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INTRODUCTION
These are weaker analgesis and non narcotic in nature i.e. do not depress CNS.
CLASSIFICATION
1.Nonselective cox inhibitorsSalicylates-aspirin,diflunisal Pyrazolone derivativesphenylbutazone, oxyphenbutazone
Indole derivativesindomethacin,sulindac
Oxicam derivativespiroxicam,tenoxicam
MECHANISM OF ACTION
Inhibits COX due to which there is decrease in synthesis of prostaglandin, thromboxane. Due to this there is analgesic, antipyretic, anti inflammatory action
ASPIRIN
It is acetylsalicylic acid.
PHARMACOLOGICAL ACTION
1.Analgesic action Relieves inflamation, tissue injury, integumental connective tissue
2.Antipyretic
decrease fever by sweating and cutaneous dilatation 3.Antiinflammatory Decrease pain, tenderness, swelling. Redness, leucocystic infilteration
5.Metabolic action
Decreases cell metabolism so decrease utilization of glucose and blood sugar therefore there is
decrease in liver glycogen 6.Respiratory action By periphral action it increases CO2 production And by central action increases sensitivity of respiratory center
7.Acid base balance Causes compensatory respiratory alkalosis 8.GIT Irritates mucosa due to which pain in epigastric region Stimulates CTZ which causes
Nausea, vomitting
9. CVS
PHARMACOKINETICS
absorb from stomach and small intestine alkalization of urine tend to increase elimination of aspirin freely crooses placenta
2. Hypersensitivity reaction- rashes, dermatitis, angiodema, asthma, rhinitis, urticaria, rarely anaphylactic shock
3. Acute salicylic poisoning- caused by anti inflammatory dose Causes rhinitis, vertigo, dizziness, head ache, impairment in hearing
INDICATION
Post MI and post stroke patient
As an analgesic in bodyache, joint pain, tooth ache, neuralgic pain, dysmennorhea As an antipyretic As an antiinflammatory in
CONTRAINDICATION
Hypersensitivity
Peptic ulcer
NIMESULIDE
Relatively weak inhibitor of PG synthesis
Used primarily for short long lasting painful inflamatory conditions like sport injuries, sinusitis, dental surgery, post operative pain and fever
Adverse effects are epigastralgia, heart burn, nausea, loose motions, rashes, pruritis, somnolence, dizziness.
PARACETAMOL
It is a deethylated active metabolite of phenacetin
ACTIONS
It raises pain threshold but has weak peripheral antiinflammatory component
PHARMACOKINETICS
Well absorbed orally
ADVERSE EFFECTS
It is well tolerated, nausea and rashes occur occasionally Analgesic nephropathy occurs after years of heavy dose
USES
Commonly use as an analgesic for
headache, musculoskeletal pain, dysmenorrhea Much safer than aspirin as does not cause any hypersensitivity reaction It is the first choice for osteoarthritis
Best drug to be used as antipyretic
Mechanism of toxicity
N-acetyl-p-benzoquinoneimine is a
highly reactive arylating minor metabolte of paracetamol which is detoxified by congugation with glutathione
this binds covalently to protiens in liver cells causing necrosis So paracetamol is not recommended in premature infants for fear of hepatotoxicity
Treatment
Early vomiting should be induced
DICLOFENAC
Potent analgesic antipyretic and antiinflammatory drug May also inhibit lipoxygenase Plasma half life is 2-3hours
INDOMETHACIN
As an analgesic mainly relieves tissue injury and inflammatory pain
Adverse effects- aggravate pre existing renal disease and induce mental confusion
Plasma half life is 2-3hours
SULINDAC
It is a prodrug and converted into active metabolite by gut flora and hepatic enzymes
PHENYLBUTAZONE
Uricosuric by virtue of a metabolite which inhibits renal tubular reabsorption of uric acid Plasma half life is 50-100hours Clinical use is limited due to bone marrow depression
OXYPHENBUTASONE
It is a biotransformation product of phenylbutazone Clinical use is limited because is causes bone marrow depression Plasma half life is 10-14hours
PIROXICAM
long acting potent antiinflammatory, antipyretic and analgesic drug It has enterohepatic circulation Plasma half life 45hours
KETOROLAC
Potent analgesic and modest antiinflammatory agent In post operative pain efficacy is equal to morphine Used for short term management of moderate pain
IBUPROFEN
Better tolerated than aspirin Drug of choice for rheumatoid arthritis Plasma half life is 2-3 hours
NAPROXEN
Better tolerated than aspirin Second choice after ibuprofen in the treatment of rheumatoid arthritis
KETOPROFEN
Inhibits both cycloxygenase and lipoxygenase
MEPHENAMIC ACID
Lower efficacy as analgesic, antipyretic and antinflammatory agent
NEFOPAM
Non opoid analgesic
It does not inhibit prostaglandin synthesis Useful to relieve traumatic and musculoskeletal pain
Side effects are blurred vision, tachycardia,urinary retention
TOPICAL NSAIDS
Preparations are being used for osteoarthritis, sprains, sports injuries, tenosinovitis, backache, and other forms of soft tissue rheumatism the drug would penetrate to the subjacent tissues attaining high concentrations in the affected
muscles or joint while maintaining low blood levels Topical NSAIDs preparations are slow taking~10 times longer time to attain peak concentration compared to oral dosing.
Better response have generally been obtained in short lasting musculo-skeletal pain.