MEDICINE II
3B POISONING, DRUG OVERDOSE AND ENVENOMATION
Dr. Christine B. Subia | M ay 11, 2020
M-21
POISONING
 Poisoning refers to the development of dose-related adverse effects
following exposure to chemicals (commonly used in the farm,
industrial), drugs, or other xenobiotics (substances that are foreign
to the body and to the environment)
 Substances commonly regarded as poisons (arsenic and cyanide)
can be consumed without ill effect.
 Depends on the amount you ingested
 Most poisons have predictable dose related effects
 Individual responses to a given dose may vary because of genetic
polymorphism, enzymatic induction or inhibition in the presence of
other xenobiotics, or acquired tolerance
 Poisoning may be local (e.g., skin, eyes, or lungs) or systemic
depending on the:
 Route of exposure
 Chemical and physical properties of the poison
 Mechanism of action
EPIDEMIOLOGY
 > 5 million poison exposures occur in the US/ year.
 Most are acute, are accidental (unintentional), involve a single
agent, occur in the home, result in minor or no toxicity, and involve
children <6 years of age (most common because of mislabelling)
 Pharmaceuticals 47% of exposures and in 84% of serious or fatal
poisonings.
 Unintentional exposures can result from:
 Improper use of chemicals at work or play
 Label misreading
 Product mislabelling
 Mistaken identification of unlabelled chemicals
 Uninformed self-medication
 Dosing errors by nurses, pharmacists, physicians, parents, and
the elderly.
 Most common cause: ABUSE and MISUSE
 ABUSE
 Psychotropic or euphoric effects
 MISUSE
 Excessive self-dosing
 is increasingly common and may also result in unintentional
self-poisoning
 About 20–25% of exposures require bedside health-professional
evaluation, and 5% of all exposures require hospitalization
 Up to 30% of psychiatric admissions are prompted by attempted
suicide via overdosage.
 Mortality rate is low: <1% of all exposures.
 Acetaminophen
 Agent most often implicated in fatal poisoning
 Carbon Monoxide
 Leading cause of death from poisoning
 This prominence is not reflected in hospital or poison center
statistics because patients with such poisoning are typically
dead when discovered and are referred directly to medical
examiners.
CONCHA | LAPPAY
HISTORY
 Time (very important), route (Oral, nasal, IV), duration, and
circumstances (location, surrounding events, and intent) of
exposure
 The name and amount of each drug, chemical, or ingredient
involved (Sometimes they will bring the bottle of the pesticide; if
multi-drug overdose – ask for maintenance)
 Time of onset, nature, and severity of symptoms (vomiting-when,
burning sensation of the esophagus)
 The time and type of first-aid measures provided (milk, water)
 Medical and psychiatric history (very important to consider;
depression – common)
PHYSICAL EXAMINATION AND CLINICAL COURSE
 Vital signs, the cardiopulmonary system, and neurologic status.
 The neurologic examination: neuromuscular abnormalities such as
dyskinesia, dystonia, fasciculation, myoclonus, rigidity, and tremors.
 Evidence of trauma and underlying illnesses. (sometimes they can
acquire trauma due to history of fall)
 Eyes: for nystagmus and pupil size and reactivity
 Abdomen: for bowel activity and bladder size (distended bladder)
 Skin: burns, bullae, color, warmth moisture, pressure sores, and
puncture marks
 History is unclear: all orifices should be examined for the presence
of chemical burns and drug packets
 The odor of breath or vomitus and the color of nails, skin, or urine
may provide important diagnostic clues
 The diagnosis of poisoning in cases of unknown etiology primarily
relies on pattern recognition.
 The first step is to assess the pulse, BP, RR, Temp and
neurologic status (you can differentiate it thru physiologic
state)
 Characterize the overall physiologic state as stimulated,
depressed, discordant, or normal
 There’s a specific drug that causes the physiologic states:
called TOXIDROME
 TOXIDROME – If you don’t know the poison, you get the H&PE,
Neurologic exam and then consider the underlying causes of
the physiologic state and to attempt to identify a
pathophysiologic pattern or toxic syndrome based on the
observed findings.
 After getting the physiologic state, you have to grade them:
*See last page for a larger picture
*See last page for the table of drugs that will tell your physiologic state
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 M-21 POISONING, DRUG OVERDOSE AND ENVENOMATION
STIMULATED PHYSIOLOGIC STATE
 Increased pulse, BP, RR, temperature, and neuromuscular activity
 Stimulated physiologic state: reflect sympathetic, antimuscarinic
(anticholinergic), or hallucinogen poisoning or drug withdrawal (most
common)
 MYDRIASIS: characteristic feature of all stimulants is most marked in
antimuscarinic (anticholinergic) poisoning since pupillary reactivity
relies on muscarinic control.
 COCAINE: pupils are also enlarged, but some reactivity to light
remains.
 Antimuscarinic (anticholinergic) toxidrome is also distinguished by:
 Hot, dry, flushed skin
 Decreased bowel sounds
 Urinary retention (palpation: distended or not)
 Markedly increased vital signs and organ ischemia suggest
sympathetic poisoning
 DECONGESTANTS: reflex bradycardia from selective α-adrenergic
stimulants
 ASTHMA THERAPEUTICS: hypotension from selective β-adrenergic
stimulants
 Phencyclidine and Ketamine: limb ischemia from ergot alkaloids,
rotatory nystagmus
 High doses of cocaine and some anticholinergic agents (e.g.,
antihistamines, cyclic antidepressants, and antipsychotics): delayed
cardiac conduction
 Anticholinergic agent with membrane-active properties (e.g., cyclic
antidepressants, orphenadrine, phenothiazines): Seizures suggest a
sympathetic etiology
DEPRESSED PHYSIOLOGIC STATE
 Decreased pulse, BP, RR, temperature, and neuromuscular activity
are indicative of the depressed physiologic state caused by:
 “Functional” sympatholytics (agents that decrease cardiac
function and vascular tone as well as sympathetic activity)
 Cholinergic (muscarinic and nicotinic) agents
 Opioids
 Sedative-hypnotic γ-aminobutyric acid (GABA)-ergic agents
 MIOSIS: common and is most pronounced in opioid and cholinergic
poisoning
 Pronounced cardiovascular depression in the absence of significant
CNS depression suggests a direct or peripherally acting
sympatholytic.
 Other clues:
 Cardiac arrhythmias and conduction disturbances: due to
antiarrhythmics, β-adrenergic antagonists, calcium channel
blockers, digitalis glycosides, propoxyphene, and cyclic
antidepressants
 Mydriasis: due to tricyclic antidepressants, some
antiarrhythmics, meperidine, and diphenoxylate-atropine
[Lomotil]
 Nystagmus: due to sedative-hypnotics
 Seizures: due to cholinergic agents, propoxyphene, and cyclic
antidepressants
CONCHA | LAPPAY
DISCORDANT PHYSIOLOGIC STATE
 Mixed vital-sign and neuromuscular abnormalities, as observed in
poisoning by asphyxiants, CNS syndromes, membrane active agents,
and anion-gap metabolic acidosis (AGMA) inducers
 Membrane-active agents can cause simultaneous coma, seizures,
hypotension, and tachyarrhythmias.
 Alternatively, vital signs may be normal while the patient has an
altered mental status or is obviously sick or clearly symptomatic.
 Early, pronounced vital-sign and mental-status changes suggest
asphyxiant or membrane-active agent poisoning
NORMAL PHYSIOLOGIC STATE
 normal physiologic status and physical examination may be due to:
 Nontoxic exposure
 Psychogenic illness
 Poisoning by “toxic time-bombs”: agents that are slowly
absorbed, are slowly distributed to their sites of action, require
metabolic activation or disrupt metabolic processes (slow effect
to the body)
LABORATORY ASSESSMENT
 Increased AGMA: Electrolytes: to check for Anion Gap Metabolic
Acidosis (AGMA); is most common in advanced methanol, ethylene
glycol, and salicylate intoxication:
 Ketosis: Acetone, isopropyl alcohol, salicylate poisoning, or alcoholic
ketoacidosis.
 Hypoglycemia: β-adrenergic blockers, ethanol, insulin, oral
hypoglycemic agents, quinine, and salicylate
 Hyperglycemia: Acetone, β-adrenergic agonists, caffeine, calciblocs,
iron, theophylline
 Hypokalemia: Barium, β-adrenergic agonists, caffeine, diuretics,
theophylline, or toluene; hyperkalemia: α-adrenergic agonist, a β-
adrenergic blocker, cardiac glycosides, or fluoride.
 Hypocalcemia: Ethylene glycol, fluoride, and oxalate poisoning.
 The electrocardiogram (ECG) can be useful for rapid diagnostic
purposes. (It is important to check in drug-overdose)
 Bradycardia and AV blocks: α-adrenergic agonists, antiarrhythmic
agents, beta blockers, calcium channel blockers, cholinergic agents
(carbamate and organophosphate insecticides), cardiac glycosides,
lithium, or tricyclic antidepressants.
 QRS- and QT-interval prolongation: Hyperkalemia (maybe drugs
causing hyperkalemia), various antidepressants, and other
membrane-active drugs
 Ventricular tachyarrhythmias : Poisoning with cardiac glycosides,
fluorides, membrane-active drugs, methylxanthines,
sympathomimetics, antidepressants, and agents that cause
hyperkalemia or potentiate the effects of endogenous
catecholamines
RADIOLOGIC STUDIES
 Pulmonary edema (adult respiratory distress syndrome (ARDS):
especially heavy metals: can cause immediate ARDS; Carbon
Monoxide: most common causing sudden pulmonary edema;
cyanide, an opioid, paraquat, phencyclidine, a sedative-hypnotic, or
salicylate; by inhalation of irritant gases, fumes, or vapors (acids and
alkali, ammonia, aldehydes, chlorine, hydrogen sulfide, isocyanates,
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metal oxides, mercury, phosgene, polymers) or by prolonged anoxia,
hyperthermia, or shock.
 Aspiration pneumonia is common in patients with coma, seizures,
and petroleum distillate aspiration. (Right lung most commonly
affected and presence of infiltrates)
 The presence of radiopaque densities on abdominal x-rays: ingestion
of calcium salts, chloral hydrate, chlorinated hydrocarbons, heavy
metals, illicit drug packets, iodinated compounds, potassium salts,
enteric-coated tablets, or salicylates.
TOXICOLOGY STUDIES
 Urine and blood (and occasionally of gastric contents and chemical
samples)
 Most common is urine in our setting.
 Rapid qualitative hospital-based urine tests for drugs of abuse are
only screening tests that cannot confirm the exact identity of the
detected substance and should not be considered diagnostic or used
for forensic purposes
 False-positive and false-negative results are common.
 You have to do a good H&PE neurologic exam and Toxidrome.
 Confirmatory testing with gas chromatography/mass spectrometry
can be requested, but it often takes weeks to obtain a reported
result.
 Negative screening result may mean that the responsible
substance is not detectable by the test used or that its
concentration is too low for detection at the time of sampling.
POISONING AND DRUD OVERDOSE TREATMENT
General Principles
 Treatment goals:
 Support of vital signs
 Prevention of further poison absorption (decontamination)
 Enhancement of poison elimination (can give antidote for
faster elimination)
 administration of specific antidotes
 Prevention of re-exposure
MUST KNOW!
CONCHA | LAPPAY
THREE PHASES OF TOXIC
PRETOXIC PHASE
 (+) exposure but (-) symptoms
 Decontamination is the highest priority
 Treatment is based solely on the history
 The maximal potential toxicity based on the greatest possible
exposure should be assumed. Since decontamination is more
effective when accomplished soon after exposure and when the
patient is asymptomatic, the initial history and physical examination
should be focused and brief.
 IV access and initiate cardiac monitoring, particularly in patients with
potentially serious ingestions or unclear histories
 During poison absorption and distribution  blood levels may be
greater than those in tissue and may not correlate with toxicity.
 High blood levels of agents whose metabolites are more toxic than
the parent compound may indicate the need for additional
interventions (antidotes, dialysis).
 Acetaminophen
 Ethylene glycol
 Methanol
 Most patients who remain asymptomatic or who become
asymptomatic 6 h after ingestion are unlikely to develop subsequent
toxicity and can be discharged safely.
TOXIC PHASE
 The interval between the onset of poisoning and its peak effects—
management is based primarily on clinical and laboratory findings.
 Effects after an overdose usually begin sooner, peak later, and last
longer than they do after a therapeutic dose
 Resuscitation and stabilization are the first priority
 Symptomatic patients should have an IV line placed and should
undergo oxygen saturation determination, cardiac monitoring, and
continuous observation.
 Baseline laboratory, ECG, and X-ray evaluation may also be
appropriate.
 Intravenous glucose (unless the serum level is documented to be
normal), naloxone, and thiamine should be considered in patients
with altered mental status, particularly those with coma or seizures
(you can give Anticonvulsants)
 Intestinal (gut) dialysis with repetitive doses of activated charcoal
can enhance the elimination of selected poisons such as
theophylline or carbamazepine.
 Urinary alkalinization may enhance the elimination of salicylates and
a few other poisons.
 Chelation therapy can enhance the elimination of selected metals
RESOLUTION PHASE
 Supportive care and monitoring should continue until clinical,
laboratory, and ECG abnormalities have resolved.
 Since chemicals are eliminated sooner from the blood than from
tissues, blood levels are usually lower than tissue levels during this
phase and again may not correlate with toxicity.
 When a metabolite is responsible for toxic effects, continued
treatment may be necessary in the absence of clinical toxicity or
abnormal laboratory studies.
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SUPPORTIVE CARE
 GOAL: Maintain physiologic homeostasis until detoxification is
accomplished and to prevent and treat secondary complications
such as aspiration, bedsores, cerebral and pulmonary edema,
pneumonia, rhabdomyolysis, renal failure, sepsis, thromboembolic
disease, coagulopathy, and generalized organ dysfunction due to
hypoxemia or shock.
 Admission to an intensive care unit is indicated for the following:
 Patients with severe poisoning (coma, respiratory depression,
hypotension, cardiac conduction abnormalities, cardiac
arrhythmias, hypothermia or hyperthermia, seizures)
 Those needing close monitoring, antidotes, or enhanced
elimination therapy
 Those showing progressive clinical deterioration
 Those with significant underlying medical problems
RESPIRATORY CARE
 Endotracheal intubation: protection against the aspiration of
gastrointestinal contents is of paramount importance in patients
with CNS depression or seizures as this complication can increase
morbidity and mortality rates.
 Mechanical ventilation: may be necessary for patients with
respiratory depression or hypoxemia and for facilitation of
therapeutic sedation or paralysis of patients in order to prevent or
treat hyperthermia, acidosis, and rhabdomyolysis associated with
neuromuscular hyperactivity.
 Drug-induced pulmonary edema: usually noncardiac rather than
cardiac in origin
CARDIOVASCULAR THERAPY
 Hypotension is unresponsive to volume expansion: norepinephrine,
epinephrine, or high-dose dopamine(Inotropes)
 Glucagon, calcium, and high-dose insulin with dextrose effective in
beta blocker and calcium channel blocker poisoning.
 SVT associated with hypertension and CNS excitation is almost
always due to agents that cause generalized physiologic excitation
sedation with a benzodiazepine
 For ventricular tachyarrhythmias (VTAC) due to TCA and other
membrane-active agents sodium bicarbonate is indicated
 Arrhythmias may be resistant to drug therapy until underlying acid-
base, electrolyte, oxygenation, and temperature derangements are
corrected—for anti arrthymic drugs to work
 Magnesium sulfate and overdrive pacing (by isoproterenol or a
pacemaker): torsades des pointes and prolonged QT intervals.
 Magnesium and anti-digoxin antibodies: severe cardiac glycoside
poisoning
CENTRAL NERVOUS SYSTEM THERAPY
 Neuromuscular hyperactivity and seizures can lead to hyperthermia,
lactic acidosis, and rhabdomyolysis should be treated aggressively
 Seizures caused by excessive stimulation of catecholamine receptors
(sympathomimetic or hallucinogen poisoning and drug withdrawal)
or decreased activity of GABA (isoniazid poisoning) or glycine
(strychnine poisoning) benzodiazepine or barbiturates
 Seizures caused by isoniazid, which inhibits the synthesis of GABA at
several steps by interfering with the cofactor pyridoxine (vitamin
B6) high doses of supplemental pyridoxine.
PHENYTOIN – is contraindicated in toxicologic seizures!!!
CONCHA | LAPPAY
PREVENTION OF POISON ABSORPTION
GASTROINTESTINAL DECONTAMINATION
 Whether or not to perform gastrointestinal decontamination and
which procedure to use depends on:
 time since ingestion (know when did he take the drug)
 the existing and predicted toxicity of the ingestant
 the availability, efficacy, and contraindications of the procedure
 nature, severity, and risk of complications
The average time from ingestion to presentation for treatment:
 >1 h for children
 >3 h for adults (effective)
ACTIVATED CHARCHOAL
 Comparable or greater efficacy
 Has fewer contraindications and complications
 Less aversive and invasive than ipecac or gastric lavage
 Recommended dose: 1 g/kg body weight
 Charcoal adsorbs ≥90% of most substances when given in an
amount equal to 10 times the weight of the substance
 Charcoal adsorbs ingested poisons within the gut lumen, allowing
the charcoal-toxin complex to be evacuated with stool
 Charcoal decreases the absorption of ingestants by an average of:
 73% when given within 5 min
 51% when given at 30 min
 36% when given at 60 min
 S/E: mechanical obstruction of the airway, aspiration, vomiting, and
bowel obstruction (Charcoal will form a ball and cause blockage to
lumens) and infarction caused by inspissated charcoal.
GASTRIC LAVAGE
 Should be considered for life-threatening poisons that cannot be
treated effectively with other decontamination, elimination, or
antidotal therapies (e.g., colchicine)
 Performed by sequentially administering and aspirating ~5 mL of
fluid per kilogram of body weight
 The patient should be placed in Trendelenburg and left lateral
decubitus positions to prevent aspiration
 Lavage decreases ingestant absorption by an average of:
 52% if performed within 5 min
 26% if performed at 30 min
 16% if performed at 60 min
 COMPLICATIONS: aspiration, gastric perforation, tube misplacement
in the trachea
SYRUP OF IPECAC
 Being utilized long time ago
 An emetogenic agent that was once the substance most commonly
used for decontamination
 No longer has a role in poisoning management.
 Chronic ipecac use (by patients with anorexia nervosa or bulimia)
has been reported to cause:
 electrolyte and fluid abnormalities
 cardiac toxicity
 myopathy
WHOLE BOWEL IRRIGATION
 Performed by administering a bowel cleansing solution containing
electrolytes and polyethylene glycol (Golytely, Colyte) orally or by
gastric tube at a rate of 2 L/h (0.5 L/h in children) until rectal effluent
is clear.
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 The patient must be in a sitting position
 It is most appropriate for those who have ingested foreign bodies,
packets of illicit drugs, and agents that are poorly adsorbed by
charcoal (e.g., heavy metals).
 Contraindicated in patients with bowel obstruction, ileus,
hemodynamic instability, and compromised unprotected airways.
CATHARTICS
 Are salts (disodium phosphate, magnesium citrate and sulfate,
sodium sulphate) or saccharides (mannitol, sorbitol) that historically
have been given with activated charcoal to promote the rectal
evacuation of gastrointestinal contents.
 Given 30 mins after the administration of Activated charcoal.
Activated C for binding and Cathartics for defecation.
 S/E: Abdominal cramps, nausea, and occasional vomiting.
 Complications of repeated dosing include severe electrolyte
disturbances and excessive diarrhea.
 Contraindicated in patients who have ingested corrosives agents and
in those with preexisting diarrhea
DILUTION
 Drinking water, another clear liquid, or milk at a volume of 5 mL/kg
of body weight) is recommended only after the ingestion of
corrosives (acids, alkali).
 It may increase the dissolution rate (and hence absorption) of
capsules, tablets, and other solid ingestants and should not be used
in these circumstances.
ENDOSCOPIC OR SURGICAL REMOVAL
 Useful in rare situations, such as ingestion of a potentially toxic
foreign body that fails to transit the gastrointestinal tract, a
potentially lethal amount OF:
 Heavy metal (arsenic, iron, mercury, thallium)
 Agents that have coalesced into gastric concretions or bezoars
(heavy metals, lithium, salicylates, sustained-release
preparations).
 Patients who become toxic from cocaine due to its leakage from
ingested drug packets require immediate surgical intervention.
ENHANCEMENT OF POISON ELIMINATION
MULTIPLE DOSE ACTIVATED CHARCOAL
 Repetitive oral dosing with charcoal can enhance the elimination of
previously absorbed substances by binding them within the gut as
they are:
 Excreted in the bile
 Secreted by gastrointestinal cells
 Passively diffuse into the gut lumen (reverse absorption or
enterocapillary exsorption).
 Doses: 0.5–1 g/kg of body weight every 2–4 h.
 Multiple-dose therapy should be considered only for selected agents
(theophylline, phenobarbital, carbamazepine, dapsone, quinine).
 Complications: intestinal obstruction, pseudoobstruction, and
nonocclusive intestinal infarction in patients with decreased gut
motility.
 Sorbitol and other cathartics are absolutely contraindicated when
multiple doses is given
CONCHA | LAPPAY
URINARY ALKALINIZATION
 Ion trapping via alteration of urine pH may prevent the renal
reabsorption of poisons that undergo excretion by glomerular
filtration and active tubular secretion.
 Urinary alkalinization (producing a urine pH ≥7.5 and a urine output
of 3–6 mL/kg of body weight per hour by the addition of sodium
bicarbonate to an IV solution) enhances the excretion of
chlorophenoxyacetic acid herbicides, chlorpropamide, diflunisal,
fluoride, methotrexate, phenobarbital, sulfonamides, and
salicylates.
 Contraindications: congestive heart failure, renal failure, and
cerebral edema—Because you may kill the patient in congestion.
 Acid-base, fluid, and electrolyte parameters should be monitored
carefully
EXTRACORPOREAL REMOVAL
 Hemodialysis, charcoal or resin hemoperfusion, hemofiltration,
plasmapheresis, and exchange transfusion capable of removing
any toxin from the bloodstream.
 Agents most amenable to enhanced elimination by dialysis:
 Have low molecular mass (<500 Da)
 High water solubility
 Low protein binding
 Small volumes of distribution (<1 L/kg of body weight)
 Prolonged elimination (long half-life)
 High dialysis clearance relative to total body clearance.
 Dialysis should be considered in cases of severe poisoning due to
carbamazepine, ethylene glycol, isopropyl alcohol, lithium, methanol,
theophylline, salicylates, and valproate
 Candidates for extracorporeal removal therapies include:
 Patients with severe toxicity whose condition deteriorates
despite aggressive
 Supportive therapy
 Those with potentially prolonged, irreversible, or fatal toxicity
 Those with dangerous blood levels of toxins
 Those who lack the capacity for self-detoxification because of
liver or renal failure
 Px with a serious underlying illness or complication that will
adversely affect recovery.
ENVENOMATION
 The venom apparatus Venomous snakes:
• Have a pair of enlarged teeth
• Fangs, at the front of their upper jaw
 If a human is bitten, venom is usually injected subcutaneously or
intramuscularly.
 Epidemiology (US based)
• 1.2 million- 5.5million worldwide/year
• 421,000-1841,000 envenomation
• 20,000-94,000 deaths/ year
 Bite rates are highest in temperate and tropical climates where
populations subsist by manual agriculture and fishing
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 Asia is included to have high incidence of snake bite. We are  PROCOAGULANT ENZYMES: activates blood clotting causing
included. YES DAMING AHAS SA PINAS! :3 coagulopathy
 Highest in Africa and Asia: because of unavailability of anti-venom  ACETYLCHOLINESTERASE
 Three major families of venomous snakes PATHOGENESIS
1. ELAPIDAE  Snake venom is a mixture of polypeptides, proteolytic enzymes, and
a. Cobra toxins, which are species-specific
b. King cobra – most common venomous snake in the  Primarily neurotoxic
Philippines, thus only anti-venom available. o Hydrophidae: poisonous sea snakes
c. Krait o Elapidae: cobras, kraits, coral snakes
d. Coral snakes  Venom have curare-like effect by blocking neurotransmission at
2. VIPERIDAE – vipers neuromuscular junction
3. HYDROPHIDAE – sea snakes  Death results from respiratory depression

IDENTIFICATION FEATURES TYPES OF VENOMS

1. NEUROTOXIC – most common cause of Cobra; Common cause of
death(COD) is respiratory failure
2. HEMOTOXIC – Common COD is hypovolemic shock
3. CYTOTOXIC – Common COD is septic shock
NEUROTOXIC VENOM
PRESYNAPTIC (beta) NEUROTOXINS
 Inhibits the release of
neurotransmitter—neuromuscular
blockade
POSTSYNAPTIC (alpha) NEUROTOXINS
Venomous Non-Venomous
HEAD Triangular Round  Binds to postsynaptic nicotinic
EYES Elliptical Round acetylcholine receptor--preventing
TAIL Single row of subcaudal Double row of subcaudal the depolarizing action--respiratory
scales scales failure and death by asphyxiation.
SNAKE VENOM  More easily affected by antivenom
 Promote vascular leaking, causes tissue necrosis, affect coagulation PATHOGENESIS
cascade, and impair organ function  Viperidae – vipers
 Complex mixture of proteins including large enzymes—local tissue  Primarily hemotoxic and cytotoxic:
destruction. o Crotalidae (subfamily of viperidae)
 Low molecular weight polypeptides—lethal systemic effects:  Tissue necrosis, vascular leaks, coagulopathies
o Acidic  Death results from hemorrhagic shock, ARDS, and renal failure.
o Sp gravity 1.030-1.070  BLEEDING: most common cause of VIPERS
o On drying: Fine needle like crystals  Most common death of hemotoxic is HEMORRHAGIC SHOCK
 Systemic symptoms may include: hypotension, pulmonary edema, HEMOTOXIC VENOM
hemorrhage, altered mental status, or paralysis (including muscles of  Acts by lysing erythrocytes
respiration)  VIPERS
 Water soluble  Proteolytic action
 Lethal dose: Cobra- 0.12gm; Krait-0.06gm; Russell’s V-0.15gm  They produce swelling, cardiovascular damage, and eventual
 Prognosis: Overall mortality rate for venomous snakebite is <1% necrosis.
among US victims who receive ASV; the incidence of permanent  Disrupt blood clotting and, in the process of destroying the blood's
functional loss in a bitten extremity is substantial. functionality, severely damage internal organs and other body
tissues, which can be extremely painful.
COMPONENTS OF SNAKE VENOM  The immediate cause of death in such cases is usually hypovolemic
Four broad categories: enzymes, polypeptides, glycoproteins, low shock.
molecular weight compounds.  envenomation increases capillary permeability that results in blood
 PHOSPHOLIPASE A2: damages the blood vessels, skeletal muscles and plasma loss from the intravascular to the extracellular space,
 HYALURONIDASE: responsible for local edema, necrosis creating edema
 Alpha and B NEUROTOXINS: binds to Acetylcholine receptor at the CYTOTOXIC VENOM
motor end plate; spastic patient; can lead to flaccid paralysis of  Has cytolytic properties which cause local necrosis and secondary
the patient infection, which could result in sepsis and death.
 ZINC METALLOPROTEINASE HAEMORRHAGINS: damages the
vascular permeability causing edema

CONCHA | LAPPAY 6
 M-21 POISONING, DRUG OVERDOSE AND ENVENOMATION
CLINICAL FEATURES ELAPIDAE Cobra, Kraits Neurotoxic
 Pain of the bite – increasing local pain (burning, bursting, throbbing) VIPERIDAE (VIPERS) Russell’s Vipers, Saw scaled Hemotoxic
at the site of the bite Vipers, Pit Vipers
 Local swelling that gradually extends proximately up the bitten limb HYDROPHIDAE Sea Snakes Myotoxic
MUST KNOW: COBRA!
 Tender, painful enlargement of the regional lymph nodes draining
the site of the bite
 Bites by kraits, sea snakes may be virtually painless and may cause
negligible local swelling.
LOCAL SYMPTOMS AND SIGNS IN THE BITTEN PART
 Fang marks
 Local pain
 Local bleeding from fang marks 40 min after bite of pit viper
 Bruising
 Lymphangitis
MANAGEMENT
 Lymph node enlargement
 inflammation (swelling, redness, heat)
 Blistering
 Local infection, abscess formation and Necrosis – common caused
by cytotoxic venom
SYSTEMIC SIGNS AND SYMPTOMS
 Nausea, vomiting, malaise, abdominal pain, weakness, drowsiness,
prostration
 Cardiovascular (Viperidae) : Dizziness, faintness, collapse, shock,
hypotension, cardiac arrhythmias, pulmonary edema, cardiac arrest
 Bleeding and clotting disorders (viperidae): Hemotoxic Venom
Bleeding from recent wounds (including fang marks, venepunctures DO NOTs IN FIRST AID
etc.) and from old partly-healed wounds.  Do not apply a tourniquet – In cytotoxic venom (worsen the
 Spontaneous systemic bleeding necrotized tissue)
 Neurological (Elapidae, Russells’s viper): Neurotoxic venom  Do not wash the bite site with soap or any other solution to remove
 Drowsiness the venom
 Paraesthesiae  Do not make cuts or incisions on or near the bitten area
 Abnormalities of taste and smell  Do not use electrical shock
 “Heavy” eyelids  Do not freeze or apply extreme cold to the area of bite
 Ptosis (classic sign)  Do not apply any kind of potentially harmful herbal or folk remedy
 External ophthalmoplegia  Do not attempt to suck out venom with your mouth
 Paralysis of facial muscles  Do not give the victim drink, alcohol or other drugs
 Difficulty in opening mouth  Do not attempt to capture, handle or kill the snake and patients
 Aphonia should not be taken to quacks
 Difficulty in swallowing secretions  Not that tight to increase necrosis
 Respiratory and generalized flaccid paralysis (respiratory
failure): mc cod ng neurotoxic
 Skeletal muscle breakdown (sea snakes, Russell’s viper)
 Generalized pain
 Stiffness and tenderness of muscles
 Trismus
 Myoglobinuria
 Hyperkalemia
 Cardiac arrest Renal (Viperidae, sea snakes)
 Hematuria, haemoglobinuria, myoglobinuria, oliguria/anuria
 Symptoms and signs of uremia

 Dark/brown urine is due to bleeding in the kidneys.

CONCHA | LAPPAY 7
 M-21 POISONING, DRUG OVERDOSE AND ENVENOMATION
SNAKE BITE TREATMENT PROTOCOL
 WHO Guidelines for the management of snake-bites
o Rapid clinical assessment and resuscitation: ABCDE approach
 Airway
 Breathing (respiratory movements)
 Circulation (arterial pulse)
 Disability of the nervous system (level of consciousness)
 Exposure and environmental control (protect from cold,
risk of drowning, etc.)
 Journal of Emergencies, Trauma, and Shock
o IV access established in unaffected extremity
o CBC, coagulation profile, fibrinogen concentration, should be
assessed (if hemotoxic envenomation or not)
o Tourniquets placed in field should be carefully removed if anti-
venom has been administered already.
o The bitten extremity should be marked at 2 or more sites
proximal to the bite and the circumference at these locations
should be assessed every 15min to monitor for progressive
edema-indicative of ongoing venom effects.
o All the patients should be kept under observation for a
minimum of 24 hours.
o Many species, particularly the Krait and the hump-nosed pit
viper are known for delayed appearance of symptoms which
can develop after 6–12 hours
 If more than 24 hrs, no symptoms: advice the patient and send
home. DO NOT admit patient with a snake bite 24 hrs ago.
TH
 HARRISON’S MANUAL OF MEDICINE 19 EDITION
 FIELD MANAGEMENT
 Get the victim to definitive care as soon as possible.
 Splint a bitten extremity and keep it at heart level to lessen
bleeding and discomfort.
 Avoid incisions into the bite wound, cooling, consultation with
traditional healers, tourniquets, and electric shock because
these measures are ineffective and may increase local tissue
damage.
 If the offending snake is reliably identified and known to be
primarily neurotoxic, pressure immobilization (wrapping of the
entire limb in a bandage at a pressure of 40–70 mmHg for
upper limbs or 55–70 mmHg for lower limbs) may be used. The
victim must be carried to medical care, because walking will
disperse venom from the bite site regardless of its anatomic
location.
 HOSPITAL MANAGEMENT
 Monitor vital signs, cardiac rhythm, urine output, and O2
saturation closely, and watch for evidence of cranial nerve
dysfunction (e.g., ptosis), which may precede difficulty
swallowing or respiratory insufficiency.
 Note the level of swelling and the circumference of the affected
limb every 15 min until swelling has stabilized.
 Treat shock initially with isotonic saline (20–40 mL/kg IV); if
hypotension persists, try 5% albumin (10–20 mL/kg IV) and
vasopressors.
 Begin the search for appropriate, specific antivenom early in all
cases of known venomous snakebite. In the United States,
CONCHA | LAPPAY
round-the-clock assistance is available from regional poison
control centers.
1. Any evidence of systemic envenomation (systemic
symptoms or signs, laboratory abnormalities) and
significant, progressive local findings (e.g., swelling that
crosses a joint or involves more than half of the bitten
limb) are indications for antivenom administration.
2. Treating physicians should seek advice from snakebite
experts regarding indications for and dosing of antivenom.
The duration of antivenom administration depends on the
offending snake species, but multiple doses are not
effective in reversing bite responses that have already
been established (e.g., renal failure, established paralysis,
necrosis).
3. Worldwide, antivenom quality varies; rates of
anaphylactoid reaction can exceed 50%, prompting some
authorities to recommend pretreatment with IV
antihistamines (diphenhydramine, 1 mg/kg to a maximum
of 100 mg; and cimetidine, 5–10 mg/kg to a maximum of
300 mg) or even a prophylactic SC or IM dose of
epinephrine (0.01 mg/kg, up to 0.3 mg). CroFab, an
antivenom used in the United States against North
American pit viper species, poses a low risk of allergy
elicitation.
4. A trial of acetylcholinesterase inhibitors should be
undertaken for pts with objective evidence of neurologic
dysfunction because this treatment may cause neurologic
improvement in pts bitten by snakes with postsynaptic
neurotoxins.
 Elevate the bitten extremity above heart level once antivenom
administration has been initiated.
 Update tetanus immunization.
 Observe pts for muscle-compartment syndrome.
 Observe pts with signs of envenomation in the hospital for at
least 24 h. Pts with “dry” bites should be watched for at least 8
h because symptoms are commonly delayed.
INVESTIGATIONS/DIAGNOSTICS
 Twenty-minute whole blood clotting test (20WBCT)
 Hgb/platelet count/peripheral smear
 Prothrombin time (PT)/activated partial thromboplastin time
 serum creatinine/Urea/Potassium
 ECG/X-ray/CT/Ultrasound
 Arterial blood gas
 Enzyme-linked immunosorbent assay (ELISA) to confirm snake
species.
 Kidney Function Test for Acute Kidney Injury
SEVERITY OF ENVENOMATION (*See last page)
COBRA ANTIVENOM
 Mainstay of treatment
 Antivenom is immunoglobulin
 ASV is produced both in Liquid and Lyophilized forms.
 There is no evidence to suggest which form is more effective.
 Liquid ASV requires a reliable cold chain and has 2-year shelf life.
8
 M-21 POISONING, DRUG OVERDOSE AND ENVENOMATION
 Lyophilized ASV in powder form has 5-year shelf life and requires
only to be kept cool.
 Only free unbound fraction of venom can be neutralized by anti-
snake venom(ASV)
INDICATIONS FOR ANTI-VENOM
 According to WHO
 Hemotoxic venom: correct the bleeding parameters: you may give
blood products- plasma concentrate (contains coagulation factors)
 Presence of hemoglobinuria: indication to start anti-venom
medication
NEOSTIGMINE TEST/ TENSILON TEST
CRITERIA FOR REPEATING THE INITIAL DOSES OF ANTIVENOM
 Criteria for giving more antivenom [level of evidence O, E]:
o Persistence or recurrence of blood incoagulability after 6 hours
or of bleeding after 1-2 hours
o Deterioration in neurotoxic or cardiovascular signs after 1-2
hours.
 Maximum dose of ASV: around 25 vials
 ASV should be administered over a period of 1 hour.
 ASV TEST DOSE: have not been shown to have predictive value in
predicting anaphylactic reactions or late serum sickness, and not
recommended.
 SERUM SICKNESS SYNDROME: Most Common ADVERSE EFFECT
INITIAL DOSE
 The recommended dose is often the amount of antivenom required
to neutralize the average venom yield when captive snakes are
milked of their venom. In practice, the choice of an initial dose of
antivenom is usually empirical.
 Each vial is 10 ML of reconstituted ASV
 8-10 vials for both adults and children.
o Common krait – 100 mL ASV
o Russell’s viper – 100 mL
o Saw scaled viper – 50 mL
o Indian cobra – 100 mL
REFERENCES:
DR SUBIA’S LECTURE | HARRISON’S MANUAL OF MEDICINE 19TH EDITION
CONCHA | LAPPAY
RESPONSE TO INITIAL DOSE OF ASV
 General: The patient feels better. Nausea, headache and generalized
aches and pains may disappear very quickly.
 Spontaneous systemic bleeding: usually stops within 15-30 minutes.
 Blood coagulability: restored in 3-9 hours.
 In shocked patients: Blood pressure may increase within the first 30-
60 minutes and arrhythmias such as sinus bradycardia may resolve.
 Neurotoxic envenoming: begin to improve as early as 30 minutes
after antivenom, eg ptosis:30 mins
 Active haemolysis may cease within a few hours and the urine
returns to its normal color
 Used if there’s a neurotoxic envenomation
 Can be given first while waiting for anti-venom to arrive
 Atropine sulphate (0.6 mg for adults; 50 μg/kg for children) or
glycopyrronium is given by intravenous injection followed by
neostigmine bromide by intramuscular injection 0.02 mg/kg for
adults, 0.04 mg/kg for Children.
o The patient is observed over the next 30-60 minutes
(neostigmine) or 10-20 minutes (edrophonium)
o If positive institute regular atropine & neostigmine
USE OF ACETYLCHOLINESTERASE INHIBITORS IN NEUROTOXIC SNAKE
ENVENOMATION
1. Patient with clear, objective evidence of neurotoxicity should
receive a test dose of endrophonium or neostigmine.
2. Pretreat with atropine 0.6mg IV
3. Treat with: Endrophonium 10mg IV or neostigmine 1.5 to 2 mg IM
4. If objective improvement is evident after 5 mins, treat with:
 Neostigmine: 0.5mg IV or SQ every 30mins as needed
 Atropine: 0.6 mg IV continuous infusion over 6 hours
ADVERSE REACTION TO ANTI- SNAKE VENOM (ASV)
1. EARLY ANAPHYLACTC REACTION
 10-180mins
 Itch, urticarial, dry cough, fever, nausea, vomiting, abdominal
colic, diarrhea, tachycardia
2. PYROGENIC (ENDOTOXIN) REACTION
 1-2 hours
 Shaking chills, fever, vasodilation, hypotension, febrile
convulsion
3. LATE (SERUM SICKNESS TYPE) REACTION
 1-12 days
 Fever, nausea, vomiting, diarrhea, itching, recurrent urticarial,
arthralgia, myalgia, lymphadenopathy, periarticular swelling
FOLLOW-UP
 After discharge from hospital, victim should be followed
 If discharged within 24 hours, patient should be advised to return if
there is any worsening of symptoms such as bleeding, pain or
swelling at the site of bite, DOB, altered sensorium, etc.
 The patient should also be explained about serum sickness which
may manifest after 5-10 days
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 M-21 POISONING, DRUG OVERDOSE AND ENVENOMATION

SEVERITY OF
ENVENOMATION

TYPE OF SIGNS OR
MINIMAL MODERATE SEVERE
SYMPTOMS
Swelling, erythema, or ecchymoses Progression of swelling, erythema, Rapid swelling or ecchymosis involving the
LOCAL
confined to the site of bite ecchymoses beyond the site of bite entire body part
No systemic S/SX Non-life threatening S/SX Marked severe signs and symptoms:
Start 5 VIALS Start 5-1O VIALS  hypotension
 altered sensorium
SYSTEMIC
 Tachycardia
 Tachypnea
10-20 VIALS Anti-Venom
No coagulation abnormalities or Mildly abnormal coagulation profile without Marked abnormal coagulation profile
COAGULATION other important laboratory clinically significant bleeding (+) evidence of bleeding or threat of
abnormalities Mild abnormalities on other lab test spontaneous hemorrhage

CONCHA | LAPPAY 10