Pharmacology Flashcards: Opioid Analgesics, NSAIDs, Acetaminophen, Pain Management

Opioids relieve pain by binding to mu, kappa, and delta opioid receptors in the brain, spinal cord, and peripheral tissues, reducing the perception of pain and the emotional response to it. Common opioids include morphine, oxycodone, hydrocodone, fentanyl, and codeine. Major risks include respiratory depression, which is the primary cause of opioid overdose death; physical dependence developing within days to weeks of regular use; constipation that persists throughout treatment without tolerance developing; and sedation. Naloxone is the reversal agent.

Naloxone, brand name Narcan, is an opioid antagonist that rapidly reverses opioid overdose by competitively binding to opioid receptors and displacing the opioid molecule. It is administered intranasally, intramuscularly, or intravenously, with effects beginning within two to five minutes. Naloxone reverses respiratory depression, sedation, and hypotension caused by opioid overdose. Its duration of action is 30 to 90 minutes, which is shorter than most opioids, so patients may require repeated doses or continuous monitoring as the naloxone wears off.

Nonsteroidal anti-inflammatory drugs, or NSAIDs, work by inhibiting cyclooxygenase enzymes COX-1 and COX-2, reducing the production of prostaglandins that mediate pain, inflammation, and fever. Common NSAIDs include ibuprofen, naproxen, diclofenac, and ketorolac. Side effects include gastrointestinal irritation, ulceration, and bleeding because COX-1 prostaglandins normally protect the stomach lining. NSAIDs also increase cardiovascular risk, impair renal blood flow, and can worsen hypertension and heart failure.

The maximum recommended daily dose of acetaminophen is 4,000 milligrams for healthy adults, though many guidelines now suggest a lower maximum of 3,000 milligrams to reduce liver damage risk. Exceeding the maximum dose causes hepatotoxicity because a toxic metabolite called NAPQI overwhelms the liver's glutathione stores. Acetaminophen overdose is the leading cause of acute liver failure in the United States. The antidote is N-acetylcysteine, or NAC, which replenishes glutathione.

Tolerance is a physiological adaptation where higher doses are needed to achieve the same pain relief, developing predictably with regular use. Physical dependence is a physiological state where abrupt discontinuation causes withdrawal symptoms like anxiety, sweating, nausea, and muscle aches. Addiction is a behavioral disorder characterized by compulsive drug seeking, continued use despite harm, and loss of control. Tolerance and dependence are expected pharmacological responses that occur in anyone taking opioids regularly and do not indicate addiction.

Equianalgesic dosing compares the pain-relieving potency of different opioids to allow safe conversion between medications. Morphine 10 milligrams intravenously or 30 milligrams orally is the standard reference point. For example, hydromorphone is approximately seven times more potent than morphine, so 1.5 milligrams of hydromorphone equals roughly 10 milligrams of morphine intravenously. Fentanyl is approximately 100 times more potent than morphine.

Ketorolac is a powerful injectable and oral NSAID used for moderate to severe acute pain, but it is limited to a maximum of five days of treatment because of its high risk of serious gastrointestinal bleeding, ulceration, and perforation. Ketorolac provides pain relief comparable to moderate-dose opioids without the sedation and respiratory depression, making it valuable for postoperative and emergency department pain management. However, its potent inhibition of COX-1 prostaglandins that protect the stomach lining makes prolonged use dangerous.

The World Health Organization analgesic ladder is a stepwise approach to pain management with three levels. Step one uses non-opioid analgesics like acetaminophen and NSAIDs for mild pain. Step two adds weak opioids like codeine or tramadol for moderate pain not controlled by non-opioids alone. Step three uses strong opioids like morphine, oxycodone, or fentanyl for severe pain. Adjuvant medications like anticonvulsants, antidepressants, and corticosteroids can be added at any step. ---