NSAIDBy: Mrs. Kalaivani Sathish, M. Pharm.
Assistant Professor – PIMSPanipat
NSAID• NSAIDs means.. “Non Steroidal Anti
Inflammatory Drugs”• What is inflammation ?...
– “Response of the body to injurious stimuli”
• Features of Inflammation1. Heat/fever 2. Swelling 3. Pain 4. Redness5. Loss of function
• NSAIDS addresses mainly FEVER, PAIN AND SWELLING.
• CLASSIFICATION OF NSAIDSA.Nonselective COX inhibitors (traditional
NSAIDs)1.Salicylic acid derivatives – Aspirin, Sodium
Salicylate.2.Para Amino Phenol Derivatives – Paracetamol3.Pyrazolone Derivatives – Phenyl butazone
4. Indole Acetic Acid Derivatives – Indomethacin
5. Aryl Acetic Acid Deivatives – Diclofenac, Aceclofenac
6. Propionic Acid Derivatives – Ibuprofen, Fenoprofen.
7. Anthranilic Acid – Mefenamic acid8. Oxicams – Piroxicam9. Alkanones - Nabumetone
B. Selective COX – 2 Inhibitors1. Celecoxib2. Nimesulide
MECHANISM OF ACTION• During Inflammation, Arachidonic acid
Liberated from Membrane Phospholipid is converted to prostaglandins (PG’s), Catalyzed by the enzymes Cyclo – Oxygenase (COX).
• These NSAID’s inhibits the PG’s synthesis by inhibiting the enzyme COX.
• There are 2 forms of COX (COX – 1 & COX – 2)
• COX – 1 is found in most of the normal cells. It is involved in maintaining Tissue Homeostasis.
• COX – 2 is induced in the inflammatory cells, by cytokinin and other mediators of inflammation.
• Most NSAID’s inhibits both COX – 1 and COX – 2.
Membrane Phospholipids Phospholipase
A2 Arachidonic Acid COX LOX
PG’S Leukotrines
SALICYLATES• They are salts of salicylic acids. e.g. Methyl
Salicylate.• Pharmacological Action• Analgesia – Aspirin is a good analgesics and
relieves pain of inflammatory origin.Aspirin inhibits PG’s synthesis and there by acts as analgesics. The pain is relieved w/o euphoria and hypnosis.
SALICYLATES• Antipyretic Action – In fever, salicylate
reduce the temp to normal level. In normal individual there is no change in temp.Aspirin inhibits PG’s synthesis in the hypothalamus and reset the thermostat at the normal level.
* Anti Inflammatory Action – PG’s present in inflammatory tissues are responsible for edema, erythema and Pain. Aspirin acts asanti inflamatory agents.
SALICYLATES• Respiration – Saliyclates increase
consumption of O2 by skeletal muscle, as a result there is an increased CO2 Production, this stimulates Respiration. In toxic doses the respiratory centre is depressed leading to respiratory failure.
• Acid – Base Balance – Salicylate normal dose ph becomes alkaline. In toxic dose ph decreases.
• Metabolic Effect – it enhances the cellular metabolism as a result more O2 is used and More Co2 is produced.
• GIT – Aspirin is a gastric irritant, it produce epigastric distress, nausea and vomiting.
• CVS – in normal dose CVS effect are seen. Toxic dose it depresses the circulation
• Immunological Effect – in higher dose salicylate suppress the several antigen – antibody reaction and antibody production.
• Uric Acid Excretion – Aspirin increases the plasma urate level by urate retention.
• Blood – Aspirin interferes with platelet aggregation and prolongs the bleeding time.
• Local Effects – Salicylates when applied locally, it is a keratolytic. (A substance that promotes the softening and peeling of epidermis). It also has mild antiseptic and fungistatic property.
PHARMAKOKINETICS Absorption (Stomach & Small Intestine)
Bounds to Plasma Protein
Metabolized in Liver
Excretion by urine
ADVERSE EFFECTS• GIT – Nausea, Vomiting, Peptic Ulcer, blood loss in
stool.• CNS – Headache, Confusion, Allergic Reactions,
Rashes, Photosensitivity, Urticaria• Respiratory System – Bronchial Asthma• Hemolysis, Nephrotoxicity, Hepatotoxicity• Reye’s syndrome – A rare condition in children
which causes swelling in brain and Liver. • Pregnancy and Labour – Delays onset of labour,
Portal hypertension, increase Post Partum Bleeding
• Salicylism – Higher dose given for a long time in the treatment of Rheumatoid arthritis may cause chronic salicylate intoxication.• Treatment : Symptoms & Signs–Dehydration, Hyperpyrexia, GI
Irritation, Vomiting, Tremor, Delirium, Convulsion, Coma and Death due to respiratory failure and CV Collapse.
• Treatment includes– Gastric Lavage to eliminate unabsorbed drugs– IV Fluids to correct acid base imbalance and
dehydration– Cold water sponge to bring down elevated body
temp.– Blood transfusion and Vitamin – K are
administerd for haemorrhagic complications– IV Fluids should contain (Na, K, HCO3 & Glucose).– Blood ph should be monitored.– In severe cases administer diuretics.
PRECAUTIONS & CONTRA INDICATIONS
• Peptic ulcer, Liver diseases, Viral fever in children's are contra Indicate the use of aspirin and salicilate.
• During Pregnancy aspirin should be avoided.
• NSAID should be stopped one week before surgery due to anti platelet effect.
USES• Analgesics – Headache, Backache, Myalgia,
Dysmennorhea, arthralgia.• Fever – used as antipyretic• Inflammation – Effective in arthritis and
fibromyositis • Acute Rheumatic Fever – Aspirin is used very
effectively.• Rheumatoid Arthritis – Aspirin release pain, reduces
swelling and redness of joints in RA.• Osteoarthritis • Post Myocardial Infraction & Post Stroke
USES• Inflammatory Bowel Disease• 0ther Uses • To Delay labour,• Prevention of colon cancer.• Eclampsia• Locally used as Keratolytic and Fungistatic and
Mild antiseptic
PARAMINO PHENOL DERIVATIVES
• Paracetamol• it has analgesics, good anti pyretic and weak anti
inflammatory properties.• Adverse Effects – Nausea, Rashes, when large dose
taken acute paracetamol poisoning occurs.• Symptoms – Nausea, Vomiting, Anorexia,
abdominal pain during first 24 Hrs, Nephrotoxicity and cause severe Hepatic damage.
• Treatment for acute paracetamol poisoning:– Gastric Lavage, Activated charcoal prevents
further absorption.– Anti dote is N – Acetyl cysteine is more
effective, when given early.Uses :Analgesics in painful condition like, tooth ache,
headache and myalgia.Antipyretic
Pyrazolone Derivatives – Phenyl butazone
• Has good anti inflammatory activity.• It is more potent, but has poor analgesic
and anti pyretic effect.• It is a uricosuric agent.
PHARMACOKINETICS• Oral absorption (Complete)
98 % bound to plasma protein
Metabolized in liver
• Excreted in Kidney
• Dose : 100 – 200 mg Bd.• Adverse Effects: it is more toxic than aspirin.• Nausea, Vomiting, Epigastric Pain,
Dyspepsia, Peptic ulcer and Diarrhoea. Anemia etc.
• Uses: Rheumatoid Arthritis, Ankylosing spondolytis. Osteo arthritis, Gout and other musculo skeletal disorders.
Indole Acetic Acid Derivatives – Indomethacin
• It is a potent anti inflammatory agent, anti pyretic and good analgesic.
• It is well absorbed, 90 % bound to plasma protein.• Dose : 25 to 50 mg Bd, tds.• Adverse Effects: Nausea, Vomiting, GI Bleeding and
Diarrhoea and peptic ulcer.• CNS Effect: Headache, Ataxia, Confusion, Depression
and psychosis, Hypersensitivity etc. • Uses: Rheumatoid arthritis, Gout, Ankylosing
spondolyits etc.
Aryl Acetic Acid Deivatives – Diclofenac, Aceclofenac
• It is an analgesic and anti pyretic and anti inflammatory agent. With mild adverse side effects.
• Uses: Rheumatoid arthritis, Osteoarthritis, Musculo Skeletal Pain, in eye to reduce occular inflammation.
• Dose: 50 mg bd or tds
Propionic Acid Derivatives – Ibuprofen
• It is better tolerated than aspirin. It has an analgesic, anti pyretic and anti inflammatory action.
PHARMACOKINETICS• Oral absorption (Complete)
90 % bound to plasma protein
Crosses BBB
Metabolized in Liver
Excreted in Kidney & Bile
Anthranilic Acid – Fenamates• It has an analgesic, anti pyretic and anti
inflammatory action.less efficay and more toxic.
• Adverse Effects – Similar to Aspirin.• Uses – Analgesics in Myalgia. Mefenamic
acid is used in dysmenorrhoea.• Dose – 250 – 500 Mg tds.
Oxicams – Piroxicam
• It is long acting good analgesic, anti pyretic and anti inflammatory action.
• Dose: 20 mg.• Uses: Rheumatoid arthritis, Osteoarthritis.
Ankylosing spondolytis. Musculo Skeletal Pain and Post Operative pain.
Alkanones - Nabumetone
• good analgesic, anti pyretic and anti inflammatory action. It is good for osteoarthritis.
Selective COX – 2 InhibitorsCelecoxib
• It can cause HT and edema in CV Problem patient
• It is used for post operative pain and dysmennorhea and osteoarthritis and rheumatoid arthrits.
• Dose – 100 – 200 Mg.
Nursing Implications
• BP Checked regularly• Regulate Sodium intake• Body weight is checked everyday