SPECIFIC THERAPY OF ACUTE INTOXICATION

Ngatidjan

Department of Pharmacology and Therapy Faculty of Medicine UGM

THERAPEUTICAL PROCESS
Establish diagnosis of intoxication
(taking history, clinical and laboratory examinations)

Clinical intervention
(surgical, drug therapy, etc.)

what kind of drug (age, BW, main and concomitant disease, genetic)

how much (the dose, frequency)

how to give (route of administration)
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Diagnosis
Physical clinical examination :
- skin pale, chery red, cyanotics, dry, wet, etc. - eye pupil miosis, mydriasis, dry, unisochoric, etc. - mouth dry, hypersalivation, asymetrics, etc. - heart tachycardia, bradycardia, arrhythmia, etc. - lung normal, hyperventilation, etc. - abdomen hypoactivity, methalic sound, etc. - pulse rythmic, weak, normal, tachy or bradycardia, etc. - blood pressure high BP, low BP, etc.
scientific guessing - symptom causative agent - sign

Diagnosis
Laboratory examination
- the rest toxin or suspect substance - the rest of suspect material - washing container - vomiting material - gastric lavage - urine - blood - serum - etc. identify of suspected toxin
- medical aspect - therapy - medico legal aspect
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Laboratory examination

harmless substance, good vital function

consciousness
harmful

vital function disturbed

vital function undisturbed

specific measure 1. emesis 2. gastric lavage 3. adsorbent 4. antidotal agents 5. forced diuresis 6. dialysis 7. hemoperfusa
2. 3. 4. 5. 6. 7.

good vital function unconsciousness cardiopulmonary resuscitation vital function disturbed

THERAPY OF ACUTE INTOXICATION

Supportive / nonspecific measurements Specific measurements
inhibits further absorption of toxic substances increase elimination process inhibit or antagonize of toxic effects
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Therapy of acute intoxication

First aid assessment of ABCD
(airway breathing, brain, circulation, disability)

cardiopulmonary resuscitation

prevent the progression of intoxication

keep the victim away from source of poison

decontamination (wash the area of body contact,

emesis, gastric lavage, laxant)
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Supportive measurements
- Life saving maintenance vital function (heart and lung) - Remove mucus (from airway) - Use appropriate suction pump (if necessary) - Give O2 (as carbogen,
CO2 5 %)

- Artificial respiration ( respirator) - Corticosteroids

(if pneumonitis is the most undesired complication)
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ACUTE INTOXICATION
Specific measurements
inhibit further absorption of suspected toxic agent
emesis, gastric lavage, adsorben, laxants.

increase the elimination of suspected agent

forced diuresis, dialysis, hemoperfusion, acidify or alkalinize of urine

inhibit or antagonize the emerging toxic effects

antidote
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Emesis
- An oral intoxication - Consciousness

- Less than 1 4 hrs.

- The ingested thing was not a corrosive

material or distillated petroleum oil

- a orally route intoxication
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Emesis
- Physical stimulation :
(stimulate uvula or pharynx wall)

- Pharmacological stimulation :
* apomorphine subcutaneous injection. * ipecac (7 g in 100 ml syrup : 30 ml in 100 ml distilled water in adult).

* do not give any salt solution

or any vegetable oil to induce emesis.
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Gastric lavage
- Oral intoxication

- Consciousness unconsciousness :
* not shock, delirium or convulsive patients

- 4 hours or less
- Not corrosive material - Procedure (using a gastric tube)
give 150 - 300 ml saline or water or KMnO4, 37o C, few minutes aspirated using a syringe. Do again 5 - 10 times the last aspirate leave 30 - 50 g activated charcoal in the stomach 13

Adsorbent
- Inhibit gastrointestinal absorption.
(by form a physicochemical bound with toxin)

- Orally
* activated charcoal
* resin (cholestyramine) * kaolin. - bentonite (for bipyridil intoxication)
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universal antidote

* evaporated milk (weak adsorbent)

Forced diuresis
- Requirement : good heart and kidney function - Drink water
coconut ( green coconut)

- intravenous ringer / ringer dextrose :

* drops according to the needs.
* monitor the urine production. * monitor the side effect occurred.
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Forced diuresis
- Harmful effect and side effect :
lung and cerebral edema

- Contraindication :
* shock
* cardiac or / renal insufficiency * edema, suspect cerebral edema, convulsion. 16

Dialysis
- Hemodialysis :
(machine dialysis)

- Peritoneal dialysis :
* dialysis fluid 100 - 250 ml (37o C, sterile,
isotonic, iso-pH), intraperitoneal injection * wait 1/2 -1 hrs aspirate again. * do again 8 - 12 times.
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Hemodialysis
- Patient blood dialysis machine which is equipped with :
- membrane dialysis (semi permeable)
- dialysis fluid ( counter direction to the blood)

- peristaltic pump (to draw the blood and

dialysis fluid)
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Hemodialysis

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Dialysis
- Indication :
- life-threatening poisoning (caused by ethanol,
methanol, ethylene glycol, isopropanol)

- substance with small volume distribution

- substance with small MW - substance (water soluble) - nonprotein binding (blood and tissue)
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Hemodialysis
- Factors affecting the rate of dialysis :
- Toxin properties (BM, protein binding, lipid solubility,
distribution volume, dissociation)

- Dialyzer properties (dialysis area, dialysis pressure)

- Flow rate of dialysis fluid - Volume of dialysis fluid
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Hemoperfusa
- Patients blood was perfused into a machine

(which was filled with adsorbent : activated

charcoal, polystyrene resin)

blood was recirculated in the body.

side effects : * thrombocytopenia, leucopenia. * micro emboli charcoal (rare).
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Antidotes
Substance used to counteract the effects of poison :
- Neutralizing the toxic substance (poison)
(antigen-antibody reaction, chelation, chemical binding)

- Antagonize the poison physiological effects

(activation of the opposing nerve system, competitiveness in metabolism or receptors)
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Antidotes
Counteract the effects of the poison by :
Chemical reaction chemical antidotes Physiological reaction physiological antidotes

It can be Specific antidotes Nonspecific antidotes

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Chemical Antidotes
- Chelators :
EDTA and CaNa2EDTA (edatamil) for Pb, Au and Cd intoxication BAL (dimercaprol) for As, Pb, Fe, Se, and U intoxication deferoxamine ? (for Fe intoxication is doubfuly its effectivity may increase absorption) penicilamine (for Cu, Hg and Zn intoxication)

- KMnO4 (oxidize the alkaloids for alkaloids intoxication) - Activated charcoal

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CaNa2-edetate
EDTA (ethylenediamine tetraacetic acid) To chelate many heavy metals especially Pb An ionic freely water soluble compound Vd is small extracellular fluid compartment

Excretion via kidney half life 20 60 minutes

Should be given intramuscularly
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CaNa2-edetate

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DIMERCAPROL (BAL : British Anti Lewisite)

Dithiol,2,3-dimercaptopropanol
for inorganic or elemental mercury, As (arsen) toxicity and Pb.

Metal chelator As (arsen) bind to sulfhydryl SH group ( cell damage)

effective at lo concentration administered up to 1 hrs after skin contaminatio.

Dimercaprol
3 mg / kg i.m. (every 4 hrs 2 days, than every 12 hrs 7 10 days)
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Dimercaprol (BAL)

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Activated charcoal
Fine black odorless powder To adsorb the toxic molecules Adsorptive capacity
depends on its internal surface area and external pores diameter

May decrease the absorption of drugs given in the same time

(aspirin, acetaminophen, barbiturates, phenytoin, theophyline, cyclic antidepresants)

Best administered as a water slurry

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Physiological antidote
ethanol (for methanol intoxication) anticonvulsants (for caffeine intoxication) atropine (for AChE inhibitor intoxication) antihistamines (for histamine intoxication) anticonvulsants (for chlorine intoxication) naloxone (for morphine intoxication) acetylcystein (for acetaminophen intoxication)
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ETHANOL
For methanol and ethylene glycol intoxication. Competitive inhibition on alcohol dehydrogenase inhibits the formation of formic acid. Can be given orally or intravenously
ethanol alcoholdehydrogenase methanol

acetaldehyde alcoholdehydrogenase
Acetic acid further metabolism

formaldehyde

formic acid toxic to retina32

Physiological Antidote
CNCytochrome oxydase

Na-nitrit
Hb++ nitrite metHb+++ + CNCyano-metHb Cyano cytochrome

Na-thiosulfat

Cytochrome oxydase

CN rhodanase

Thiocyanat

metHb+++

metHb reductase Hb++ 33

Physiological antidote
atropine as antidote for
cholinergic drug poisoning
cholinergic drugs stimulate r-M

(direct or indirectly by inhibit AChE)

atropine or atropinic drugs, block r-M,

prevent the stimulation of r-M (by ACh or muscarinic durg).

competitive antagonism.
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Physiological antidote
physostigmine as antidote for
anticholinergic poisoning reverse coma, seizures, severe myoclonic and choreoathetoid activities caused by anticholinergic drugs reverse peripheral manifestation such as mydriasis, hyperthermia, dry skin and mucosa, tachycardia, constipation, urine retention etc.

transverse blood brain barrier.

inhibit AChE ACh accumulation
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Acetaminophen (paracetamol, APAP : N-acetyl p-aminophenol)

Side effect caused by NABQI

- Hemolytic anemia - Liver damage (large dose)
(7-10%)

Paracetamol

(90-93%)

NABQI (N-asetyl benzoquinoneimine)

gluthation
conjugation (sulfate or glucuronate) excretion

conjugation (sulfate or glucuronate)

excretion

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Paracetamol intoxication
Large dose of paracetamol. Acetylcysteine.

stimulate gluthation syntesis.

substitute gluthation. facilitates NABQI elimination
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APAP (N-acetyl-p-aminophenol, acetaminophen) NABQI (N-acetylbenzoquinoneimin) [Ca2+]

Blocked by EGTA
(ethylene glycol bis tetra acetic acid)

Activation of endonucleases DNA damage (single strand breaks) Necrotic cell death
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List of recommended antidote

activated charcoal (general adsorbent)

antivenin polyvalent (for crotalidae snake bite)

antivenin Lactrodectus (for black widow spider bite)

atropine (for ACh E inhibitor intoxication)

botulinal antitoxin (ABE trivalent)
(for botulinus intoxication)

cyanide kit (amylnitrite, Na-nitrite and Na-thiosulfate)

(for cyanide poisoning)
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List of recommended antidote

deferoxamine mesylate (for Fe intoxication)

dextrose water solution (50%, 20%)

(for hypoglycemic agent intoxication)

diazepam, midazolam (for seizure intoxication) digoxin specific antibodies (for digoxin intoxication) dimercaprol BAL (for As, Pb, Hg poisoning) diphenhydramine (for histamine containing food or
others poisoning)
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List of recommended antidote

ethanol 100% or 10% (for methanol intoxication) ipecac, syrup of (for emeticum to induce emesis) naloxone (for opioid intoxication) oxygen hyperbaric (for CO and cyanide poisoning) phenobarbitan injection (anticonvulsant) phenytoin injection (anticonvulsant) pralidoxime (for / as AChE reactivator)
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