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dr.Datten Bangun MSc,SpFK
Dept.Farmakologi & TerapeutikFak.Kedokteran U H N
M E D A N
Any substance that can harm the body by altering cell structure or functions
(cont.)
ToxinA poisonous substance secreted by bacteria, plants, or animals
Examples: Mushrooms Variety of house plants Bacterial contaminants in food
"All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy.“
Paracelsus (1493-1541)
Try and get as much history as possible including witnesses
People truly wanting to commit suicide often lie
History is often absent or unreliable Information from any source usually
helpful Physical exam is very important When, what, how much ?Why? Circumstances PMHx, Drug history Psychiatric history Assess mental status and capacity
Analgesic agents Cosmetics/ personal care products Household cleaning products Sedative hypnotics/ antipsychotics Foreign bodies/ toys Cough/ cold OTC preparations Topical preparations Pesticides
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1. Stabilization (A,B ,C approaches)2. Rapid Patient Evaluation (Physical,
Lab)3. Prevention of further toxin
absorption4. Enhancement of toxin elimination 5. Specific antidote 6. Supportive therapy
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A (Airway) B (Breathing) C (Circulation) D (Disability-AVPU/ Glasgow Coma
Scale) DEFG ( Don’t ever forget the
Glucose) GET A SET OF BASIC OBSERVATIONSGeneral Management -2
Use all your senses, search for the cluesLOOK -Track Marks
- Pupil SizeFEEL - Temperature, SweatingSMELL - Alcohol
Largely supportive !oxygen, iv access & fluids
Decrease drug absorptionactivated charcoal within 1 hour( whole bowel irrigation )( gastric lavage )
Increase drug eliminationurinary alkalisationhaemodialysis/perfusion /plasma
exchange
Physiologically based abnormalities that are known to occur with specific classes of substances and typically are helpful in diagnosis
Patterns of signs and symptomsPatterns of signs and symptoms
Useful to help in diagnosis and treatment of unknown poisons
Odor PoisonBitter almonds cyanideEggs hydrogen
sulfide,
mercaptansMothballs naphthalene,
camphorWintergreen methylsalicylate Garlic As, org- phosphates,,
Thallium10
Vital signs: = Tachycardia, = hypertension, = hyperpyrexia. Clinical appearance: =diaphoresis (sweating), =piloerection, mydriasis and hyperreflexia.= In severe cases, seizures, hypotension
(later effect) and dysrhythmias may occur.
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Sympathomimetic syndrome
Sometimes confused with the anticholinergic syndrome, but the later is associated with dry skin and diminished bowel sounds.
Mechanism
A drug mimicking the action of the sympathetic system;Alpha/beta adrenergic stimulation
What compounds may induce this type of syndrome? =Cocaine = Amphetamines and amphetamine-like compounds = OTC decongestants (pseudoephedrine, ephedrine, =phenylpropanolamine),Theophylline, caffeine
Myocardial ischemia may occur following sympathomimetic overdose due to coronary artery vasoconstriction, thrombus formation and platelet aggregation.
Myocardial ischemia can progress to infarction. Use of beta-adrenergic receptor blockers is contra-indicated. Recommended management of this condition includes:
BenzodiazepineNitroglycerinPhentolamine
Acute Coronary Syndrome
Vital signs: Bradycardia, increased respiratory rate (initially)
Clinical appearance: SLUDGESalivationLacrimationUrinationDefecation – Diaphoresis Gastrointestinal distressEdema (Pulmonary)
Also see: miosis (pinpoint pupils), muscle fasciculations, CNS depression
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1.Initial management: Stabilization: a.ABC’s: airway protection most commonly needed b.Orogastric lavage or NG tube: if
liquid ingestion and pt has not vomited yet c.IV access for antidotes and fluids
2.Antidotes (1) Atropine: a.effect: competitive inhibition of Ach at muscarinic receptors in smooth
muscles and CNS No effect on nicotinic receptor (N-M junction):can’t reverse muscle weakness
b.bronchorrheahypoxiatachycardia more atropin
(2) Pralidoxime (2-PAM,Protopam) a.effect: form a complex of PAM-OP-AchE PAM-OP released from
complex AchE reactivation metabolize Ach b.decreases atropine effect c.treatment as early as possible decreased effect after 36-48 hrs exposure aging effect (OP ;organophospor)
Most affect muscarinic receptors in brain, secretory glands, heart and smooth muscle
Few affect nicotinic receptors, e.g., Robinul (glycopyrolate)
Effects of anticholinergics are diffuse Indications—GI (gastritis, irritable bowel;
GU antispasmotic in overactive bladder; ophthalmology for exams, glaucoma; respiratory for bronchodilation; cardiology to increase heart rate
Antilirium for overdose of anticholinergics
Atropine Atrovent Scopolamine—antiemetic, motion
sickness Spiriva (tiotropium) Bentyl (antiscretory/antispasmotic) Cogentin Trihexyl (Parkinson’s)
Monalisa
Atropa belladonna (Solanaceae
Vital signs: Tachycardia, hypertension, hyperpyrexia
Clinical appearance: Hot, dry skin, mydriasis, diminished or absent bowel sounds, urinary retention, confusion and delirium. Sinus tachycardia is most common but other cardiac conduction abnormalities may occur. Seizures may occur with agents that enter the CNS.
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Central Anticholinergic Syndrome Delirium (Hyperactive or Hypoactive) Seizures
Peripheral Anticholinergic Syndrome thirst, dry mouth, dilated pupils,
tachycardia, flushed face, slowed gastric emptying and decreased bowel sounds, dry skin, hyperthermia, urinary retention.
Treatment /management: Reassurance Physical Containment Sedation - benzodiazepines Physostigmine--- cross the BBB Close observation Risk of medical complications
Treatment
Anticholinergic Toxic Syndrome
Most common drug taken in overdose
Few symptoms or early signs As little as 12g can be fatal Hepatic and renal toxin
Centrolobular necrosis More toxic if liver enzymes induced
or reduced ability to conjugate toxin
General measures including paracetamol and salicylate levels Activated charcoal
<8 hours Take level after four hours Start N-aceylcysteine if above treatment
line Patients are usually declared fit for
discharge from medical care on completion of its administration. However, check INR, creatinine and ALT before discharge. Patients should be advised to return to hospital if vomiting or abdominal pain develop or recur
>8 hours Urgent action required because the
efficacy of NAC declines progressively from 8 hours after the overdose
Therefore, if > 150mg/kg or > 12g (whichever is the smaller) has been ingested, start NAC immediately, without waiting for the result of the plasma paracetamol concentration
>24 hours Still benefit from starting NAC
Precursors of glutathione Dosage for NAC infusion - ADULT
(1) 150mg/kg IV infusion in 200ml 5% dextrose over 15 minutes, then
(2) 50mg/kg IV infusion in 500ml 5% dextrose over 4 hours, then
(3) 100mg/kg IV infusion in 1000ml 5% dextrose over 16 hours
Side-effects Flushing, hypotension, wheezing,
anaphylactoid reaction Alternative is methionine PO (<12
hours)
Aspirin (acetylsalicylic acid) Methyl salicylate (Oil of
Wintergreen) 5 ml = 7g salicylic acid Herbal remedies Fatal intoxication can occur after the
ingestion of 10 to 30 g by adults and as little as 3 g by children
Plasma salicylate concentration Rapidly absorbed; peak blood levels
usually occur within one hour but delayed in overdose 6-35 hrs
Measure @ 4 hrs post ingestion & every 2 hrs until they are clearly falling
Most patients show signs of intoxication when the plasma level exceeds 40 to 50 mg/dL (2.9 to 3.6 mmol/L)
Inhibition of cyclooxygenase results in decreased synthesis of prostaglandins, prostacyclin, and thromboxanes
Stimulation of the chemoreceptor trigger zone in the medulla causes nausea and vomiting
Direct toxicity of salicylate species in the CNS, cerebral edema, and neuroglycopenia
Activation of the respiratory center of the medulla results in tachypnea, hyperventilation, respiratory alkalosis
Early symptoms of aspirin toxicity include
tinnitus, fever, vertigo, nausea,
hyperventilation, vomiting, diarrhoea
More severe intoxication can cause altered
mental status, coma, non-cardiac
pulmonary oedema and death
Salicylate overdose (Cont’d) Uncoupled oxidative phosphorylation in
the mitochondria generates heat and may increase body temperature
Interference with cellular metabolism leads to metabolic acidosis
directed toward increasing systemic pH by the administration of sodium bicarbonate
IV fluids +/- vasopressors
Avoid intubation if at all possible (↑ acidosis)
Supplemental glucose (100 mL of 50 percent dextrose in adults) to patients with altered mental status regardless of serum glucose concentration to overcome neuroglycopaenia
Hemodialysis
Antidote – naloxone MOA: Pure opioid antagonist competes and
displaces narcotics at opioid receptor sites I.V. (preferred), I.M., intratracheal, SubQ: 0.4-2
mg every 2-3 minutes as needed Lower doses in opiate dependence Elimination half-life of naloxone is only 60 to
90 minutes Repeated administration/infusion may be
necessary S/E BP changes; arrhythmias; seizures;
withdrawal
Antidote – flumazenil MOA: Benzodiazepine antagonist IV administration 0.2 mg over 15 sec to
max 3mg S/E N&V; arrhythmias; convulsions C/I concomitant TCAD; status epilepticus Should not be used for making the
diagnosis Benzodiazepines may be
masking/protecting against other drug effects
Deaths from poisoning with benzodiazepines alone are rare, but may be lethal in combination with other CNS depressants
Treatment is supportive and aimed at maintaining adequate ventilation whilst supporting cardiovascular depression
Flumazenil (specific benzodiazepine antidote) is not licensed (in the UK) for routine use in benzodiazepine overdoses
Flumazenil may induce seizures; particularly dangerous where tricyclic antidepressants have been taken
Flumazenil, may however, be used in the differential diagnosis of unclear cases of multiple overdoses but expert advice is ESSENTIAL.
PHARMACOLOGY — TCAs have several important cellular effects,
including inhibition of: - Presynaptic neurotransmitter reuptake
- Cardiac fast sodium channels
- Central and peripheral muscarinic acetylcholine receptors
- Peripheral alpha-1 adrenergic receptors
- Histamine (H1) receptors
- CNS GABA-A receptors
Arrhythmias
- widening of PR, QRS, and QT intervals;
heart block; VF/VT Hypotension Anticholinergic toxicity
- hyperthermia, flushing, dilated pupils,
intestinal ileus, urinary retention, sinus tachycardia
Confusion, delirium, hallucinations Seizures
History Blood/urine toxicology screen Levels not clinically useful
ABC – many require intubation Consider gastric lavage if taken < 2hrs Activated charcoal Treatment of hypotension with isotonic
saline Sodium bicarbonate for cardiovascular
toxicity Alpha adrenergic vasopressors
(norepinephrine) for hypotension refractory to aggressive fluid resuscitation and bicarbonate infusion
Benzodiazepines for seizures
Carbon monoxide (CO) intoxication is one of the most common causes of accidental and intentional poisoning
Atmospheric composition <0.001% Blood carboxyhaemoglobin
Nonsmokers 1-3% Smokers 10-15%
Sources of CO Motor vehicle exhaust fumes Heating systems Inhaled smoke Propane-powered forklift trucks Methylene chloride
Pathophysiology of CO poisoning
CO is colourless, odourless, nonirritant toxic gas
CO toxicity due to Cellular hypoxia Direct cellular injury
Cellular hypoxia CO competes with O2 for binding to Hb Affinity of Hb for CO x 200-250 > affinity
for O2 O2-Hb dissociation curve shift to the left Impaired tissue release of O2 and
cellular hypoxia
High level of clinical suspicion Serum COHb level Exhaled breath COHb level Measured by spectrophotometry Pulse oximetry cannot distinguish
between HbO2 and COHb Comprehensive neurological and
neuropsychological assessment CO Neuropsychological Screening
Battery CT brain to exclude other conditions
High-flow, FiO2 ~100%, normobaric O2 O2 shortens the half life of COHb
21% O2 = 4-6 hours 100% O2 = 40-80 minutes 100% O2 2.5atm = 15-30 minutes
Continue O2 until COHb normal Beware concomitant smoke inhalation
and burn injury Normobaric v Hyperbaric O2 therapy
HBO hastens resolution of acute symptoms Unclear evidence for effect of HBO on late
complications and mortality
Irritant Poisons
Definition:Those agents that set up an inflammatory process at the site
of application or contact. They do not destroy body tissues
The most common signs and symptoms of irritant and poisons are due to their local action on the mucosa of the GIT, causing inflammatory changes and partial desquamation of the intestinal mucosa
This leads to burning pain, vomiting and diarrhea with bloody stools
After absorption, the main symptoms of toxicity include rapid irregular pulse, fall in blood pressure, convulsions and coma
Examples: mercuric chloride, silver nitrate, iodine, bromine, hydrogen peroxide
Poisoning by Silver Silver nitrate is used as local styptic (astringent) and antiseptic Ingestion of a silver salt solution causes burning sensation of GIT,
abdominal pain, vomiting with black vomitus, diarrhea, severe shock and convulsions
Repeated use of silver preparations may result in deposition of greyish-blue metallic silver in the pigment layer of the skin
Treatment: 1. Gastric lavage with NaCl to precipitate silver 2. Administration of demulcents, e.g., milk and egg white
which combines with sliver as proteinate3. Administration of cathartics and cleansing enemas
Poisoning by Hydrogen Peroxide Hydrogen peroxide is used in medicine as antiseptic and
disinfectant
Hydrogen peroxide has two mechanisms of toxicity; local tissue injury and gas formation. The extent of local tissue injury is determined by the strength of the hydrogen peroxide solution:
Dilute hydrogen peroxide (usually 3%) is an irritant Concentrated hydrogen peroxide (10-30%) is a caustic
Gas formation results when hydrogen peroxide interacts with tissue catalase, liberating molecular oxygen and water.
The main symptoms of toxicity are vomiting, abdominal pain and gastric mucosal erosions
Treatment: 1. Give water or milk to dilute2. Use gastric tube to prevent increased pressure
Poisoning by Sulphuric Acid Treatment:
Skin Contacta. Remove acid by flooding with water for at least 15 minutesb. Do not use chemical antidotesc. Treat damaged areas as for thermal burns
Ingestion1. Do not use gastric lavage or emesis because of the danger of perforation 2. Ingested acid may be diluted by drinking large quantities of water or milk 3. Treat shock by administration of 5% dextrose in saline4. Give morphine sulphate to relieve pain5. Treat asphyxia by maintaining an adequate airway6. If perforation of the stomach or esophagus is suspected
Inhalationa. Give artificial respirationb. Treat bacterial pneumonia with organism specific chemotherapy
Common chemical Rapidly acting
No direct effect in blood
Where is cyanide found?
Occurs naturally in foods (some fruits, lima beans)Cyanide salts used in industry
Produced in smoke of burning plastics/syntheticsElectroplatingMetal polishingSmells like “bitter almonds”
Inhibits cellular respiration Cytochrome a-a3
Tissues cannot utilize oxygen “Arterialization of venous blood”
Pulmonary Dyspnea Tachypnea Pulmonary edema Apnea
Gastrointestinal Nausea, vomiting Caustic effects
Clinical picture Lactic acidosis ABG:
metabolic acidosis
ABG sample
Parameter Finding
PO2 Normal
Calc O2 Sat Normal
Venous O2 Sat Increased
Remove from source Oxygen Cyanide antidote kit Cyanide kit causes methemoglobinemia Nitrite oxidizes the central iron atom of hemoglobin
from the ferrous (Fe2+) to the ferric (Fe3+) state, producing methemoglobin, and is therefore a potential antidote for cyanide poisoning.
Amyl nitrite perle until IV established Sodium Nitrite (300mg IV)
Peds: 0.33 ml/kg of 10% solution) Sodium Thiosulfate (12.5gm IV)
Peds: 1.65 ml/kg of 25% solution)
Exact mechanism of kit is controversial Basic goal of antidote is to reactivate the
cytochrome oxidase system by providing an alternative, high-affinity source of ferric ions (Fe3+) for cyanide to bind
Cyanide antidote kit
Acetaminophen N-acetyl cysteine Anti-cholinergics Physostigmine Benzodiazepenes Flumazenil Ca channel blockers Glucagon, Insulin + dextrose, Calcium Carbamate Atropine Cyanide Thiosulphate, nitrate Digoxin Digoxin antibodies INAH Pyridoxine Methanol Ethanol, Fomepizole Glycol Ethanol, Fomepizole Opioid Naloxone Oral hypoglycaemics Glucose Organophosphate Atropine,? P2AM Warfarin Vitamin K
A systematic approach has proven to be the most efficacious way to treat critically ill poisoned patients.
Categorization of the poisoned patient’s clinical appearance into a toxic syndrome allows the clinician to initiate effective treatment without knowing the specific poison involved. =toxidrome
More research is needed to develop new and more effective treatments for poisoning.
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