Acenofenac and acetaminophen( paracetamol) role as N.S.I.D in the treatment of pain and Inflammation with pharmacology and indication, adverse effects and contraindications

1. Pain and inflammation have been classically treated by NSAIDs.
The choice of an NSAID requires a balance of efficacy, cost-
effectiveness, safety, and numerous other factors. At present
there is no best NSAIDS for all patients. Aceclofenac is a novel
NSAIDS with multifactorial mechanism of action, resulting in
effective anti- inflammatory action with a reduced side-effect
profile. Acetaminophen is NSAID with both antipyretic and
analgesic action and has been in use for a long time.
Both these drugs compliment each other resulting in effective
analgesia with an antipyretic action.
PHARMACOLOGY
Aceclofenac:

2. Aceclofenac is a novel NSAID of the phenylacetic acid class (2,6-
dicholorophenyl amino phenyl acetic acid) which acts
specifically the inflammatory sites and thereby decreasing
inflammation. It is a potent inhibitor of the enzyme COX with a
greater COX-2 specificity at the site of inflammation, thus
preventing the production of prostaglandins and an
inflammatory response.
It is known to have a site-specific multifactorial mechanism of
action.
It directly blocks PGE2 secretion by inhibiting the cytokinetics of
inflammation like IL-1 Beta IL-6, and TNF

3. at the intracellular levels. It stimulates the synthesis of
extracellular matrix of the human articular cartilage by
increasing the synthesis of GAG (glucosamine glycans) and has
a synovial fluid concentration, which reaches approximately
60% of that in plasma. It also inhibits neutrophil adhesion and
accumulation at the inflammatory site in the early phase and
thus blocks the proinflammatory action of neutrophils.
After oral administration Aceclofenac is rapidly absorbed and
the bioavailability is almost 100%. Peak plasma concentrations
are reached in approximately 1-3 hours following ingestion.
Tmax is delayed with food intake whereas the degree of
absorption is not influenced. It is highly protein bound (>99%).
The volume of distribution is approximately 30L and its plasma
elimination half-life is 4-5 hours. About 2/3 of the dose is
excreted in the urine as hydroxy metabolites (4 - hydroxy
aceclofenac).

4. Acetaminophen
Acetaminophen is a centrally and peripherally acting analgesic
agent. It predominantly inhibits prostaglandins in the central
nervous system and acts by elevation of the pain threshold.
The peripheral action may also be due to inhibition of
prostaglandin synthesis or inhibition of the synthesis or actions
of other substances that sensitize pain receptors to mechanical
or chemical stimulation.
Acetaminophen is readily absorbed from the gastro-intestinal
tract with peak plasma concentrations occurring about 10 to 60
minutes after oral administration. Acetaminophen is distributed
into most body tissue. It crosses the placenta and is present in
breast milk. Plasma- protein binding is negligible at usual

5. therapeutic concentrations but increases with increasing
concentration.
The elimination half-life of Acetaminophen varies from about 1
to 3 hours.
Acetaminophen is metabolised predominantly in the liver and
excreted in the urine mainly as the glucuronide and sulphate
conjugates. Less than 5% is excreted as unchanged
Acetaminophen.
INDICATIONS:
Osteoarthritis, mourmatoid arthritis and ankylosing spondylitis
Cervical pain, and low back pain. pain, cervical pain, and
Sümptomatic treatment of pain and inflammation with fever.
CONTRAINDICATIONS

6. Combination contraindicated in the following situations:
Patients previously sensitive to any of the ingredients.
> PatientsPatientpost traumatic
Patients in whom substance with a similar action (6.9. Aspirin, .
Aspirin, or other NSAIDS) precipitate attack of asthma,
bronchospasm, acute miniGIs urticaria or patients
hypersensitive to these drugs.
> Patients with active or suspected peptic or duodenal ulcer or
history o recurrent peptic or duodenal ulcer or who have
gastrointestinal bleeding or other active bleeding or bleeding
disorders.
Patients with severe heart failure or severely impaired hepatic
or renal organ function.
ADVERSE EFFECTS:

7. The majority of side effects are of gastrointestinal system like
dyspepsia, abdominal pain, nausea and diarrhoea.
Uncommon: (1/100 - 1/1000): Dizziness, flatulence, gastritis,
constipation, vomiting, ulcerative stomatitis, pruritus, rash,
dermatitis and increased serum creatinine.
Rare: (<1/1000) Headache, fatigue, face oedema, allergic
reactions, increase in weight.
DRUG INTERACTIONS:
Aceclofenac is metabolized through cytochrome P450 2C9 and
a risk of pharmacokinetic interaction is therefore possible with
Phenytoin, Digoxin, Cimetidine, Tolbutamide, Phenylbutazone,
Amiodarone. Miconazole and Sulphaphenazole. As with other
products within the NSAID-group, there also exists a risk of
pharmacokinetic interactions with other drugs Eliminated by
active renal secretion, such as Methotrexate and Lithium.
Aceclofenac was not found to affect blood pressure control
when it was co-administered with Bendrofluazide, although an
interaction with other antihypertensive drugs, such as beta-
blockers, cannot be ruled out.

8. PRECAUTIONS:
Combination should be administered with caution and under
close medical surveillance to patients suffering from
gastrointestinal disease and to those with a history of peptic
ulceration, cerebrovascular bleeding, ulcerative colitis, Crohn's
disease, SLE, porphyria, hematopoietic or coagulation disorders.
Combination should not be given during lactation and
pregnancy unless considered essential by the Physician.
Caution should be exercised in patients with mild to moderate
impairment of hepatic, renal or cardiac function as well as in
patients with other conditions predisposing to fluid retention.
Patients who experience dizziness or other central nervous
system disturbances while taking NSAIDs should refrain from
driving or operating machinery