Module 9 - Pain & Inflammation Flashcards
What type of drug is Acetaminophen and what is its MOA?
- Type: Analgesic & antipyretic
- MOA: Unclear MOA, possibly inhibits prostaglandin synthesis however it has little or no anti-inflammatory action and does not inhibit platelet aggregation. Acts within the CNS to reduce fever and pain.
What are the indications for using acetaminophen?
Analgesic - for mild pain & antipyretic
- It is equal in effectiveness to aspirin and NSAIDs as an analgesic and antipyretic (325 - 500 mg qid) but lacks anti-inflammatory properties
What are the s/x associated with acetaminophen?
- No remarkable SE.
- May cause elevated ALT levels in hispanic patients
What are some toxicities that can occur with acetaminophen?
- Toxicity often occurs with acetaminophen overdoses, and 15g of it is fatal
- Often no early s/x, just mild GI cramping, nausea or vomiting.
- Later urine output decreases with hematuria and upper right abdominal pain. Liver enzymes (LDH, SGOT, SGPT) are increased and irreversible hepatic necrosis occurs with increased abdominal pain, jaundice, and anuria. The patient becomes hypoglycemia, goes into a coma and dies.
- Maximum FDA recommended dosage is 3g/day
What is the antidote for an acetaminophen overdose?
- N-acetylcysteine (Mucomyst) given IV over 15minutes along with gastric lavage, cathartics, and activated charcoal.
What are the drug interactions associated with acetaminophen?
- Acetaminophen can increase the anticoagulant effect of warfarin but it does so inconsistently. The mechanism is not established.
- The Medical letter suggests monitoring the INR in patients on chronic warfarin therapy more closely when they take more than 2 g per day of acetaminophen for more than a few days
What are the indications for using Transdermal Fentanyl (Duragesic)?
Transdermal fentanyl [Duragesic] offers ease of dosing, consistent effects, and convenience for chronic pain control in patients with chronic or terminal cancer pain.
Describe how Transdermal fentanyl [Duragesic] is used
- It is placed on nonirradiated skin of the upper torso (clip - do not shave- hair) for 72 hours (based on morphine equivalency dose) and makes repeated injection or continuous IV infusion unnecessary.
- After 72 h remove old system and apply new patch. Do not wash skin with soaps, alcohol, or lotions (may alter skin characteristics & absorption).
- Drug release is proportional to the surface area of the patch.
What is the onset of action of Transdermal fentanyl [Duragesic]?
- Blood levels may be detected as early as 1-2 h after application but delays up to 17-48 h occur (due to accumulation of drug within the skin).
- Elimination half-life is 13-25 h, greater in elderly (43 vs. 20 h).
What are the contraindications to using Transdermal fentanyl [Duragesic]?
It is contraindicated in patients with acute postoperative pain; deaths reported with the drug have usually been in patients treated for postoperative pain.
What is the MOA of Opioids?
Opioid analgesics act on specific receptors (most importantly mu & kappa receptors) on neurons in the spinal cord and brain to raise pain threshold and reduce pain perception and the emotional reaction to pain.
What is the MOA of NSAIDS?
In contrast, nonopioids (e.g., aspirin) act on peripheral nerves by blocking synthesis of substances that stimulate peripheral nerve endings in damaged tissue.
Opioids are the DOC in which type of situations?
- Although opioids are usually considered the drugs of choice for severe acute pain and chronic cancer pain, the effectiveness of opioids overlaps that of the NSAIDs.
- Oral codeine, propoxyphene, tramadol, & pentazocine are no more effective when taken alone than aspirin or acetaminophen.
- Morphine & other full agonists, unlike NSAIDs, have no ceiling of their analgesic effectiveness, except that imposed by adverse effects.
What are the adverse effects associated with opioid administration?
- Sedation, grogginess, dizziness, nausea, vomiting, and constipation are the most common adverse effects.
- Respiratory depression is the most serious.
- Even usual doses of opioids may decrease respiratory drive and cause apnea in patients with COPD, cor pulmonale, decreased respiratory reserve, or preexisting respiratory depression.
- May cause Hypotension & bradycardia
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What are the indications for using opioids?
- Relief of moderate to severe pain (affects both perception of & reaction to pain)
- Adjunctive treatment of acute CHF, pulmonary edema, or dyspnea (relief of pulmonary edema is remarkable but the mechanism of action is unclear. Opioids decrease the perception of shortness of breath & anxiety and decrease cardiac preload & afterload).
- Ventilator control
- Special anesthesia (fentanyl IV may be the primary anesthetic in cardiovascular & high risk surgery. Epidural and subarachnoid administration provides long-lasting effect with a minimum of side effects).
- Relief of cough (requires doses lower than needed for analgesia and there are effective non-analgesic nonaddictive synthetic compounds. Cough suppression may lead to accumulation of secretions).
- Pre- and post-operative analgesia
- Treatment of diarrhea (effective but do not substitute for chemotherapy if diarrhea is associated with infection).
What happens when Mu receptors are activated in the CNS?
Activation of mu receptors produces analgesia, respiratory depression, sedation, euphoria, physical dependence and constipation.
What are the signs of opioid toxicity?
- Cause of death is respiratory depression
- Triad symptoms include pin point pupils, respiratory depression, and loss of consciousness with decreased blood pressure.
- Treatment is naloxone or nalmefene, ventilatory support, parenteral fluids and/or sympathomimetics to support CV status.
What are some drug interactions associated with opioids?
- Additive effect with other CNS depressants.
- Cimetidine may prolong and intensify effect.
- Prolongation of neuromuscular block.
- When given with MAO inhibitors, they may cause excessive CNS depression or hyperpyresis and hypertension. Death (due to serotonin syndrome) has been reported with meperidine & MAOI and serious reactions with dextromethorphan and MAOI.
- Change in urine pH has been reported to affect methadone excretion.
- Certain fluoroquinolones (levofloxacin, ofloxacin, perfloxacin and enoxacin) were shown to cause false-positive opiate results in urinary assays
- Alcohol: A Black Box Warning has been added to the labeling of extended-release morphine capsules (Avinza) regarding the potential for fatal dose dumping when the product is administered with alcoho
How much stronger is oxycodone compared with codeine?
Oxycodone and oxycodone ER is 9.5 times more effective than codeine as an analgesic and more potent than oral morphine.
What type of drug is Ketorolac and what is its MOA?
- Type: NSAID
- MOA: Act on peripheral nerves by blocking synthesis of substances that stimulate peripheral nerve endings in damaged tissue.
What are the indications for using Ketorolac?
- When given as an IM injection in doses of 30-60 mg (followed by 15-30 mg q6h), it is an alternative to morphine or meperidine. It may also be given IV or orally
- It is indicated only for short-term (up to 5 days) management of moderately severe acute pain.
What are some adverse effects of using Ketorolac?
- Causes peptic ulcers (with GI bleeding or perforation)
- Renal failure in patients who may be volume depleted or elderly subjects
- Because it inhibits platelet function, it is contraindicated in patients at risk of bleeding.
- Its use in labor and delivery is contraindicated because it may adversely affect fetal circulation and inhibit uterine contractions.
What type of drug is Asprin and what is its MOA?
- Type: 1st generation NSAID / salicylate
- MOA: Aspirin irreversibly inhibits the cyclooxygenase enzymes which are responsible for vasodilation and platelet aggregation as well as for the formation of prostaglandins by injured or inflamed tissue. The duration of action depends on how quickly specific tissues can synthesize new molecules of COX-1 and COX-2. Aspirin inhibits synthesis of prostaglandins that have inflammatory effects and inhibits platelet thromboxane, which, having no nucleus, the platelet cannot replenish the cyclooxygenase.
This is the prototype drug
What are the indications for using Asprin?
- Analgesia, anti-inflammatory (including rheumatoid arthritis; osteoarthritis), antipyretic, and antiplatelet (reduces recurrent strokes or MI).
- Aspirin is considered by many as the 1st line drug for both rheumatoid and osteoarthritis; others prefer a nonacetylated salicylate, NSAIDs or acetaminophen as the preferred drug for osteoarthritis.
How does Aspirin act as an antipyretic?
- Pyrogens in the blood (released by bacteria or trauma or found in fluids) cause release of prostaglandins that act on the temperature control center in the hypothalamus, setting it at a higher level. This causes shivering (muscle contraction) and an increase in body temperature.
- Antipyresis occurs by inhibition of cyclooxygenase and the release of prostaglandins. This resets the “thermostat” in the hypothalamus to a lower value. Salicylates (and NSAIDs) do NOT lower normal body temperature or the increase in temperature caused by exercise or hot weather.
- The dose of aspirin to produce antipyresis (325-650 mg q4h) is less than that needed for anti-inflammatory action. Toxic doses of salicylates may cause hyperpyrexia.
How does Aspirin produce analgesia?
Analgesia is qualitatively and quantitatively different from that produced with opioids and essentially the same as that produced by NSAIDs. These agents appear to reduce pain sensation by inhibiting cyclooxygenase that forms pain-producing prostaglandins. Salicylates (and NSAIDs) do NOT affect lipoxygenase enzymes, which form the leukotrienes.
How does aspirin produce an antiplatelet effect?
- The acetyl part of aspirin dissociates then binds irreversibly to platelet COX. This action prevents synthesis of thromboxane A2 Thromboxane (TXA2) is a prostaglandin that enhances platelet aggregation while prostacyclin (PGI2) decreases aggregation.
- Low doses (60-80 mg daily) of aspirin can irreversibly inhibit thromboxane production in platelets (which have no nucleus to form additional thromboxane, hence the action of aspirin persists for the life of the platelet or 3-7 d) without markedly affecting prostacyclin in the endothelial cells of the blood vessels.
What are the s/x associated with Aspirin?
- CNS: Dizziness, confusion, tinnitus, drowsiness, and headache.
- Blood: Abnormal bruising or bleeding and increased bleeding time.
- Respiratory: Wheezing and bronchoconstriction. This can be fatal, especially in patients with nasal polyps.
- CV: Edema, hypertension, and premature closure of fetal ductus arteriosus.
- GI: Aspirin and NSAIDs prevent prostaglandins (COX-1) from being formed resulting in epigastric distress. Nausea and vomiting are most common with abdominal pain and bleeding occurring in some patients. Not only is salicylic acid irritating to the gastric mucosa, its antiprostaglandin effect reduces the cytoprotective mechanisms of the stomach.
- Renal: Certain prostaglandins, produced by the kidneys, are responsible for maintaining renal blood flow. Cyclooxygenase inhibitors prevent the synthesis of these prostaglandins, which may result in retention of sodium and water and, consequently, edema. Interstitial nephritis may occur with all NSAIDs.
- Skin: Aspirin& NSAIDs are cross allergenic. Urticaria may occur. Hypersensitivity reactions occur especially in patients with rhinitis, nasal polyps and asthma.
- Reproduction: Prolonged labor. In the pregnant woman, salicylates (and NSAIDs) may delay gestation and cause premature closure of the ductus arteriosus in utero. Maternal use has been linked to low birth weight infants and hemorrhage in premature infants. Salicylates are excreted in breast milk
- Acid-base balance: Salicylates stimulate the respiratory center resulting in respiratory alkalosis
- Reye syndrome: Reye syndrome is characterized by encephalopathy, liver dysfunction and death. It occurs most often in children and teenagers infected with influenza or chickenpox viruses (Box Warning). Administration of aspirin appears to increase the risk of its development.
- Otic: There is a linear relationship between plasma concentration and intensity of tinnitus and degree of hearing loss.
