CHAPTER 33 NONSTEROIDAL ANTIINFLAMMATORY DRUGS AND ACETAMINOPHEN Robert A. Duarte, MD, Charles E. Argoff, MD 1. List the indications for treatment with aspirin, acetaminophen, and nonsteroidal antiinflammatory drugs (NSAIDs)? Aspirin, acetaminophen, and other NSAIDs are generally considered to be the drugs of choice for mild to moderate pain. They represent the first step in the analgesic ladder proposed by the World Health Organization. These agents have a relatively low abuse potential and are primarily used in nociceptive somatic pain syndromes, e.g., arthritis. They do, however, have a ceiling effect. Pure opioid analgesics such as hydromorphone and morphine do not. The ceiling effect refers to the dose after which additional quantities of an analgesic no longer provide additional analgesia. For example, 2000 mg of aspirin does not provide more analgesia than 1000 mg of aspirin and may lead to more side effects. 2. Describe the mechanism of action of the NSAIDs The antiinflammatory effect of nonsteroidal antiinflammatory agents is due mainly to inhibition of the enzyme cyclooxygenase (COX), which is required for synthesis of prostaglandins and thromboxanes. There are two COX isoforms: COX1, which is expressed constitutively in most tissues and is thought to protect the gastric mucosa and platelets, and COX2, which is expressed constitutively in the brain and kidney but can be induced at sites of inflammation. Traditional NSAIDs are nonselective COX1 and COX2 inhibitors, whereas celecoxib is a selective COX2 inhibitor. 3. What are the major pharmacokinetic differences among the NSAIDs? All the NSAIDs possess similar absorption characteristics. In general, they are rapidly absorbed after oral and rectal administration. They are highly protein-bound and metabolized primarily in the liver. However, durations of action vary markedly. Some drugs, such as ibuprofen, require dosing every 4 to 6 hours, whereas piroxicam can be given once a day. The newer COX2 inhibitors also require only once or twice daily dosing. 4. List the most common side effects associated with the traditional NSAIDs Gastrointestinal (GI) irritation, nausea, and impairment of platelet aggregation are the most common side effects associated with the traditional NSAIDs. These side effects may lead to dyspepsia, GI ulcers, and bleeding. Some of the nonacetylated salicylates (e.g., choline magnesium trisalicylate) do not inhibit platelet function. Other known side effects include peripheral edema and elevated blood pressure. 5. Describe the clinical presentation for acute acetaminophen overdose Symptoms of acetaminophen overdose include vague abdominal pain during the first week, followed by signs of hepatic failure. At doses of 200 to 250 mg/kg, acetaminophen is hepatotoxic. Acetaminophen, at doses of 400 mg/kg, can be fatal. 6. What are the risks of combining NSAIDs with acetaminophen? The risk of analgesic nephropathy appears to increase when different NSAIDs are used together or in combination with acetaminophen. This effect is generally seen in long-term use. The primary lesion is papillary necrosis with secondary interstitial nephritis. 7. What is the risk of nephrotoxicty with NSAIDs? Aspirin and NSAIDs at therapeutic doses generally do not cause renal disease in patients with normal renal function. However, problems such as nephrotic syndrome, acute interstitial nephritis, and acute renal failure have been observed when aspirin and other nonsteroidals are given to patients with abnormal renal function. This can occur as a result of the inhibition of renal prostaglandin production by NSAIDs and the coxibs. Congestive heart failure, hepatic cirrhosis, collagen vascular disease, intravascular volume depletion, and arthrosclerotic heart disease are known contributing factors that may increase the risk of renal failure. 8. Which groups of NSAIDs are available in the United States? Traditional, or nonselective, COX1 and COX2 Inhibitors Salicylate (salsalate, diflunisal, and choline magnesium trisalicylate) Proprionic (ibuprofen, ketoprofen, naproxen, fenoprofen) Indole (indomethacin, sulindac, tolmetin) Fenamate (mefenamic, meclofenamate) Only gold members can continue reading. Log In or Register to continue Share this:Click to share on Twitter (Opens in new window)Click to share on Facebook (Opens in new window) Related Related posts: Neuroimaging in the Patient with Pain Pharmacologic Management Tension-Type Headache Neuropathic Pain Migraine Temporary Neural Blockade Stay updated, free articles. Join our Telegram channel Join Tags: Pain Management Secrets Jun 14, 2016 | Posted by admin in PAIN MEDICINE | Comments Off on Nonsteroidal Antiinflammatory Drugs and Acetaminophen Full access? Get Clinical Tree
CHAPTER 33 NONSTEROIDAL ANTIINFLAMMATORY DRUGS AND ACETAMINOPHEN Robert A. Duarte, MD, Charles E. Argoff, MD 1. List the indications for treatment with aspirin, acetaminophen, and nonsteroidal antiinflammatory drugs (NSAIDs)? Aspirin, acetaminophen, and other NSAIDs are generally considered to be the drugs of choice for mild to moderate pain. They represent the first step in the analgesic ladder proposed by the World Health Organization. These agents have a relatively low abuse potential and are primarily used in nociceptive somatic pain syndromes, e.g., arthritis. They do, however, have a ceiling effect. Pure opioid analgesics such as hydromorphone and morphine do not. The ceiling effect refers to the dose after which additional quantities of an analgesic no longer provide additional analgesia. For example, 2000 mg of aspirin does not provide more analgesia than 1000 mg of aspirin and may lead to more side effects. 2. Describe the mechanism of action of the NSAIDs The antiinflammatory effect of nonsteroidal antiinflammatory agents is due mainly to inhibition of the enzyme cyclooxygenase (COX), which is required for synthesis of prostaglandins and thromboxanes. There are two COX isoforms: COX1, which is expressed constitutively in most tissues and is thought to protect the gastric mucosa and platelets, and COX2, which is expressed constitutively in the brain and kidney but can be induced at sites of inflammation. Traditional NSAIDs are nonselective COX1 and COX2 inhibitors, whereas celecoxib is a selective COX2 inhibitor. 3. What are the major pharmacokinetic differences among the NSAIDs? All the NSAIDs possess similar absorption characteristics. In general, they are rapidly absorbed after oral and rectal administration. They are highly protein-bound and metabolized primarily in the liver. However, durations of action vary markedly. Some drugs, such as ibuprofen, require dosing every 4 to 6 hours, whereas piroxicam can be given once a day. The newer COX2 inhibitors also require only once or twice daily dosing. 4. List the most common side effects associated with the traditional NSAIDs Gastrointestinal (GI) irritation, nausea, and impairment of platelet aggregation are the most common side effects associated with the traditional NSAIDs. These side effects may lead to dyspepsia, GI ulcers, and bleeding. Some of the nonacetylated salicylates (e.g., choline magnesium trisalicylate) do not inhibit platelet function. Other known side effects include peripheral edema and elevated blood pressure. 5. Describe the clinical presentation for acute acetaminophen overdose Symptoms of acetaminophen overdose include vague abdominal pain during the first week, followed by signs of hepatic failure. At doses of 200 to 250 mg/kg, acetaminophen is hepatotoxic. Acetaminophen, at doses of 400 mg/kg, can be fatal. 6. What are the risks of combining NSAIDs with acetaminophen? The risk of analgesic nephropathy appears to increase when different NSAIDs are used together or in combination with acetaminophen. This effect is generally seen in long-term use. The primary lesion is papillary necrosis with secondary interstitial nephritis. 7. What is the risk of nephrotoxicty with NSAIDs? Aspirin and NSAIDs at therapeutic doses generally do not cause renal disease in patients with normal renal function. However, problems such as nephrotic syndrome, acute interstitial nephritis, and acute renal failure have been observed when aspirin and other nonsteroidals are given to patients with abnormal renal function. This can occur as a result of the inhibition of renal prostaglandin production by NSAIDs and the coxibs. Congestive heart failure, hepatic cirrhosis, collagen vascular disease, intravascular volume depletion, and arthrosclerotic heart disease are known contributing factors that may increase the risk of renal failure. 8. Which groups of NSAIDs are available in the United States? Traditional, or nonselective, COX1 and COX2 Inhibitors Salicylate (salsalate, diflunisal, and choline magnesium trisalicylate) Proprionic (ibuprofen, ketoprofen, naproxen, fenoprofen) Indole (indomethacin, sulindac, tolmetin) Fenamate (mefenamic, meclofenamate) Only gold members can continue reading. Log In or Register to continue Share this:Click to share on Twitter (Opens in new window)Click to share on Facebook (Opens in new window) Related Related posts: Neuroimaging in the Patient with Pain Pharmacologic Management Tension-Type Headache Neuropathic Pain Migraine Temporary Neural Blockade Stay updated, free articles. Join our Telegram channel Join Tags: Pain Management Secrets Jun 14, 2016 | Posted by admin in PAIN MEDICINE | Comments Off on Nonsteroidal Antiinflammatory Drugs and Acetaminophen Full access? Get Clinical Tree
