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Chapter 24

Drugs Treating Mild to Moderate Pain, Fever, Inflammation, and

Migraine Headache

Chapter 24

Drugs Treating Mild to Moderate Pain, Fever, Inflammation, and

Migraine Headache


Fever Fever

• Temperature regulation is a function of the hypothalamus.

• Normally, a homeostatic balance exists between body heat generated and body heat lost.

• Fever is the result of fever-inducing substances called pyrogens.

• Fever causes activation of monocytes/macrophages, which in turn secrete cytokines.

• Cytokines increase the synthesis and secretion of prostaglandin in the hypothalamus.

• This causes the hypothalamus to reset the body temperature.


Inflammation Inflammation

• Numerous types of stimuli cause the inflammatory response.

• The classic signs of local inflammation are swelling, heat, redness, pain, and loss of function.

• Acute inflammation is divided into vascular and cellular responses.

• The vascular response occurs almost immediately after the injury.


Inflammation (cont.)Inflammation (cont.)

• The cellular response is divided into four phases:

– Margination of white blood cells (WBCs) to the periphery of the blood vessels

– Emigration of WBCs—the WBCs migrate into the tissue spaces.

– Chemotaxis—cellular debris become more “attractive” to the WBCs.

– Phagocytosis—neutrophils and monocytes engulf cellular debris.


Prostaglandin Synthesis Prostaglandin Synthesis • Prostaglandins modulate some components of

inflammation, body temperature, pain transmission, platelet aggregation, and many other body actions.

• They are derived from arachidonic acid, which is liberated from the cell membrane in response to physical, chemical, hormonal, bacterial, or other stimuli.

• They are converted from arachidonic acid to prostaglandins by the enzyme cyclooxygenase (COX).

• There are two forms of the COX enzyme: COX-1 and COX-2.

• COX-1 synthesizes prostaglandins that are involved in the regulation of normal cell activity.

• COX-2 appears to produce prostaglandins mainly at the sites of inflammation.


Prostaglandin Synthesis (cont.)Prostaglandin Synthesis (cont.)


PainPain

• The physiologic mechanisms involved in the pain response are complex.

• The sensation of peripheral pain begins in afferent neurons called nociceptors.

• These receptors are activated by chemical mediators, such as prostaglandins, histamine, bradykinin, and serotonin.


Platelet Aggregation Platelet Aggregation

• Simply speaking, platelet aggregation is the clumping together of platelets in the blood.

• Platelet aggregation can be a beneficial process.

• Platelet aggregation can also be harmful. It is the first step in a sequence of events that leads to the formation of a thrombus.

• The risk of platelet aggregation is increased in patients who smoke and have hypercholesterolemia.


Migraine Headache Migraine Headache

• The two major types of migraine headache:

– Migraine with aura

– Migraine without aura

• It is postulated that migraine begins when intracranial blood vessels dilate.

• This dilation stimulates the trigeminovascular system, resulting in abnormally excitable neurons that send pain impulses to the brain’s pain receptors.


Drugs to Treat Inflammation and Fever Drugs to Treat Inflammation and Fever

• Salicylates, NSAIDs, and para-aminophenol derivative drugs are used to treat inflammation and fever in a variety of conditions.

• Salicylates are used in managing conditions ranging from a simple headache to acute myocardial infarction (MI).

• NSAIDs are used primarily as anti-inflammatory drugs but are also used extensively as analgesics.

• Prototype drug: acetylsalicylic acid (aspirin)


Aspirin: Core Drug Knowledge Aspirin: Core Drug Knowledge

• Pharmacotherapeutics

– Treat mild-to-moderate pain, prevent platelet aggregation

• Pharmacokinetics

– Absorbed in the stomach and small intestines; highly protein bound

• Pharmacodynamics

– Fever: inhibited PGE2 synthesis in the hypothalamus

– Inflammation: peripheral inhibition of prostaglandin

– Antiplatelet: irreversible inhibition of thromboxane A2


Aspirin: Core Drug Knowledge (cont.)Aspirin: Core Drug Knowledge (cont.)

• Contraindications and precautions

– Hypersensitivity, peptic ulcer disease, or bleeding disorders, and children with illness

• Adverse effects

– Renal failure, abnormal bleeding, GI upset, drowsiness, and confusion

• Drug interactions

– Other drugs that are highly protein bound


Aspirin: Core Patient Variables Aspirin: Core Patient Variables

• Health status

– Assess for contraindications to therapy.

• Life span and gender

– Contraindicated in the last trimester of pregnancy

• Lifestyle, diet, and habits

– Assess use of OTC medications.

• Environment

– Assess understanding of drug therapy.


Aspirin: Nursing Diagnoses and Outcomes Aspirin: Nursing Diagnoses and Outcomes

• Acute or chronic pain related to ineffectiveness of aspirin

– Desired outcome: The patient will contact the prescriber if pain persists.

• Risk for Injury: GI bleeding, hepatic or renal toxicity related to aspirin therapy

– Desired outcome: The patient will avoid injury by contacting the prescriber if any signs of toxicity occur.


Aspirin: Nursing Diagnoses and Outcomes (cont.)Aspirin: Nursing Diagnoses and Outcomes (cont.)

• Disturbed Sensory Perception (visual and auditory) related to blurred vision or tinnitus

– Desired outcome: The patient will contact the prescriber if blurred vision or tinnitus occurs.

• Ineffective Protection related to blood dyscrasias or rash

– Desired outcome: The patient will contact the prescriber if any signs of blood dyscrasias or rash occur.


Aspirin: Nursing Diagnoses and Outcomes (cont.)Aspirin: Nursing Diagnoses and Outcomes (cont.)

• Deficient Fluid Volume related to nausea and vomiting

– Desired outcome: The patient will avoid dehydration by contacting the prescriber if persistent nausea or vomiting occurs.

• Risk for Injury related to self-medication

– Desired outcome: The patient will avoid injury by taking aspirin as prescribed.


Aspirin: Planning and InterventionsAspirin: Planning and Interventions

• Maximizing therapeutic effects

– Give with milk or food to decrease GI upset.

– When giving aspirin for its cardiovascular properties, use uncoated aspirin.

• Minimizing adverse effects

– Do not administer aspirin to a patient with a medical condition that contraindicates its use.

– It is important to monitor closely patients with pre-existing medical conditions or those on drug therapy that may interact with aspirin.


Aspirin: Teaching, Assessment, and EvaluationsAspirin: Teaching, Assessment, and Evaluations

• Patient and family education

– Teach proper administration of medication.

– Discuss side effects of therapy.

• Ongoing assessment and evaluation

– Monitor the patient who is taking aspirin for signs and symptoms of GI distress or bleeding, anemia, hepatotoxicity, and renal failure.


QuestionQuestion

• Why is aspirin contraindicated in children with varicella?

– A. Can cause bleeding from skin lesions

– B. Will decrease effectiveness of antibiotic therapy

– C. Can cause increased fever

– D. Can cause Reye syndrome


AnswerAnswer

• D. Can cause Reye syndrome

• Rationale: Aspirin is contraindicated in children with varicella or flu-like illness because it is associated with the occurrence of Reye syndrome.


Nonsteroidal Anti-Inflammatory Drugs Nonsteroidal Anti-Inflammatory Drugs

• The NSAIDs are grouped by chemical classes.

• NSAIDs all inhibit COX and prostaglandin synthesis.

• The therapeutic efficacy of an NSAID in a particular patient is based on clinical response and usually cannot be predicted before its use.

• All NSAIDs carry a Black Box warning stating that they increase the risk of MI and stroke.

• Prototype drug: ibuprofen


Ibuprofen: Core Drug Knowledge Ibuprofen: Core Drug Knowledge


– Arthritis, mild-to-moderate pain, primary dysmenorrhea, migraine headache, and fever


– Absorbed from the GI system. Peak: 1 to 2 hours. Highly protein bound and is metabolized in the liver


– Inhibited synthesis or release of prostaglandins


Ibuprofen: Core Drug Knowledge (cont.)Ibuprofen: Core Drug Knowledge (cont.)


– GI disease

• Adverse effects

– GI upset and bleeding, hepatotoxicity, and acute renal failure. Increases risk of CVA or MI with prolonged use.


– Similar to those of salicylates


Ibuprofen: Core Patient Variables Ibuprofen: Core Patient Variables

• Health status

– Assess for contraindications to therapy.


– Assess age before administration of drug.


– Assess other OTC use.

• Environment

– Assess environment where drug will be given.


Ibuprofen: Nursing Diagnoses and Outcomes Ibuprofen: Nursing Diagnoses and Outcomes

• Acute or Chronic Pain related to ineffectiveness of ibuprofen

– Desired outcome: The patient will contact the prescriber if pain persists.

• Increased Risk for Injury related to incorrect self-administration or to drug-induced GI bleeding or hepatic and renal toxicity

– Desired outcome: The patient will remain free of injury by taking the drug only as directed. In addition, the patient will be able to explain the importance of contacting the health care provider immediately if any adverse effects occur.


Ibuprofen: Nursing Diagnoses and Outcomes (cont.)Ibuprofen: Nursing Diagnoses and Outcomes (cont.)

• Increased Risk for Deficient Fluid Volume related to nausea and vomiting

– Desired outcome: The patient will contact the prescriber immediately if intractable nausea or vomiting occurs.

• Disturbed Sensory Perception (visual) related to blurred vision

– Desired outcome: The patient will discontinue ibuprofen immediately and contact the health care provider if vision is affected.


Ibuprofen: Nursing Diagnoses and Outcomes (cont.)Ibuprofen: Nursing Diagnoses and Outcomes (cont.)

• Ineffective Protection related to blood dyscrasias

– Desired outcome: The patient will contact the prescriber immediately if any signs and symptoms of blood dyscrasias occur.


Ibuprofen: Planning and InterventionsIbuprofen: Planning and Interventions


– Give ibuprofen with milk or food to decrease gastric distress.


– Closely monitor patients with pre-existing medical conditions or drug therapy that may interact with ibuprofen.


Ibuprofen: Teaching, Assessment, and EvaluationsIbuprofen: Teaching, Assessment, and Evaluations


– Teach patient about cardiovascular risk from medication.

– Teach about side effects of drug therapy.


– Monitor for side effects of therapy.

– Therapy is considered effective if the patient is free of fever, pain, or inflammation and is free from adverse effects.


QuestionQuestion

• Why were all NSAIDs given a Black Box warning by the FDA?

– A. Risk of MI and CVA is increased with use of NSAIDs.

– B. Risk of GI bleeding is increased with use of NSAIDs.

– C. NSAIDs can cause kidney failure.

– D. NSAIDs can cause hepatic failure.


AnswerAnswer

• A. Risk of MI and CVA is increased with use of NSAIDs.

• Rationale: All NSAIDs have a risk of causing MI or CVA; the risk increases with prolonged use of the medication.


Para-Aminophenol Derivatives Para-Aminophenol Derivatives

• Para-aminophenol derivative is an analgesic and antipyretic available in the United States.

• Prototype drug: acetaminophen (Tylenol)


Acetaminophen: Core Drug Knowledge Acetaminophen: Core Drug Knowledge


– Used to treat fever or mild pain


– Administered orally. Absorbed: GI tract. Peak: 60 minutes. T1/2: 1 to 3.5 hours


– Primarily centrally acting; inhibits prostaglandin synthesis in the CNS


Acetaminophen: Core Drug Knowledge (cont.)Acetaminophen: Core Drug Knowledge (cont.)


– Hepatic disease, viral hepatitis, or alcoholism

• Adverse effects

– Generally well tolerated; overdose of medication can be fatal


– Activated charcoal, antacids, ethanol, hydantoins, warfarin, and sulfinpyrazone


Acetaminophen: Core Patient Variables Acetaminophen: Core Patient Variables

• Health status

– Assess pain level and current medical conditions.


– Pregnancy category B


– Ask about other OTC medication use.

• Environment

– Determine patient’s understanding of drug use.


Acetaminophen: Nursing Diagnoses and Outcomes Acetaminophen: Nursing Diagnoses and Outcomes • Acute or Chronic Pain related to ineffectiveness of

acetaminophen

– Desired outcome: The patient will contact the health care provider if pain persists.

• Risk for Injury related to drug-induced hepatic and renal toxicity or to improper self-medication

– Desired outcome: The patient will take drug as directed and contact the health care provider if any signs of toxicity occur.

• Ineffective Protection related to potential blood dyscrasias

– Desired outcome: The patient will contact the health care provider if any signs of blood dyscrasias occur.


Acetaminophen: Planning and InterventionsAcetaminophen: Planning and Interventions


– Acetaminophen can be administered without regard to meals.


– Assess patients for medical conditions that contradict the use of acetaminophen.

– Coordinate periodic CBC, platelet count, and liver and renal function tests for patients on long-term therapy.


Acetaminophen: Teaching, Assessment, and EvaluationsAcetaminophen: Teaching, Assessment, and Evaluations


– Teach patient to take medication as prescribed.

– Teach side effects of medication.

– Instruct that many OTC medications contain Tylenol.


– Monitor patient for side effects from the medication.

– Therapy is considered effective if patient is free of fever and pain.


QuestionQuestion

• Which of the following patients is Tylenol contraindicated in?

– A. 25 year old with headache

– B. 45 year old with GI bleeding

– C. 52 year old with hepatitis C

– D. 62 year old with osteoarthritis


AnswerAnswer

• C. 52 year old with hepatitis C

• Rationale: Tylenol is contraindicated in patients with impaired liver/hepatic function.


Serotonin-Selective Drugs Serotonin-Selective Drugs

• Serotonin-selective drugs are used to relieve pain and inflammation related to migraine headache.

• They are not useful for other types of headache or inflammation that occur elsewhere in the body.

• These drugs are also known as “triptans” because the generic name of these drugs ends as such.

• The triptans are considered first-line drugs for the treatment of acute migraine headache.

• Prototype drug: sumatriptan (Imitrex)


Sumatriptan: Core Drug Knowledge Sumatriptan: Core Drug Knowledge


– Acute migraine headache and cluster headache


– Administered orally, intranasally, or subcutaneously. Metabolized in the liver and excreted by the kidneys.


– Selective for 5-HT1B/1D receptors located on cranial blood vessels and sensory nerves of the trigeminovascular system.

– Stimulation of these receptors results in vasoconstriction.


Sumatriptan: Core Drug Knowledge (cont.)Sumatriptan: Core Drug Knowledge (cont.)


– Coronary artery disease and ischemic cardiac diseases

• Adverse effects

– Coronary artery vasospasm, cardiac dysrhythmias angina, myocardial ischemia, and dizziness


– Selective serotonin reuptake inhibitors and monoamine oxidase inhibitors


Sumatriptan: Core Patient Variables Sumatriptan: Core Patient Variables

• Health status

– Assess the characteristics of the headache.


– Pregnancy category C


– Identify trigger factors for headaches.

• Environment

– Given in the outpatient setting


Sumatriptan: Nursing Diagnoses and Outcomes Sumatriptan: Nursing Diagnoses and Outcomes

• Risk for Tissue Perfusion, Impaired, related to cardiovascular or cerebrovascular events

– Desired Outcome: The patient will recognize the signs and symptoms of cardiovascular or cerebrovascular events and seek medical assistance immediately.

• Risk for Injury related to weakness, dizziness or syncope, or lightheadedness

– Desired Outcome: The patient will remain free of injury while taking sumatriptan.


Sumatriptan: Planning and InterventionsSumatriptan: Planning and Interventions


– Confirm diagnosis of type of headache the patient is having.

– Administer drug as soon as headache begins.


– Assess the patient for a history of cardiovascular or cerebrovascular disorder.

– After administering sumatriptan, monitor for signs and symptoms of vasospasm and allergy.


Sumatriptan: Teaching, Assessment, and EvaluationsSumatriptan: Teaching, Assessment, and Evaluations


– Teach how to take medication properly.

– Teach side effects of medication.

– Teach patient to identify triggers.


– Evaluate patients taking sumatriptan for the cessation of headache and for signs and symptoms of vasospastic events.


QuestionQuestion

• Which of the following is the most serious adverse effect of sumatriptan?

– A. Cardiac event

– B. Respiratory event

– C. Urinary event

– D. GI event


AnswerAnswer

• A. Cardiac event

• Rationale: The most serious adverse effect is cardiac events, however, they rarely occur.

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