Toxicology

Question 1

Antidote for Acetaminophen poisoning?

MOA?

Answer 1

N-aceylcysteine.
• supplies cysteine as a precursor for increased glutathione production, and also reacts directly with, and thereby detoxifies, NAPQI.

Liver transplant

Question 2

Aspirin Poisoning tx.?

Answer 2

Moderate intoxication
- IV sodium Bicarbonate

Severe intoxication
- Hemodialysis

Question 3

AMPHETAMINES & OTHER STIMULANTS

Tx.?

Answer 3

• Acidification of urine with ammonium chloride.
• For HTN: phentolamine or nitroprusside.
• For tachyarrhythmias: propranolol or esmolol.
• For seizures: IV benzodiazepines.
• Very high body temperatures: neuromuscular paralysis.

Question 4

B-BLOCKERS TOXICITY - TREATMENT

Answer 4

• IV Glucagon is a useful antidote.
• Increases cAMP in cardiac cells, but through stimulation of glucagon receptors, not B-receptors

used to raise blood pressure and heart rate, such as B-agonists and atropine, are generally ineffective

Question 5

The antidote for quinidine-like cardiac toxicity is?
DON’T give what drug to a patient w/ TCA overdose?
hypotension tx?

Answer 5

1. sodium bicarbonate.
2. Physostigmine
3. Norepinephrine

Question 6

MAOIs-TOXICITY

• Cause severe HTN when taken with?
• Tx?

Answer 6

• when tyramine-containing foods or drugs such as phenylpropanolamine or ephedrine are taken.

TREATMENT
•For hypertension: phentolamine or labetalol

Question 7

Whats the most toxic combination of drug that can cause serotonin syndrome?

Answer 7

Administration of an irreversible MAOI with a serotonergic agent may result in a serotonin syndrome (the most toxic reported combination).

• Involves excessive selective stimulation of serotonin 5-HT 2A and perhaps 5-HT 1A receptors

Question 8

SEROTONIN SYNDROME-MANAGEMENT

Answer 8

• Serotonin syndrome has been successfully treated with Cyproheptadine (5HT2 receptor antagonist).
• Rigidity, seizures, and agitation are treated with benzodiazepines.

Question 9

OPIOIDS TOXICITY Tx?

Answer 9

•Naloxone or nalmefene

Question 10

THEOPHYLLINE -ACUTE INTOXICATION

Answer 10

Usual manifestations include:

1. GI manifestations: Vomiting (sometimes hematemesis), Abdominal pain and Diarrhea.
2. Metabolic effects: decreased k+, Po43-, increased/decreased Ca+2, increased Glucose and metabolic acidosis.
3. Musculoskeletal: Coarse tremor (results from disturbances in skeletal muscle homeostasis of potassium).
4. Neurological: Anxiety.
5. Cardiovascular: Tachycardia.

Severe intoxication is characterized by:
1. Seizures:
•The major cause of morbidity and mortality in theophylline intoxication.
2.Hypotension and ventricular arrhythmias:
•Caused primarily by excessive beta-adrenergic stimulation.
•The other major concern, but usually do not cause QT prolongation.

Question 11

THEOPHYLLINE -CHRONIC INTOXICATION

Answer 11

• Cardiac dysrhythmias are more common following a chronic overdose rather than acute overdose and occur with lower serum concentrations.
• Seizures are more common with acute overdose than with chronic overdose however, in chronic exposures, seizures may develop at lower serum concentrations.
• Chronic theophylline overdose has minimal GI signs or symptoms.

Question 12

THEOPHYLLINE TOXICITY-MANAGEME

Answer 12

• Tachyarrhythmias and hypotension are best treated with a beta-adrenergic receptors blocker (propranolol or esmolol).
• Theophylline-induced seizures benzodiazepines and barbiturates are the most effective agents.

Question 13

SULFONYLUREAS & MEGLITINIDES

1. MOST common AE?
2. Tx?

Answer 13

1. Hypoglycemia
2. patient with a sulfonylurea overdose and symptomatic hypoglycemia should be treated with both intravenous dextrose and octreotide
   - Diazoxide is an alternative to octreotide. It also inhibits insulin release. Octreotide is preferred due to its safety and efficacy.

Question 14

NEUROLEPTIC MALIGNANT SYNDROME?

- Prefered tx?

Answer 14

•Characterized by hyperthermia (altering the core temperature set point), lead pipe muscle rigidity(Blockade of striatal D2 receptors), metabolic acidosis and confusion.
- Bromocriptine prefered
•Bromocriptine and dantrolene for moderate to severe NMS.
•Dantrolene most beneficial when profound rigidity is present.
•If temperature ≥40°C neuromuscular paralysis and aggressive external cooling should be done.

Question 15

What toxic chemical is Methanol metabolized to?

Answer 15

Formic acid

- Formic acid can cause severe acidosis, retinal damage and blindness.

Question 16

METHANOL POISONING - MANAGEMENT

Answer 16

• Ethanol: to saturate alcohol dehydrogenase and reduce production of formic acid.
• Or fomepizole**: inhibitor of alcohol dehydrogenase.
• Bicarbonate to treat metabolic acidosis.
• Hemodialysis.

Question 17

ORGANOPHOSPHATE INSECTICIDES Tx?

Answer 17

•Atropine in large doses.
Initial management must focus on adequate use of atropine.
•If given before ageing has occurred, pralidoxime (2-PAM) splits the phosphate-enzyme bond and acts as cholinesterase regenerator. Because of its positive charge, it doesn’t enter the CNS: does not reverse central effects.
•For convulsions: diazepam or thiopental.

Question 18

CARBAMATE INSECTICIDES

Answer 18

• The antidote is atropine.
• Pralidoxime is not recommended because the inhibition is spontaneously reversible and short-lived.
• But if the exact agent is not identified and the patient has significant toxicity, pralidoxime should be given empirically

Question 19

RONDENTICIDE (WARFARIN) MOA?

Answer 19

• One of the most frequently used rodenticides.
• Vitamin K1 restores the production of clotting factors.
• Vitamin K will not begin to restore clotting factors for 6 or more hours (peak effect 24 hours).
• Therefore, patients with active hemorrhage may require fresh-frozen plasma or fresh whole blood.

Question 20

CYANIDE-MECHANISM OF TOXICITY?

Answer 20

• Cyanide has a very high affinity for Fe3+.
• It binds to the Fe3+ in the heme of cytochrome a,a3 in mitochondria, and prevents oxygen from serving as the final electron acceptor.
• Cellular respiration is inhibited, resulting in lactic acidosis and cytotoxic hypoxia.

Question 21

CYANIDE POISONING Tx?

Answer 21

TREATMENT
•CYANIDE ANTIDOTE KIT: Amyl nitrite pearls
Sodium nitrite
Sodium thiosulfate
•CYANOKIT®:

treatment is aimed at reversal of such binding by providing a large pool of ferric iron to compete for cyanide.

Question 22

CHELATORS

Answer 22

• Dimercaprol (BAL): supplied in peanut oil (IM).
• Unithiol: water soluable analog of BAL (IV and oral ).
• Succimer: water soluable analog of BAL (oral).
• Edetate calcium disodium (EDTA).
• Penicillamine.
• Deforoxamine.

Question 23

ORGANIC LEAD POISONING?

Answer 23

tetraethyl lead or tetramethyl lead antiknock gasoline additives, no longer used.
• readily absorbed through skin and lungs.
•Primary signs occur in the CNS and may include hallucinations, headache, irritability, convulsions and coma.

Question 24

LEAD POISONING- TREATMENT

Answer 24

1.Supportive management:
•For seizures: diazepam.
•For cerebral edema: mannitol and dexamethasone.
2. Chelation therapy:
•EDTA (given by continuous infusion)
•Dimercaprol (given IM),
•succimer (given orally)
•unithiol.

Question 25

ACUTE INORGANIC ARSENIC POISONING - MANAGEMENT

Answer 25

1.Supportive therapy.
2. Chelating therapy:
•Dimercaprol IM: (First-line agent available in the US).
•Unithiol IV: Has the most favorable pharmacologic profile for treatment of acute arsenic intoxication(not approved or marketed in the Unite States).
•Once patients are hemodynamically stable and GI symptoms have subsided, oral chelation with either oral unithiol or oral succimer.

Question 26

CHRONIC INORGANIC ARSENIC POISONING

Answer 26

•Succimer is the chelator of choice for subacute and chronic toxicity.

Question 27

ACUTE MERCURY POISONING- TREATMENT

Answer 27

•Oral or IV unithiol, IM dimercaprol or oral succimer.

Question 28

IRON Tx?

Answer 28

• Deferoxamine is the chelator of choice.

* Activated charcoal, a highly effective adsorbent for most toxins, does not bind iron and thus is ineffective