Non-narcotic analgesics and NSAIDs Flashcards
1
Q
Metabolism of aspirin
A
- Not a prodrug, salicylate is metabolized by liver into 2 conjugated forms for renal excretion
- Aspirin is broken into salicylate (in liver, plasma and RBCs), which still has some activity
- Unconjugated aspirin is not excreted (lipophilic)
2
Q
Analgesic action of aspirin
A
- Good for post-op and inflammatory pain, does not help pain from hollow viscera
- Acts to irreversibly inhibit COX (acetylates COX1 and COX2), thereby inhibiting the synthesis of prostaglandins
- Do not affect the prostaglandin receptor
- Prostaglandin increases pain by inducing hyperanalgesia by lowering the threshold of polymodal nociceptors
- Does not change the perception of other modalities
- Salicylate and other NSAIDs reversibly inhibit COX
3
Q
Antipyretic, antithrombitic, and gastric affects of aspirin
A
- Elevated body temp is due to pyrogens form bacteria and IL1 from macs during inflammation
- Aspirin blocks the action of pyrogens and IL1 in the hypothalamus by inhibiting prostaglandin synthesis (COX)
- The preoptic region then facilitates vasodilation
- By inhibiting COX1 aspirin lowers the synthesis of thromboxane, thus preventing platelet aggregation/thrombus generation
- COX1 also is found in the stomach where it facilitates protection from gastric acid, thus inhibiting COX1 can lead to gastric irritation
4
Q
Acute overdose of aspirin
A
- Due to saturation of salicylate metabolizing nzs in liver and limited ability of kidney to excrete salicylate
- Leads to fluid, electrolyte and acid-base disturbances
5
Q
Metabolic and respiratory abnormalities
A
- Uncoupling of oxidative phosphorylation increases heat production
- This increases O2/glc consumption and thus CO2 production
- Metabolic acidosis occurs due to lactic acid generation
- CO2 exchange from RBCs to air in alveoli inhibited by salicylate
- Overall, increase in CO2 leads to stimulation of medulla to induce hyperventilation
- Hyperventilation results in respiratory alkalosis: increases renal excretion of Na, K, and HCO3
6
Q
Therapy for aspirin poisoning
A
- Urine alkalization to increase salicylate excretion via sodium bicarb
- This also corrects the metabolic acidosis
- Hypokalemia by giving K separately from NaHCO3
- Also IV glucose
7
Q
Aspirin and Reye’s syndrome in children
A
- Reye’s syndrome develops from a virus-host reaction, mostly from varicella and influenza
- Salicylate can modify the course of the syndrome
- Aspirin not given to children under 12, or to children w/ chickenpox or the flu
8
Q
Actions of acetaminophen (tylenol)
A
- Analgesic and antipyretic action equal to aspirin/other NSAIDs, but does not reduce inflammation (is not an NSAID)
- Does not inhibit peripheral COX thus does not affect inflammation (not used in RA)
- However this also means it doesn’t have some of the side effects NSAIDs have
- Preferred choice for pregnant women or children w/ influenza or chickenpox (no reyes syndrome)
9
Q
Overdose of acetaminophen
A
- Overdose (10g) can produce a delayed (3-5 days) hepatic necrosis
- This results from the way acetaminophen is metabolized and excreted
- CYP450 in the liver converts acetaminophen to quinoneimine, which conjugates w/ glutathione and is excreted
- In high doses, this process depletes the liver of glutathione, resulting in large amount of apoptosis and necrosis of hepatocytes
10
Q
Rx of acetaminophen OD
A
- Goal is to restore glutathione in liver
- Giving glutathione will not work b/c it cannot pass the membrane
- Must give one of the following, all of which are precursors to glutathione
- N-acetylcysteine is the first choice
- Then go to methionine, then cysteamine
11
Q
Commonalities/differences of NSAIDs
A
- All inhibit COX, thus reducing the synthesis of prostaglandins and prostacyclins (both vasodilate and induce inflammation) and some reduce the synthesis of thromboxane (vasoconstricts and causes platelet activation)
- Most prostaglandins/prostacyclins are made in response to local inflammatory stimuli, thus are mainly produced by COX2
- Thromboxane is made from COX1
- Some NSAIDs can also inhibit LOX, thereby reducing the synthesis of leukotrienes
12
Q
Selective COX2 inhibitors (NSAIDs)
A
- COX2 activity is usually low in peripheral tissues, but rapidly increases in response to local inflammatory stimuli
- Celecoxib, a selective COX2 NSAID, has lower gastric irritation and platelet function disturbances due to not having any function on COX1
13
Q
Common side effects of NSAIDs: antithrombotics
A
- Inhibition of platelet functioning comes from inhibiting COX1, thereby reducing thromboxane synthesis (thereby increasing vasodilation and reducing platelet activation)
- This increases the bleeding time but also decreases chance of thrombosis (antithrombotic)
- COX2 inhibitors do not have this effect, and instead they reduce PC synthesis, which increases vasoconstriction and are therefore prothrombotic
14
Q
Common side effects of NSAIDs: gastric irritation
A
- Inhibition of COX1 reduces synthesis of PGs in the gastric mucosa
- PGs in the stomach promotes the secretion of mucus and bicarb, thus inhibiting PGs reduces the secretion of these
- All NSAIDs have a direct acid affect on the gastric mucosa causing irritation (proton doesn’t dissociate until w/in the epithelial cells)
- Inhibition of platelet aggregation prolongs the bleeding time of GI bleeds
15
Q
Common side effects of NSAIDs: hypersensitivity rxn
A
- Caused by COX1 inhibition, only in pts w/ asthma or nasal polyps
- All NSAIDs are contraindicated for these pts
- Causes bronchoconstriction and anaphylactic shock
