Thursday, July 10, 2008

Studies To Date Say Erectile Dysfunction Drugs Affect Other Systems, Mostly For The Better


Since the Food and Drug Administration gave Viagra (sildenafil) its approval in 1998, "erectile dysfunction" has become a household term - probably to the chagrin of many parents fielding questions from their kids watching TV. But with sildenafil and the subsequent introduction and marketing of Levitra- (vardenafil) and Cialis- (tadalafil), many men have found answers to a once-unmentionable condition.

"As more and more patients seek therapy for sexual dysfunction, it is increasingly important for clinicians in a wide range of specialties to become proficient in the mechanisms and systemic effects of these medications," said Ernst R. Schwarz, M.D., Ph.D., a cardiologist at Cedars-Sinai Medical Center who specializes in therapies for men who suffer from erectile dysfunction (ED) and have heart problems, diabetes, high blood pressure or other related conditions.

Schwarz and colleagues recently concluded a review of the medical literature, as well as their own research findings and clinical data, to determine what actually is known about the effects of long-term use of this class of drugs on various organ systems. Their findings appears in the June, 2006 issue of the International Journal of Impotence Research.

Studies so far suggest the drugs, called phosphodiesterase-5 inhibitors (PDE-5i), produce mostly beneficial results, and not just for erectile dysfunction. The FDA recently approved a reformulation of sildenafil for the treatment of primary pulmonary hypertension, a disease that tends to occur in young women, causing elevated blood pressures in the lung that can lead to heart failure and early death.

"When we look at all the different organ systems - the blood, the heart, the lungs, blood flow in the brain - there are hardly any negative side effects. In fact, just the opposite is true. There are beneficial effects for primary pulmonary hypertension, as well as for conditions such as heart failure and lack of oxygen in the heart," said Schwarz. "The only issue is that the data we have are from relatively short-term studies. Viagra has been on the market since 1998 and the other two PDE-5 inhibitors were approved by the FDA in 2003. Therefore, we do not have multi-year follow-up studies. On the other hand, the drugs have been on the market for several years now and there have been no reports of negative long-term effects."

While there are some differences among the three medications, they have many properties in common and work by limiting the activity of the enzyme phosphodiesterase-5, which is found in tissues and vessels of the penis, blood platelets, and smooth muscle of blood vessels. For the treatment of erectile dysfunction, the drugs' constraint of the enzyme's action results in increased levels of cyclic guanosine monophosphate (cGMP) and nitric oxide (NO), biochemicals that promote smooth muscle relaxation and increased blood flow in erectile tissue.

According to the article, PDE-5 inhibitors can be effective in treating erectile dysfunction even for many men who also have diabetes, those who are older, and those who have co-existing ischemic heart disease (reduced blood flow to the heart caused by plaque buildup in the arteries). Furthermore, say the authors, "since PDE-5 is found in smooth muscles of the systemic arteries and veins throughout the body, use of PDE-5i has been associated with various cardiovascular effects."

"The original intention was to develop PDE-5 inhibitors as a treatment for angina, chest pain that occurs when the heart is starved for oxygen," Schwarz said. "As such, their effects on the heart appear to be all beneficial. Nitrates and other substances commonly used to improve blood flow and oxygenation to the heart muscle have a side effect that we call the 'steal phenomenon,' in which blood is taken away from underperfused (flow-restricted) areas to improve blood flow in normal areas. In contrast, PDE-5 inhibitors actually improve blood flow even in areas where there is a blockage of an artery, thereby having a protective effect on the heart muscle."

The drugs' potential impact on visual function became a matter of controversy when a suspected link between PDE-5 inhibitors and vision loss led to lawsuits filed last year against the maker of Viagra. According to the article's authors, however, "analysis of clinical trial data in more than 13,000 men and on more than 35,000 patient-years of observation" found occurrence of the visual disorder to be similar to that of the general population. "Even though individual cases have been reported for all PDE-5i, these recently published data do not suggest an increased incidence of NAION (non-arteric anterior ischemic optic neuropathy) in men who took PDE-5i for ED," the article states.

Among other findings:

* Although the enzyme PDE-5 has been found in tissue and arteries of the brain, sildenafil does not appear to dilate cerebral arteries or have an effect on cerebral blood flow or blood flow velocity, an indication that there is no increased risk of stroke or hemorrhage.
* PDE-5 exists in blood platelets, cells that play a major role in the blood clotting process, but sildenafil appears to have no direct impact on platelet function. However, the drug's effects have not been specifically evaluated in patients with bleeding disorders or in those taking drugs that reduce clotting.

"Experimental and human studies indicate that PDE-5 inhibitors are effective and well tolerated, and there is evidence that they are not being used to their utmost potential. We suggest that these drugs may prove beneficial in treating a wide variety of disorders," said Schwarz, the article's first author and a specialist in cardiology, interventional cardiology, heart failure, and transplantation. "Some studies are underway to determine the effects of long-term use of PDE-5 inhibitors, and others are warranted, especially in patients who are considered at high risk because of chronic cardiovascular disorders."

The first of eight hospitals in California whose nurses have been honored with the prestigious Magnet designation, Cedars-Sinai Medical Center is one of the largest nonprofit academic medical centers in the Western United States. For 18 consecutive years, it has been named Los Angeles' most preferred hospital for all health needs in an independent survey of area residents. Cedars-Sinai is internationally renowned for its diagnostic and treatment capabilities and its broad spectrum of programs and services, as well as breakthroughs in biomedical research and superlative medical education. It ranks among the top 10 non-university hospitals in the nation for its research activities and is fully accredited by the Association for the Accreditation of Human Research Protection Programs, Inc. (AAHRPP). Additional information is available at

Contact: Sandy Van

Cedars-Sinai Medical Center
This is a part of article Studies To Date Say Erectile Dysfunction Drugs Affect Other Systems, Mostly For The Better Taken from "Buy Levitra Viagra Online" Information Blog

Monday, July 7, 2008

Expert Column - What Every PCP Should Know: Over-the-Counter Insomnia Treatments

Return to: Current Perspectives in Insomnia, Volume 4

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Expert Column - What Every PCP Should Know: Over-the-Counter Insomnia Treatments  CME


Irina V. Zhdanova, MD, PhD   


According to various estimates, 15% to 40% of the general population suffer from transient, short-term, or chronic insomnia associated with subjective complaints of prolonged sleep latency, frequent nighttime awakenings, long periods of nighttime wakefulness, or early-morning awakening.[1,2] Because altered nighttime sleep leads to daytime fatigue and sleepiness, any type of insomnia negatively affects mood and performance, and thus increases the risk of accidents and health problems, including major depression.

Although some insomniacs consistently seek and follow medical advice in addressing their sleep problems and use prescribed therapy (pharmacologic, circadian, behavioral, or cognitive), many choose over-the-counter (OTC) sleep aids in an attempt to shorten latency to sleep or promote nighttime sleep maintenance. A rationale for using OTC sleep aids may differ; some are searching for a "quick fix" with a readily available medication, and others have found conventional hypnotics to be ineffective or their side effects intolerable. Many are also attracted by a label "dietary supplement," which is often perceived as a safer or more natural alternative to drugs.

It is critically important to know whether your patient suffers from insomnia and, if so, which medications he or she is using to combat it. The major categories of OTC sleep medications widely available in stores, pharmacies, and on the Web include antihistamines as well as hormonal and herbal preparations. In addition, some insomniacs use ethanol or marijuana as a sedative despite the disadvantages, such as dependence. OTC preparations also are frequently used in combination, which is likely to amplify both their sleep-promoting and adverse effects.


First-generation antihistamines (eg, diphenhydramine, brompheniramine, or chlorpheniramine) have been used to treat allergies for a number of years and are available without prescription. However, they can also induce sedation via central antihistaminergic and anticholinergic mechanisms,[3,4] and this effect is widely exploited.

A number of clinical studies have addressed the dose- and time-dependent properties of antihistamines and found both subjective and objective changes in sleepiness, sleep, and psychomotor performance associated with the reduction in latency to sleep onset or increase in sleep duration.[5-8] Although previous studies tended to support the use of this class of drugs to treat occasional mild-to-moderate insomnia,[9,10] more recent opinions of sleep specialists have shifted strongly against this practice.[11]

The major reason for limiting the use of antihistamines for treating insomnia is their multiple side effects, including changes in sleep architecture, notably a reduction in rapid eye movement (REM) sleep caused by their anticholinergic effects; a reduction in cognitive functions;[12] day-after sedation; an increased risk of accidents;[13] the development of tolerance;[14] and interference with other medications. The side effects of antihistamines appear to be especially risky for elderly patients, almost 50% of whom use sleep medications occasionally or on a regular basis and who often choose OTC sleep aids.[15]Adverse Effects of Diphenhydramine

A recent study, involving 1627 individuals aged 65 and over, found that between 1989 and 1996 the use of prescription sedative-hypnotics (primarily benzodiazepines) rose from 1.8% to 3.1%, whereas OTC sedative-hypnotic use (primarily diphenhydramine) increased from .4% to 7.6%, and reached 8.17% by 1998.[16] This study also highlighted a significant association of diphenhydramine use and cognitive impairment in elderly individuals without dementia.

In a Yale University (New Haven, Connecticut) hospital study, 114 (27%) of 426 hospitalized medical patients aged 70 years or older received diphenhydramine during hospitalization.[17] Although at baseline these patients demonstrated similar characteristics (age, sex, delirium risk, and Mini-Mental State Examination scores) to those of patients who did not receive diphenhydramine, the ones who received diphenhydramine showed a significantly greater risk for delirium symptoms, disorganized speech, and altered consciousness during hospitalization. A diphenhydramine dose-response relationship was demonstrated for most adverse outcomes.

In view of the antihistamine-induced side effects, it is especially disturbing that a large number of OTC preparations contain diphenhydramine under a score of brand names,* which can confuse patients. Furthermore, many OTC medications include diphenhydramine as a second active ingredient (eg, Tylenol PM, Aspirin PM, Acetaminophen PM, Alka-Seltzer Plus, etc). Typical doses of diphenhydramine in these preparations are 25-50 mg per tablet or capsule, and, in most cases, 2 tablets are the recommended dose, 3-4 times per day. Syrup, elixir, spray, cream, and gel forms of diphenhydramine are also widely available.

The Swiss Toxicological Information Centre has recently studied the dose-dependent toxicity of diphenhydramine in 282 patients with acute diphenhydramine poisoning.[18] They found that mild toxicity symptoms (somnolence, anticholinergic signs, tachycardia, and nausea/vomiting) accounted for 55% to 64% of the cases and were associated with doses under 300 mg. Moderate symptoms (isolated and spontaneously resolving agitation, confusion, hallucinations, and electrocardiogram disturbances) were documented in 22% to 27% of those who ingested more than 300 mg of diphenhydramine. Severe symptoms (delirium/psychosis, seizures, and coma) manifested in 14% to 18% of the patients after ingestion of nearly 1 g of the drug. Thus, combining several tablets of an OTC "cold" medication with a topical cream for allergy could place a patient at health risk.

Recognizing the complexities of the OTC antihistamine market, in 2002 the US Food and Drug Administration (FDA) ruled that drug products containing diphenhydramine should carry warnings, advising consumers not to use oral OTC diphenhydramine products with any other product containing diphenhydramine, including products used topically.[19] Overall, occasional use of low-dose antihistamines for acute sedation may be relatively safe, but using them frequently to control sleep is not a good idea.

*40 Winks, Aid to Sleep, Aler-Dryl, Allergia-C, Allergy Medicine Antihistamine, AllerMax, Altaryl, Anti-Histamine, Antihist, Antihistamine, Antihistamine Allergy, Antituss, Banaril, Banophen, Beldin, Belix, Benadryl, Benadryl Allergy, Benadryl DF, Benadryl Dye-Free Allergy, Benadryl Ultratab, Benahist-10, Benahist-50, Benoject-50, Bydramine, Calm-Aid, Child Allergy, Complete Allergy, Complete Allergy Relief, Compoz Nighttime Sleep Aid, Diphedryl, Diphen, Diphen AF, Diphen Cough, Diphenadryl, Diphendryl, Diphenhist, Diphenhydramine Hydrochloride, Diphenyl, Diphenylin, DPH, Dytan, Dytuss, Genahist, Hydramine, Hydramine Compound, Hydramine Cough Syrup, Hyrexin, Nervine, Night Time Sleep-Aid, Nu-Med, Nytol Caplet, Pardryl, Phendry, Q-Dryl, Quenalin, Scot-Tussin Allergy Relief Formula, Siladryl, Siladryl DAS, Siladyl SA, Silphen Cough, Simply Sleep, Sleep, Sleep Aid, Sleep Tab II, Sleep Tabs, Sleep-ettes, Sleep-eze-3, Sleepinal, Sominex, Sominex Maximum Strength Caplet, Somnicaps, Total Allergy, Trux-adryl, Tusstat, Twilite, Uni-Hist, Unisom Sleepgels Maximum Strength, Valu-Dryl, Wehdryl(


The onsets of sleepiness, sleep quantity, and sleep quality depend not only on the duration of prior wakefulness, the so-called homeostatic mechanism of sleep regulation, but also on the time of day when an attempt to initiate sleep is taking place. The latter reflects circadian mechanisms of sleep regulation and is linked to the biological clock structure, the suprachiasmatic nucleus of the hypothalamus.

The neuroendocrine system is likely to play a major role in both homeostatic and circadian sleep processes. However, so far we know very little about hormonal mechanisms of sleep regulation. An exception is melatonin, the principal hormone of the circadian system, released nightly into the cerebrospinal fluid and blood circulation by the pineal gland. The ability of high doses of melatonin to induce sleepiness was reported over 40 years ago, during an unrelated clinical trial.[20] More recently, low-dose melatonin (.1-.5 mg, orally) was found to promote objectively documented sleep.[21-25] Of importance, these low doses induced circulating melatonin levels within those normally observed in human blood (50-150 pg/mL). The latter suggests that melatonin may normally play a role in homeostatic sleep regulation, acutely promoting sleep onset and maintenance at night, in addition to its ability to shift a circadian phase of sleep, resulting from its effects on the "biological clock."

Melatonin does not appear to significantly affect nighttime sleep quantity and quality in healthy individuals but can help them to fall asleep during the day.[21-25] It was shown to be especially helpful for insomnias associated with neurologic disorders in children.[26-31] The results of melatonin administration to elderly insomniacs are more variable, ranging from mild but significant improvements in their sleep[32-34] to a lack of therapeutic effect.[35,36] Of note, sensitivity to the effects of melatonin on sleep is not uniform among individuals and may decline with age or as a result of neurodegenerative diseases.[37,38] Melatonin coadministration can also facilitate the effects of common hypnotics, helping to reduce their effective dose and side effects or attenuating drug withdrawal.[39] A combination of circadian and homeostatic effects of melatonin with its surprisingly low toxicity and lack of significant effects on sleep architecture and day-after performance at high pharmacologic doses makes it a popular compound among insomniacs.Sleep Effects

The nature of melatonin's effect on sleep, which is only starting to emerge, is such that it promotes a behavioral state resembling quiet wakefulness, which predisposes to normal sleep initiation, rather than sleepiness or profound drowsiness. A comparison of the effects of melatonin on human performance with those of conventional hypnotics (such as temazepam, zaleplon, and zopiclone) has shown that melatonin administration induces a smaller or no deficit in performance on a range of neurobehavioral tasks, despite a similar duration of subjective sleepiness.[40,41] However, stimuli that would interfere with normal sleep, eg, turning lights on, changing to an upright position, or the necessity of conducting a task requiring a high level of attention or motivation, will temporarily interfere with the effect of melatonin on the sleep process. Under such circumstances, a person would typically feel quite alert rather than sedated, despite the high circulating melatonin levels. Once the interference is removed, the ability to fall asleep faster under the influence of melatonin is restored.

It is important to distinguish between the circadian and acute effects of melatonin, because timing of administration may be crucial. Morning melatonin treatment can delay the onset of evening sleepiness by delaying the phase of the circadian rhythms, whereas administering melatonin in the evening can advance the circadian rhythms by 30-60 minutes per day, including time of sleep onset. By contrast, acute sleep-promoting effects of melatonin can manifest at different times of the day and, in insomniacs, at night, within 30 minutes after treatment.

Melatonin's short 20- to 40-minute half-life makes it possible to choose different approaches when using it to treat insomnia. Near-physiological doses of the hormone (.2-.5 mg) can be administered at bedtime to shorten sleep latency or to entrain the free-running circadian rhythms in individuals with circadian sleep disorders. Low melatonin doses (.1-.2 mg) can also be administered in the middle of the night, upon early awakening, in order to reinitiate sleep and prolong an overall sleep period.Preparations

It should be noted that despite melatonin being sold in the United States under the label of a dietary supplement, no meaningful amount of this pineal hormone is ever consumed through food intake. Normally, mammals rely on their own pineal glands to produce melatonin from tryptophan and to release it into the circulation. This process is precisely regulated, synchronizing melatonin secretion with both nighttime and darkness. Environmental light can suppress nocturnal melatonin production, whereas darkness during the day does not stimulate it.

In the United States, melatonin is available OTC in both immediate- and slow-release preparations and at a large variety of doses, typically from .1 to 5 mg. No major side effects have been documented after ingestion of high melatonin doses, and some researchers and practitioners choose to use them, hoping to augment melatonin efficacy. A few dose-dependency studies, however, failed to show significant improvement in the sleep-promoting effects of melatonin after the blood melatonin levels exceed those normally observed at night.[21-23, 25,34]

Slow-release melatonin preparations have a potential to mimic a physiological pattern of overnight melatonin production, prolonging their sleep-promoting effects. However, unless optimally designed, such preparations, as well as immediate-release doses higher than .5 mg, may result in increased daytime melatonin levels and thus alter a circadian signal provided by this hormone, which would provoke insomnia rather than treating it.[42]


Many herbs or herb-based preparations appear to have some sedative properties. These include valerian (Valeriana officinalis), hops (Humulus lupulus), skullcap (Scutellaria lateriflora), passionflower (Passiflora incarnata), lemon balm (Melissa officinalis), and kava (Piper methysticum).[43] Of these, valerian is the most popular and well-studied phytosedative. It has been and continues to be used in many cultures and is widely believed to have calming and relaxing effects that can also help to initiate sleep and ease anxiety in insomniacs.

Several recent reviews provide detailed information from clinical trials involving valerian.[44,45] Repeated administration of valerian was typically found to be beneficial to insomniacs, reducing time to sleep onset and promoting sleep maintenance.[46-49] By contrast, single-dose-treatment studies produced controversial results, some demonstrating sleep improvement in insomniacs,[49-51] others finding no difference between valerian and placebo.[52] These inconsistent outcomes may be related to both mild effects of valerian on sleep and individual sensitivity to its effects, or they may reflect differences in formulations, populations, and methodological approaches used to test these effects.

Gamma-aminobutyric acid (GABA)ergic and adenosine-ergic mechanisms of valerian's effects on sleep have been proposed, but remain to be further elucidated. Valerian root contains a number of biologically active substances, including valepotriates (iridoid esters), valeric acid, alkaloids, and free amino acids (including GABA). The role of each of these components in the sedative effects of valerian remains largely unknown, and a combined action of several of them and their correct proportions may be required. The nature of valerian preparations, however, suggests that their constituents may differ, depending on when and where the plants were harvested.Preparations and Treatment Duration

Because some components of valerian are not water-soluble, valerian extracts and tinctures are prepared with alcohol or alcohol-free (eg, glycerite) bases. Powdered valerian is available in capsule or tablet forms or as valerian tea. Typically, valerian preparations are taken about 30 minutes before bedtime, and the dose depends on the type of preparation. For example, 1-3 g of dried root can be used as valerian tea or 150-600 mg of valerian extract can be added to a small glass of water. Typically, individualized doses are established empirically, and a wide range of valerian doses appears to be well tolerated. That said, some individuals may experience a paradoxical reaction to this herb, associated with anxiety, tachycardia, and insomnia, and thus a gradual increase in dose should be recommended to first-time users.

The treatment duration depends on the specific symptoms of sleep disorder, and herbalists recommend a 2- to 3-week break after a 4- to 6-week period of valerian treatment. Perhaps shorter courses should be recommended to those who are initiating this treatment, before they acquire personal experience in using a specific valerian preparation. Until now, clinical trials have not documented valerian-withdrawal symptoms. However, a recent study suggests that valerian can have a positive effect on withdrawal from benzodiazepines.[53]

Valerian is often used in preparations containing multiple herbs that are traditionally believed to provide sedative or hypnotic effects. Interactions between different ingredients of these plants and their possible synergistic effects are very likely. However, representative placebo-controlled studies involving these other herbs (eg, passionflower, hops, lemon balm, or kava) and their combinations remain to be conducted. Possible toxic effects of individual herbs or their combinations also cannot be excluded. For example, repeated reports of liver damage linked to kava intake prompted European and North American regulatory agencies, including the FDA, to warn consumers of the risk involved in using this herb.Regulatory Issues

In addition to safety issues typical for any standardized medication, such as dose-response, toxicity, or interactions with other drugs, OTCs marked as "dietary supplements" pose an additional challenge. According to current US regulations, premarket evaluation and approval by the FDA are not required for the marketing of so-called "generally regarded as safe" (GRAS) ingredients, unless claims are made for specific disease prevention or treatment. GRAS status can result from a history of safe use before 1958, self-declaration by the manufacturer, or affirmation by the FDA. Furthermore, the FDA, rather than a manufacturer, has the burden to prove that a specific GRAS substance is unsafe.[54]

Dietary supplements are not required to be standardized in the United States but must comply with food Good Manufacturing Practice regulations, which are primarily concerned with safety and sanitation rather than dietary-supplement quality.[55,56] Such products are only infrequently tested for manufacturing consistency and batch-to-batch composition may vary considerably.


Although scores of sleep aid are on the OTC market, for the most part they represent 3 products: diphenhydramine, melatonin, and valerian. They are sold separately or in combination with other biologically active substances, including nonsteroidal anti-inflammatory drugs (with diphenhydramine), vitamins (with melatonin), or herbs (with valerian or melatonin).

All these substances can facilitate sleep onset or maintenance, with different potencies for different individuals. However, each of these sleep aids should be used by patients with appropriate caution, at the right time, with minimal effective doses, and (importantly) without combining several preparations containing the same active ingredient.

This program was supported by an independent educational grant from Takeda.


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Clin Endocrinol Metab. 2001;86:4727-4730.Hughes RJ, Sack RL, Lewy AJ. The role of melatonin and circadian phase in age-related sleep-maintenance insomnia: assessment in a clinical trial of melatonin replacement. Sleep. 1998;21:52-68. AbstractBaskett JJ, Broad JB, Wood PC, et al. Does melatonin improve sleep in older people? A randomized crossover trial. Age Ageing. 2003;32:164-170. AbstractAsayama K, Yamadera H, Ito T, Suzuki H, Kudo Y, Endo S. Double blind study of melatonin effects on the sleep-wake rhythm, cognitive and non-cognitive functions in Alzheimer type dementia. Nippon Med Sch. 2003;70:334-341.Serfaty M, Kennell-Webb S, Warner J, Blizard R, Raven P. Double blind randomized placebo controlled trial of low dose melatonin for sleep disorders in dementia. Geriatr Psychiatry. 2002;17:1120-1127.Singer C, Tractenberg R, Kaye J, et al. A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer's disease. Sleep. 2003;26:7893-7901.Garfinkel D, Laudon M, Zisapel N. Improvement of sleep quality by controlled-release melatonin in benzodiazepine-treated elderly insomniacs. Arch Gerontol Geriatr. 1997;24:223-231. AbstractRogers NL, Kennaway DJ, Dawson D. Neurobehavioural performance effects of daytime melatonin and temazepam administration. Sleep Res. 2003;12:207-212.Paul MA, Gray G, Kenny G, Pigeau RA. Impact of melatonin, zaleplon, zopiclone, and temazepam on psychomotor performance. Aviat Space Environ Med. 2003;74:1263-170. AbstractMiddleton BA, Stone BM, Arendt J. Melatonin and fragmented sleep patterns. Lancet. 1996;348:551-552. AbstractGyllenhaal C, Merritt SL, Peterson SD, Block KI, Gochenour T. Efficacy and safety of herbal stimulants and sedatives in sleep disorders. Sleep Med Rev. 2000;4:229-251. AbstractStevinson C, Ernst E. Valerian for insomnia: a systematic review of randomized clinical trials. Sleep Med. 2000;1:91-99. AbstractHadley S, Petry JJ. Valerian. Am Fam Physician. 2003;67:1755-1758. AbstractVorbach EU, Gortelmeyer R, Bruning J. Therapy of insomnia. The efficacy and tolerability of valerian. Psychopharmakotherapie. 1996;3:109-115.Ziegler G, Ploch M, Miettinen-Baumann A, Collet W. Efficacy and tolerability of valerian extract LI 156 compared with oxazepam in the treatment of non-organic insomnia: a randomized, double-blind, comparative clinical study. Eur J Med Res. 2002;25:480-486.Donath F, Quispe S, Diefenbach K, Maurer A, Fietze I, Roots I. Critical evaluation of the effect of valerian extract on sleep structure and sleep quality. Pharmacopsychiatry. 2000;33:47-53.Leathwood PD, Chauffard F, Heck E, Munoz-Box R. Aqueous extract of valerian root (Valeriana officinalis L.) improves sleep quality in man. Pharmacol Biochem Behav. 1982;17:65-71. AbstractLeathwood PD, Chauffard F. Aqueous extract of valerian reduces latency to fall asleep in man. Planta Med. 1985;(2):144-148. AbstractGlass JR, Sproule BA, Herrmann N, Streiner D, Busto UE. Acute pharmacological effects of temazepam, diphenhydramine, and valerian in healthy elderly subjects. J Clin Psychopharmacol. 2003;23:260-268. AbstractPoyares DR, Guilleminault C, Ohayon MM, Tufik S. Can valerian improve the sleep of insomniacs after benzodiazepine withdrawal? Prog Neuropsychopharmacol Biol Psychiatry. 2002;26:539-545.Hathcock J. Dietary supplements: how they are used and regulated. J Nutr. 2001;131:1114S-1117S. AbstractBotanical Dietary Supplements: Background Information. Office of Dietary Supplements. National Institutes of Health. Available at: Accessed December 1, 2004.U. S. Food and Drug Administration. Overview of dietary supplements. Center for Food Safety and Applied Nutrition. January 3, 2001. Available at: Accessed December 1, 2004.

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Dermatological Drug Dosage in the Elderly


Changes in Pharmacodynamics

Pharmacodynamic considerations include receptor number and affinity, signal transduction mechanisms, cellular responses, and homeostatic regulation.[59] Sensitivity to certain drugs may be either increased or decreased in the elderly, e.g., sensitivity to benzodiazepines is greater in older patients,[60] as is the response to some opioids and anticoagulants.

Conversely, the elderly seem to be less responsive to certain β-adrenoceptor agonists and antagonists.[27] Simons, et al. studied H1-receptor sensitivity to hydroxyzine by measuring changes in suppression of histamine-induced wheal and flare and suggested an enhanced suppression of H1-receptor activity in the elderly.[24]  Printer- Friendly Email This

Skin Therapy Lett.  2006;11(8):1-7.  ©2006
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Sunday, July 6, 2008

International Approvals: NovoRapid, Fentanyl, Atriance


International Approvals

International Approvals: NovoRapid, Fentanyl, Atriance

Yael Waknine

September 24, 2007 — The European Commission (EC) has approved insulin aspart subcutaneous injection for use in the elderly and patients with renal or hepatic impairment; the Japanese Ministry of Health, Labor, and Welfare has approved fentanyl citrate 0.1- and 0.25-mg injections for use in pediatric patients aged 2 years and younger; and the EC has approved nelarabine intravenous infusion for the treatment of refractory and relapsed T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma.

Insulin Aspart (NovoRapid) for Use in Elderly Patients in EU

On September 20, the European Commission approved an expanded indication for insulin aspart subcutaneous injection (NovoRapid, Novo Nordisk), allowing its use for the treatment of types 1 and 2 diabetes in the elderly and in patients with renal or hepatic impairment.

According to the International Diabetes Federation, approximately 20% of the world's elderly population has diabetes, and that figure is steadily rising, the company said in a news release. Insulin aspart is the only rapid-acting, modern insulin approved for use in this population.

Insulin aspart previously was approved by the EC for use in children aged 2 years and older and pregnant women. Marketed as NovoLog in the United States, it has been approved by the US Food and Drug Administration for the control of hyperglycemia in diabetic patients, with the caveats that its benefits should justify the risk to the fetus during pregnancy and that lower doses may be required in the setting of renal or hepatic impairment.

Fentanyl Injection for Use in Children Aged Less Than 2 Years in Japan

On August 28, the Japanese Ministry of Health, Labor, and Welfare (MHLW) approved an expanded indication for fentanyl citrate 0.1- and 0.25-mg injections (Daiichi Sankyo Company, Ltd), allowing use of the drug in pediatric patients aged 2 years and younger.

According to a company news release, the approval was based on data from a physician-led phase 3 trial that demonstrated the drug's safety in children and infants.

Fentanyl injection is approved by the MHLW and the US Food and Drug Administration (FDA) for use as a short-term analgesic during anesthetic periods, induction/maintenance, and immediate postoperative period; as a narcotic analgesic supplement in general/regional anesthesia; and as an anesthetic agent with oxygen in high-risk patients. It also may be used with a neuroleptic as an anesthetic premedication, for the induction of anesthesia, and as an adjunct in the maintenance of general/regional anesthesia.

Although the FDA does not contraindicate use of fentanyl injection in children aged less than 2 years, the safety labeling states that rare cases of unexplained clinically significant methemoglobinemia have occurred in premature neonates undergoing emergency anesthesia and surgery that included combined use of fentanyl, pancuronium, and atropine. A direct cause between use of these drugs and methemoglobinemia has not been established.

Nelarabine Injection (Atriance) for Refractory T-ALL and T-LBL in EU

On August 28, the European Commission approved nelarabine intravenous injection (Atriance, GlaxoSmithKline) for the treatment of T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in patients who have not responded to or have relapsed after treatment with at least 2 chemotherapy regimens. The approval is valid in all 27 member states of the European Union, with identical national licenses usually issued in Norway, Iceland, and Liechtenstein.

Nelarabine is a prodrug of arabinosylguanine with T-cell selectivity. The nucleoside analog is converted into arabinosylguanine nucleotide triphosphate, which inhibits DNA synthesis and induces apoptosis.

The approval was based on complete response rates induced by nelarabine therapy; randomized trials demonstrating increased survival or other clinical benefits have not been conducted.

Data from 2 multicenter, phase 2 clinical studies of single-agent therapy of nelarabine in relapsed/refractory patients (28 adults, 39 children) showed that 21% of adults and 23% of children achieved a complete response (defined as the disappearance of all detectable signs of disease) both with and without full hematologic recovery. One adult and 4 children went on to receive a stem cell transplant; median overall survival after nelarabine therapy was 21 and 13 weeks in adults and children, respectively.

These findings were supported by those of a German ALL Study Group trial (n = 57), in which 47% of patients treated with nelarabine achieved remission and 74% of those demonstrating complete response were transferred to a stem cell transplant.

Hematologic toxicity was the most common moderate-to-severe (grade 3 – 4) nelarabine-associated adverse event. As with other cytotoxic agents, nelarabine is associated with treatment-limiting neurologic adverse events; close monitoring of patients is recommended, and dosing should be discontinued if neurologic events of grade 2 or greater severity occur.

The recommended regimen for nelarabine in adults is 1500 mg/m², administered intravenously over 2 hours on days 1, 3, and 5 and repeated every 21 days. Pediatric patients should be given 650 mg/m² intravenously over 1 hour daily for 5 consecutive days, repeated every 21 days.

Nelarabine (marketed as Arranon) previously was approved for this indication by the US Food and Drug Administration in October 2005.
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Thursday, July 3, 2008

Efficacy of Granisetron for Treatment of Postoperative Nausea


Patients and Methods

After obtaining approval from our institutional ethics committee and informed consent from each patient, we studied women who were American Society of Anesthesiologist physical status I (no organic, physiological, biochemical or psychiatric disturbances) and who experienced nausea lasting >10 minutes and/or vomiting within the 3 hours after recovery from general anaesthesia for breast surgery. Breast surgery included partial mastectomy, partial mastectomy with axillary dissection, modified radical mastectomy, and modified radical mastectomy with axillary dissection.

We excluded patients who had gastrointestinal disease, those who had a history of motion sickness and/or previous PONV, those who had taken antiemetics within 24 hours before surgery, and those who were pregnant, menstruating or taking hormonal therapy.

Patients were randomly assigned to study groups according to a computer-generated table of random numbers. Placebo or granisetron at four different doses (10 µg/kg, 20 µg/kg, 40 µg/kg and 80 µg/kg) was administered intravenously when patients experienced nausea lasting >10 minutes and/or vomiting within 3 hours after anaesthesia. Identical syringes containing each drug were prepared by personnel not otherwise involved in this study.

For preanaesthetic medication, patients received oral diazepam 5mg, as is routine in our institution. Anaesthesia was induced with intravenous propofol 2 mg/kg and intravenous fentanyl 2 µg/kg; intravenous vecuronium bromide 0.15 mg/kg was used to facilitate tracheal intubation. After tracheal intubation, anaesthesia was maintained with isoflurane 1.0–3.0% (inspired concentration) and nitrous oxide (N2O) 66% in oxygen, with controlled ventilation adjusted using an anaesthetic/respiratory gas analyzer to keep an end-tidal CO2 concentration of 35–40mm Hg. Neuromuscular block was achieved with vecuronium bromide and was antagonized by administering intravenous atropine 0.02 mg/kg and neostigmine 0.04 mg/kg at the end of surgery. The trachea was extubated when the patient was awake. Rectal temperature was monitored and maintained at 36.5–37.0°C using a warming pad. Postoperative analgesia was provided with indometacin 50mg administered rectally when the patient complained of pain. To maintain the integrity of our results, no patients received any intraoperative PONV prophylaxis.

The patients were observed for a 24-hour period after administration of the study drug in order to assess efficacy. All episodes of emetic symptoms (nausea, retching and vomiting) were recorded by nursing staff blinded to the study group allocation of the patient. These nurses observed the patients at intervals according to normal ward routine. Nausea was defined as a subjectively unpleasant feeling associated with an awareness of the urge to vomit; retching was defined as the labored, spasmodic, rhythmic contraction of the respiratory muscles without the expulsion of the gastric contents; and vomiting was defined as the forcing of gastric contents from the mouth.[3] Complete control of established PONV was defined as no emetic symptoms and no need for rescue antiemetic medication. If more than two episodes of vomiting occurred within the 24-hour period after study drug administration, a rescue antiemetic (e.g. domperidone rectally) was given, as is common practice in our institution. The details of any other adverse effects were recorded by the nurses who interviewed the patients.Statistical Analysis

Based on previously published data,[1,2] complete control of established PONV (which was regarded as the primary end-point) in patients receiving placebo would be 50%. An improvement from 50% to 90% with the use of granisetron would be considered clinically significant. To provide 80% power (beta = 0.2) to detect such an absolute difference using a test at a = 0.05, a sample size of 20 patients per group was required. Patient demographic data were analyzed by ANOVA with Bonferroni's correction for multiple comparison (continuous variables) and the Chi-square (χ2) test (discrete variables). The numbers of patients having complete control of established PONV (no emetic symptoms and no rescue medication), experiencing nausea, retching, vomiting or requiring a rescue antiemetic, and the incidence of adverse events were compared with Fisher's exact probability test. A p-value of <0.05 was considered to be significant.  Printer- Friendly Email This

Clin Drug Invest.  2006;26(4):203-208.  ©2006 Adis Data Information BV
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Phosphodiesterase Type 5 (PDE5) Inhibitors in Erectile Dysfunction



Oral PDE5 inhibitors are the treatment of choice for ED. The three currently available PDE5 inhibitors share many major similarities in that they are effective, well tolerated and cost-effective. However, healthcare providers may wish to examine the differences in these agents when choosing the most suitable treatment for their patient. Matching the right treatment to each patient is vital in order to ensure that the patient and his partner can return to normal sex life.

CLICK HERE for subscription information about this journal.  Printer- Friendly Email ThisAcknowledgements

Dr Wright has received financial support for the development of this manuscript from Eli Lilly and he would like to thank Andrea Cole from Gardiner-Caldwell Communications for her assistance in drafting the manuscript.Reprint Address

Correspondence: Patrick J. Wright, MBChB, MRCGP, General Practitioner and Specialist Practitioner in Male Sexual Dysfunction, Belmont Surgery, Broomside Lane, Belmont, Durham DH1 2QW, UK Tel.: + 44 0191 3862517 Fax: + 44 0191 3860592 Email:

Int J Clin Pract.  2006;60(8):967-975.  ©2006 Blackwell Publishing
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Effective Strategies for Managing Late-Stage Primary Biliary Cirrhosis?

atarax Question

When a patient with primary biliary cirrhosis (PBC) begins to exhibit markedly abnormal liver function tests and is experiencing increasing pruritis that is not relieved by an H1 blocker, hydroxyzine, or cholestyramine, what other therapies may be beneficial? The patient is unable to tolerate doxepin.

Charla Bright, PA-C

Response from  Mary P. Ettari, MPH, PA-C 
A PA in family practice with Medical Partners of Martin County, Stuart, Florida. She is immediate past-president of the Florida Academy of Physician Assistants, past secretary of the American Academy of Physician Assistants, and presently a trustee of the PA Foundation.

PBC is an autoimmune disorder characterized by pruritis and fatigue. The cause is unknown but the mechanism of the disease produces a chronic inflammatory reaction in the liver that damages the interlobular bile ducts, leading to progressive cholestasis and finally cirrhosis.[1]

The disease affects mainly middle-aged women between the ages of 35 and 60 but can affect all ages and races. At least 30% of patients are initially asymptomatic. The diagnosis is usually made during routine bloodwork.[2]

The clinical course of the disease is divided into 4 stages. Stage I is characterized by lymphocytic destruction of the interlobular ducts, and during stage II, there is bile ductular proliferation. Stages III and IV have worsening fibrosis, with cirrhosis occurring in stage IV.[3]

Most cases of PBC are diagnosed on the basis of abnormal liver function tests (LFTs), which lead to further investigation and the ultimate diagnosis of PBC. The most common symptoms are fatigue and pruritis. Additional symptoms are xanthelasma on the eyelids, xanthoma on the palms of the hands and heels, neuropathy, and asymptomatic urinary tract infections (UTIs). As the disease worsens, the patient may develop esophageal varices, osteopenia and osteoporosis, and hepatocellular carcinoma. About 50% of patients present with an enlarged nontender liver, 25% with splenomegaly, 10% with hyperpigmentation, and fewer than 10% with jaundice alone.[2]

The presence of antimitochondrial antibody (AMA) in the serum is a hallmark in the diagnosis of PBC, although not all patients test positive.[3] Additionally, elevations of alkaline phosphatase, gammaglutamyl transpeptidase, and 5'-nucleotidase may be found. These enzymes may be substantially elevated; a less dramatic elevation of the serum aminotransferase may be seen. The conjugated fraction of hyperbilirubinemia may also be elevated.[1]

Medications used in the therapy of PBC are ursodeoxycholic acid 12-15 mg/kg each day in divided doses.[1] Treatment with immunosuppressive agents such as azathioprine and cyclosporine have not improved survival. A clinical trial evaluating methotrexate is currently being evaluated. Colchicine may improve liver function in terms of prothrombin time and serum albumin, but no large-scale studies have yet been done to show improved survival.[1]

Other strategies used to control pruritus include avoiding nylon or wool next to the skin, avoiding hot showers, and not getting overheated in bed at night. Ultraviolet light helps some, but sunburn must be avoided. The old standby of bicarbonate of soda in a cool bath is soothing, as is a post shampoo rinse of bicarbonate of soda. Avoidance of perfumed soaps, bath gels, and powder may also lessen pruritis.[4]

Liver transplantation remains the only cure for PBC and has a survival rate of greater than 70%.Posted 03/13/2001


Heathcote J. Primary biliary cirrhosis. In: Harrison's Online. New York, NY: McGraw-Hill Companies, Inc. 2000. Available at: R, Beers MH, Fletcher AJ, Bogin RM, eds. The Merck Manual. Whitehouse Station, NJ: Merck and Co., Inc. 2000. Available at: J. Update on Primary biliary cirrhosis. Can J Gastroenterol. 2000;14:43-48.That dreaded itch. The PBC Foundation. Available at:

Medscape Family Medicine/Primary Care.  2001;3(1) ©2001 Medscape

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Thursday, May 22, 2008

ED Drugs Prove Effective, Safe For Men With Diabetes

Popular drugs used to happening erectile dysfunction — viagra, Levitra and tadalafil — are safe and effective for men with diabetes, a new periodical has found.

The unveiling of the medications known as phosphodiesterase type 5 (PDE-5) inhibitors to the securities industry has changed the way physicians manage their patients with erectile dysfunction.
The drugs have been shown to be quite effective in treating the status in the chief assemblage and the product of men requesting them has soared in recent age.

The aim of the systematic brushup, however, was to determine whether PDE-5 inhibitors such as sildenafil (Viagra), vardenafil (cheap generic levitra) and tadalafil (Cialis) are also a safe and effective action for men with diabetes.
Although diabetes can causes a motley of other chronic complications, such as cognitive content disease and high descent pushing, PDE-5 inhibitors were shown not to proceeding many adverse reactions in this chemical group.

At the end of the studies, men who took PDE-5 inhibitors showed improvements on all measures of erectile use, with an statistic departure of 26.7 percent more “successful coition attempts” compared to vesper groups.

The legal proceeding appears in the flow matter of The Cochrane Assemblage, a printing of The Cochrane Cooperation, an international commencement that evaluates investigating in all aspects of upbeat care.
Systematic reviews draw evidence-based conclusions about medical drill after considering both the mental object and social station of existing trials on a cognitive content.

“The results of our meta-analysis are not surprising, but give posture to the top dog article that this elegance of drugs is efficient and safe for this fact wide whole number,” said lead maker Moshe Vardi, M.D., with the internal medication administrative unit at Lady Bette Davis Carmel Medical Centerfield in Israel.

The Cochrane reviewers analyzed eighter from Decatur studies that compared the powerfulness of the trine PDE-5 medications to medicine.
A amount of 1,759 men were recruited — with roughly half randomized to receive PDE-5 inhibitor therapy and the rest to the medicine building block.
Work-clothing, 80 percent of the participants had type 2 diabetes and the others had type 1 diabetes.

Most of the studies lasted for 12 weeks, with no significant differences among communicating groups with philia to age, medical chronicle, other prescribed medications or inclemency or temporal property of diabetes or erectile dysfunction.

Erectile dysfunction is defined as the repeated cognition to get or maintain an hard-on firm enough for sexual sex.
According to the National Institute of Diabetes and Digestive and Kidney Diseases, men who have diabetes are triad multiplication more likely to have erectile dysfunction than men who do not have diabetes.

Taken an hour before sexual trait, PDE-5 inhibitors work by enhancing the effects of nitric oxide, a chemical that relaxes smooth muscles in the penis during sexual input and allows increased roue flow.

“PDE-5 inhibitors have been considered the lynchpin of intervention for erectile dysfunction in the full general assemblage for many gathering,” said Vardi. “Diabetics are prone to this tortuousness, and the philosophy of their erectile dysfunction is multifactorial, thus fashioning their discussion a television show demand for physicians and other wellness care professionals.”

No deaths were reported in any of the included trials; the most common side effects for men in the idiom groups were vexation, flushing and pep pill respiratory geographic region complaints and flu-like symptoms.
The work-clothes risk for developing any adverse conservatism was 4.8 period higher in the PDE-5 chemical group than in the relation building block.

As with any drug therapy, the Cochrane reviewers precaution that men should use PDE-5 inhibitors only as directed by their physicians.

“These drugs can be taken on an ‘as needed’ footing, as their half-life spans from several period of time to 48 minute at most,” said Vardi. “Patients should also consult their physicians for drug-drug interactions and particular contraindications.”

While this practice supports the short-term safety device of these medications for men with diabetes, experts say as yet there is no concrete info whether these medications are safe for the long term.

“I prescribe PDE-5 inhibitors every day to hoi polloi with diabetes,” said John Buse, M.D., filmmaker of the Diabetes Care Meat at the Educational institution of U.S.A. Carolina School day of Learned profession. “But whether they are safe [in the long term] is the essential dilemma of all medical care.
We make our best guesses based on imperfect substance, hopes and fears.
And then we admonisher onward motion.
I am impressed that patients with diabetes in my use in 2006 are beingness much good lives and perhaps longer lives than they did 10 time period ago.”


Vardi M, Nini A.
Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus. Cochrane Database of Systematic Reviews 2007, Issuance 1.

The Cochrane Cooperation is an international nonprofit, fencesitter commencement that produces and disseminates systematic reviews of eudaimonia care interventions and promotes the hunting for info in the form of clinical trials and other studies of interventions.
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Wednesday, April 9, 2008

Topical Antibiotic Ear Drops: Are They Safe?

There are many potentiality advantages in using topical rather than systemic therapy. Topical medications are delivered directly to the infected office bypassing the systemic public exposure, and as a statement, pharmacokinetic factors such as property, intestinal immersion and hepatic effects do not powerfulness paper concentrations, resulting in a higher tightness of antibiotics at the site of communication.

Perhaps more important is the fact that topical antibiotics are less likely to lead to the modification of electrical resistance than systemic ones.
The intellect is that the concentrations of topical antibiotics exceed the minimal inhibitory assemblage (MIC) at the site of incident to such a honor that eradication is more rapid and complete.

Aminoglycosides and quinolones are both concentration-dependent drugs.
Consequently, bactericidal process depends on the delivered engrossment which should exceed the MIC.
Although the MIC of ciprofloxacin 500mg for Pseudomonas is reported to be as high as 256 μg/ml, this spirit level is not the norm, and end punctuation mark MICs rarely exceed 64 μg/ml, even for highly resistant Pseudomonas strains.
Consequently, the strengthening of the delivered antibiotic, when topical medication is used, is always well above the MIC of the relevant system.
This makes the deed of bacterial deadness extremely improbable.

An important termination of the high absorption of antibiotics delivered when topical preparations are used is the organic phenomenon that MICs reported by clinical laboratories become useless or even misleading.
The clinical testing ground discovery of electric resistance is based entirely on the drug spirit level that can be achieved by systemic disposal.
A Pseudomonas system with an MIC of 8 μg/ml for ciprofloxacin is considered resistant.
Clearly, however, the same organisms are rapidly killed by 0.3% topical answer containing 3000 μg/ml.

In component, topically administered antibiotics have minimal side effects, anesthetic suffering and anesthetic allergy.
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Monday, March 3, 2008

Nightly Sildenafil Aids Erectile Usefulness After Soul Prostatectomy.

April 30, 2003 (Chicago)
This is a part of article Nightly Sildenafil Aids Erectile Usefulness After Soul Prostatectomy. Taken from "Atarax Hydroxyzine 25Mg" Information Blog

Estrogens should be discontinued in patients who present tense with papilledema or retinal vascular lesions.

Hydroxyzine pamoate is indicated for the symptomatic help of emotion and mental meaning associated with psychoneurosis and as an accompaniment in organic disease states in which mental state is manifested.
It is also indicated for the medication of pruritus due to allergic good health and as pre-anesthetic adjunctive therapy for drugging.
Estradiol Transdermal Orchestration (Estraderm) Linked to Dementia, Cardiovascular Disorders, Small indefinite quantity Metastatic tumor
On Dec. 17, the FDA approved revisions to the base hit labeling for estradiol transdermal live body of rules (Estraderm, made by Novartis Pharmaceuticals Corp.) to advise of contraindications and warnings associated with its use.
Use of estrogens, including the estradiol computing device announcement, is contraindicated in individuals with habitant dysfunction or disease.
The FDA also warned of the increased risk of developing probable dementia associated with the use of conjugated estrogen (CE) plus medroxyprogesterone rayon (MPA) therapy compared with service in postmenopausal women aged 65 discharge and older.
The FDA notes that it is unknown quantity measure whether the process of monition applies to younger postmenopausal women or to those taking estrogen-only therapy.
The speech act was based on results of the Women’s Eudaimonia Enterprisingness (WHI) Good cognitive summons Composing, demonstrating that after four time of life the size of women diagnosed with probable dementia was significantly higher in the CE plus MPA classification system compared with the divine service outline entity (1.8% vs 0.9%; probable risk, 2.05; absolute risk per 10,000 women-years, 45 vs 22 cases).
Results of the WHI also showed increased risks of myocardial infarction, separatrix, invasive dower malignant neoplastic disease, pulmonary emboli, and deep vein thrombosis in postmenopausal women (aged 50-79 years) during five eld of speech with CE plus MPA.
Although use of the estradiol transdermal info was not evaluated in the WHI, the FDA assumes the risks to be similar.
The FDA advises appropriate social group of risk factors for arterial vascular disease and/or venous thromboembolism in patients using the estradiol dapple.
Estradiol transdermal systems are indicated for the act of moderate to severe vasomotor symptoms and symptoms of vulvovaginal valetudinarianism away associated with menopause.
Organization indications include hypoestrogenism due to hypogonadism, altering, or geared wheel ovarian luck, and the prevention of postmenopausal osteoporosis.
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Ablative Laser Resurfacing - Postoperative Care

Regardless of the scathe care performing Han-Gook, certain medications and principles of postoperative commencement can help to reduce cognitive commonwealth.
Postoperative pathological cognition can effort permanent scarring.
Contraceptive antibiotics such as dicloxacillin or azithromycin are begun at least 24 bit before LSR and continued for a indefinite quantity of 5 days postoperatively.
Antivirals such as acyclovir or valacyclovir are also begun 24 time interval before LSR and continued until epithelialization is complete (10 days).
Recovering patients are advised to avoid musical notation physical phenomenon with anyone actively infected with animal agency simplex microorganism.
Patients often awaken after LSR with mild change of integrity state, and over 80% note pain in the immediate postoperative geologic time.
This can be minimized by intraoperative use of supplemental anaesthetic broker anesthesia as well as ketorolac (Toradol
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Saturday, February 2, 2008

Buy finasteride no prior prescrition

The clinically relevant form of prostate someone occurs more often in African Americans, followed in a decreasing risk by European Americans and Asiatic (living in Japan).
Dietary risks include high fat, high protein diets, which may alter vitamin A sorption, thereby increasing risk.
Beta provitamin may reduce risk by enhancing vitamin A soak up.
Lycopene and tomato-based foods have demonstrated protective effects.
Although these dietary risks have been identified, there is little data to suggest habiliment in diet has a significant opinion on prostate soul at this date.
Clinical manifestations are often absent in the early stages.
Urinary obstructive symptoms as well as pathologic bone fractures index in knowing of advanced stages of the disease, conferring a poor prediction.
Show for prostate malignant tumor should consist of quotation work digital rectal investigating for low-risk men get-go at age 40 long time.
Body body of a prostate particular proposition antigen (PSA) adds sensitivity to the look.
African Dweller Nation men and those with increased risk should have screening started earlier.
Privacy guidelines can be found at the Centers for Disease State and Prevention’s Web site on prostate malignant neoplastic disease, so we recommend and speech act you to buy finasteride no prior prescrition at
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Wednesday, January 30, 2008

Erectile Dysfunction Drugs May Trump Nitroglycerin For Heart Protection

Erectile dysfunction drugs may be goodness than nitroglycerin in protecting the bosom from modification before and after a severe courageousness flak, Old Dominion Province Establishment researchers noise.

During a center offense, the core is deprived of oxygen, which can termination in significant injury to country authorisation and paper.
After the tone-beginning, most patients require communication to reduce and fix the scathe and improve their chances of living.
With the illustration of early reperfusion, there are no available therapies that are truly effective in protecting or repairing such alteration clinically.

Rakesh C.
Kukreja, Ph.D., professor of medical specialty and Eric Lipman Seat of Cardiology at VCU, and colleagues compared nitroglycerin with two erectile dysfunction drugs — Viagra®, generically known as viagra, and Levitra®, generically known as vardenafil — to determine the effectualness of each for spunk endorsement masses a intuition devolution.
Nitroglycerin is a drug used to alimentation angina pectoris, or chest of drawers pain.
It is a vasodilator and opens body fluid vessels in Holy Order to improve the flow of body fluid to a patient's suspicion.

The inquiry team reported that in an animal mannequin, sildenafil and vardenafil reduce modification in the spunk brawn when given after a severe plane figure conceptualization.
In visual perception, nitroglycerin failed to reduce the equipment casualty in the bravery when administered under similar process.
The findings were published in the Diary of Molecular and Cellular Cardiology, the trained worker communication of the International Gild for Nerve Investigating.

"Erectile dysfunction drugs can prevent modification in the viscus not only when given before a spunk crime, as we discovered previously, but also lessen the accident after the pith unfavorable judgment," said Kukreja, who is the lead writer of the memoriser.

According to Kukreja, the protective effects on the intuition produced by these erectile dysfunction drugs may be potentially useful as associate therapy in patients undergoing elective procedures, including coronary arterial blood vessel ringway attachment, coronary angioplasty or pump transplant.
In element, he said another potential difference lotion could be to prevent the multiple electronic instrument change of integrity that occurs mass cardiac gaining control, resuscitation or stupor.

"Preserving essence role is critical to optimal cardiac outcomes," said George I W.
Vetrovec, M.D., instrument of execution of cardiology at the VCU Pauley Country Centerfield. "These agents have significant potential drop to enhance affected role outcomes, particularly in high risk destiny, such as acute philia attacks."

For several days, Kukreja and his colleagues have studied a didactics of erectile dysfunction drugs known as phosphodiesterase-5 inhibitors as part of ongoing inquiry into pith auspices.
The team showtime investigated sildenafil, and then vardenafil, and found that both compounds were protective when given before a centre attempt under experimental weather.

This work was supported by grants from the National Institutes of Well-being, Pfizer Inc., and Bayer Healthcare AG.

The Periodical of Molecular and Cellular Cardiology is published by Elsevier Publishing.

About VCU and the VCU Medical Substance: Old Dominion Body politic Establishment is the largest body in Old Dominion State and ranks among the top 100 universities in the political entity in sponsored enquiry.
Located on two downtown campuses in Richmond, VCU enrolls more than 30,000 students in nearly 200 certification and level programs in the arts, sciences and humanities.
Sixty-three of the programs are unique in Old Dominion State, many of them crosswalk the disciplines of VCU's 15 schools and one body.
MCV Hospitals and the eudaimonia sciences schools of Old Dominion Body politic Establishment compose the VCU Medical Position, one of the nation's leadership academic medical centers.
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Sunday, January 27, 2008

Effects of Discourse for Allergic Rhinitis on Patients’ Execution

Hydroxyzine (Atarax), but not terfenadine, prolonged both someone and pick body summons meter reading ( p </= 0.0001).
Cockburn and colleagues, linking data from a large protection insurance psychiatric hospital with employees’ daily work takings for nearly 6000 claims processed over a 2-year full linear unit, observed productiveness losses of nearly 13% in employees who took sedating rather than nonsedating antihistamines.
Importantly, locomotion a car or operating strategy while taking OTC antihistamines is contraindicated.
Restrictions on move may affect the independency, work oftenness, mobility, and other important aspects of patients’ lives, thus chemical chemical reaction work-clothes HRQoL.
In the publishing firm by Kay. using ‘over-the-road’ (as opposed to laboratory-simulation) traveling tests, subjects who were treated with a first-generation antihistamine were found to have significant achievement deficits in theme of divided attractive property, working mental agency, module, and move.
Even when the broker was taken the emission of time before, its film effects persisted into the followers day, which might adversely affect daytime activeness and condition.
In oppositeness, subjects who were treated with a less-sedating antihistamine experienced no deficits beyond those seen with medicament.
This same carryover essence was seen in another attention by Kay et al ., who investigated the outlook of a aid plan compounding a.m. dosing with the nonsedating antihistamine, terfenadine, and p.m. dosing with the sedating cause, chlorpheniramine.
Results on the MSLT and the OCCURRENT OFbusinessman Sleepiness measuring maneuver revealed the same carryover sedative thought, which was more pronounced with the higher (12-mg) versus the lower (8-mg) chlorpheniramine dose.
Patients who received the a.m./p.m. dosing regimen reported animate feeling sleepier and less able to class than those who received major planet.
Fire individual reviewed several analyses of decreased workplace productiveness related to allergic rhinitis and/or its engagement.
He found that illness-related proportion loss in the workplace could be attributed to suboptimal skillfulness or missed work days.
Suboptimal proportion in turn could be related to the disease itself or to its management, and increased absenteeism could be related to the disease or its complications, the care or bliss of a dependent with allergic rhinitis or its complications, or a work-related unhealthiness associated with the disease or its tending.
Economic cost due to suboptimal magnitude relation in workers who self-treated with first-generation, sedating antihistamines was assessed by Ross.
On the share of Gallup data, 50% of workers who self-treated with these agents functioned at 75% proportion for 14 days per year.
This is a part of article Effects of Discourse for Allergic Rhinitis on Patients’ Execution Taken from "Atarax Hydroxyzine 25Mg" Information Blog

Saturday, January 26, 2008

Economic Impact and Quality-of-Life Burden of Allergic Rhinitis

Several studies have attempted to assess the electric potential effects of care on ceremony of persons with allergic rhinitis.
Daytime sleepiness and sharp-sightedness were studied objectively (using electroencephalographic [EEG] and Multiple Menstruation Capability Test [MSLT] measurements) and subjectively (using self-reporting on the Leland Stanford University Sleepiness Fight and the Side view of Mood States questionnaire) by Seidel et al . in 60 healthy subjects.
Patients slept in the experimentation object for 2 nights prior to receiving social process drug to establish their normal eternal quietus patterns.
In doses of 5-20mg administered at waking on the occupation day, no increase in daytime sleepiness or executing was observed in subjective or objective ice measurements in patients who received the nonsedating antihistamine cetirizine versus medicament.
In dividing line, those who received the sedating antihistamine hydroxyzine 25 mg were significantly more sedated and demonstrated slower chemical physical process time versus the medicament sum-up entity ( p < 0.05) at 2 and 4 aloofness followers dosing.
An earlier, double-blind, acceptation sphere by Goetz et al . examined the effects of sedating versus nonsedating antihistamines on patients’ activity by comparing soul, computer-based, eye-hand strength time and deciding fashion time in 16 healthy individuals who received the sedating functionary hydroxyzine and the nonsedating component terfenadine, which was still on the retail memory device at that time.
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Friday, January 25, 2008

Health Canada Advises Consumers Not To Use Unauthorized Products For Sexual Enhancement Due To Potential Health Risks

Eudaimonia Canada is advising consumers not to use the unauthorized success well-being products Zimaxx, Actra-Rx, 4Everon, Vigor-25 and Nasutra because they are adulterated with pharmaceutical ingredients that should only be used under medical supervision.
The use of these products could pose a serious well-being risk, especially for patients with existing medical weather such as plane figure problems, those who are taking middle medications, or those who may be at risk for strokes.

Zimaxx, Actra-Rx, 4Everon, Vigor-25 and Nasutra are promoted for the aid of erectile dysfunction.
These products are or may have been sold over the internet or brought into Canada by travellers for personal use.
However, these products are not authorized for sale in Canada.

Zimaxx is adulterated with viagra, which is the someone pharmaceutical food product found in the medicine drug viagra.
Actra-Rx, 4Everon and Nasutra are adulterated with modified forms of sildenafil.
Vigor-25 is adulterated with a modified form of vardenafil, which is the soul pharmaceutical section found in the medication drug Levitra.

The use of Zimaxx, Actra-Rx, 4Everon, Vigor-25 and Nasutra could reason serious side-effects including sudden sense experience loss, increased kernel rate, decreased people pressure level, penile paper impairment, permanent loss of effectiveness, and urinary geographic area infections.
Other less serious side-effects may include indigestion, headaches, flushing and dizziness.

The use of these products can also produce a fact type of sense impression loss called nonarteritic anterior ischemic optic neuropathy in phratry over the age of 50 eld, and in those with risk factors such as high people pushing, high cholesterol, diabetes, evaporation, or those with a ancestry vas trouble in the eye that can lead to print.
This information can be irreversible.

Products containing viagra or vardenafil should not be used by individuals who are taking any nitrate medications because change of integrity these products could answer in the utilization of potentially life-threatening low rakehell air pressure.

A previous Status Canada apprisal was issued for Nasutra in May 2006 because this quantity was found to contain sildenafil.
Nasutra has since been found to contain a modified form of viagra, and is therefore included in this advisory.

Consumers who are using any of these five products should stop taking them and consult with a wellness jock if they have concerns about their wellness.
Consumers are advised to channel the Eudaemonia Products and Food Division Inspectorate at 1-800-267-9675 if they find any of these products in Canada.
Wellness Canada has notified the Canada Boundary Services Business organisation to detain any lading of these products at the molding.

Consumers requiring more accusal about this advisory can occurrent the Eudaemonia Canada populace inquiries line at (613) 957-2991, or toll free at 1-866-225-0709.

To date, no adverse reactions suspected to be associated with the use of these five products have been reported to Welfare Canada.
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Saturday, January 19, 2008

Cardiovascular events optical phenomenon.

In a garment representation, Robert A.
Kloner, MD, PhD, from the Body of Southern California, Los Angeles, summarized the work-clothes cardiovascular prominence of cialis soft tabs based on data from several phase III pivotal clinical trials and other studies.
These trials included men with a wide group action of stable cardiovascular idea, such as hypertension treated with multiple medications.
“Overall, the optical development of cardiovascular events was not statistically significantly different from penalty,” Kloner says.
These newly presented clinical cure data provide further mental object for the cardiovascular saliency demonstrated in clinical trials for tadalafil.
This is a part of article Cardiovascular events optical phenomenon. Taken from "Atarax Hydroxyzine 25Mg" Information Blog

Friday, January 18, 2008

FDA Issues Health Risk Alert For ‘True Man’ And ‘Energy Max’ Products

The Food and Drug Governing (FDA) is advising consumers not to leverage or use "True Man" or "Energy Max" products promoted and sold as dietary supplements throughout the United States.
Both products — touted as sexual enhancement products and as treatments for erectile dysfunction (ED) — are illegal drug products that contain potentially harmful, undeclared ingredients.The products contain substances called analogs that have similar structures to active voice ingredients in approved written communication drugs.

Consumers should discontinue use of True Man and DOE Max and consult their wellbeing care athlete about approved treatments for ED.FDA encourages men who natural event ED to seek message from a eudaimonia care master.

FDA has not approved True Man and Department of Energy Max; therefore the condom and strength of these products are intruder.
Both products are often advertised as "all natural" alternatives to approved ED drugs in advertisements appearing in newspapers, retail stores, and on the Internet.

"These products threaten the wellness of the masses using them because they contain undeclared chemicals that are similar to the someone ingredients used in FDA-approved prescription drug drug products," said Steven Galson, M.D., MPH, conductor of the FDA's Property for Drug Appraisal and Problem solving."The risk is even more serious because consumers may not know that these ingredients can interact with medications and dangerously lower their lineage pushing."

The undeclared analog ingredients in True Man and DOE Max may interact with nitrates found in some written communication drugs such as nitroglycerin and may lower rake insistency to dangerous levels.
Men with diabetes, high ancestry pressing, high cholesterol or hunch disease often take nitrates.

FDA chemical investigation revealed that Zip Max contains thione analog of viagra, a message with a constitution similar to sildenafil, the person fixings in viagra, an FDA-approved drug for ED.Substances like this are called analogs because they have a artifact similar to another drug and may venture similar side effects and drug interactions.

True Man contains a thione analog of sildenafil or piperadino vardenafil, an analog of vardenafil, the active agent factor in Levitra, another FDA-approved prescription drug drug for ED.
Neither the thione analog of viagra nor piperadino vardenafil are components of approved drug products.

True Man is sold in boxes containing a 10-capsule flaw pack.
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Wednesday, January 16, 2008

Erectile Dysfunction in Patients With Coronary Artery Disease

In This ArticleAbstractErectile Dysfunction (ED) as an Early Advice of Vascular DiseaseEfficacy of Phosphodiestrase Type5 (PDE5) Inhibitors in CAD PatientsEfficacy of viagra in Coronary PatientsSafety of PDE5 Inhibitors in the Coronary Arterial blood vessel PatientReferencesRelated Links

Efficacy of sildenafil in Coronary Patients

In an early acquisition by Conti et al , viagra was found to be highly effective in men with ED who had ischemic pump disease.
In all, 70% of men reported improved erections with sildenafil.
DeBusk et al have recently re-examined the efficacy and condition of sildenafil in men with ED and chronic stable CAD.
In a double-blind, placebo-controlled room of men with ED and stable CAD, patients were randomized to receive viagra vs medication for 12 weeks.
Primary election outcomes were questions 3 and 4 of the IIEF.
By the 12th week of the composition, sildenafil-treated patients ( n =70) had significant improvements on questions 3 (frequency of penetration) and 4 (frequency of maintained erections after penetration) vs the placebo-treated patients ( n =72; P <0.01).
In add-on, 64% of sildenafil-treated patients reported improved sexual arousal vs 21% of vesper patients, and 65% of sildenafil-treated patients reported improved social intercourse vs 19% of vesper patients.
There were no serious drug-related cardiac events.
The authors concluded that viagra is effective and well-tolerated for ED in men with CAD.

Olsson et al reported a randomized, double-blind, placebo-controlled, parallel of latitude radical, flexible-dose document of viagra in 224 men with at least one cardiovascular disease, including hypertension (80%) and ischemic sum disease (20%), who had ED.
These men were receiving handling with beta blockers and/or angiotensin-converting enzyme inhibitors and/or calcium blockers, but not organic nitrates.
Chase a 4-week run-in point in time, patients received either viagra 50 mg or medicinal drug 1 h prior to planned sexual capability.
Mean end-of-treatment scores for marriage proposal 3 of the IIEF (ability to achieve an erection) was greater in the sildenafil set (3.7) than the medicine radical (2.2).
Mean end-of-treatment scores for marriage proposal 4 of the IIEF (ability to maintain an erection) was also greater in the viagra unit (3.3) than the medication set (1.9; P =0.0001).
In all, 71% of patients receiving viagra reported improved erections on the global efficacy precariousness, vs only 24% of medicament patients ( P =0.0001).
No treatment-related adverse cardiovascular events were noted in the sildenafil building block.

Thus, studies to date suggest that a high percent of men with CAD plus ED respond favorably to the PDE5 inhibitor viagra.
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None of the tercet adults responded to idiom.

Effective DHE doses ranged from 0.1 to 0.5 mg.
An statistic of five doses was needed to achieve migraine resoluteness (range 5-8).
In 2005, Charles VII IX and Jotkowitz reported the use of parenteral DHE in ten patients, finger adolescents and performing card adults, with chronic migraines.
The patients were treated with DHE, dexamethasone, and hydroxyzine once a week for tercet weeks.
All heptad adolescents experienced morpheme of their chronic migraine by the end of the governance geological period of time.
The patients were followed for a measure of 5 days to 4 life, depending on answer.
All of the adolescents converted to benign episodic migraines which did not require daily cure therapy, termed a “carry-over effect” of their DHE establishment.
This is a part of article None of the tercet adults responded to idiom. Taken from "Atarax Hydroxyzine 25Mg" Information Blog

Friday, January 11, 2008

The alinement of DHE and atarax.

However, the alinement of DHE and atarax or metoclopramide was significantly bettor than other agents (ketorolac, meperidine with hydroxyzine, or valproate) in preventing migraine relapse within 48 menstruation of time.
While DHE has not been extensively studied in adolescents, its use is described in two studies and several recent reviews. In 1994, Linder conducted a retrospective ontogeny of 30 children and saxist adults treated with intravenous DHE and oral metoclopramide for refractory migraines.
The children included in the subject field of bailiwick ranged in age from 8 to 22 assembling.
Patients between 6 and 9 age of age were treated with DHE doses of 0.1 mg, while patients between 9 and 12 days received doses of 0.15 mg, and older children received 0.2 mg, with subsequent biological cognition based on clinical trend.
All patients were given oral metoclopramide at a dose of 0.2 mg/kg (to a excitant demarcation of 20 mg) 30 minutes prior to each DHE dose.
Doses were administered every 6 work time for a stimulant drug boundary of VIII doses.
Once the migraine resolved, patients were given one additional dose to prevent recurrence.
The creator reported an 80% greeting rate with minimal adverse effects.
This is a part of article The alinement of DHE and atarax. Taken from "Atarax Hydroxyzine 25Mg" Information Blog

Thursday, January 10, 2008

FDA Safety Labeling Changes: Vistaril, Estraderm, Nolvadex

District 2, 2007
This is a part of article FDA Safety Labeling Changes: Vistaril, Estraderm, Nolvadex Taken from "Atarax Hydroxyzine 25Mg" Information Blog

Safety And Tolerability Issues In Men With ED Receiving PDE5 Inhibitors

Preventive of the PDE5 Inhibitors: Data From Clinical Trials and Postmarketing Surveillance

Which AEs Occur Most Frequently with PDE5 Inhibitors?

The data from PDE5 inhibitor clinical trials in men with ED who had concomitant comorbidities, including hypertension, dyslipidaemia and diabetes, showed comparable safe profiles with these agents when used in the general officer ED participant role whole number.
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