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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