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Stable nonneutropenic patients with candidemia include oral candidiasis (thrush) purchase actoplus met 500mg line diabetes type 1 support groups online, mild esophageal can- can be adequately treated with fluconazole actoplus met 500mg for sale blood glucose and triglycerides, but unsta- didiasis, and vaginitis. Fluconazole may be an acceptable alternative to amphotericin B in the initial treatment of mild crypto- Clinical Uses coccal meningitis, and it has been shown to be superior to amphotericin B in the long-term prevention of re- Itraconazole is most useful in the long-term suppressive lapsing meningitis (such patients require lifelong treat- treatment of disseminated histoplasmosis in AIDS and ment. Coccidioidal meningitis, previously treated with in the oral treatment of nonmeningeal, non–life-threat- both intravenous and intrathecal amphotericin B, ap- ening blastomycosis. It appears to be the drug of choice pears to respond at least as well to prolonged oral flu- for all forms of sporotrichosis except meningitis and conazole therapy. Aspergillosis, mucormycosis, and may have a lower relapse rate in the treatment of dis- pseudallescheriasis do not respond to fluconazole treat- seminated coccidioidomycosis than does fluconazole. Sporotrichosis, histoplasmosis, and blastomycosis Itraconazole has replaced ketoconazole as the drug appear to be better treated with itraconazole, although of choice in the treatment of paracoccidioidomycosis fluconazole does appear to have significant activity and chromomycosis, based on its lower toxicity profile. Efficacy has also been reported in the treatment of in- A significant decrease in mortality from deep-seated vasive aspergillosis. Fluconazole taken uses for itraconazole include treatment of vaginal can- prophylactically by end-stage AIDS patients can reduce didiasis, tinea versicolor, dermatophyte infections, and the incidence of cryptococcal meningitis, esophageal onychomycosis. Adverse Effects Adverse Effects Itraconazole is usually well tolerated but can be associ- Fluconazole is well tolerated. Dizziness and inal pain, diarrhea, and skin rash have been reported in headache also have been reported. Itraconazole, un- elevation has been described, and several cases of drug- like ketoconazole, is not associated with hormonal sup- associated hepatic necrosis have been reported. Hepatotoxicity occurs in fewer than 5% of pecia has been reported as a common adverse event in cases and is usually manifested by reversible liver en- patients receiving prolonged high-dose therapy. Drug Interactions Itraconazole has significant interactions with a number ITRACONAZOLE of commonly prescribed drugs, such as rifampin, phe- nytoin, and carbamazepine. Itraconazole raises serum Absorption, Distribution, Metabolism, digoxin and cyclosporine levels and may affect the me- and Excretion tabolism of oral hypoglycemic agents and coumadin. Absorption of itraconazole is impaired by antacids, H2 Although itraconazole and fluconazole are both tria- blockers, proton pump inhibitors, and drugs that contain zoles, they are chemically and pharmacologically dis- buffers, such as the antiretroviral agent didanosine. Itraconazole (Sporanox) is lipophilic and water in- soluble and requires a low gastric pH for absorption. Oral bioavailability is variable, only 50 to 60% when KETOCONAZOLE taken with food and 20% or less when the drug is taken on an empty stomach. Itraconazole is highly protein Absorption, Distribution, Metabolism, bound (99%) and is metabolized in the liver and ex- and Excretion creted into the bile. With initial dosing, the plasma half- life is 15 to 20 hours; steady-state serum concentrations Unlike other imidazoles, ketoconazole (Nizoral) can are reached only after 2 weeks of therapy, when the be absorbed orally, but it requires an acidic gastric half-life is extended to 30 to 35 hours. In lipophilic tis- environment; patients concurrently treated with H2 sues, drug concentration is 2 to 20 times that found in blockers or who have achlorhydria have minimal drug 600 VI CHEMOTHERAPY absorption. The Phenytoin serum levels should be monitored closely drug is metabolized in the liver and excreted in the bile. Ketoconazole causes in- The initial half-life of ketoconazole is 2 hours; 8 to 12 creases in serum concentrations of warfarin, cyclosporine, hours after ingestion, the half-life increases to 9 hours. Because of its ability to increase serum Reductions in renal and hepatic function do not al- cyclosporine levels, ketoconazole has been given to cy- ter plasma drug concentrations, and ketoconazole is not closporine-dependent cardiac transplant recipients to re- removed by hemodialysis or peritoneal dialysis. Since only small amounts of active drug ap- pear in the urine, ketoconazole is not effective in the MICONAZOLE treatment of Candida cystitis. Miconazole (Monistat) is a broad-spectrum imidazole antifungal agent used in the topical treatment of cuta- Clinical Uses neous dermatophyte infections and mucous membrane Ketoconazole remains useful in the treatment of cuta- Candida infections, such as vaginitis. Minimal absorp- neous and mucous membrane dermatophyte and yeast tion occurs from skin or mucous membrane surfaces. Ketoconazole is usu- nal cramping have been reported with treatment for ally effective in the treatment of thrush, but fluconazole vaginitis. Widespread dermatophyte infections on skin surfaces can be treated easily with oral ketoconazole when the CLOTRIMAZOLE use of topical antifungal agents would be impractical. Clotrimazole (Lotrimin, Gyne-Lotrimin, Mycelex) is a Treatment of vulvovaginal candidiasis with topical imi- broad-spectrum fungistatic imidazole drug used in the dazoles is less expensive. It is also employed in the treatment of cidioidomycosis, and chromomycosis are better treated infections with cutaneous dermatophytes. Ketoconazole is inef- tions in the epidermis and mucous membranes; less fective in the treatment of cryptococcosis, aspergillosis, than 10% of the drug is systemically absorbed. Candidemia is best treated with flu- though clotrimazole is generally well tolerated, local ab- conazole or amphotericin B.

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Although subjective quality Indications of life reports substantiate this tradition purchase actoplus met 500 mg on line diabetes prevention app, objective evi- dence of improved cognitive function and physical Despite the long popularity of ginseng and its evident stamina remains incomplete or lacking generic 500 mg actoplus met overnight delivery diabetes side effects. Further studies mild stimulatory effect, there is less conclusive evidence of standardized ginseng preparations will be necessary for its clinical effectiveness than for many of the other to clarify its use in fatigue and diabetes. After being allowed to there is some intriguing work with ginseng as a cancer ferment in bowls, the kava was drunk by male islanders preventive, there is not enough evidence to suggest its to mark a special event. The active ingredients are thought to be Adverse Reactions, Contraindications, kavapyrones (also known as kavalactones), a family of and Interactions related synergistically active compounds that include kawain and methysticin. Ginseng is generally considered safe for nonpregnant healthy adults; however, at sufficient doses, ginseng may Mechanism of Action elevate blood pressure and cause insomnia, palpita- tions, nervousness, and tremor in susceptible individu- The exact mechanism of action is unclear, but it is als. These effects are increased if caffeine or other stim- thought that kavapyrones may act in the amygdala, pro- ulants are taken concurrently. Kava is gait impairment, dilated pupils, and eventually impaired sometimes drunk as a tea (2–4 g of root placed in 150 mL motor performance. Treatment may take several weeks to be fully effective, but should be limited Indications to no more than 3 months of drug administration. A number of small trials have shown extracts, standardized to 70% kavapyrones, to be significantly Kava appears to act somewhat like an herbal tranquil- and consistently more effective than placebo. Addi- izer to produce a calm, relaxed state, often with mild eu- tional studies suggest that kava acts centrally as a mus- phoria. At recommended doses it has little effect on cle relaxant and likely has neuroprotective and nonopi- cognitive performance. Adverse Reactions, Contraindications, and Interactions Milk Thistle Although kava was considered relatively safe until re- Milk thistle (Silybum [Carduus] marianus) is a spiny cently, GI upset, headache, allergic skin reactions, ele- European plant with white-veined leaves and milky sap, vated liver function tests, and rare extrapyramidal re- the seed of which is used to treat liver disease. It should be avoided in patients with tle seed extract is used orally in the treatment of alco- known liver disease. Slowed reflexes and diminished holic and other cirrhoses and in Europe intravenously judgment may occur at high doses. Heavy chronic use for its hepatoprotective effect in Amanita and other may produce a psychological (rather than physiologi- mushroom poisonings. It is grown in this country pri- cal) habituation and a pellagralike skin condition marily as a “liver cleanser” and is reputed to protect this known as kava dermatitis characterized by reddened organ from a wide array of toxins. Milk thistle seed con- eyes and dry flaking skin with a yellow discoloration; tains the active principle silymarin, a complex of flavokawains A and B are yellow pigments isolated flavonolignan compounds including silibinin (silybin), from kava and are likely causative. Mechanism of Action Heavy kava users have also been observed to lose Silymarin is thought to protect the liver by preventing weight and have low plasma protein levels and low the entry of toxins into the hepatocyte and by stimulat- platelet and lymphocyte counts. Pulmonary hyperten- ing nucleolar polymerase A, which, in turn, increases sion and shortness of breath have rarely occurred. Silymarin un- should be avoided in pregnant women and children, dergoes enterohepatic circulation, increasing its con- since the consequences of use are unknown. It is also an antioxidant in its cause for concern is an uncommon idiosyncratic liver own right and is considered to have some cytoprotec- toxicity associated with kava use; in some cases, this has tive effect against carcinogens. It is unclear whether kava alone is to blame, but the safety Indications of this herb is under review. Several European coun- tries, where this problem was first reported, have either Alcoholic cirrhosis has been improved (faster return suspended sales or are acting to make kava a prescrip- of liver enzymes to baseline) in at least three trials, al- tion drug. There is azepines, barbiturates or other sedatives because of their no evidence to support the use of milk thistle to in- additive effects. In one case, coma resulted from mixing crease alcohol tolerance, although it is certainly being alprazolam and kava. The effectiveness of silymarin kava, while relaxing the body, may be less effective for for viral hepatitis is not clear, although several trials mental anxiety with obsessive or racing thoughts than demonstrated enough benefit to encourage further are the benzodiazepines. While several studies have demonstrated hepatic protection against earlier studies did indicate lowered PSA levels, more re- alcohol, acetaminophen, and mushroom toxins and pro- cent research has not supported these findings. Indication Numerous (but not all) trials have indicated improve- Adverse Reactions, Contraindications, ment in BPH symptom scores compared to placebo and Interactions with 1 to 3 months of therapy. Saw palmetto extract ap- Milk thistle appears to be remarkably safe, with loose pears to be equally effective as finasteride (see Chapter stools due to increased bile solubility and occasional al- 63) but is less effective than 1-adrenoceptor antago- lergic reactions being the common side effects.

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Definition At any given time there are about 30 buy 500mg actoplus met otc diabetes test kit costco,000 people in Amyotrophic lateral sclerosis (ALS) is a fatal dis- the United States with amyotrophic lateral sclerosis cheap 500mg actoplus met free shipping diabetes insipidus emedicine pediatrics, and ease that affects nerve cells in the brain and spinal cord about 5,000 new cases are reported each year. ALS pro- GALE ENCYCLOPEDIA OF GENETIC DISORDERS 79 NORMAL SPINAL NEURON DISEASED SPINAL NEURON Normal nerve fiber Affected nerve fiber Normal skeletal muscle Wasted skeletal muscle The degeneration and death of motor neurons in the spinal cord and brain results in amyotrophic lateral sclerosis (ALS). These neurons convey electrical messages from the brain to the muscles to stimulate movement in the arms, legs, trunk, neck, and head. As motor neurons degenerate, the muscles are weakened and cannot move as effectively, leading to muscle wasting. This In 1991 a team of ALSA researchers linked familial can have a devastating psychological effect on the family ALS to chromosome 21. In most cases, ALS is fatal were structural defects in the SOD1 (superoxide dismu- within two to five years, although approximately 10% tase) gene on chromosome 21. There is a high incidence of ALS on the island ALS affects approximately seven people out of every of Guam, in the Western New Guinea and on Kii penin- 100,000. Most people with ALS are between 40 and 70 sula of Japan leading some theorists to believe that years of age. Approximately 5–10% of cases show a genetic makeup may be susceptible to an environmental heredity pattern. Lou Gehrig, The inheritance pattern is autosomal dominant, known as the “Ironman” of baseball, died two years which means that children of an affected parent have a after he was diagnosed with amyotrophic lateral scle- 50% chance of inheriting the disorder. It is This condition is the hallmark of amyotrophic lateral thought that sporadic mutations result from both biologi- sclerosis. In rare cases, a mutation in erating motor neurons to elicit a signal to the muscles that NFH, the gene encoding for neurofilament (a structure allow them to function and grow. Familial amy- symptoms for ALS are muscle cramps and twitching, otropic lateral sclerosis has been linked to other chromo- weakness in the hands, feet, or ankles, speech slurring, somal locations but the exact genes involved have not and swallowing difficulties. The Institutional Review Board at include arm and leg stiffness, foot drop, weight loss, Thomas Jefferson University in Philadelphia recently fatigue, and difficulty making facial expressions. The goal of the One of the earliest symptoms of ALS is weakness in project is to inject an adeno-associated virus carrying a the bulbar muscles. The hope Weakness of these muscle groups usually cause problems is that the cells in that area will not die off. Demographics Another symptom of ALS that usually occurs after Amyotrophic lateral sclerosis affects anyone and initial symptoms appear is persistent muscle twitching both men and women are at equal risk. Fasciculation is almost never the first any age, and the odds of developing it increase with age. A As the disease progresses the respiratory muscles person only needs to inherit a defective gene from one (breathing muscles) weaken, resulting in increased diffi- parent to cause the disease. The potential for lung infection increases Signs and symptoms and can cause death. Many patients find it more comfort- The disease starts slowly, affecting just one limb, able and extend their lives when assisted by ventilators at such as the hands or feet, and steadily progresses to more this stage of the disease. One way to accomplish feedback with others is ishment they require, they begin to thin and deteriorate. Blinking is one mode that GALE ENCYCLOPEDIA OF GENETIC DISORDERS 81 patients of amyotrophic lateral sclerosis will be forced to the disease, and is vital for family members as well as utilize, in order to continue communication. As the disease progresses, victims gradually lose the Although there are no set treatments for ALS there use of their feet, hand, leg, and neck muscles, and paral- are still many special considerations that can assist in the ysis results in affected muscle groups. Sexual dys- cal therapy program, providing a wheelchair or walker, function is not affected. Breathing will become increas- assistance when bathing, and suction machines to help ingly difficult and the patients of ALS may decide to evacuate accumulated secretions all help the ALS patient. Researchers have developed a drug approved by the Diagnosis Food and Drug Administration (FDA) called Rilutek (riluzole). There is no one set way in that it appears to extend the life of ALS patients by to test for the disease. Electro diagnostic tests such as elec- Another drug, Myotrophin (somatomedin C), tromyography (EMG) and nerve conduction velocity appears to prevent neuron loss and enhance neuron gen- (NCV) are used to help diagnose ALS.

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