Pharmacology – II [PHL 322] Non Steroidal Anti- Inflammatory Drugs (NSAIDS) Dr. Mohd Nazam Ansari.
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Pharmacology – II [PHL 322]
Non Steroidal Non Steroidal Anti- Inflammatory Anti- Inflammatory
Drugs (NSAIDS)Drugs (NSAIDS)
Dr. Mohd Nazam Ansari
TerminologyAnalgesic: A drug given to reduce pain without
resulting in loss of consciousness.
Antipyretic: A drug given to reduce or stop fever.
Inflammation: A basic way in which the body reacts to infection, irritation or other injury, the key feature being redness, warmth, swelling and pain.
NSAID’s: Non-Steroidal Anti-inflammatory Drugs.
Narcotic: is an addictive drug that reduces pain, dulls the senses, alters mood and behavior, and usually induces sleep or stupor.
Narcotic Analgesics1. Opiates: are the alkaloids found in opium, a
white liquid extract of unripe seeds of the poppy plant (morphine and codeine).
2. Opioids: are derivatives of opiates, they bind to opioid receptors in the central nervous system or gastrointestinal tract.
1. Endogenous opioid peptides produced in the body (endorphins, dynorphins, enkephalins)
2. Semi-synthetic opioids (heroin, oxycodone, hydrocodone)
3. Fully synthetic opioids (Demerol, methadone, fentanyl, tramadol)
NSAID’sHave antipyretic, analgesic and anti-
inflammatory activities.Not as effective as narcotic analgesics.Unlike narcotics, the site of action of NSAID’s
is peripheral tissues.Examples include:
PyrazolonPhenylbutazone IndomethacinIbuprofen
Inflammation is a defense reaction caused by tissue damage or injury
Characterized by:
1. Redness: vasodilation of capillaries to increase blood flow
2. Heat: vasodilation
3. Pain: Hyperalgesia, sensitization of nociceptors
4. Swelling: Increased vascular permeability (microvascular structural changes and escape of plasma proteins from the bloodstream)
5. Loss of function
• Inflammatory cell transmigration through endothelium and accumulation at the site of injury
Prostaglandins (PGs) are Prostaglandins (PGs) are derived from arachidonic acidderived from arachidonic acid
Cell Membrane (phospholipids) phospholipase A2
Arachidonic acid
cyclooxygenase aspirin, indomethacin
(COX1 & COX2)
Cyclic endoperoxides (PGG2, PGH2)
prostacyclin prostaglandin thromboxane synthetase synthetase synthetase
prostacyclin PGE2 PGF2 Thromboxane A2
PDX, PGI2 (vasodilator, (erythma (vasodilator
(vasoconstriction antiaggregating) edema uterus contractor) platelet
aggregation) pain, fever)
Lipoxygenase (LOX)Leukotrienes
How do they work? - NSAID v COX2
Arachidonic acidArachidonic acid
COX-1COX-1 COX-2COX-2
thromboxane / prostaglandins prostaglandins
NSAIDs
Primarily support platelet function
Primarily protect GI mucosa
Maintenance Induced
Primarily mediate inflammation, pain & fever
Effects of COX Inhibition
COX-1
Gastric ulcers
Bleeding
Acute renal failure
COX-2
Reduce inflammation
Reduce pain
Reduce fever
Beneficial actions of NSAIDs due to prostanoid synthesis inhibition
1. Analgesia: prevention of pain
2. Antipyretic: connected with influence of thermoregulatory centre in the hypothalamus
3. Anti-inflammatory action: mainly antiexudative effect
4. Antithrombotic action: in very low daily doses
5. Closure of ductus arteriosus
Shared toxicities of NSAIDs due to prostanoid synthesis inhibition
1. Gastric mucosal damage: connected with PGE inhibition
2. Bleeding: inhibition of platelet function (TxA2 synthesis)
3. Limitation of renal blood flow Na+ and water retention
4. Delay / prolongation of labourconnected with PGF2α inhibition
5. Asthma and anaphylactic reactionsconnected with PGF2α inhibition
NSAIDs: NSAIDs: Classifications Classifications based on chemistrybased on chemistry
Salicylic acid derivativesAspirin
Para-aminophenol derivativesAcetaminophen
Indole and indene acetic acids Indomethacin
Pyranocarboxylic acidsEtodolacKetorolac
Propionic acids IbuprofenNaproxenKetoprofenCarprofenVedaprofen
FenamatesMeclofenamic acidTolfenamic acid
Pyrazolones or enolic acidsPhenylbutazoneDipyrone
OxicamsPiroxicam,Meloxicam
Nicotinic acid derivativesFlunixin meglumine
Hydroxamic acid derivativesTepoxalin
Coxib-class NSAIDsDeracoxib, Firocoxib
Acetaminophen: Paracetamol
Acetaminophen (Paracetamol) is the most commonly used over-the-counter (OTC), non-narcotic analgesic.
Used as an analgesic and antipyretic.
No clinically significant anti-inflammatory effect.
Paracetamol is found in more than 600 over-the-counter drugs.
It can be found in combination with other active ingredients in many cold, sinus, and cough medications
Rapidly and completely absorbed from the GI tract.
Drug Interactions / Adverse EffectsDrug Interactions / Adverse EffectsParacetamol is remarkably free of drug interactions
at its usual therapeutic doses.
It exerts little or no pharmacologic effect on the cardiovascular, respiratory, or gastrointestinal systems, on acid-base regulation, or on platelet function.
With large doses (>4g/day), an intermediate metabolite is produced that is thought to be hepatotoxic and possibly nephrotoxic.
Alcohol induces drug-metabolizing enzymes in liver, resulting rapid metabolism of acetaminophen produces and accumulation of toxic metabolites.
The Salicylates: AspirinHas antipyretic, analgesic and anti-inflamatory activities.
It is useful as analgesics for certain categories of pain, such as headache and arthritis.
It remains the standard, first-line drug in the therapy of rheumatoid arthritis, and can provide relief of symptoms in acute rheumatic fever.
Some clinicians recommend small daily doses of aspirin for stroke or myocardial infarction because of its antiplatelet activity.
Pharmacologic effectsAnalgesic effects: Aspirin is as effective as
Acetaminophen for low- to moderate-intensity pain treatment
Antipyretic action: is rapidly effective in febrile patients, yet has little effect on normal body temperature.
Anti-inflammatory effects: the primary clinical application is in the treatment of musculoskeletal disorders, such as rheumatoid arthritis
Respiratory effects: high doses result in medullary stimulation, leading to hyperventilation and respiratory alkalosis
Pharmacologic effectsCardiovascular effects: high doses may cause
peripheral vasodilation by exerting a direct effect on smooth muscle and Toxic doses depress circulation.
Hepatic effects: aspirin can cause dose-dependent hepatic damage.
Hematologic effects: It can inhibits platelet aggregation and reduce plasma prothrombin levels.
Gastrointestinal effects: It can cause nausea and vomiting by irritating the gastric mucosal lining. It may also cause a dose-related gastric ulceration, bleeding.
Pharmacologic effectsRenal effects: It can result in salt and water
retention because of decreasing renal blood flow.
Metabolic effects: It can produce hyperglycemia and glycosuria in large doses.
Endocrine effects: In very large doses, it can stimulate steroid secretion
Uses of Aspirin• As analgesic (300 to 600 mg during 6 to 8 h) for headache,
backache, pulled muscle, toothache, neuralgias.
• As antipyretic in fever of any origin in the same doses as for analglesia. However, paracetamol and metamizole are safer, and generally preferred.
• Acute rheumatic fever. Aspirin is the drug of choice. Antirheumatic doses are 75 to 100 mg/kg/day.
• Rheumatoid arthritis. 3-5 g/day after meal is effective in most cases. Since large doses of Aspirin are poorly tolerated for a long time, the new NSAIDs (diclofenac, ibuprofen, etc.) in depot form are preferred.
• Salicylic acid is used topically to treat: plantar warts , fungal infections, corns
Aspirin Toxicity Aspirin Toxicity In adults, salicylism (tinnitus, hearing loss,
vertigo) occurs as initial sign of toxicity after aspirin or salicylate overdose or poisoning.
In children, the common signs of toxicity include hyperventilation and acidosis, with accompanying lethargy and hyperventilation.
Drugs Result
Diuretics Decrease diuresis
Beta-blockers Decrease antihypertensive effect
ACE inhibitors Decrease antihypertensive effect
Anticoagulants Increase of GI bleeding
Sulfonylurea Increase hypoglycemic risk
Cyclosporine Increase nephrotoxicity
Alcohol Increase of GI bleeding
Drug interactions with NSAIDs
COX-2 inhibitors (1) Selective COX-2inhibitors (Coxibs)• Celecoxib, Rofecoxib• Etoricoxib, Valdecoxib• Parecoxib (2) PreferentialCOX-2 inhibitors• Meloxicam• Nimesulide• Nabumetone
•Coxibs are selective COX-2 inhibitors. •They exert Anti-inflammatory, analgesic, and antipyretic action with low ulcerogenic potential.
•Coxibs can cause infertility. •The ulcerogenic potential of preferential COX-2 inhibitors (Meloxicam, and Nimesulide) is significant.
•Celecoxib is as effective as other NSAIDs in the treatment of rheumatoid arthritis and osteoarthritis, and in trials it has caused fewer endoscopic ulcers than most other NSAIDs.
•Probably because it is a sulfonamide, celecoxib may cause rashes.
• It does not affect platelet aggregation at usual doses. It interacts occasionally with warfarin – would be expected of a drug metabolized via CYP 2C9.
Rofecoxib and valdecoxib Rofecoxib and valdecoxib have been removed from the market due to a doubling in the incidence of heart attack and stroke
CelecoxibCelecoxib remains on the market and is approved for:
Osteoarthritis and rheumatoid arthritisPain including bone pain, dental pain, and
headache Ankylosing spondylitis.
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