CH. 16 Drug Therapy to Decrease Pain, Fever, and Inflammation

NSAID Mechanism of Action #1

• inhibit prostaglandin synthesis in CNS and PNS

• inhibit COX-1 and COX-2 enzymes

• relieve pain by acting centrally and peripherally to block pain impulse transmission

NSAID Mechanism of Action #2

• relieve fever by decreasing hypothalamic response and resetting “thermostat” at a lower level

• aspiring and nonselective NSAIDs have anti-platelet effect

• Tylenol is no an NSAID

Functions of Prostaglandins in the Stomach

gastric mucosal protection

Functions of Prostaglandins in the Kidneys:

help maintain adequate blood flow and function

Functions of Prostaglandins in the Cardiovascular System:

help regulate vascular tone (i.e vasoconstriction and vasodilation) and platelet function

Functions of Prostaglandins:

• drug-induced inhibition of these prostaglandins results in the adverse effects associated with aspirin and related nonselective NSAIDs, especially gastric irritation, ulceration, and bleeding

• therapeutic and most adverse effects are related to the inhibition of COX-1 (normal cell activity and homeostasis

Gout:

• arthritic condition characterized by an

  • overproduction of uric acid

  • or an inability to excrete uric acid

resulting in hyperuricemia (high uric acid in the blood)

What is colchicine used for in gout?

mitotic agent used to treat and prevent gout by inhibiting white blood cell movement into tissues containing urate crystals, which decreases inflammation

How does colchicine help with gout?

it prevents white blood cells from moving toward urate crystals, reducing the body’s inflammatory response

What is allopurinol used for in gout?

uricosuric agent used to reduce serum uric acid levels

Colchicine (Colcrys)

prototype of Mitotic Agent

Common GI adverse effects of colchicine (Colcrys) (Mitotic Agent):

• nausea

• vomiting

• abdominal pain

• dyspepsia

Common Hematologic adverse effects of colchicine (Colcrys) (Mitotic Agent):

bone marrow depression

aplastic anemia

hepatotoxicity (liver toxicity)

Nursing Implications: Preventing Interactions for colchicine (Colcrys) (Mitotic Agent)

several medications, when combined with colchicine, result in toxicity and severe adverse effects

should not be combined with grapefruit juice or alcohol

decreases cyanocobalamin (vitamin B12) absorption

Prototype Allopurinol (Zyloprim):

• helps decrease uric acid levels in the blood

• drug class: Uricosuric agent

• Action: Xanthine oxidase inhibitor

CNS Adverse Effects of Allopurinol (Zyloprim):

• drowsiness

• headache

• vertigo

Hematologic Adverse Effects of Allopurinol (Zyloprim):

• agranulocytosis

• aplastic anemia

• bone marrow depression

GI Adverse Effects of Allopurinol (Zyloprim):

• nausea

• vomiting

• diarrhea

• abdominal pain

• indigestion

Risk Factors of of Allopurinol (Zyloprim):

• hepatotoxicity

• renal insufficiency

Contraindications of Allopurinol (Zyloprim):

• known hypersensitivity

• family history or history of idiopathic hemochromatosis

Medications Administered for Pain, Fever, and Inflammation:

Aspirin (acetylsalicylic acid)

Acetaminophen (Tylenol)

Ibuprofen (Motrin)

Meloxicam (Mobic)

Indomethacin (Indocin)

Celecoxib (Celebrex)

Prototype Aspirin (acetylsalicylic acid):

Drug Class: salicylates

Prototype Acetaminophen (Tylenol):

Drug Class: non-narcotic analgesic antipyretics

Prototype Ibuprofen (Motrin):

Drug Class: non-steroidal anti0inflammatory drugs (NSAIDs) (propionic acid derivatives)

Other Drugs in Class:

• Naproxen (Naprosyn)

• Oxaprozin (Daypro)

Prototype Meloxicam (Mobic):

Drug Class: Oxicam derivatives

Other Drugs in Class: Piroxicam (Feldene)

Prototype Indomethacin (Indocin):

Drug Class: Acetic acid derivatives

Other Drugs in Class: Ketorolac (Toradol)

Prototype Celecoxib (Celebrex):

Drug Class: Selective COX-2 inhibitors

Nonsteroidal Anti-Inflammatory Drugs

Prototype:Ibuprofen (Motrin, Advil) Indications:

rheumatoid arthritis and osteoarthritis; relief to mild to moderate pain; dysmenorrhea; fever reduction; unlike acetaminophen is anti-inflammatory

Nonsteroidal Anti-Inflammatory Drugs

Prototype:Ibuprofen (Motrin, Advil) Actions:

inhibits prostaglandin synthesis by blocking COX-1 and COX-2 receptor sites, leading to an anti-inflammatory effect, analgesia, and antipyretic effects

Nonsteroidal Anti-Inflammatory Drugs

Prototype:Ibuprofen (Motrin, Advil) Pharmacokinetics:

• 80% absorbed in the GI tract

• onset of action is 1 hour

• duration of action is 6-8 hours

• metabolized in the liver and excreted in the urine

Nonsteroidal Anti-Inflammatory Drugs

Prototype:Ibuprofen (Motrin, Advil) Use in Children:

recommended for reduction of fever for children older than 6 months of age

Nonsteroidal Anti-Inflammatory Drugs

Prototype:Ibuprofen (Motrin, Advil) Use in Older Adults:

relatively safe in therapeutic doses for occasional use as an analgesic

monitor for:

• GI blood loss

• renal dysfunction

• edema hypertension

• drug interactions for long term use

Nonsteroidal Anti-Inflammatory Drugs

Prototype:Ibuprofen (Motrin, Advil) Use for Pts with Renal Impairment:

• high risk-preexisting renal impairment, >50 years of age, diuretics, HBP, DM, HF

• can aggravate renal impairment even though eliminated mainly by hepatic metabolism

• inhibits prostaglandins that dilate renal blood vessels and decreases blood flow to kidneys

Nonsteroidal Anti-Inflammatory Drugs

Prototype:Ibuprofen (Motrin, Advil) Use for Pts with Hepatic Impairment:

• metabolized in liver

• decreased dosage in patients with hepatic problems

Nonsteroidal Anti-Inflammatory Drugs

Prototype:Ibuprofen (Motrin, Advil) Increased risk of serious GI adverse events:

• bleeding

• ulceration

• perforation of stomach and intestines

Nonsteroidal Anti-Inflammatory Drugs

Prototype:Ibuprofen (Motrin, Advil) Preventing Interactions:

• anticoagulants increase the risk of bleeding

• codeine, oxycodone, hydrocodone, alcohol, garlic, ginger, and ginkgo, feverfew have an additive analgesic effect

• corticosteroids have additive gastric irritant and possible ulcerogenic effects

Nonsteroidal Anti-Inflammatory Drugs

Prototype:Ibuprofen (Motrin, Advil) Administration:

• oral = total daily dose should not exceed 3200 mg

• intravenously - not usual

• patient should be well hydrated

• rapid infusion of ibuprofen intravenously was safe and effective treatment for pain

Nonsteroidal Anti-Inflammatory Drugs

Prototype:Ibuprofen (Motrin, Advil) Therapeutic Effects:

• decreased pain

• fever

• inflammation

take temperature every 2-4 hours

Nonsteroidal Anti-Inflammatory Drugs

Prototype:Ibuprofen (Motrin, Advil) Contraindications:

• patients who are allergic to NSAIDs and salicylates, treatment of preoperative pain after CABG

• allergic reactions are more common in patients with rhinitis, asthma, chronic urticaria, and nasal polyps

Nonsteroidal Anti-Inflammatory Drugs

Prototype:Ibuprofen (Motrin, Advil) Patient Teaching:

take this drug with food to decrease gastric irritation

drink 2-3 quarts of fluid daily when taking drug regularly

report any signs of bleeding, difficulty breathing, severe stomach upset, swelling, or weight gain to health care provider

alternating acetaminophen and ibuprofen every 4 hours over a 3 day period to control fever in young children (6-36 months of age) has been shown to be more effective than mono-therapy with either agent

Oxicam Derivatives

Prototype Meloxicam (Mobic) Ineractions:

• treatment of osteoarthritis and rheumatoid arthritis

• children 2 and older for relief of signs and symptoms of juvenile rheumatoid arthritis

Oxicam Derivatives

Prototype Meloxicam (Mobic) Pharmacokinetics:

• metabolized by the liver and excreted in the feces and urine

• onset of action is 1 hour, and peak serum concentrations occur in 5-6 hours

• the drug crosses the placenta and enters breast milk

Oxicam Derivatives

Prototype Meloxicam (Mobic) Actions:

• COX-1 and COX-2 inhibitor, producing anti-inflammatory, analgesic, and antipyretic effects

• it’s more selective for COX-2 inhibition in the brain, kidney, ovary, uterus, cartilage, bone, and sites of inflammation

Oxicam Derivatives

Prototype Meloxicam (Mobic) Renal:

creatinine clearance < 20 mL/min not recommended

hemodialysis max 7.5 mg/d

Oxicam Derivatives

Prototype Meloxicam (Mobic) Nursing Implications: Preventing Interactions

• alcohol, garlic, ginseng, and ginger increase the risk of bleeding

• lithium increases the risk of lithium toxicity

Oxicam Derivatives

Prototype Meloxicam (Mobic) Nursing Implications: Administration

take with food or fluids to reduce gastric irritation

Oxicam Derivatives

Prototype Meloxicam (Mobic) Nursing Implications: Therapeutic Effects

assess for pain relief, reduced fever and inflammation

Oxicam Derivatives

Prototype Meloxicam (Mobic) Nursing Implications: Adverse Effects

hypersensitivity reactions such as shortness or breath and bronchospasm, assess for hemoptysis as well as blood in the stool or urine

Oxicam Derivatives

Prototype Meloxicam (Mobic) Nursing Implications: Assess For

signs and symptoms of cardiovascular events

Oxicam Derivatives

Prototype Meloxicam (Mobic) Nursing Implications: Patient Teaching

take with food, take only prescribed dose, report any signs of bleeding

Oxicam Derivatives

Prototype Meloxicam (Mobic) Nursing Implications: Contraindications

known aspirin allergy, postoperatively in patients who have just undergone coronary artery bypass surgery

Acetic Acid Derivatives

Prototype Indomethacin (Indocin, Tivorbex) Indications:

pain associated with rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, bursitis, tendonitis, and gouty arthritis

Acetic Acid Derivatives

Prototype Indomethacin (Indocin, Tivorbex) Pharmacokinetics:

• oral administration onset of action is 30 minutes

• peak in 1-2 hours

• duration of action of 4-6 hours

• excreted by the kidneys, cross the placenta and enter the breast milk

Acetic Acid Derivatives

Prototype Indomethacin (Indocin, Tivorbex) Use in Pts with Renal Impairment

caution, severe renal impairment is a contraindication

Acetic Acid Derivatives

Prototype Indomethacin (Indocin, Tivorbex) Use in Patients with Hepatic Impairment

caution, dosage reduction is appropriate

Acetic Acid Derivatives

Prototype Indomethacin (Indocin, Tivorbex) Use in Children:

approved for IV use for treatment of patent ductus arteriosus in premature infants

Acetic Acid Derivatives

Prototype Indomethacin (Indocin, Tivorbex) Nursing Implications: Use in Older Adults

inappropriate in the geriatric population, lowest recommended dose and frequency

Acetic Acid Derivatives

Prototype Indomethacin (Indocin, Tivorbex) Nursing Implications: Preventing Interactions:

alcohol, feverfew, garlic, ginger, and ginkgo also increases the bleeding potential

Acetic Acid Derivatives

Prototype Indomethacin (Indocin, Tivorbex) Nursing Implications: Administration

• administer oral indomethacin after meals or with an antacid to decrease GI irritation

• always assess pain before giving

Acetic Acid Derivatives

Prototype Indomethacin (Indocin, Tivorbex) Nursing Implications: Adverse Effects

assess for bleeding, monitor cardiovascular status

Acetic Acid Derivatives

Prototype Indomethacin (Indocin, Tivorbex) Nursing Implications: Patient Teaching

take medication with food or antacid

Acetic Acid Derivatives

Prototype Indomethacin (Indocin, Tivorbex) Nursing Implications: Contraindications

• salicylate hypersensitivity

• history of GI bleeding

• postoperatively to patients who have just had a coronary artery bypass graft

Selective COX-2 Inhibitor

Prototype Celecoxib (Celebrex):

acute and long-term treatment of juvenile rheumatoid arthritis, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute pain, dysmenorrhea, to reduce the number of colorectal polyps

Selective COX-2 Inhibitor

Prototype Celecoxib (Celebrex) Pharacokinetics:

• oral route has a slower onset of action

• peak in 3 hours

• serum half-life is 11 hours

• metabolized in the liver, excreted in the urine

• celecoxib crosses the placenta and enters the breast milk

Selective COX-2 Inhibitor

Prototype Celecoxib (Celebrex) Action:

• COX-2 is activated with inflammation

• Celecoxib inhibits the COX-2 enzyme to decrease inflammation

• it does not affect the COX-1 enzyme, thus protecting the lining of the GI tract and not inhibiting clotting factors

Selective COX-2 Inhibitor

Prototype Celecoxib (Celebrex) Use in Children:

recommended only for children ages 2 and older to treat juvenile rheumatoid arthritis

Selective COX-2 Inhibitor

Prototype Celecoxib (Celebrex) Use in Pts with Renal Impairment:

patients with significant renal impairment should not use

Selective COX-2 Inhibitor

Prototype Celecoxib (Celebrex) Nursing Implications: Use in Pts with Hepatic Impairment

dosage of celecoxib should be reduced by 50%

Selective COX-2 Inhibitor

Prototype Celecoxib (Celebrex) Nursing Implications: Contraindications

• known allergy to sulfonamides, NSAIDs, and aspirin; renal impairment, perioperative pain or to those who have just undergone coronary artery bypass graft surgery (CABG)

• also contraindicated in patients with asthma and cardiovascular disease

Selective COX-2 Inhibitor

Prototype Celecoxib (Celebrex) Nursing Implications: Preventing Interactions

• anticoagulants or aspirin increases the risk of bleeding, lithium toxicity

• alcohol and smoking increases the patient’s risk of GI bleeding

Selective COX-2 Inhibitor

Prototype Celecoxib (Celebrex) Nursing Implications: Administration

administer 2 hours before or after an antacid to ensure absorption

Selective COX-2 Inhibitor

Prototype Celecoxib (Celebrex) Nursing Implications: Patient Teaching

take as directed, take with food to reduce gastric irritation, report rash, itching, weight gain and edema to healthcare provider

Non-Narcotic Analgesic/Antipyretic

Prototype Acetaminophen (Tylenol) Indications:

treatment of mild to moderate pain, fever, or signs and symptoms of the common cold or flu; musculoskeletal pain associated with arthritis and rheumatic disorders

Non-Narcotic Analgesic/Antipyretic

Prototype Acetaminophen (Tylenol) Actions:

acts directly on the hypothalamus to cause vasodilation and sweating, which will reduce fever; mechanism of action as an analgesic is not understood

Non-Narcotic Analgesic/Antipyretic

Prototype Acetaminophen (Tylenol) Pharmacokinetics:

metabolized in the liver and excreted in the urine

Non-Narcotic Analgesic/Antipyretic

Prototype Acetaminophen (Tylenol) Use in Children:

• drug of choice for fever in children

• children seem less susceptible to liver toxicity than adults

• concentrations are different and cannot be given interchangeably

• measure infant doses using a dropper and child doses using a teaspoon

• alternating acetaminophen and ibuprofen every 4 hours over a 3 day period to control fever in young children (6-36 months of age) is effective

Non-Narcotic Analgesic/Antipyretic

Prototype Acetaminophen (Tylenol): Use in Older Adults

• initial consideration for middle to moderate pain of musculoskeletal origin

• usually safe in recommended doses unless liver damage is present or the person is a chronic alcohol abuser

Non-Narcotic Analgesic/Antipyretic

Prototype Acetaminophen (Tylenol) Use in Pts with Renal Impairment:

nephrotoxic in overdose because it forms a metabolite that attacks kidney cells and may cause necrosis

Non-Narcotic Analgesic/Antipyretic

Prototype Acetaminophen (Tylenol) Use in Pts With Hepatic Impairment:

can cause fatal liver necrosis

patients who consume large quantities of alcohol, smoke, and take anti-seizure medications are at high risk for hepatotoxicity with usual therapeutic doses

Non-Narcotic Analgesic/Antipyretic

Prototype Acetaminophen (Tylenol) Contraindication:

hypersensitivity to the drug

caution is necessary with administration in impaired hepatic and renal function

drug crosses the placenta and enters the breast milk; therefore, caution is also required in pregnancy and lactation

Non-Narcotic Analgesic/Antipyretic

Prototype Acetaminophen (Tylenol) Medication Administration:

• administered orally or by rectal suppository

• do not exceed recommended dose

• give with food to reduce GI upset

• maximum daily dose 4g for adults (risk for toxicity)

  • some people think the drug is so safe that they can take any amount without harm

  • people take the drug in several formulations without calculating or realizing that they are taking potentially harmful amounts

  • numerous brand name of acetaminophen are available OTC, and acetaminophen is an ingredient in many prescription and OTC combination products

Non-Narcotic Analgesic/Antipyretic

Prototype Acetaminophen (Tylenol) Pt Teaching Guidelines:

• do not exceed the recommended dosage and do not take any other medications containing acetaminophen

• inform health care provider of the development of a rash or fever

• for better absorption, chew chewable tablets and do not swallow them whole

• herbal supplements may increase the risk of adverse effects

• people who ingest more than 3 alcoholic drinks daily should avoid acetaminophen

Acetaminophen Toxicity:

• maximum daily dose is 4g from all sources

• overdose causes hepatotoxicity and may be accidental or intentional

Acetaminophen Toxicity: Hepatotoxicity

• 24-48 hours after overdose, liver function tests begin to show increased levels

• later manifestations may include jaundice, vomiting, CNS stimulation with excitement, and delirium followed by coma and death

Acetaminophen Toxicity: Treatment

• gastric lavage and activated charcoal IF overdose detected within 4 hours of ingestion

• Antidote - Acetylcysteine

  • oral or IV

  • most beneficial if given 8-10 hours after ingestion, may be helpful within 36 hours

  • can decrease hepatotoxicity

  • does not reverse damage already sustained

Salicylates

Prototype Aspirin Indications:

• mild to moderate pain, fever, inflammatory conditions

• low-dose aspirin (usually 81 mg) is indicated for patients who have experienced an ischemic stroke, transient ischemic attach, angina, and acute myocardial infraction

Salicylates

Prototype Aspirin Actions:

• inhibits the synthesis of prostaglandins

• blocks the effects of pyrogens at the hypothalamus

• inhibits platelet aggregation

• diminishes inflammation by preventing prostaglandins from increasing pain and edema

Salicylates

Prototype Aspirin Pharmacokinetics:

metabolized in the liver and excreted in the urine

Salicylates

Prototype Aspirin Use in Pts with Renal Impairment

• nephrotoxic in high doses

• protein binding of aspirin is reduced in patients with renal failure

• decrease the blood flow in the kidneys by inhibiting the synthesis of prostaglandins that dilate renal blood vessels

Salicylates

Prototype Aspirin Use in Childen:

not recommended because of its association with Reye’s syndrome

Salicylates

Prototype Aspirin Use in Older Adults:

safe in therapeutic doses for analgesic and antipyretic use

safe in the low doses prescribed for prevention of myocardial infractions and cerebrovascular accidents

Salicylates

Prototype Aspirin Contraindications:

• known sensitivity to aspirin

• allergic to tartrazine due to a cross-sensitivity

• known risk for bleeding

• administer cautiously to patients with impaired renal function

• crosses the placenta entering the fetal circulation placing the fetus at risk for adverse effects

• low birth risk, increase intracranial bleeding, and stillbirth have been reported in infants of mothers who took aspirin late in pregnancy

Salicylates

Prototype Aspirin Nursing Implications: Preventing Interactions

alcohol and ginkgo increase the effects of aspirin

Salicylates

Prototype Aspirin Nursing Implications: Administering the Medication

• take with a full glass of water or other fluid and with food or just following food

  • decreases gastric irritation

• crushing of tablets or capsules results in faster absorption

  • destroys the long-acting feature and increases the risk of adverse effects and toxicity

Salicylates

Prototype Aspirin Nursing Implications: Assessing for Therapeutic Effects

• pain:

  • use a pain scale to assess the intensity of the patient’s pain

• fever:

  • regularly monitor patient temperature

• inflammation:

  • assess for signs of inflammation

• preventative agent for myocardial infraction or transient ischemic attack

  • no chest pain or confusion

Salicylates

Prototype Aspirin Nursing Implications: Assessing for Adverse Effects

• assess bleeding tendencies, GI irritation, nausea, vomiting, and diarrhea

• assess the skin for signs of decreased coagulation

• pulmonary and integumentary assessment

• hypersensitivity to aspirin

  • dyspnea, bronchospasm, and rash

Toxicity: Recognition and Management Salicylate Intoxication (Salicylism)

• acute overdose or with chronic use of therapeutic doses

• therapeutic serum level of salicylate is 100 to 300 mcg/mL for the treatment of arthritis and rheumatic fever

• toxicity occurs at levels above 300 mcg/mL

• characterized by dizziness, tinnitus, difficultly hearing, and mental confusion

Salicylates

Prototype Aspirin Additional Manifestations:

• nausea

• vomiting

• fever

• fluid and electrolyte deficiencies

• visual changes

• drowsiness

• hyperventilation

• severe central nervous system (CNS) dysfunction (e.g., delirium, stupor, coma, seizures) indicates life threatening toxicity

Salicylates

Prototype Aspirin Patient Teaching Guidelines:

• keep aspirin out of the reach of children

• use the drug as directed and do not over-administer the medication

• take the medication with food or after meals to prevent stomach upset

• do not crush or chew enteric-coated or sustained-release tablets

• aspirin is as effective as more costly medications

• watch for bleeding, ringing in the ears, or diminished hearing

• understand that fever is one way the body fights infection- do not take unless fever is high or other symptoms

• avoid aspirin for approximately 2 weeks before and after major surgery or dental procedures to decrease the risk or excessive bleeding