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I. Larson. Mount Mary College.
Because most drugs are metabolized rash order 40 mg lasix amex blood pressure chart conversion, hives, joint and muscle pain, enlarged lymph by the liver, the liver is especially susceptible to drug- glands, eosinophilia) and its pattern may be low induced injury. Drugs that are hepatotoxic include ac- grade and continuous or spiking and intermittent. It etaminophen (Tylenol), isoniazid (INH), methotrexate may begin within hours after the first dose if the client (Mexate), phenytoin (Dilantin), and aspirin and other has taken the drug before, or within approximately salicylates. In the presence of drug- or disease-induced 10 days of continued administration if the drug is new liver damage, the metabolism of many drugs is im- to the client. Consequently, drugs metabolized by the liver fever usually subsides within 48 to 72 hours unless 24 SECTION 1 INTRODUCTION TO DRUG THERAPY drug excretion is delayed or significant tissue dam- must have a high index of suspicion so that toxicity can be age has occurred (eg, hepatitis). Many drugs have been implicated as causes of drug fever, including most antimicrobials, several cardiovascular agents (eg, beta blockers, hydralazine, Drug Overdose: General Management methyldopa, procainamide, quinidine), drugs with anti- cholinergic properties (eg, atropine, some antihista- Most poisoned or overdosed clients are treated in emergency mines, phenothiazine antipsychotic agents, and tricyclic rooms and discharged to their homes. Idiosyncrasy refers to an unexpected reaction to a ness and the need for endotracheal intubation and mechani- drug that occurs the first time it is given. Serious cardiovascular effects mind-altering drugs, such as opioid analgesics, (eg, cardiac arrest, dysrhythmias, circulatory impairment) are sedative-hypnotic agents, antianxiety agents, and CNS also common and warrant admission to an ICU. Dependence may be physiologic or psy- The main goals of treatment for a poisoned patient are sup- chological. Physiologic dependence produces unpleas- porting and stabilizing vital functions (ie, airway, breathing, ant physical symptoms when the dose is reduced or circulation), preventing further damage from the toxic agent the drug is withdrawn. Psychological dependence by reducing additional absorption or increasing elimination, leads to excessive preoccupation with drugs and drug- and administering specific antidotes when available and in- seeking behavior. Carcinogenicity is the ability of a substance to cause antidotes are listed in Table 2–2; and specific aspects of care cancer. Several drugs are carcinogens, including are described in relevant chapters. For patient who are seriously ill on first contact, enlist ity apparently results from drug-induced alterations in help for more rapid assessment and treatment. Teratogenicity is the ability of a substance to cause ingestion leads to better patient outcomes. Standard cardiopulmonary Toxic Effects of Drugs resuscitation (CPR) measures may be needed to maintain breathing and circulation. An intravenous (IV) line is Drug toxicity (also called poisoning, overdose, or intoxica- usually needed to administer fluids and drugs, and inva- tion) results from excessive amounts of a drug and may sive treatment or monitoring devices may be inserted. It Endotracheal intubation and mechanical ventilation is a common problem in both adult and pediatric popula- are often required to maintain breathing (in uncon- tions. It may result from a single large dose or prolonged scious patients), correct hypoxemia, and protect the ingestion of smaller doses. Hypoxemia must be corrected quickly to avoid scription, over-the-counter, or illicit drugs. Poisoned pa- brain injury, myocardial ischemia, and cardiac dys- tients may be seen in essentially any setting (e. In some cases, the patient or someone accompanying the Serious cardiovascular manifestations often require patient may know the toxic agent (eg, accidental overdose of pharmacologic treatment. Hypotension and hypoperfu- a therapeutic drug, use of an illicit drug, a suicide attempt). Dysrhythmias are treated according to Advanced causative drug or drugs are unknown, and the circumstances Cardiac Life Support (ACLS) protocols. For unconscious patients, as soon as an IV line is es- and may indicate other disease processes. Because of the vari- tablished, some authorities recommend a dose of able presentation of drug intoxication, health care providers naloxone (2 mg IV) for possible narcotic overdose CHAPTER 2 BASIC CONCEPTS AND PROCESSES 25 TABLE 2–2 Antidotes for Overdoses of Selected Therapeutic Drugs Overdosed Drug (Poison) Antidote Route and Dosage Ranges Comments Acetaminophen (see Chap. Give IV slowly, over Infrequently used because of its (atropine; see Chap. If cardiac arrest seems immi- nent, may give the dose as a bolus injection. If amount seizures and correction of of INH unknown, give 5 g; may be acidosis repeated.
CHAPTER 7 ANALGESIC–ANTIPYRETIC–ANTI-INFLAMMATORY AND RELATED DRUGS 115 6 buy 100 mg lasix with mastercard prehypertension treatment. In general, clients taking low-dose aspirin to prevent lead to gastric ulceration and bleeding. Because NSAIDs lead myocardial infarction or stroke should continue the to renal impairment in some clients, blood urea nitrogen and aspirin if prescribed a COX-2 inhibitor NSAID. The serum creatinine should be checked approximately 2 weeks COX-2 inhibitors have little effect on platelet function. NSAIDs inhibit platelet activity only while drug mol- ecules are in the bloodstream, not for the life of the platelet Toxicity: Salicylate Poisoning (approximately 1 week) as aspirin does. Thus, they are not Salicylate intoxication (salicylism) may occur with an acute prescribed therapeutically for antiplatelet effects. Chronic in- gestion of large doses saturates a major metabolic pathway, Effects of NSAIDs on Other Drugs thereby slowing drug elimination, prolonging the serum half- life, and causing drug accumulation. NSAIDs decrease effects of ACE inhibitors, beta blockers, and diuretics. With ACE inhibitors, there are decreased anti- Prevention hypertensive effects, probably because of sodium and water To decrease risks of toxicity, plasma salicylate levels should retention. With beta blockers, decreased antihypertensive ef- be measured when an acute overdose is suspected and peri- fects are attributed to NSAID inhibition of renal prostaglandin odically when large doses of aspirin are taken long term. Ther- synthesis, which allows unopposed pressor systems to pro- apeutic levels are 150 to 300 mcg/mL. With diuretics, decreased effects on toxicity occur at serum levels > 200 mcg/mL; severe toxic ef- hypertension and edema are attributed to retention of sodium fects may occur at levels > 400 mcg/mL. With anti- Recognition: Signs and Symptoms coagulants, prothrombin time may be prolonged and risks of Manifestations of salicylism include nausea, vomiting, fever, bleeding are increased by NSAID-induced gastric irritation fluid and electrolyte deficiencies, tinnitus, decreased hearing, and antiplatelet effects. With cyclosporine, nephrotoxicity visual changes, drowsiness, confusion, hyperventilation, and associated with both drugs may be increased. Severe central nervous system dysfunction (eg, delir- ibuprofen and indomethacin may increase serum levels. With Treatment lithium, serum drug levels and risk of toxicity may be in- In mild salicylism, stopping the drug or reducing the dose is creased (except with sulindac, which has no effect or may de- usually sufficient. In severe salicylate overdose, treatment is crease serum lithium levels). With methotrexate, risks of symptomatic and aimed at preventing further absorption from toxicity (eg, stomatitis, bone marrow suppression, nephro- the GI tract; increasing urinary excretion; and correcting toxicity) may be increased. Celecoxib and meloxicam appar- fluid, electrolyte, and acid–base imbalances. Intravenous (IV) sodium bicar- bonate produces an alkaline urine in which salicylates are Guidelines for Therapy more rapidly excreted, and hemodialysis effectively removes With Acetaminophen salicylates from the blood. The specific content of IV flu- Acetaminophen is effective and widely used for the treat- ids depends on the serum electrolyte and acid–base status. Two major advantages over aspirin are that acetaminophen does not cause gastric irritation or increase the risk of bleeding. Many NSAIDs are prescription drugs sociated with several maternal and fetal disorders, including used primarily for analgesia and anti-inflammatory effects in bleeding). However, sev- Despite its high degree of safety when used appropri- eral are approved for more general use as an analgesic or an- ately, acetaminophen is probably not the drug of choice for tipyretic. Ibuprofen, ketoprofen, and naproxen are available people with hepatitis or other liver disorders or those who by prescription and OTC. Clients must be instructed to avoid drink substantial amounts of alcoholic beverages. The major combined use of prescription and nonprescription NSAIDs drawback to acetaminophen use is potentially fatal liver because of the high risk of adverse effects. The kidneys and myocardium may monly cause gastric mucosal damage, and prolonged use may also be damaged. Potentially fatal hepatotoxicity is the main con- cysteine (Mucomyst), a mucolytic agent given by inhalation cern and is most likely to occur with doses of 20 g or more. For acetaminophen poisoning, it is Metabolism of acetaminophen produces a toxic metabolite usually given orally (dosage is listed with other antidotes in that is normally inactivated by combining with glutathione. The drug provides cysteine, a precursor substance In overdose situations, the supply of glutathione is depleted required for the synthesis of glutathione.
The role of locus coeruleus in the regulation of neurotrophic factor and nerve growth factor in rat cognitive performance order 40 mg lasix amex pulse pressure variation ppt. Nat long-term synaptic depression in visual cortex by Rev Neurosci 2001; 2:24–32. Serotonergic functions in arousal and mo- rotrophic factor to postsynaptic neurons. Jovanovic J, Czernik A, Fienberg A, Greengard P, Curr Opin Neurobiol 1997; 7:820–825. Nat Neurosci 2000; 3:323– tonin and human information processing: Fluvox- 329. Smit A, Syed N, Schaap D, van Minnen J, Klumper- ple 5-HT, autoreceptors: Parallel purposes or point- man J, Kits K, Lodder H, Van Der Schors R, Van Elk less plurality? Dinse H, Ragert P, Pleger B, Schwenkreis P, Tegen- glia-derived acetylcholine-binding protein that mod- thoff M. Pharmacological control of short-term plas- ulates synaptic transmission. Nature 2001; 411:261– ticity in human somatosensory cortex: Correlation be- 268. Ann Neu- vents expansion of topographic maps in somatosen- rol 2002; 51:59–68. Role of individual neurons and neural sponses comply with basic assumptions of formal networks in cognitive functioning: A new insight. NMDA re- hippocampal neurons predict how well word pairs ceptor-dependent synaptic reinforcement as a cru- will be remembered. Principles of Behavioral and Cog- tion learning requires sleep after training. Cortical regions involved C, Phillips C, Aerts J, Del Fiore G, Degueldre C, in perceiving object shape. Neuroscience 2000; 20: Meulemans T, Luxen A, Franck G, Van Der Lin- 3310–3318. Category-related recognition defects as cium signaling controls CREB-mediated gene ex- a clue to the neural substrates of knowledge. Nature 2001; 410:372– Parallel brain systems for item memory and cate- 375. Neuroanatomy of mem- creases cell proliferation and neurogenesis in the ory. Interactive mem- rotrophic factor in spatial memory formation and ory systems in the human brain. Neural bases of learning and dala impair enhanced perception of emotionally memory: Functional neuroimaging evidence. Sepa- critical for stress-induced modulation of hippocam- rate neural bases of two fundamental memory pal long-term potentiation and learning. Eldridge L, Knowlton B, Furmanski C, Bookheimer Neuroscientist 1998; 4:285–300. Functional magnetic resonance frontal-temporal circuitry for episodic encoding sub- imaging (fMRI) activity in the hippocampal region sequent memory. Retrieval and reconsolidation: Toward a neu- experience as predicted by brain activity. Fernandez G, Weyerts H, Schrader-Bolsche M, 74 Neuroscientific Foundations for Rehabilitation Tendolkar I, Smid H, Tempelmann C, Hinrichs H, ham R. The prefrontal cortex: Response selection or Scheich H, Elger C, Mangun G, Heinze H. Science cessful verbal encoding into episodic memory en- 2000; 288:1656–1660. Working memory for loca- analyzed functional magnetic resonance imaging tion and time: Activity in prefrontal area 46 relates study. Jonides J, Schumacher E, Smith E, Koeppe R, Awh NeuroImage 2001; 11:77–86. J Neurosci 1998; 18:5026– the neural circuitry of emotion regulation-a possible 5034.
The main conclusion Back to the example of the periodontal study in of studies relating to sugar and dental caries which the number of sites assessed was 2236 dis- has been that (1) consumption of sugar generic 100mg lasix fast delivery pulse pressure table, even tributed on 559 teeth in 22 subjects. A three-level model at meals is associated with a marked increase was built with site as level 1, tooth as level 2 in caries increment. At the site level, 12 vari- shaped key dental education messages of oral ables were constructed (e. The above analysis was performed using in caries incidence with different types of sugars, the software MLn (the non-WindowsTM version notably, the low caries rate associated with the of MLwiN). With the use of MLM, it is then pos- use of sugar alcohols like xylitol. Systematic reviews of IMPACT OF TRIALS ON DENTAL PRACTICE the effectiveness of water fluoridation have con- cluded that it is an effective, efficient and safe DIET AND DENTAL CARIES method of preventing dental caries and possibly promotes equity in oral health in society. However, the only a handful of countries where it is widely studies have suggested that there is little ben- available and consumed. Concerns about the efit where water fluoride concentrations exceed appropriate dosage (a minimum of 200 mg/l F is 1 ppm. These findings have resulted in the imple- recommended) and safety for general health may mentation of water fluoridation in many indus- impede its widespread implementation. It to drops have long been considered an alterna- remains a key World Health Organization goal tive to water fluoridation. However, in oride from other sources such as toothpaste, the the most part such mottling is unlikely to be marginal effect of fluoride supplements is very of aesthetic concern. Despite strong evidence of small and there is substantial risk of fluorosis if the effectiveness and safety of water fluoridation supplements are used by young children. Evidence of a lower concentration of fluoride in dentifrices the effectiveness of salt fluoridation has largely (250–500 ppm F) be used and that only a mini- come from test and control community studies mum amount (less than 5 mm) should be placed in several different countries. A key focus of research has been the perfor- mance of direct posterior restorations (fillings), OTHER FORMS OF TOPICAL FLUORIDE the longevity and reasons for failure of direct resin-based composite (RBC), amalgam and glass Many forms of professionally applied fluoride ionomer cement (GIC) restorations in stress- have been studied, including solutions, gels or bearing posterior cavities. Predominantly studies foams of sodium fluoride, stannous fluoride, have been either of the longitudinal or retro- organic amine fluoride, acidulated phosphate flu- spective cross-sectional type, with few controlled oride and non-aqueous fluoride varnishes in an clinical studies. GIC perform significantly worse alcoholic solution of natural resins and difluorosi- 82 compared with amalgam and RBC. However, a recent resultedinanincreaseduseofRBCorGIC systematic review of the periodic scientific liter- 83 restorations in posterior teeth. The handling and ature undertaken to determine the strength of the fluoride leaching properties of GIC have made evidence for the efficacy of professional caries 84 them popular in general practice. Evidence of other fluoride sources, reports of inconclusive has largely been collated from longitudinal or evidence and because of health care reimburse- case–control studies with relatively few RCTs. Implant-retained overdentures are reported to be superior to complete dentures. However, the widespread use of Most carious lesions occur in the pit and fis- implants in practice has been limited by a number sure on the occlusal surface of posterior teeth. However, the cost-effectiveness of fissure a greater degree of conservation of tooth struc- sealants in clinical trials remains questionable. Increasingly RBBs are being employed in den- oral health care usually require detailed justifica- tal practice in the treatment of short edentu- tion for surgical periodontal care. ORTHODONTICS TRIALS RELATING TO PERIODONTAL While there has been considerable growth in DISEASE the practice of orthodontics there is a dearth of evidence-based research, particularly RCTs. Stud- result that many clinicians decide, on a case- ies have shown that the most important plaque by-case basis, when to provide orthodontic treatment. While such aids have been shown to be to the need for extraction of teeth for orthodon- effective in plaque control with minimum damage tic purposes, has resulted in clinicians decid- if used correctly, they are generally prescribed ing on a case-by-case basis without any clinical guidelines. In particular the use of chlorhexidene in the Currently the lack of high-quality research within chemical control of plaques has widely been dentistry, namely the lack of RCTs, has impeded advocated, particularly in acute phases and in the identification of best dental practice and preventing post-surgical infection. There is however widespread is a tendency for it to stain (extrinsic) teeth.
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