NSAIDs Mechanism and Background

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meaning of NSAIDs

Non-steroidal Anti-Inflammatory Drugs

NSAIDs Property

* Anti-inflammatory (dec. inflammation)
* Analgesic (relieve of mild to mod pain)
* Antipyretic (dec. ELEVATED body temp d/t fever)
* Anticoagulant (dec. blood clotting via inhibitting platelet aggregation)

Glucocorticoids

Other inflammatory drug that is steroidal

Acute and Chronic musculoskeletal (MSK) disorders

NSAIDs treat what best?

Reason why Acetaminophen isn’t an NSAID

Acetaminophen isn’t anti-inflammatory or an anticoagulant

Aspirin

Best NSAID frfr

Prostaglandin

* Group of lipid-like compound that exhibit a wide range of physiologic activities.
* Appear to be hormones that act locally to help regulate cell function under normal and pathologic conditions.

Red Blood cell

Cell that doesn’t produce Prostaglandin, Thromboxane and Leukotrienes

Eicosanoid

Precursor of Prostaglandin, Thromboxane and Leukotrienes.

Arachidonic acid

* needed for the synthesis of Prostaglandin, Thromboxane and Leukotrienes.


* stored in the phospholipid of cell membranes.

CycloOXygenase

the side of NSAID action w/in the cell

COX-1

* Help regulate normal cell activity and maintain cellular homeostasis.
* Enzymes located in the stomach mucosa synthesize prostaglandins that help protect the stomach lining from gastric acid.
* Enzymes in the kidneys produce beneficial prostaglandins that help maintain renal function, especially when kidney function is compromised.,
* Also, the enzyme responsible for synthesizing prostaglandins and thromboxanes regulating normal platelet activity.

COX-2

* Seems to be produced primarily in injured cells - other chemical mediators (cytokines) induce the injured cell to synthesize the COX-2 enzyme, and this enzyme then produces prostaglandins that mediate pain and other aspects of the inflammatory response.


* There is also considerable evidence that the COX-2 enzyme, may help lower BP and prevent arterial thrombosis that would otherwise cause heart attack and stroke in susceptible individuals.

Salicylates

Major form of a group of drugs that Aspirin represents.

Yes

Can Aspirin be used to treat Primary dysmenorrhea and RA and OA?

Ketorolac tromethamine

* Postoperative NSAID that is relatively new but shows exceptionally promising results.


* can be given orally or intramuscularly.
* its analgesic properties are like those of opioid drugs but without the adherent effects and risks.

Ibuprofen

* Known NSAID for fever for both adults and children.


* nonprescription antipyretic

Reye’s syndrome (mitochondria damage)

Reason why Aspirin is not used in treating fever in children.

40 to 50 percent

Proven lowered risk of fatal colon cancer in people that taken aspirin in a daily basis.

GIT damage

Primary problem w/ all NSAIDs

Prostaglandin (PGI PGE) that create a protective lining in the mucosal lining of the stomach is lost.

Reason why NSAIDs cause GIT damage

Helicobacter pylori

Bacterium that is sometimes present in the stomach and contributes to the increased risk of GIT irritation via NSAIDs.

Enteric coated aspirin, Buffer, Food, Misoprostol, H2 antagonist

Solution for GIT damage caused by NSAIDs

Headache, Tinnitus, Hearing difficulty, Confusion, GIT distress.

If severe, metabolic acidosis and dehydration, fatal.

Symptoms of Aspirin toxicity

10-30g

fatal dose of Aspirin for adults

130g

Highest documented amount of Aspirin that was ingested in which the patient didn’t die.

Influenza or Chicken pox

Precursor conditions for children that contract Reye syndrome

High Fever, Vomitting, Liver Dysfunction, Unresponsiveness leading to delirium, convulsions, coma and possibly death.

Symptoms of Reye syndrome

10% to 25%

percent of people with asthma (or other hypersensitivity reaction) that exhibit aspirin intolerance

Acute Bronchospasm

Urticaria

Severe Rhinitis

Symptoms of Aspirin Intolerance

Yes

do NSAIDs inhibit bone healing and certain bone surgeries like spinal fusion?

No

do NSAIDs inhibit tissue healing, inhibitting the transport of connective tissue like proteoglycans?

COX 2 Selective Inhibitors

* Coxibs
* Inhibits COX 2 that show up at sites of inflammation w/o affecting COX 1 found in the GIT, kidneys and platelets.
* Analgesic, antipyretic and anti-inflammatory
* Less GIT adverse effects
* No impact on platelet aggregation
* Doesn’t offer cardioprotective effects of traditional nonselective NSAIDS.
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