Term
| ASA is absorbed ___ from the ___ |
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Definition
Rapidly
Upper small intestine (and stomach) |
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Term
| Rate/extent of ASA absorption determined by... (3) |
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Definition
Disintegration/dissolution rate of tablets
Mucosal pH (acid = better absorption)
Gastric emptying time |
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Term
| ASA is rapidly hydrolyzed by tissue and blood esterases to ___ and ___ |
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Definition
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Term
| Peak salicylate concentrations occur... |
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Definition
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Term
| Free salicylate is distributed throughout ___ and is available for ___ or ___. Most salicylate is ___. |
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Definition
Most body tissues
Hepatic metabolism or renal excretion
Most is bound to plasma proteins |
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Term
| In the liver, salicylate is either ___, ___, or ___ |
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Definition
+glycine = salicyluric acid
+glucuronic acid = ester/ether glucuronides
Metabolized to gentisic acid |
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Term
| t1/2 for salicylate is ___ because ___ |
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Definition
Dose dependent
Limited ability of the liver to +glucuronic acid |
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Term
| Renal excretion of free salicylate is ___ and ___ |
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Definition
Highly variable
pH dependent |
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Term
| Propionic acid derivatives suffix |
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Definition
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Term
| Propionic acid derivatives: pharmacokinetics (5) |
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Definition
Rapidly absorbed
Highly bound to plasma protein
May have higher concentration in synovial fluid
Extensively metabolized in liver
Most excreted as water soluble metabolite or conjugate |
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Term
| PG or PG intermediates ___ pain receptors |
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Definition
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Term
| Salicylates, propionic acid derivatives: analgesic and anti-inflammatory MOA |
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Definition
Inhibit COX 1 and 2 = decrease PG synthesis at central and peripheral sites
Inhibit PMNL/macro migration to inflamm
Stabilize lysosomal membranes = decreased release of inflamm mediators
Inhibit Ag-Ab aggregation |
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Term
| COX1: what you need to know (2) |
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Definition
Constitutive
Expressed in most tissues including renal blood flow and gastric protection |
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Term
| COX2: what you need to know |
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Definition
Inducible
Activated by mediators released in response to tissue damage |
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Term
| Salicylates, propionic acid derivatives: antipyretic MOA |
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Definition
Inhibit PG synthesis in the hypothalamus (caused by bacterial pyrogens stimulating production of IL1, which stimulates PG synthesis, which interferes with hypothal temperature control)
Only works on elevated body temp |
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Term
| Salicylates: platelet, urate MOA |
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Definition
ASA (prior to deacetylation in portal system) acetylates COX in plt = can't make new COX and/or TXA2
High doses decrease tubular reabsorption of urate |
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Term
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Definition
Gastric irritation
Prolonged bleeding time
Renal disease or dehydration: reversible decrease in RBF and GFR, maybe edema and interstitial nephritis
Kids with viruses: Reye's syndrome = damage to mito membranes causing hepatic injury and encephalopathy
Hypersensitivity: asthma, rash, angiodema, anaphylactoid
-+nasyl polyps: bronchospasm and hypotension |
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Term
| Propionic acid derivatives: S/E (3) |
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Definition
Renal disease or dehydration: reversible decrease in RBF and GFR, maybe edema and interstitial nephritis
Hypersensitivity
1st tri: heart defects and other congenital anomalies |
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Term
| Salicylism/mild aspirin toxicity (5) |
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Definition
Tinnitus
Headache
Dizziness
Mental confusion
n/v
Dose dependent, resolve with reducing dosage |
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Term
| Severe aspirin toxicity: MOA, S/E (2), tx (2) |
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Definition
Uncouples ox. metab in skeletal muscle = increased CO2
Directly stimuates medullary respiratory center
Acid-base issues
-Respiratory alkalosis
-Increased bicarb excretion
Convulsions, coma, death (resp. failure)
Correct acid-base issues
Alkalinize urine to increase excretion of free salicylate |
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Term
| ASA: drug interactions (4) |
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Definition
Inhibition of tubular secretion of uric acid = blocks uricosuric effect of probenecid
+EtOH: GI bleed (propionic acid derivatives, too)
Displacement of other drugs from plasma proteins
-Oral anticoags = increased anticoag action
-Phenytoin
Ibuprofen: interfere with ASA anti-plt |
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Term
| Acetaminophen: pharmacokinetics (5) |
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Definition
Rapid/complete absorption
Peak concentration 30-60 min
Uniformly distributed (20-50% bound to plasma proteins)
Most hepatically +glucuronic/sulfuric acid = almost none of it is excreted unchanged
Only a bit is metabolized by CYP450 to NABQ then +glutathione |
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Term
| Acetaminophen: effects (2) |
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Definition
Analgesia
Antipyresis
No anti-inflamm! |
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Term
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Definition
Rash, other allergic reactions
But usually well-tolerated |
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Term
| Acetaminophen toxicity: MOA |
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Definition
Dose-dependent hepatic overload = liver can't conjugate everything = more of it's available for CYP450 conversion to NABQ
NABQ usually +glutathione, but there's excess NABQ
The leftover NABQ reacts with sulfhydryl groups in hepatic proteins = hepatic necrosis |
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Term
| Acetaminophen toxicicty: S/E, problem with EtOH (2) |
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Definition
Signs of liver damage within 2-4 days: n/v, ab pain
Chronic EtOH
-Increases CYP450 metabolism to NABQ = lower threshold for acetaminophen-induced damage
-Depletes hepatic glutathione = increases severity of injury |
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Term
| Acetaminophen toxicity: tx |
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Definition
Induce vomiting/pump stomach followed by charcoal
Hemodialysis
Administer sylfhydryl compounds (N-acetyl cysteine) = increase hepatic glutathione |
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Term
|
Definition
Renal tubular necrosis
-Acetaminophen metabolite concentrates in renal papillae
-Induces depletion of reduced glutathione = necrosis
-Potentiated by aspirin's renal effects |
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Term
| Ketorolac: pharmacokinetics (5) |
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Definition
Rapidly absorbed (oral, IM, IV, intraocular)
Peak within 30-60 min
Mostly bound to plasma protein
Metabolized in liver +glucuronic acid
Most excreted unchanged |
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Term
| Ketorolac: MOA, effects (3) |
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Definition
Inhibition of COX 1 and 2
Analgesia: but potency of this effect outweighs use as anti-inflamm or antipyretic
No tolerance/dependence
Anti-inflammatory
Antipyresis |
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Term
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Definition
| Multimodal acute pain (short-term = <5 days) |
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Term
|
Definition
GI discomfort
Dizziness
Headache
Increased bleeding time (plt inhibition)
Asthma, nasyl polyps, aspirin sensitivity: bronchospasm
Administration >5 days: gastric ulcers, renal impairment
Don't use in patients with renal dysfunction |
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