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A. Aschnu. Rider University.

The treatment modalities are generally comparable with respect to efficacy and safety even when used in combination [3] order gemfibrozil canada. The Baylor bleeding score best 300 mg gemfibrozil, using patient age buy gemfibrozil 300mg online, number of illnesses, illness severity, site of bleeding, and stigmata of bleeding, has been proposed to predict the likelihood of rebleeding [54] and may be useful in determining which patients may benefit from second-look endoscopy [30]. Angiotherapy Intra-arterial vasopressin and/or embolization are used for angiographic control of various bleeding lesions [8,55]. A recent randomized study comparing urgent colonoscopy to radionuclide scanning followed by angiography demonstrated no differences in hospital stay and transfusion requirements despite the fact that colonoscopy identified a definitive bleeding source more often. However, this study used only vasopressin infusion and did not use embolization as a mode of angiotherapy [56]. Gelfoam and metal coils used for embolic therapy after superselective cannulation of the bleeding artery are effective because they can be delivered close to the terminal bleeding vessel and result in localized thrombosis with vessel occlusion. Embolization successfully controls bleeding in 52% to 94% of patients, with approximately 10% of these patients requiring repeat embolization for recurrent bleeding [57]. There is a risk of bowel ischemia following embolization, but this is usually minor and self- limited [55]. Angiotherapy can be comparable to surgical intervention when endoscopic therapy fails for bleeding peptic ulcers. A retrospective analysis demonstrated no difference between embolization and surgery in recurrent bleeding (29. The timing for the use of angiography and angiotherapy must be individualized and usually is a consensus decision by the involved physicians. Surgical Therapy the appropriate timing of when a surgeon should be involved in the care of a bleeding patient is physician and institution dependent, and ranges from an early team approach at presentation to involvement once the risk of significant morbidity and mortality are established after a poor response to medical and endoscopic therapy. Surgical intervention is an effective and safe alternative for patients with uncontrollable bleeding or those unable to tolerate additional bleeding [59]. Prior to surgical intervention, a repeat endoscopy for a patient with persistent or recurrent bleeding can be considered owing to lower risks of side effects from endoscopy compared to surgery [60,61]. A possible exception may be ulcers >2 cm in hypotensive patients where the risk of rebleeding is extremely high with repeat endoscopic therapy [26,61]. Patients with massive hemorrhage that overwhelms the resuscitation effort may need to proceed directly to the surgical suite during ongoing resuscitation. If these patients are high-risk surgical candidates, angiotherapy or a percutaneously or surgically placed portal-hepatic shunt for variceal bleeding may be alternatives. Bleeding from gastroesophageal varices characteristically is brisk and typically presents as hematemesis, melena, or hematochezia in association with hemodynamic instability. The presentation may be less dramatic because acute blood loss can be self- limited in 50% to 60% of cases [62]. Once active bleeding stops, the likelihood of recurrent variceal hemorrhage is 40% within 72 hours and 60% within 10 days if no definitive treatment is pursued [48]. Risk factors associated with variceal rupture include a portal pressure gradient greater than 12 mm Hg, large variceal size (greater than 5 mm), and progressive hepatic dysfunction [66]. Endoscopic findings that implicate esophageal or gastric varices as the bleeding source include the red sign, where one varix is brighter red than the others from microtelangiectasia (red-sign variants include red- wale marks, cherry-red spots, hematocystic spots, and diffuse redness of varix), and the white-nipple sign, in which a fresh fibrin clot may be seen protruding from a varix [66,67]. Endotracheal intubation protects the airway from aspiration of blood in obtunded patients, especially in the setting of massive bleeding [68]. Additional complications that must be addressed include alcohol withdrawal, aspiration, infection, and electrolyte imbalances. Octreotide is a somatostatin analog that decreases splanchnic blood flow and portal pressure, controlling variceal bleeding in as many as 85% of patients [69,70] with an efficacy approaching that of endoscopic therapy and providing improved visibility during subsequent endoscopy [70–72]. Aside from transient nausea and abdominal pain with bolus doses, significant adverse effects from octreotide are rare. Vasopressin, once widely used in this setting, has a significant cardiovascular side effect profile and for this reason has been replaced by octreotide. Endoscopic evaluation should be performed urgently (within 12 hours) in patients in whom variceal bleeding is suspected [79]. Endoscopic band ligation has gained acceptance as the preferred endoscopic treatment for patients with bleeding esophageal varices, with rapid obliteration of varices, and low rates of complications and rebleeding (Table 203. Endoscopic variceal sclerotherapy (injecting a sclerosing solution into the variceal lumen or into the adjacent submucosa), although successful in controlling variceal bleeding, is associated with a 20% to 40% incidence of complications, and has largely been relegated to a second-line therapeutic modality, reserved for patients in whom band ligation is technically difficult [66,81]. Complications of band ligation include recurrent bleeding from treatment-induced esophageal ulcers, stricture formation, esophageal perforation, and acceleration of portal hypertensive gastropathy [82]. Repeat variceal band ligation is performed until varices are obliterated because this approach reduces the incidence of rebleeding [66]. Appropriate interval for repeat band ligation is controversial, with recommendations ranging from 1 to 8 weeks [79]. Gastric varices are detected in approximately 20% of patients with portal hypertension, but can also occur from splenic vein thrombosis. Gastric varices bleed less often, but blood loss can be more substantial compared to esophageal varices [83]. Complications include a propensity for embolic phenomenon posttreatment, including massive pulmonary embolism [85]. Embolization of the short gastric veins and varices is a potential management option for isolated gastric varices. Complications include transient deterioration of liver function, new or worsened hepatic encephalopathy (25%), and shunt insufficiency from thrombosis or stenosis [86]. When placed in an emergency setting to control active bleeding, a 10% in-hospital mortality and 40% 30-day mortality have been reported [86,88,89]. This technique requires a natural gastrorenal or gastrophrenic shunt, which occur in 95% of cases of gastric varices [90]. A balloon catheter is used to occlude the shunt, following which a sclerosant, for example, ethanolamine is injected into the varix [90]. A recent meta-analysis found a pooled clinical success rate of 97% with a major complication rate of 2. Surgically created shunts reliably control acute bleeding (>90%) and prevent rebleeding (<10%) [92,93] but are limited by high operative mortality and postprocedure encephalopathy. Therefore, surgical shunts are only considered in well-compensated cirrhotic patients with good long-term prognoses [93]. Esophageal or gastric balloon devices may be used for direct tamponade of the bleeding source when definitive therapy is not immediately available. There are two basic types of balloon tubes: those with gastric and esophageal balloons (Sengstaken–Blakemore and Minnesota tubes) and those with a large gastric balloon alone (Linton– Nachlas). Other complications (aspiration, balloon migration, airway occlusion, perforation, pressure necrosis) occur in 15% to 30% of patients, including death in 6% [94]. Instructions for correctly placing and maintaining a specific balloon device are included as a product insert and should be reviewed before balloon use. Other cofactors, including older age, a history of past peptic ulcers (especially with ulcer bleeding), and a history of coronary disease, may be independent risk factors for ulcer bleeding [96,97]. In a proportion of patients, the disorder remains idiopathic, because of either an inability to demonstrate H. A recent meta-analysis demonstrated a clear relationship between presence of comorbid conditions and risk of death from peptic ulcer bleed [102]. Other prognostic information can be obtained from endoscopy findings, which should detail whether stigmata of recent bleeding (active bleeding, nonbleeding visible vessel, adherent clot, flat pigment spots) or no stigmata (clean ulcer base) were found in association with the ulcer (Table 203.

Drugs with greater response at maximally effective concentrations are more efficacious than drugs with a lower maximal response gemfibrozil 300mg overnight delivery. Choice B is incorrect since no information is given about the half maximal concentrations of either drug order gemfibrozil without a prescription. Choices C and D are incorrect since it is not known if both drugs bind to the same receptor population order gemfibrozil 300 mg free shipping. Since propranolol decreases the effect of epinephrine but the inhibition can be overcome by giving a higher dose of epinephrine, propranolol must be a competitive antagonist. If D were correct, even very high concentrations of epinephrine would not be able to elicit a maximal effect in the presence of propranolol. Since picrotoxin decreases the maximal effect of diazepam regardless of the diazepam dose, it is a noncompetitive antagonist. Which statement would have to be correct to conclude that the mechanism of antipsychotic effects for these drugs is via binding to D2 receptors? D2 receptor binding should also be related to the potency of these drugs in causing Parkinson’s-like adverse effects. A positive correlation should exist between the affinity of these drugs to bind to D2 receptors and their potency for antipsychotic actions. Clozapine would have to be more potent than chlorpromazine for decreasing psychosis. To conclude that the mechanism of antipsychotic effect for these drugs is via binding to D2 receptors, there should be a positive correlation between the affinity of the drugs for D2 receptors and their potency for antipsychotic actions. Haloperidol should have the highest antipsychotic potency and clozapine the lowest. There is no guarantee the therapeutic effects and adverse effects are mediated by the same receptor population; therefore, a different correlation may exist for the adverse effects and D2 receptor affinity. The number of spare β -adrenergic receptors determines the size of the maximum effect of the agonist1 epinephrine. Spare β adrenergic receptors make the cardiac tissue less sensitive to epinephrine. A maximal effect of epinephrine is seen when only a portion of β adrenergic receptors are occupied. Only a fraction of the total receptors need to be bound to elicit a maximum cellular response when spare receptors are present. The other choices do not accurately describe the effects of having spare receptors. Up-regulation of receptors occurs when receptor activation is lower than normal, such as when the receptor is continuously exposed to an antagonist for that receptor. Down-regulation of receptors occurs when receptor activation is greater than normal because of continuous exposure to an agonist, as described in A, B, and C. Warfarin treatment has a high chance of resulting in dangerous adverse effects if bioavailability is altered. Penicillin treatment has a high chance of causing dangerous adverse effects if bioavailability is altered. The endocrine system sends signals to target tissues by varying the levels of blood-borne hormones. By contrast, the nervous system exerts effects by the rapid transmission of electrical impulses over nerve fibers that terminate at effector cells, which specifically respond to the release of neuromediator substances. The peripheral nervous system is subdivided into the efferent and afferent divisions. Afferent neurons provide sensory input to modulate the function of the efferent division through reflex arcs or neural pathways that mediate a reflex action. The somatic efferent neurons are involved in the voluntary control of functions such as contraction of the skeletal muscles essential for locomotion. It is composed of efferent neurons that innervate visceral smooth muscle, cardiac muscle, vasculature, and the exocrine glands, thereby controlling digestion, cardiac output, blood flow, and glandular secretions. The preganglionic neurons emerge from the brainstem or spinal cord and make a synaptic connection in ganglia (an aggregation of nerve cell bodies located in the peripheral nervous system). The ganglia function as relay stations between the preganglionic neuron and the second nerve cell, the postganglionic neuron. It is generally nonmyelinated and terminates on effector organs, such as visceral smooth muscle, cardiac muscle, and the exocrine glands. The preganglionic neurons of the sympathetic 122 system come from the thoracic and lumbar regions (T1 to L2) of the spinal cord, and they synapse in two cord-like chains of ganglia that run close to and in parallel on each side of the spinal cord. Axons of the postganglionic neuron extend from the ganglia to tissues they innervate and regulate (see Chapter 6). In most cases, the preganglionic nerve endings of the sympathetic nervous system are highly branched, enabling one preganglionic neuron to interact with many postganglionic neurons. The adrenal medulla, in response to stimulation by the ganglionic neurotransmitter acetylcholine, secretes epinephrine (adrenaline), and lesser amounts of norepinephrine, directly into the blood. Postganglionic neurons from this nerve innervate most organs in the thoracic and abdominal cavity. In most instances, there is a one-to-one connection between the preganglionic and postganglionic neurons, enabling discrete response of this system. Functions of the sympathetic nervous system Although continually active to some degree (for example, in maintaining tone of vascular beds), the sympathetic division is responsible for adjusting in response to stressful situations, such as trauma, fear, hypoglycemia, cold, and exercise (ure 3. Effects of stimulation of the sympathetic division the effect of sympathetic stimulation is an increase in heart rate and blood pressure, mobilization of energy stores, and increase in blood flow to skeletal muscles and the heart while diverting flow from the skin and internal organs. Sympathetic stimulation results in dilation of the pupils and bronchioles (ure 3. ht or flight response the changes experienced by the body during emergencies are referred to as the “fight or flight” response (ure 3. These reactions are triggered both by direct sympathetic activation of effector organs and by stimulation of the adrenal medulla to release epinephrine and lesser amounts of norepinephrine. Hormones released by the adrenal medulla directly enter the bloodstream and promote responses in effector organs that contain adrenergic receptors (see Chapter 6). The sympathetic nervous system tends to function as a unit and often discharges as a complete system, for example, during severe exercise or in reactions to fear (ure 3. This system, with its diffuse distribution of postganglionic fibers, is involved in a wide array of physiologic activities. Although it is not essential for survival, it is essential in preparing the body to handle uncertain situations and unexpected stimuli. Functions of the parasympathetic nervous system the parasympathetic division is involved with maintaining homeostasis within the body. It is required for life, since it maintains essential bodily functions, such as digestion and elimination. The parasympathetic division usually acts to oppose or balance the actions of the sympathetic division and generally predominates the sympathetic system in “rest-and-digest” situations. Unlike the sympathetic system, the parasympathetic system never discharges as a complete system. If it did, it would produce massive, undesirable, and unpleasant symptoms, such as involuntary urination and defecation. Instead, parasympathetic fibers innervating specific organs such as the gut, heart, or eye are activated separately, and the system affects these organs individually.

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The vasoconstriction causes the feeling of chills which may lead to rigors with sudden elevation of body temperature buy generic gemfibrozil 300 mg line. Also the thermoregulatory center sends signal to cerebral cortex to initiate behavioral changes like seeking warm environment generic 300mg gemfibrozil with visa, extra clothing and flexed 213 Table 5 buy gemfibrozil 300mg amex. Tuberculosis is common and Viral infections Bacterial infections diagnosis can be established by appropriate investigations. Abrupt onset Insidious onset the second most common causes include autoimmune dis- Duration usually 3–5 days May last for more than 7 days eases such as juvenile rheumatoid arthritis or inflammatory Prodrome usually present No prodrome bowel disease. Relatively small numbers are due to Presence of rash almost always Very few bacterial conditions malignancies, the most common being leukemia and suggests viral etiology produce rash lymphoma. Bacteria: Salmonella, Tuberculosis, Brucellosis, minimum requirement for this diagnosis. Meningococcemia, Actinomycosis, Mycoplasma pneumoniae • neutropenic fuo: Temperature of 38. Spirochetes: Borrelia burgdorferi, relapsing fever, leptospirosis, occasions in a patient whose neutrophil count is less syphilis than 500/cells/mm3. Parasites: Amoebiasis, babesiosis, giardiasis, malaria, toxoplasmosis is invoked if a specific cause is not identified after 3 days d. Fungi: Blastomycosis, coccidioidomycosis, histoplasmosis of investigations including at least 2 days incubation of e. Local septic infections: Dental abscess, hepatic abscess, subphrenic abscess, bronchiectasis, investigations over 3 days including 2 days incubation sinusitis, mastoditis, tonsillitis of culture reveal no organism. Metabolic : Gout, porphyria infectious causes accounting for 65% followed by neoplastic 4. Hypersensitive reaction: Serum sickness, drug fever between 7 years and 12 years, infective causes accounts for 6. Miscellaneous: Cirrhosis of liver, sarcoidosis, familial mediterranean 38%, neoplastic 4% and autoimmune 23%. Enquire carefully for the exposure to animals or Serology may be negative in children rendering diagnosis animal products such as cheese made from unpasteurized difficult. In many cases a definite diagnosis cannot be established because of negative cultures and Factitious Fever failure to demonstrate serological titers. If the patient is an infant or young child, parent or caretaker Salmonellosis is the one who is fabricating. In most cases, factitious fever is excluded by recording of temperature by healthcare Non-specificity of signs and symptoms accounts for worker. Repetitive blood and stool cultures are It is considered if patient is taking any drugs. Tuberculosis Withdrawal of the drug is associated with resolution of fever within 72 hours. Active disseminated tuberculosis has been documented in children with normal chest X-ray and the diagnostic approach for each child has to be indi- negative Mantoux test. Infection diagnostic evaluation may be initiated on an outpatient of pelvic bone is commonly implicated. However young infants and children who appear required to locate the site of infection. Liver Abscess Hospitalization helps in documenting the fever, exploring Pyogenic liver abscesses are encountered most frequently the history further, repeating the physical examination and in immunocompromised patients but can occur in normal maintaining constant observation along with laboratory children. The combination of history of intra-abdominal disease, • Age: Neonates and young children are susceptible to recent abdominal surgery, and abdominal pain heightens specific organisms like Listeria monocytogenes and the suspicion of accumulation of pus. Connective tissue • Jaundice: Infectious hepatitis, Weil’s disease, tuber- disorders are four times more common in children who culosis, acute lymphatic leukemia, malaria, liver are more than 6 years old. Investigations • Note should be made about the presence of epidemics Investigations should be appropriate and based on in the community like dengue, enteroviral, leptospiral clinical history and physical findings. Further investigations depend on the child’s • Recent history of surgery suggests possibility of occult presentation and are listed as advanced investigations. Conversely, absolute neutrophil count of less including atropine (atropine induced fever). Direct blood smear examination Physical examination with Giemsa or Wright stain reveals organisms of malaria, Careful and meticulous physical examination is mandatory toxoplasma and relapsing fever. Repetitive examinations, preferable mm/hour indicates inflammation and need for further daily examination is important to pick-up subtle or new evaluation. Lumbar puncture is necessary in young infant or child with bibliography meningeal signs and altered mental status. Bronchoscopy, laparoscopy, gastrointestinal approach based on clinical clues from the history, physical endoscopy and mediastinoscopy may be warranted examination, and laboratory tests. Mild antipyretics are given for the patient Pediatrics: Principles and Practice, 3rd edition. They can be caused by a drug reaction, an • Drug rash infection, or an allergic reaction (Table 5. The skin can • Allergic vasculitis only react to injury in a few ways, and many different agents Infection can cause rashes that look the same. Often, the symptoms • Measles in addition to the rash help make the diagnosis, such as • Varicella a history of insect bites, exposure to other ill children or • Dengue fever adults, recent use of medication, environmental exposure, • Typhoid • Rubella or prior immunizations. However, • Meningococcemia some childhood rashes have serious or even life-threatening Other illnesses causes. About 10% of all febrile children have a • Erythema multiforme dermatological problem. It is common An algorithmic or stereotyped approach to a child with fever and skin to see more than one type of morphology at a given point rash would not sound meaningful. At times the lesions go through stages, and • Careful history taking in such cases the presenting lesion along with relevant • Astute clinical examination evidence from the history on evolution will help clinch • Relevant laboratory work-up the diagnosis. Yet others may start in a particular form and In history taking with regard to the fever, the points to be considered continue the same morphology, as in measles and rubella. Definitions of these • Itching/burning/pain patterns are given in the chapter on skin diseases in • Other symptoms children. With regard to the skin rash, the points to be considered include: Some examples are shown in Table 5. These are • Distribution of rash only guidelines and should not be considered as complete • Morphology or pattern of skin rash and comprehensive. The vaginal kind should be taken seriously, however, and may require a tract epithelium also may be involved. Many Life-Threatening Vascular reactions and patients require ventilator support because of respiratory failure. These two • Basic laboratory tests may be helpful in planning symptoms are present with many rashes and are often symptomatic or supportive therapy.

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These devastating illnesses are characterized by the progressive loss of selected neurons in discrete brain areas buy cheap gemfibrozil on line, resulting in characteristic disorders of movement cheap 300mg gemfibrozil with mastercard, cognition order gemfibrozil master card, or both. Overview of Parkinson Disease Parkinsonism is a progressive neurological disorder of muscle movement, characterized by tremors, muscular rigidity, bradykinesia, and postural and gait abnormalities. Most cases involve people over the age of 65, among whom the incidence is about 1 in 100 individuals. The disease is correlated with destruction of dopaminergic neurons in the substantia nigra with a consequent reduction of dopamine actions in the corpus striatum, parts of the basal ganglia system that are involved in motor control. Substantia nigra the substantia nigra, part of the extrapyramidal system, is the source of dopaminergic neurons (shown in red in ure 8. Each dopaminergic neuron makes thousands of synaptic contacts within the neostriatum and therefore modulates the activity of a large number of cells. These dopaminergic projections from the substantia nigra fire tonically rather than in response to specific muscular movements or sensory input. Thus, the dopaminergic system appears to serve as a tonic, sustaining influence on motor activity, rather than participating in specific movements. Neostriatum Normally, the neostriatum is connected to the substantia nigra by neurons (shown in orange in ure 8. In turn, cells of the substantia nigra send neurons back to the neostriatum, secreting the inhibitory transmitter dopamine at their termini. This mutual inhibitory pathway normally maintains a degree of inhibition of both areas. In Parkinson disease, destruction of cells in the substantia nigra results in the degeneration of the nerve terminals that secrete dopamine in the neostriatum. Thus, the normal inhibitory influence of dopamine on cholinergic neurons in the neostriatum is significantly diminished, resulting in overproduction, or a relative overactivity, of acetylcholine by the stimulatory neurons (shown in green in ure 308 8. This triggers a chain of abnormal signaling, resulting in loss of the control of muscle movements. Secondary parkinsonism Drugs such as the phenothiazines and haloperidol, whose major pharmacologic action is blockade of dopamine receptors in the brain, may produce parkinsonian symptoms (also called pseudoparkinsonism). Strategy of treatment In addition to an abundance of inhibitory dopaminergic neurons, the neostriatum is also rich in excitatory cholinergic neurons that oppose the action of dopamine (ure 8. Many of the symptoms of parkinsonism reflect an imbalance between the excitatory cholinergic neurons and the greatly diminished number of inhibitory dopaminergic neurons. Therapy is aimed at restoring dopamine in the basal ganglia and antagonizing the excitatory effect of cholinergic neurons, thus reestablishing the correct dopamine/acetylcholine balance. These agents offer temporary relief from the symptoms of the disorder, but they do not arrest or reverse the neuronal degeneration caused by the disease. It restores dopaminergic neurotransmission in the neostriatum by enhancing the synthesis of dopamine in the surviving neurons of the substantia nigra. In early disease, the number of residual dopaminergic neurons in the substantia nigra (typically about 20% of normal) is adequate for conversion of levodopa to dopamine. Thus, in new patients, the therapeutic response to levodopa is consistent, and the patient rarely complains that the drug effects “wear off. Relief provided by levodopa is only symptomatic, and it lasts only while the drug is present in the body. Without carbidopa, much of the drug is decarboxylated to dopamine in the periphery, resulting in diminished effect, nausea, vomiting, cardiac arrhythmias, and hypotension. The addition of carbidopa lowers the dose of levodopa needed by four- to five-fold and, consequently, decreases the severity of adverse effects arising from peripherally formed dopamine. Therapeutic uses Levodopa in combination with carbidopa is an efficacious drug regimen for the treatment of Parkinson disease. In approximately two-thirds of patients with Parkinson disease, levodopa–carbidopa substantially reduces the severity of symptoms for the first few years of treatment. Patients typically experience a decline in response during the 3rd to 5th year of therapy. Absorption and metabolism the drug is absorbed rapidly from the small intestine (when empty of food). Levodopa has an extremely short half- life (1 to 2 hours), which causes fluctuations in plasma concentration. This may produce fluctuations in motor response, which generally correlate with the plasma concentration of levodopa, or perhaps give rise to the more troublesome “on–off” phenomenon, in which the motor fluctuations are not related to plasma levels in a simple way. Motor fluctuations may cause the patient to suddenly lose normal mobility and experience tremors, cramps, and immobility. Thus, levodopa should be taken on an empty stomach, typically 30 minutes before a meal. Peripheral effects Anorexia, nausea, and vomiting occur because of stimulation of the chemoreceptor trigger zone (ure 8. Tachycardia and ventricular extrasystole result from dopaminergic action on the heart. In some individuals, blood dyscrasias and a positive reaction to the Coombs test are seen. Saliva and urine may turn brownish color because of the melanin pigment produced from catecholamine oxidation. These effects are the opposite of parkinsonian symptoms and reflect overactivity of dopamine in the basal ganglia. Interactions the vitamin pyridoxine (B ) increases the peripheral breakdown of6 levodopa and diminishes its effectiveness (ure 8. In many psychotic patients, levodopa exacerbates symptoms, possibly through the buildup of central catecholamines. Cardiac patients should be carefully monitored for the possible development of arrhythmias. Antipsychotic drugs are generally contraindicated in Parkinson disease, because they potently block dopamine receptors and may augment parkinsonian symptoms. However, low doses of atypical antipsychotics, such as quetiapine or clozapine, are sometimes used to treat levodopa-induced psychotic symptoms. By decreasing the metabolism of dopamine, selegiline increases dopamine levels in the brain (ure 8. When selegiline is administered with levodopa, it enhances the actions of levodopa and substantially reduces the required dose. However, the drug loses selectivity at high doses, and there is a risk for severe hypertension. Selegiline is metabolized to methamphetamine and amphetamine, whose stimulating properties may produce insomnia if the drug is administered later than mid-afternoon. Unlike selegiline, rasagiline is not metabolized to an amphetamine-like substance. Both of these agents reduce the symptoms of “wearing-off” phenomena seen in patients on levodopa–carbidopa. The two drugs differ primarily in their pharmacokinetic and adverse effect profiles. Pharmacokinetics Oral absorption of both drugs occurs readily and is not influenced by food.

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