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Leakage of mineral oil ficulties with evacuation in which firm stool is seen pri- past the anal sphincter may lead to soiling of clothing buy 75 mg sildenafil mastercard. Docusate dioctyl sodium sulfosuccinate (Colace) buy discount sildenafil 100 mg on-line, The dangers of excessive purging are salt and fluid dioctyl calcium sulfosuccinate (Surfak) cheap sildenafil 75 mg on-line, and dioctyl loss and gradually increasing desensitization of the potassium sulfosuccinate (Diocto-K) are surface-active bowel to normal stimuli; the latter effect forces the agents that produce fecal softening in 1 or 2 days proven 100 mg sildenafil. Orally ingested do- laxatives and pure osmolar laxatives do not predispose cusate may also act as a stool softener by stimulating patients to formation of a cathartic-type colon and the secretion of water and electrolytes into the intes- should be the initial agents used for chronic constipa- tinal lumen. Docusate has been used both alone and in tion after a structural obstructing lesion has been ex- combination with other laxatives. Laxatives are also used before radiological, en- appears to be relatively nontoxic, it may, when taken in doscopic, and abdominal surgical procedures; such combination with other laxatives, increase their absorp- preparations quickly empty the colon of fecal material. Caution is necessary when Nonabsorbable hyperosmolar solutions or saline laxa- docusate is prescribed together with mineral oil, since tives are used for this purpose. Bulk Forming Laxatives Stool Softeners The bulk-forming laxative group includes the hy- Fecal softeners are substances that are not absorbed drophilic substances described previously: calcium from the alimentary canal and act by increasing the polycarbophil (FiberCon, Equalactin), methylcellulose bulk of the feces and softening the stool so that it is eas- (Citrucel), and various psyllium seed derivatives ier to pass. All act by increasing the bulk of the feces, either as the oil or as a white emulsion; it is a mixture of part of this action being due to their capacity to attract liquid hydrocarbons. It dissolves the fat-soluble vitamins and ces stretches the walls of the GI tract and stimulates prevents their absorption. Their action may not be evident for 2 to 3 and appears in the mesenteric lymph nodes, and if it is days after starting treatment. These salts should always be given with substantial The use of high-fiber diets has recently received a amounts of water; otherwise the patient may be purged great deal of publicity, and many claims have been at the expense of body water, resulting in dehydration. Fiber in the diet is de- Sodium-containing laxatives should not be used in pa- rived entirely from plant material, either from fruit and tients with congestive heart failure, since the patient vegetables or from cereals, the latter being known as may absorb excessive sodium. The fiber content in each case is a complex carbo- failure, magnesium or phosphate-containing products hydrate in the form of cellulose, pectin, and lignin. A high-fiber diet is effective in the prevention of Enemas may contain water, salts, soap, mineral de- constipation and diverticulitis. Claims also have been tergent (docusate potassium), or hypertonic (sorbitol, made that such diets prevent cancer of the colon. Many of Since clear advantages accrue from a high-bran diet these solutions irritate the mucosa and may produce ex- (a reduction in both constipation and diverticulitis) and cessive mucus in the stool. Excessive use of these enema since there is no associated toxicity, a bulk-forming lax- products may result in water intoxication and hypona- ative is the laxative of choice for constipated patients. A new formulation of a saline laxative, Visicol, that Osmotic Laxatives is useful to prepare patients for procedures, was ap- proved for use in 2001. Visicol tablets, taken in two creases, and fluid movement occurs secondary to os- doses of 30 g approximately 12 hours apart, induce di- motic pressure. Lactulose is a synthetic disaccharide arrhea that rapidly and effectively cleanses the entire that is poorly absorbed from the GI tract, since no colon. Each administration has a purgative effect for mammalian enzyme is capable of hydrolyzing it to its approximately 1 to 3 hours. It therefore reaches the colon unchanged and is metabolized by colonic bacteria to lactic acid and to small quantities of formic and acetic Stimulant Cathartics acids. Since lactulose does contain galactose, it is con- The stimulant cathartics contain a variety of drugs traindicated in patients who require a galactose-free whose exact mode of action is not known, although it is diet. Metabolism of lactulose by intestinal bacteria may thought that they act on the mucosa of the intestine to result in increased formation of intraluminal gas and stimulate peristalsis either by irritation or by exciting abdominal distention. Polyethylene glycol (Miralax) is another osmotic They produce irritation of the mucosa if given in large laxative that is colorless and tasteless once it is mixed. It has been suggested that these drugs may Saline laxatives are soluble inorganic salts that contain act by stimulating afferent nerves to initiate a reflex in- multivalent cations or anions (milk of magnesia, mag- crease in gut motility. These charged particles do not readily cross the senna, and rhubarb) are among the oldest laxatives intestinal mucosa and therefore tend to remain in the known. They act on the colon rather than on the ileum lumen of the GI tract, where they help retain fluid and produce evacuation 8 to 10 hours after administra- through the osmotic effect exerted by the unabsorbed tion.

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Local Anesthetics 209 Procaine Lidocaine Prilocaine Articaine Mepivacaine Benzocaine [H+] Proton concentration 100 0 80 20 60 40 40 60 20 80 0 100 6 7 8 9 10 pH value Active form Membrane- cationic- permeable amphiphilic form Ability to penetrate Poor lipophilic Good barriers and cell membranes A discount 100mg sildenafil with amex. Local anesthetics and pH value Lüllmann sildenafil 75mg sale, Color Atlas of Pharmacology © 2000 Thieme All rights reserved buy generic sildenafil 100mg line. Aside from the relief associated opium contains alkaloids devoid of an- with the abatement of strong pain proven sildenafil 100mg, algesic activity, e. All semisynthetic deriva- (euphoria), particularly after intrave- tives (hydromorphone) and fully syn- nous injection and, hence, rapid build- thetic derivatives (pentazocine, pethi- up of drug levels in the brain. The desire dine = meperidine, l-methadone, and to re-experience this state by renewed fentanyl) are collectively referred to as administration of drug may become opioids. The high analgesic effectiveness overpowering: development of psycho- of xenobiotic opioids derives from their logical dependence. The atttempt to quit affinity for receptors normally acted repeated use of the drug results in with- upon by endogenous opioids (enkepha- drawal signs of both a physical (cardio- lins,! They cal (restlessness, anxiety, depression) are found in various brain regions and nature. Opioids meet the criteria of “ad- the spinal medulla, as well as in intra- dictive” agents, namely, psychological mural nerve plexuses that regulate the and physiological dependence as well as motility of the alimentary and urogeni- a compulsion to increase the dose. There are several types of opi- these reasons, prescription of opioids is oid receptors, designated µ, ", #, that subject to special rules (Controlled Sub- mediate the various opioid effects; all stances Act, USA; Narcotic Control Act, belong to the superfamily of G-protein- Canada; etc). All contain the ami- sued on special forms the completion of no acid sequence of the pentapeptides which is rigorously monitored. The ef- opioid analgesics, such as codeine and fects of the opioids can be abolished by tramadol, may be prescribed in the usu- antagonists (e. Ca2+ influx into nerve ter- minals during excitation is decreased, leading to a decreased release of excita- tory transmitters and decreased synap- tic activity (A). Depending on the cell population affected, this synaptic inhi- bition translates into a depressant or ex- citant effect (B). The analge- sic effect results from actions at the lev- el of the spinal cord (inhibition of noci- ceptive impulse transmission) and the brain (attenuation of impulse spread, inhibition of pain perception). Attention Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Effects of opioids Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Likewise, garding efficacy and potential for de- bladder function is affected; specifically pendence probably reflect differing af- bladder emptying is impaired due to in- finity and intrinsic activity profiles for creased tone of the vesicular sphincter. A giv- Uses: The endogenous opioids en sustance does not necessarily behave (metenkephalin, leuenkephalin,! The abuse potential brain barrier, thus preventing access to is also determined by kinetic properties, their sites of action even after parenter- because development of dependence is al administration (A). With any of the high-effica- parenterally, as well as epidurally or cy opioid analgesics, overdosage is like- intrathecally in the spinal cord. The opi- ly to result in respiratory paralysis (im- oids heroin and fentanyl are highly lipo- paired sensitivity of medullary chemo- philic, allowing rapid entry into the receptors to CO2). Because of its high potency, fenta- sible extent of respiratory depression is nyl is suitable for transdermal delivery thought to be less in partial agonist/ (A). The user may also resort to vomiting, particularly after first-time ad- other more unusual routes: opium can ministration or in the ambulant patient. Like other opioids the emetic center then predominates, bearing a hydroxyl group, morphine is which overrides the stimulation of area conjugated to glucuronic acid and elim- postrema chemoreceptors. Glucuronidation of the Opioids elicit pupillary narrowing OH-group at position 6, unlike that at (miosis) by stimulating the parasympa- position 3, does not affect affinity. The thetic portion (Edinger-Westphal nu- extent to which the 6-glucuronide con- cleus) of the oculomotor nucleus.

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As a result sildenafil 75 mg with amex, enzymes are not used up in chemical PERIODICALS reactions generic sildenafil 25mg with amex, but rather recycled buy 75mg sildenafil visa. Rosick generic sildenafil 50 mg with mastercard, DO, MPH, MS ous reactions of human life are produced within the body by genes. Genetic enzyme deficiency disorders, such as acid maltase deficiency, result from only one cause: the affected individual cannot produce enough of the neces- sary enzyme because the gene designed to make the enzyme is faulty. Enzymes are not used up in chemical reactions, but they do eventually wear out, or accidentally IAcid maltase deficiency get expelled. Also, as an individual grows, they may Definition require greater quantities of an enzyme. Therefore, most enzyme deficiency disorders will have a time component Acid maltase deficiency, also called Pompe disease, to them. Individuals with no ability to produce a particu- is a non-sex linked recessive genetic disorder that is the lar enzyme may show effects of this deficiency at birth or most serious of the glycogen storage diseases affecting shortly thereafter. It is one of several known congenital to produce a particular enzyme may not show the effects (present at birth) muscular diseases (myopathies), as dis- of this deficiency until their need for the enzyme, because tinct from a muscular dystrophy, which is a family of of growth or maturation, has outpaced their ability to pro- muscle disorders arising from faulty nutrition. Pompe first described this genetic disor- The level of ability of individuals with acid maltase der in 1932. Some of the sugars and deficiency usually begins to produce observable symp- starches from the diet that are not immediately put to use toms in affected individuals between the ages of two and are converted into glycogen and then stored in the mus- five months. Type b, or childhood, acid maltase defi- GALE ENCYCLOPEDIA OF GENETIC DISORDERS 23 ciency usually begins to produce observable symptoms in prevent the production of acid maltase and lead to infan- affected individuals in early childhood. Type c, or adult, acid maltase defi- the adult (type c) and the remainder of the childhood ciency generally begins to produce observable symptoms (type b) acid maltase deficiency cases have not yet been in affected individuals in the third or fourth decades of determined. Demographics Genetic profile Acid maltase deficiency is observed in approxi- mately 1 in every 100,000 live births. In 2000, it was esti- The locus of the gene responsible for acid maltase mated that between 5,000 and 10,000 people were living deficiency has been localized to 17q23. The severity of somewhere in the developed world with a diagnosed case the associated symptoms and the age of onset in affected of acid maltase deficiency. It is observed in equal num- individuals have been closely tied to the particular muta- bers of males and females and across all ethnic subpopu- tion at this locus. Since acid maltase deficiency is a recessive disorder, Each of these is associated with varying symptoms. In the case of carrier parents A gene is a particular segment of a particular chro- with one child affected by acid maltase deficiency, there mosome. However, within the segment containing a par- is a 25% likelihood that their next child will also be ticular gene there are two types of areas: introns and affected with the disorder. Introns are sections of the segment that do not (adult) acid maltase deficiency generally does not show actively participate in the functioning of the gene. Exons symptoms in the affected individual until that individual are those sections that do actively participate in gene is past 30, it is possible for an affected individual to par- function. In this case, the probability of a second child exons divided by several areas of introns. One mutation on the gene responsible for the pro- Should two affected individuals bear offspring; the prob- duction of acid maltase is a deletion of exon 18. A second ability of their child being affected with acid maltase mutation on the gene responsible for the production of deficiency is 100%. Both these mutations are associated with a complete symptoms of the siblings will closely correspond. That is, inability of the affected individual to produce acid mal- if one child develops infantile acid maltase deficiency, a tase. Individuals with these mutations will invariably be second child, if affected with the disorder, will also affected with infantile (type a) acid maltase deficiency. The third mutation on the gene responsible for the production of acid maltase is a complicated mutation Signs and symptoms within intron 1 that causes the cutting out of exon 2. This mutation is generally not complete in every copy of the The symptoms of acid maltase deficiency vary gene within a given individual so it is associated with a depending on the severity of the deficiency of acid mal- partial ability of the affected individual to produce acid tase in the affected individual. Individuals with this mutation will be affected deficient individuals will develop infantile acid maltase with either childhood (type b), or, more commonly, adult deficiency and will exhibit the most severe symptoms.

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It has been reported that expectations of benefit can significantly influence the outcome of comparison trials of interventions for back pain 75mg sildenafil free shipping, indicating that 7 buy 100mg sildenafil free shipping,8 studies not controlling for expectation must be considered in this light buy sildenafil 100 mg line. Given these important barriers 25 mg sildenafil mastercard, the application of traditional epidemiological research methods devised for pharmacological studies (such as the randomized, placebo- controlled, double-blinded trial) to CAM therapies may be difficult. Although researchers are beginning to develop methodologies that are particular to CAM therapies, this process is only in its infancy and the results of these efforts may not be visible for several more years. Perhaps CAM researchers will eventually apply research methods similar to those used for surgical interventions (e. LITERATURE REVIEWED This discussion focuses almost exclusively on the existing body of randomized clinical trials and, where available, on systematic reviews of a particular CAM therapy. Some CAM therapies have yet to be studied with regard to treatment of back and neck pain. These include aromatherapy, craniosacral therapy, reflexology, homeopathy and ayuvedic medicine. Despite limitations, randomized trials remain the best available methodology with which to evaluate the potential efficacy of a CAM therapy for the treatment of neck or patients with back pain. Randomization deals effectively with the issue that a significant percentage of patients with back and neck pain improve spontaneously with time. The most obvious limitation to randomized trials in investigation of CAM relates to difficulty in the identification of appropriate placebo or comparison groups. Studies have utilized groups with several types of comparison, including comparison to conventional medical treatment, no treatment, patient self-education, or a devised sham treatment (e. Other trials have been conducted on a pragmatic basis, comparing two or more specific treatment approaches, one of which is a CAM therapy. Acupuncture Although traditional Chinese medicine practitioners routinely use and recommend acupuncture to treat a variety of conditions, it has achieved its widest acceptance in the Complementary therapies in neurology 290 West in the management of acute and chronic pain. Acupuncture has established some 9 firm theoretical underpinnings in the systems controlling endogenous analgesia. This has resulted in a large and growing body of research and has provided the basis for 10 11–13 systematic reviews of acupuncture for pain, and in particular back pain, and neck 11,14 pain. There are several relatively distinct procedures that fall under the rubric of acupuncture. For example, there is traditional Chinese acupuncture that uses needles (among other methods) to affect energy flow along meridians. These treatments are applied according to unique methods of analysis (such as pulse diagnosis) and according to unique theories (such as the four-element theory and specific patterns of flow of energy, called chi). Other practitioners place needles based on a Western medical diagnosis or location of pain, while still other forms of practice use electrical resistance to determine the patterns of treatment. These other methods may or may not rely on the original theories or meridians or energy flow. In addition to placing needles in a specific pattern, there may be specific patterns of needle movement, certain composition of the needles and even certain times of the day in which treatments are applied. Some use electrical stimulation, either through the needles or independent of them, or other methods of stimulating acupuncture points (including pressure or heat). There is no reason to believe that any one method is superior, but, similarly, there is no reason to accept that results derived from one method can be applied to other methods of acupuncture. The literature from Table 1 Summary of results from systematic reviews and meta-analyses of acupuncture for back and/or neck pain Reference Back pain Back Back pain Neck pain Neck Neck pain (general) pain (chronic) (general) pain (chronic) (acute) (acute) Aker et al. Where separate conclusions have been reached for acute and chronic pain, results are listed separately. Acupuncture for back pain There have been a large number of studies and several recent systematic reviews of 13 acupuncture for the treatment of low back pain (Table 1). In 1998, Ernst and co-workers reviewed 12 studies of acupuncture for back pain and identified nine containing data that could be incorporated into a meta-analysis. These reviewers reported a significant advantage for acupuncture versus several comparison treatments.

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