Drugs and Pain Control

Drugs used to control pain range from mild, over-the-counter (OTC) preparations, such as paracetamol, to potent general anesthetics. Drug classes in this category include:

  • non-opioid analgesics, antipyretics, and nonsteroidal anti-inflammatory drugs (NSAIDs)
  • opioid agonist and antagonist drugs
  • opioid analgesics, antipyretics, and NSAIDs

Non-opioid analgesics, antipyretics, and NSAIDs are a broad group of pain medications. In addition to pain control, they also produce antipyretic (fever control) and anti-inflammatory effects. They can be used alone or as adjuvant medications. These drugs have a ceiling effect (where an increasing dose has a progressively smaller incremental response) and no physical dependence is associated with them.

The drug classes included in this group are:

  • salicylates (especially aspirin), which are widely used
  • the para-aminophenol derivative paracetamol
  • NSAIDs.

Salicylates

Salicylates are among the most commonly used pain medications. They’re used to control pain and reduce fever and inflammation.

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 for anti-inflammatory drug therapy.

Other salicylates include:

  • choline salicylate
  • diflunisal

Pharmacokinetics

Taken orally, salicylates are partially absorbed in the stomach, but are primarily absorbed in the upper part of the small intestine. The pure and buffered forms of aspirin reabsorb readily, but for sustained-release and enteric-coated salicylate preparations, food or antacids in the stomach delay absorption. Salicylates given rectally have a slower, more erratic absorption. Entericcoated products are slowly absorbed and not suitable for acute effects. They cause less GI bleeding and may be better suited for long-term therapy such as for arthritis. Absorption after rectal administration is slow and variable, depending on how long the suppository is retained.

Excellent distribution

Salicylates are distributed widely throughout body tissues and fluids, including breast milk. In addition, they easily cross the placenta. The liver metabolises salicylates extensively into several metabolites. The kidneys excrete the metabolites and some unchanged drug.

Pharmacodynamics

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

Salicylates reduce fever by stimulating the hypothalamus, and producing peripheral blood vessel dilation 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.

Bonus effect

One salicylate, aspirin, inhibits platelet aggregation (the clumping of platelets to form a clot) permanently by interfering with the production of thromboxane A2, a substance necessary for platelet aggregation. Unlike aspirin, NSAIDs’ effects on platelet aggregation are temporary. As a result, aspirin can be used to enhance blood flow during myocardial infarction (MI) and to prevent an event such as recurrent MI.