非類固醇抗發炎用藥


 

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非類固醇抗發炎用藥

Anti-inflammatory Drugs

  • NSAIDs

        Aspirin , Diclofenac , Ibuprofen , Indomethacin , Nabumetone……

  • Non-Narcotic Analgesics

        Acetaminophen , Phenacetin

  • Anti-R.A Drugs

        Chloroquine , Gold salts , MTX , D-Penicillamine

  • Anti-Gout Drugs

        Allopurinol , Colchicine , Probenecid , Sulfinpyrazone

非類固醇抗發炎藥物依化學結構分類

  • Carboxylic acids:

            → Salicylate:Aspirin , Diflunisal

            → Propionic acid derivatives:Ibuprofen , Naproxen , Fenoprofen , Ketoprofen ,

            → Fenamates:Mefenamic acid , Meclofenamate

            → Indoleacetic acids:Indomethacin , Sulindac , Etodolac

  • Enolic acids:

            → Oxicam derivatives:Piroxicam , Meloxicam

            → Phenybutazone:Phenylbutazone

  • Other agents:

            → Diclofenac , Ketorolac , Tolmetin , Nabumetone

Discorvery of two different

isoforms of COX

Using a molecular biology approach an alternative mRNA species coding for a different COX was found:COX-2

COX-2 is aninducible protein–COX-2 is not normally present in cells , but appears after exposure of the cell to inflammatory stimuli

COX-1 is a constitutive protein

Therapeutic effects of NSAIDs

versus side effects

Therapeutic anti-inflammatory effects–Inhibition of Prostaglandin synthesis at inflammation / pain sites

Adverse effects–Inhibition of Prostaglandin synthesis , particularly in the stomach and kidney

Hypothesis for inhibition of

COX-1 and COX-2 by NSAIDs

Therapeutic effects of NSAIDs due to inhibition of COX-2

Side effects of NSAIDs due to inhibition of COX-1

Therefore:

Selective COX-2 inhibition promises maximal anti-inflammatory activity with minimal gastric and renal side effects

NSAIDs 之適應症(一)

  • FDA approved:

            → Rheumatoid arthritis(R.A)類風濕性關節炎

            → Osteoarthritis(O.A)骨關節炎

            → Alkylosing spondylitis 僵直性脊椎炎

            → Primary dysmenorrhea

            → Bursitis 滑曩炎

            → Acute pain shoulder

            → Acute gout

            → Fever

            → Mild to moderate pain

NSAIDs 之適應症(二)

Rheumatoid arhtritis(R.A):

    →下列除外:Etodolac, Ketorolac, Mefenamic acid

Osteoarthritis(O.A):

    →下列除外:Ketorolac, Mefenamic acid

Alkylosing spondylitis

            → Diclofenac, Indomethacin/SR,Napoxin

Primary dymenorrhea

            → Ibuprofen, Ketoprofen, Mefenamic acid, Napoxin

Tendinitis, Bursitis, Acute gout

            → Indomethacin/SR, Napoxin, Sulindac

Acute pain shoulder

            → Indomethacin/SR

Fever

            → Ibuprofen

Mild to moderate pain

COX-2 Inhibitors

Celecoxib(Celebrex)

            → 為第一個被 FDA 認證上市之 selective COX-2 inhibitor.

            → 口服約3小時達最高血中濃度

            → T1/2:11.2 hours

            → Indications:O.A,R,A

            → O,A:Adult Dosage:200mg/day.Qd or BID

            → R.A:Adult Dosage:100-200mg Bid

Rofecoxib(Vioxx)

            → 為第二個被 FDA 認證上市之 selective COX-2 inhibitor.

            → 口服約2-3小時達最高血中濃度

            → T1/2:17 hours

            → Indications:O.A,急性疼痛及經痛

            → O,A:Adult Dosage:12.5-25mg Qd

            → 急性疼痛及經痛:Loading dose:50mg, maitance dose:25mg Qd

Meloxicam(Mobic)

            Adult Dosage:7.5-15mg/day.Dosages over 15mg/day appear to lose COX-2 selectivity.

            Pharmacokinetics:B:89%, Css:5-6hr p.o,metabolised(up to 99%)in liver with t1/2 20hrs.

Nimesulide(Mesulid)

Gastrointesinal Adverse Reactions of NSAIDs

Dyspepesia(Etodolac 10%, Ketoprofen 11.5%, Ketorolac 12%, Nabumetone 13%)

Nausea (Ketorolac 12%, Tolmetin 11%)

Vomiting

Abdominal distress/ cramps/ pain(Ketorolac 13%, Nabumetone 12%, Sulindac 10%

Constipation, Ative gastrointestinal hemorrhage, Gastritis

Nephrotoxic Adverse Reactions of NSAIDs

Interstitial nephritis

Irreversible acute renal failure

Sodium chloride and water retention

Hyperkalemia

Hypertension

Pregnancy

Category B:

            Ketoprofen, Naproxen, Flurbiprofen, Diclofenac

Category C:

            Etodolac, Ketorolac, Mefenamic, Nabumetone, Oxaprozin, Tolmetin

Lactation:Excreted in breast milk

非類固醇抗發炎藥品服藥指示

            → 與食物或胃藥(制酸劑)併服

            → 大便變黑色,不正常出血或排尿困難等症狀出現時,請先停藥並連絡醫師或藥師

            → 服用 NSAIDs 類藥品期間不可飲酒

            → NSAIDs 類藥品在懷孕最後三個月均不可長期服用,因為 NSAIDs 會抑制 prostaglandin 之生合成而導致母親懷孕與生產時間延長並影響胎兒出生後之血肺循環    

Drug Interactions

NSAID Drug Interactions

Precipitant drug

Object drug*

Description

NSAIDs
Anticoagulants

Coadministration may prolong prothrombin trime (PT).Also consider the effects NSAIDs have on platelet function and gastric mucosa. Monitor PT and patients closely and instruct patients to watch for signs and symptoms of bieeding.

NSAIDs
ACE inhibitors

Antihypertensive effects of captopril may be blunted or completely abolished by indomethacin.

NSAIDs
Beta blockers

The antihypertensive effect of the beta blockers may be impaired. Sulindac and naproxen did not affect atenolol.

NSAIDs
Cyclosporine

Nephrotoxicity of both agents may be increased.

NSAIDs
Digoxin

Ibuprofen and indomethacin may increase digoxin serum levels.

NSAIDs
Dipyridamole

Indomethacin and dipyridamole coadministration may augment water retention.

NSAIDs
Hydantoins

Serum phenytoin leveis may be increased, resulting in an increase in pharmacologic and toxin effects of phenytoin.

NSAIDs
Lithium

Serum lithium levels may be increased; however,sulindac has no effect or may decrease lithium levels.

NASIDs
Loop diuretics

Effects of the loop diuretics may be decreased.

NSAIDs
Methotrexate

The risks of methotrexate toxicity(eg, stomatitis, bone marrow suppression, nephrotoxicity) maybe increased.

NSAIDs
Penicillamine

Indomethacin may increase the bioavailability of penicillamine.

NSAIDs
Sympathomimetics

Indomethacin and phenylpropanolamine coadministration may result in increased blood pressure.

NSAIDs
Thiazide diuretics

Decreased antihypertensive and diuretic action of thiazides may occur with concurrent indomethacin. Naproxen has also been implicated. Sulindac may enhance the effects of thiazides.

Cimetidine
NSAIDs

←→

NSAID plasma concentrations may be increased or decreased by cimetidine;some studies report no effect. Also, indomethacin and sulindac have increased ranitidine and cimetidine bioavailability.

Probenecid
NSAIDs

Probenecid may increase the concentrations and possibly the toxicity of the NSAIDs.

Salicylates
NSAIDs

Plasma concentrations of NSAIDs may be decreased by salicylates. Avoid concurrent use since it offers no therapeutic advantage and may significantly increase the incidence of GI effects. Use of salicylates resulted in decreased binding of ketorolac (twofold increase of free drug).

DMSO
Sulindac

DMSO may decrease the formation of the active metabolite of sulindac, possibly resulting in a decreased therapeutic effect. Also, topical DMSO with sulindac has resulted in serere peripheral neuropathy.

          *↑=Object drug increased   ↓=Object drug decreased  ←→Undetermined effect

非類固醇抗發炎用藥

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