By R. Murat. University of Arkansas, Fayetteville.

It penetrates the brain rapidly whereupon it is metabolised to morphine which then binds to the mu receptor discount sildigra 25 mg with amex erectile dysfunction doctor philippines. Tramadol: a weak opioid that also blocks the reuptake of NA and 5-HT Ð these combined actions synergise to give a good analgesia that lacks some of the typical opioid side-effects buy sildigra 120mg on line best erectile dysfunction pump. OPIATE ANTAGONISTS There are now selective antagonists for all three opiate receptors (see Table 21. Naloxone is a potent competitive antagonist at all three receptors with highest affinity for the mu receptor. It will rapidly reverse all opiate PAIN AND ANALGESIA 473 actions but has a short half-life compared to morphine itself. It is used in cases of overdose, usually to reverse the respiratory depression but with the cost of also reversing the analgesia. INTERACTIONS WITH OTHER NEUROTRANSMITTERS Some opioids, such as methadone and ketobemidone, have been reported to bind additionally to NMDA receptors and so may be different in their pharmacological profile. However, it is very unclear that this has any bearing on their effects in patients, especially in cases where morphine effectiveness is reduced, such as in neuropathic pain. In terms of changes in opioid systems relevant to the control of pain after nerve injury, nerve damage can lead to a loss of opioid receptors such as the marked reduction in spinal opioid receptor number seen after nerve section. Although this may be an explanation of the poor effectiveness of opioids in post-amputation pains, less severe nerve damage, where opioids can also lack effectiveness, only slightly alters opioid receptor number. However, the levels of the non-opioid peptide, cholecystokinin (CCK), can determine the potency of morphine and the peptide may, in turn, be upregulated after nerve damage. Activation of the CCKB receptor mobilises internal calcium whereas opioid receptors hyperpolarise Ð these actions of CCK thereby physiologically antagonise those of opioids. Antagonists at the CCKB receptor have been predicted to enhance or restore morphine analgesia after nerve injury but none have been tested in patients as yet. As discussed earlier, the changes that occur in the periphery and spinal cord after nerve damage can result in overexcitability of spinal neurons so that a hypersensitive state is induced. The N-methyl-D-aspartate (NMDA) receptor is a major candidate in the generation of hyperalgesic states in neuropathic and tissue damage pain states. Quite simply, if neuronal excitability is dramatically increased then opioid controls may be insufficiently efficacious unless doses are increased sufficiently to increase the degree of inhibition required to balance the level of excitation. Here, the combination of a low dose of opioid, increasing inhibition, with a drug that blocks excitation such as ketamine may result in synergistic or additive effects that result in the desired degree of analgesia without adverse side-effects. Other combinations could include the use of anti-convulsants with opioids. In common with neuropathy, NMDA receptor activation occurs after inflammation but here opioid actions are enhanced since CCK levels decrease. Thus, this augmented opioid actions may counter the increased excitability without the need for large increase in doses of opioid. BEHAVIOUR AND PAIN Finally, as outlined above, descending monoamine systems, originating in the midbrain and brainstem that act through the spinal release of noradrenaline and 5-HT, modulate the spinal transmission of pain. Alpha2 adrenoceptors appear to be important in this role but it is unlikely that behavioural effects such as sedation can be separated from the analgesia. Since both noradrenaline and 5-HT are key transmitters in the control of mood and anxiety and yet also participate in the control of sensory events that lead to 474 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION pain we can start to see links between state of mind and the level of pain experienced. This may be just one early step in the understanding of some of the chemistry of the psychological aspects of pain. Independently of their effects on mood, antidepressants increase activity in these descending control systems and are used as analgesics in neuropathic pain states. Individual differences in levels of pain, in the transition from acute to chronic pain, in susceptibility to neuropathic pain after nerve damage and in analgesic effectiveness may have a genetic basis. There is marked variability in animal genetic strains in terms of the sequelae of tissue and nerve damage and even in their responses to morphine. Given the huge range of human phenotypes, this may indicate important individual differences in susceptibility to pain and analgesia but we have no way of monitoring this possibility. Dray, A, Urban, L and Dickenson, AH (1994) Pharmacology of chronic pain. McMahon, SB, Lewin, GR and Wall, PD (1993) Central excitability triggered by noxious inputs. Edited by Roy Webster Copyright & 2001 John Wiley & Sons Ltd ISBN: Hardback 0-471-97819-1 Paperback 0-471-98586-4 Electronic 0-470-84657-7 Section N SM IT S A IO Neurotransmitters, Drugs and Brain Function. Edited by Roy Webster Copyright & 2001 John Wiley & Sons Ltd ISBN:Hardback 0-471-97819-1 Paperback 0-471-98586-4 Electronic 0-470-84657-7 22 Sleep and aking R. STANFORD INTRODUCTION There have been many references in this book to the role of neurotransmitters in the control of CNS excitability.

In approximately 85% of people with MS order 25 mg sildigra otc erectile dysfunction doctor san jose, the course is described as relapsing-remitting at the time of diagnosis d order 25 mg sildigra mastercard erectile dysfunction research. The course of MS is invariably characterized by progressive deterioration 19. Four disease-modifying agents have been approved in relaps- ing-remitting MS b. Glatiramer acetate’s mode of action involves inhibition of the immune response to myelin basic protein and other myelin antigens d. Adherence to medications is independent of sex, age, and other demographics b. Information should imply that there is no real risk associated with MS with or without treatment c. Healthcare professionals should always be in charge of mak- ing decisions about treatment d. People who think that their disease is not under their control adhere more readily to treatment 21. You are caring for a patient with relapsing-remitting MS who has just started treatment with interferon therapy. Interferon reduces the frequency of exacerbations but does not restore function b. Interferon can be associated with unpleasant side effects but these must be weighed against potential benefits CHAPTER 22: CERTIFICATION STUDY QUESTIONS 117 d. Which of the following is not generally considered a barrier to adherence? Many people with MS retire from work early because of phys- ical and/or cognitive impairments c. Relatively mild and subtle cognitive deficits may have an impact on patients’ lives 25. Which of the following cognitive functions is least likely to be affected in people with MS? The prevalence of MS-related cognitive impairment is estimat- ed to be less than 20% b. Studies using sensitive neuropsychologic instruments suggest that approximately half of the MS population experience cog- nitive dysfunction c. Until recently, the prevalence of cognitive impairment in peo- ple with MS was overestimated d. Studies using sensitive neuropsychologic instruments suggest that approximately 80% of the MS population experience cognitive dysfunction 27. People with minimal sensory and motor impairment are not at risk of cognitive impairment 118 NURSING PRACTICE IN MULTIPLE SCLEROSIS: A CORE CURRICULUM b. A high correlation between the extent of cognitive impair- ment and indices of disability has not been demonstrated c. There is a strong positive correlation between disease course and the development of cognitive impairment 28. In which of the following scenarios is neuropsychologic evalua- tion not indicated? An employer reports that a patient is not working as produc- tively as he had been b. A baseline assessment of cognitive function is desired prior to initiating immunomodulating therapy c. A family is concerned that a patient may have cognitive impairment, but the patient denies any problems and there is no clinical evidence for such impairment d. The patient reports cognitive deficits that, although subtle or fluctuating, may have functional impact 29. Which of the following strategies is unlikely to help patients with severe cognitive deficits? Which of the following is probably the best approach that nurs- es can adopt when addressing quality of life issues with people with MS? Nurses should recognize that each patient may have different expectations and aspirations c. It is important to use quality of life questionnaires before ini- tiating conversations about quality of life 31. The degree of disability is the sole determinant of quality of life in MS b. Recognizing the need to respond to change is more important than the ability to socialize in MS c. Developing and sustaining satisfying relationships is an important factor in MS CHAPTER 22: CERTIFICATION STUDY QUESTIONS 119 32. In general terms, which of the following would be least likely to influence a person’s quality of life in MS?

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It is found at the symphysis (la˘-kyoo′ne—singular lacuna) discount sildigra 50 mg online erectile dysfunction medications, within the matrix sildigra 25mg online erectile dysfunction causes and symptoms. Most cartilage is pubis, where the two pelvic bones articulate, and between the surrounded by a dense irregular connective tissue called peri- vertebrae as intervertebral discs. Cartilage at the articular surfaces wedges within the knee joint, called menisci (see chapter 8). Because ma- By the end of the day, the intervertebral discs of the vertebral ture cartilage is avascular, it must receive nutrients through diffu- column are somewhat compacted. So a person is actually sion from the perichondrium and the surrounding tissue. For this slightly shorter in the evening than in the morning, following a recu- reason, cartilaginous tissue has a slow rate of mitotic activity; if perative rest. Aging, however, brings with it a gradual compression of the intervertebral discs that is irreversible. There are three kinds of cartilage: hyaline (hi′a˘-lı¯n) cartilage, fibrocartilage, and elastic cartilage. They are distinguished by the Elastic Cartilage type and amount of fibers embedded within the matrix. Elastic cartilage is similar to hyaline cartilage except for the pres- ence of abundant elastic fibers that make elastic cartilage very Hyaline Cartilage flexible without compromising its strength (fig. This tis- Hyaline cartilage, commonly called “gristle,” has a homogeneous, sue is found in the outer ear, portions of the larynx, and in the bluish-staining matrix in which the collagenous fibers are so fine auditory canal. When viewed through a light microscope, hyaline cartilage has a clear, glassy appearance (fig. Hyaline cartilage is the most abundant cartilage within the Bone Tissue body. It covers the articular surfaces of bones, supports the tubu- lar trachea and bronchi of the respiratory system, reinforces the Bone tissue is the most rigid of all the connective tissues. Unlike nose, and forms the flexible bridge, called costal cartilage, be- cartilage, bone tissue has a rich vascular supply and is the site of considerable metabolic activity. The hardness of bone is largely due to the calcium phosphate (calcium hydroxyapatite) deposited lacuna: L. Histology © The McGraw−Hill Anatomy, Sixth Edition of the Body Companies, 2001 96 Unit 3 Microscopic Structure of the Body Lacuna Intercellular matrix Thyroid Chondrocyte Larynx cartilage (b) (c) Cricoid cartilage Tracheal cartilages Paras (a) FIGURE 4. It occurs in places such as the larynx (a), trachea, portions of the rib cage, and embryonic skeleton. Lacuna Chondrocyte Intercellular matrix Collagenous fibers (b) (c) (a) FIGURE 4. A photomicrograph of the tissue is shown in (b) and a labeled diagram in (c). Histology © The McGraw−Hill Anatomy, Sixth Edition of the Body Companies, 2001 Chapter 4 Histology 97 Lacuna Chondrocyte Elastic fibers Auricular cartilage (b) (c) Paras (a) FIGURE 4. A photomicrograph of the tissue is shown in (b) and a labeled diagram in (c). In calcium deficiency diseases, such as rickets, the bone tissue becomes pliable and bends under the weight of the body (see fig. Based on porosity, bone tissue is classified as either com- pact or spongy, and most bones have both types (fig. Com- pact (dense) bone tissue constitutes the hard outer portion of a bone, and spongy (cancellous) bone tissue constitutes the porous, highly vascular inner portion. The outer surface of a bone is cov- ered by a connective tissue layer called the periosteum that serves as a site of attachment for ligaments and tendons, provides pro- tection, and gives durable strength to the bone. Spongy bone tis- sue makes the bone lighter and provides a space for red bone marrow, where blood cells are produced. In compact bone tissue, mature bone cells, called osteocytes, are arranged in concentric layers around a central FIGURE 4. Histology © The McGraw−Hill Anatomy, Sixth Edition of the Body Companies, 2001 98 Unit 3 Microscopic Structure of the Body (b) Lamellae Central canal (a) Osteocyte within a lacuna Canaliculi (c) FIGURE 4. An injury to a portion of the body may stimulate tissue repair Each osteocyte occupies a cavity called a lacuna. A minor scrape or cut results in platelet and plasma activity of the exposed blood and each lacuna are numerous minute canals, or canaliculi, which the formation of a scab. The epidermis of the skin regenerates be- traverse the dense matrix of the bone tissue to adjacent lacunae. A severe open wound heals through connective tis- Nutrients diffuse through the canaliculi to reach each osteocyte. In this process, collagenous fibers form from The matrix is deposited in concentric layers called lamellae. Blood (Vascular Tissue) Knowledge Check Blood, or vascular tissue, is a highly specialized fluid connective 9. List the basic types of connective tissue and describe the tissue that plays a vital role in maintaining homeostasis. Which of the previously discussed connective tissues matrix called blood plasma (fig.

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This graph shows crovilli cheap 120 mg sildigra amex impotence from smoking, content of brush border enzymes and transporters) spine bone density in young adult women who that lead to more rapid digestion and absorption; these are nonathletes (controls) effective 25 mg sildigra impotence lipitor, distance runners with regular men- same effects likely take place in humans rendered hyper- strual cycles (cyclic runners), and distance runners with amenor- phagic by regular physical activity. Differences from controls indicate Blood flow to the gut decreases in proportion to exercise the roles that exercise and estrogen play in determination of bone intensity, as sympathetic vasoconstrictor tone rises. Because exercise may also improve gait, balance, malabsorption as a consequence of acute or chronic exercise coordination, proprioception, and reaction time, even in does not occur in healthy people. While exercise may not older and frail persons, the risk of falls and osteoporosis improve symptoms or disease progression in inflammatory are reduced by chronic activity. In fact, the incidence of bowel disease, there is some evidence that repetitive dy- hip fracture is reduced nearly 50% when older adults are namic exercise may reduce the risk for this illness. However, even when Although exercise is often recommended as treatment for activity is optimal, it is apparent that genetic contribu- postsurgical ileus, uncomplicated constipation, or irritable tions to bone mass are greater than exercise. However, of the population variance is genetic, and 25% is due to chronic dynamic exercise does substantially decrease the different levels of activity. In addition, the predominant risk for colon cancer, possibly via increases in food and fiber contribution of estrogen to homeostasis of bone in young intake, with consequent acceleration of colonic transit. These exceptionally active women are typically very thin and exhibit low levels of Chronic Exercise Increases Appetite Slightly circulating estrogens, low trabecular bone mass, and a Less Than Caloric Expenditure in Obese People high fracture risk (Fig. Exercise also plays a role in the treatment of os- Obesity is common in sedentary societies. Controlled clinical trials find that appropriate, creases the risk for hypertension, heart disease, and dia- regular exercise decreases joint pain and degree of disabil- betes and is characterized, at a descriptive level, as an ex- ity, although it fails to influence the requirement for anti- cess of caloric intake over energy expenditure. In rheumatoid arthritis, ex- exercise enhances energy expenditure, increasing physical ercise also increases muscle strength and functional activity is a mainstay of treatment for obesity. For exceptionally active people, exercise expendi- in either rheumatoid arthritis or osteoarthritis is not known. At high levels of activity, appetite and food intake match caloric expenditure (Fig. The biologi- GASTROINTESTINAL, METABOLIC, cal factors that allow this precise balance have never been AND ENDOCRINE RESPONSES defined. In obese people, modest increases in physical ac- The effects of exercise on gastrointestinal (GI) function re- tivity increase energy expenditure more than food intake, main poorly understood. However, chronic physical activ- so progressive weight loss can be instituted if exercise can ity plays a major role in the control of obesity and type 2 be regularized (see Fig. Frank hypoglycemia rarely oc- curs in healthy people during even the most prolonged or in- Lean tense physical activity. When it does, it is usually in association with the depletion of muscle and hepatic stores 2,500 and a failure to supplement carbohydrate orally. Exercise suppresses insulin secretion by increasing sym- pathetic tone at the pancreatic islets. Despite acutely Obese (initially falling levels of circulating insulin, both non-insulin-de- stable weight) pendent and insulin-dependent muscle glucose uptake in- crease during exercise. Exercise recruits glucose trans- 2,000 porters from their intracellular storage sites to the plasma membrane of active skeletal muscle cells. Because exercise increases insulin sensitivity, patients with type 1 diabetes (insulin-dependent) require less insulin when activity in- creases. However, this positive result can be treacherous 1,500 because exercise can accelerate hypoglycemia and increase the risk of insulin coma in these individuals. Chronic exer- 1,500 2,000 2,500 3,000 cise, through its reduction of insulin requirements, up-reg- Caloric expenditure (kcal/day) ulates insulin receptors. This effect appears to be due less to training than simply to a repeated acute stimulus; the effect FIGURE 30. For lean individuals, intake matches expenditure over a wide and can be lost as quickly. For obese individuals during periods of weight gain or peri- people show strikingly greater insulin sensitivity than do ods of stable weight, increases in expenditure are not matched by their sedentary counterparts (Fig. Exercise has other, subtler, positive effects on the energy balance equation as well. A single exercise episode may in- 100 crease basal energy expenditure for several hours and may increase the thermal effect of feeding. The greatest practi- cal problem remains compliance with even the most precise 50 After repeated exercise “prescription”; patient dropout rates from even 100 g glucose daily exercise short-term programs typically exceed 50%. For very short-term exercise, stored phosphagens (ATP and creatine 140 phosphate) are sufficient for crossbridge interaction between actin and myosin; even maximal efforts lasting 5 to 10 seconds 105 require little or no glycolytic or oxidative energy production. When work to exhaustion is paced to be somewhat longer in duration, glycolysis is driven (particularly in fast glycolytic 70 After repeated fibers) by high intramuscular ADP concentrations, and this daily exercise form of anaerobic metabolism, with its by-product lactic acid, 35 is the major energy source.

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