Non- Narcotic Analgesics Flashcards
What is the role of Prostaglandins in producing Pain?
Noxious stimuli cause the release of Prostaglandins by COX, which increase the sensitivity of nociceptors, transmitting an ascending pain signal.
Ibuprofen (Advil):
- NSAIDS
- Non selective COX inhibitor
Celecoxib:
NSAID
-COX-2 Inhibitor
Acetylsalicylic Acid (Aspirin):
- Salicylic acid is obtained from Willow Bark
- Is an effective analgesic/ anti-inflammatory, however it is VERY hard on the stomach.
- Aspirin has an anti- platelet effect at low doses (80 mg)
- ASA acetylates COX-1 in platelets, irreversibly inhibiting its actions.
- Used less as an antipyretic
- Contraindicated in children
- ->Analgesic (600-900 mg)
- ->Anti-inflammaotry (3000-6000mg)
What are the enzymes and products of Arachidonic Acid?
- Cyclooxyrgenase (COX) which leads to the production of Prostaglandins, Prostacyclins and Thromboxanes.
- Lipooxygenase (LOX) leads to the production of Leukotreines
- Lead to inflammation.
What are the role of Prostacyclins in the clotting cascade?
- Important for checks and balances of vessel clotting.
- Stops the clotting cascade through platelet inhibitor.
What are the positive and negative effects of COX inhibitors?
- Antipyretic, Analgesic and Anti-inflammatory
- BAD: Decrease GI mucous (lead to ulceration)
Explain the mechanism of NSAIDS as an anti-pyretic:
- Fever occurs due to actions of bacteria/ viruses in the hypothalamus.
- Stimulating COX-2 results in a large increase in prostaglandins (PGE2 is a potent pyrogen)
- Fever has a role in fighting infection.
Explain the mechanism of NSAIDS as an Analgesic/ Anti- Inflammatory:
- PG’s increase vasodilation to injured tissues and enhance infiltration of leukocytes
- NSAIDS block release of prostaglandins and prostacyclins (reduce inflammation)
NSAID Side Effects:
- Renal Dysfunction (decrease PG’s, decrease vasodilation of afferent arterioles to the kidney… reduce GFR)
- Edema
- Gastrointestinal Ulceration
Why is a COX-2 inhibitor less problematic than a non- selective COX inhibitor?
- COX-1 is important in protection and maintenance, as well as important for GI cytoprotection and platelet aggregation.
- Blocking COX-1 blocks these beneficial protective roles.
Early signs of ASA Toxicity:
–Early signs of Toxicity include Tinnitus, GI Irritation, Hyperventilation and Lethargy.
Severe Signs of ASA Toxicity:
-Restlessness, Hallucinations, Seizures, Coma, Respiratory and Metabolic Acidosis and Respiratory Failure
Treatment of ASA Toxicity:
Alkalinize urine to enhance solubility.
Aspirin Induced Asthma:
-Occurs as COX enzymes are blocked, shunting to the LOX pathway at which leukotrienes are released. Leukotrienes act as broncho-constrictors and this can lead to asthma.
Acetaminophen:
- Not an NSAID but shares many features.
- Also inhibits COX enzymes, however acts primarily on the CNS to cause analgesia and anti-pyretic effects.
–>Lacks Adverse Effects of NSAIDs, and lacks anti- inflammatory effects.
Acetaminophen Side Effects:
- Generally well tolerated
- Compared to NSAIDS, lower risk of:
- GI adverse Effects
- Cardiovascular/ renal dysfunction
-High (toxic) doses damage the liver.
Acetaminophen Toxicity:
- Risk increases with Chronic Ethanol Abuse
- Concerns with combination products, such as cold/ cough preparations.
- Concerning in pediatrics.
Acetaminophen in Combination:
- -Combined with Opioids:
- Codeine: Tylenol 1, 2, 3 and 4
- Tramadol (Tramaset)
Why is Chronic Ethanol Abuse increase risk of Acetaminophen toxicity?
-Ethanol induces CYP2E1, lowering threshold for toxicity.
-CYP2E1 also converts Acetaminophen to a toxic metabolite- damaging the liver.
Ethanol also produces Glutathione which INHIBITS NAPQI, the enzyme responsible for metabolizing Acetaminophen in the liver.
