Drug Interactions: ANALGESICS AND ANTI-INFLAMMATORY DRUGS

Drug Interactions

     

These are various reactions of a certain drug to other drugs, food, laboratory tests, and herbal products which can either be beneficial or detrimental to the patient depending on the result of the interaction.

In general, drug interactions can occur due to chemical, physiologic, or pharmacological actions. The object drug (one with desired effect) can be altered by a precipitant drug (one causing the interaction) by several mechanism. Pharmacokinetic alterations can be brought up by any alteration in gastric pH, complexation and adsorption of object drug, delayed or rapid rate of gastric emptying, malabsorption, displacement from protein binding sites, induction or inhibition of biotransformation, and alteration of excretion. Pharmacodynamic interactions can occur from antagonism, potentiation/addition/synergistic effects, alteration of electrolytes, interactions at receptor sites, alteration of gastrointestinal flora, and different drug combinations.

Overview of Analgesics and NSAIDs' Mechanism of Action

Analgesia, or loss of sensitization to pain, can be achieved using drug groups such as opioids, acetaminophen, steroids, and non-steroidal anfi-inflammatory agents. Other drugs such as local and general anesthetics can also give the same effect although their use is more on the loss of sensitization to stimuli rather than pain alone.

Steroids, acetaminophen and NSAIDs are more directed to the inhibition of prostaglandin production. Prostaglandins are endogenous substances which are considered to be a chemical mediator for pain and inflammation. These substances are derived as end products from the metabolic pathway of arachidonic acid (ARA). Free ARA, the one undergoes biotransformation,  is cleaved out from the phosphobilipid layer of the cell membrane by the enzyme phospholipase A2. The free ARA will be enacted by cyclooxygenase (COX) enzyme and/or lipooxygenase enzyme, however the latter is not directly relevant to pain and inflammation. The cycooxygenase enzyme will act on the arachidonic acid to form prostaglandins which as discussed earlier will contribute to the pain sensation. Steroids, such as prednisone, will act on the phospholipase A2 enzyme which will limit the amount of free ARA to be converted to prostaglandins. NSAIDs can inhibit either COX1 or COX 2 or both to prevent the formation of prostaglandins. Acetamiinophen is a weak inhibitor of COX1 and COX in the periphery due to the presence of peroxidases in inflammatory sites but pose its inhibition on COX3 found in the central nervous system in which the analgesic effect is directed to the brain pain centers.

A more powerful group of analgesics are called collectively as opioids. With morphine as the prototype, they will act not on the ARA-COX-prostaglandin pathway but mimics the action of endorphins and they bind to opioid receptors. Such receptors are called mu, kappa, delta, and iota receptors. When opioid drugs will bind to these receptors especially to mu receptors, this will result to depression of certain brain functions that will lead to analgesia.

Morphine is a drug that is used for patients who are terminally ill and requires analgesia for hospice treatment. NSAIDs like aspirin, ibuprofen, and mefenamic acids are over the counter drugs that may be used by anyone even without medical advice. Acetaminophen is the most commonly used drug for fever due to safety profile.

List of Drug-Drug Interactions for Analgesics and NSAIDs
List of Drug-Food Interactions for Analgesics and NSAIDs
List of Drug-Laboratory Interactions for Analgesics and NSAIDs

References:


Brunton, L. et.al. (2006). Goodman and gilman's the pharmacologic basis of therapeutics. New York: McGraw Hill. 11th Ed.
Hacker, M. et.al. (2009). Pharmacology principles and practice. San Diego, CA: Elsevier
Katzung, B. (2007). Basic and clinical pharmacology. New York: McGraw Hill. 10th Ed.
Rybacki, J. (2004). Essential guide to prescription drugs. New York: Harper Collins