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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
Diflunisal is used for
- 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
26
Diflunisal MOA
- Competitive inhibition of cyclooxygenase
27
Diflunisal Metabolism
- 99% bound to plasma albumin - Competes w/oral hypoglycemics and anticoagulants
28
Diflunisal Side Effects
- Dizziness - Nephritis - Gastric ulceration - No tinnitus
29
Diflunisal Contraindications
- Asthma \*higher incidence of complications in pts.; unknown reason
30
Acetaminophen (TYLENOL) is used for
- Analgesic - Antipyretic - Weak antiinflammatory effect - Where aspirin and other NSAIDs are contraindicated - Used concomitantly w/probenecid in the treatment of gout
31
Acetaminophen MOA
- Antipyretic; Blocks cyclooxygenase in hypothalamus only in environments w/low levels of peroxides \*high concentrations of peroxides in inflammatory lesions - Analgesic- unknown
32
Acetaminophen Metabolism
- 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
33
Acetaminophen Side Effects
- Hepatotoxicity - NO GI effects - NO prolongation of bleeding time - NO effects on renal function or acid-base equilibrium
34
Acetaminophen Acute Intoxication
- 12 hrs. \*nausea, vomiting, lethargy - 48hrs. \*potentially fatal hepatic necrosis (dose-dependent), renal tubular necrosis, hypoglycemic coma
35
Acetaminophen Contraindications
- NOT FOR INFLAMMATORY CONDITIONS - Analgesia adjunct w/other antiinflammatory agents - Use w/caution w/liver disease
36
Propionic Acid Derivatives
- Ibuprofen - Naproxen
37
Ibuprofen (MOTRIN, RUFIN) Effects
- Analgesic - Antiinflammatory - Antipyretic - Antiplatelet (reversible)
38
Ibuprofen used for
- Same as aspirin \*pain, inflammation, fever (pyrogen-induced and CNS response), cardiac conditions to reduce blood clotting
39
Ibuprofen MOA
- Competitive inhibition of cyclooxygenase
40
Ibuprofen Metabolism
- 99% bound to plasma proteins - NO interaction w/oral hypoglycemics or oral anticoagulants)
41
Ibuprofen Side Effects
- 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
Naproxen (NAPROSYN, ANAPROX) Effects
- Analgesic - Antiinflammatory - Antipyretic - Antiplatelet (reversible)
43
Naproxen used for
- Same as aspirin \*pain, inflammation, fever (pyrogen-induced and CNS response), cardiac conditions to reduce blood clotting
44
Naproxen MOA
- Competitive inhibitor of cyclooxygenase - Inhibits hydrolytic enzymes of lysosomal system - Inhibits migration of PMN leukocytes
45
Naproxen Metabolism
- 99% bound to plasma proteins - NO interaction w/oral hypoglycemics or oral anticoagulants
46
Naproxen Side Effects
- Occult blood loss less than aspirin - CNS \*drowsiness, vertigo, headache, fatigue, ototoxicity - GI \*emesis, dyspepsia, gastric bleeding - Pruritus
47
Heteroaryl Acetic Acids
- Ketorolac (Toradol) - Tolmetin (Tolectin) - Diclofenac (Voltaren)
48
Ketoroac (TORADOL) Effects
- Analgesic - Antiinflammatory - Antipyretic - Prolongs bleeding time (reversible 24-48hrs.)
49
Ketorolac used for
- Short term management of pain
50
Ketorolac MOA
- Completely absorbed following I.M. injection - Very potent inhibitor of cyclooxygenase
51
Ketorolac Metabolism
- 99% plasma protein bound - Little if any interaction w/other bound drugs
52
Ketorolac Side Effects
- Nausea - Dyspepsia - GI pain - Drowsiness
53
Ketorolac Contraindications
- Additive side-effects w/other NSAIDs - Partial or complete syndrome of nasal polyps, angioedema and bronchospasm - Previously demonstrated hypersensitivity to ketorolac
54
Tolmetin (TOLECTIN) Effects
- Analgesic - Antiinflammatory - Antipyretic - Prolongs bleeding time - Less occult blood loss than aspirin
55
Tolmetin used for
- Rheumatoid arthritic and osteoarthrits pain
56
Tolmetin MOA
- Competitive inhibitor of cyclooxygenase
57
Tolmetin Metabolism
- 99% plasma protein bound \*does not compete w/warfarin or oral hypoblycemic agents
58
Tolmetin Side Effects
- 25-40% experience, 5-10% discontinue - 15% epigastric pain, nausea and emesis - Gastric and duodenal ulceration - CNS effects: tinnitus, nervousness, anxiety, drowsiness
59
Diclofenac (VOLTAREN) Effects
- Analgesic - Antiinflammatory - Antipyretic
60
Diclofenac used for
- Approved for long term treatment of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis - Some use for post-op pain, bursitis, acute musculoskeletal injury
61
Diclofenac MOA
- Competitive inhibitor of cyclooxygenase - Reduces intracellular concentrations of free arachidonate in leukocytes
62
Diclofenac Metabolism
- 99% plasma protein bound - Minimal competition w/warfarin, no affect on oral hypoglycemics - 50% first pass effect
63
Diclofenac Side Effects
- 20% experience, 2% discontinue - Epigastric pain, also nausea and emesis - Gastric ulceration - CNS effects (tinnitus, nervousness, anxiety, drowsiness) - Skin rashes, allergic reactions
64
Enolic Acids
- Piroxicam (Feldene) - Phenylbutazone (BUTAZOLIDIN)
65
Piroxicam (Feldene) Effects
- Analgesic - Antiinflammatory - Antipyretic - Prolongs bleeding time - Equivalent to aspirin, indomethacin or naproxen, but much better tolerated
66
Piroxicam used for
- Osteoarthritis - Rheumatoid arthritis - Acute gout
67
Piroxicam MOA
- Potent inhibitor of cyclooxygenase - Also inhibits activation of neutrophils and hemostasis
68
Piroxicam Metabolism
- 99% plasma protein bound - May compete w/warfarin - Enterohepatic recycling
69
Piroxicam Side Effects
- 11-46% experience, 4-12% discontinue - GI symptoms: 1% incidence of peptic ulcers
70
Phenylbutazone (Butazolidin) Effects
- Analgesic (inferior to aspirin for non-rheumatic pain) - Antiinflammatory (most prominent) - Antipyretic - Very toxic - Uricosuric similar to aspirin
71
Phenylbutazone used for
- Acute gout - Rheumatoid arthritis
72
Phenylbutazone MOA
- Inhibitor of cyclooxygenase
73
Phenylbutazone Metabolism
- 98% plasma protein bound - Competes w/NSAIDs, warfarin, oral hypoglycemics and sulfonamides)
74
Phenylbutazone Side Effects
- 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
Phenylbutazone Contraindications
- 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
Indole and Indene Acetic Acids
- Indomethacin (INDOCIN) - Sulindac (CLINORIL)
77
- Indomethacin (INDOCIN) and Sulindac Effects
- Analgesic - Antiinflammatory - Antipyretic - Significant occult blood loss
78
Indomethacin or Sulindac used for
- Rheumatoid arthritis, ankylosing spondylitis, acute gout - Neonates: close patent ductus arteriosus
79
Indomethacin or Sulindac MOA
- Potent inhibitor of cyclooxygenase - Inhibitis mobility of PMN leukocytes
80
Indomethacin or Sulindac Metabolism
- Absorbed following oral administration (available for I.V. injection) - 90% plasma protein bound (and also extensively bound to tissues)
81
Indomethacin or Sulindac Side Effects
- 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
Indomethacin or Sulindac Contraindications
- NO concurrent administration w/warfarin b/c of the increased risk of GI bleeding
83
Indomethacin or Sulindac Drug Interactions
- Diuretics - Antihypertensives of thiazide diuretic class, B-blockers and ACE inhibitors
84
Sulindac Effects
- 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
Selective COX2 Inhibitors
- Celecoxib (CELEBREX) - Rofecoxib (VIOOX)
86
Celecoxib or Rofecoxib MOA
- Selective inhibition of cyclooxygenase 2 - No inhibition of COX1 (at therapeutic concentrations)
87
Celecoxib Effects
- Antiinflammatory - Analgesic - Antipyretic
88
Celecoxib Metabolism
- 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
Celecoxic Side Effects
- GI ulceration, bleeding and perforation \*lower incidence than other NSAIDs - May cause premature closure of the ductus arteriosus
90
Risk of GI ulceration Graph
91
Rofecoxib (VIOOX) Effects
- REMOVED from market due to heart attack and stroke risk - Antiinflammatory - Analgesic - Antipyretic
92
Agent used to minimize side effects of NSAIDs
- Misoprotosol (CYTOTEC)
93
Misoprotosol (CYTOTEC) used for
- Suppress gastric ulceration - Used w/patients on chronic treatment w/NSAIDs
94
Misoprotosol (CYTOTEC) MOA
- PGE1 analog
95
Misoprotosol Contraindications
- Pregnancy \*has abortifacient property

CMBM Exam 4 (14 decks)

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