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Pharmacology > NSAIDs and Gout > Flashcards

NSAIDs and Gout Flashcards

1
Q

NSAIDs - MoA

A

Inhibition of prostaglandin synthesis by competitive cyclooxygenase (COX) inhibition

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2
Q

NSAIDs - Clinical use

A 
Low dose: mild-moderate pain, antipyretic
Higher doses: inflammation.
Postop pain (often combined with opioid)
Chronic pain
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3
Q

NSAIDs - Contraindications

A

Avoid treatment with two NSAIDs (increased GI bleeding risk).

Generally not recommended for second half of pregnancy

Previous severe hypersensitivity to salicylates (cross-sensitivity)

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4
Q

NSAIDs - Adverse

A 
GI bleeding, peptic ulcers, renal & hepatic dysfunction.
Lithium toxicity.
Hyperkalemia
Platelet inhibition
Premature closure of ductus arteriosus
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5
Q

NSAIDs - Interactions

A

Inhibit renal excretion of lithium.

Reduced clearance of aminoglycosides & methotrexates.

Interfere with antihypertensive effect of: diuretics, β-adrenoceptor antagonists, angiotensin inhibitors & others.

Potassium-sparing diuretics: hyperkalemia

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6
Q

Salicylates - MoA

A

Nonspecific inhibition of COX

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7
Q

Salicylates - Clinical use

A

Pain, fever, inflammation

Prophylaxis for MI, stroke, thromboembolic disorders

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8
Q

Salicylates - Contraindications and Overdose treatment

A

Avoid in children: Reye syndrome (in virus infected children).

Overdose treatment: 
Vomiting
IV sodium bicarbonate (alkalization of the urine, increases ionization and elimination)
Fluids
Electrolytes
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9
Q

Salicylates - Adverse

A

Reye syndrome

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10
Q

Salicylates - Interaction

A

Hypoglycemic effect alter antidiabetic drugs

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11
Q

Aspirin - MoA

A

Forms covalent, irreversible inhibition of COX in platelets

Nonspecific inh of COX in peripheral tissues and CNS

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12
Q

Aspirin - Clinical use

A

Analgesic
Antipyretic
Anti-inflammatory

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13
Q

Aspirin - Adverse

A

Aspirin toxicity

High dose:
Tinnitus (early sign of salicylate toxicity)
Hyperventilation
Fever, dehydration, severe metabolic acidosis
If not treated: Shock, coma, organ system failure, death

Hypoprothrombinemia – impairment of hemostatis and bleeding

Hypersensitivity – anaphylaxis (mostly pt with asthma, nasal polyps, chronic urticaria)

Symptoms of aspirin intolerance: vasomotor rhinitis, angioedema, urticaria

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14
Q

Aspirin - Interactions and contraindication

A

Adm with antacids: slows absorption rate

Contraindication:
Persons who have has severe hypersensitivity reaction to aspirin or another salicylate should not be treated with another type of NSAID (cross-sensitivity)

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15
Q

Ibuprofen - MoA

A

Reversible and nonselective inh of COX

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16
Q

Ibuprofen, Ketoprofen, Naproxen - Clinical use

A

Analgesic, antipyretic and anti-inflammatory effects

Low dose: mild pain & inflammation

Higher dose: arthritis

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17
Q

Ibuprofen - Special

A

Combo with H2 receptor antagonist famotidine for RA & OA (less GI ulcers)
Half-life: 2h

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18
Q

Ibuprofen - Adverse

A

GI irritation, nausea, dyspepsia, bleeding.
Long-term: PUD,
Hepatotoxicity, renal toxicity
Failure of ingesting adequate fluid: acute renal failure

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19
Q

Naproxen - Special

A

Combo with esomeprazole: arthritis, reduces risk of ulcers

Longer halflife (14h)

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20
Q

Acetaminophen - MoA

A

COX3 inhibitor

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21
Q

Acetaminophen - Clincal use

A

Mild fever & pain
Mild arthritis

Analgesic and antipyretic effects via inh of COX

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22
Q

Acetaminophen - Special consideration and Overdose treatment

A

Safe for children with viral inf.

Overdose treatment: acetylcysteine

Can be used with other NSAID of supplemental analgesia. Should be avoided.

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23
Q

Acetaminophen - Adverse

A

Fewer GI problems
Low doses ok in pregnancy for analgesia & antipyresis

High dose: hepatic necrosis, hepatotoxicity

Long-term use: Increased risk of renal dysfunction

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24
Q

Acetaminophen - Interactions

A

Small amount converted by CYT P-450 to potentially hepatotoxic quinone intermediate

Patients at risk for hepatotoxicity (f.ex. overdose): given acetylcysteine (conjugates quinone and renders it harmless)

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25
Q

Indomethacin - Clinical use

A

Reserved for moderate/severe infl disorders

Patent ductus arteriosus (indomethacin inh synthesis of prostaglandins and causes the closure)

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26
Q

Indomethacin - Adverse

A

Nephrotoxicity with triamterene
Highest incidence of GI and CNS side effects
Hematologic toxicity

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27
Q

Indomethacin - Interaction

A

Reduces natriuretic effect of diuretics.

With triamterene: nephrotoxicity

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28
Q

Sulindac - MoA

A

Prodrug converted to active sulfide metabolite. Parent compound sulindac sulfoxide is inactive in COX inh

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29
Q

Sulindac - Clinical use

A

RA

Adenomas in polyp disease

30
Q

Ketorolac - Clinical use

A

Analgesic activity
Post-op moderate pain in dentistry
Allergic conjunctivitis
Post-op ocular infl.

31
Q

Ketorolac - Special consideration and contraindications

A

Treatment limited to 5 days.

Caution in pt with renal/hepatic disease

32
Q

Ketorolac - Adverse

A

Fewer GI and CNS effects than opioids.
Hematologic toxicity
Increased risk of renal or hepatic impairment

33
Q

Piroxicam - Clinical use

A

Anti-inflammatory

Chronic RA treatment

34
Q

Piroxicam - Special

A

Long half-life (50h)

35
Q

Nabumetone - MoA

A

Weak COX inhibitory activity in vitro, but converted to active metabolites with potent inhibition in vivo

36
Q

Etodolac, meloxicam - MoA

A

More selective for COX-2 than typical NSAIDs

37
Q

Diclofenac - Clinical use

A

Osteoarthritis

38
Q

Selective COX-2 inhibitors

A

Celecoxib
Rofecoxib (Removed from market)
Valdecoxib (Removed from market)

39
Q

Selective COX-2 inhibitors - MoA

A

Potent anti-inflammatory action

40
Q

Selective COX-2 inhibitors - Special

A

Decreased risk of cancer (esp colon cancer)

41
Q

Celecoxib - Clinical use

A

Rheumatoid arthritis

Osteoarthritis

42
Q

Celecoxib - MoA

A

Analgesic, antipyretic, antiinflammatory

43
Q

Celecoxib - Adverse

A

Increased risk of cardiovascular events

Low incidence: diarrhea, dyspepsia, abd pain

44
Q

Celecoxib - Interactions

A

Metabolized by CYT P-450, excreted in feces and urine

Metabolism is inhibited & increased serum levels by fluconazole, fluvastatin, zafirlukast.

45
Q

Uricosuric drugs

A

Probenecid
Sulfinpyrazone
Lesinurad

46
Q

Uricosuric drugs - Clinical use

A

Prevent gout attacks in persons who under-excrete uric acid.

47
Q

Probenecid - MoA

A

Increases excretion of uric acid by competitive inhibition of uric acid reabsorption

48
Q

Probenecid - Interactions

A

Aspirin and salicylates: interfere with the uricosuric effect.

High dose of salicylates: inh uric acid reabsorption
Low doses of salicylates: inh uric acid secretion

49
Q

Sulfinpyrazone - MoA

A

Complete inhibition of urate reabsorption, increasing uric acid excretion

50
Q

Sulfinpyrazone - Adverse

A

GI, renal and hematologic adverse effects

51
Q

Lesinurad - MoA

A

Reduces uric acid levels by inh the function of transporters responsible for uric acid reabsorption, uric acid transporter 1 and organic anion transporter 4.

52
Q

Xanthiine oxidase inhibitors

A

Allopurinol and Febuxostat

53
Q

Xanthiine oxidase inhibitors - MoA

A

Decreases production of uric acid

54
Q

Xanthiine oxidase inhibitors - Clinical use

A

Prevent gout attacks in people who overproduce uric acid.

Prevent hyperuricemia and gout in persons having cancer chemotherapy and whose rate of purine catabolism is high.

55
Q

Allopurinol - MoA

A

Competitive inhibitor of xanthine oxidase

Converted to active metabolite oxypurinol in the liver.

Decrease in uric acid excretion and corresponding increase in urinary excretion of hypoxanthine.

56
Q

Allopurinol - Clincal use

A

Hyperuricemia and gout in cancer patients with high purine catabolism

Prevent the occurrence or progression or both gouty arthritis and urate nephropathy

57
Q

Allopurinol - Adverse

A

Nausea, vomiting, hepatitis, skin rashes, hypersensitivity.

58
Q

Allopurinol - Interactions

A

Inhibits catabolism of azathioprine and mercaptopurine

59
Q

Febuxostat - MoA

A

Competitive inhibitor of xanthine oxidase

60
Q

Febuxostat - Adverse

A

Liver enzyme elevations, nausea, arthralgia, rash

61
Q

Catabolic enzyme preparations

A

Pegloticase and Rasburicase

62
Q

Catabolic enzyme preparations - MoA

A

Reverse hyperuricemia

63
Q

Pegloticase - Clinical use

A

Refractory chronic gout

64
Q

Pegloticase - Adverse

A

Life-threatening allergic reactions

65
Q

Rasburicase - Clinical use

A

ONLY: initial management of plasma uric acid in pediatric and adults with leukemia, lymphoma and solid tumor malignancies who are receiving anticancer therapy

66
Q

Rasburicase - Adverse

A

Allergic reactions

67
Q

Drugs for treating gout attacks

A

Indomethacin and Clochicine

68
Q

Indomethacin - MoA

A

Anti-inflammatory drug for rapid relief of pain

69
Q

Clochicine - MoA

A

Disrupting microtubules and inh of inflammatory leukocyte motility –> blocking their ability to cause urate crystal-induced joint inflammation.

70
Q

Clochicine - Adverse

A

Nausea, vomiting, diarrhea, abdominal cramps

71
Q

Indomethacin and Clochicine - Clinical use

A

Acute gout

Pharmacology (55 decks)

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