Lecture 7 - Salicylates Flashcards
Describe absorption of salicylates
very well absorbed from the stomach and small intestine
What is the peak time for immediate release?
30 min (within 1 hour)
What is the peak time in OD?
4-6 hours (or longer)
What factors affect absorption?
- formulations (effervescent, EC)
- pylorospasm (delay of passage of stomach contents into duodenum)
Describe how Vd of salicylates changes in overdose
- small Vd
- increases in OD
Describe how protein binding of salicylates changes in overdose
- high protein binding
- decreases in OD
Describe the elimination of salicylates
- First order kinetics
- 5 pathways of elimination
- Liver metabolism
- Renal elimination (if we aklynize the urine, we create iron trapping and impair reabsorption of the drugs)
Describe how half life changes in overdose
- normally 2-4.5 hours
- 18-36 hours in OD
What is therapeutic dose for adults?
325-650 mg (4-6 times/day)
What is therapeutic dose for children? (>12)
10-15mg/kg (4-6 times/day)
What is mild intoxication?
150-200 mg/kg
What is severe intoxication?
300-500 mg/kg
What is potentially lethal intoxication?
500 mg/kg
What is chronic intoxication of salicylates?
> 100mg/kg/day for 2 or more days
What serum levels indicate toxicity in acute OD?
> 90-100mg/dL
What are chronic therapeutic values?
10-30 mg/dL
What level is considered serious when combined with acidosis and altered mental status?
> 60 mg/dL
Describe the central stimulation of the respiratory centre
- Hyperventilation
- Respiratory alkalosis
- Dehydration
How much bicarbonate do you need?
replacement of 2-3 mEq/L of plasma bicarbonate in toxic concentrations
Salicylate overdose interferes with ____ cycle
Krebs
Salicylate toxicity causes ____ _____
metabolic acidosis
How does salicylate toxicity affect blood glucose?
hyper and then hypoglycemia
Salicylates can cause ____ and _____ edema
cerebral and pulmonary
What renal effects does salicylates have?
- tubular damage
- proteinuria
Salicylates have ototoxicity. What does this cause?
- tinnitus
- hearing loss
Describe the acute salicylate toxicity
- vomiting
- hyperpnea
- tinnitus
- lethargy
- mixed respiratory alkalosis and metabolic acidosis
- coma
- seizures
- hypoglycemia
- hyperthermia
- cerebral and pulmonary edema
Why don’t we want to cause emesis?
tend not to intubate patients bc the hyperventilation is actually helping to counteract the metabolic acidosis (gastric lavage is not good then?)
Describe chronic toxicity
- ingestions of more than 100mg/kg/day for 2 days or more
- elderly
- slow on-set
- less severe appearance
- misdiagnosis
- hearing loss and tinnitus
- n/v
- dyspnea, hyperventilation
- hyperthermia
- neurologic manifestations (confusion, agitation, seizures, coma)
- cerebral and pulmonary edema (more common)
Describe who is more at risk of acute salicylate poisoning
- younger
- usually intentional overdose
- easily recognized
- no other disease states
- suicidal ideation is typical
- serum concentration has a marked elevation
- mortality is uncommon if properly diagnosed and treated
Describe who is more at risk of chronic salicylate poisoning
- older
- therapeutic error; iatrogenic
- frequently unrecognized
- underlying disorders (chronic pain)
- no suicidal ideation
- intermediate elevation in serum concentration
- high mortality (25%) because it’s unrecognized
Describe the management of salicylate toxicity
- emergency management
- lab tests (salicylates, arterial blood gases, electrolytes)
- monitoring
What are some interventions we can use for salicylate poisoning?
- gastric emptying
- AC
- sodium bicarbonate (to counteract the acid)
- urinary alkalization (ion trapping of salicylates in urine)
- hemodialysis
- hemoperfusion
- MDAC
- CVVHF (continuous venovenous hemofiltration)
Is emesis a good idea?
if lots is still in the stomach - yes
*however there is a risk of seizures and aspiration pneumonitis
Is gastric lavage a good idea?
useful if drug is still in the stomach
What dose of activated charcoal do you give?
Very large doses (300-600g) with large ingestions (30-60g)
- 25-50g of AC at 3-5 hour intervals
- whole-bowel irrigation
Describe sodium bicarbonate for correction of metabolic acidemia
- 5-2 mEq/kg bolus
* for salicylates OD: bring pH to 7.4-7.5
Describe sodium bicarbonate to obtain urinary alkalization
as continuous titration over 4-8 hours to get pH 7.5-8
*44-100 mEq in 1L (5% dextrose in 0.25% normal saline) at 150mL/h
How will we treat hypokalemia?
30-40 mEq potassium/L
Is hemodialysis good for removing salicylates?
Yes, very effective
- remove salycilates
- correct acid/base abnormalities
- correct fluid abnormalities
When is HD indicated for salycilate toxicity?
- acute ingestion serum levels > 100 mg/dL, with severe acidosis or other manifestations of toxicity
- chronic intoxication serum levels higher than 60 mg/dL
- renal failure (obvs)
- deterioration (CNS, acute lung injury, hepatic compromise with coagulopathy)
