Salicylate Toxicity/Iron Toxicity Flashcards


Set Details Share
created 1 year ago by taniaharper
2 views
show moreless
Page to share:
Embed this setcancel
COPY
code changes based on your size selection
Size:
X
Show:

1

Salicylate sources

  • Acetylsalicylic acid (ASA)- aspirin
  • Salicylic acid- topical acne products wart removers (3-10%)
  • Methyl salicylate (MS)- oil of wintergreen (98%), topical analgesics (10-30%)
  • Bismuth subsalicylate- pepto bismol

2

MOA of aspirin

non-selective inhibition of COX-> blocks synthesis of prostaglandins-> inhibition of inflammation, pain, fever, aggregation

3

Therapeutic concentration of Aspirin

15-30 mg/dL

4

Pharmacokinetics of salicylate (absorption)

  • oral, dermal, rectal
  • pKa: 3.5 (weak acid)
  • time to peak (PO): 0.5-2 hours

5

Pharmacokinetics of salicylate (Distribution)

  • Vd: 0.2 L/kg
  • PB: ~90%
  • Therapeutic: 15-30 mg/dL

6

Pharmacokinetics of salicylate (Metabolism)

Hepatic

7

Pharmacokinetics of salicylate (Elimination)

  • renal
  • half life: 2-4 hours
  • first order kinetics

8

Toxicokinetics of salicylate (absorption)

  • time to peak (PO): ~4 hours

9

Toxicokinetics of salicylate (distribution)

  • Vd: 0.3-0.5 L/kg
  • PB: ~70%
  • Toxicity: >30 mg/dL

10

Toxicokinetics of salicylate (metabolism)

  • hepatic, saturable

11

Toxicokinetics of salicylate (elimination)

  • half life: up to 20 hours
  • zero-order kinetics

12

Threshold for salicylate toxicity (standard recommendation)

150 mg/kg PO

13

Threshold for salicylate toxicity (GA poison center)

240 mg/kg PO

14

Mechanism of salicylate toxicity

direct CNS stimulation- stimulation of the respiratory center in the brain induces hyperventilation, leading to a respiratory alkalosis

inhibition of ATP generation- salicylates uncouple oxidative phosphorylation and inhibit the Krebs cycle, leading to energy failure and metabolic acidosis

15

Organ systems affected by salicylate toxicity

CNS, respiratory, GI, metabolic

16

Symptoms expected with the CNS affected-salicylate toxicity

AMS, lethargy, tinnitus, seizure, coma

17

Symptoms expected with the respiratory affected-salicylate toxicity

hyperventilation, respiratory alkalosis, pulmonary edema, ARDS

18

Symptoms expected with GI affected-salicylate toxicity

N/V, abdominal pain, hemorrhage

19

Symptoms expected with metabolic affected- salicylate toxicity

metabolic acidosis, electrolytes disturbances, hypoglycemia, hyperthermia

20

Clinical plan for salicylate toxicity

  1. ABCs
  2. discontinue agent
  3. external decontamination (topical salicylates)
  4. internal decontamination- activated charcoal
  5. labs/monitoring- STAT aspirin level, BMP, blood gas, lactate, RR, HR/BP, O2 saturation, temperature
  6. treatment- supportive care, antidote: sodium bicarbonate

21

When to give sodium bicarbonate for salicylate toxicity

ASA level >30 mg/DL

22

MOA of sodium bicarbonate for salicylate toxicity

increasing pH favors formation of ionized salicylate, which is excreted by the kidneys

23

Dosing for sodium bicarbonate

1-2 mEq/kg IV bolus + maintenance infusion

5: D5W

4: 20-40 mEq K+

3: 3 amps of sodium bicarbonate (150 mEq)

2: 2x maintenance rate

1: 1 liter bag

24

Goal of therapy when using sodium bicarbonate

  • target urine pH 7.5-8
  • serum pH 7.55

25

Endpoints of sodium bicarbonate treatment

  • ASA <30 mg/dL and downtrending
  • resolution of symptoms

26

If potassium is not optimized ____, bicarbonate treatment will be ineffective

K>4

27

Aspirin has ____; in toxicity, time to peak and half life are prolonged, volume of distribution increases, and protein binding decreases

saturable kinetics

28

Most potent salicylate

oil of wintergreen

29

Iron is a critical element to

organ function

30

Iron is a transition metal that readily accepts and

donates electrons

*shifts between ferric (Fe3+) and ferrous (Fe2+)*

31

Iron is stored as ferritin or

released to the serum as transferrin for transfer to tissue

(stores via iron absorption from GI tract)

32

What percent of elemental iron is in ferrous gluconate?

12%

33

What percent of elemental iron is in ferrous sulfate

20%

34

What percent of elemental iron is in ferrous fumarate

33% (most potent)

35

What percent of elemental iron is in carbonyl iron

>98%

poor oral bioavailability

36

Pharmacokinetics of iron (absorption)

  • total body stores ~3-5 grams

37

Pharmacokinetics of iron (distribution)

  • serum: transferrin; stores: ferritin
  • 80% bound to heme
  • normal range: ~80-180 mcg/dL

38

Pharmacokinetics of iron (metabolism)

  • stored in liver as ferritin

39

Pharmacokinetics of iron (elimination)

1-3 mg/day by sloughing of GIT

40

Toxicokinetics of iron (absorption)

  • increased absorption 2/2 GIT damage

41

Toxicokinetics of iron (distribution)

  • saturable
  • <300 mcg/dL: mild
  • 300-500 mcg/dL: moderate
  • 500-1000 mcg/dL: severe
  • >1000 mcg/dL: mortality

42

Toxicokinetics of iron (metabolism)

  • saturated uptake (free iron floating around)

43

Toxicokinetics of iron (elimination)

  • enhanced elimination with antidote+ 1-3 mg/day

44

How many milligrams of the iron adult formulation is toxic (>18 mg elemental iron)

60 mg/kg

45

How many milligrams of the iron pediatric formulation is toxic ( 18 mg elemental iron)

100 mg/kg

46

How many milligrams of the carbonyl iron formulation is toxic

200 mg/kg

47

Mechanisms of iron toxicity

  • catalyst of free radical formation
  • ferric iron reacts with water to generate 3 H+ ions-> acidemia
  • ferric iron directly inhibits thrombin-> coagulopathy

48

Stage I of iron toxicity (0.5 to 6 hours)

GI irritation 2/2 direct mucosal injury

49

Stage II of iron toxicity (6 to 24 hours)

recovery from GI symptoms without any systemic symptoms

(latent stage)

50

Stage III of iron toxicity (6 to 72 hours)

shock 2/2 hypovolemia, vasodilation, poor CO, poor CNS effects, 2/2 systemic toxicity, iron-induced coagulopathy, worsened bleeding

(shock and metabolic acidosis)

51

Stage IV of iron toxicity (12-96 hours)

fulminant hepatic failure

(hepatotoxicity/necrosis)

52

Stage V of iron toxicity (2-8 weeks)

GI mucosa healing leads to scarring and strictures

53

If GI symptoms do not develop within ___ hours post-ingestion, toxicity is HIGHLY unlikely

6

54

Organ systems affected by iron toxicity

CNS, cardiovascular, respiratory, GI (local), liver, metabolic

55

Symptoms expected with the CNS affected-iron toxicity

lethargy, AMS, seizure, coma

56

Symptoms expected with the cardiovascular affected- iron toxicity

hypovolemic shock, hypotension, tachycardia

57

Symptoms expected with the respiratory affected- iron toxicity

pulmonary edema, ARDS

58

Symptoms expected with the GI affected- iron toxicity

N/V, diarrhea, abdominal pain, hematochezia, hematemesis

59

Symptoms expected with the liver affected- iron toxicity

hepatotoxicity, liver failure

60

Symptoms expected with the metabolic affected- iron toxicity

metabolic acidosis

61

Clinical plan for iron toxicity

  1. ABCs
  2. discontinue agent
  3. internal decontamination- whole bowel irrigation
  4. labs/monitoring- STAT iron level (repeat q4h), CMP, CBC, blood gas, lactate, abdominal x-ray, RR, HR/BP, O2 saturation
  5. treatment- supportive care, antidote: deferoxamine

62

Indication for deferoxamine

serum iron >500 mcg/dL

serum iron >300 mcg/dL + systemic symptoms

63

mechanism of deferoxamine

chelates free Fe3+ iron to form complex (ferrioxamine), which is renally eliminated

64

Dosing for deferoxamine

  • 90 mg/kg as IV infusion
  • initiate at 5 mg/kg/hr and titrate up to 15 mg/kg/hr
  • max 6 g/24 hours; do not exceed 24 hours of therapy

65

AEs of deferoxamine

hypotension (infusion rates >15 mg/kg/hr)

ARDS (prolonged infusions >24 hours)

66

Endpoints of deferoxamine

iron <180 mcg/dL, resolution of symptoms

*may turn urine "vin rose"

67

Iron primarily induces toxicity through lipid peroxidation of mitochondrial and capillary membranes and proton generation, leading to

metabolic acidosis, hypotension, and shock