Komiskey 1-22-08 Toxicologic Emergencies 2

Front 1

use toxidrome patterns and symptoms of toxic agents to identify the poison.

describe initial assessment and management considerations in the treatment of toxic emergencies, especially when antidotes or chelating agents are needed
describe adverse effects of antidotes and chelating agents

Back 1

-

Front 2

Dosages causing acute and chronic toxicity from acetaminophen

Back 2

Acute ingestion: >7.5 grams/24 hours is toxic – a guide
Chronic ingestion: >4 grams a day

Front 3

Symptoms of acetaminophen toxicity

Back 3

Symptoms:
1st 24 hours to 48 hours-Asymptomatic.
24-48 hours – Rise of aminotransferases, jaundice, encephalopathy

Front 4

Treatment of acetaminophen toxicity

Back 4

Treatment:
Lavage & Activated Charcoal indicated.
Rumack-Matthew Nomogram utilized to decide whether treatment with N-acetylcysteine is required.

Front 5

N-Acetylcysteine increases the availability of ______, decreasing hepatic toxicity.

Back 5

glutathione

Front 6

In what cases is the nomogram not useful for deciding whether to use N-acetylcysteine

Back 6

Nomogram not useful for chronic overdoses and for overdoses that may be associated with ingestion of another drug that delays GI motility.

Front 7

Why has Acetonitrile in some fingernail glues caused pediatric deaths

Back 7

Acrylonitrile is metabolized to cyanide

Front 8

What emergency blood pressure reducer if given too long is metabolized to cyanide

Back 8

Nitroprusside (Nipride)

Front 9

Cyanide is so common that all mammals have an enzyme called ______ that detoxifies cyanide by converting it to thiocyanate

Back 9

rhodonase

Front 10

Cyanide PoisoningSigns and Symptoms

Back 10

Headache, vertigo, dizziness, giddiness, inebriation, confusion
Seizures
Coma
Shortness of breath, tachypnea, apnea
Abd pain, nausea, vomiting
General weakness, malaise
Initial bradycardia and hypertension may quickly change to hypotension
Pulse oximetry inaccurate
Cherry red skin color (rare and late)
Smell of bitter almonds on breath (60% of population)
Soot in mouth and nose if smoke inhalation

Front 11

Suspect cyanide poisoning in patients with an unexplained metabolic ________ and elevated ______ ____ levels because shifts cellular metabolism from aerobic to anaerobic

Back 11

Suspect cyanide poisoning in patients with an unexplained metabolic acidosis and elevated lactic acid levels because shifts cellular metabolism from aerobic to anaerobic

Front 12

Cyanide Poisoning Treatment

Back 12

Scene safety/Decontaminate
Airway protection
EKG
May show AV blocks, SVT, Ischemia, Asystole
Sodium Bicarb if unconscious or hemodynamically unstable and acidotic
Cyanide antidote kit =amyl nitrite, sodium nitrite, and sodium thiosulfate
Don’t use sodium nitrite in smoke inhalation because ↓ carrying capacity if blood

Front 13

Amyl Nitrite?

Back 13

Temporizing agent for reversal of cyanide toxicity
Has same effect on vascular smooth muscle as other nitrates.
1 amp crushed under nose or in O2 mask. 15 sec on 15 sec off.
Indications:
Significant Cyanide Poisoning
pt. comatose, bradycardic and known cyanide exposure.

Front 14

Precautions when using Amy Nitrate:

May cause profound hypotension.
Stop administration prior to Sodium ___________.
Not administered to the patient improving on their own.
Adequate oxygenation is imperative especially with smoke inhalation.

Back 14

Precautions when using Amy Nitrate:

May cause profound hypotension.
Stop administration prior to Sodium Thiosulfate.
Not administered to the patient improving on their own.
Adequate oxygenation is imperative especially with smoke inhalation.

Front 15

Precautions when using Sodium Thiosulfate
:

Not administered to the patient improving on their own.
Adequate ___________ is imperative especially with smoke inhalation.

Back 15

Precautions when using Sodium Thiosulfate
:

Not administered to the patient improving on their own.
Adequate oxygenation is imperative especially with smoke inhalation.

Front 16

Mechanism of Salicylate Toxicity:
Direct stimulation of respiratory center, causing respiratory __________
Irritation of gastrointestinal tract, causing decreased motility, pylorospasm, nausea, vomiting, hemorrhagic gastritis
Decreased ___________ levels/platelet dysfunction, causing prolonged clotting times
Uncoupling of oxidative phosphorylation

Back 16

Mechanism of Salicylate Toxicity:
Direct stimulation of respiratory center, causing respiratory alkalosis
Irritation of gastrointestinal tract, causing decreased motility, pylorospasm, nausea, vomiting, hemorrhagic gastritis
Decreased prothrombin levels/platelet dysfunction, causing prolonged clotting times
Uncoupling of oxidative phosphorylation

Front 17

Results of Oxidative Phosphorylation Uncoupling

ATP production decreases, resulting in CNS and cardiovascular failure.
Cells attempt to compensate by increasing the rate they process glucose anaerobically through __________.
Lactic and pyruvic acids accumulate, leading to metabolic ________.
Hypoglycemia results as liver sugar stores are depleted.
In absence of sugar cells begin to metabolize lipids, ______ bodies are produced, acidosis worsens.
Energy normally trapped as ATP is wasted as heat, causing a rise in body temperature.
The rise in body temperature accelerates metabolism, increasing tissue oxygen demand and worsening acidosis.

Back 17

Results of Oxidative Phosphorylation Uncoupling

ATP production decreases, resulting in CNS and cardiovascular failure.
Cells attempt to compensate by increasing the rate they process glucose anaerobically through glycolysis.
Lactic and pyruvic acids accumulate, leading to metabolic acidosis.
Hypoglycemia results as liver sugar stores are depleted.
In absence of sugar cells begin to metabolize lipids, ketone bodies are produced, acidosis worsens.
Energy normally trapped as ATP is wasted as heat, causing a rise in body temperature.
The rise in body temperature accelerates metabolism, increasing tissue oxygen demand and worsening acidosis.

Front 18

Therapy for salicylate poisoning

Back 18

General:
Activated charcoal( 10:1 by weight).
NaHCO3: Critical for therapy as acidosis promotes the entry of salicylic acid into the cells. (keep>7.4).
Specific:
Urinary alkalization .
Hemodialysis ( >1000-2000mg/L after acute overdose or> 60-70mg/dl with sub acute or chronic overdose).

Front 19

Most dangerous of overdoses.
(25% of fatalities occur in patients who are awake, alert, and at time of presentation)

Back 19

Tricyclic Antidepressants

Front 20

Clinical findings of Tricyclic overdose

Back 20

(1) Anticholinergic:
Tachycardia, dry mouth, flushed skin, decreased peristalsis.

(2) Cardiotoxicity:
Quinidine like effect. Blocks sodium channels. Therefore widening of the QRS interval , ventricular arrhythmias, AV nodal block.

Front 21

Treatment for tricyclic overdose

Back 21

Alkalinization either using sodium bicarbonate and hyperventilation if intubated to a pH of 7.45-7.55. The sodium in the NaHCO3 alleviates depression of the sodium channels. Also acidosis impairs sodium channels so alkalinization beneficial.
Manage arrhythmias with lidocaine, magnesium, isoproterenol, and pacing

Neuro symp: benzodiazepines

Front 22

What are antidotes for the following:
APAP
Tricyclics
Opiates
Organophosphates
Heavy metals
Ca and beta blockers
Iron
Digoxin
Cesium, thallium

Back 22

---- --- antidotes --- --- ---------:
N acetylcysteine
Na bicarbonate
Naloxone
Atropine/2 PAM
BAL,CaNaEDTA
Glucagon
Desferoxamine
Dig Fab (Digibind)
Prussian blue

Front 23

What are antidotes for the following:
Methanol, ethylene glycol
Methemoglobinemia
Anticholinergics
Isoniazid
Snakebites

Back 23

---- --- antidotes --- --- ---------:
Fomepizole (Antizole)
Methylene blue
Physostigmine
Pyridoxine
Antivenom

Front 24

How do chelators work?

Back 24

Chelators (Greek = claw) bind directly with metal ions to form stable complexes that remove the metal from competition with the body's cells. Because a chelated metal is water soluble, it can be excreted readily by the kidney

Front 25

By definition, Chelation is the formation of a metal ion complex in which the metal ion is associated with a charged or uncharged electron donor, referred to as a ______. A chelate is a cyclic complex formed between a metal and a compound that contains two or more ligands (binding sites). The most stable chelates are those with a ____ or ___ membered ring.

Back 25

By definition, Chelation is the formation of a metal ion complex in which the metal ion is associated with a charged or uncharged electron donor, referred to as a ligand. A chelate is a cyclic complex formed between a metal and a compound that contains two or more ligands (binding sites). The most stable chelates are those with a five or six membered ring.

Front 26

An agent frequently used in chelation therapy is ___________ (also known as BAL or British Anti-Lewisite). Oral chelating agents used as alternatives to BAL are 2,3-__________________ acid (DMSA), dimercaptopropanesulfonate (DMPS),

Back 26

An agent frequently used in chelation therapy is dimercaprol (also known as BAL or British Anti-Lewisite). Oral chelating agents used as alternatives to BAL are 2,3-dimercaptosuccinic acid (DMSA), dimercaptopropanesulfonate (DMPS),

Front 27

Wilson's disease chelator

Back 27

D-penicillamine

Front 28

______, is often used to chelate iron

Back 28

Deferoxamine

Front 29

_________ also has an affinity for lead and was one of the first chelators developed

Back 29

Ethylenediamintetraacetic acid (ETDA)

Front 30

BAL clinically useful for treating acute and chronic poisoning by organic or inorganic arsenals and for protecting against _______-induced renal damage. Not effective in treating _______-induced neurological conditions or CNS damage. Not useful to chelate _______ because it can partially dissociate in urine and enhance renal damage. Also true for iron and ________.

Back 30

BAL clinically useful for treating acute and chronic poisoning by organic or inorganic arsenals and for protecting against mercury-induced renal damage. Not effective in treating mercury-induced neurological conditions or CNS damage. Not useful to chelate cadmium because it can partially dissociate in urine and enhance renal damage. Also true for iron and selenium.

Front 31

Adverse effects of BAL:

Tachycardia, hypertension, anxiety, nausea, vomiting, abdominal pain, headache, agitation, salivation, lacrymation,
Dental and muscle pains
Pain at the site of injection.
_______ sensation of the lips, mouth, throat and eyes, conjunctivitis,rhinorrhoea, tingling of the hands and other extremities, a feeling of constriction in the chest and throat, sweating of the forehead and _____.

Back 31

Adverse effects of BAL:

Tachycardia, hypertension, anxiety, nausea, vomiting, abdominal pain, headache, agitation, salivation, lacrymation,
Dental and muscle pains
Pain at the site of injection.
Burning sensation of the lips, mouth, throat and eyes, conjunctivitis,rhinorrhoea, tingling of the hands and other extremities, a feeling of constriction in the chest and throat, sweating of the forehead and hands.

Front 32

What will chelate any metal that has a higher binding affinity than Ca (lead, iron, zinc, manganese, beryllium and copper)

Back 32

Calcium Disodium Edetate – CaNa2 - EDTA

Front 33

CaNa2EDTA does not enter host cells but relies on excretion of lead into blood from ____. Lead chelates with EDTA to form a complex that is much greater than that of the Ca complex

Back 33

CaNa2EDTA does not enter host cells but relies on excretion of lead into blood from bone. Lead chelates with EDTA to form a complex that is much greater than that of the Ca complex

Front 34

Adverse effects of EDTA

Back 34

Toxicity to EDTA partly restricts its usage. After IV administration, severe proximal nephron degeneration may occur. Other symptoms include fever, nasal congestion, and dermatitis.

Front 35

Penicillamine is formed from hydrolysis of penicillin. It forms tight chelates with what metals

Back 35

copper, lead, mercury, and zinc

Front 36

An advantage of Penicillamine is that it is well absorbed from the ________ after oral administration. Penicillamine is often given for long-term treatment of chronic metal poisoning, after the patient has been removed from immediate danger.

Back 36

GI tract

Front 37

is penicillamine universally recognized as the first-choice antidote?

Back 37

no

Front 38

Added advantage of pen is that it facilitates removal of methyl _______ and enhances urinary _______ excretion after inhalation of _______ vapor

Back 38

Added advantage of pen is that it facilitates removal of methyl mercury and enhances urinary mercury excretion after inhalation of mercury vapor

Front 39

Methylmercury has a high affinity for __________ groups, which attributes to its effect on enzyme dysfunction. One enzyme that is inhibited is choline acetyl transferase, which is involved in the final step of acetylcholine production. This inhibition may lead to acetylcholine deficiency, contributing to the signs and symptoms of _____ dysfunction.

Back 39

Methylmercury has a high affinity for sulfhydryl groups, which attributes to its effect on enzyme dysfunction. One enzyme that is inhibited is choline acetyl transferase, which is involved in the final step of acetylcholine production. This inhibition may lead to acetylcholine deficiency, contributing to the signs and symptoms of motor dysfunction.

Front 40

Succimer is chemically similar to ___________ (___) but is more water soluble, has a high therapeutic index, and is absorbed well from the GI tract. (It is given orally). It produces a lead diuresis comparable to that of CaNa2-EDTA and reverses the biochemical toxicity of lead, as indicated by normalization of circulatory delta-aminolevulinic acid dehydratase (an enzyme necessary for heme synthesis). The most common adverse effects include nausea, vomiting, diarrhea and anorexia

Back 40

Succimer is chemically similar to dimercaprol (BAL) but is more water soluble, has a high therapeutic index, and is absorbed well from the GI tract. (It is given orally). It produces a lead diuresis comparable to that of CaNa2-EDTA and reverses the biochemical toxicity of lead, as indicated by normalization of circulatory delta-aminolevulinic acid dehydratase (an enzyme necessary for heme synthesis). The most common adverse effects include nausea, vomiting, diarrhea and anorexia

Front 41

Succimer, AKA

Back 41

Dimercaptosuccinic acid (DMSA)

Front 42

____________ possesses high affinity for both ferrous and ferric iron; especially in acute iron poisoning in small children. It is also used to chelate aluminum. It is given parenterally(IV), since less than 15% is absorbed from the GI tract 
Defer______-recently approved for oral treatment of iron overload

Back 42

Deferoxamine possesses high affinity for both ferrous and ferric iron; especially in acute iron poisoning in small children. It is also used to chelate aluminum. It is given parenterally(IV), since less than 15% is absorbed from the GI tract 
Deferasirox-recently approved for oral treatment of iron overload

Front 43

Chelating agents for Arsenic Lead Mercury toxicity

Back 43

Dimercaprol (BAL) (not methylmercury) (IM)

Dimercaptosiccinic acid (DMSA, Succimer) (PO)

D-pencillamine (PO)

Front 44

Chelating agents for Arsenic

Back 44

Dimercaptopropane- sulfonate (DMPS) (PO, IM)

Front 45

Chelating agents for Lead

Back 45

Ethylenediamintetra- acetic acid (EDTA) (Edetate disodium) (IV)

Front 46

Dimercaprol (British Anti-Lewisite, 2,3dimercaptopropanol)
BAL is widely used for inorganic mercury; effective for protection of kidney (Hg++) ineffective protection of _____ (CH3Hg+) cannot be given orally, side effects

Back 46

brain

Front 47

Pencillamine
given orally effective for Hg, less so for -_____ some side effects

Back 47

CH3Hg+