By C. Bozep. San Diego State University.
Migraine—a type of headache characterized by periodic at- Pain in and around the knee occurs early in the disease tacks of pain purchase 100 mg zudena free shipping, nausea buy generic zudena 100 mg on-line, and increased sensitivity to light and process; joint stiffness, edema, and deformity occur as the sound. The disorder that affects hingelike joints, tissues around these etiology is unknown, but one theory is that certain circum- joints, and eventually other body organs (systemic effects). It stances cause an imbalance of chemicals (eg, serotonin, is considered an autoimmune disorder in which the body at- prostaglandins) in the brain. Juvenile rheumatoid arthritis is a sodilation, release of inﬂammatory mediators, and irritation chronic, inﬂammatory, systemic disease that may cause joint of nerve endings. Numerous circumstances have been im- or connective tissue damage and visceral lesions throughout plicated as triggers for the chemical imbalance and mi- the body. In inﬂamed sorbed into the bloodstream, the acetyl portion dissociates, tissues, COX-2 is induced by inﬂammatory chemical media- then binds irreversibly to platelet COX-1. This action pre- tors such as interleukin-1 (IL-1) and tumor necrosis factor vents synthesis of thromboxane A2, a prostaglandin deriva- alpha (TNF alpha). In the GI tract, COX-2 is also induced by tive, and thereby inhibits platelet aggregation. A small single trauma and Helicobacter pylori infection, a common cause of dose (325 mg) irreversibly acetylates circulating platelets peptic ulcer disease. Overall, prostaglandins produced by within a few minutes, and effects last for the lifespan of the COX-2 are associated with pain and other signs of inﬂam- platelets (7 to 10 days). Inhibition of COX-2 results in the therapeutic effects with platelet COX-1 so that antiplatelet effects occur only of analgesia and anti-inﬂammatory activity. Thus, aspirin has hibitor drugs are NSAIDs designed to selectively inhibit greater effects, but all the drugs except acetaminophen and COX-2 and relieve pain and inﬂammation with fewer adverse the COX-2 inhibitors inhibit platelet aggregation, interfere effects, especially stomach damage. To relieve pain, aspirin acts both centrally and peripher- ally to block the transmission of pain impulses. Related drugs act peripherally to prevent sensitization of pain receptors to INDICATIONS FOR USE various chemical substances released by damaged cells. To relieve fever, the drugs act on the hypothalamus to decrease These drugs are widely used to prevent and treat mild to its response to pyrogens and reset the thermostat at a lower moderate pain and/or inflammation associated with muscu- level. For inﬂammation, the drugs prevent prostaglandins loskeletal disorders (eg, osteoarthritis, tendinitis, gout), from increasing the pain and edema produced by other sub- headache, dysmenorrhea, minor trauma (eg, athletic injuries stances released by damaged cells. Despite and quality of life, they do not cure the underlying disorders many similarities, however, aspirin and other NSAIDs dif- that cause the symptoms. Although aspirin is effective in Aspirin and traditional NSAIDs also have antiplatelet ef- many disorders, its usage has declined for most indications, fects that differ in mechanism and extent. When aspirin is ab- largely because of adverse effects on the gastrointestinal CHAPTER 7 ANALGESIC–ANTIPYRETIC–ANTI-INFLAMMATORY AND RELATED DRUGS 103 Cell activated by physical, chemical, or hormonal stimuli Arachidonic acid Traditional NSAIDs block COX-1 and COX-2 enzymes COX-2 inhibitor NSAIDs block COX-2 enzyme Cyclooxygenase-1 (COX-1) Cyclooxygenase-2 (COX-2) Physiologic prostaglandins Pathologic prostaglandins Figure 7–1 Physiologic and patho- logic (ie, inflammatory) prostaglan- GI protection (↓ gastric acid, Inflammation dins: Actions of antiprostaglandin ↑ mucus production, Vasodilation drugs. Prostaglandins play important maintain blood flow to ↑ Capillary permeability roles in normal body functions as well mucosa) Edema as inﬂammatory processes. Inhibition Renal protection (help Pain of both COX-1 and COX-2 by traditional maintain blood flow and Leukocytosis NSAIDs produces adverse effects on function) Activate white blood cells to the stomach (eg, irritation, ulceration, Regulate smooth muscle tone release inflammatory bleeding) as well as anti-inﬂammatory in blood vessels cytokines effects. Selective inhibition of COX-2 (eg, vasodilation) and lungs produces anti-inflammatory effects (eg, bronchodilation) while maintaining protective effects Regulate blood clotting on the stomach. At the same time, low- for pain and fever, but it lacks anti-inﬂammatory and anti- dose aspirin is increasingly prescribed for clients at risk of platelet effects. This indi- cation stems from its antiplatelet activity and resultant ef- fects on blood coagulation (ie, decreased clot formation). CONTRAINDICATIONS TO USE Some NSAIDs such as ibuprofen (Motrin) and related drugs are widely used as anti-inflammatory agents and analgesics; Contraindications to aspirin and nonselective NSAIDs include ketorolac (Toradol), which can be given orally and parenter- peptic ulcer disease, gastrointestinal (GI) or other bleeding ally, is used only as an analgesic. Most of the other NSAIDs disorders, history of hypersensitivity reactions, and impaired are too toxic to use as analgesics and antipyretics. In people who are allergic to aspirin, nonaspirin used primarily in rheumatoid arthritis and other muscu- NSAIDs also are contraindicated because hypersensitivity re- loskeletal disorders that do not respond to safer drugs. Cele- actions may occur with any drugs that inhibit prostaglandin coxib (Celebrex) is also used to treat familial adenomatous synthesis. In children and adolescents, aspirin is contraindi- polyposis, in which the drug reduces the number of polyps cated in the presence of viral infections such as inﬂuenza or and may decrease risks of colon cancer. In addi- and other NSAIDs, is commonly used as an aspirin substitute tion, celecoxib and valdecoxib are contraindicated in clients 104 SECTION 2 DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM who are allergic to sulfonamides and ketorolac is contraindi- and osteoarthritis.
Do not increase the dose Self-administration and do not take medication more often than prescribed cheap 100mg zudena amex. The tablets are formulated to release the ac- dependence generic zudena 100 mg amex, and because analgesics may mask pain for tive drug slowly, over several hours. Combining drugs with similar effects may (eg, excessive drowsiness, difﬁculty in breathing, severe lead to excessive sedation, even coma, and difﬁculty in nausea, vomiting, or constipation) and report to a health breathing. Teach clients interventions to prevent or etiology of pain, fever, and inﬂammation. Identify factors influencing the use of mechanism of action, indications for use, aspirin, NSAIDs, and acetaminophen in contraindications to use, nursing process, special populations. Discuss the use of NSAIDs, triptans, and and anti-inﬂammatory doses of aspirin. Differentiate between traditional NSAIDs and cyclooxygenase-2 inhibitors. Critical Thinking Scenario You are working in an emergency room when parents bring in their 2-year-old son who has just ingested half a bottle of acetaminophen (Tylenol). His parents have recently come to this country from Mexico and speak very little English. The child does not appear acutely ill and the parents become very upset when the physi- cian wants to admit the child. Reﬂect on: Why is Tylenol overdose potentially so serious for this young child? OVERVIEW Aspirin, NSAIDs, and acetaminophen can also be called antiprostaglandin drugs, because they inhibit the synthesis of The analgesic–antipyretic–anti-inﬂammatory drug group in- prostaglandins. Prostaglandins are chemical mediators found cludes chemically and pharmacologically diverse drugs that in most body tissues; they help regulate many cell func- share the ability to relieve pain, fever, and/or inﬂammation, tions and participate in the inflammatory response. Drugs are formed when cellular injury occurs and phospholipids discussed in this chapter include aspirin (acetylsalicylic in cell membranes release arachidonic acid. Arachidonic acid acid or ASA); the prototype, aspirin-related drugs that are is then metabolized by cyclooxygenase enzymes to produce often called nonsteroidal anti-inﬂammatory drugs (NSAIDs, prostaglandins, which act brieﬂy in the area where they are eg, ibuprofen); acetaminophen; and drugs used to prevent or produced and are then inactivated. Both local fever, and inﬂammation are described in the following section. PAIN, FEVER, AND INFLAMMATION Because inﬂammation may be a component of virtually any illness, anti-inﬂammatory drugs are needed when the in- Pain is the sensation of discomfort, hurt, or distress. It is a ﬂammatory response is inappropriate, abnormal, or persistent, common human ailment and may occur with tissue injury and or destroys tissue. Prostaglandins sensitize pain receptors and in- by pain, fever, and inﬂammation, and for which the drugs dis- crease the pain associated with other chemical mediators cussed in this chapter are used, are described in Box 7–2. Body temperature is controlled by a regulating MECHANISM OF ACTION center in the hypothalamus. Normally, there is a balance be- tween heat production and heat loss so that a constant body Aspirin, NSAIDs, and acetaminophen inactivate cyclooxy- temperature is maintained. When there is excessive heat pro- genases, the enzymes required for prostaglandin formation duction, mechanisms to increase heat loss are activated. Two forms of cyclooxygenase, called COX-1 result, blood vessels dilate, more blood ﬂows through the and COX-2, have been identified. Aspirin and traditional skin, sweating occurs, and body temperature usually stays NSAIDs inhibit both COX-1 and COX-2 enzymes. When fever occurs, the heat-regulating COX-1 is normally synthesized continuously and present in center in the hypothalamus is reset so that it tolerates a higher all tissues and cell types, especially platelets, endothelial cells, body temperature. Fever may be produced by dehydration, the gastrointestinal (GI) tract, and the kidneys. Prostaglandins inﬂammation, infectious processes, some drugs, brain injury, produced by COX-1 are important in numerous homeostatic or diseases involving the hypothalamus. Prostaglandin for- functions and are associated with protective effects on the mation is stimulated by such circumstances and, along with stomach and kidneys.
When these required conditions were established discount zudena 100mg mastercard, the objec- tive was to have the child independently use the toilet to urinate generic 100mg zudena. The author explained that, if this condition takes place all the time, the child will regain consciousness and will be able to hold their urine. In addition, the child was supervised so as to drink a lot of water during the day and then lengthen the intervals between uri- nation to two times its current length. At the same time, the child was encouraged during urination to suspend the expulsion of urine, hold their breath, and count to 10. Hu, nocturnal enuresis basically develops because of constitutional insufficiency, a vacuous, weak constitu- tion, kidney yang depletion and damage, and, therefore, the kid- neys not securing and containing and the bladder not restraining. In the above formula, Rou Gui is acrid and warm and warms the kid- neys. Yi Zhi Ren is acrid and warm and supplements the kidneys and reduces urination. Wu Bei Zi has a sour flavor and astringent nature and also reduces urination. From [Achieving] Good Results in the Treatment of Pediatric Enuresis with Cong Liu Gao (Scallion & Sulfur Paste) by Liu Jun-yun & Zhao Xiu-ling, Guo Yi Lun Tan (Chinese Medicine Tribune), 1998, #2, p. Treatment method: Seven pieces of fresh Cong Bai (Bulbus Allii Fistulosi) were washed, cleaned, and pounded with a pestle until they were like mud in consistency. This paste was applied to Shen Que (CV 8) each night before sleep after cleaning the area with 75% alcohol. A piece of gauze was placed over the area to secure the paste in the navel. Chinese Research on the Treatment of Pediatric Enuresis 111 Study outcomes: All 132 cases obtained a complete cure in 2-4 days, and there was no reoccurrence of enuresis in any of the cases two years after treatment. From Clinical Observations of Using Yi Shen San (Boost the Kidneys Powder) Externally to Treat 60 Cases of Pediatric Enuresis by Lin Jie, Hu Bei Zhong Yi Za Zhi (Hubei Journal of Chinese Medicine), 2002, #9, p. The course of diseases in these children was as short as two months and as long as nine years. The course of diseases in these children was as short as three months and as long as 8. Therefore, there was no significant statistical difference in the data of both groups. Treatment method: All members of the treatment group were treated with Yi Shen San (Boost the Kidneys Powder) which consisted of equal amounts of: Rou Gui (Cortex Cinnamomi) Fu Pen Zi (Fructus Rubi) Yi Zhi Ren (Fructus Alpiniae Oxyphyllae) Qian Shi (Semen Euryalis) Wu Wei Zi (Fructus Schisandrae) mix-fried Gui Ban (Plastrum Testudinis) Ding Xiang (Flos Caryophylli) Thirty grams of this powder was applied externally before sleep to 112 Treating Pediatric Bed-wetting with Acupuncture & Chinese Medicine Shen Que (CV 8) and Ming Men (GV 4), secured in place with a piece of gauze one time each night, and then replaced the follow- ing evening. In both groups, eight weeks equaled one course of treatment and, during the course of treatment, all other methods of treat- ment were stopped. The patients were advised not to have any water or other fluids to drink two hours before bed and to also uri- nate before going to bed. During the day, they were encouraged to drink a lot of water and other fluids. They were asked to try and increase the length of the intervals between urinations in order to strengthen the function of the bladder. Study outcomes: In the treatment group 34 cases registered obvious improve- ment, meaning that the main symptoms were reduced by more than or equal to 50%. In the comparison group, there were nine cases of obvious improvement, 15 other cases improved, and 36 cases got no improvement. On a follow-up visit three months after treatment was suspended, there were 30 cases of obvious improvement, 19 cases of some improvement, and 11 cases of no improvement in the treatment group for a total amelioration rate of 81. In the comparison group, there were six cases of obvious improvement, 17 cases of improvement, and 37 cases of no improvement for a total amelioration rate of 38. This meant that, after three months, there was still a significant statis- tical difference between the treatment group and the comparison group. Lin, the main treatment of this condition should be to enrich and supplement the kidneys, warm yang, transform the qi, secure and contain, and reduce urination. Correspondingly, Chinese Research on the Treatment of Pediatric Enuresis 113 within Yi Shen San, Ding Xiang, and Rou Gui warm the kidneys and assist yang. Fu Pen Zi and Qian Shi boost the kidneys, reduce urina- tion, and stop enuresis.
Modiﬁed from Pauvert zudena 100mg without prescription, Pierrot-Deseilligny & Rothwell (1998) ((b)–(g)) 100 mg zudena with amex, and Pierrot-Deseilligny (2002)(h), with permission. The same result is illustrated in common interneurones another way in Fig. As sketched in effects of separate stimuli) shows the extra facilita- Fig. Because the two conditioning volleys are weak, been found in almost all motor units tested (48 out some inactive interneurones in that population will of 51, 94%). Initial sparing Disappearance of the extra facilitation when the peripheral volley is increased Convergence of the two volleys onto interneurones is further supported by the absence of extra facil- A further argument favouring the view that extra itation in the ﬁrst bins of the corticospinal peak facilitation of the corticospinal peak takes place in (see the vertical dashed and dotted lines in Figs. Such sparing was found with vir- 2001), much as it suppresses the peripheral pro- tually all motor units, with a mean duration of 0. This corresponds to the delay required for trans- mission across one interneurone in human path- ways (Pierrot-Deseilligny et al. This is what would be expected if neurones at rest the two volleys converged onto common interneu- The FCR H reﬂex was conditioned by a weak (0. There was extra facil- thedirectrapidlyconductingmonosynapticcortico- itation of the reﬂex on combined stimulation over motoneuronalinput. Thusinterneuronalfacilitation and above that expected from the sum of the effects would be unable to affect the onset of the corti- of the two separate conditioning stimuli. It has been shown that the mean ISI at which the extra facilita- With the artiﬁcially synchronised volleys used in tionﬁrstoccursbecomesgreaterthemorecaudalthe these experiments, excitation is invariably reversed motoneurone pool tested in the spinal cord (Nicolas to inhibition when the input (peripheral or corti- et al. This suppression eachmotoneurone(Malmgren&Pierrot-Deseilligny, at higher stimulus intensities by the same affer- 1988b). Pro- is longer the more caudal the motoneurone pool priospinally mediated excitation has also been (see p. In addition, in the PSTHs of single showntobeconsistentlysuppressedwhenweakvol- units, suppression of the peak of excitation – when leys in two different nerves (e. Cutaneous suppression Corticospinal excitation of feedback Cutaneous afferents also suppress the pro- inhibitory interneurones priospinally mediated excitation. Evidence for disfacilitation Increasing TMS intensity results in a decrease The suppression seen above could reﬂect inhi- in the peripheral extra facilitation of the bition exerted directly onto motoneurones (i. Two arguments favour musculo-cutaneous-inducedextrafacilitationofthe disfacilitation: (i) the peak of monosynaptic excita- corticospinal peak with TMS at 26% was reversed tion (whether Ia or corticospinal) is less suppressed to strong inhibition with TMS at 32%. This reversal Organisation and pattern of connections 465 Feedback FCU MU (a) inhibitory IN 8 (b) C4 PN Median C5 0. Peripheral inhibition of the peak of propriospinally mediated excitation in single units. Peripheral (group I in (a), cutaneous in (d)) volleys inhibit propriospinal neurones (PN) projecting to a ﬂexor carpi ulnaris (FCU, (a)) and an extensor carpi radialis (ECR, (d )) motoneurone (MN) through activation of feedback inhibitory interneurones (IN). The monosynaptic latency (dotted vertical lines) was 19 ms in (b), (c), and 30 ms in (e)–(g) (without allowance for the trigger delay of the units). Modiﬁed from Malmgren & Pierrot- Deseilligny (1988b)((b), (c)), and Nielsen & Pierrot-Deseilligny (1991)((e)–(g)), with permission. Inhibi- stronger TMS, both appearing at the 8 ms ISI and tion with stronger TMS had the same time course as disappearing at the 9 ms ISI (Nicolas et al. Musculo-cutaneous (MC) and corticospinal volleys converge on both propriospinal neurones (PN) and feedback inhibitory interneurones (IN). The thick dashed line indicates that the feedback to inhibitory INs is stronger than to PNs. Dashed and dotted vertical lines in (c) (placed between the two columns of a pair of open and ﬁlled columns with the same latency) indicate the onset of the corticospinal peak and of the inhibition on combined stimulation, respectively. Mechanisms underlying the reversal of the musculo-cutaneous-induced non-reciprocal group I inhibition (∼0. The reversal was not due to occlusion in pro- The peripheral suppression spared the initial bin(s) priospinal neurones of the effects of two excitatory of the corticospinal peak (see the 18-ms bin in inputs (cortical and peripheral) because the corti- Fig. As mentioned above, the central reversal was due to inhibition of premotoneurones delay of the inhibition was the same as that of transmitting indirect corticospinal excitation (i. The mean interval between the onset of the mono- synaptic corticospinal excitation and the onset of inhibition(i. This suggests that inhibition is exerted at the premotoneuronal level of a disynaptic path- Convergence of peripheral and corticospinal inputs waymediatingcorticospinalexcitation. Theﬁndings onto both propriospinal neurones and feedback that suppression of the corticospinal peak consis- inhibitory interneurones (sketched in Fig.
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