Linton: Introduction to Medical-Surgical Nursing, 4th Edition

Pharmacology Tutorial

Chapter 4: Anti-Inflammatory Drugs

Anti-Inflammatory agents fall into two categories: steroidal and nonsteroidal. The steroidal anti-inflammatory drugs are corticosteroids produced by the adrenal cortex. These naturally occurring hormones, when are used pharmacologically, are discussed with drugs affecting the endocrine system. Therefore, this chapter will focus on the nonsteroidal anti-inflammatory agents, which are commonly referred to as NSAIDs.
Nonsteroidal anti-inflammatory drugs are classified as prostaglandin synthetase inhibitors (PSIs) or non–prostaglandin synthetase inhibitors (non-PSIs). 

PROSTAGLANDIN SYNTHETASE INHIBITORS
PSIs include carboxylic acids and enolic acids. Examples of carboxylic acids are salicylic, acetic, propionic, and anthranilic acids. The prototype you will probably recognize is aspirin (acetylsalicylic acid). Enolic acids include oxicams and pyrazolones (Table 4-1). 

Table 4-1
Miscellaneous Prostaglandin Synthetase Inhibitors
Type	Examples	Specific Considerations	
Arylacetic acid derivatives 	naproxen (Naprosyn)
naproxen sodium (Anaprox)
fenoprofen calcium (Fenoprofen)	Naproxen and naproxen sodium should not be given concurrently. Be alert for fluid retention with sodium preparation. 	
Anthranilic acid derivatives	mefenamic acid (Ponstel)
meclofenamate sodium         (Meclomen)	Both have significant adverse gastrointestinal effects. Mefenamic acid can cause agranulocytosis. Meclofenamate sodium has especially high incidence of colitis and diarrhea; also can cause renal and liver damage with long-term therapy.	

Table 4-1
Miscellaneous Prostaglandin Synthetase Inhibitors–cont’d
Type	Examples	Specific Considerations	
Phenylalkanoic acid derivatives	flurbiprofen (Ansaid)	Similar to other PSIs.	
Oxicams	piroxicam (Feldene)	In addition to other PSI effects, can cause drowsiness and reduced hemoglobin and hematocrit.	
Pyrrolacetic acid derivatives	ketorolac tromethamine (Toradol)	Only injectable NSAID. In addition to other PSI effects, is nephrotoxic with long-term use and causes drowsiness.	

Actions and Uses
Prostaglandin synthetase inhibitors prevent the synthesis and release of prostaglandins. They are useful in a variety of situations in which there is inflammation, pain, and/or fever. This could include acute infectious conditions as well as chronic inflammatory conditions such as osteoarthritis. 

Side and Adverse Effects
Adverse effects of PSIs most commonly affect the gastrointestinal (GI) tract, kidneys, and the blood cells. Central nervous system effects are less common.
•	GI effects: heartburn, nausea, vomiting, ulceration and bleeding, abdominal pain 
•	Kidneys: renal impairment, retention of sodium and water, hyperkalemia
•	Blood cells: decreased platelet aggregation (clumping), decreased white blood cells
•	Central nervous system effects: tinnitus, vertigo, altered vision, confusion, drowsiness, dizziness, headache 
•	Allergic reactions: itching, rash, wheezing, edema 

Interactions and Contraindications
Even though PSIs are available as over-the-counter drugs, it is necessary to assess for any potential interactions with other drugs the patient is taking because PSIs interact with many other drugs. Some important examples are diuretics and antihypertensives, which may be counteracted by PSIs. If given with anticoagulants, PSIs increase the risk of bleeding. GI adverse effects are enhanced by alcohol.

Nursing Actions
•	Assess for GI symptoms, edema, decreased urine output, easy bruising or bleeding. 
•	Be aware that older adults taking PSIs are at greater risk for adverse effects, especially confusion. 
•	Evaluate local pain, swelling, redness, and warmth. 
•	With long-term therapy, monitor complete blood cell counts for decreased platelets and white blood cells.

PATIENT TEACHING
Patient teaching is especially important because these drugs are widely used and can be obtained without a prescription. 
•	Take PSIs 15 to 30 minutes before meals and with 8 ounces of water.
•	PSIs may be taken with a little food or milk to reduce gastrointestinal upset. 
•	Do not exceed the recommended dosage.
•	Alcohol and caffeine tend to increase gastrointestinal distress with these drugs.

Salicylic Acid Prototype: Acetylsalicylic Acid (Aspirin)

Actions and Uses
Aspirin has anti-inflammatory, antipyretic, and analgesic effects. It is used to treat various symptoms including headache, fever, and joint and muscle pain. Because of its antiplatelet effects, small daily doses are used to prevent thrombosis responsible for myocardial infarction and stroke. 

Side and Adverse Effects
Aspirin has the general PSI adverse effects (GI distress, renal damage, bleeding) already discussed. In addition, with prolonged or excessive use, there is a risk of salicylate poisoning (called salicylism). Symptoms of salicylism are tinnitus (“ringing” in the ears), headache, sweating, nausea and vomiting, and hyperventilation. In older adults, the only symptom may be confusion. Allergic reactions occur most often in people with asthma or nasal polyps. 

Interactions and Contraindications
Aspirin interacts with many other drugs. For example, excretion of aspirin is enhanced by antacids and urine alkalinizers. Aspirin enhances the effects of insulin, oral hypoglycemics, and anticoagulants. It also increases the risk of toxicity from methotrexate and zidovudine.
General contraindications to aspirin therapy are bleeding disorders, anticoagulant therapy, history of asthma or nasal polyps, and the third trimester of pregnancy. If aspirin is given to young children or adolescents for viral infections, there is a risk of Reye’s syndrome. Reye’s syndrome is an often fatal syndrome that affects the central nervous system, kidneys, and the liver. 

Nursing Actions and Patient Teaching
Same as general PSI implications.

Acetic Acid Derivative Prototype: Indomethacin (Indocin)
Indomethacin (Indocin) is similar to aspirin in action, adverse effects, interactions, and contraindications. It is, however 20 to 30 times more potent than aspirin. One unique action is that indomethacin causes the ductus arteriosus to close. Therefore, it is not given during the last trimester of pregnancy when it could cause the ductus to close prematurely. However, the drug may be given to premature infants to induce closure of the ductus. Some older people may experience depression when on indomethacin. 
Other acetic acid derivatives are sulindac (Clinoril), tolmetin sodium (Tolmetin), and diclofenac sodium (Voltaren). 

Propionic Acid Derivative Prototype: Ibuprofen (E.G., Motrin, Advil)
Ibuprofen (Motrin) and another propionic acid derivative, ketoprofen (Orudis), are similar to aspirin in action, adverse effects, interactions, and contraindications. In addition to assessing for GI bleeding, renal function must be monitored with long-term therapy. Many patients who are allergic to aspirin are also allergic to ibuprofen or ketoprofen. These drugs can cause photosensitivity, so patients should protect their skin from direct sunlight. 

COX-2 INHIBITORS
Theoretically, COX-2 inhibitors (coxibs) selectively inhibit COX-2 to suppress pain and inflammation with little or no risk of serious side effects. However, although coxibs are safer than traditional NSAIDs, there is still a risk of serious GI complications in some patients (gastroduodenal ulceration and bleeding). Impaired renal function can occur, causing hypertension and edema. Coxibs do not inhibit platelet aggregation, so do not increase risk of bleeding. Because these drugs are much more expensive than generic forms of traditional NSAIDs, their use should be reserved for those patients at high risk for a major GI event. Drugs in this category are celecoxib (Celebrex), rofecoxib (Vioxx), and valdecoxib (Bextra).
•	Celecoxib (Celebrex): contains a sulfur molecule that can precipitate an allergic reaction in patients allergic to sulfonamides; may increase anticoagulant effects of warfarin (increases warfarin levels).
•	Rofecoxib (Vioxx): increased risk of myocardial infarction, particularly at higher than recommended doses; increases plasma levels of lithium and methotrexate; enhanced warfarin effects.
•	Valdecoxib (Bextra): has molecular structure similar to sulfonamides (contraindicated for persons with sulfonamide allergy); may increase plasma levels of warfarin; may antagonize antiplatelet effects of aspirin.

NON–PROSTAGLANDIN SYNTHETASE INHIBITORS
Acetaminophen (e.g., Tylenol) is an example of a non-PSI. It is often used with inflammatory conditions, but it actually does not reduce inflammation. It is effective as an antipyretic and analgesic, so it is commonly used to treat mild pain and fever. It is discussed in greater detail with analgesics. 

GOLD SALTS

Action and Uses
One other type of drug that is used specifically for rheumatoid arthritis is gold salts. The prototype is gold sodium thiomalate (Myochrysine). This drug seems to suppress the immune response in joint tissues, thereby decreasing inflammation and slowing disease progression. 

Side and Adverse Effects
Gold salts are very toxic. They can cause dermatitis, pruritus, skin pigmentation, stomatitis, renal toxicity, and bone marrow suppression. Some people are allergic to this drug. 

Interactions and Contraindications
Do not give gold salts with other drugs that can suppress bone marrow. Use is contraindicated with diabetes mellitus, renal or hepatic dysfunction, enterocolitis, congestive heart failure, hypertension, and blood dyscrasias. 

Nursing Actions
Gold sodium thiomalate is given intramuscularly on a weekly basis until a specific total dose has been given. For the injection, the patient should lie down and remain recumbent for at least 10 minutes. Toxic or anaphylactic reactions are treated with dimercaprol (BAL).