NSAID selection tool – NSAID classification

NSAID Selection Tool - Recommended NSAID based on patient data

Instructions

Select all drug classes that did not produce an adequate response

Additional options

Background Info 

         Nonsteroidal anti-inflammatory drugs (NSAIDs) have several benefits when it comes to managing pain and inflammation and are effective for numerous acute and chronic conditions (Examples include: ankylosing spondylitis, low back pain, dental pain, dysmenorrhea, acute gout, headache, migraine, osteoarthritis, psoriatic arthritis, and rheumatoid arthritis). 

Multiple NSAID classes are available based on the chemical structure (e.g. propionic acid, acetic acid derivatives, etc.). These agents can have significant differences in the mechanism of action (degree of prostaglandin-mediated and nonprostaglandin-mediated actions), possible toxicities, pharmacokinetics, pharmacodynamics, and metabolism.

Variability:
Individual responses to a particular NSAID can vary greatly, although when equipotent dosages are used, the clinical efficacy of a particular NSAID will likely be similar to other NSAIDs. Toxicity is one area where the variability can be significant. For example, some individuals will experience GI distress with one agent but not with another. Other side effects or adverse effects may also be related to a particular agent while other NSAIDs do not cause the same effects.

Purpose of this program:
The main reason for this program is that it provides quick access to the six major classes of NSAIDs. Each class has differences in their biochemical and physiological effects that may ultimately determine the efficacy of a particular class.  Other factors such as the absorption, distribution, and metabolism are less important in determining the efficacy of a particular agent, however may play a greater role in possible toxicities.

The six major classes are:

1. Salicylates
2. Propionic acid derivatives
3. Acetic acid derivatives
4. Enolic acid (Oxicam) derivatives
5. Anthranilic acid derivatives (Fenamates)
6. Selective COX-2 inhibitors

1. Increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. Risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.
2. Can cause or worsen renal insufficiency.
3. NSAID's cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines.
4. Anemia, increased bleeding time.
5. GI other: Anorexia, abdominal pain, dyspepsia, elevated liver enzymes, gross bleeding/perforation.

Generally avoid NSAID therapy if any of the following are present:

1. GI bleeding
2. Platelet dysfunction
3. Moderate to severe renal insufficiency
4. Uncontrolled hypertension
5. Cirrhosis
6. Reduced cardiac output
7. Concomitant anticoagulant therapy
8. Hypovolemia

Gastrointestinal (GI) side effects (trends):
Among the older NSAIDs, Ibuprofen is the least likely to cause adverse GI effects. Newer agents such as  etodolac, meloxicam, and nabumetone are also less likely to cause injury.

Worst offenders  (higher GI toxicity) include:

1. Flurbiprofen
2. Ketoprofen
3. Ketorolac
4. Oxaprozin
5. Piroxicam

Lower risk of adverse GI events:

1. Celecoxib
2. Etodolac
3. Ibuprofen
4. Meloxicam
5. Nabumetone

Damage to the GI tract is due primarily to inhibition of COX-1 which leads to:

1. Decreased bicarbonate secretion
2. Decreased mucosal blood flow
3. Decrease epithelial mucus
4. Decreased mucosal resistance to injury - Increased susceptibility to local effects of gastric acid, pepsin and bile acids.

NSAIDs can also damage the gastric mucosa directly. NSAIDs with longer half-lives or those available in sustained-release forms (e.g. diclofenac) are associated with an increased risk of adverse GI effects such as GI bleeding and perforation.  NSAIDs with shorter half-lives such as ibuprofen cause fewer adverse GI events (may permit recovery of critical COX enzyme functions), as well as a lower risk of developing impaired renal function.

Reducing the risk of GI toxicity:

1. Switch to alternative agents if possible such as acetaminophen or other Non-NSAID analgesics.
2. Add a PPI:  
   Omeprazole 20mg qd OR
   Lansoprazole 15 mg qd  OR
   Esomeprazole: 20-40 mg qd OR
   pantoprazole: 20-40 mg qd
3. Consider adding Misoprostol: 200 mcg tid-qid - often associated with intolerable abdominal discomfort and diarrhea
4. Switch to a selective COX-2 inhibitor

Cardiovascular risk factors present: 

AHA's Stepped Care Approach to Pharmacologic Therapy for Musculoskeletal Symptoms With Known Cardiovascular Disease or Risk Factors for Ischemic Heart Disease:   (order of use) - Focus on agents with the lowest reported risk of cardiovascular events and progress to other agents based on the balance between benefit and risk.

1. acetaminophen
2. aspirin
3. tramadol
4. narcotic analgesics (short term)
5. nonacetylated salicylates (e.g., diflunisal)
6. ------------Increased risk below this line - additional considerations------
7. Non COX-2 selective NSAIDs [Best bet: Naproxen]
8. NSAIDs with some COX-2 activity
9. COX-2 Selective NSAIDs [LEAST DESIRABLE]

 
Guidance from AHA includes (selections below horizontal line):

1. Select patients at low risk of a thrombotic event
2. Prescribe lowest dose required to control symptoms
3. Add ASA 81 mg and PPI to patients at increased risk of thrombotic events
4. Regular monitoring for possible adverse effects such as sustained hypertension, worsening renal function, edema, GI bleeding.

References  

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