PPT

on

Non steroidal anti- inflammatory drugs.

NSAIDS
by Dr.Saloni Gupta ,Dr. Prashant ,MD

drprashantw@gmail.com
www.pharmacology4students.com

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

Proionic acid derivativesibuprofen,naproxen,ketoprofen

Anthranilic acid derivativesmephenamic acid Aryl acetic acid derivativesdiclofenac

Oxicam derivativespiroxicam,tenoxicam

Pyrrolo pyrrole derivativesketorolac 2.Prefential COX-2 inhibitorsnimesulide,meloxicam, nabumetone

3.Selective COX-2 inhibitorscelecoxib, rofecoxib, valdecoxib

4.Analgesic antipyretic with poor antiinflammatory actionParaaminophenol derivativesparacetamol

Pyrazolone derivatives-metamizol, propiphenzone Benzoxazocine derivatives- nefopam

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.

it is one of the oldest analgesic.

it is converted into salicylic acid in our body

PHARMACOLOGICAL ACTION
1.Analgesic action Relieves inflamation, tissue injury, integumental connective tissue

No effect on visceral pain, ishaemic pain

2.Antipyretic
decrease fever by sweating and cutaneous dilatation 3.Antiinflammatory Decrease pain, tenderness, swelling. Redness, leucocystic infilteration

4.Antiplatlet action Inhibits platlet aggregation and decreases thromboxaneA2 synthesis

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

Increases CO2 production

10. Urate excretion It is not suitable in chronic gout

PHARMACOKINETICS
absorb from stomach and small intestine alkalization of urine tend to increase elimination of aspirin freely crooses placenta

t1\2 = 15-20min but taken together with salicylic acid so t1\2=3-5hrs

ADVERSE DRUG REACTION

1.GIT- nausea, vomiting, epidistress, gastric mucosal damage, gastritis, peptic ulceration, occluted blood stool

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

Blurring of vision, mental confusion, exitement, electrolyte imbalance, sound in ear

4.Ryes syndrome- occurs in children Causes hepatic encephalopathy during viral influenza

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

Rheumatic arthritis, osteoarthritis, acute rheumatic fever

Potential use in patent ductus arteriosus. Premature labour, pregnancy induce HTN

CONTRAINDICATION
Hypersensitivity
Peptic ulcer

Chronic liver disease

During normal pregnancy at full time

Avoided 1 week before surgery

Patient having bleeding disorder

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

Poor inhibitor of PG synthesis

PHARMACOKINETICS
Well absorbed orally

Excreted rapidly in urine

Plasma t1\2 is 2-3 hours Effect of oral dose last for 3-5hrs

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

ACUTE PARACETAMOL POISONING

Occurs specially in small children Early manifestations are nausea, vomiting, abdominal pain and liver tenderness, jaundice starts after 2 days

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

Gastric lavage should be done

Activated charcoal is given orally Nacetylcysteine should be infused i.v. over 15min

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

Safe in presence of renal disease

Long acting drug

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

Plasma half life is 12-14hours

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.