presentation about NSAIDs

1. NSAIDs
Prepared by
 Mohammed Tariq
 Rzgar Zrar
Supervised by
Dr.Rebin

2. Contents
Definition
Classification
Mechanism of action
Pharmacokinetics
Adverse effect
Contra indication

3. NSAIDs
It is a group of drug which usually used to treat the pain , fever ,and
inflammation
In some condition used to decrease blood clotting .

4. Non-steroidal anti-inflammatory drugs can be
classified by action (effect on the COX enzymes)

5. Non-steroidal anti-inflammatory drugs can be
classified by chemical structure as traditional

6. Mechanism of action of NSAIDs
Activation of
(phospholipase A2) to
degrade cell membrane
phospholipids
Formation of
arachidonic
acid
Cyclooxygenas
e pathway
Lipooxygina
se
pathway
Formation of
(PGs,prostacyclins
and thromboxane
)
Formation of
leukotrienes
Injury ,trauma ,
infection which
attacks cell
membrane

7. All NSAIDs exert analgesic , anti-inflammatory and
antipyretic action by inhibiting PG synthesis via
blocking COX

8. How prostaglandins produce pain ??????
Peripherally : PGs sensitize the nerve ending
to bradykinin and histamin
Centrally : PGs lower threshold for central
pain circuits

9. How NSAIDs act as analgesic ???
it block PGE2- mediated enhancement of
pain sensitization produced by
proinflamatory mediator such bradykinin

10. How fever will be made ????
Normally the hypothalamus is adjusted to a
setpoint . When the temperature is elevated
beyond level , hypothalamus activate heat losing
mechanisms like sweating and vasodilataion .
In fever the setpoint elevated
COX-2 enzyme which stimulate by IL-1 cause
increase PGE2 synthesis in hypothalamus
PGE2 has two mechanisms
1- increase heat production
2- shut down heat-losing mechanism

11. How NSAIDs make antipyretic effect ???
Antipyretic action works only in presence of a fever
because they impair the ability of pyrogens to raise
temperature set point of hypothalamus

12. How NSAIDs act as anti-inflammatory ??
Due to inhibition of PGE2 synthesis it cause
 Stabilization of lysosomal membrane
 Inhibition of complement system
 Inhibition phagocytosis
 inhibition Leukocyte accumulation
 Inhibit synthesis of mucopolysaccharide and histamin
 Antagonist of bradykinin

13. Is paracetamol NSAIDs ?????
It inhibits prostaglandin synthesis in the CNS ,this explain its
antipyretic and analgisic properties.
Acetaminophen has less effect on COX in peripheral tissue it
make acetaminophen has low anti-inflammatory effect .
Acetaminophen Is NOT NSAIDs

15. Aspirin as anticoagulant
Thrombin
Collagen
ADP
Activation of plat
Membrane
phospholipase
Libiration of
AA
AA
convert
to PGH2
by COX-
1
PGH2
Platelet
aggregation is
stimulated
Aspirin
TXA2 promote aggregation process
TXA2

16. Pharmacokinetics
 Absorption
-can absorbed through intact skin
-GIT
Solubility of salicylate preparation(dissolution of the
tablets is favored in at the higher PH
Presence of food
 distribution
 80% albumin
 Achieves significant concentration in saliva, milk ,spinal
synovial fluid,
 Peritoneal fluid, and in RBC
 High amount in liver , heart , muscle
 Small amount in brain

17. Pharmacokinetics
Metabolism
Aspirin salicylate
Salicylic acid
deacetaliation
 300 – 600mg dose:1th order kinetics
 1—2mg dose: zero order kinetics toxicity
cyclooxygenase

18. Excretion
Pharmacokinetics
salicylate
Glycine
conjugation
Glucuronic acid
conjugation
Oxidized to
gentisic acid

19. Adverse effect
Adverse Effects of NSAIDs At therapeutic
doses
1. Gastric Intolerance: The most common &
serious is gastritis, Gastric ulceration
or Exacerbation of Peptic ulcer
symptoms.
 Dyspepsia & Heart burn , Abdominal
Pain .
 Nausea & Vomiting, Hematemesis
 Fecal blood loss
 Iron deficiency Anemia

20. Adverse effect
2. Impaired hemostasis:
↓ Platelet Aggregation & Hypoprothrobinaemia:
3. Allergic / Hyper sensitivity
Reactions:
Skin rashes, Rhinitis, Bronchial asthma
4. Hyperuricemia:
Retention of uric acid at low doses<2.5 g/d ,
(although at high doses> 3.6g/d –increases uric acid
excretion).

21. 5. Decreased renal function:
Normally PGE2 & PGI2are responsible for
maintaining renal flow specially in presence of
circulating vasoconstrictors.
Inhibition of PGs synthesis may
produce:
 Retention of Sodium & water
 Edema
 Hyperkalemia.
 Interstitial nephritis with other
NSAIDs , but not Aspirin
Adverse effect

22. 6-Effect on respiration
7-Effect on CNS
8-in pregnancy & during lactation:
Avoid in pregnancy & lactation
Aspirin & salicylates cross placental
barrier & are secreted in breast milk
Adverse effect

23. Contra indication
Contraindications / Precautions:
 Peptic ulcer.
 Hemophilia.
 Aspirin hypersensitivity
 Children with a viral illness.
 Chronic liver disease.
 Aspirin should be stopped one week before elective
surgery.
 Avoid high doses in G-6-PD deficient.
 Avoid in pregnancy & lactation.