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