Lecture 21 - Peripherally Acting Analgesics (NSAIDs) Flashcards
Prostaglandins are produced from ________ acid via the COX enzymes during the ______ (Stage 2) inflammatory stage which occurs hours to days post initial injury.
Arachidonic Acid
Subacute
Dorsal Root Ganglion (DRG) nociceptors transmit pain and are active participants in the inflammatory response to tissue damage. The process is as follows:
Tissue damage releases inflammatory mediators (i.e. histamine, bradykinin, and PG) –> mediators are detected by DRG nociceptors –> transmit pain and release Substance ___, which adds to the inflammatory response from the local cells –> Production of more Prostaglandins by local cells sensitizes nociceptors to increase pain and inflammatory response.
The process is called the _____ reflex arc.
Substance P
Axon reflex arc
Aspirin is made by adding an Acetyl group to ______ acid, both of which are active.
Salicylic acid
Aspirin (NOT slicylate) is unique among all NSAIDs in that it _______ binds and inhibits COX enzymes. This is significant because Platelets do not have protein synthesis, so they much be regenerated to be active.
Irreversibly
One of the CNS effects of Aspirin is to reset the temp control center in the ______ (which brain structure?).
Hypothalamus
Because Aspirin is a weak acid (pKa = 3.5) it favors absorption in the ______. It enters the blood within 2 mins of ingestion, but it only has a half-life of about ____mins. It is metabolized to salicylate (which has a half-life of a 2-3 hours) by gastric and plasma esterases.
Stomach
15mins
Chronic use of Apirin leads to gastric issues bc PGs normally mediate cytoprotective mechanisms in gastric ______ cells to resist penetration by acid.
Mucosal cell
PG__ and PG__ mediate vasodilation in renal arterioles, so their inhibition can lead to ischemia in the kidney. Thus, chronic use of aspirin and other NSAIDs is associated with ________.
PG12 and PGE2
Nephrotoxicity
A single 325mg dose of aspirin can ______ (increase by how much?) the normal bleeding time.
Double
_____ syndrome is most common in children aged 3-16 years receiving Aspirin when recovering from viral infection. It produces rapidly developing encephalopathy and fatty degeneration of viscera.
Reye’s syndrome
Acute toxicity with Aspirin (aka Salicylism) is diagnosed by a complex of four early warning signs:
- _____
- Hearing loss (reversible)
- Headache
- Confusion
If left untreated, it can be followed by respiratory stimulation or depression, ____-____ imbalance (very serious), Coma and Death.
- Tinnitus
Acid-base imbalance
20% of people with ______ have intolerance to Apirin and NSAIDs.
Asthma
Acetominophen acts by blocking COX enzymes INDIRECTLY. It is particularly effective in the _____ (which part of the body?) and endothelial cells, but has only weak effects as a ______ inhibitor, so good when you want to preserve clotting.
Brain
Prostaglandin inhibitor
Acetominophen can be potentially lethal in overdose - it accounts for for almost 40% of liver failure cases in the US. This is bc the recommended dose is 0.5-1g every 4 hours, but doses of 7.5g for an adult are likely to cause ______, and ____g is often fatal.
Hepatotoxicity
15g
The major route for metabolism of Acetominophen in the Liver is via glucuronidation, and the minor route is via conjugation with ______. The minor route becomes dominant once the major route is saturated, and one of the intermediate metabolites of the minor route causes liver necrosis when it builds up. N-________ can be used as an antidote if caught early –> it acts by restoring _______ stores.
Glutathione
Glutathione stores
