Lecture 7 - Salicylates

Question 1

Describe absorption of salicylates

Answer 1

very well absorbed from the stomach and small intestine

Question 2

What is the peak time for immediate release?

Answer 2

30 min (within 1 hour)

Question 3

What is the peak time in OD?

Answer 3

4-6 hours (or longer)

Question 4

What factors affect absorption?

Answer 4

• formulations (effervescent, EC)

- pylorospasm (delay of passage of stomach contents into duodenum)

Question 5

Describe how Vd of salicylates changes in overdose

Answer 5

• small Vd

- increases in OD

Question 6

Describe how protein binding of salicylates changes in overdose

Answer 6

• high protein binding

- decreases in OD

Question 7

Describe the elimination of salicylates

Answer 7

• 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)

Question 8

Describe how half life changes in overdose

Answer 8

• normally 2-4.5 hours

- 18-36 hours in OD

Question 9

What is therapeutic dose for adults?

Answer 9

325-650 mg (4-6 times/day)

Question 10

What is therapeutic dose for children? (>12)

Answer 10

10-15mg/kg (4-6 times/day)

Question 11

What is mild intoxication?

Answer 11

150-200 mg/kg

Question 12

What is severe intoxication?

Answer 12

300-500 mg/kg

Question 13

What is potentially lethal intoxication?

Answer 13

500 mg/kg

Question 14

What is chronic intoxication of salicylates?

Answer 14

> 100mg/kg/day for 2 or more days

Question 15

What serum levels indicate toxicity in acute OD?

Answer 15

> 90-100mg/dL

Question 16

What are chronic therapeutic values?

Answer 16

10-30 mg/dL

Question 17

What level is considered serious when combined with acidosis and altered mental status?

Answer 17

> 60 mg/dL

Question 18

Describe the central stimulation of the respiratory centre

Answer 18

• Hyperventilation
• Respiratory alkalosis
• Dehydration

Question 19

How much bicarbonate do you need?

Answer 19

replacement of 2-3 mEq/L of plasma bicarbonate in toxic concentrations

Question 20

Salicylate overdose interferes with ____ cycle

Answer 20

Krebs

Question 21

Salicylate toxicity causes ____ _____

Answer 21

metabolic acidosis

Question 22

How does salicylate toxicity affect blood glucose?

Answer 22

hyper and then hypoglycemia

Question 23

Salicylates can cause ____ and _____ edema

Answer 23

cerebral and pulmonary

Question 24

What renal effects does salicylates have?

Answer 24

• tubular damage

- proteinuria

Question 25

Salicylates have ototoxicity. What does this cause?

Answer 25

- tinnitus | - hearing loss

Question 26

Describe the acute salicylate toxicity

Answer 26

- vomiting - hyperpnea - tinnitus - lethargy - mixed respiratory alkalosis and metabolic acidosis - coma - seizures - hypoglycemia - hyperthermia - cerebral and pulmonary edema

Question 27

Why don't we want to cause emesis?

Answer 27

tend not to intubate patients bc the hyperventilation is actually helping to counteract the metabolic acidosis (gastric lavage is not good then?)

Question 28

Describe chronic toxicity

Answer 28

- 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)

Question 29

Describe who is more at risk of acute salicylate poisoning

Answer 29

- 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

Question 30

Describe who is more at risk of chronic salicylate poisoning

Answer 30

- 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

Question 31

Describe the management of salicylate toxicity

Answer 31

- emergency management - lab tests (salicylates, arterial blood gases, electrolytes) - monitoring

Question 32

What are some interventions we can use for salicylate poisoning?

Answer 32

- gastric emptying - AC - sodium bicarbonate (to counteract the acid) - urinary alkalization (ion trapping of salicylates in urine) - hemodialysis - hemoperfusion - MDAC - CVVHF (continuous venovenous hemofiltration)

Question 33

Is emesis a good idea?

Answer 33

if lots is still in the stomach - yes *however there is a risk of seizures and aspiration pneumonitis

Question 34

Is gastric lavage a good idea?

Answer 34

useful if drug is still in the stomach

Question 35

What dose of activated charcoal do you give?

Answer 35

Very large doses (300-600g) with large ingestions (30-60g) - 25-50g of AC at 3-5 hour intervals - whole-bowel irrigation

Question 36

Describe sodium bicarbonate for correction of metabolic acidemia

Answer 36

0. 5-2 mEq/kg bolus | * for salicylates OD: bring pH to 7.4-7.5

Question 37

Describe sodium bicarbonate to obtain urinary alkalization

Answer 37

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

Question 38

How will we treat hypokalemia?

Answer 38

30-40 mEq potassium/L

Question 39

Is hemodialysis good for removing salicylates?

Answer 39

Yes, very effective - remove salycilates - correct acid/base abnormalities - correct fluid abnormalities

Question 40

When is HD indicated for salycilate toxicity?

Answer 40

- 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)