ANTI-INFLAMMATORY AGENTS

ANTI-INFLAMMATORY AGENTS

ADAPTED FROM MATERIALS ORIGINALLY PREPARED BY AND USED WITH PERMISSION OF

Ray Colucci, RN MSN

Anti-Inflammatory Agents

Non-Steroidal Anti-inflammatory Drugs [ NSAIDs ]

Quick FactsNSAIDs

One of most frequently prescribed drug categories

> 70 million prescriptions / year

represent more than 5% of all prescriptions

> 70 different agents; 20 are commonly used

Use of Plants Containing Salicylates

common for > 1,000 years

North American Indians willow bark juice [antipyretic]

South African Hottentots similar mixture as an [anti-rheumatic]

Early Greek & Roman physicians willow & poplar [medicinal compounds]

gout / fever / sciatica / earaches

NSAIDs

Most common & first drug:

acetylsalicylic acid

– ASA

– aspirin

The Success of Aspirin

1899 economical procedure for manufacturing synthetic salicylic acid

rapidly became most widely used drug in the world

antipyretic, analgesic, antiinflammatory, & anti-rheumatic

Toxicity of Aspirin aspirin’s wide spread use produced

evidence of its major toxicologic potential gastrointestinal intolerance

bleeding

renal impairment

tinnitus, hearing loss– lead to development of NSAIDs

Specific NSAIDsSix structurally related groups:

acetic acids [6] carboxylic acids [6] propionic acids 7] enolic acids [2] fenamic acids [2] nonacidic compounds [1]

Acetic Acid NSAIDs

Diclofenac sodium [Voltaren]

Diclofenac potassium [Cataflam]

Etodolac [Lodine]

Indomethacin [Indocin]

Sulindac [Clinoril]

Tolmetin [Tolectin]

Carboxylic AcidsNSAIDs

Acetylated Aspirin [many]

Magnesium choline salicylate[Trilisate]

Diflunisal [Dolobid]

Nonacetylated Salicylamide [many]

Salsalate [Disalcid]

Sodium salicylate [many]

Other NSAIDs

Enolic AcidsPhenybutazone [Butazolidin]Piroxicam [Feldene]

Fenamic AcidsMeclofenamic Acid [Meclomen]Mefenamic Acid [Ponstel]

Nonacidic CompoundsNabumetone [Relafen]

Propionic Acid NSAIDs

Fenoprofen [Nalfon]

Flurbiprofen [Ansaid]

Ibuprofen [Motrin, others]

Ketoprofen [Orudis]

Ketorolac [Toradol]

Naproxen [Naprosyn]

Oxaprozin [DayPro]

MOA of NSAIDsArachidonic Acid Pathway

. Phospholipids

Arachidonic AcidPhospholipase

Prostaglandin Pathway Leukotriene Pathway

Prostacyclin Synthetase

Thromboxane Synthetase

Leukotrienes (A-E)

Prostacyclin

[PGI2]

Thromboxane[TXA2]

vasoconstrictionbronchosconstriction+vascular permeabilityInflammation[platelets]

+PLT aggregationvasoconstriction

[bv wall]-PLT aggregationvasodilationInflammation

cyclooxygenase lipooxygenase

NSAIDs

Treating Headaches & Pain [analgesics]

PROSTAGLANDINS cause HA by dilating

blood vessels in the brain

PROSTAGLANDINS sensitize one to pain by

sensitizing nerve endings to painful stimuli

NSAIDs blocks the bad effects of prostaglandins

NSAIDs

Treating Headaches & Pain [analgesics]

PROSTAGLANDINS cause HA by dilating

blood vessels in the brain

PROSTAGLANDINS sensitize one to pain by

sensitizing nerve endings to painful stimuli

NSAIDs blocks the bad effects of prostaglandins

NSAIDsRelief Inflammation [Anti-inflammatory]

inflammatory response mediated by host of endogenous compounds:

proteins of complement system histamine serotonin bradykinin leukotrienes prostaglandins

NSAIDsRelief Inflammation [Antiinflammatory]

NSAIDs relief inflammation by

inhibiting either

– the leukotriene pathway,

– the prostaglandin pathway,

– or both

NSAIDs: Indications

gout various bone, joint, and muscle pain osteoarthritis [OA] rheumatoid arthritis [RA] juvenile rheumatoid arthritis dysmenorrhea

NSAIDsPrimary Therapeutic Effects

Summary:

analgesic [mild to moderate]

anti-gout

anti-inflammatory

antipyretic

relief of vascular headaches

platelet inhibition

GOUT

Metabolic disease affecting mostly men which involves a defect in purine metabolism leading to an increase in uric acid which crystallizes in the small joints causing pain– purines are found highly concentrated in

sardines, venison, shell fish, organ meats,

Anti-gout Drugs

Colchicine– inhibits leukocyte activity (part of

inflammation) in joint synovial fluid– can stop an acute attack- usually after a

high purine meal.– Needs to be used in conjunction with

another anti-gout med which inhibits uric acid synthesis or promotes uric acid excretion

Anti-gout Meds

Allopurinol (zyloprim)– inhibits the formation of uric acid

Probenecid (benemid)– promotes the excretion of uric acid at the renal

tubule– inhibits the secretion of penicillin, OHAs, ASA,

and rifampin– Patients must increase fluids while on these

meds

Specific Agents

salicylates

more potent effects on platelet aggregation & thermal regulatory center in brain

more common for tx of fever & arterial and possibly venous thrombosis

NSAIDsSide Effects

Gastrointestinal

dyspepsia, heartburn, epigastric distress

GI bleeding mucosal lesions erosions or ulcerations

misoprostol (cytotec)

NSAIDsSide Effects

Renal

reductions in creatinine clearance

acute tubular necrosis [renal failure]

NSAIDsSide Effects

cardiovascular

moderate to severe

non-cardiogenic pulmonary edema– Fluid retention