ivms principles of toxicology and anidotes -in special topics pharmacology

7/29/2019 IVMS Principles of Toxicology and Anidotes -In Special Topics Pharmacology

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Special Topic Pharmacology

Principles of Toxicology and Specific Antidotes

Prepared byMarc Imhotep Cray, M.D.Pharmacology Teacher

Companion Learning toolsReading:

Lecture PDF Notes/Epidemiology of Poisoning andAntidotes Used In Toxicology

Video:IVMS-General Principles of

Pharmacology Animations Playlist

Clinical:E-Medicine Article

Toxicity, Carbon MonoxideFull article table at the end
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Marc Imhotep Cray, M.D.

12 LEARNING OBJECTIVES

1. To understand the general principles ofclinical toxicology

2. To know general factors that influencetoxicity

3. To understand the initial approach to thepoisoned patient in terms of settingimmediate priorities

4. To appreciate the necessity to conduct, asthe first order of business, those proceduresthat evaluate and preserve vital signs

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5. To know what aspects of the physicalexamination and what diagnostic tests are tobe conducted to evaluate the general type aswell as the specifics of the poisoning

6. To understand the goals of treatment e.g. totreat the patient, not the poison, promptly

7. To know and understand strategies for

treatment8. To know and understand specific

approaches for reducing the body burden ofvarious poisons

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9. To know how to counteract toxicologicaleffects at receptor sites, if possible

10.To know and understand importanttreatment contraindications that preventserious injury or death of patients

11. To be aware of newer approaches andtreatment modalities

12.To know where to rapidly obtain facts,specific antidotes, or other information onpoison control needed immediately to treat

the patient 4


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Common Causes of Death in

Acutely Poisoned Patient Comatose patient:

Loss of protective reflexes

Airway obstruction by flaccid tongueAspiration of gastric contents into

tracheobronchial tree

Loss of respiratory drive

Respiratory arrest

Hypotension due to depression ofcardiac contractility

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the Acutely Poisoned Patient Shock due to hemorrhage or internal

bleeding

Hypovolemia due to vomiting, diarrhea orvascular collapse

Hypothermia worsened by i.v. fluidsadministered rapidly at room temperature

Cellular hypoxia in spite of adequateventilation and O2 admin. due to CN, CO orH2S poisoning

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the Acutely Poisoned Patient Seizures may result in pulmonary

aspiration;asphyxia

Muscular hyperactivity resulting inhyperthermia, muscle breakdown,myoglobinemia, renal failure, lacticacidosis and hyperkalemia

Behavioral effectstraumatic injuryfrom fights, accidents, fall from highplaces. Suicides, etc

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the Acutely Poisoned Patient Massive damage to a specific organ

system:

Liver (acetaminophen; amanita phylloides[poison mushroom]

Lungs (paraquat)

Brain (domoic acid) Kidney (ethylene glycol)

Heart (cobalt salts)

Note: death may occur in 48 72 hrs 8
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APPROACH TO THE POISONED

PATIENT History; Oral statements concerning

details

Call Poison Control Center re: druglabeling

Initial physical examination

Assessment of vital signs

Eye examination

CNS and mental status examination9



APPROACH TO THE POISONED

PATIENT Examination of the skin

Mouth examination

Lab (clinical chemistry and x-rayprocedures

Renal function tests

EKG

Other screening tests

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TREATMENT OF ACUTE

POISONING Treat the patient, not the poison", promptly

Supportive therapy essential

Maintain respiration and circulationprimary

Judge progress of intoxication by:

Measuring and charting vital signs andreflexes

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TREATMENT OF ACUTE

POISONING - 1st Goal - keep concentration of

poison as low as possible by preventing

absorption and increasing elimination

- 2nd Goal - counteract toxicological

effects at effector site, if possible

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Prevention of Absorption of

Poison Decontamination from skin surface

Emesis: indicated after oral ingestion of

most chemicals; must consider time since chemical ingested

Contraindications: ingestion ofcorrosives such as strong acid or alkali;

if patient is comatose or delirious;

if patient has ingested a CNS stimulant or is convulsing;

if patient has ingested a petroleum distillate

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Poison Induce emesis in the following ways:

1. mechanically by stroking posterior

pharynx;

2. use ofsyrup of ipecac, 1 ozfollowed by one glass of water;

3. use ofapomorphine parenterally

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Poison Gastric lavage: insert tube into

stomach and wash stomach with

water or normal saline to removeunabsorbed poison

Contraindications are the same as for

emesis except that the procedureshould not be attempted with

young children

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Prevention of Absorption ofPoison

Chemical Adsorption

activated charcoal will adsorb many

poisons thus preventing their absorption

do not use simultaneously with ipecac if

poison is excreted into bile in active form

adsorbent in intestines may interruptenterohepatic circulation

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Purgation Used for ingestion of enteric coated tablets

when time after ingestion is longer than onehour

Use saline cathartics such as sodium ormagnesium sulfate

Chemical Inactivation Not generally done, particularly for acids or

bases or inhalation exposure

For ocular and dermal exposure as well asburns on skin; treat with copious water

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Alteration of biotransformation

Interfere with metabolic conversion of

compound to toxic metabolite

Increasing urinary excretion byacidification or alkalinization

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Decreasing passive resorptionfrom nephron lumen

1. Diuresis

2. Cathartics

3. Peritoneal dialysis

4. Hemodialysis

5. Hemoperfusion

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Antagonism of the absorbedpoison (see PDF Notes)

If poisoning is due to agonist acting atreceptors for which specific antagonist

is available; antagonist may beavailable

Drugs that stimulate antagonistic

physiologic mechanisms may of littleclinical value; titration difficult

Use of antibodies

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Strategies for Treatment ofthe Poisoned Patient

Evaluate and stabilize vital signs

Give supportive therapy, if needed

Determine the type and specifics of thepoison

Time of exposure

Determine the presumed current locationof the poison

Determine Volume of Distribution for the

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Use the drug dissociation constant, presumedpH based on location and the Henderson-Hasselbach equation to determine the ratio

of ionized to non-ionized poison

Determine the immediate (real time) risk orhazard for absorption

Initiate body burden reduction procedures orspecific antidotes based on the aboveinformation

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If volume of distribution is very large; do not

waste time on any type of dialysis

X-ray for location of enteric coated pills anduse cathartics if in the stomach

Use hypocholesteremics for poisonstrapped in enterohepatic biliary system

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Acute organophosphatepesticide toxicityClick for: CASE PRESENTATION

A 6 month-old girl is irritable andcongested.

Rosa brings her 6 month-old daughter to yourrural clinic. She is new to the community,having arrived from Mexico about one monthago. She came to join her husband who

recently established a steady job as apesticide applicator on a large orchard

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Acute organophosphate pesticide

toxicity Mechanism of acute OP pesticide toxicity

discerned from clinical diagnostic tools

and antidotes used to treatorganophosphate poisonings.

Namely, determination of red blood cell

and plasma pseudocholinesterase activity

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Acute organophosphatepesticide toxicity (see notes page)

Acute organophosphate toxicity occursthrough inhibition of acetylcholinesterase

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SIGNS AND SYMPTOMS

M-U-D-D-L-E-S: miosis, urination, diarrhea, diaphoresis, lacrimation,

excitation of the central nervous system, and salivation.This works reasonably well in adults

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SIGNS AND SYMPTOMS

CHILDRENVS. ADULTS

Reviews of case series indicate that

pediatric organophosphate poisoningsoften manifest with hypotonia or mentalstatus changes such as lethargy and

coma, as well as seizures, the latterbeing relatively rare in adult OPpoisoning

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DIAGNOSIS AND TREATMENT

Diagnosis of organophosphate poisoning isoften made based on the history of significant

exposure and consistent symptoms, as in thecase described. If probable organophosphatepoisoning is suspected, immediate treatmentis recommended without waiting for

laboratory confirmation. Early consultationwith a poisoning specialist is recommended

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Cholinesterase(ChE) Depression as aDiagnostic Tool

Remember: Individual baseline ChE levels are

variable To confirm suspected OP poisoning:

Compare post-exposure ChE levels to those attime of illness

Clinically significant OP exposure: 20% depression of plasma pseudocholinesterase 15% depression of RBC ChE

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Treatments for OP Poisoning

Supportive Care

Atropine

2-PAM

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eMedicine Toxicology Articles

Toxicity, Acetaminophen Toxicity, Amphetamine Toxicity, Anticholinergic Toxicity, Antidepressant Toxicity, Antidysrhythmic Toxicity, Antihistamine Toxicity, Arsenic Toxicity, Barbiturate Toxicity, Benzodiazepine Toxicity, Beta-blocker Toxicity, Calcium Channel

Blocker

Toxicity, Carbon Monoxide Toxicity, Caustic Ingestions Toxicity, Clonidine Toxicity, Cocaine

Toxicity, Cyanide Toxicity, Cyclic Antidepressants Toxicity, Digitalis Toxicity, Lead Toxicity, Medication-Induced

Toxicity, Narcotics Toxicity, Salicylate

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