycystic ovary syndrome and other conditions of infertility with underlying ovarian dysfunction; such a strategy also clearly enhances the efficiency of in vitro fertilisation programmes. Initial studies suggest its potential usefulness as a female contraceptive when administered intermittently in conjunction with a progestogen. Buserelin represents a first-line treatment of central precocious puberty. In endometriosis the adverse effect profile of buserelin is generally favourable, with hypoestrogenic effects such as hot flushes and vaginal dryness, and decreased libido, predominating. There is no apparent detrimental effect on lipid metabolism. The potential for adverse hypoestrogenic effects on bone mineral content with long term administration remains to be clarified. Thus, the GnRH agonist buserelin represents an advance in the treatment of a variety of gynaecological and andrological as well as paediatric and oncological conditions, infertility and other sex-hormone dependent conditions, with a low incidence of adverse treatment effects.     

Ceforanide. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy

Ceforanide is a 'second generation' cephalosporin administered intravenously or intramuscularly. It is similar to cefamandole and cefonicid in its in vitro superiority to 'first generation' cephalosporins against several species of Enterobacteriaceae as well as its activity against Haemophilus influenzae, including beta-lactamase-producing strains. Its activity against Staphylococcus aureus is less than that of cefamandole, cefuroxime and first generation cephalosporins. The in vitro activity against Neisseria gonorrhoeae is excellent. Pseudomonas, Acinetobacter and Serratia species, and Bacteroides fragilis are resistant, as are many strains of Proteus and Providencia species. The elimination half-life is relatively long, although shorter than that of cefonicid, and in most clinical trials ceforanide has been administered twice daily. It appeared to be comparable in therapeutic efficacy to procaine penicillin and cephazolin in the treatment of patients with community-acquired pneumonia, to cephazolin in the treatment of skin and soft tissue infections due to S. aureus or beta-haemolytic streptococci and to cefapirin in S. aureus endocarditis in parenteral drug abusers. Also, it was comparable in efficacy to cephalothin in the prophylaxis of infection in patients undergoing open heart surgery or vaginal hysterectomy, and to cephazolin in patients undergoing cholecystectomy. Thus, ceforanide is an alternative to first and certain other second generation cephalosporins in several important therapeutic and prophylactic situations. It has no advantage over other cephalosporins with regard to spectrum of antibacterial activity, but has a longer half-life than other second generation cephalosporins, except cefonicid, and can be administered according to a twice daily dosage schedule.     

Roxithromycin. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy

Roxithromycin is an acid-stable orally administered antibacterial macrolide structurally related to erythromycin. It has an in vitro antibacterial profile similar to that of erythromycin, with activity against Staphylococcus aureus, S. epidermidis, Streptococcus pneumoniae, S. pyogenes, Branhamella catarrhalis, Mycoplasma pneumoniae, Legionella pneumophila, Chlamydia trachomatis, Gardnerella vaginalis, Haemophilus ducreyi, some anaerobes and other less common pathogens. Roxithromycin has a pharmacokinetic profile that is characterised by excellent enteral absorption achieving high concentrations in most tissues and body fluids. The results of clinical studies with roxithromycin have confirmed the potential for its use in a variety of infections, which was suggested by its antibacterial activity in vitro and pharmacokinetic profile. Clinical efficacy has been confirmed in the treatment of respiratory tract infections, including community-acquired and atypical pneumonias, ear, nose and throat infections, genitourinary tract infections, and skin and soft tissue infections. In a relatively small number of patients roxithromycin has generally been shown to be as effective as erythromycin and other appropriate antibacterial drugs in some of the above indications. Roxithromycin is well tolerated and has less potential than erythromycin to produce clinically significant drug interactions. Thus, roxithromycin is an orally active drug which should prove a useful alternative when selecting antibacterial therapy for indications where macrolides are appropriate.     

Azithromycin. A review of its antimicrobial activity, pharmacokinetic properties and clinical efficacy.

Azithromycin is an acid stable orally administered macrolide antimicrobial drug, structurally related to erythromycin, with a similar spectrum of antimicrobial activity. Azithromycin is marginally less active than erythromycin in vitro against Gram-positive organisms, although this is of doubtful clinical significance as susceptibility concentrations fall within the range of achievable tissue azithromycin concentrations. In contrast, azithromycin appears to be more active than erythromycin against many Gram-negative pathogens and several other pathogens, notably Haemophilus influenzae, H. parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Urea-plasma urealyticum and Borrelia burgdorferi. Like erythromycin and other macrolides, the activity of azithromycin is unaffected by the production of beta-lactamase. However, erythromycin-resistant organisms are also resistant to azithromycin. Following oral administration, serum concentrations of azithromycin are lower than those of erythromycin, but this reflects the rapid and extensive movement of the drug from the circulation into intracellular compartments resulting in tissue concentrations exceeding those commonly seen with erythromycin. Azithromycin is subsequently slowly released, reflecting its long terminal phase elimination half-life relative to that of erythromycin. These factors allow for a single dose or single daily dose regimen in most infections, with the potential for increased compliance among outpatients where a more frequent antimicrobial regimen might traditionally be indicated. The potential disadvantage of low azithromycin serum concentrations, however, is that breakthrough bacteraemia may occur in patients who are severely ill; nevertheless, animal studies suggest that tissue concentrations of azithromycin are more important than those in serum when treating respiratory and other infections. The clinical efficacy of azithromycin has been confirmed in the treatment of infections of the lower and upper respiratory tracts (the latter including paediatric patients), skin and soft tissues (again including paediatric patients), in uncomplicated urethritis/cervicitis associated with N. gonorrhoeae, Chlamydia trachomatis or U. urealyticum and in the treatment of early Lyme disease. Azithromycin was as effective as erythromycin and other commonly used drugs including clarithromycin, beta-lactams (penicillins and cephalosporins), and quinolone and tetracycline antibiotics in some of the above infections. Some patients with acute exacerbations of chronic bronchitis due to H. influenzae may be refractory to therapy with azithromycin (as is the case with erythromycin) indicating the need for physician vigilance, although it should be noted that azithromycin is of equivalent efficacy to amoxicillin in the treatment of such patients. In the therapy of urethritis/cervicitis associated with C. trachomatis, N. gonorrhoea or U. urealyticum, a single dose azithromycin regimen offers a distinct advantage over currently available pharmacological options, while providing effective therapy.(ABSTRACT TRUNCATED AT 400 WORDS)     

Statins and osteoporosis: a clinical review

Osteoporosis is a leading public health threat affecting approximately 44 million people in the United States. Most of the therapies for this disease work to prevent further bone loss, improve bone mineral density, and reduce the risk of fractures. These agents, however, have not been proved to increase bone formation significantly. Therefore, the ideal agent would not only improve bone strength by decreasing bone breakdown, but also promote bone formation in the ultimate quest to prevent fractures. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have become an area of research in the battle against osteoporosis. Two mechanisms for beneficial effects of statins on bones have been proposed, and although in vitro, in vivo, and animal studies have shown positive effects on bone mineralization and reductions in bone resorption, clinical data on surrogate markers and fracture rates are conflicting. The inherent problems with observational studies also must be addressed. Until that time, the use of statins in the prevention of fractures or the treatment of osteoporosis requires further study.     

Methadone: a review of its pharmacokinetic/pharmacodynamic properties

During the past decades the use of methadone has been increased as a result of the interest of optimizing its therapeutics in opioid addicts, one of the groups with higher risk for AIDS infection. However standard dose of methadone are far from being the appropriate for relief pain or prevent withdrawal signs in maintenance programs in many patients. To achieve an optimal dose regimen for an individual, the knowledge of the relationship between the pharmacokinetics/pharmacodynamics (pk/pd) drug properties and the demographic and physiopathological characteristics of the subject is required. Unfortunately, there is a lack of studies dealing with the population pk/pd properties of methadone. In the current study, a review of the pk/pd properties of methadone is presented with the aim of understanding the sources of variability in response. This will help in the design of prospective pk/pd studies; in particular, individual data including sex, weight, alpha(1)-acid glycoprotein levels in plasma, concomitant medications, time after starting treatment with methadone and previous exposure to other opioids should be requested. In addition, designs for drug administration should allow the characterization of the plasma-versus-biophase distribution and the development of tolerance processes. Because methadone is usually administered as a racemic mixture, the use of enantioselective techniques to determine both enantiomers in plasma is also highly recommended.     

Ivermectin. A review of its antifilarial activity, pharmacokinetic properties and clinical efficacy in onchocerciasis.

Ivermectin, a derivative of avermectin B, is an orally effective microfilaricidal agent. It is the current drug of choice for treating patients infected with the nematode Onchocerca volvulus, which is a major cause of blindness in inhabitants of some tropical areas. Ivermectin is administered orally as a single dose of 150 micrograms/kg given annually. Skin and ocular microfilarial counts are dramatically reduced after the first dose, with some evidence for a resulting decrease in transmission of infection by the blackfly vector. With the exception of rare serious reactions such as severe systemic postural hypotension, ivermectin is generally well tolerated. The drug has the clear advantages of ease of administration and better tolerability compared with diethylcarbamazine and suramin, agents previously used to treat onchocerciasis. Thus, ivermectin is suitable for inclusion in mass treatment programmes and is the best therapeutic option presently available to combat onchocerciasis. As such it provides hope for many thousands of people at risk of becoming blind, and represents a major contribution to tropical medicine.     

Ertapenem. A review of its microbiologic,pharmacokinetic and clinical aspects

Ertapenem sodium (trade name Invanz, also designated as MK-0826, MK-826 and L-749345), manufactured by Merck & Co., Inc. is a structurally unique parenteral 1 beta-methyl carbapenem. It has a broad spectrum of antimicrobial activity, including common community-acquired Gram-positive and Gram-negative aerobic and anaerobic pathogens, and restricted activity against nosocomial pathogens such as Pseudomonas aeruginosa, Acinetobacter species, methicillin-resistant staphylococci and enterococci. Ertapenem demonstrates excellent activity against cephalosporin-resistant enteric organisms producing extended spectrum beta-lactamases (ESBLs) or AmpC beta-lactamases and excellent activity against penicillin-resistant Streptococcus pneumoniae. Its high level of protein binding and serum half-life of 4 h allows it to be dosed once daily. Ertapenem may be administered intravenously or intramuscularly and has an excellent adverse reaction and tolerability profile. Invanz was approved by the United States Food and Drug Administration in November 2001 for the treatment of adult patients with moderate to severe infections caused by designated strains of susceptible microorganisms. The infections include complicated intraabdominal infections, complicated skin and skin structure infections, community-acquired pneumonia, complicated urinary tract infections including pyelonephritis and acute pelvic infections including postpartum endomyometritis, septic abortion and post surgical gynecologic infections. Invanz has also been approved in Mexico, Brazil and New Zealand.     

Nafarelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical potential in sex hormone-related conditions

Nafarelin, a synthetic agonist of gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LH-RH); gonadorelin] appears likely to join the other GnRH analogues currently used in a range of conditions reliant on gonadotrophins or sex hormones. With repeated administration, the pituitary becomes desensitised, and gonadotrophin release, and therefore sex hormone synthesis, are inhibited. Nafarelin has proved to be comparable to danazol in the management of women with endometriosis, with fewer potentially harmful adverse effects. Nafarelin has also been used effectively in in vitro fertilisation programmes, and in hirsute women and those with uterine leiomyoma, particularly to induce preoperative fibroid shrinkage. The drug shrinks hypertrophic tissue in men with benign prostatic hyperplasia, although treatment would need to be maintained indefinitely and therefore should probably be reserved for those unsuitable for prostatectomy. Preliminary data suggest that nafarelin is equivalent to diethylstilbestrol (stilboestrol) in terms of disease-free survival in men with prostate cancer. As a reliable method of contraception, nafarelin gives unpredictable results in men and the promising results in women may be offset by hypoestrogenic side effects. Nafarelin may join other GnRH agonists which are now routinely used in the management of children with central or combined precocious puberty. Nafarelin is readily and rapidly absorbed following intranasal delivery, and is protected to some extent from enzymatic degradation. The resultant relatively long elimination half-life allows once- or twice-daily administration. Estrogen depletion accounts for the most common side effects associated with nafarelin, including hot flushes and vaginal dryness, which are mild and tolerable in most patients. Reversible resorption of trabecular bone can occur during nafarelin therapy, perhaps necessitating cyclical treatment to enable bone mass to recover. Nafarelin, therefore, looks likely to find a role in the treatment of women with endometriosis, and results achieved in other conditions dependent on the pituitary-gonadal axis are promising.     

Pharmacodynamic and pharmacokinetic properties of enoxaparin : implications for clinical practice

Enoxaparin is a low-molecular-weight heparin (LMWH) that differs substantially from unfractionated heparin (UFH) in its pharmacodynamic and pharmacokinetic properties. Some of the pharmacodynamic features of enoxaparin that distinguish it from UFH are a higher ratio of anti-Xa to anti-IIa activity, more consistent release of tissue factor pathway inhibitor, weaker interactions with platelets and less inhibition of bone formation. Enoxaparin has a higher and more consistent bioavailability after subcutaneous administration than UFH, a longer plasma half-life and is less strongly bound to plasma proteins. These properties mean that enoxaparin provides a more reliable anticoagulant effect without the need for laboratory monitoring, and also offers the convenience of once-daily administration. Clinical studies have confirmed that these pharmacological advantages translate into improved outcomes. There are important pharmacokinetic and pharmacodynamic differences between enoxaparin, other LMWHs and UFH, and therefore these molecules cannot be regarded as interchangeable.