week 5: Ch. 41 [Inflammation/Fever Pharm] Flashcards
Inflammation is the response to agents that could:
damage tissue
Acute VS chronic inflammation
–Acute =________ onset
▪Result of influx of _____________
▪Pain and edema result
▪Lasts ___________________
–Chronic = ________ onset
▪Caused by _________________________________________
▪Scar tissue can result
▪May last __________
–Acute = immediate onset
▪Result of influx of neutrophils
▪Pain and edema result
▪Lasts 1 to 2 weeks
–Chronic = slow onset
▪Caused by lymphocytes and macrophages
▪Scar tissue can result
▪May last years
Both types of inflammation may have a febrile response:
–Body temperature over ______
–Pulse over ____ beats/minute
–Respirations greater than ____ breaths/min
–WBC count over __________/mm3
–Body temperature over 102°F
–Pulse over 90 beats/minute
–Respirations greater than 20 breaths/min
–WBC count over 12,000/mm3
Inflammation is not a disease, it is a
symptom of an underlying disorder/cause
To treat inflammation, the
underlying cause must be treated
2 main goals of pharmacotherapy of inflammation:
–Prevent/decrease intensity of inflammation
response
–Reduce fever
Nonspecific inflammations treated with:
–NSAIDs
–Corticosteroids
Fever treated with :
antipyretics
Three major classes of NSAIDs
–Salicylates
–Ibuprofen and ibuprofen-like agents
–Cyclooxygenase-2 (COX-2) inhibitors
Salicylates
–Aspirin first-generation salicylate
▪Originally derived from_______________
▪Indications
–>Analgesic
–>Anti-inflammatory
–>Antipyretic
–>Suppression of platelet aggregation
–Aspirin first-generation salicylate
▪Originally derived from willow bark
▪Indications
–>Analgesic
–>Anti-inflammatory
–>Antipyretic
–>Suppression of platelet aggregation
Salicylates–Mechanisms of actions
▪Prostaglandins are local hormones found in every tissue
▪Aspirin blocks the synthesis of prostaglandins by
inhibiting enzyme cyclooxygenase (COX)
Aspirin [prototype drug]
–Therapeutic classification
–Pharmacologic classification
–Therapeutic classification
▪Nonnarcotic analgesic
▪Antipyretic
▪Antiplatelet
–Pharmacologic classification
▪Salicylate
▪NSAID
Therapeutic effects and uses of Aspirin
▪Mild-moderate intensity _________,_____________, _________
▪Prevention of thromboembolic event
▪Stroke prophylaxis in patients with history of TIAs or persistent or paroxysmal atrial fibrillation
▪MI prophylaxis
▪Suspected coronary thrombosis
▪Off-label use to prevent ________________________________
▪Mild-moderate intensity pain, inflammation, fever
▪Prevention of thromboembolic event
▪Stroke prophylaxis in patients with history of TIAs
or persistent or paroxysmal atrial fibrillation
▪MI prophylaxis
▪Suspected coronary thrombosis
▪Off-label use to prevent colorectal cancer
Mechanism of action of Aspirin
▪Reduces _________________ synthesis
▪_________body temperature
▪Causes centrally mediated peripheral vasodilation and __________
▪Reduces prostaglandin synthesis
▪Lowers body temperature
▪Causes centrally mediated peripheral vasodilation and sweating
Adverse effects of Aspirin
– Serious adverse effects
▪Hypersensitivity reaction
▪GI bleeding
▪Thrombocytopenia
▪Hemolytic anemia
▪Occult bleeding
▪Nephrotoxic effects
▪Hepatotoxicity
▪Tinnitus and hearing loss with high doses
– Adverse effects
▪Stomach irritation
▪Heartburn
▪Nausea
▪Vomiting
▪Diarrhea
▪Stomach pain
Contraindications/precautions with Aspirin
▪Hypersensitivity to any___________ (including in food)
▪“Aspirin triad”
▪Agranulocytosis
▪_______ trauma or increased intracranial pressure
▪History of _____ bleeding
▪Hypoprothrombinemia
▪Vitamin K deficiency
▪Heart failure (HF)
▪Flu or flulike illness in ______________________________
▪Pregnancy, especially in the ________ trimester
More precautions: patients with…
–Hypothyroidism
–Immunosuppression
–Asthma, gout, or anemia
–Chronic kidney disease (CKD)
–Hepatic impairment
–G6PD deficiency
▪Hypersensitivity to any salicylate (including in food)
▪“Aspirin triad”
▪Agranulocytosis
▪Head trauma or increased intracranial pressure
▪History of GI bleeding
▪Hypoprothrombinemia
▪Vitamin K deficiency
▪Heart failure (HF)
▪Flu or flulike illness in children or teens
▪Pregnancy, especially in the third trimester
More precautions: patients with…
–Hypothyroidism
–Immunosuppression
–Asthma, gout, or anemia
–Chronic kidney disease (CKD)
–Hepatic impairment
–G6PD deficiency
Drug interactions with Aspirin
▪Other ________________ (additive effect)
▪Ammonium chloride and other acidifying agents
▪Anticoagulants, thrombolytics, or antiplatelet agents
▪Oral ______________ agents
▪______ alcoholic drinks per day
▪Corticosteroids
▪Methotrexate
▪Probenecid and sulfinpyrazone
▪_______blockers
▪Herbal/food
–Feverfew, garlic, ginger, horse chestnut, red clover
–Caffeine
–St. John’s wort
▪Other salicylates (additive effect)
▪Ammonium chloride and other acidifying agents
▪Anticoagulants, thrombolytics, or antiplatelet agents
▪Oral antidiabetic agents
▪3+ alcoholic drinks per day
▪Corticosteroids
▪Methotrexate
▪Probenecid and sulfinpyrazone
▪Beta blockers
▪Herbal/food
–Feverfew, garlic, ginger, horse chestnut, red clover
–Caffeine
–St. John’s wort
Treatment for Aspirin overdose
▪Emesis (vomiting), gastric lavage, and alkalinization of urine
▪Hemodialysis
Most common drugs for mild to moderate pain and inflammation:
Ibuprofen-like drugs
Ibuprofen-like drugs all have same mechanism of action:
inhibit COX
Most Ibuprofen-like drugs are weak acids > easily absorbed in :
GI tract
*Prototype drug: Ibuprofen (Advil, Motrin, others)
–Therapeutic classification?
–Pharmacologic classification?
–Therapeutic classification
▪Analgesic
▪Anti-inflammatory drug
▪Antipyretic
–Pharmacologic classification
▪NSAID
Therapeutic effects and uses of Ibuprofen
▪Relief of fever and mild to moderate pain associated with chronic symptomatic __________________________ and osteoarthritis
▪Myalgia, ______________, ________________ & dysmenorrhea
▪Relief of fever and mild to moderate pain associated with chronic symptomatic rheumatoid
arthritis (RA )and osteoarthritis
▪Myalgia, headache, dental pain, & dysmenorrhea
Mechanism of action of Ibuprofen
▪Inhibits ____________________, which block __________________ synthesis and modulate T-cell function
▪Inhibits inflammatory cell chemotaxis
▪Decreases release of superoxide radicals
▪Increases scavenging of superoxide radicals at inflammatory sites
▪Inhibits COX-1 and COX-2, which block prostaglandin synthesis and modulate T-cell function
▪Inhibits inflammatory cell chemotaxis
▪Decreases release of superoxide radicals
▪Increases scavenging of superoxide radicals at inflammatory sites
Ibuprofen adverse effects
▪Most common: GI related–Bleeding, anorexia, heartburn, N/V, Constipation or diarrhea
▪CNS effects: Dizziness, headache, drowsiness, tinnitus
▪Rare but serious: Peripheral edema, aplastic anemia, leukopenia and anaphylaxis
▪Chronic use may lead to: Polyuria, azotemia, cystitis, hematuria, & increased creatinine and blood urea nitrogen (BUN) levels
Black box warnings of Ibuprofen
[Can be fatal]
▪Risk of serious and potentially fatal cardiovascular
thrombotic events, MI, and stroke
▪Risk of serious GI adverse effects (bleeding,
ulcer, and stomach or intestine perforation)
Contraindications/precautions with Ibuprofen
▪Allergy to aspirin or___________________
▪Peptic Ulcer Disease (PUD)
▪________________ abnormalities
▪Perioperative pain related to coronary artery bypass graft (CABG)
▪Severe hepatic impairment
▪Hypertension (HTN)
▪History of GI bleeding
▪Diabetes mellitus
▪Impaired ______________________ function
▪Heart failure, serious HTN, or history of stroke/MI
▪Diminished respiratory function in children with asthma
▪Allergy to aspirin or other NSAIDs
▪Peptic Ulcer Disease (PUD)
▪Bleeding abnormalities
▪Perioperative pain related to coronary artery bypass graft (CABG)
▪Severe hepatic impairment
▪Hypertension (HTN)
▪History of GI bleeding
▪Diabetes mellitus
▪Impaired renal or hepatic function
▪Heart failure, serious HTN, or history of stroke/MI
▪Diminished respiratory function in children with asthma
Drug interactions with Ibuprofen
▪Oral anticoagulants and antiplatelet drugs can increase risk of______________
▪May increase toxicity of digoxin, lithium, or methotrexate
▪Other NSAIDs, alcohol, or corticosteroids may cause serious adverse __________________
▪Reduced antihypertensive action of diuretics, beta blockers, and angiotensin-converting enzyme (ACE) inhibitors
▪Herbal/food
–Feverfew, garlic, ginger, ginkgo may increase risk of ____________
▪Oral anticoagulants and antiplatelet drugs can increase risk of bleeding
▪May increase toxicity of digoxin, lithium, or methotrexate
▪Other NSAIDs, alcohol, or corticosteroids may cause serious adverse GI events
▪Reduced antihypertensive action of diuretics, beta blockers, and angiotensin-converting enzyme (ACE) inhibitors
▪Herbal/food
–Feverfew, garlic, ginger, ginkgo may increase risk of bleeding.
Treatment of Ibuprofen overdose
Administration of activated charcoal and
nasogastric suction
Cyclooxygenase-2 inhibitors
–Celecoxib (Celebrex) is second-generation NSAID
–Blocks COX-2 without inhibiting COX-1
–Less GI bleeding and ulcer formation than with
ibuprofen or aspirin
–Limited use due to risk of MI and stroke
–Therapeutic classification ?
–Pharmacologic classification ?
–Therapeutic classification = Anti-inflammatory
–Pharmacologic classification
▪COX-2 inhibitor
▪NSAID
Prototype drug: Celecoxib (Celebrex)
Therapeutic effects and uses:
▪ ________________________________________________________________________ associated with RA, osteoarthritis, dysmenorrhea, dental procedures, headache, and ankylosing spondylitis
▪Prophylaxis of adenomas or colorectal polyps
▪Mild - moderate pain and inflammation associated with RA, osteoarthritis, dysmenorrhea, dental procedures, headache, and ankylosing spondylitis
▪Prophylaxis of adenomas or colorectal polyps
Celecoxib (Celebrex) mechanism of action
▪Selectively inhibits the enzyme _____
▪Inhibits ____________ synthesis
▪Selectively inhibits the enzyme COX-2
▪Inhibits prostaglandin synthesis
*Acetaminophen
–Used to: [1]
–Has no anti-inflammatory properties = Not an : [2]
–Does not cause GI bleeding or ulcers
–Often combined with opioid analgesics
1- relieve pain and to reduce fever
2- Not an NSAID
*Acetaminophen
–Therapeutic classification ?
–Pharmacologic classification ?
–Therapeutic classification
▪Nonopioid analgesic
▪Antipyretic
–Pharmacologic classification
▪Para-aminophenol derivative
Acetaminophen (Tylenol) therapeutic effects/uses:
▪Mild to moderate pain
▪Osteoarthritis of the hip or knee
▪Dysmenorrhea
▪Dental procedures
▪Headache and myalgia
▪Fevers
Mechanism of action of Acetaminophen (Tylenol)
▪Inhibits ________
▪May inhibit chemical _____________ of pain
▪Direct action on ______________ center of hypothalamus
▪Inhibits COX
▪May inhibit chemical mediators of pain
▪Direct action on heat-regulating center of hypothalamus
Acetaminophen (Tylenol) adverse effects
– Adverse effects
▪At recommended doses, _______________________
▪Acute ___________ failure
– Serious adverse effects
▪Acute acetaminophen poisoning
–Symptoms: anorexia, nausea, vomiting, dizziness, lethargy, diaphoresis, chills, epigastric/ abdominal pain, diarrhea
▪Chronic use can lead to:
–Neutropenia
–Pancytopenia
–Leukopenia
–Thrombocytopenic purpura
–Hepatotoxicity in alcoholics
–Chronic Kidney Disease (CKD)
–Stevens–Johnson syndrome
– Adverse effects
▪At recommended doses,well tolerated
▪Acute hepatic failure
– Serious adverse effects
▪Acute acetaminophen poisoning
–Symptoms: anorexia, nausea, vomiting, dizziness, lethargy, diaphoresis, chills, epigastric/ abdominal pain, diarrhea
▪Chronic use can lead to:
–Neutropenia
–Pancytopenia
–Leukopenia
–Thrombocytopenic purpura
–Hepatotoxicity in alcoholics
–Chronic Kidney Disease (CKD)
–Stevens–Johnson syndrome
Black box warning on Acetaminophen (Tylenol)
▪Potential to cause severe _______ injury
▪Serious _______________________
–Symptoms: angioedema, difficulty breathing, itching, or rash
▪Potential to cause severe liver injury
▪Serious allergic reactions
–Symptoms: angioedema, difficulty breathing, itching, or rash
Contraindications/precautions with Acetaminophen (Tylenol)
▪Allergy to ______________
▪Anemia
▪G6PD deficiency
▪___________ disease
▪Rheumatoid or osteoarthritis
▪Malnutrition
▪_______________ depression
▪Immunosuppression
▪CKD
▪Allergy to acetaminophen
▪Anemia
▪G6PD deficiency
▪Hepatic disease
▪Rheumatoid or osteoarthritis
▪Malnutrition
▪Bone marrow depression
▪Immunosuppression
▪CKD
Drug interactions with Acetaminophen (Tylenol)
▪Alcohol increases risk of ______________________
▪Increase anticoagulant actions with warfarin
▪Can increase the risk of bone marrow suppression
with zidovudine
▪Herbal/food
–___________ enhances analgesic effects
–Hepatotoxicity reported with echinacea
▪Alcohol increases risk of hepatotoxicity
▪Increase anticoagulant actions with warfarin
▪Can increase the risk of bone marrow suppression
with zidovudine
▪Herbal/food
–Caffeine enhances analgesic effects
–Hepatotoxicity reported with echinacea
Treatment of Acetaminophen (Tylenol) overdose
▪Treat within __________ of ingestion
▪Three-bag method of acetylsteine (_______________)
▪Treat within 8 hours of ingestion
▪Three-bag method of acetylsteine (Acetadote)
