Salicylates Flashcards
What are examples of salicylates?
oral:
-ASA, bismuth subsalicylate, sodium salicylate
-willow bark
topical:
-methyl salicylate
-trolamine salicylate
-oil of wintergreen
What is the issue with oil of wintergreen?
5 ml of wintergreen = 7 g salicylate (21.5 ASA tabs)
-easy for kids to overdose
Do salicylates change the course of disease?
do not generally change the course of disease
-symptomatic relief
Describe salicylate metabolism.
salicylate –> salicylic acid (hydrolysis)
salicylic acid –> glycine/glucuronide (conjugatin, saturable)
salicylic acid –> renally excreted unchanged
What is responsible for therapeutic and toxic effects of salicylates?
salicylic acid
Describe salicylate ADME at therapeutic doses.
absorption:
-Tmax <1h
PPB:
-90%
t1/2:
-2-4h
metabolism/elimination:
-first order kinetics
Describe salicylate ADME at toxic doses.
absorption:
-reduced rates, tmax > 4-6h
PPB:
-<75% (saturated)
t1/2:
-18-36h (6-8h if urine pH > 7.4)
metabolism/kinetics:
-zero order kinetics
At what concentration do toxicities of salicylate occur?
> 30 mg/dL
At what concentration must we do hemodialysis for salicylates?
> 80 mg/dL
-regardless of symptoms
What is the key presentation of early toxicity due to salicylates?
respiratory alkalosis
metabolic acidosis
What is the presentation of blood glucose levels in early salicylate poisoning?
periphery only: normo-hyperglycemia
CNS glucose may be low
What is the key presentation of late toxicity due to salicylates?
respiratory acidosis
metabolic acidosis
hypoglycemia
Summarize the major findings of salicylate toxicity.
early –> metabolic acidosis, respiratory alkalosis
late –> metabolic acidosis, respiratory acidosis
electrolyte disturbances
abnormal glucose
-administer glucose regardless of serum glucose levels
mental status changes
What might be an early sign of salicylate toxicity?
tinnitus
What might be seen in older adults with chronic salicylate toxicity?
slow onset and less severe appearance - often misdiagnosed with dementia, respiratory failure, CHF
What is the antidote for salicylates?
no antidote
What is the management of salicylate toxicity?
ABCs/symptomatic & supportive care
pay attention to hydration, oxygenation, elytes, glucose
What is the therapeutic salicylate concentration?
5-25 mg/dL (0.4-1.8 mmol/L)
What is the Done Nomogram?
validated in pediatrics with single ingestions
poorly predictive of toxicity, not widely used
What are two lab markers that must be monitored in salicylate poisoning?
serum levels
blood pH
-until clinical improvement AND low salicylate [] AND normal-high pH
Why is it important to monitor blood pH in salicylate poisoning?
low pH favors salicylate entering CSF & tissues
-increased proportion of non-ionized salicylate at low pH
What is the role of elimination in salicylate poisoning?
alkalinization;
-mainstay of treatment
-salicylate = weak acid
-increased pH = ionized salicylate = ion trapping
hemodialysis:
-very effective since increased fraction of free salicylate following saturation of protein binding
-recommended in severe toxicity
What is the MOA of NSAIDs?
inhibit COX –> inhibit synthesis of prostaglandins
-prostaglandins = prostacyclins, thromboxane
What is the most important prostaglandin in regards to NSAIDs?
PGE2
What does PGE2 cause?
pain
fever
What do COX-2 inhibitors end in?
-coxib
What are the most toxic NSAIDs?
phenylbutazone
mefenamic acid
What is the life-threatening dose of ibuprofen?
> 400 mg/kg
True or false: life threatening toxicity is common with NSAIDs
false
What is the management of NSAID toxicity?
supportive and symptomatic care
-milk for children
decontamination:
-avoid ipecac
-if no evidence of GI perforation = SDAC
elimination:
-MDAC: meloxicam, phenylbutazone, piroxicam
-hemodialysis: not beneficial for reducing lvls, maybe acute renal failure
What is the antidote for NSAIDs?
no antidote
