– Describe the sites of action of the various anti-inflammatory agents.
– Describe the therapeutic actions, indications, pharmacokinetics, contraindications, most
common adverse reactions, and important drug–drug interactions associated with each class of anti-inflammatory agents:
– nonsteroidal anti-inflammatory drugs, and
– miscellaneous agents.
– Discuss the use of anti-inflammatory drugs across the lifespan.
– Compare and contrast the prototype drugs for each class of anti-inflammatory drugs with the other drugs in that class.
– Outline the nursing considerations and teaching needs for patients receiving each class of anti-inflammatory agents.
classes of anti-inflammatory agents:
– Nonsteroidal Anti-inflammatory Drugs
– celecoxib diclofenac diflunisal etodolac fenoprofen flurbiprofen ibuprofen indomethacin ketoprofen ketorolac mefenamic acid meloxicam nabumetone naproxen oxaprozin piroxicam sulindac tolmetin
– Related Drugs
– acetaminophen anakinra auranofin aurothioglucose etanercept gold sodium thiomalate hyaluronidase derivatives leflunomide penicillamine sodium hyaluronate
– The inflammatory response is designed to protect the body from injury and pathogens.
– It employs a variety of potent chemical mediators to produce the reaction that helps to destroy pathogens and promote healing.
– As the body reacts to these chemicals, it produces some signs and symptoms of disease, such as
– pain, and aches,
– Occasionally, the inflammatory response becomes a chronic condition and can actually result in body damage, leading to increased inflammatory reactions.
– Anti-inflammatory agents generally block or alter the chemical reactions associated with the inflammatory response to stop one or more of the signs and symptoms of inflammation.
– Corticosteroids are used systemically or locally to block the inflammatory and immune systems. Blocking these important protective processes may produce many adverse effects, including decreased resistance to infection and neoplasms.
– Antihistamines are used to block the release of histamine in the initiation of the inflammatory response.
– are popular anti-inflammatory agents, not only because of their ability to block the inflammatory response, but also because of their antipyretic (fever-blocking) and analgesic (pain-blocking) properties. They are generally available without prescription and are relatively nontoxic when used as directed
– Nonsteroidal anti-inflammatory drugs (NSAIDs)
– They provide strong anti-inflammatory and analgesic effects yet do not have the adverse effects that are associated with the corticosteroids.
– other related drugs.
– Acetaminophen also is a widely used agent. It has antipyretic and analgesic properties but does not have the anti-inflammatory effects of the salicylates or the NSAIDs.
– Because many anti-inflammatory drugs are available over the counter (OTC), there is a potential for abuse and overdosing. In addition, patients may take these drugs and block the signs and symptoms of a present illness, thus potentially causing the misdiagnosis of a problem. Patients also may combine these drugs and unknowingly induce toxicity. All of these drugs have adverse effects that can be dangerous if toxic levels of drug circulate in the body
Anti-inflammatory Agents Salicylates
Salicylates are some of the oldest anti-inflammatory drugs used. The synthetic salicylates include
– Aspirin (Bayer, Empirin, and others) is one of the most widely used drugs for treating inflammatory conditions; it is available OTC.
– Therapeutic Actions and Indications
– Salicylates inhibit the synthesis of prostaglandin, an important mediator of the inflammatory reaction
– At low levels, aspirin also affects platelet aggregation by inhibiting the synthesis of thromboxane A2, a potent vasoconstrictor that normally increases platelet aggregation and blood clot formation.
– Treatment of fever, pain, inflammatory conditions; including rheumatoid arthritis and osteoarthritis
– at low dose to prevent the risk of death and MI in patients with history of MI, prevention of transient ischemic attacks.
– Adult: 325–650 mg P0 or PR q4h Myocardial infarction (MI):300–325 mg P0
– Pediatric: 65–100 mg/kg/day P0 or PR in four to six divided doses;
Salicylates ;Contraindications and Cautions
– Allergy to salicylates, or other NSAIDs
– bleeding abnormalities, because of the changes in platelet aggregation associated with these drugs;
– impaired renal function, because the drug is excreted in the urine;
– chickenpox or influenza, because of the risk of Reye’s syndrome in children and teenagers;
– surgery or other invasive procedures scheduled within 1 week, because of the risk of increased bleeding; and
– pregnancy or lactation, because of the potential adverse effects on the neonate or mother.
– direct drug effects on the stomach (nausea, dyspepsia, heartburn, epigastric discomfort) and
– on clotting systems (blood loss, bleeding abnormalities).
– Salicylism can occur with high levels of aspirin;
– ringing in the ears,
– difficulty hearing,
– nausea, vomiting, diarrhea,
– mental confusion, and lassitude can occur.
– Acute salicylate toxicity may occur at doses of 20 to 25 g in adults or 4 g in children.
– Signs of salicylate toxicity include hyperpnea; tachypnea; hemorrhage; excitement; confusion; pulmonary edema; convulsions; tetany; metabolic acidosis; fever; coma; and cardiovascular, renal, and respiratory collapse.
– Salicylates block prostaglandin activity, which decreases the inflammatory response and relieves the signs and symptoms of inflammation.
– Salicylates can cause
– GI irritation,
– eighth cranial nerve stimulation, and
– salicylism—ringing in the ears,
– nausea, vomiting, diarrhea,
– mental confusion, and lassitude.
– The NSAIDs are a drug class that has become one of the most commonly used types . This group of drugs includes the following agents
– Propionic Acids
– Ibuprofen (Motrin, Advil, and others) is used as an OTC pain medication and for long-term management of arthritis pain and dysmenorrhea; it is the most widely used of the NSAIDs.
– Naproxen (Naprosyn) is available for OTC pain relief and to treat arthritis and dysmenorrhea.
– Acetic Acids
– Diclofenac (Voltaren, Cataflam) is used to treat acute and long-term pain associated with inflammatory conditions.
– Indomethacin (Indocin) is available in oral, topical, and rectal preparations for the relief of moderate to severe pain associated with inflammatory conditions and in intravenous form to promote closure of the patent ductus arteriosus in premature infants.
– Ketorolac (Toradol) is used for short-term management of pain and topically to relieve ocular itching.
– Piroxicam (Feldene) is used to treat acute and chronic arthritis.
– Oxicam Derivative
– Meloxicam (Mobic) is used for the relief of the signs and symptoms of juvenile arthritis, osteoarthritis, and rheumatoid arthritis.
– Cyclooxygenase-2 Inhibitor
– Celecoxib (Celebrex) is used for
the acute and long-term treatment of arthritis, particularly in patients who cannot tolerate the GI effects of other NSAIDs;
for acute pain in adults;
for ankylosing spondylitis; and
for primary dysmenorrhea.
– Therapeutic actions
– analgesic, and
– antipyretic effects of the NSAIDs are largely related to inhibition of prostaglandin synthesis .
– The NSAIDs block the synthesis of prostaglandins by blocking two enzymes, known as cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2).
– COX-1 is present in all tissues and seems to be involved in many body functions, including
– blood clotting,
– protecting the stomach lining, and
– maintaining sodium and water balance in the kidney.
– The adverse effects associated with most NSAIDs are related to blocking of both of these enzymes and changes in the functions that they influence—GI integrity, blood clotting, and sodium and water balance.
– The NSAIDs are indicated for
– relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis,
– relief of mild to moderate pain,
– treatment of primary dysmenorrhea, and
– fever reduction.
– Contraindicated in the
– Allergy to any NSAID or salicylate, and celecoxib is also contraindicated in the presence of allergy to sulfonamides.
– Cardiovascular dysfunction or hypertension
– peptic ulcer or known GI bleeding,
– pregnancy or lactation, because of potential adverse effects on the neonate or mother.
– Caution should be used with
– renal or hepatic dysfunction,
– with any other known allergies, which indicate increased sensitivity.
– Acetaminophen (Tylenol),
– Acetaminophen is used to treat moderate to mild pain and fever and often is used in place of the NSAIDs or Salicylates
– The gold compounds
– are used to prevent and suppress arthritis in selected patients with rheumatoid arthritis
– Therapeutic Actions
– Acts directly on the thermoregulatory cells in the hypothalamus to cause sweating and vasodilation; this in turn causes the release of heat and lowers fever.
– The mechanism of action related to the analgesic effects of acetaminophen has not been identified.
– treatment of pain and fever associated with a variety of conditions, including influenza;
– for the prophylaxis of children receiving diphtheria–pertussis–tetanus (DPT) immunizations (aspirin may mask Reye’s syndrome in children); and
– for the relief of musculoskeletal pain associated with arthritis.
Focus on Patient Safety
– These products are available without a prescription. Many people are unaware of their potential hazards, and they do not report the use of these products to their health care provider, even when specifically asked about drug use.
– Health care providers need to be alert for signs and symptoms of acetaminophen toxicity—initially nausea, vomiting, and GI upset. They need to ask patients specifically about whether they are using OTC products to reduce pain, control coughs, or help them sleep through the night.
– Contraindications and Cautions
– Allergy to acetaminophen.
– It should be used cautiously in pregnancy or lactation and
– in hepatic dysfunction or chronic alcoholism because of associated toxic effects on the liver.
– Adverse Effects
– hemolytic anemia,
– renal dysfunction, skin rash, and fever.
– Hepatotoxicity is a potentially fatal adverse effect that is usually associated with chronic use and overdose and is related to direct toxic effects on the liver.
– Clinically Important Drug–Drug Interactions
– increased risk of bleeding with oral anticoagulants because of effects on the liver;
– of toxicity with chronic ethanol ingestion because of toxic effects on the liver; and
– of hepatotoxicity with barbiturates, carbamazepine, hydantoins, rifampin, or sulfinpyrazone.
These combinations should be avoided, but if they must be used, appropriate dosage adjustment should be made and the patient should be monitored closely.
– NSAIDs block prostaglandin synthesis at cyclooxygenase-1 and -2 sites. This blocks inflammation but also blocks protection of the stomach lining, as well as the kidneys’ regulation of water.
– There are many different NSAIDs. If one does not work for a particular patient, another one might.
– Acetaminophen causes vasodilatation and heat release, lowering fever and working to relieve pain.
– Acetaminophen can cause liver failure. It is found in many OTC products. Patients need to be taught to avoid toxic doses of acetaminophen.
– The inflammatory response, which is important for protecting the body from injury and invasion, produces many of the signs and symptoms associated with disease, including fever, aches and pains, and lethargy.
– Chronic or excessive activity by the inflammatory response can lead to tissue destruction.
– Anti-inflammatory drugs block various chemicals associated with the inflammatory reaction. Anti-inflammatory drugs also may have antipyretic (fever-blocking) and analgesic (pain-blocking) activities.
– Salicylates block prostaglandin activity. NSAIDs block prostaglandin synthesis. Acetaminophen causes vasodilation and heat release, lowering fever and working to relieve pain.
– Salicylates can cause acidosis and eighth cranial nerve damage. NSAIDs are most associated with GI irritation and bleeding. Acetaminophen can cause serious liver toxicity.
– Many anti-inflammatory drugs are available OTC, and care must be taken to prevent abuse or overuse of these drugs.
– Multiple Choice
– Select the best answer to the following.
– An analgesic is a drug that
– reduces fever.
– reduces swelling.
– reduces redness.
– reduces pain.
– An antipyretic is a drug that can
– block pain.
– block swelling.
– block fever.
– block inflammation.
– Salicylates are very popular anti-inflammatory agents for all of the following reasons, except
– they have antipyretic properties.
– they have analgesic properties.
– they are available without a prescription.
– they must be given parenterally.
– The NSAIDs affect the COX-1 and COX-2 enzymes. By blocking COX-2 enzymes, the NSAIDs block inflammation and the signs and symptoms of inflammation at the site of injury or trauma. By blocking COX-1 enzymes, these drugs block
– fever regulation.
– prostaglandins that protect the stomach lining.
– swelling in the periphery.
– liver function.
– Your patient has been receiving ibuprofen for many years to relieve the pain of osteoarthritis. Assessment of the patient should include
– an electrocardiogram.
– CBC with differential.
– respiratory auscultation.
– renal evaluation.
– Patients taking NSAIDs should be taught to avoid the use of OTC medications without checking with their prescriber because
– many of the OTC preparations contain NSAIDs and inadvertent toxicity could occur.
– no one should take more than one type of pain reliever at a time.
– increased GI upset could occur.
– there is a risk of Reye’s syndrome
– Chronic or excessive activity by the inflammatory response can lead to
– loss of white blood cells.
– coagulation problems.
– release of lysosomal enzymes and tissue destruction.
– adrenal suppression
– A patient with rheumatoid arthritis who is on a fixed income and who is being treated with aspirin should be advised
– to use only brand-name aspirin.
– to use only enteric-coated aspirin.
– to use generic aspirin, checking the expiration date before use.
– to switch to one of the NSAIDs.