NSAIDSNSAIDS

Algesia (pain) It is an ill defined, unpleasant sensation, usually evoked

by an external or internal noxious stimulus.

Analgesics

A drug that selectively relieves pain by acting in the CNS or on peripheral pain mechanisms, without significantly altering consciousness.

Analgesics are divided into two groups.

1. Narcotic (opioid) analgesics

2. Non-opioid analgesics

NON- STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)

• NSAIDS: non steroidal anti-inflammatory drugs• They have the important property of inhibiting

prostaglandins biosynthesis• Principal actions of NSAIDS are:

1. Analgesic action

2. Anti-inflammatory action

3. Antipyretic action

• Although there are many components to inflammation, only the prostaglandin component is substantially reduced by the action of an NSAIDS.

• The process of PG synthesis begins with arachidonic acid, this acid is converted by the enzyme cycloxygenase to synthesize different prostaglandins.

• NSAIDS drugs work by interfering with cycloxygenase pathway.

• There are two types of cycloxygenase denoted COX-1 and COX-2 .

Classification of NSAIDS:

A. Nonselective COX inhibitors1.Salicylates: Aspirin, Diflunasil2.Pyrazolone derivatives: Phenylbutazone,

Oxyphenbutazone3.Indole derivatives: Indomethacin4.Propionic acid derivatives: Ibuprofen, Naproxen,

Ketoprofen5.Anthranilic acid derivatives: Mephenamic acid6.Aryl-acetic acid derivatives: Diclofenac7.Oxicam derivatives: Piroxicam8.Pyrrolo-pyrrole derivatives: Ketorolac

B.Preferential COX-2 inhibitors• Nimesulide, Meloxicam, Nabumetone

C.Selective COX-2 inhibitors• Celecoxib, Rofecoxib, Valdecoxib

D.Analgesic-antipyretics with poor anti-inflammatory action

1.Paraaminophenol derivatives: Paracetamol (Acetaminophen)

2.Pyrazolone derivatives: Metamizol

3.Benzoxazocine derivatives: Nefopam

Common adverse effects of NSAIDS:

1. GIT• Gastric ulceration• Nausea • Vomiting

2. Hypersensitivity• Rashes• Rhinitis• Asthma

3. Liver• Liver damage

4. Kidney• Chronic intestinal nephritis• Renal tubular necrosis• Reversible acute renal failure

5. Blood• Thrombocytopenia• Decreased platelet aggregation• Impaired clotting

6. CVS

• Hypertension

• Congestive heart failure

7. CNS

• Headache

• Confusion

• Hallucinations

• Depression

• Tremor

ASPIRIN

(ACETYLSALICYLIC ACID)

• Source: natural from Willow bark,synthetic

• Chemical nature: weak organic acid

• Non-opioid analgesics

• Aspirin is the initial drug of choice for treating the majority of articular (arrthritis) and musculoskeletal disorders.

The principal effects of aspirin are:

1. Anti-inflammatory action

2. Analgesic action

3. Antipyretic action

4. Antiplatelet action

Pharmacokinetics of aspirin:

1. Routes of administration: oral, parenteral

2. Absorption: well absorbed from stomach

3. Distribution: highly protein bound

4. Metabolism: hydrolysis

5. Excretion: renal

Indication of aspirin:

1. To relieve mild to moderate pain:• Headache• Myalgia• Arthralgia• Osteoarrthritis

2. Acute rheumatic fever

3. Rheumatoid arrthritis

4. Arterial thromboembolism

5. Myocardial infarction

6. Treatment of migraine

Contraindication of aspirin:

1. Pre-existing ulceration in the GIT

2. Coagulation disorders

3. Hepatic and renal disease

4. Any hypersensitivity to aspirin

5. Pregnancy (last trimester)• Causes prolongation of labor• Chance of intra-cranial hemorrhage• Causes premature closure of ductus arteriosus

Adverse effects of aspirin:

1. Gastric and duodenal ulceration

2. Impaired clotting

3. Hepatic and renal damage

4. Deafness (overdose)

5. Allergic manifestations

PARACETAMOL

(ACETAMINOPHEN)

• Popular domestic antipyretic and analgesic drug• Normally a safe drug, acute overdose causes

hepatotoxicity• Useful in patients who should avoid aspirin

( because of gut intolerance, bleeding tendency, allergy)

Pharmacological actions of paracetamol1. Weak analgesic potency

2. Antipyretic

3. Little or no anti-inflammatory action

4. No anti-platelet action

Pharmacokinetics of paracetamol1. R/A: orally administered

2. Absorption: rapidly from the GIT

3. Metabolism: liver

4. Excretion: kidney

Indication of paracetamol

1. Febrile condition

2. Musculoskeletal pain

3. Headache

4. Toothache

5. Dysmenorrhoea

Adverse effects:

1. Skin rash, allergy

2. Chronic renal disease (long term use)

3. Hepatotoxicity in acute overdose

INDOMETHACIN

Pharmacological actions

1. Strong anti-inflammatory agent than aspirin

2. Antipyretic

3. Analgesic

4. Rapid absorption from the GIT

5. Safe in patient with gout

6. Does not modify the action of oral anticoagulants

Indications:

1. Rheumatoid arthritis

2. Ankylosing spondylitis

3. Osteoarthritis

4. Acute Gout

5. Treatment of patent ductus arteriosus in premature infant

6. Pericarditis

Contraindications

1. Pre-existing gastric ulcer

2. Pregnancy, nursing mother

3. Renal disorders

4. Psychiatric disorders

5. Epilepsy

6. Parkinsonism

Adverse effects of indomethacin:

1. GIT: nausea, vomiting, ulceration

2. CNS: dizziness, vertigo, confusion

3. Hypersensitivity: rash, itching

4. Hematological: neutropenia, thrombocytopenia

IBUPROFEN

Pharmacological actions of ibuprofen:1. Potent analgesic than aspirin or paracetamol2. Anti-inflammatory action3. Antiplatelet action

Indications:1. Rheumatoid arthritis2. Osteoarthritis(adverse effects, contraindication same as aspirin)Advantage over aspirin: less incidence of GIT ulceration

with low dose

DICLOFENAC

Pharmacological action of diclofenac:1. Potent anti-inflammatory action2. Potent analgesic action3. Potent antipyretic action

Pharmacokinetics of diclofenac:1. R/A: oral, injectable2. Absorption: rapid from the GIT3. Plasma half life: 12hrs4. Distribution: highly protein bound

Indications:

1. Rheumatoid arthritis

2. Osteoarhtritis

3. Ankylosing spondylitis

4. Post-operative patient

5. Dysmenorrhoea

(adverse effects, contraindication same as aspirin)