Antidotes (Exam 1 Cut Off)

Question 1

Properties of Ideal Antidote

Answer 1

• Completely reverses or neutralizes the effects of the poison
• No action of its own
• Easy to administer
• No unpleasant SE

Question 2

Chelators

Answer 2

• EX: Dimercaprol (BAL), penicillamine, DMSA, EDTA, Deferoxamine (used for Fe)
• BAL: pain, peanut allergy
• EDTA: nephrotoxicity
• Deferoxamine: hypotension, anaphylactoid rxn, ARDS

Question 3

Chronic Lead Poisoning

Answer 3

• KUB: gastric lavage
• Whole bowel irrigation
• Aggressive hydration
• BAL: 4-5 mg/kg IM 4h if Pb >= 70 mcg/dL
• PO DMSA + IV EDTA preferred

Question 4

Iron Chelation

Answer 4

• Deferoxamine colorless compound when Fe+3 is removed
• Avidly binds to iron form ferrioxamine
• Eliminated urine is “pink rose” color - endpoint of therapy

Question 5

Iron Poisoning

Answer 5

• KUB for retained pills
• Fe++ > 500 mcg/dL or > 350 mcg/dL with symptoms
• WBC > 15, BS > 150
• TIBC useless
• Lavage? WBI, aggressive fluids
• IV Deferoxamine 15 mg/kg/hour, NMT 24 hours

Question 6

Antivenins/Biologics

Answer 6

• Crotalidae Antivenin: rattlesnake
• Lactrodectus Antivenin: black widow spider
• Elapidae antivenin: eastern/texan coral snake
• Trivalent botulinum: Botulism types A, B, and E
• Digoxin Immune Fab: digoxin/digitoxin poisoning

Question 7

Digoxin Immune Fab Indications/Dosing

Answer 7

• K > 5.5 mEq/L, progressive heart block, Ventricular dysrhytmias, CV collapse
• Dose >= 10 mg in adults of 0.1 mg/kg in children
• # vials = serum levels x weight in kg/100
• Must measure > 6 hours after last dose OR # vials = dose in mg/0.5 mg/vial

Question 8

N-acetylcysteine

Answer 8

• For APAP Poisoning

- Prevents NAPQI binding at hepatocyte

Question 9

Naloxone

Answer 9

• For Opioid poisoning

- Opioid receptor antagonist

Question 10

Flumazenil

Answer 10

• For Benzo poisoning
• Benzo receptor antagonist
• Can be CI due to risk of seizures, reversing dependence

Question 11

Atropine

Answer 11

• For OP and carblnsecticides poison

- Muscarinic receptor antagonists

Question 12

Fomepizole

Answer 12

• For Methanol and ethylene glycol poisoning
• Blocks metabolite formation
• Potential ADH competitive inhibitor
• Prolongs half life, methanol from 20 to 54 hours, and ethylene glycol from 4 to 20 hours
• Often need hemodialysis for methanol
• Dose: 15 mg/kg IV then 10 mg/kg q12h x 4 doses, then 15 mg/kg q12h
• If hemodialysis is needed, give every 4 hours

Question 13

Idarucizumab

Answer 13

• For dagibatran poisoning

- Monoclonal antibody

Question 14

Coagulation Factor XA recombinant

Answer 14

• For apixaban/rivaroxaban poisoning

- Binds and sequesters Xa inhibitors

Question 15

Prussian Blue

Answer 15

• For thalium cesium isotopes poisoning

- Binds and inactivates thallium and cesium

Question 16

Glucarpidase

Answer 16

• For methotrexate poisoning

- Enzymatic cleavage of methotrexate

Question 17

Silymarin

Answer 17

• For amantoxin poisoning

- Unclear mechanism, but likely antioxidant

Question 18

Nomogram

Answer 18

• Cannot plot a level prior to 4 hours: starts at elimination phase and peak level is 1-2 hours
• Cannot plot chronic supratherapeutic levels
• Slope is based on 4 hour half-life: most have a shorter one
• Toxic 4 hour level is 150 mcg/mL: mental math for other times (8 = 75, 12 = 37.5, etc.)

Question 19

Anaphylactoid Rxn Risk

Answer 19

• More common in lower APAP levels
• 25% if APAP < 150, but only 3% if APAP > 300
• APAP decreases histamine release from mononucleocytes and mast cell (dose-dependent)

Question 20

Antidotes + Preventing Hypoglycemia + Sulfonylurea Overdose

Answer 20

• Oral dextrose
• IV dextrose
• Sumatriptan
• Octreotide

Question 21

Why glucose fluctuations?

Answer 21

• Duration of drug longer than duration of glucose
• Glucose enters the beta cell without insulin
• Sulfonylurea blocks closure of K-ATP channel
• Additional glucose yields additional insulin

Question 22

Octreotide

Answer 22

-Somatostatin analog, blocks beta-cell calcium channels to reduce insulin secretion
Doses
-Children: 1-1.5 mcg/kg IV or SC followed by 2-3 more doses 6 hours apart
-Adult: 50-100 mcg SQ or IV, followed by three 50 mcg doses every 6 hours
-During treatment, IV dextrose infusion should be gradually tapered off

Question 23

HIE Therapy Maintenance

Answer 23

• High dose insulin euglycemia
• Insulin: 1 unit/kg/hour, increasing by 0.5 unit/kg/hour every 30 minutes up to max of 15
• Titrate to BP (MAP >= 60), no effect on HR
• Use concentrated as 5,000u in 500 mL NS
• Glucose bolus of 0.25 g/kg if glucose <200
• Start D5W or D10W at 0.15 g/h
• Maintain serum K+ at 2.5-2.8 mEq/L, permissive hypokalemia might be helpful

Question 24

HIE Pitfalls

Answer 24

• Stopping insulin before stopping pressor: pressor-sparing
• Stopping insulin and glucose at the same time: continue glucose 24-36 hours after D/C insulin
• volume overload if insulin is dilute

Question 25

L-Carnitine Rational

Answer 25

• High first pass, only 15% oral bioavailability
• Manufacturer suggests q3-4h, never q<6h
• Mechanism: clears acyl CoA esters by forming acylcarnitine, shifts metabolism of VPA away from hepatoxic metabolites
• Reverses acquired urea cycle defect, resolving hyperammonemia

Question 26

L-Carnitine Indications

Answer 26

• Serum VPA > 450 mcg/mL
• Severe coma
• Hyperammonemia (>80 mcg/dL)
• CCB overdose refractory to pressors and HEI: increases calcium channel sensitivity, decreases insulin resistance, facilitates metabolism of FFAi