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CMBM Exam 4 > NSAIDs > Flashcards

NSAIDs Flashcards

1
Q

Arachidonic Acid Cascade

A
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2
Q

Fever

A
  • Increased synthesis of PGE2 in hypothalamus
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3
Q

Prostaglandins effect on renal function

A
  • Increase renal blood flow
  • Increase glomerular filtration rate
  • Cause renal vasodilation
  • Increase the excretion of Na+, K+, H2O
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4
Q

Prostaglandins effects on GI function

A
  • Promote the secretion of mucous
  • Inhibit the secretion of acid
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5
Q

PGI2 Hematological function

A
  • Inhibits aggregation (antithrombogenic effects)
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6
Q

TXA2 Hematological function

A
  • Induces platelet aggregation (thrombogenic effects)
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7
Q

NSAIDs low doses hematologic effect

A
  • Antithrombotic effects

*inhibit thromboxane synthesis in platelets

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8
Q

NSAIDs high doses hematologic effect

A
  • Thrombotic effects

*inhibit prostacyclin synthesis

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9
Q

Anti-inflammatory/Analgesic Agents

A
  • Salicylates
  • Para-aminophenol derivatives
  • Propionic acid derivatives
  • Heteroaryl acetic acids
  • Enolic acids
  • Indole and indene acetic acids
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10
Q

NSAIDs General Characteristics (most NSAIDs)

A
  • Inhibit COX
  • Analgesic, Anti-inflammatory, Antipyretic, Antiplatelet
  • Absorbed from stomach, small intestines
  • Metabolized by liver, excreted by kidney
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11
Q

NSAIDs Contraindications (most NSAIDs)

A
  • Aspirin hypersensitivity; may have an allergy to a # of other NSAIDs
  • Liver dysfunction
  • Renal dysfunction
  • Alcoholism, smoking (factors contributing to ulcers)
  • Caution during pregnancy or during breast feeding
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12
Q

Salicylates

A
  • Salicylic acid
  • Aspirin
  • Diflunisal
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13
Q

Asprin Effects

A
  • Acetylsalicylic acid
  • Analgesic, Antiinflammatory, Antipyretic, Antiplatelet
  • Stimulates respiration
  • Uncouples oxidative phosphorylation
  • Stimulates the medullary respiratory center
  • Alters acid-base equilibrium
  • All other NSAIDs activity is compared to Aspirin
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14
Q

Asprin is used for

A
  • Pain
  • Inflammation
  • Fever (pyrogen-induced and CNS response)
  • Cardiac conditions to reduce blood clotting
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15
Q

Aspirin MOA

A
  • Irreversible inhibition of cyclooxygenase
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16
Q

Aspirin Metabolism

A
  • 80-90% plasma protein bound
  • Competes w/ thyroxine, penicillin, phenytoin, naproxen, sulfinpyrazone, and bilirubin
  • Hydrolyzed to salicylate in the plasma
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17
Q

Aspirin Side Effects

A
  • CNS: tinnitus, vertigo, confusion, delirium
  • GI: nausea and emesis, local gastric irritation w/bleeding
  • Hepatotoxicity

*prolonged high doses, viral infection

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18
Q

Aspirin Contraindications

A
  • Aspirin hypersensitivity
  • Chronic liver disease
  • Gout

*has adverse effects on liver function

  • Peptic ulcer
  • Hemophilia, Vitmin K deficiency
  • Diabetes
  • Chickenpox or influenza in children

*Reyes Syndrome

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19
Q

Salicylism

A
  • Aspirin overdose
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20
Q

Mild chronic salicylate intoxication

A
  • Headache
  • Dizziness
  • Ringing in the ears
  • Difficulty in hearing
  • Dimness of vision
  • Mental confusion
  • Lassitude
  • Drowsiness
  • Sweating
  • Thirst
  • Hyperventilation
  • Nausea
  • Vomiting
  • Diarrhea
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21
Q

High chronic salicylate intoxication

A
  • Generalized convulsion
  • Skin eruptions
  • Marked alterations in acid-base balance
  • Fever
  • Dehydration
  • Hyperpyrexia, sweating, vomiting and loss of water vapor during hyperventilation
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22
Q

Aspirin Blood levels- Effects- Toxicity chart

A
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23
Q

Aspirin toxicity treatment

A
  • Induce emesis
  • Gastric lavage
  • Activated charcoal
  • Hydrate
  • Correct acid-base balance
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24
Q

Diflunisal (DOLOBID) Effects

A
  • Antiinflammatory; more potent than aspirin
  • Analgesic
  • No antipyretic effects; poor CNS penetration
  • Insignificant prolongation of bleeding time; less antiplatelet activity
  • Less occult blood loss than aspirin
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25
Q

Diflunisal is used for

A
  • Pain
  • Osteoarthritis
  • Rheumatoid arthritis

*is only managing the pain and inflammation of the diseases listed- not stemming the disease itself as they are autoimmune conditions

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26
Q

Diflunisal MOA

A
  • Competitive inhibition of cyclooxygenase
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27
Q

Diflunisal Metabolism

A
  • 99% bound to plasma albumin
  • Competes w/oral hypoglycemics and anticoagulants
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28
Q

Diflunisal Side Effects

A
  • Dizziness
  • Nephritis
  • Gastric ulceration
  • No tinnitus
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29
Q

Diflunisal Contraindications

A
  • Asthma

*higher incidence of complications in pts.; unknown reason

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30
Q

Acetaminophen (TYLENOL) is used for

A
  • Analgesic
  • Antipyretic
  • Weak antiinflammatory effect
  • Where aspirin and other NSAIDs are contraindicated
  • Used concomitantly w/probenecid in the treatment of gout
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31
Q

Acetaminophen MOA

A
  • Antipyretic; Blocks cyclooxygenase in hypothalamus only in environments w/low levels of peroxides

*high concentrations of peroxides in inflammatory lesions

  • Analgesic- unknown
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32
Q

Acetaminophen Metabolism

A
  • 20-50% plasma protein bound
  • 90%+ is conjugated in liver w/glucuronic acid, sulfuric acid or cysteine
  • Small portion is metabolized by the liver microsomal enzymes
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33
Q

Acetaminophen Side Effects

A
  • Hepatotoxicity
  • NO GI effects
  • NO prolongation of bleeding time
  • NO effects on renal function or acid-base equilibrium
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34
Q

Acetaminophen Acute Intoxication

A
  • 12 hrs.

*nausea, vomiting, lethargy

  • 48hrs.

*potentially fatal hepatic necrosis (dose-dependent), renal tubular necrosis, hypoglycemic coma

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35
Q

Acetaminophen Contraindications

A
  • NOT FOR INFLAMMATORY CONDITIONS
  • Analgesia adjunct w/other antiinflammatory agents
  • Use w/caution w/liver disease
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36
Q

Propionic Acid Derivatives

A
  • Ibuprofen
  • Naproxen
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37
Q

Ibuprofen (MOTRIN, RUFIN) Effects

A
  • Analgesic
  • Antiinflammatory
  • Antipyretic
  • Antiplatelet (reversible)
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38
Q

Ibuprofen used for

A
  • Same as aspirin

*pain, inflammation, fever (pyrogen-induced and CNS response), cardiac conditions to reduce blood clotting

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39
Q

Ibuprofen MOA

A
  • Competitive inhibition of cyclooxygenase
40
Q

Ibuprofen Metabolism

A
  • 99% bound to plasma proteins
  • NO interaction w/oral hypoglycemics or oral anticoagulants)
41
Q

Ibuprofen Side Effects

A
  • GI

*epigastric pain, nausea, heartburn, sensation of “fullness”, duodenal/intestinal erosions (but less than aspirin)

  • Occult blood loss uncommon
  • Ocular disturbances
  • Skin rashes
  • Headache
42
Q

Naproxen (NAPROSYN, ANAPROX) Effects

A
  • Analgesic
  • Antiinflammatory
  • Antipyretic
  • Antiplatelet (reversible)
43
Q

Naproxen used for

A
  • Same as aspirin

*pain, inflammation, fever (pyrogen-induced and CNS response), cardiac conditions to reduce blood clotting

44
Q

Naproxen MOA

A
  • Competitive inhibitor of cyclooxygenase
  • Inhibits hydrolytic enzymes of lysosomal system
  • Inhibits migration of PMN leukocytes
45
Q

Naproxen Metabolism

A
  • 99% bound to plasma proteins
  • NO interaction w/oral hypoglycemics or oral anticoagulants
46
Q

Naproxen Side Effects

A
  • Occult blood loss less than aspirin
  • CNS

*drowsiness, vertigo, headache, fatigue, ototoxicity

  • GI

*emesis, dyspepsia, gastric bleeding

  • Pruritus
47
Q

Heteroaryl Acetic Acids

A
  • Ketorolac (Toradol)
  • Tolmetin (Tolectin)
  • Diclofenac (Voltaren)
48
Q

Ketoroac (TORADOL) Effects

A
  • Analgesic
  • Antiinflammatory
  • Antipyretic
  • Prolongs bleeding time (reversible 24-48hrs.)
49
Q

Ketorolac used for

A
  • Short term management of pain
50
Q

Ketorolac MOA

A
  • Completely absorbed following I.M. injection
  • Very potent inhibitor of cyclooxygenase
51
Q

Ketorolac Metabolism

A
  • 99% plasma protein bound
  • Little if any interaction w/other bound drugs
52
Q

Ketorolac Side Effects

A
  • Nausea
  • Dyspepsia
  • GI pain
  • Drowsiness
53
Q

Ketorolac Contraindications

A
  • Additive side-effects w/other NSAIDs
  • Partial or complete syndrome of nasal polyps, angioedema and bronchospasm
  • Previously demonstrated hypersensitivity to ketorolac
54
Q

Tolmetin (TOLECTIN) Effects

A
  • Analgesic
  • Antiinflammatory
  • Antipyretic
  • Prolongs bleeding time
  • Less occult blood loss than aspirin
55
Q

Tolmetin used for

A
  • Rheumatoid arthritic and osteoarthrits pain
56
Q

Tolmetin MOA

A
  • Competitive inhibitor of cyclooxygenase
57
Q

Tolmetin Metabolism

A
  • 99% plasma protein bound

*does not compete w/warfarin or oral hypoblycemic agents

58
Q

Tolmetin Side Effects

A
  • 25-40% experience, 5-10% discontinue
  • 15% epigastric pain, nausea and emesis
  • Gastric and duodenal ulceration
  • CNS effects: tinnitus, nervousness, anxiety, drowsiness
59
Q

Diclofenac (VOLTAREN) Effects

A
  • Analgesic
  • Antiinflammatory
  • Antipyretic
60
Q

Diclofenac used for

A
  • Approved for long term treatment of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis
  • Some use for post-op pain, bursitis, acute musculoskeletal injury
61
Q

Diclofenac MOA

A
  • Competitive inhibitor of cyclooxygenase
  • Reduces intracellular concentrations of free arachidonate in leukocytes
62
Q

Diclofenac Metabolism

A
  • 99% plasma protein bound
  • Minimal competition w/warfarin, no affect on oral hypoglycemics
  • 50% first pass effect
63
Q

Diclofenac Side Effects

A
  • 20% experience, 2% discontinue
  • Epigastric pain, also nausea and emesis
  • Gastric ulceration
  • CNS effects (tinnitus, nervousness, anxiety, drowsiness)
  • Skin rashes, allergic reactions
64
Q

Enolic Acids

A
  • Piroxicam (Feldene)
  • Phenylbutazone (BUTAZOLIDIN)
65
Q

Piroxicam (Feldene) Effects

A
  • Analgesic
  • Antiinflammatory
  • Antipyretic
  • Prolongs bleeding time
  • Equivalent to aspirin, indomethacin or naproxen, but much better tolerated
66
Q

Piroxicam used for

A
  • Osteoarthritis
  • Rheumatoid arthritis
  • Acute gout
67
Q

Piroxicam MOA

A
  • Potent inhibitor of cyclooxygenase
  • Also inhibits activation of neutrophils and hemostasis
68
Q

Piroxicam Metabolism

A
  • 99% plasma protein bound
  • May compete w/warfarin
  • Enterohepatic recycling
69
Q

Piroxicam Side Effects

A
  • 11-46% experience, 4-12% discontinue
  • GI symptoms: 1% incidence of peptic ulcers
70
Q

Phenylbutazone (Butazolidin) Effects

A
  • Analgesic (inferior to aspirin for non-rheumatic pain)
  • Antiinflammatory (most prominent)
  • Antipyretic
  • Very toxic
  • Uricosuric similar to aspirin
71
Q

Phenylbutazone used for

A
  • Acute gout
  • Rheumatoid arthritis
72
Q

Phenylbutazone MOA

A
  • Inhibitor of cyclooxygenase
73
Q

Phenylbutazone Metabolism

A
  • 98% plasma protein bound
  • Competes w/NSAIDs, warfarin, oral hypoglycemics and sulfonamides)
74
Q

Phenylbutazone Side Effects

A
  • 10-45% experience, 10-15% discontinue
  • Epigastric pain, nausea, emesis and skin rashes most frequent
  • Gastric ulceration
  • CNS effects: vertigo, insomnia, euphoria, nervousness
  • Skin rashes, allergic reactions, nephritis, hepatitis, aplastic anemia, agranulocytosis
75
Q

Phenylbutazone Contraindications

A
  • Cardiac, hepatic or renal dysfunction
  • Blood dyscrasias
  • Promotes retention of Na+ and Cl- w/water leading to cardiac decompensation and pulmonary edema in some patients
76
Q

Indole and Indene Acetic Acids

A
  • Indomethacin (INDOCIN)
  • Sulindac (CLINORIL)
77
Q
  • Indomethacin (INDOCIN) and Sulindac Effects
A
  • Analgesic
  • Antiinflammatory
  • Antipyretic
  • Significant occult blood loss
78
Q

Indomethacin or Sulindac used for

A
  • Rheumatoid arthritis, ankylosing spondylitis, acute gout
  • Neonates: close patent ductus arteriosus
79
Q

Indomethacin or Sulindac MOA

A
  • Potent inhibitor of cyclooxygenase
  • Inhibitis mobility of PMN leukocytes
80
Q

Indomethacin or Sulindac Metabolism

A
  • Absorbed following oral administration (available for I.V. injection)
  • 90% plasma protein bound (and also extensively bound to tissues)
81
Q

Indomethacin or Sulindac Side Effects

A
  • 35-50% experience, 20% discontinue
  • Abdominal pain, nausea, anorexia
  • Gastric ulceration
  • Significant occult blood loss
  • CNS effects: severe frontal headache, vertigo, mental clouding, depression, psychosis
  • Skin rashes, allergic reactions, nephritis, aplastic anemia, thrombocytopenia
82
Q

Indomethacin or Sulindac Contraindications

A
  • NO concurrent administration w/warfarin b/c of the increased risk of GI bleeding
83
Q

Indomethacin or Sulindac Drug Interactions

A
  • Diuretics
  • Antihypertensives of thiazide diuretic class, B-blockers and ACE inhibitors
84
Q

Sulindac Effects

A
  • A congener of indomethacin
  • Prodrug
  • Sulfide metabolite is the active agent
  • Less irritating to the gastric mucosa than indomethacin
  • More irritating to the gastric mucosa than other NSAIDs
  • Toxic effect similar to indomethacin
85
Q

Selective COX2 Inhibitors

A
  • Celecoxib (CELEBREX)
  • Rofecoxib (VIOOX)
86
Q

Celecoxib or Rofecoxib MOA

A
  • Selective inhibition of cyclooxygenase 2
  • No inhibition of COX1 (at therapeutic concentrations)
87
Q

Celecoxib Effects

A
  • Antiinflammatory
  • Analgesic
  • Antipyretic
88
Q

Celecoxib Metabolism

A
  • Absorbed following oral admin.
  • Peak plasma levels - 3 hrs.
  • Steady state reached - day 5
  • 97% plasma protein bound
  • Metabolized by P450 (inactive metabs.)
  • Excreted in feces and urine
89
Q

Celecoxic Side Effects

A
  • GI ulceration, bleeding and perforation

*lower incidence than other NSAIDs

  • May cause premature closure of the ductus arteriosus
90
Q

Risk of GI ulceration Graph

91
Q

Rofecoxib (VIOOX) Effects

A
  • REMOVED from market due to heart attack and stroke risk
  • Antiinflammatory
  • Analgesic
  • Antipyretic
92
Q

Agent used to minimize side effects of NSAIDs

A
  • Misoprotosol (CYTOTEC)
93
Q

Misoprotosol (CYTOTEC) used for

A
  • Suppress gastric ulceration
  • Used w/patients on chronic treatment w/NSAIDs
94
Q

Misoprotosol (CYTOTEC) MOA

A
  • PGE1 analog
95
Q

Misoprotosol Contraindications

A
  • Pregnancy

*has abortifacient property

CMBM Exam 4 (14 decks)

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