Clinical Director, Florida State University College of Medicine
Two recent reviews have assessed the efficacy of echinacea for this primary indication blood pressure questions order 10mg amlodipine with visa. A review by the Cochrane Collaboration involved 16 randomized trials with 22 comparisons blood pressure numbers what do they mean amlodipine 2.5mg low cost. Trials were included if they involved monopreparations of echinacea for cold treatment or prevention arteriosclerosis vs atherosclerosis cheap amlodipine 5mg. Prevention trials involving rhinovirus inoculation versus natural cold development were excluded blood pressure how to read cheap 10 mg amlodipine overnight delivery. Overall, the review concluded that there was some evidence of efficacy for the aerial (above-ground) parts of E purpurea plants in the early treatment of colds but that efficacy for prevention and for other species of echinacea was not clearly shown. Among the placebo-controlled comparisons for cold treatment, echinacea was superior in nine trials, showed a positive trend in one trial, and was insignificant in six trials. A separate meta-analysis involving 14 randomized, placebocontrolled trials of echinacea for cold treatment or prevention was published in Lancet. In this review, echinacea decreased the odds of developing clear signs and symptoms of a cold by 58% and decreased symptom duration by 1. This review, however, was confounded by the inclusion of four clinical trials involving multi-ingredient echinacea preparations, as well as three studies using rhinovirus inoculation versus natural cold development. Echinacea has been used investigationally to enhance hematologic recovery following chemotherapy. It has also been used as an adjunct in the treatment of urinary tract and vaginal fungal infections. These indications require further research before they can be accepted in clinical practice. Dried and powdered formulations contain many of the organosulfur compounds found in raw garlic and will likely be standardized to allicin or alliin content. Allicin is responsible for the characteristic odor of garlic, and alliin is its chemical precursor. Dried powdered formulations are often enteric-coated to protect the enzyme allinase (the enzyme that converts alliin to allicin) from degradation by stomach acid. Aged garlic extract has also been studied in clinical trials, but to a lesser degree than dried, powdered garlic. Its primary constituents are water-soluble organosulfur compounds, and packages may carry a standardization to the compound S-allylcysteine. Cardiovascular Effects In vitro, allicin and related compounds inhibit HMG-CoA reductase, which is involved in cholesterol biosynthesis (see Chapter 35), and exhibit antioxidant properties. The most recent meta-analysis involved 29 randomized, double-blind, placebo-controlled trials and found a small but significant reduction in both total cholesterol (-0. These results echoed another review in patients with baseline hypercholesterolemia (total cholesterol > 200 mg/dL) that found a significant reduction in total cholesterol of 5. Adverse effects with oral commercial formulations are minimal and most often include unpleasant taste, gastrointestinal upset, or rash. In one large clinical trial, pediatric patients using an oral echinacea product were significantly more likely to develop a rash (5%) than those taking placebo. The effect of garlic became insignificant, however, when dietary controls were in place. Cumulatively, these data indicate that garlic is unlikely to be effective in reducing cholesterol to a clinically significant extent. Clinical trials report antiplatelet effects (possibly through inhibition of thromboxane synthesis or stimulation of nitric oxide synthesis) following garlic ingestion. These effects in combination with antioxidant effects (eg, increased resistance to lowdensity lipoprotein oxidation) and reductions in total cholesterol might be beneficial in patients with atherosclerosis. A randomized, controlled trial among persons with advanced coronary artery disease who consumed dried powdered garlic for 4 years showed significant reductions in secondary markers (plaque accumulation in the carotid and femoral arteries) as compared with placebo, but primary endpoints (death, stroke, myocardial infarction) were not assessed. There have been a limited number of randomized, controlled trials in humans for this indication. Ten trials were included in a systematic review and meta-analysis that found no effect on systolic or diastolic pressure in patients without elevated systolic blood pressure but a significant reduction in systolic and diastolic pressure among the three trials involving patients with elevated systolic blood pressure. Endocrine Effects the effect of garlic on glucose homeostasis does not appear to be significant in persons with diabetes. Certain organosulfur constituents in garlic, however, have demonstrated hypoglycemic effects in nondiabetic animal models. Antimicrobial Effects the antimicrobial effect of garlic has not been extensively studied in clinical trials. Allicin has been reported to have in vitro activity against some gram-positive and gram-negative bacteria as well as fungi (Candida albicans), protozoa (Entamoeba histolytica), and certain viruses. The primary mechanism involves the inhibition of thiol-containing enzymes needed by these microbes. Given the availability of safe and effective prescription antimicrobials, the usefulness of garlic in this area appears limited. Antineoplastic Effects In rodent studies, garlic inhibits procarcinogens for colon, esophageal, lung, breast, and stomach cancer, possibly by detoxification of carcinogens and reduced carcinogen activation. Several epidemiologic case-control studies demonstrate a reduced incidence of stomach, esophageal, and colorectal cancers in persons with high dietary garlic consumption. Adverse Effects Following oral ingestion, adverse effects may include nausea (6%), hypotension (1. Drug Interactions & Precautions Because of reported antiplatelet effects, patients using anticlotting medications (eg, warfarin, aspirin, ibuprofen) should use garlic cautiously. Additional monitoring of blood pressure and signs and symptoms of bleeding is warranted.
Later studies found that the concentration required for this inhibition was higher than that achieved with recommended dosages hypertension differential diagnosis order discount amlodipine on line. In vitro studies using the commercially formulated hydroalcoholic extract have shown inhibition of nerve terminal reuptake of serotonin blood pressure diastolic buy on line amlodipine, norepinephrine 01 heart attackm4a demi effective 5mg amlodipine, and dopamine arrhythmia diet buy discount amlodipine 2.5mg on line. While the hypericin constituent did not show reuptake inhibition for any of these systems, the hyperforin constituent did. Chronic administration of the commercial extract has also been reported to significantly down-regulate the expression of cortical adrenoceptors and up-regulate the expression of serotonin receptors (5-HT2) in a rodent model. Other effects observed in vitro include sigma receptor binding using the hypericin fraction and GABA receptor binding using the commercial extract. Clinical trials for depression-The most recent systematic review and meta-analysis involved 29 randomized, double-blind, controlled trials (18 compared St. Only studies meeting defined classification criteria for major depression were included. A systematic review of 13 randomized trials involving 915 patients with alcoholic liver disease or hepatitis B or C found no significant reductions in all-cause mortality, liver histopathology, or complications of liver disease with 6 months of use. A significant reduction in liver-related mortality was claimed using the data from all the surveyed trials, but not when the data were limited to trials of better design and controls. It was concluded that the effects of milk thistle in improving liver function or mortality from liver disease are currently poorly substantiated. Until additional welldesigned clinical trials (possibly exploring higher doses) can be performed, a clinical effect can be neither supported nor ruled out. Although milk thistle has not been confirmed as an antidote following acute exposure to liver toxins in humans, parenteral silybin is nevertheless marketed and used in Europe as an antidote in Amanita phalloides mushroom poisoning. Adverse Effects Milk thistle has rarely been reported to cause adverse effects when used at recommended doses. Depression severity was mild to moderate in 19 trials, moderate to severe in 9 trials, and not stated in one trial. These studies are too few in number, however, to draw any firm conclusions regarding efficacy. Parenteral formulations of hypericin (photoactivated just before administration) have been used investigationally to treat HIV infection (given intravenously) and basal and squamous cell carcinoma (given by intralesional injection). In vitro, photoactivated hypericin inhibits a variety of enveloped and non-enveloped viruses as well as the growth of cells in some neoplastic tissues. Inhibition of protein kinase C and inhibition of singlet oxygen radical generation have been proposed as possible mechanisms. The recommended dosing for mild to moderate depression is 900 mg of the dried extract per day in three divided doses. Phytosterols (eg, -sitosterol), aliphatic alcohols, polyprenic compounds, and flavonoids are all present. Pharmacologic Effects Saw palmetto is most often promoted for the treatment of benign prostatic hyperplasia (BPH). Enzymatic conversion of testosterone to dihydrotestosterone (DHT) by 5-reductase is inhibited by saw palmetto in vitro. Specifically, saw palmetto shows a noncompetitive inhibition of both isoforms (I and II) of this enzyme, thereby reducing DHT production. Additional effects that have been observed in vitro include inhibition of prostatic growth factors, blockade of 1 adrenoceptors, and inhibition of inflammatory mediators produced by the 5-lipoxygenase pathway. One week of treatment in healthy volunteers failed to influence 5-reductase activity, DHT concentration, or testosterone concentration. Six months of treatment in patients with BPH also failed to affect prostate-specific antigen (PSA) levels, a marker that is typically reduced by enzymatic inhibition of 5-reductase. In contrast, other researchers have reported a reduction in epidermal growth factor, DHT levels, and antagonist activity at the nuclear estrogen receptor in the prostate after 3 months of treatment with saw palmetto in patients with BPH. Adverse Effects Photosensitization is related to the hypericin and pseudohypericin constituents in St. Consumers should be instructed to wear sunscreen and eye protection while using this product when exposed to the sun. Hypomania, mania, and autonomic arousal have also been reported in patients using St. Drug Interactions & Precautions Inhibition of reuptake of various amine transmitters has been highlighted as a potential mechanism of action for St. Drugs with similar mechanisms (ie, antidepressants, stimulants) should be used cautiously or avoided in patients using St. This herb may induce hepatic CYP enzymes (3A4, 2C9, 1A2) and the P-glycoprotein drug transporter. This has led to case reports of subtherapeutic levels of numerous drugs, including digoxin, birth control drugs (and subsequent pregnancy), cyclosporine, HIV protease and nonnucleoside reverse transcriptase inhibitors, warfarin, irinotecan, theophylline, and anticonvulsants. Clinical Trials the most recent review involved 30 randomized controlled trials in men with symptoms consistent with BPH. Fourteen trials used saw palmetto monotherapy compared to placebo and found no significant improvement in most urologic symptoms (eg, international prostate symptom scores, peak flow, prostate size). Although nocturia was significantly improved with saw palmetto compared to placebo, when studies were limited to those of higher quality and larger sample size, this significance was lost. In contrast, saw palmetto, 320 mg/d, was shown to have comparable efficacy to 5 mg/d of finasteride (a prescription 5-reductase inhibitor) and 0. The most common include abdominal pain, nausea, diarrhea, fatigue, headache, decreased libido, and rhinitis. Saw palmetto has been associated with a few rare case reports of pancreatitis, liver damage, and increased bleeding risk, but due to confounding factors, causality remains inconclusive. In comparison to tamsulosin and finasteride, saw palmetto was claimed to be less likely to affect sexual function (eg, ejaculation).
An instruction to "take as directed" may save the time it takes to write the orders out but often leads to noncompliance blood pressure medication side effects cough generic 2.5mg amlodipine free shipping, patient confusion heart attack in dogs buy generic amlodipine 5mg line, and medication error hypertension 3rd trimester purchase 2.5 mg amlodipine fast delivery. The directions for use must be clear and concise to prevent toxicity and to obtain the greatest benefits from therapy heart attack las vegas buy amlodipine with paypal. Although directions for use are no longer written in Latin, many Latin apothecary abbreviations (and some others included below) are still in use. Knowledge of these abbreviations is essential for the dispensing pharmacist and often useful for the prescriber. Elements [12] to [14] of the prescription include refill information, waiver of the requirement for childproof containers, and additional labeling instructions (eg, warnings such as "may cause drowsiness," "do not drink alcohol"). Pharmacists put the name of the medication on the label unless directed otherwise by the prescriber, and some medications have the name of the drug stamped or imprinted on the tablet or capsule. If the patient or prescriber does not request waiver of childproof containers, the pharmacist or dispenser must place the medication in such a container. Pharmacists may not refill a prescription medication without authorization from the prescriber. Prescribers may grant authorization to renew prescriptions at the time of writing the prescription or over the telephone. Furthermore, a good prescription or chart order should contain sufficient information to permit the pharmacist or nurse to discover possible errors before the drug is dispensed or administered. These include errors involving omission of needed information; poor writing perhaps leading to errors of drug dose or timing; and prescription of drugs that are inappropriate for the specific situation. Omission of Information Errors of omission are common in hospital orders and may include instructions to "resume pre-op meds," which assumes that a full and accurate record of the "pre-op meds" is available; "continue present IV fluids," which fails to state exactly what fluids are to be given, in what volume, and over what time period; or "continue eye drops," which omits mention of which eye is to be treated as well as the drug, concentration, and frequency of administration. Abbreviation a ac agit Aq Aq dest bid c cap D5W, D5W dil disp, dis elix ext g gr gtt h hs IA IM IV IVPB kg mcg, g (do not use) mEq, meq mg no non rep OD OS, OL OTC OU p pc Explanation before before meals shake, stir water distilled water twice a day with capsule dextrose 5% in water dissolve dilute dispense elixir extract gram grain drops hour at bedtime intra-arterial intramuscular intravenous IV piggyback kilogram microgram (always write out "microgram") milliequivalent milligram number do not repeat right eye left eye over-the-counter both eyes after after meals Abbreviation PO PR prn q qam, om qd (do not use) qh, q1h q2h, q3h, etc qhs qid qod (do not use) qs rept, repet Rx s SC, SQ sid (veterinary) Sig, S sos ss, ss stat sup, supp susp tab tbsp, T (do not use) tid Tr, tinct tsp (do not use) U (do not use) vag i, ii, iii, iv, etc (do not use) (do not use) Explanation by mouth per rectum when needed every every morning every day (write "daily") every hour every 2 hours, every 3 hours, etc every night at bedtime four times a day every other day sufficient quantity may be repeated take without subcutaneous once a day label if needed one-half at once suppository suspension tablet tablespoon (always write out "15 mL") three times a day tincture teaspoon (always write out "5 mL") units (always write out "units") vaginal one, two, three, four, etc dram (in fluid measure 3. Poor Prescription Writing Poor prescription writing is traditionally exemplified by illegible handwriting. On the other hand, appending an unnecessary zero after a decimal point increases the risk of a tenfold overdose, because "1. The slash or virgule ("/") was traditionally used as a substitute for a decimal point. Doses in micrograms should always have this unit written out because the abbreviated form ("g") is very easily misread as "mg," a 1000-fold overdose! Orders for drugs specifying only the number of dosage units and not the total dose required should not be filled if more than one size dosage unit exists for that drug. For example, ordering "one ampule of furosemide" is unacceptable because furosemide is available in ampules that contain 20, 40, or 100 mg of the drug. The abbreviation "OD" should be used (if at all) only to mean "the right eye"; it has been used for "every day" and has caused inappropriate administration of drugs into the eye. Acronyms and abbreviations such as "ASA" (aspirin), "5-ASA" (5-aminosalicylic acid), "6MP" (6-mercaptopurine), etc, should not be used; drug names should be written out. Unclear handwriting can be lethal when drugs with similar names but very different effects are available, eg, acetazolamide and acetohexamide, methotrexate and metolazone. In this situation, errors are best avoided by noting the indication for the drug in the body of the prescription, eg, "acetazolamide, for glaucoma. The prescriber selects the medication, strength, dosage form, quantity, and directions for use and the prescription is transmitted to the pharmacy where the appropriate data fields are populated. Prescribers can obtain decision support information such as disease-drug and drug-drug interaction information or cost information prior to prescribing as part of the health plan information. Prescriptions can be clear in their writing, but pull-down drug lists can create new errors. Prescription renewals can be processed electronically and drug misuse or abuse may be identifiable. Theoretically, time to process prescription orders should be reduced and patients would have their medication ready when they arrive at the pharmacy. The Drug Enforcement Administration has begun to issue tentative rules for e-prescribing of controlled substances. Currently, only registered prescribers can e-prescribe, and there will be several independent identification proofing sources required: a unique pin number, or retinal scan, or a finger print. Pharmacies currently can order controlled drugs via computer using a specific form once they are certified. Inappropriate Drug Prescriptions Prescribing an inappropriate drug for a particular patient results from failure to recognize contraindications imposed by other diseases the patient may have, failure to obtain information about other drugs the patient is taking (including over-the-counter drugs), or failure to recognize possible physicochemical incompatibilities between drugs that may react with each other. Contraindications to drugs in the presence of other diseases or pharmacokinetic characteristics are listed in the discussions of the drugs described in this book. Some of the important drug interactions are listed in Chapter 66 of this book as well as in package inserts. Physicochemical incompatibilities are of particular concern when parenteral administration is planned. Similarly, the simultaneous administration of antacids or products high in metal content may compromise the absorption of many drugs in the intestine, eg, tetracyclines. The package insert and the Handbook on Injectable Drugs (see References) are good sources for this information. Some studies suggest that one third of patients never have their prescriptions filled. Some patients leave the hospital without obtaining their discharge medications, whereas others leave the hospital without having their prehospitalization medications resumed.
Some brominated flame retardants are now being investigated as possible endocrine disrupters hypertension vasoconstriction 2.5mg amlodipine visa. Concerns exist because of their increasing contamination of the environment pulse pressure readings purchase amlodipine visa, the appearance of bioaccumulation arrhythmia young purchase amlodipine mastercard, and their potential for toxicity pulse blood pressure normal purchase amlodipine 5 mg amex. In vitro assays alone are unreliable for regulatory purposes, and animal studies are considered indispensable. Modified endocrine responses in some reptiles and marine invertebrates have been observed. In humans, however, a causal relation between exposure to a specific environmental agent and an adverse health effect due to endocrine modulation has not been established. Epidemiologic studies of populations exposed to higher concentrations of endocrine disrupting environmental chemicals are underway. There are indications that breast and other reproductive cancers are increased in these patients. Prudence dictates that exposure to environmental chemicals that disrupt endocrine function should be reduced. Exposure in the workplace is found in many industries, and exposure in the home and elsewhere in the nonoccupational environment is widespread. The classic metal poisons (arsenic, lead, and mercury) continue to be widely used. Beryllium Beryllium (Be) is a light alkaline metal that confers special properties on the alloys and ceramics in which it is incorporated. One attractive property of beryllium is its nonsparking quality, which makes it useful in such diverse applications as the manufacture of dental appliances and of nuclear weapons. Beryllium-copper alloys find use as components of computers, in the encasement of the first stage of nuclear weapons, in devices that require hardening such as missile ceramic nose cones, and in the space shuttle heat shield tiles. Because of the use of beryllium in dental appliances, dentists and dental appliance makers are often exposed to beryllium dust in toxic concentrations. Beryllium is highly toxic by inhalation and is classified by IARC as a class 1, known human carcinogen. Inhalation of beryllium particles produces progressive pulmonary fibrosis and may lead to cancer. The pulmonary disease is called chronic beryllium disease (CBD) and is a chronic granulomatous pulmonary fibrosis. Although some treatment approaches to the management of chronic beryllium disease show promise, the prognosis is poor in most cases. Environmental beryllium exposure is not generally thought to be a hazard to human health except in the vicinity of industrial sites where air, water and soil pollution have occurred. Asbestos Asbestos in many of its forms has been widely used in industry for over 100 years. All forms of asbestos that have been used in industry have been shown to cause progressive lung disease that is characterized by a fibrotic process. Lung damage develops even at low concentrations of shorter fibers, whereas higher concentrations of longer fibers are required to cause lung damage. Every form of asbestos, including chrysotile asbestos, causes an increase in lung cancer. Lung cancer occurs in people exposed at fiber concentrations well below concentrations that produce asbestosis. Cigarette smoking and exposure to radon daughters increase the incidence of asbestos-caused lung cancer in a synergistic fashion. All forms of asbestos also cause mesothelioma of the pleura or peritoneum at very low doses. Other cancers including colon cancer, laryngeal cancer, stomach cancer, and perhaps even lymphoma are increased in asbestos-exposed patients. Arguments that chrysotile asbestos does not cause mesothelioma are contradicted by many epidemiologic studies of worker populations. Recognition that all forms of asbestos are dangerous and carcinogenic has led many countries to ban all uses of asbestos. Countries such as Canada, Zimbabwe, and others that still produce asbestos argue that asbestos can be used safely with careful workplace environmental controls. However, studies of industrial practice make the "safe use" of asbestos highly improbable. Workers are exposed to cadmium in the manufacture of nickel cadmium batteries, pigments, low-melting-point eutectic materials; in solder; in television phosphors; and in plating operations. When metals that have been plated with cadmium or welded with cadmiumcontaining materials are vaporized by the heat of torches or cutting implements, the fine dust and fumes released produce an acute respiratory disorder called cadmium fume fever. This disorder, common in welders, is usually characterized by shaking chills, cough, fever, and malaise. However, chronic exposure to cadmium dust produces a far more serious progressive pulmonary fibrosis. Cadmium also causes severe kidney damage, including renal failure if exposure continues. Cadmium is a human carcinogen and is listed as a group 1, known human carcinogen by the IARC. This PEL, considered by OSHA to be the lowest feasible limit for the dust, is insufficiently protective of worker health. Buckley A et al: Hyperbaric oxygen for carbon monoxide poisoning: A systematic review and critical analysis of the evidence. Casals-Casas C, Desvergne B: Endocrine disruptors: from endocrine to metabolic disruption. Crisp TM et al: Environmental endocrine disruption: An effects assessment and analysis.
One such agent is the small molecule inhibitor erlotinib hypertension updates discount 5 mg amlodipine overnight delivery, which targets the EGFR-associated tyrosine kinase hypertension medication order amlodipine 5 mg. This agent is now approved for use in combination with gemcitabine in locally advanced or metastatic pancreatic cancer although the improvement in clinical benefit is relatively small hypertension brochure discount amlodipine 10mg amex. There is also evidence to support the use of adjuvant chemotherapy with either single-agent gemcitabine or 5-FU/leucovorin in patients with early-stage pancreatic cancer who have undergone successful surgical resection arrhythmia normal cheap amlodipine 2.5 mg free shipping. For patients with good performance status and those with non-squamous histology, the combination of the anti-VEGF antibody bevacizumab with carboplatin and paclitaxel is a standard treatment option. In patients deemed not to be appropriate candidates for bevacizumab therapy and those with squamous cell histology, a platinum-based chemotherapy regimen in combination with the anti-EGFR antibody cetuximab is a reasonable treatment strategy. Small cell lung cancer is the most aggressive form of lung cancer, and it is exquisitely sensitive, at least initially, to platinum-based combination regimens, including cisplatin and etoposide or cisplatin and irinotecan. When diagnosed at an early stage, this disease is potentially curable using a combined modality approach of chemotherapy and radiation therapy. Unfortunately, drug resistance eventually develops in nearly all patients with extensive disease. The topoisomerase I inhibitor topotecan is used as second-line monotherapy in patients who have failed a platinum-based regimen. It is important to accurately stage this cancer with laparoscopy, ultrasound, and CT scanning. Patients with stage I disease appear to benefit from whole-abdomen radiotherapy and may receive additional benefit from combination chemotherapy with cisplatin and cyclophosphamide. Combination chemotherapy is the standard approach to stage III and stage IV disease. Randomized clinical studies have shown that the combination of paclitaxel and cisplatin provides survival benefit compared with the previous standard combination of cisplatin plus cyclophosphamide. In patients who present with recurrent disease, the topoisomerase I inhibitor topotecan, the alkylating agent altretamine, and liposomal doxorubicin are used as single agent monotherapy. It is clear that prevention (primarily through avoidance of cigarette smoking) and early detection remain the most important means of control. Moreover, recent studies have shown that adjuvant platinum-based chemotherapy provides a survival benefit in patients with pathologic stage IB, II, and IIIA disease. However, in most cases, distant metastases have occurred at the time of diagnosis. In certain instances, radiation therapy can be offered for palliation of pain, airway obstruction, or bleeding and to treat patients whose performance status would not allow for more aggressive treatments. In patients with advanced disease, systemic chemotherapy is generally recommended. Combination regimens that include a platinum agent ("platinum doublets") appear superior to non-platinum doublets, and either cisplatin or carboplatin are appropriate platinum agents for such regimens. Presently, chemotherapy is recommended for patients with stage IIC or stage III seminomas and nonseminomatous disease. In patients with high-risk disease, the combination of cisplatin, etoposide, and ifosfamide can be used as well as etoposide and bleomycin with high-dose cisplatin. However, once spread to metastatic sites has been diagnosed, it is one of the most difficult cancers to treat because it is a relatively drug-resistant tumor. While dacarbazine, temozolomide, and cisplatin are the most active cytotoxic agents for this disease, the overall response rates to these agents remain low. Biologic agents, including interferon- and interleukin-2 (IL-2), have greater activity than traditional cytotoxic agents, and treatment with high-dose IL-2 has led to cures, albeit in a relatively small subset of patients. Significant efforts have focused on utilizing biologic therapy with combination chemotherapy in what have been labeled biochemotherapy regimens. Although overall response rates as well as complete response rates appear to be much higher with biochemotherapy regimens compared with chemotherapy alone, treatment toxicity also seems to be increased. This mutation results in constitutive activation of BRAF kinase, which then leads to activation of downstream signaling pathways involved in cell growth and proliferation. Further studies are ongoing to confirm its activity as a single agent as well as in combination with other cytotoxic and biologic agents. Carmustine (BCNU) can be used as a single agent, or lomustine (CCNU) can be used in combination with procarbazine and vincristine (PCV regimen). In addition, the newer alkylating agent temozolomide is active when combined with radiotherapy and used in patients with newly diagnosed glioblastoma multiforme (GBM) as well as in those with recurrent disease. The histopathologic subtype oligodendroglioma has been shown to be especially chemosensitive, and the PCV regimen is the treatment of choice for this disease. There is growing evidence that the antiVEGF antibody bevacizumab alone or in combination with chemotherapy has promising activity in adult GBM, and bevacizumab was recently approved as a single agent for GBM in the setting of progressive disease following first-line chemotherapy. With improvements in the clinical efficacy of various combination chemotherapy regimens resulting in prolonged survival and in some cases actual cure of cancer, the issue of how second cancers may affect long-term survival assumes greater importance. There is already evidence that certain alkylating agents (eg, cyclophosphamide) may be less carcinogenic than others (eg, melphalan). Chabner BA, Longo DL: Cancer Chemotherapy and Biotherapy: Principles and Practice, 4th ed. DeVita VT Jr, Hellman S, Rosenberg SA: Cancer: Principles and Practice of Oncology, 9th ed. Hoskins WJ, Perez CA, Young RC: Principles and Practice of Gynecologic Oncology, 4th ed.
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