NON-STEROIDAL ANTI- Ariel Yudkovich

INFLAMMATORY DRUGS (NSAID’s)

 Definition
• NSAID’S are drugs with analgesics and
antipyretic effects and which have in
higher dose, anti inflammatory effects.
• The most prominent members of this
group of drugs are Aspirin, ibuprofen
and naproxen, all are which available
over the counter in many areas.
• weak acids, PH 3-5, well absorbed from
stomach and intestinal mucosa protein-
bound in plasma ( albumin),
metabolised in the liver.
Classification of NSAID’s
Non-Selective COX-1 Inhibitors:
• Salicylates e.g.-Aspirin
• Propionic acid derivative e.g.- Ibuprofen , naproxen
• Anthranilic acid derivative e.g.- Mephenamic acid
• Aryl acetic acid derivative e.g.- Diclofenac
• Oxicam derivative e.g.- Piroxicam
• Pyrrole – pyrrole derivative e.g.- Ketorolac
• Indole derivative e.g.- Indomethacin
Classification of NSAID’s
COX-2 Inhibitor:
• Preferential COX-2 Inhibitor e.g.- Nimesulide
• Selective COX-2 Inhibitor e.g.- Celecoxib
Analgesic- Antipyretics with poor Anti-inflammatory action:
• Paracetamol
• Metamizol
Prostaglandin synthesis
• Prostaglandins : produced by the cells, promote inflammation, pain,
and fever; blood clotting function of platelets; protect the lining of
the stomach from damaging effects of acid.
• NSAIDs act by inhibiting the synthesis of prostaglandin.
• Prostaglandins, prostacycline(PGI2) and thromboxane A2 ( Tx A2) are
produce from archidonic acid by enzyme cyclooxygenase (COX)
iso -forms.
• Most of NSAIDs inhibit COX-1 and COX-2 non-selective.
• but now same selective COX-2 inhibitors have been produce.
 What are NSAIDs and how do they work ?

• NSAIDs block the COX enzymes ,

reduce prostaglandins, inflammation,
pain, and fever.
• COX-1 produced prostaglandins that
support platelets and protect the
stomach.
• Reduced prostaglandins that protect
the stomach and support blood
clotting,
• so NSAIDs can cause ulcers in the
stomach and promote bleeding.
NSAID’s indication
• RA
• OA
• Infalmmatory arthritis
• psoriatic arthritis,
• Reter’s syndrome
• Acute goutMetastatic
• bone pain
• Dysmenohhoea
• Headache
• Migrain
• Postoperative pain
• Pyrexia ( fever)
• Renal colic
Differences between NSAIDs
• vary in potency, duration , eliminated from body, how strongly they
inhibit COX-1(tendency to cause ulcers and promote bleeding )
• The more an NSAID blocks COX-1, the greater to cause ulcers and
promote bleeding.
• Celecoxib (Arcoxia), blocks COX-2 but also little on COX-1, classified as
a selective COX-2 inhibitor ,cause less bleeding and fewer ulcers.
• Aspirin is a unique NSAID, the only NSAID inhibits clotting of blood for
a prolonged period (4 to 7 days), ideal for preventing blood clots that
cause heart attacks and strokes.
 Cardiovascular Events Associated with Rofecoxib
During the trial, 2.4 percent of the 1,287
participants who took rofecoxib suffered a
serious cardiac event, including heart attack,
angina or sudden death, compared with less
than 1 percent of the patients who received a
placebo.
A total of 15 patients given rofecoxib had a
cerebrovascular event, such as stroke, deadly
stroke or transient ischemic attack, while 7 of
the participants given a placebo suffered the
same reactions.
Figure 3. Kaplan–Meier Estimates of the Cumulative
Some patients who took the drug also
Incidence of Investigator-Reported Congestive
developed high blood pressure, fluid build-up
Heart Failure (CHF), Pulmonary Edema (PE), or
known as edema and congestive heart failure,
Cardiac Failure (CF).
according to a 2005 report in the New England
Journal of Medicine.
SUMMARY OF UK GUIDELINES FOR ASPIRIN
PRIMARY PREVENTION OF CARDIOVASCULAR DISEASE
• NICE CKS Antiplatelet treatment: Primary prevention of CVD Last
revised September 2018 “Do not routinely prescribe antiplatelet
treatment for the primary prevention of cardiovascular disease
(CVD).” It then states “Consider prescribing aspirin in people with a
high risk of stroke or myocardial infarction.” The guidelines remind
readers that aspirin is not licensed for the primary prevention of CVD
and that people can reduce their CVD risk by other means such as
smoking cessation or taking at statin. The guidelines emphasise “if
aspirin is being considered, discuss the likely benefits (reduced CVD
risk) and risks (such as gastrointestinal bleeding) with the person.”
SUMMARY OF UK GUIDELINES FOR ASPIRIN
SECONDARY PREVENTION OF CARDIOVASCULAR DISEASE
• NICE Antiplatelet secondary prevention of CVD guidelines (last revised September 2018) state;
“Antiplatelet treatment should be prescribed for the secondary prevention of cardiovascular events in
people with”:
* Acute coronary syndrome (ACS)
* Angina
* A previous MI
* A previous stroke or transient ischaemic attack (TIA).
* Peripheral Arterial disease
* Atrial Fibrillation – although anticoagulants are normally used.
* Stent implantation
NSAID’s CONTRAINDICATION
NSAID’S should be used with caution in patient with:
1. Astama
2. CVD
3. Renal disease with fluid retention
4. Coaugulation problem
5. Peptic ulcer disease
6. Ulcerative Colitis
7. Pregnancy