Pain (MC) - Block 2 Flashcards
What type of compounds of PPB?
- Lipophilic
- Acidic
What are the indications for non-narcotic?
- Mild to moderate pain without altering consciousness
- Dull aches
- Ceiling effect
- No tolerace/physial dependence
What is the difference between Cox 1 and 2?
What is an analdesic?
Relief of pain, minor aches
What is anti-inflammatory?
Reduction of inflammation associated with arthritic syndromes
What is antipyretic?
Reduction of elevated body temp
Acetaminophen
MOA, BBW, Metabolism, Elimination, Dosing
MOA: analgesic, antipyretic (NOT anti-inflammatory)
BBW: hepatotoxicity
Metabolism: Both CYP2E1 and CYP3A4 are induced by ingestion of alcohol
Elimination: Gluthione and renal
Dosing: 4 g/day
What is the antidote for tylenol?
N-acetylcysteine
Why is APAP not considered an NSAID?
- Not anti-inflammatory
- Weak acid
- Doesn’t have antiplatelet or gastric ulcerogenic activity
How are NSAIDs excreted?
Renal
How are NSAIDs distributed?
All in synovial fluid after repeated dosing
Describe the toxicity of NSAIDs?
Nephro (interference with autoreg of renal blood flow) and hepatotoxic
NSAIDs
MOA, Interaction
MOA: inhibti PG synthesis via inhibition of COX1/2
Interactions: highly acidic so it interferes with drug that PPB, inhibits metabolism PG
What is the function of PGE2?
Enhanes local inflammation -> localized edema and hyperalgesia
Ihibition of prostanoid synthesis causes:
- Anagesia
- Antipyretics
- Anti-inflam
- Anti-thrombotic
- Closure of ductus arteriosis (X in pregnancy)
- GI tox
Why do NSAIDs cause gastric damage?
How does aspirin differ from other NSAIDs?
Covalently modifies COX enzymes (irreversible)
Aspirin
MOA, PK
MOA: 10-100 more potent against COX1 than COX2
PK: Absorption is sensitive to pH of stomach, raising gastric pH slows absorption, more ionized
ADR of aspririn?
Mostly GI
Hypersensitivity rare but fatal (skin rahses, watersecretions, uricaria, rhinitis, edema, bronchoconstriction, anaphylaxis)
Indicatiosn for aspirin?
Ana;gesia, antipyretic, anti-inflammatory, uricosuric, CV effects
How does aspirin bind to receptor?
Ser initiates nucleophilic attack on acetoxy on aspirin -> salicylate anion leaves and acetoxy group irreversibily covalently bind to ser
What is the warning when using salicylates in children?
Development of Reyes: sudden vomiting, violent HA, and unusual behavior
* Warning against their use in children under 16 with influenza, chicken pox, or flu-like illness
What is the SAR of arylalkanoic acids?
a-carbon = unsubstituted = arylacetic acid
* aryl group = phenyl -> “fenac”
a-carbon has a methyl = arylpropionic acid (chiral – racemic mixture because rapid epimerization but S enantiomer = active)
* aryl group = phenyl -> “profen”
Second aromatic ring good for activity (noncoplanar increased lipophilicity or blocked CYP metabolism)
Stable para substituents -> longer DOA