Georgia Massage Therapy Ebook Continuing Education

NSAIDS and the role of cyclooxygenase inhibition NSAIDs work to block the effect of an enzyme called cyclooxygenase . This enzyme is critical in the body’s production of prostaglandins. It is prostaglandins that cause swelling and pain in a condition such as arthritis or bursitis. Therefore, by interfering with cyclooxygenase, you decrease the production of prostaglandins, and decrease pain and swelling associated with this condition. However, prostaglandins also have other important functions in the body. One type of prostaglandin (there are many varieties) helps line the stomach with a protective fluid (called gastric mucosa ). When the production of this protective fluid is diminished, some people are at risk for developing stomach ulcers. Aspirin’s anti-inflammatory effects are due to its nonselective inhibition of both cyclooxygenase (COX) forms. Aspirin is a more potent inhibitor of both prostaglandin synthesis and platelet aggregation than other salicylic acid derivatives. The differences in activity between aspirin and salicylic acid are thought to be due to the acetyl group on the aspirin molecule. This acetyl group is responsible for the inactivation of cyclooxygenase via acetylation. In general, immediate release aspirin is nearly completely absorbed from the gastrointestinal (GI) tract. Following absorption, aspirin is hydrolyzed to salicylic acid with peak plasma levels of salicylic acid occurring within 1-2 hours of dosing. The rate of absorption from the GI tract is dependent upon the dosage form, the presence or absence of food, gastric pH (the presence or absence of GI antacids or buffering agents), and other physiologic factors. Enteric-coated aspirin products are unevenly absorbed from the GI tract. Salicylic acid is widely distributed to all tissues and fluids in the body including the central nervous system (CNS), breast milk, Contraindications of aspirin ● Allergy : Aspirin is contraindicated in people with known allergy to nonsteroidal anti-inflammatory drug products and in patients with the syndrome of asthma, rhinitis, and nasal polyps. Aspirin may cause severe urticaria, angioedema, or bronchospasm (asthma). ● Reye’s syndrome: Aspirin should not be used in children or teenagers for viral infections, with or without fever, because of the risk of Reye’s syndrome with concomitant use of aspirin in certain viral illnesses. ● Alcohol warning: People who consume three or more alcoholic drinks every day should be counseled by their doctor about the bleeding risks involved with chronic, heavy alcohol use while taking aspirin. ● Coagulation abnormalities: Even low doses of aspirin can inhibit platelet function leading to an increase in bleeding time. This can adversely affect people with inherited (hemophilia) or acquired (liver disease or vitamin K deficiency) bleeding disorders. ● Gastrointestinal side effects: GI side effects include stomach pain, heartburn, nausea, vomiting, and gross GI bleeding. Although minor upper GI symptoms, such as Drug interactions Angiotensin converting enzyme (ACE) inhibitors The hyponatremic and hypotensive effects of ACE inhibitors may be diminished by the concomitant administration of aspirin due to its indirect effect on the renin-angiotensin conversion pathway. ● Acetazolamide: Concurrent use of aspirin and acetazolamide can lead to high serum concentrations of acetazolamide (and toxicity) due to competition at the renal tubule for secretion. ● Anticoagulant therapy (heparin and warfarin): People on anticoagulation therapy are at increased risk for bleeding because of drug interactions and the effect on platelets.

and fetal tissues. The highest concentrations are found in the plasma, liver, renal cortex, heart, and lungs. The protein binding of salicylate is concentration-dependent, i.e., nonlinear. An early sign of salicylic overdose (salicylism) is tinnitus (ringing in the ears). Aspirin is rapidly hydrolyzed in the plasma to salicylic acid such that plasma levels of aspirin are essentially undetectable 1-2 hours after dosing. The elimination of salicylic acid follows zero order pharmacokinetics; (i.e., the rate of drug elimination is constant in relation to plasma concentration). Renal excretion of unchanged drug depends upon urine pH. Following therapeutic doses, approximately 10 percent is found excreted in the urine as salicylic acid, 75 percent as salicyluric acid, and 10 percent phenolic and 5 percent acyl glucuronides of salicylic acid. Aspirin affects platelet aggregation by irreversibly inhibiting prostaglandin cyclooxygenase. This effect lasts for the life of the platelet and prevents the formation of the platelet-aggregating factor. Non-acetylated salicylates (see below) do not inhibit this enzyme and have no effect on platelet aggregation. At somewhat higher doses, aspirin reversibly inhibits the formation of prostaglandin I2 (prostacyclin), which is an arterial vasodilator and inhibits platelet aggregation. At higher doses, aspirin is an effective anti-inflammatory agent, partially due to inhibition of inflammatory mediators via cyclooxygenase inhibition in peripheral tissues. Studies suggest that other mediators of inflammation may also be suppressed by aspirin administration, although the precise mechanism of action has not been explained. It is this nonspecific suppression of cyclooxygenase activity in peripheral tissues following large doses that leads to its primary side effect of gastric irritation. dyspepsia, are common and can occur anytime during therapy, physicians should remain alert for signs of ulceration and bleeding, even in the absence of previous GI symptoms. Physicians should inform patients about the signs and symptoms of GI side effects and what steps to take if they occur. ● Peptic ulcer disease: People with a history of active peptic ulcer disease should avoid using aspirin, which can cause gastric mucosal irritation and bleeding. ● Renal failure: Avoid aspirin in people with severe renal failure (glomerular filtration rate less than 10 mL/minute). ● Hepatic insufficiency: Avoid aspirin in people with severe hepatic insufficiency. ● Sodium restricted diets: People with sodium-retaining states, such as congestive heart failure or renal failure, should avoid sodium-containing buffered aspirin preparations because of their high sodium content. ● Aspirin : Has been associated with elevated hepatic enzymes, blood urea nitrogen and serum creatinine, hyperkalemia, proteinuria, and prolonged bleeding time. Aspirin can displace warfarin from protein binding sites, leading to prolongation of both the prothrombin time and the bleeding time. Aspirin can increase the anticoagulant activity of heparin, increasing bleeding risk. ● Anticonvulsants: Salicylate can displace protein-bound phenytoin and valproic acid, leading to a decrease in the total concentration of phenytoin and an increase in serum valproic acid levels. ● Beta blockers: The hypotensive effects of beta blockers may be diminished by the concomitant administration of aspirin due to inhibition of renal prostaglandins, leading to decreased renal blood flow, and salt and fluid retention.

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Book Code: MGA1224

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