Caffeine/NSAID combinations

Papillary necrosis NSAIDs, combined phenacetin, aspirin, and caffeine analgesics... 

When linezolid is used with antiplatelet drugs such as aspirin or die NSAIDs (see Chap. 18) diere is an increased risk of bleeding and thrombocytopenia When administered widi die MAOIs (see Chap. 31) the effects of the MAOIs are decreased. There is a risk of severe hypertension if linezolid is combined widi large amounts of food containingtyramine (eg, aged cheese, caffeinated beverages, yogurt, chocolate, red wine, beer, pepperoni). 

Simple analgesics (alone or in combination with caffeine) and NSAIDs are the mainstay of acute therapy. 

The most prominent mixed Ai/A2 receptor antagonist is caffeine which is currently used clinically as an adjunctive analgesic in combination with acetaminophen and other NSAIDs. Its adjuvant activity has been demonstrated in both clinical and preclinical studies and it is extremely successful on the OTC market. Other mixed Ai/A2 receptor antagonist are currently being investigated in preclinical studies (Akahane et al. (Fujisawa Pharm Co), 2001). 

Nonsteroidal anti-inflammatory drugs (NSAIDs) are helpful for early and mild headache. NSAIDs include acetaminophen, ibuprofen, naproxen, and others. A recent study concluded that a combination of acetaminophen, aspirin, and caffeine could effectively relieve symptoms for many migraine patients. One such over-the-counter preparation is available as Exedrin Migraine. 

The chronic progression of events that lead to NSAID/analgesic related papillary necrosis are well known since the days of the first descriptions of chronic combined analgesics abuse nephropathy and the subsequent extensive investigations which defined the consequences of chronic (5-20 years) exposure of the kidney to high doses of analgesic combinations such as salicylate and acetaminophen (the metabolite of phenacetin) often with the addition of caffeine [106]. 

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