Salicylates

Salicylates

Salicylates are among the most commonly used pain medications.They’re used regularly to control pain and reduce fever and in-flammation.

Cheap, easy, and reliable

Salicylates usually cost less than other analgesics and are readily available without a prescription. Aspirin is the most commonly used salicylate. Other common salicylates include:

·                 choline magnesium trisalicylate

·                 choline salicylate

·                 diflunisal

·                 salsalate

·                 sodium salicylate.

Pharmacokinetics (how drugs circulate)

Taken orally, salicylates are absorbed partly in the stomach, but primarily in the upper part of the small intestine. The pure and buffered forms of aspirin are absorbed readily, but sustained-release and enteric-coated salicylate preparations are absorbed more slowly. Food or antacids in the stomach also delay absorp-tion. Salicylates given rectally have a slower, more erratic absorp-tion.

Distribution, metabolism, and excretion

Salicylates are distributed widely throughout body tissues and fluids, including breast milk. In addition, they easily cross the placental barrier.

The liver extensively metabolizes salicylates into several metabolites. The kidneys excrete the metabolites along with some unchanged drug.

Pharmacodynamics (how drugs act)

The different effects of salicylates stem from their separate mech-anisms of action. They relieve pain primarily by inhibiting the syn-thesis of prostaglandin. (Recall that prostaglandin is a chemical mediator that sensitizes nerve cells to pain.) In addition, they may also reduce inflammation by inhibiting the prostaglandin synthesis and release that occurs during inflammation.

Hot and bothered

Salicylates reduce fever by stimulating the hy-pothalamus, producing dilation of the peripher-al blood vessels and increased sweating. This promotes heat loss through the skin and cooling

by evaporation. Also, because prostaglandin E increases body temperature, inhibiting its production lowers a fever.

No clots allowed

One salicylate, aspirin, permanently inhibits platelet aggregation (the clumping of platelets to form a clot) by interfering with the production of a substance called thromboxane A₂, necessary for platelet aggregation. Not all salicylates have this effect. For exam-ple, choline magnesium doesn’t increase bleeding time.

Pharmacotherapeutics (how drugs are used)

Salicylates are used primarily to relieve pain and reduce fever. However, they don’t effectively relieve visceral pain (pain from the organs and smooth muscle) or severe pain from trauma.

You give me fever…

Salicylates won’t reduce a normal body temperature. They can re-duce an elevated body temperature, and will relieve headache and muscle ache at the same time.

What kind of joint is this?

Salicylates can provide considerable relief in 24 hours when they’re used to reduce inflammation in rheumatic fever, rheuma-toid arthritis, and osteoarthritis.

Go with the flow

As a result of its anticlotting properties, aspirin can be used to en-hance blood flow during myocardial infarction (MI) and to pre-vent recurrence of MI.

How low can you go?

No matter what the clinical indication, the main guideline of sali-cylate therapy is to use the lowest dose that provides relief. This reduces the likelihood of adverse reactions. (See Adverse reac-tions to salicylates.)

Drug interactions

Because salicylates are highly protein-bound, they can interact with many other protein-bound drugs by displacing those drugs from sites to which they normally bind. This increases the serum concentration of the unbound active drug, causing increased phar-macologic effects (the unbound drug is said to be potentiated).

The following drug interactions may occur:

·                 Oral anticoagulants, heparin, methotrexate, oral antidiabetic agents, and insulin are among the drugs that have an increased ef-fect or risk of toxicity when taken with salicylates.

·                 Probenecid, sulfinpyrazone, and spironolactone may have a de-creased effect when taken with salicylates.

·                 Corticosteroids may decrease plasma salicylate levels and in-crease the risk of ulcers.

·                 Alkalinizing drugs and antacids may reduce salicylate levels.

·                 The antihypertensive effect of angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic blockers may be reduced when these drugs are combined with salicylates.

·                 NSAIDs may have a reduced therapeutic effect and an increased risk of GI effects when taken with salicylates. (See Using salicy-lates safely.)