NON-Opioid Analgesics (Exam #2) Flashcards
What is the rate limiting step of PG synthesis, and what are the two possible pathways following this step (what is made in each)?
RLS is Arachidonic Acid
- Lipoxygenase = leukotrienes
- Cyclooxygenase = PGs
Prostacyclin:
- Produced by COX-1 or COX-2?
- Vasoconstriction or Vasodilation?
- Inhibit platelet aggregation or promote platelet aggregation?
PROSTACYCLIN (PGI2)
- COX-2
- Vasodilation
- Inhibits platelet aggregation
Thromboxane:
- Produced by COX-1 or COX-2?
- Vasoconstriction or Vasodilation?
- Inhibit platelet aggregation or promote platelet aggregation?
THROMBOXANE (TXA2)
- COX-1
- Vasoconstriction
- Promote platelet aggregation
What is one additional benefit and one additional risk associated with COX-1 (NOT seen with COX 2)?
- Benefit: protects against GI irritation
- Risk: promotes inflammation
What is the MOA of ASA?
IRREVERSIBLE inhibitor of COX-1 AND COX-2
What is the metabolism of ASA (2)?
- Low dose = first order kinetics
- High dose = zero order kinetics
What are the four uses/properties of ASA? Which are also seen with NSAIDs (3) and Acetaminophen (2)?
ALL 3: analgesic, antipyretic
- ASA: also anti-inflammatory, anti-platelet
- NSAIDs: also anti-inflammatory
What AE is seen with ASA at low doses? High doses?
- Low dose = respiratory ALKAlosis
- High dose = metabolic and respiratory ACIDosis
Use of ASA with which condition should be avoided, and why (think excretion)?
GOUT
- ASA is an acid so it competes with uric acid for excretion → uric acid buildup = Gout
What respiratory AE is seen with ASA? What other two systems are affected?
- Respiratory = “aspirin asthma”
- GI UPSET (COX-1 protects GI and it is inhibited)
- Renal failure (inhibit PGs causes vasoconstriction)
What condition can be induced with the use of ASA in children (hence it is CI)? What is the DOC instead?
Reye’s Syndrome
- DOC is Acetaminophen
How do Non-Acetylated Salicylates differ from ASA (think MOA)?
Non-Acetylated Salicylates = reversible inhibition of COX
What are the two possible MOAs of NSAIDs?
- Specific reversible inhibitors of COX-2
- NON-specific reversible inhibitors of COX-1 AND COX-2
What is the MOA of Celecoxib (Celebrex)?
Selective reversible inhibitor of COX-2
What AE is decreased with Celecoxib (Celebrex)? What AE are you at increased risk for, and why?
ONLY COX-2 is inhibited and COX-1 is not…
- LESS GI issues (COX-1 protection of GI is intact)
- Increased risk for CV diseases (COX-1 causes vasoconstriction and platelet aggregation - balance of COX-1 and COX-2 is off so COX-1 dominates)
Of the NSAID drugs that are NON-specific reversible inhibitors of COX-1 AND COX-2, which is preferred and which two are least preferred?
- PREFERRED = Ibuprofen
- Worst (most potent): Indomethacin, Phenylbutazone
Which NSAID reduces PMN migration, is very potent and has a high incidence of AEs?
Indomethacin
- One of last options, used for patent ductus arteriosus
Which NSAID decreases arachidonic acid availability? What other drug is it often combined with, and why?
Diclofenac
- Combined with Misoprostol to decrease GI AEs
Which NSAID is used as an analgesic post-operatively?
Ketorolac (Toradol)
Which NSAID is often stopped after 5 days of use, and why?
Ketorolac (Toradol)
- Frequent GI AEs after 5 days of use
What is the DOC of NSAIDs, and why?
Ibuprofen
- Lowest incidence of AEs
How does Naproxen (Naprosyn) differ from other NSAIDs
Half life is 13 hours = can be taken ONCE daily
Why is Acetaminophen often preferred to ASA (2)?
- Better tolerated
- Lacks undesirable AEs
What is the most serious AE associated with Acetaminophen?
Fatal hepatic necrosis
Describe the metabolism of Acetaminophen?
Dose dependent free radical production = eliminated by GSH (reduced glutathione)
What are the two primary uses of Acetaminophen? How is it NOT used (2)?
- Mild/moderate pain
- Fever in children
NOT anti-inflammatory, NOT anti-platelet
What is the antidote for Acetaminophen poisoning?
N-acetylcysteine
If a patient has NO hx of PUD, what is the recommended tx?
ANY NSAID
If a patient has hx of PUD but it is NOT active, what is the recommended tx (2)?
- Celecoxib (Celebrex) +/- antacids
- Some NSAIDs WITH Misoprostol/PPIs
If a patient has ACTIVE PUD, what is the recommended tx (2)?
- Acetaminophen
- Opioids
What group of medications decreases absorption of ASA?
Antacids (decreases AEs)
