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Non-Steroidal anti-inflammatory


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What are the two types of NSAIDs?
1. COX - non-selective
2. COX2 - selective
What effect does the inhibition of Cox cause?
Reduces the production of pain and inflammation mediators such as prostaglandins (beneficial) as well as some important vasodilators (adverse effects).
What is the scientific name for aspirin?
Acetylsalicylic acid (ASA)
Aspirin and COX2 inhibitors, which are NSAIDs, are preferred because...
They are reported to have less GI side effects
What are some examples of COX2 inhibitors?
Which COX2 inhibitor/NSAID was recently taken off the market? And why?
Vioxx because it had SE of increased risk of CV events including heart attack and stroke.
What are some examples of Non-selective COX inhibitors?
Ibuprofen (Motrin, Advil), Indomethacin, Piroxicam, naproxen, diclofenac, toradol.
Which non-selective COX inhibitor is available as an injection? What is it used for? SE?
Toradol, short-term acute pain. Has too many SE such as bleeding, GI ulcers. Not intended for chronic use.
What is the drug class for non-narcotic analgesics? What is it's brand name?
Acetaminophen (AAP), known as Tylenol
What are the drug classes for gout? (3)
1. Colchicine
2. Allopurinol
3. Probenecid
What are some other drug classes for arthritis?
Gold salts
What pharmacological actions does Aspirin have? (6)
1. Analgesia
2. Anti-inflammatory
3. Antipyresis
4. Uric Acid Excretion
5. Antiplatelet actions
6. Prevention
What are the specific analgesic actions of Aspirin? (2)
-Pain of low intensity (headache, myalgia and toothache)
-Analgesia due to prevention of the sensitization of sensory nerve endings to chemical mediators such as serotonin and bradykinin.
What are the specific anti-inflammatory actions of Aspirin? (1)
Reduce swelling and redness of inflammation. (Prostaglandins are mediators of inflammation)
What are the specific antipyresis actions of Aspirin? (2)
1. Reduce body temperature in fever.
2. Inhibition of formation of pyrogenic substances such as prostaglandins, kinins. However, Aspirin has no effect on normal body temperature at rest or during exercise when it is elevated.
What are the specific uric acid excretion actions of Aspirin? (1) Specific disease use? Long term effect?
Increases uric acid excretion in large does. Used for gout, but if used long term, can create kidney problems.
What are the specific antiplatelet actions of Aspirin? (2)
1. Prolongation of bleeding time due to inhibition of platelet aggregation.
2. Inhibition of platelet thromboxane A2 (enzyme) biosynthesis.
What are the specific prevention actions of Aspirin? (2)
1. MI prevention and treatment. Acutely, the soluble form of aspirin (non-coated should be chewed) is used if MI is suspected. Adult, 1-2 Aspirin/day
2. Prevention of colon cancer, chronic treatment.
What two systems and two organs experience SE from Aspirin?
1. GI
2. CNS
3. Liver
4. Renal-kidney
What are some GI SE caused by Aspirin? (3)
1. Epigastric distress, nausea and vomiting.
2. Exacerbation of gastric ulceration.
3. Gastric bleeding which may be painless, but is detectable in stools with a simple test.
What are some CNS SE of Aspirin?
Hyperventilation due to the stimulation of the respiratory center in the medulla. Caused by medium to large doses of Aspirin.

This is an important distinguishing side effect that is specific to aspirin and not Tylenol.
What are some hepatic SE of Asprin?
Mild hepatitis, esp. in pts w/ RA taking large doses for an extended time.
What are some SE of aspirin that affect the kidneys?
Retention of salt and water due to renal destruction. Nephron damage w/ prolonged/over use.
Why is renal damage so serious?
Because loss of renal function is cumulative and irreversible.
What are some hypersensitivity reactions of aspirin? (2)
-Skin rashes, urticaria and angioedema (rare).

-Drug resistant form of asthma (may be due to the formation of leukotrienes).
What is methyl salicylate used for?
Topical product used in sports creams for pain releif in joints.
What is applied topically as a keratolytic agent?
Salicylic acid, which is a derivative of aspirin.
What are some therapeutic uses for aspirin? (5)
1. Analgesia
2. Antipyresis
3. Acute rheumatic fever
4. RA
5. Prevention of colon cancer
What is the "non-aspirin"?
What is Acetaminophen's MOA?
It's a weak inhibitor of COX.
What are the pharmacological actions of Acetaminophen?
Analgesic and antipyretic actions are similar to that of aspirin.
Name 7 reasons why Acetaminophen is not like Aspirin.
1. Lacks anti-inflammatory action
2. Does not inhibit platelet aggregation, so can't take it to prevent HR.
3. Does not cause gastric irritation or bleeding
4. Has no effect on the respiratory system
5. Does not alter uric acid excretion.
6. Not likely to trigger bronchoconstriction in persons who are hypersensitive to aspirin.
7. Does not increase the risk of Reye's syndrome in children w/ viral infection.
What are the SE of Acetaminophen?
Ther are no major side effects at therapeutic doses. Very well tolerated, esp. in the GI system
What kind of toxicity occurs with Acetaminophen overdose? How does it happen?
Fatal hepatic necrosis caused by a metabolite formed in the liver. Develops with chronic use of Acetaminophen.
What are some early symptoms of hepatic damage caused by Acetaminophen?
Nausea, vomiting, diarrhea and abdominal pain. Children may appear well, so if you don't know how much Acetaminophen was ingested, go to ER.
What is the antidote treatment for acetaminophen toxicity? How does it work? Administration?
Oral N - acetylcysteine (MUCOMYST). This drug replaces antioxidant in liver that Acetaminophen toxicity takes out. Must be administered in-time, otherwise liver damage is permanent and often lethal.
Approximately how many deaths does Acetaminophen (Tylenol) poisoning cause? Hospitalizations? ER visits? Liver failures?
458 deaths
2600 hospitalizations
56,000 ER visits
700 liver failures, which accounts for 50% of all acute liver failures in the US
What are some therapeutic uses of Acetaminophen?
Useful in mild to moderate pain such as headache, myalgia, postpartum pain and other cirumstances in which aspirin is an effective analgesic.
To avoid toxicity, Acetaminophen doses should be limited to....for healthy adults? Alcoholics?
4 grams/day (8 extra strength Tylenol's) for healthy adults, 2 grams or less of alcoholics due to liver damage.
Describe the pathophysiology of gout.
A metabolic disorder involving the overproduction of purines, which are metabolic byproducts of food, leading to elevated levels of uric acid in the blood.
Inadequate urinary elimination of uric acid leads to...
Deposition of urate crystals in the synovial tissue of joints and tissues such as the kidney.
Gout is characterized by...
Intermittent attacks of acute arthritis.
Symptoms are most often presented as...most common location?
Severe pain in one joint, especially in the great toe
What are four MOA of anti-gout drugs? Give an example for each.
1. Inhibiting leukocyte migration into the joint which will prevent inflammation (Colchicine)
2. Inhibit uric acid/urate synthesis (Allopurinol)
3. Increasing uric acid secretion (Probenecid)
4. General anti-inflammatory and analgesic effects (NSAIDs) that work acutely and do not prevent gout
Colchicine is an example of what kind of drug?
Anti-gout drug
How does Colchicine work? How is it active?
When should Colchicine be used?
Colchicine interferes with the mobility of neutrophils leading to a decrease of their migration into the inflamed area.

Active orally.

Use during an attack, because it works acutely.
What are some SE of Colchicine? (5)
Nausea, vomiting, abdominal pain, aplastic anemia (bone marrow) and alopecia.
What are two therapeutic uses for Colchicine?
Prophylaxis and acute treatment of gout.
What gout drug is used for the PREVENTION of gout?
Allopurinol - primarily used for the prevention of gout attacks, not treatment
How does Allopurinol work?
Reduces the synthesis of uric acid. It's a anti-metabolite that prevents accumulation and production of uric acid.
Acute attacks of gout sometimes occur during the early stages of therapy, so what preventative measure should be taken?
Colchicine and NSAIDs should be administered concurrently.
What are some SE of Allopurinol?
Only mild GI disturbances, generally well tolerated.
What kind of drug is Probenecid?
Uricosuric agent
How does Probenecid work? How is it active?
Inhibits reabsorption of uric acid in proximal tubules which leads to an increased urate excretion.

Active orally
What are some SE of Probenecid? (2)
Generally well tolerated by most patients. Mild GI irritation and hypersensitivity reactions.
What are the therapeutic uses of Probenecid? (2)
1. Chronic gout
2. Cancer patients that accumulate uric acid, due to the use of cytotoxic antineoplastic agents.
What are three implications for PT's with use of NSAIDs?
1. Many patients will be using them for pain, stiffness and inflammation and will have decreased ROM and exercise capacity.
2. Anti-inflammatory meds can improve exercise capacity.
3. Pt's can educate patients who misuse OTC products. i.e. use acetaminophen instead of aspirin or NSAIDs because of advertising.
What is a particularly important SE difference between Aspirin and Acetaminophen?
Aspirin can cause hyperventilation and Acetaminophen does not. Acetaminophen will not cause bronchoconstriction, aspirin could.

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