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Clinical Management of
Poisoning
4th Year Clinical Pharmacology
Toxicology
Department of Pharmacy
School of Health Sciences
LMMU
3rd Lecture
Andrew M Bambala
bambalaandrew@gmail.com
9/9/2022
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General Outline
 Introduction and Principles of Toxicology
 Specific poisons (Gases, Pesticides heavy metals)
 Drug overdose (Aspirin, paracetamol, quinine, benzodiazepines, herbal medicine
toxicity)
 Drug abuse, drug dependence and its management
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Potential Sources of Toxicity
•
Therapeutic agents –due to over doses, unusual adverse effects, frequent administrations
of therapeutic doses & drug interactions
•
Industrial chemicals- environmental pollution & they may be a direct hazard in the work
place they are used.
•
House-hold chemicals – The top household products ingested are cleaning agents,
cosmetics & personal products & berries.
•
Environmental contaminants- main sources of pollution to the environment are industrial
processes, pesticides &smokes from factories & vehicles. Environmental pollutants may be
released into the air, water, or dumped onto land.
Potential Sources of Toxicity
• Natural toxicants• Plants & animals produce toxic substances for both defense & offensive
•
by accidental ingestions of poisonous plants or animals & by stinging & biting
• Food additives –
• low biological activity.
• Many different additives are added to food to alter the flavor or colour,
prevent spoilage
• potentially toxic substances which are regarded as contaminants.
Potential Sources of Toxicity
•
Traditional medicines (Botanicals) –
• the medical use of botanicals in their natural & unprocessed form
• misconceptions regarding safety &efficacy of the agents are common.
• These products can be adulterated, misbranded or contaminated.
• Doses for active botanical substances may be higher.
•
Drugs of abuse
• Excessive or improper use of drugs or other substances for non-medical purposes.
• There are a lot of drugs of abuse with high potential of dependence &
tolerance(e.g alcohol, nicotine…)
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Human Poisoning
Death Due to Poisoning Globally2019
Drugs
Cleaning substances
Cosmetics and personal care
products
Foreign bodies
Plants
Bites and envenomation (venoms)
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Extent of the problem
• Drug overdose was the leading cause of injury death in 2012
• Among people of 25 to 60 years old
• Among children under age 6, pharmaceuticals account for about 40% of all
exposures
• Drug Overdose (OD) is the ingestion, inhalation, injection or application of a
drug or other substance in quantities greater than medically recommended.
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Drugs classes Overdosed
• Opioids: heroin, codeine, morphine
• Depressants: barbiturates,
benzodiazepines
• Antidepressants:
• Antipsychotics
• Cannabinoids: marijuana
• Non-Opioid Analgesics: paracetamol
• Stimulants: amphetamines , cocaine,
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Categories
with largest number of
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deaths
 Analgesics & Pain killers

involved in 30% of fatalities

Acetaminophen, Aspirin, Naproxen, Celecoxib= 72%

84% of the fatalities were intentional
 Antidepressants

69% involved TCA’s
 Sedatives/hypnotics/antipsychotics

benzodiazepines account for 36%
 Cardiovascular drugs
 Alcohol
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Reasons for Drug Overdose
 Accidental
 Failure to follow instructions
 Medication error
 Intentional, to cause harm
 Suicide
 Addiction
 Habituation
 Physiological dependence
 Psychological dependence
 Tolerance
 Withdrawal
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Common features of poisoning
• No single symptom and no definite group of symptoms
• A case of poisoning should be suspected if the following things are observed:
 Symptoms appearing suddenly in an otherwise healthy individual
 Symptoms appearing within a short period after food or drink
 In a group or gathering, if similar symptoms are seen in all
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Common risk factors:
• Low physical tolerance
• Previous suicide attempts
• Leaving substance abuse treatment early
• Abusing multiple substances
• Prior overdoses
• Men have a higher risk than women to die from OD
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SIGNS AND SYMPTOMS OF OD
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Death due Poisoning (Drug Overdose)
Mechanism of death due poisoning
Central nervous system (CNS), resulting in coma
 Comatose- Lose of airway protective reflexes and respiratory function
(Respiratory depression) e.g. narcotics and sedative barbiturates
 Airway obstruction by the flaccid tongue, aspiration of gastric contents into
the tracheobronchial tree, or respiratory arrest.
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Death due Poisoning (Drug Overdose)
Cardiovascular toxicity
 Hypotension due to depression of cardiac contractility
 Hypovolemia resulting from vomiting, diarrhea,
 Fluid sequestration; peripheral vascular collapse due to blockade
of α-adrenoceptor-mediated vascular tone; or cardiac arrhythmias
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Death due Poisoning (Drug Overdose)
 Hypothermia or hyperthermia due temperature-dysregulating
effects
 Lethal arrhythmias such as ventricular tachycardia and fibrillation
 Drugs such as ephedrine, amphetamines, cocaine, digitalis, and
theophylline are cardio active
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Death due Poisoning (Drug Overdose)
Cellular hypoxia
E.g. due to cyanide, hydrogen sulfide, carbon monoxide interfere with
transport or utilization of oxygen
Development of tachycardia, hypotension, severe lactic
acidosis, and signs of ischemia on the electrocardiogram
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Death due Poisoning (Drug Overdose)
Seizures, muscular hyperactivity, and rigidity
Seizures may cause pulmonary aspiration, hypoxia, and brain damage
Hyperthermia may result from sustained muscular hyperactivity and can
lead to muscle breakdown and myoglobinuria, renal failure, lactic
acidosis, and hyperkalemia
Examples are antidepressants, isoniazid, diphenhydramine, cocaine,
and amphetamines
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Death due Poisoning (Drug Overdose)
Other organ system damage (Often delayed)
Paraquat attacks lung tissue, resulting in pulmonary fibrosis, beginning
several days after ingestion
Massive hepatic necrosis due to poisoning by acetaminophen or certain
mushrooms results in hepatic encephalopathy and death 48–72 hours or
longer after ingestion
Behavioral effects of the ingested drug may result in traumatic injury
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Principles
of Clinical Management of
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Poisoning
1. Clinical stabilization of the patient (Supportive Care)
2. Clinical evaluation (history, physical, laboratory, radiology)
3. Prevention of further toxicant absorption (Decontamination)
4. Enhancement of toxicant elimination
5. Administration of antidote
6. Supportive care, close monitoring, and clinical follow-up
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1. Clinical
stabilization of the patient (Supportive Care)
 It include support of ABC & vital signs.
 Airways (A) – Clear of obstruction such vomits, Oral endotracheal tube
inserted
 Breathing (B)- Assessed by observation and pulse oximetry , intubated
and mechanical ventilation
 Circulation (C)-Continuous monitoring of pulse rate, blood pressure,
urinary output
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1. Clinical
stabilization of the patient (Supportive Care)
• An intravenous line and bloods for serum glucose and other routine
determinations
• Altered mental status should receive a challenge with concentrated dextrose,
Prevent and treat secondary complications
• aspiration, cerebral and pulmonary edema, pneumonia, renal failure, sepsis,
thromboembolic disease, and generalized organ dysfunction due to
hypoxemia or shock
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2.
23 Clinical evaluation (history, physical,
laboratory, radiology )
Historical Evaluation from family members, coworkers, health workers
Which drug(s) were taken? When was it taken?
How much was taken? How was it taken?
Why was it taken? Was anything else taken?(Consider possible coingestants: other things which may be in this
person’s medicine cupboard)
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Physical
Examination
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• A brief examination should be performed, emphasizing those areas most
likely to give clues to the toxicological diagnosis.
• These include vital signs, eyes and mouth, skin, abdomen, and nervous
system
• Vital signs: blood pressure, pulse, respirations, and temperature) is
essential in all toxicological emergencies
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Physical exam:
Mouth
Signs of burns due to corrosive substances, or soot from smoke inhalation
Typical odors of alcohol, hydrocarbon solvents, or ammonia may be noted
Skin
The skin often appears flushed, hot, and dry in poisoning with atropine and other
antimuscarinics
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Physical exam:
Abdomen
Hyperactive bowel sounds, abdominal cramping, and diarrhea are
common in poisoning with organophosphates, iron, arsenic,
Eyes
Constriction of the pupils (miosis) and Dilation of the pupils
(mydriasis)
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Physical: Neurologic exam
• Mental status
Seizures
• Alcohol
Organophosphates
• Endocrine/Epilepsy
Ethanol
• Intoxication
INH/Insulin
• Oxygen
Sympathomimetic
• Trauma/Tumor
Amphetamine
• Shock/Strokes
Benzodiazepines withdrawal
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LABORATORY INVESTIGATION
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 The toxicology laboratory must provide appropriate testing:
 Identification of agents responsible for acute or chronic poisoning
 Detection of drugs of abuse
 And therapeutic drug monitoring.
 If the diagnosis is in doubt,
 The administration of antidotes or protective agents is contemplated, or
 The use of active elimination therapy is being considered.
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Basic information necessary for
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toxicology
laboratory
• Suspected agent(s)
• Suspected dose
• Time of ingestion and sampling
• Clinical presentation
• Location of the victim
LAB SPECIMEN
• The selection of specimen type is based on both the
toxicokinetics of the suspected agent and
• laboratory methodology.
•
Quantitative tests are performed on serum or whole
• blood,
• Qualitative tests are performed on urine and gastric
contents.
•
In emergency toxicology minimally, blood and urine
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 Urine
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Specimen collection
•
Urine is useful for screening tests as it is often available in large volumes
•
contains higher concentrations of drugs or other poisons than blood.
•
The presence of metabolites may sometimes assist identification
 Stomach contents
•
include vomit, gastric aspirate and stomach washings - it is
•
important to obtain the first sample of washings, since later samples may be very dilute.
 Scene residues (non-biological)
•
It is important that all bottles or other containers and other suspect materials found with
or near the victim (scene residues) are retained for analysis
 Blood
•
Blood (plasma or serum) is normally reserved for quantitative assays but for some
poisons,such as carbon monoxide, whole blood has to be used for qualitative tests.
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General laboratory tests in clinical
Biochemical tests
31  A.toxicology
 Blood glucose:
•
A toxicant that causes hypoglycemia includes insulin, iron, acetyl salicylic acid
•
Hyperglycemia is a less common complication of poisoning than hypoglycemia
 Electrolytes, blood gases and pH
•
Toxic substances or their metabolites cause metabolic acidosis owing to the
accumulation of organic acids, notably lactate.
•
Measurement of the serum or plasma anion gap can be helpful.
•
((Na++k+) + (Cl- + HCO3).It is normally about 10mmol/l.
•
If arterial blood gas measurement is performed, direct measurement of oxygen
saturation with a CO-oximeter allows detection of methemoglobin, resulting from
intoxication with various oxidizing drugs or Carbon monoxide-hemoglobin.
 .
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 Plasma enzymes
• The plasma activities of liver enzymes, such as aspartate aminotransferase, alanine
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 aminotransferase may increase rapidly after absorption of toxic doses of substances
that can cause liver necrosis, notably paracetamol, carbon tetrachloride, and copper
salts.
 Cholinesterase activity
•
Plasma cholinesterase is a useful indicator of exposure to organophosphorus
compounds or carbamates, and a normal plasma cholinesterase activity effectively
excludes acute poisoning by these compounds.
 Measurement of serum osmolality
•
The normal osmolality of plasma (280-295mOsm/Kg) is largely accounted by sodium,
urea &glucose. However, large increases (especially methanol, ethanol, or propan-2-
ol) in relatively large amounts.
•
Osmolsl gap (Osmolarity) = 2(Na+) + Glucose ÷18 + BUN ÷ 2.8
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 Hematological tests Hematocrit (Erythrocyte volume fraction)
• Acute or acute-on-chronic over dosage with iron salts, acetylsalicylic acid, indomethacin, and
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other non-steroidal anti-inflammatory drugs may cause gastrointestinal bleeding leading to
anemia.
•
Anaemia may also result from chronic exposure to toxins that interfere with haem synthesis, such as
lead.
 Leukocyte count
•
acute poisoning, in response to an acute metabolic acidosis, resul ingestion of ethylene
 glycol or methanol, or secondary to hypostatic pneumonia following prolonged coma.
 Blood clotting
•
The prothrombin time and other measures of blood clotting are likely to be abnormal in acute
poisoning with rodenticides such as Coumarin anticoagulants.
 Carboxyhemoglobin
•
Measurement of blood carboxyhemoglobin can be used to assess the severity of acute carbon
monoxide poisoning.
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Investigations
Laboratory Examinations
 Arterial blood gases
Instrumental Examinations
 ECG
 Endoscopic examination
 Plasma electrolytes
 X ray examination
 Laboratory tests for renal function
 CT scan
 Laboratory tests for hepatic function
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Investigations
Laboratory Examinations
 Arterial blood gases
Instrumental Examinations
 ECG
 Endoscopic examination
 Plasma electrolytes
 X ray examination
 Laboratory tests for renal function
 CT scan
 Laboratory tests for hepatic function
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3. Prevention
of further toxicant absorption (Decontamination)
 Decontamination of the skin
 Cleansing with soap + water: used after dermal exposure to
organophosphate
 Cleansing with acetic acid (vinegar): for Nicotine
 Decontamination of the stomach
 Emesis

It is useful within 3 hrs of ingestion

Done with ipecac syrup(30 ml)
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3. Prevention
of further toxicant absorption (Decontamination)
 Gastric lavage
 It is useful within 3hrs of ingestion
 Tube used is Boas tube or Nasogastric tube
 Activated Charcoal
 Endoscopic surgical removal
 Decontamination of the intestines by whole bowel irrigation (WBI)
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4.Enhancement
of toxicant elimination
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Extracorporeal techniques
 Dialysis Procedures
 Peritoneal dialysis— relatively simple and available technique, inefficient in removing most
drugs.
 Hemodialysis- more efficient than peritoneal dialysis; correction of fluid and electrolyte
imbalance
 Hemoperfusion (carbamazepine, theophylline, digitoxin, phenobarbital, valproic acid
 Plasmapheresis (Verapamil, Thyroxine)
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4.Enhancement of toxicant elimination
 Intracorporal techniques
 Urinary pH Manipulation and Charcoal
Renal elimination of toxins can be enhanced by alteration of urinary pH.
Urinary alkalinization is useful in cases of salicylate overdose.
Acidification may be useful for amphetamines but is not advised because
it may worsen renal complications from rhabdomyolysis
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5. Administration of antidote
According to WHO
“Antidote defined as a therapeutic substance used to counteract the toxic
action(s)of a specified xenobiotic.”
Classification of antidote
According to mode of action
According to site of action
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According to Site of Action
1. Interacts with the poison to form a non toxic complex that can be excreted. Chelators
2. Accelerates the detoxification of the poison: N- acetylcystine,thiosulfate
3. Decrease the rate of conversion of poison into toxic metabolite: Ethanol, Fomepizole
4. Compete with the poison for certain receptors :Naloxone
5. Block the receptor through which the toxic effect of the poison is mediated:Atropine
6. Bypass the effect of Poison: O2 in the treatment of CO and cyanide toxicity
7. Antibodies to the poison : digiband and antivenoms
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According
to mode of action
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CHARCOAL:
(Universal Antidote
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Physical Antidote
Agent use to interfere with poison through physical properties, not change
their nature
a) Adsorbing: The main example is activated charcoal
b) Coating: A mixture of egg & milk make a coat over the mucosa.
c) Dissolving: 10% alcohol or glycine for carbolic acid
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Chemical Antidote
Interact specifically with a toxicant or neutralize the toxicant
Two mechanisms:
1. Complex Formation:
Antidote form complexes with the toxicant making it unavailable to
cross the membrane or to interact with receptors
 DMSA(dimercaprol and dimercaptosuccinic acid are sulfohydral
compounds that bind with metals such as arsenic acid ,lead
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Chemical Antidote cont.’
2. Metabolic conversion
 Detoxification to less toxic product
 Nitrite interact with hemoglobin and cyanide to form
cyanmethemoglobin ,which is less toxic than cyanide and interferes
with cyanide access to cytochrome oxidase system
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Pharmacological antidote
PHYSIOLOGICAL : They act by producing opposite effect to that of poison
Sodium nitrite converts hemoglobin into methemoglobin in order to bind
cyanide.
PHARMACOLOGICAL : Counteract the effects of a poison by producing the
opposite pharmacological effects
Pharmacologic antidotes may neutralize or antagonize the effects of a
toxicant.
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Mechanism
of action
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1. Preventing the formation of toxic metabolites:
 More effective when given immediately before toxic metabolic activation
 Example: Ethanol and 4-methylpyrazole(4-mp) which compete for the alcohol
dehydrogenase for the formation of toxic intermediate from ethylene glycol.
2. By facilitation of more rapid or complete elimination of A toxicant :
 Change the physiochemical nature of toxin, allowing better glomerular filtration
and prohibit tubular reabsorption.
 e.g. Molybdenum and sulfate for copper toxicity by making water soluble
complex
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27th July, 2020 Andrew Bambala
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Mechanism of action
3. By competing with the toxicant’s action at a receptor site:
a) Antagonism: Competitive antagonism:
• Naloxone/naltrexone: opioid dependence, longer action and affinity for mu
receptor.
• Flumenazil: antagonist for benzodiazepine
• Atropine: Antagonist for organophosphate, carbamate and other
parasympathomimetic antidote.
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Mechanism of action cont.’
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• B. non competitive antagonism:
• calcium gluconate: used for calcium channel blocker especially verapamil
toxicity
• Pralidoxime (Pam): ChE activator act by breaking alkyl phosphate ChE bond. it
is used in organophosphate toxicity
• Diacetyl monoxyime(dam): action same as pam but with more bbb penetration.
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Mechanism of action cont.’
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4. By blocking receptors responsible for the toxic effect :
Example: Atropine blocks the physiologic effect of acetylcholine at
cholinergic synapse and neuromuscular junction in organophosphate toxicity
5. By aiding in the restoration of normal function
The antidote promotes return to normal function by repairing a defect or
enhancing a function that correct the effect of poison.
•
Acetylcysteine supplies the precursor amino acids for glutathione
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6. Supportive
care, close monitoring, and clinical
follow-up
Generally admitted to a critical care unit for close monitoring.
 Delayed toxicity such as acetaminophen, paraquat, and diphenoxylate
 Multiple phases of toxicity that include delayed effects
 Risk for nosocomial infections and electrolyte disturbances as well as potential
harmful effects from the initial therapies
 For example, induction of emesis, gastric lavage, or orogastric infusion of
activated charcoal can cause aspiration and lead to pneumonitis
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6.
53 Supportive care, close monitoring, and
clinical follow-up
 Delayed complications such as acute renal failure, hepatic failure, and
permanent brain damage
 For intentional self poisonings, a formal psychiatric evaluation
 Minimize patient morbidity and mortality
 Report to the Poison Centers
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Measures to prevent poison ingestion
• Never take or administer medicines in the
dark
• Store all poisons in locked containers
• Store all medicines out of children’s reach
• Never allow kids to take medicines
without supervision
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Measures to prevent poison ingestion
• Do not keep poisonous plants in the house
• Keep medicines in original containers
• Never keep outdated meds
• Always give or take the whole prescription
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