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Pain and Inflammation: Afferent and Efferent Nervous System Responses 1 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Pain • 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. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 2 Pain • Pain is a multidimensional, subjective experience. • Studies indicate health care providers undertreat pain in acute care settings for fear of causing addiction. • Pain is a major indication for drug therapy. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 3 Physiology The Peripheral nervous system (PNS) and Central nervous (CNS) are an integrated system that provides a pathway for pain transmission. Pain receptors are found on the end plates of afferent neurons. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 4 Things that Influence Pain • Pain has both physical and emotional components. • How pain is perceived affects pain’s location, intensity, and quality. Some individuals are hyper-sensitive to nerve impulses Reduce perception, you can reduce pain. • Stimulation of the limbic system produces the emotional response to the physical stimulus of pain. • The limbic system is responsible for emotional arousal, anxiety, fight-or-flight response, etc. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 5 • Nociceptic pain is caused by the activation of the delta and C nociceptors in response to painful stimuli, such as injury. • Neuropathic pain is the term used to represent pain in which the underlying pathology is abnormal processing of stimuli in the peripheral or central nervous systems. Types of Pain • Acute pain, meaning the immediate phase of response to an insult or injury, results from tissue damage. • Chronic pain may persist well beyond actual tissue injury and healing. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 6 Pain Rating Tools 7 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Medications to Treat Severe Pain 8 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Narcotic Analgesics • Narcotics have an important role in pain management and control. • Narcotics are required for conditions that have moderate-to-severe pain. • The narcotic analgesics include opiate agonists, mixed agonist-antagonists, and antagonists based on their activity at opioid receptors. Prototype drug: morphine (MS Contin) Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 9 Morphine: Core Drug Knowledge • Pharmacotherapeutics • Moderate-to-severe acute or chronic pain • Pharmacokinetics • Metabolism: liver. Onset: 15 to 30 minutes. Duration: 3 to 7 hours. • Pharmacodynamics • Agonist at several opiate receptors in the central and peripheral nervous system. 10 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Morphine: Core Drug Knowledge • Contraindications and precautions • Respiratory conditions • Side effects – cholinergic and histaminergic • Sedation • Constipation • Urinary retention • Adverse effects • Respiratory depression or arrest, circulatory depression, cardiac arrest, shock, and coma • Tolerance & Dependency • Withdrawal Syndrome • Drug interactions • Multiple drug interactions Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 11 Morphine: Planning and Interventions • Maximizing therapeutic effects • Assess pain prior to and during therapy • Use a pain assessment tool • Minimizing adverse effects • Conduct frequent assessment especially for respirations • Provide additional pain medication for breakthrough pain Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 12 Mild Opioid Agonists • The mild opioid agonists include codeine, hydrocodone and oxycodone. • Examples: • Tylenol #3, Codeine cough syrup • Norco, Lortab (Hydrocodone + acetominophen 325 mg or 500 mg) • Percocet (Oxycodone + acetominophen) Prototype drug: Hydrocodone/acetominophen (Norco) Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 13 Hydrocodone/acetominophen (Norco) : Core Drug Knowledge • Pharmacotherapeutics • Treat mild-to-moderate pain • Pharmacokinetics • Absorbed from GI tract, peaks in 1 to 2 hours; crosses the placenta and secreted in breast milk • Pharmacodynamics • Acts at specific opioid receptors in the CNS to produce analgesia, euphoria, and sedation Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 14 Hydrocodone/acetominophen (Norco) : Core Drug Knowledge • Contraindications and precautions • Not given with other narcotics • Side effects – cholinergic and histaminergic • Drowsiness, sedation, dry mouth, nausea and vomiting, and constipation • Adverse Effects • Respiratory depression • Tolerance and dependency • Withdrawal syndrome • Drug interactions • Other sedating medications and alcohol Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 15 Hydrocodone/acetominophen (Norco) : Planning and Interventions • Maximizing therapeutic effects • Actions are similar to those for morphine. • Minimizing adverse effects • Provide for patient safety • Assess respiratory function prior to administration • Do not administer to patients who need to cough to clear airway. • Contraindicated in emphysema, chronic obstructive pulmonary disease (COPD) Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 16 Drugs that Treat Mild to Moderate Pain, Fever, Inflammation, and Migraine Headache 17 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Prostaglandins • Prostaglandins come from arachidonic acid, which is released from cell membranes in response to physical, chemical, hormonal, bacterial, or other stimuli. • Cyclooxygenase (COX) enzymes convert the arachidonic acid to prostaglandin. Prostaglandins modulate some of inflammation, body temperature, pain transmission, and platelet aggregation. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 18 Prostaglandin Synthesis - Review 19 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Fever - Physiology • Temperature regulation is a function of the hypothalamus. • Fever is the result of fever-inducing substances called pyrogens generated by the body in response to infection and some other causes. • Bacteria and viruses are less likely to survive in a hot environment • Fever causes activation of white blood cells that secrete cytokines. • Cytokines increase the synthesis and secretion of the hormone prostaglandin in the hypothalamus. Prostaglandin causes the hypothalamus to reset (raise or lower) the body temperature. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 20 Inflammation - Physiology • Numerous types of stimuli cause an inflammatory response in the body. • The classic signs of inflammation are: • Swelling (edema) • Heat • Redness • Pain • Loss of function 21 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Inflammation (cont.) • Acute inflammation is divided into vascular and cellular responses. • The vascular response occurs almost immediately after the injury. Video – Acute Inflammation: http://www.youtube.com/watch?v=suCKm97yvyk 22 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Platelet Aggregation • Platelet aggregation is the clumping together of platelets in the blood. • Platelet aggregation can be a beneficial process. • An early step in wound healing • Platelet aggregation can also be harmful. It is the first step in a sequence of events that leads to the formation of a thrombus. Prostaglandins increase platelet aggregation Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 23 Prostaglandin-related Drugs • Drugs work by reducing prostaglandin synthesis or by blocking the effects of the COX enzyme. • The result is less fever, pain, inflammation and slowed blood clotting. • Drugs vary in how much they effect each of these outcomes. 24 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Drug Categories that Treat Mild to Moderate Pain Drug Category Treats Mild to Moderate Pain Reduces Inflammation COX Enzyme inhibitor: celecoxib (Celebrex) Yes Yes Salicylates: aspirin Yes Yes Non-steroidal Antiinflammatory Drugs (NSAIDS): ibuprofen (Advil) Yes Yes Para-aminophenol Drug: Yes acetominophen (Tylenol) paracemetol Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins No 25 cyclooxygenase (COX) Enzymes • 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 sites of inflammation. COX-2 Enzyme Inhibitor Prototype Drug: celecoxib (Celebrex) Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 26 Drugs to Treat Inflammation and Fever • Salicylates and non-steroidal analgesic drugs (NSAIDs) 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: acetyl-salicylic acid or ASA, Aspirin (Bayer) Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 27 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 prostaglandin synthesis in the hypothalamus • Inflammation: peripheral inhibition of prostaglandin • Antiplatelet: irreversible inhibition of thromboxane A2 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 28 Aspirin: Core Drug Knowledge • Contraindications and precautions • Peptic ulcer disease, or bleeding disorders, and • Children with febrile illnesses • Side effects • Nausea & vomiting • Adverse effects • Renal failure, abnormal bleeding • Ototoxicity with long-term use • Drug interactions • Other drugs that are highly protein bound Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 29 Aspirin: Planning and Interventions • Maximizing therapeutic effects • Give with milk or food to decrease GI upset. • Minimizing adverse effects • Do not administer aspirin to a patient with a medical condition that contraindicates its use. • Monitor patients for signs of bleeding • • • • Black tarry stools Blood in the emesis Diarrhea with blood in it Multiple Bruises Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 30 Nonsteroidal Anti-Inflammatory Drugs The NSAIDs are grouped by chemical classes (many NSAIDS exist). • NSAIDs all inhibit COX and prostaglandin synthesis. • All NSAIDs carry a Black Box warning stating that they increase the risk of MI and stroke. Prototype drug: ibuprofen 31 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Ibuprofen: Core Drug Knowledge • Pharmacotherapeutics • Arthritis, mild-to-moderate pain, primary dysmenorrhea, migraine headache, and fever • Pharmacokinetics • Absorbed from the GI system. Peak: 1 to 2 hours. Highly protein bound and is metabolized in the liver • Pharmacodynamics • Inhibited synthesis or release of prostaglandins 32 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Ibuprofen: Core Drug Knowledge • Contraindications and precautions • GI disease • Side effects • Nausea & vomiting • Some risk of BP elevations • Adverse effects • GI upset and bleeding, • Hepatotoxicity, • Acute renal failure. • Increases risk of CVA or MI with prolonged use. • Drug interactions • Similar to those of salicylates Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 33 Ibuprofen: Planning and Interventions • Maximizing therapeutic effects • Give ibuprofen with milk or food to decrease gastric distress. • Minimizing adverse effects • Closely monitor patients with pre-existing medical conditions or drug therapy that may interact with ibuprofen. 34 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Para-Aminophenol Derivatives • There is only one drug in this category. • It works by slowing the production of prostaglandins. Prototype drug: acetaminophen (Tylenol) 35 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Acetaminophen: Core Drug Knowledge • Pharmacotherapeutics • Used to treat fever or mild pain • Pharmacokinetics • Administered orally. Absorbed: GI tract. Peak: 60 minutes. T1/2: 1 to 3.5 hours • Pharmacodynamics • Primarily centrally acting; inhibits prostaglandin synthesis in the CNS 36 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Acetaminophen: Core Drug Knowledge • Contraindications and precautions • Hepatic disease, viral hepatitis, or alcoholism • Side effects • Generally well tolerated. Elderly occasional report sleepiness • Adverse effects • Overdose of medication can be fatal (liver failure) • Drug interactions • Activated charcoal – used to reverse overdosage Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 37 Acetaminophen: Planning and Interventions • Maximizing therapeutic effects • Acetaminophen can be administered without regard to meals. • Minimizing adverse effects • Assess patients for medical conditions that contradict the use of acetaminophen (liver). • Periodic CBC, platelet count, and liver and renal function tests for patients on long-term therapy. Maximum safe daily dosage 3000 mg/24 hours Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 38 Corticosteroids • Glucocorticoids are hormones of the endocrine system. • They are produced by the cortex of the adrenal glands (adrenal glands are located at the top of each kidney). • The primary glucocorticoids produced by the adrenal gland are cortisol (hydrocortisone) and cortisone. • Glucocorticoids suppress immune system responses and reduce inflammation. Prototype drug: prednisone (Deltasone) Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 39 Prednisone: Core Drug Knowledge • Pharmacotherapeutics • Anti-inflammatory and immunosuppressive effects • Pharmacokinetics • Absorbed from GI tract. Metabolized: liver. Excreted: urine. • Pharmacodynamics • Primarily glucocorticoid activity, although some mineralocorticoid activity is present and more apparent when the drug is administered in high doses Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 40 Prednisone: Core Drug Knowledge • Contraindications and precautions • Systemic fungal infections • Side effects • Anxiety, mood swings, insomnia, headache, GI complaints, menstrual irregularities, hyperglycemia • Adverse effects • Agitation, psychosis, depression • Abrupt discontinuation of a glucocorticoid following prolonged administration may result in acute adrenal insufficiency. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 41 Prednisone: Planning and Interventions • Maximizing therapeutic effects • The best time for administration of doses of glucocorticoids is early in the morning in order to mimic the natural body. • Minimizing adverse effects • Monitor the patient, especially the surgical patient, carefully for signs of infection. • Administration can lead to peptic ulcer disease. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 42 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)* *not on drug list Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 43 Sumatriptan: Planning and Interventions • Maximizing therapeutic effects • Confirm diagnosis of type of headache the patient is having. • Administer drug as soon as headache begins. • Minimizing adverse effects • Assess the patient for a history of cardiovascular or cerebrovascular disorder. • After administering sumatriptan, monitor for signs and symptoms of vasospasm and allergy. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 44 Adjuvant Medications for Pain • Adjuvant Medications are used with a primary pain medication to increase pain relief in order to reduce the dosage of the primary medication. • Typical Adjuvants: • Antihistamines • Anticonvulsants • Antidepressants • Glucocorticoids (steroids) • Combining mild analgesics with opioids (e.g. hydrocodone/acetominophen [Norco]) Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 45 Challenge Questions When administering morphine, the most important things for the nurse to assess are: A. Pain level B. Respiratory rate C. Blood Pressure D. Both A and B C. All of the above 46 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Challenge Questions When administering morphine, the most important things for the nurse to assess are: D. Both A and B Rationale: The nurse should always assess the level of pain the patient is experiencing prior to administration of morphine. Also morphine can cause significant respiratory depression, so respiratory rate should also be assessed. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 47 Challenge Questions Why is aspirin contraindicated in children with varicella (Chicken Pox)? A. Can cause bleeding from skin lesions B. Will decrease effectiveness of antibiotic therapy C. Can cause increased fever D. Can cause Reye syndrome 48 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Challenge Questions Why is aspirin contraindicated in children with varicella (Chicken Pox)? 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. 49 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Reye’s Syndrome • Reye's syndrome is a rapidly progressive disorder that usually begins shortly after recovery from an acute viral illness, especially influenza and varicella (chickenpox). • The classic features are a rash, vomiting, and liver damage. • It is a potentially fatal syndrome that has numerous detrimental effects on many organs, especially the brain and liver • The exact cause is unknown and, while it has been associated with aspirin consumption by children with viral illness, it also occurs in the absence of aspirin use. • The disease causes fatty liver and cerebral edema (swelling of the brain). Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 50 Challenge Questions 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. 51 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Challenge Questions Why were all NSAIDs given a Black Box warning by the FDA? 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. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 52 Challenge Questions In which of the following patients is acetominophen (Tylenol) contraindicated? 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 53 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Challenge Questions In which of the following patients is acetominophen (Tylenol) contraindicated? C. 52 year old with hepatitis C Rationale: Acetominophen is contraindicated in patients with impaired liver/hepatic function. 54 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Challenge Questions Where are the adrenal glands located? A. Brain B. Pancreas C. Liver D. Kidneys 55 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins Challenge Questions Where are the adrenal glands located? D. Kidneys Rationale: The adrenal glands are located on top of the kidneys. Their role is to: 1) excrete chemicals that trigger the sympathetic nervous system (epinephrine); 2) release glucocorticoids that are involved with inflammation and immune response (cortisone); and, 3) release mineralocorticoids that are involved with fluid balance. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 56 Acetaminophen (Tylenol) Aspirin Ibuprofen Reduces fever Relieves mild pain Reduces fever Reduces inflammation Relieves mild pain Reduces platelet aggregation Celecoxib (Celebrex) Morphine Hydrocodone/ acetominophen (Norco) Codeine Reduces fever Reduces inflammation Relieves mild pain Relieves moderate to severe pain Potentially Addictive Suppresses respirations Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 57 Case Study – Application Margaret is a 72-year old woman with rheumatoid arthritis and peptic ulcer disease. She has normal hepatic and renal functioning but some mild hearing loss. 1. Which medication may be most appropriate for her to take on a routine basis to reduce the inflammation from her arthritis and treat her pain? 2. Which medications are contraindicated or should be used with extreme caution? 3. If she has a bout of severe pain, how might this be managed? 58 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 59 Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins