NSAIDs & Non-Narcotic Analgesics Flashcards
Which COX enzyme is considered constitutive, as it is expressed in all tissues at all times and plays a prominent role in responding to physiologic and pathologic stimuli
COX-1
Which COX enzyme is inducible in some tissues, plays a physiologic role in the kidney where it complements COX-1, and plays a prominent role in response to any pathologic stimuli?
COX-2
MOA of aspirin
Irreversible inhibition of COX1 and COX2
AEs of aspirin
Gastric ulceration
Bleeding
Renal impairment possibly leading to papillary necrosis (more common in advanced age, pre-existing renal function, hypovolemia, HTN, hepatic cirrhosis, and heart failure pts)
Aspirin-induced asthma
Reye syndrome if given during viral illness
Hypersensitivity reactions
[to minimize risk of ASA-induced ulcers, test for Hpylori before starting therapy and give a PPI. Stop high-dose ASA before surgery to prevent bleeding complications.]
Indications for aspirin use
Suppression of inflammation, relief of mild to moderate pain, reduction of fever, prevention of MI and stroke
Commonly used for RA and other chronic inflammatory conditions
Also used to control post-op pain
What effect do ibuprofen, naproxen, and other non-aspirin NSAIDs have on antiplatelet actions of aspirin?
They antagonize the antiplatelet actions of aspirin, thus decreasing protection against MI and stroke
[minimize this risk by taking ASA 2 hrs before other NSAIDs]
5 basic events in progression of aspirin/salicylate toxicity
- Salicylates uncouple mitochondrial oxphos in CNS
- Respiratory center registers decreased ATP as hypoxemia and responds with hyperventilation
- Hyperventilation leads to drop in pCO2 and respiratory alkalosis — eventually prompting kidney to deplete bicarbonate
- Organic acids accumulate because ATP is no longer generated through Krebs cycle
- Metabolic acidosis becomes life-threatening
Like aspirin, non-aspirin NSAIDs (e.g., acetaminophen) may inhibit COX-1 and/or COX-2, suppress inflammation, pain, and fever, and may increase risk of gastric ulceration, renal impairment, and bleeding.
What are some important differences in non-aspirin NSAIDs when compared to aspirin?
Reversible
Suppress platelet aggregation, but use actually increases risk of MI and stroke
Acetaminophen suppresses pain and fever, but not _________. Its mechanism of action involves inhibition of ______ synthesis in the CNS but not in the periphery, consequently: it does not cause GI ulceration, suppression of platelet aggregation, or impairment of renal function
Inflammation; prostaglandin
Toxicities of acetaminophen
Hepatic necrosis from acetaminophen overdose results from accumulation of toxic metabolites when glutathione is depleted; risk is increased by undernourishment, alcohol, and pre-existing liver dz; Tx with acetylcysteine
Acetaminophen also inhibits metabolism of warfarin, and can increase risk of bleeding
Common anti-inflammatory indications frfom NSAIDs
Osteoarthritis and other arthritides
Bursitis
Gout “flare”
Ankylosing spondylitis
Dysmenorrhea
Headache
When taken for primary prevention, low-dose aspirin reduces the risk of first ____ in men, and first _______ in women
MI; ischemic stroke
Contraindications to NSAIDs
CKD with creatinine clearance <60 mL/min per 1.73 m^2
Active duodenal or gastric ulcer
Cardiovascular disease, particularly heart failure or uncontrollable HTN
NSAID allergy
Ongoing tx with anticoagulants - warfarin
Second generation NSAID that suppresses inflammation, pain, and fever, but does not inhibit platelet aggregation, so does NOT pose a risk of bleeding, and may cause less gastric ulceration than nonselective inhibitors
Celecoxib
Celecoxib selectively blocks _____
COX-2
Celecoxib ______ risk of MI and stroke
Increases
[thought to be due to blockade of prostacyclin synthesis in blood vessels]
Diclofenac, ketorolac, and nabumetone are in what drug class?
NSAIDs
Where NSAID therapy is required for pts at risk of cardiovascular complications, ______is recommended as the NSAID of choice
Naproxen
In pts with renal disease, administration of NSAIDs rapidly reduces renal function. This is largely due to _____ inhibition
NSAID-mediated suppression of _____ in the gastric mucosa increases acid secretion and compromises integrity of gastric mucosa
_______-selective inhibitors are associated with increased risk of MI, stroke, and/or heart failure
COX-1
COX-1
COX-2
Tricyclic antidepressants have independent analgesic effects as well as an ability to relieve the depressive symptoms associated with chronic pain. ______ has been the most widely studied TCA in chronic pain
Amitriptyline
[others include doxepin, imipramine, nortriptyline, desipramine]
AEs of TCAs used to tx chronic pain
Dry mouth Constipation Tachycardia Palpitations Nausea Vomiting Sedation Mental clouding
[AEs may diminish over time]
______ and ______ are SNRIs used to treat chronic pain and are especially beneficial in pts with concurrent depression
Venlafaxine
Duloxetine
AEs of SNRIs like venlafaxine and duloxetine used to tx pain
Nausea Dizziness Diaphoresis Sexual dysfunction Insomnia/agitation Increased BP
GABA analog used for pain that exerts its effects by binding to alpha2-delta subunit of voltage-gated calcium channels within the CNS — modulates calcium influx at nerve terminals, thereby inhibiting excitatory NT release; has few interactions with other drugs, but AEs are common (e.g., dizziness, sleepiness, etc)
Pregabalin
