Pain management

Question 1

NSAID risk of GI effects

Answer 1

Lowest Risk
• Celecoxib
Low Risk
• Ibuprofen 
• Aspirin
• Diclofenac
Medium Risk
• Naproxen
• Indomethacin 
• Tolmetin
High Risk
• Piroxicam

Question 2

Renal effects of NSAIDs

Answer 2

Decrease In Renal Blood Flow
• In persons with compromised renal hemodynamics the kidney synthesizes vasodilating prostaglandins (PGE2 and PGI2) to offset the effects of vasoconstricting mediators and maintain renal perfusion.
• Decreases in PGE2 can increase sodium and water retention.
• Decreases in PGI2 may lead to hyperkalemia and acute renal failure.

Acute Interstitial Nephritis
• Type I hypersensitivity reaction leading to acute renal failure.
• Almost any drug can cause acute interstitial nephritis.
• The most common offenders are antibiotics and NSAIDs.

Analgesic Nephropathy
• Chronic interstitial nephritis caused by prolonged and excessive consumption of analgesics, particularly combinations of different agents.
• After many years, renal papillary necrosis results.
• In response to the papillary necrosis,a chronic interstitial nephritis develops leading to progressive chronic renal failure.

Question 3

NSAIDs and ACEIs

Answer 3

• ACE-inhibitors act partly by preventing breakdown of kinins that stimulate prostaglandin production.
• NSAIDs may diminish the antihypertensive effect of ACE-inhibitors by blocking the production of vasodilating prostaglandins.

Question 4

Aspirin effects on respiration

Answer 4

• Salicylates uncouple oxidative phosphorylation which leads to elevated CO2 and increased respiration.
• Higher doses stimulate the respiratory center resulting in hyperventilation.
• At toxic levels central respiratoryparalysis occurs.

Question 5

Aspirin in pregnancy

Answer 5

• Category C risk during Trimesters 1 and 2

* Category D during Trimester 3.

Question 6

Salicylate intoxication

Answer 6

• After an acute salicylate overdose patients typically present to the hospital with a mixed respiratory alkalosis and metabolic acidosis.
• Prolonged exposure to high doses of salicylates leads to depression of the medulla, with central respiratory depression and circulatory collapse.
• Respiratory failure is the usual cause of death.

Question 7

Colchicine

Answer 7

• Colchicine binds to tubulin, inhibiting its polymerization and preventing formation of microtubules.
• This disrupts mobility of granulocytes, decreasing their migration into the affected area.
• Colchicine blocks cell division by disrupting the mitotic spindle.
• Colchicine also inhibits synthesis and release of leukotrienes.

ADVERSE
• Nausea, vomiting, abdominal pain, and diarrhea.
• Chronic administration may cause myopathy, neutropenia, aplastic anemia, and alopecia.
• Should not be used in pregnancy.
• Should be used with caution in patients with hepatic, renal, or CV disease.
• NSAIDs have replaced colchicine because of the troublesome diarrhea associated with colchicine therapy.

Question 8

Allopurinol adverse effects

Answer 8

• Hypersensitivity reactions, especially skin rashes, are the most common adverse reactions.
• In rare instances the rash may progress to
Steven-Johnson syndrome.
• All patients who develop a cutaneous reaction to allopurinol should discontinue the drug.

• Drug interactions with 6-MP and azathioprine

Question 9

Uricosuric agents MOA

Answer 9

MOA for Probenecid, Sulfinpyrazone
• Urate is filtered, secreted, and reabsorbed by the kidneys.
• Reabsorption predominates: the amount excreted is 10% of that filtered.
• This process is mediated by a specific transporter.
• The transporter exchanges urate for an anion.
• Uricosuric drugs compete with urate for the
transporter, thereby inhibiting its reabsorption.

Question 10

Probenecid

Answer 10

• Probenecid should not be used in gouty patients with nephrolithiasis or with overproduction of uric acid.

ADVERSE
• Mild GI irritation.
• Hypersensitivity reactions; usually mild. Serious hypersensitivity is extremely rare.
• A liberal fluid intake should be maintained to minimize risk of renal stones.

Question 11

Sulfinpyrazone

Answer 11

ADVERSE
• GI irritation.
• Hypersensitivity reactions, usually a rash with fever, occur less frequently than with probenecid.
• Depression of hematopoiesis.
• Should not be used by patients with underlying blood dyscrasias.
• A liberal fluid intake should be maintained to minimize the risk of renal stones.
• Sulfinpyrazone inhibits warfarin metabolism.

Question 12

Rasburicase

Answer 12

• Enhances uric acid metabolism. This enzyme oxidizes uric acid to allantoin, a soluble compound that is easily excreted by the kidney.

• In cancer chemotherapy, the rapid lysis of tumor cells can release free nucleotides and increase plasma urate levels.
• This can lead to massive renal injury.
• Exogenous uricase can reduce plasma urate levels and prevent renal damage.
• Allopurinol can also be used to prevent this component of tumor lysis syndrome.