NSAIDS

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 inhibitors
1.Salicylates: Aspirin, Diflunasil
2.Pyrazolone derivatives: Phenylbutazone,
Oxyphenbutazone
3.Indole derivatives: Indomethacin
4.Propionic acid derivatives: Ibuprofen, Naproxen,
Ketoprofen
5.Anthranilic acid derivatives: Mephenamic acid
6.Aryl-acetic acid derivatives: Diclofenac
7.Oxicam derivatives: Piroxicam
8.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 paracetamol
1. Weak analgesic potency
2. Antipyretic
3. Little or no anti-inflammatory action
4. No anti-platelet action

Pharmacokinetics of paracetamol
1. 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 paracetamol
2. Anti-inflammatory action
3. Antiplatelet action

Indications:
1. Rheumatoid arthritis
2. 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 action
2. Potent analgesic action
3. Potent antipyretic action

Pharmacokinetics of diclofenac:
1. R/A: oral, injectable
2. Absorption: rapid from the GIT
3. Plasma half life: 12hrs
4. 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)