NSAID DRUGS

1. DICLOFENAC
Dr.ZIKRULLAH

2. Diclofenac is non- steriodal anti-
inflammatory drug (NSAID).
It is an over the counter available
drug, prescribed for its anti-
inflammtory and analgesic
properties.

3. HISTORY
Diclofenac was first synthesized by the
pharmaceutical company called NOVARTIS
in 1973.
For clinical use it was first launched in
United Kingdom in the year 1979.

4. CHEMICAL STRUCTURE
Its chemical name is 2-(2,6-
dichloranilino) phenylacetic acid.
It is either supplied as a Sodium or
Potassium salt.
Molecular mass – 296.198g/mol

5. C14H11CL2NO2

6. PHARMACOKINETICS
 Protein binding - around 99%
 Half life - 1.2-2 hrs (around 35% of the drug
enter the entero-hepatic circulation).
 Metabolism - chiefly hepatic, no active
metabolites are formed.
 Excretion - Biliary. Only 1% is excreted in the
urine.

7. MECHANISM OF ACTION
Inhibition of prostaglandin synthesis by the
inhibition of Cyclooxegenase enzyme.
(COX).
Diclofenac had low to moderate preference
to block the COX2 isoenzyme.

8. OTHER PROPOSED MECHANISM
Bacteriostatic activity by inhibition of DNA
sunthesis.
Inhibiton of the Lipoxygenase pathway and
phospholipase A2 thus reducing the
formation of pro-inflammatory autocoids
called Leucotrienes.
Blockade of voltage gate gated Sodium
channels.

9. Blockade of Acid sensing ion channels
(ASIC’s)
Positive allosteric modulation of KCNQ
and BK potassium channels.

10. The action of one single dose is much
longer (6 to 8 hours) than the very
short half-life that the drug
indicates.This could be partly because
it persists for over 11 hours in synovial
fluids.

11. FORMULATIONS
 Diclofenac is available in following
preparations:
 Oral
 Intravenous and Intramuscular
 Transdermal
 Rectal
 Topical

12. Diclofenac is available in stomach acid
resistant formulations (25 and 50 mg), fast-
disintegrating oral formulations (25 and
50 mg),
 Powder for oral solution (50 mg),
Slow- and controlled-release forms (75,
100 or 150 mg).

13. Injectable forms (50 and 75 mg). to
given deep intramuscularly in the
gluteal region, or as intravenous
infusion.
Topical lotion formulation of 1.5- 3 %
w/w diclofenac sodium.
Rectal suppositories (50 and 100 mg).

14. COMMONLY AVAILABLE TRADE NAMES -
VOVERAN
DICLAC
DYNAPAR
DYFENE
OFLAM
ORTOFEN
NU PATCH

15. DOSES
For pain due to musculoskeletal disorders
- 50 mg 2-3 times a day orally or 75 km
twice a day orally.
Adult dose for post operative and post
traumatic pain relief – initial 100 mg orally
once a day followed by 50 mg once daily.
Adult Parenteral dose – 1-1.5 mg/kg

16. Pediatric doses
2-3mg/kg/day orally divided in 2-4 doses
over 24 hrs .
Maximum dose not to exceed 200mg.
Pediatric parenteral dose - 0.3-0.5
mg/kg

17. CLINICAL USES
Inflammatory disorders:-
Musculoskeletal complaints arthritis,
rheumatoid arthritis, polymyositis,
dermatomyositis, osteoarthritis, dental pain,
TMJ, spondylarthritis, ankylosing
spondylitis, gout attacks.
 Pain management in cases of kidney
stones and gallstones.

18. Diclofenac is used commonly to treat
mild to moderate post-operative or
post-traumatic pain, in particular when
inflammation is also present, and is
effective against menstrual pain and
endometriosis.

19. An external, gel-based formulation
containing 3% of diclofenac is available for
the treatment of facial Actinic keratosis
caused by over-exposure to sunlight.
Diclofenac Eye-drops to treat acute and
chronic non-bacterial inflammations of the
anterior part of the eyes.

20. INVESTGATIONAL USES
Diclofenac is often used to treat chronic
pain associated with cancer, in particular if
inflammation is also present (Step I of the
World Health Organization (WHO)
Scheme for treatment of chronic pain).
Combinations with psychoactive drugs
such as chlorprothixene and/or
amitriptyline have also been investigated
and found useful in a number of cancer
patients

21. Fever due to malignant
lymphogranulomatosis (Hodgkin's
lymphoma) often responds to diclofenac.
Diclofenac has been found to be effective
against all strains of multi drug resistant E.
coli, with a MIC of 25 micrograms/mL.
Therefore, it may be suggested that
diclofenac has the capacity to treat
uncomplicated urinary tract infections (UTI)
caused by E. coli

22. ADVERSE EFFECTS
Diclofenac is among the better tolerated
NSAIDs.
Though 20% of patients on long-term
treatment experience side-effects.
 2% have to discontinue the drug, mostly
due to gastrointestinal complaints.

23. Increased risk of cardiovascular morbidity
and mortality due to increased incidence of
myocardial infarction.
Gastritis, gastric ulceration , and GI
haemorrhage.
Hepatotoxicity and hepatitis.
Nephrotoxicity

24. Bone marrow depression is noted
infrequently (leukopenia, agranulocytosis,
thrombopenia with/without purpura,
aplastic anemia). These conditions may be
life-threatening and/or irreversible, if
detected too late. All patients should be
monitored closely.
 Diclofenac is a weak and reversible
inhibitor of thrombocytic aggregation
needed for normal coagulation.

25. Induces warm antibody hemolytic
anemia by inducing antibodies to Rh
antigens, ibuprofen also does this.
Diclofenac may disrupt the normal
menstrual cycle.

26. CONTRAINDICATIONS
Hypersensitivity against diclofenac
History of allergic reactions
(bronchospasm, shock, rhinitis, urticaria)
following the use of aspirin or another
NSAID
Third-trimester pregnancy
Active stomach and/or duodenal ulceration
or gastrointestinal bleeding
Inflammatory intestinal disorders such as
Crohn's disease or ulcerative colitis.

27. Severe insufficiency of the heart (NYHA
III/IV)
Recently, a warning has been issued by
the FDA not to use for the treatment of
patients recovering from heart surgery
Severe liver insufficiency (Child-Pugh
Class C)
Severe renal insufficiency (creatinine
clearance <30 ml/min)

28. Caution in patients with preexisting hepatic
porphyria, as diclofenac may trigger attacks
Caution in patients with severe, active
bleeding such as cerebral hemorrhage.
NSAIDs in general should be avoided
during dengue fever, as it induces (often
severe) capillary leakage and subsequent
heart failure.

29. PREGNANCY AND LACTATION
Diclefenac is a category C drug in the
first and second trimester and a
category D drug in the third trimester.
Diclofenac is secreted in human milk,
however its effect on new born babies
has not been studied.

30. DRUG INTERACTIONS
Diclofenac, like other NSAIDs is
associated with several suspected or
probable interactions that affect the action
of other drugs
Diclofenac may increase the blood levels
of lithium by reducing the excretion of
lithium by the kidneys. Increased levels of
lithium may lead to lithium toxicity.

31. When diclofenac is used in combination
with aminoglycoside antibiotics for
example, gentamicin the blood levels of
the aminoglycoside may increase,
presumably because the elimination of
aminoglycosides from the body is reduced.
This may lead to more aminoglycoside-
related side effects like nephrotoxicity and
deafness.

32. Individuals taking oral blood thinners or
anticoagulants eg, warfarin should avoid
diclofenac as it may predispose to
excessive bleeding.
Diclofenac decrease the excretion of
Methotrexate from the body and may
precipitate methotrexate toxicity.

33. Diclofenac may reduce the blood
pressure lowering effects of blood
pressure medications. This may occur
because prostaglandins play a role in
the regulation of blood pressure.

34. ECOLOGICAL EFFECTS
 Use of diclofenac in animals has been reported
to have led to a sharp decline in the vulture
population in the Indian subcontinent. The
mechanism is, it is presumed, renal failure, a
known side-effect of diclofenac. Vultures eat the
carcasses of livestock that have been
administered veterinary diclofenac, and are
poisoned by the accumulated chemical.
 At a meeting of the National Wildlife Board in
March 2005, the Government of India
announced that it intended to phase out the
veterinary use of diclofenac.

35. THANKS.