Non-opioid Analgesics (NOA)

NOAs include acetaminophen and the non-steroidal anti-inflammatory drugs (NSAIDs). They are the first choice for mild pain. NOAs also play an important opioid-sparing role in multimodal pain therapy for moderate to severe pain. Unlike opioids, all NOAs have a therapeutic ceiling beyond which the beneficial effects cannot be improved by increasing the dosage.

Selecting the appropriate NOA depends on the type of pain and the patient's risk for adverse effects.

Non-selective NSAIDs, like aspirin and ibuprophen, inhibit both COX-1 and COX-2, resulting in a greater variety of side effects. Selective NSAIDs primarily inhibit COX-2 prostaglandins. Because selective and non-selective NSAIDs both inhibit COX-2, they all produce a similar level of analgesia. While COX-2 inhibitors have less risk of GI ulceration and hemorrhage they have been found to increase the risk of thromboembolic events including stroke and myocardial infarction.

Therefore, acetaminophen may be the first choice analgesic for mild to moderate pain when inflammation is of little concern or when vascular or renal disease are present. NSAIDs may be preferred if inflammation is present or hepatotoxicity is a risk. Benefits of NSAIDs must be weighed against the risk of GI bleeding and cardiovascular side effects.

Oral Non-Opioids Compared (adult)
Drug
Common PO dose
Dose Interval
Max Daily Dose
Comments
Action
Acetaminophen

325-650mg
1gm
1300mg

4-6 hrs
t.i.d-q.i.d.
q8 hrs

4000mg

(2.5gm renal impairment)

Efficacy comparable to asprin.

Does not inhibit COX in peripheral tissues or platelets.

Central analgesic/antipyretic.
Mechanism unknown.
Possible inhibition of N-methyl-D-aspartate (NMDA) and substance P receptors via nitric oxide pathway
.

NSAIDS
Common PO dose
Dose Interval
Max Daily Dose
Comments
Action
Salicylates          
Acetylsalicylic acid (aspirin)
325-1000mg 4-6 hrs 4000mg Not for use in children under 12 with possible viral illness. Non-selective COX inhibitor
Diflunisal (Dolobid)

1000mg Loading
500mg subsequent

8-12 hrs 1500mg BOX WARNING: Cardiovascular & GI risk Non-selective COX inhibitor
Magnesium salicylate tetrahydrate (Doan's)
304-607mg q4 hrs 3738mg GI risk Non-selective COX inhibitor
Fenamates          
Meclofenamate
100mg q6-8 hrs 400mg GI risk Human leukocyte 5-lipoxygenase inhibitor
Mefenamic acid
500mg Loading
250mg subsequent
q6 hrs 2000mg BOX WARNING:: Cardiovascular & GI risk Non-selective COX inhibitor
Oxicams          
Piroxicam
20mg qd   BOX WARNING:: Cardiovascular & GI risk Non-selective COX inhibitor
Meloxicam
7.5mg -15mg qd   BOX WARNING:: Cardiovascular & GI risk Non-selective COX inhibitor
Pyranocarboxylic acid          
Etodolac
200-400mg q6-8 hrs 1000mg BOX WARNING: Cardiovascular & GI risk Non-selective COX inhibitor
Phenylacetic acids          
Diclofenac
100mg loading, then 25-50mg t.i.d. - q.i.d. 200mg BOX WARNING: Cardiovascular & GI risk Non-selective COX inhibitor
Propionic acids          
Ibuprofen
200-400mg 4-6 hrs 1200mg GI risk Non-selective COX inhibitor

Naprosyn sodium

275-550mg b.i.d. 1.65gm BOX WARNING: Cardiovascular & GI risk Non-selective COX inhibitor
Pyrrolizine carboxylic acid          
Ketorolac
10mg PO only after initial parenteral dose q4-6 hrs 40mg (Short-term analgesia not more than 5 days total use) Non-selective COX inhibitor
Pyrazols          
Celecoxib
400mg loading then 200mg first day   400mg/day
(200mg b.i.d.)
BOX WARNING: Cardiovascular & GI risk Selective COX-2 inhibitor


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