Salicylate Flashcards
Forms of Salicylates
Analgesics Topical (Oil of wintergreen/ben gay) Bismuth Subsalicylate (pepto bismol)
Toxic Doses Levels
Less than 150: no toxic reaction
150-300: mild to moderate toxic reaction
300-500: Serious toxic reaction
>500 potentially lethal toxic reaction
***>100 mg/kg for 2-3 days: chronic toxicity
Salicylates Absorption/Peak
1 hour
Toxic: delayed due to concretion formation
Salicylates Distribution Protein Binding and Vd
90% and 0.17 L/kg
Toxic: 75% (more free drug) and 0.35 L/kg
Salicylates Elimination
15-20 minutes (dose dependent elimination)
Toxic: up to 30 hours
Normal Salicylate Metabolism
10% unchanged in the urine (pH dependent)
90% absorbed protein bound through glycine conjugation, glucuronidation and oxidation (75% of which is glucine conjugation to salicyluric acid)
In Overdose, what happens to Salicylate
Only 76% is absorbed and protein bound leaving more to go out into the tissue and be free drug
Acute Toxicity: victim, circumstance, time to diagnosis, mortality, suicide, serum concentration
Young adult Intentional Short Uncommon mortality Typical Marked elevation
Chronic toxicity: victim, circumstance, time to diagnosis, mortality, suicide, serum concentration
Elderly Unintentional Long More common mortality Atypical Intermediate elevation
Clinical Presentation Based on Phase of Acute
Phase 1: GI upset, tachypnea, hyperventilation, respiratory alkalosis, Na, K and bicarbonate renal secretion, N/V
Phase II: Metabolic acidosis
Phase II: Metabolic and respiratory acidosis, dehydration , severe K and bicarb depletion, coma, seizure, death
Chronic Clinical Presentation
More insidiously and may be subtle
Primarily neurologic like confusion, delirium and agitationi
Respiratory Alkalosis Look like
pH: 7.51 (high)
pCO2: 27 (low)
HCO3: 21 (low)
Respiratory alkalosis and Metabolic acidosis Looks like:
pH: 7.42 (normal)
pCO2: 15 (low)
HCO3: 9.5 (low)
Metabolic acidosis with respiratory acidosis
pH: 6.67 (low)
pCO2 (HIGH)
PO2 30 (LOW)
HCO3 9.5 (low)
What happens in respiratory alkalosis?
Direct stimulation of the respiratory center of the brain causing hyperventilation which increases depth (hyperpnea) and rate (tachypnea) –> increased CO2 exhalation leads to decreased pCO2 and rise in pH (alkalosis) –> compensatory increase in excretion of bicarbonate eventuating the decrease buffering capacity
***What happens in metabolic acidosis?
- Uncoupling of oxidative phosphorylation (decreased ATP)
- Inhibition of Kerb’s cycle (accumulation)
- Fatty acid metabolism (accumulation of ketoacids)
- Enhanced glycolysis (accumulation of lactic/pyruvic acid)
Kreb’s Cycle Normal Outcome
Acetyl CoA formed by fatty acids or glycolysis to ultimately form 4 NADH molecules
Kreb’s Cycle when NADH is too high
Acetyl CoA become B-OH butyrate which becomes ketoacids leading to ketoacidosis
Glycolysis Normal and with too much NADH
N: makes ATP and NADH
A: continues to break down the glucose to pyruvate and lactate –> lactic acidosis
***This process first shows as a increase in glucose but as the glucose is depleted, the level will drop!!
Acute VS Chronic effect of Glycolysis
Acute = hyperglycemia Chronic = hypoglycemia
What happens in respiratory acidosis
Excess CNS salicylate concentration leads to depressed respiratory center leading to loss of drive to increase respiration to compensate metabolic acidosis causing respiratory acidosis
CNS Damage is caused by
- Neuronal energy depletion from uncoupling of oxidative phosphorylation
- Release of apoptosis inducing factors like cytochrome C
- Severe cellular metabolic acidosis
- Cerebral edema
- CNS hypoglycemia
Pulmonary SE
Due to body try to increase ventilation and get rid of the CO2 (acid) as quickly as possible
Hematologic SE
Increased bleeding time and PT prolongation
