1. Non-steroidal anti-inflammatory drugs
NSAIDs

2. OBJECTIVES At the end of this work you should : Define NSAIDs
Describe the classification of this group of drugs
Describe the general mechanism of actions
Define the following terms :
Analgesic
Antipyretics
Anti-inflammatory
Anti-platelet
Describe the general pharmacological actions
Describe the general therapeutic uses
Describe the general adverse effects
Describe the general contraindications
Know some examples of each group of NSAIDs
Know the difference between the selective & non-selective NSAIDs

3. NSAIDs & Terms Non-steroidal anti-inflammatory drugs ( NSAIDs ):
are group of drugs that have analgesic , antipyretic , anti-platelet & anti-inflammatory effects.
ANALGESIC:
Drug that relieve pain.
ANTIPYRETIC
Drug that lower the elevated body temperature to normal.
Anti-inflammatory
Refers to the property of a substance or treatment that reduces inflammation or swelling.
Anti-platelet
Is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation.

4. Classification of NSAIDs
Non-Selective COXs Inhibitor:
Group of drugs that sharing the capacity to induce the following pharmacological actions:
Analgesic
Antipyretic
Anti-inflammatory
Anti-platelet
Effect on the kidney function
Selective COX2 Inhibitor.

5. MECHANISM OF ACTION OF NSAIDS
Phospholipid From Cell Membrane
Phospholipase
Arachidonic acid
CycloOxygenase 1
CycloOxygenase 2
Prostaglandin
Thromboxane
Prostaglandin
Prostacyclin
Phospholipase can be inhibit by Corticosteroid.
CycloOxygenase can be inhibit by NSAIDs.
CycloOxygenase can be inhibit by NSAIDs and COX-2 inhibitor.

6. Preferential (Meloxicam)
COX inhibitors
NSAIDs
NonSelective (NS)
COX-1/COX-2
COX-2
inhibitors
COX-3
Diclofenac
Selective (Coxibs)
Preferential (Meloxicam)
Paracetamol
Reversible inhibition of both COX-1 & COX-2 enzymes
EXCEPT Aspirin is the only NS-NSAID that
Irreversible inhibitor of both enzymes
Resulting in inhibition of the synthesis of prostaglandins & thromboxane A2.

7. Pharmacokinetics Oral administration
Most NSAIDs are weak acid (absorbed well in stomach and intestinal mucosa)
95% bound to plasma-protein (high bioavailability)
Most metabolized in liver (oxidation & conjugation)

8. Pharmacodynamics Effects
1-ANALGESIC
Bradykinin
Histamine
Factors
Nerve ending of pain
Prostaglandin
PgE2 , PgF2
2-Antiinflammatory
Bradykinin
Histamine
5-HT
Factors
Nerve ending of pain
Prostaglandin
PgE2 , PgF2
NSAIDs will block Prostaglandin production.
It happen in Peripheral tissue.

9. Pharmacodynamics Effects
3-ANTIPYRETIC
Pyrogen
Prostaglandins
PGE2
Thermoregulatory center
ꜛIncrease set point
ꜛIncrease heat production and ꜜDecrease heat dissipation
Fever
NSAIDs will block Prostaglandin production.
It happen in Central nervous system.

10. THERAPEUTIC USES SHARED BY NS-NSAIDs
Antipyretic.
Analgesic:
Headache, Migraine.
Dental pain.
Dysmenorrhea.
Common cold.
Anti-inflammatory & Antirheumatic:
Rheumatoid arthritis / myositis or other forms of inflammatory conditions.

11. Adverse effects shared by NS-NSAIDs
GIT upsets ( nausea, vomiting).
GIT bleeding & ulceration.
Bleeding.
Allergic reaction.
Inhibition of uterine contraction.
Salt & water retention.
Effect on the kidney
Inhibition of both COX-1& COX-2 enzymes (mainly COX-2), inhibit synthesis of PGE2 & PGI2 that are responsible for maintaining renal blood flow.
Salt & water retention & edema of lower limbs.
Hyperkalemia.
Interstitial nephritis.

12. Aspirin Clinical uses of Aspirin : Adverse Effects Related to:
Acute rheumatic fever (Antioxidant effect) .
Low doses used as cardio protective to reduce the incidence of myocardial infarction & unstable angina.
Large doses (5gm) used to treat chronic gouty arthritis.
Chronic use of small doses of aspirin used as protective to reduce the incidence of colorectal cancer (Antioxidant effect).
Adverse Effects Related to:
Therapeutic Doses Of Aspirin:
Aspirin asthma.
Acute Gouty arthritis.
Reye's syndrome.
Chronic use:
Salicylism (ringing of ear(tinnitus),vertigo).
OVER DOSE
Hyperthermia
Metabolic acidosis
Respiratory depression
Coma

13. Aspirin Contraindications: Peptic ulcer. Pregnancy.
Hemophilic patients.
Patients taking anticoagulants.
Children with viral infections.
Gout (small doses).

14. Paracetamol Is commonly used as analgesic And antipyretic.
Conditions in which paracetamol is a suitable drug:
Peptic or gastric ulcers.
Bleeding tendency.
Allergy to aspirin.
Viral infections especially in children .
During Pregnancy.
Adverse Effects (due to its active metabolite):
Therapeutic doses:
↑Increase liver enzymes.
Large doses :
causes kidney failure.
Over dose:
Acute toxicity: liver failure ( cause of death)
Treatment Of acute toxicity
by : N-acetylcysteine ( SH-donor) to neutralize the toxic metabolite

15. DICLOFENAC (accumulate in synovial fluid)
Clinical uses
Preparations
Rheumatoid arthritis , osteoarthritis & ankylosing spondylitis.
Acute gouty arthritis
Analgesic
Antipyretic
Locally to prevent post-opthalmic inflammation
Oral.
Oral with misoprostol to decrease upper gastrointestinal ulceration.
0.1% opthalmic ( eye drops) to decrease postoperative opthalmic inflammation.
A topical gel 3% .
Rectal suppository.
Oral mouth wash.
Intramuscular preparations.

16. Selective COX-2 inhibitors
General advantages
General adverse effects
CONTRAINDICATIONS
GENERAL CLINICAL USES
Potent anti-inflammatory.
Antipyretic & analgesic.
Lower incidence of gastric upset
(recommneded in patients with a history of gastric ulceration).
No effect on platelet aggregation.
( Have no inhibitory effect on (COX-1) so can be given in hemophilic patients).
Renal toxicity.
Dyspepsia & heartburn.
Allergy.
Increase incidence of myocardial infarction.
( lack cardioprotective effect of NS-NSAIDs as they have no effect on COX-1 enzyme)
In a patient with a history of :
Renal impairment
Myocardial infarction
Commonly used as antinflammatory drugs
Rheumatoid arthritis
Osteoarthritis
Acute gouty arthritis
Acute musculoskeletal pain
Ankylosing spondylitis
Dysmenorrhea

17. Example: Celecoxib Example: Celecoxib Half-life 11 hours (twice/day).
Food decrease its absorption.
Highly bound to plasma proteins.
Clinical uses & Adverse effects:
Discussed before with general uses and general adverse effects of selective COX-2 inhibitors.

18. Summary
NSAIDs are group of drugs that have analgesic, antipyretic, anti-platelet & anti-inflammatory effects.
They are classified according to their action on COX-enzymes into non-selective that inhibit both COX-1 & COX-2 & selective that inhibit only COX-2 enzymes.
They are sharing in common therapeutic uses as analgesic to relief mild to moderate pain not visceral pain , reducing high body temperature, preventing clot formation , so aspirin can be used as prophylaxis in ischemic heart disease.
As anti-inflammatory in rheumatic , rheumatoid arthritis, desmenrrhea and other inflammatory conditions including muscles or bones.
The common adverse effects includes :
gastric upset ( nausea, vomiting ,gastric ulceration or bleeding).
Allergy.
Edema.
They are contraindicated mainly in patients with peptic ulcer , bleeding tendency or in pregnancy .
Selective COX-2 inhibitors as celecoxib are potent anti-inflammatory & analgesic ,but have no anti-platelet effect & less gastric upset.
They can be used in patients with gastric ulcer , haemophilia .
Their common adverse is mainly on kidney & cardiovascular system.

19. THANK YOU Done By: Fahad Alfahad Mohammed Almozini Quiz