poisoning (farmakologi)
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Prof.dr.H.Aznan Lelo PhD.SpFKdr.Datten Bangun MSc,SpFK
Dept.Farmakologi & Terapeutik
Fak.Kedokteran U S U
M E D A N
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"All substances are poisons; there isnone which is not a poison. The rightdose differentiates a poison and a
remedy.
Paracelsus (1493-1541)
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Try and get as much history as possibleincluding witnesses
People truly wanting to commit suicide often
lie Remember the ABCs:
Airway Clear mouth & throat, gagreflex
Breathing O2 saturation, ABGs Circulation Venous access, IV fluids if shocked
Assess GCS
Examination
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When, what, how much ?
Why?
Circumstances PMHx, Drug history
Psychiatric history
Assess mental status and capacity
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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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All chemicals have potential to be poisons ifgiven a large enough dose
Poisoning occurs when exposure to asubstance adversely affects function of any
organ systemGeneral Approach to the Poisoned Patient
SystematicTreatment and Diagnostic Actions in Parallel
Goal is rapid stabilization, categorization of
poison class, initiation of general treatment
then specific treatment when available
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1. Stabilization
2. Rapid Patient Evaluation (Physical, Lab)
3. Prevention of further toxin absorption
4. Enhancement of toxin elimination
5. Specific antidote
6. Supportive therapy
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History is often absent or unreliable
Information from any source usually helpful
Physical exam is very important
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Largely supportive !
oxygen, iv access & fluids
Decrease drug absorption
activated charcoal within 1 hour
( whole bowel irrigation )
( gastric lavage )
Increase drug eliminationurinary alkalisation
haemodialysis/perfusion /plasmaexchange
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A (Airway)
B (Breathing)
C (Circulation)
D (Disability-AVPU/ Glasgow Coma Scale)
DEFG ( Dont ever forget the Glucose)
GET A SET OF BASIC OBSERVATIONS
General Management -2
Use all your senses, search for the clues
LOOK -Track Marks
- Pupil Size
FEEL - Temperature, Sweating
SMELL - Alcohol
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Physiologically based abnormalities that areknown to occur with specific classes ofsubstances and typically are helpful in
diagnosis Patterns of signs and symptoms
Useful to help in diagnosis and treatment ofunknown poisons
Patterns of signs and symptoms
Useful to help in diagnosis and treatment
of unknown poisons
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Odor Poison
Bitter almonds cyanide
Eggs hydrogen sulfide,
mercaptans
Mothballs naphthalene, camphor
Wintergreen methylsalicylate
Garlic As, org- phosphates,DMSO, Thallium
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Supportive Correct hypoxia, hypotension, dehydration,
hypo- hyperthermia, and acidosis
Control seizures
Monitor
TPR, BP, ECG, Oxygenation, GCS
General
Absorption Elimination
Specific antidotes
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Sympathomimetic
Anticholinergic
Cholinergic (muscarinic)
Narcotic
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Vital signs: Tachycardia, hypertension,hyperpyrexia.
Clinical appearance: diaphoresis (sweating),piloerection, mydriasis and hyperreflexia. Insevere cases, seizures, hypotension (later effect)and dysrhythmias may occur.
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Vital signs: Bradycardia, increased respiratory rate(initially)
Clinical appearance: SLUDGE
Salivation
LacrimationUrination
Defecation Diaphoresis
Gastrointestinal distress
Edema (Pulmonary)
Also see: miosis (pinpoint pupils), muscle fasciculations,CNS depression
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1.Initial management:
(2) Stabilization:
a.ABCs: airway protection mostcommonly needed
b.Orogastric lavage or NG tube: if liquid
ingestion and pt has not vomited yetc.IV access for antidotes and fluids
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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):cant reverse muscle
weakness
b.bronchorrheahypoxiatachycardia
more atropin
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(2) Pralidoxime (2-PAM,Protopam)
a.effect: form a complex of PAM-OP-AchE
PAM-OP released fromcomplex AchE reactivation
metabolize Achb.decreases atropine effect
c.treatment as early as possibledecreased effect after 36-48 hrs
exposure
aging effect
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Vital signs: Tachycardia, hypertension,hyperpyrexia
Clinical appearance: Hot, dry skin, mydriasis, diminishedor absent bowel sounds, urinary retention, confusionand delirium. Sinus tachycardia is most common butother cardiac conduction abnormalities may occur.
Seizures may occur with agents that enter the CNS.
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Most common drug taken in overdose
Few symptoms or early signs
As little as 12 gr can be fatal
Hepatic and renal toxin
Centrolobular necrosis
More toxic if liver enzymes induced or
reduced ability to conjugate toxin
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General measures including U&Es, LFTs, glucose, clotting ABG, bicarbonate,
paracetamol and salicylate levels
Activated charcoal
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>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 beeningested, start NAC immediately,
without waiting for the result of theplasma paracetamol concentration
>24 hours
Still benefit from starting NAC
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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 (
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Aspirin (acetylsalicylic acid)
Methyl salicylate (Oil of Wintergreen)
5 ml = 7g salicylic acid
Herbal remedies
Fatal intoxication can occur after the ingestionof 10 to 30 g by adults and as little as 3 g by
children
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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)
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Inhibition of cyclooxygenase results in decreasedsynthesis of prostaglandins, prostacyclin, andthromboxanes
Stimulation of the chemoreceptor trigger zone in themedulla causes nausea and vomiting
Direct toxicity of salicylate species in the CNS,cerebral edema, and neuroglycopenia
Activation of the respiratory center of the medullaresults in tachypnea, hyperventilation, respiratory
alkalosis Uncoupled oxidative phosphorylation in the
mitochondria generates heat and may increase bodytemperature
Interference with cellular metabolism leads tometabolic acidosis
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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
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directed toward increasing systemic pH by theadministration of sodium bicarbonate
IV fluids +/- vasopressors
Avoid intubation if at all possible ( acidosis)
Supplemental glucose (100 mL of 50 percent dextrosein adults) to patients with altered mental status
regardless of serum glucose concentration toovercome neuroglycopaenia
Hemodialysis
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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
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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
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Deaths from poisoning with benzodiazepines alone arerare, but may be lethal in combination with other CNSdepressants
Treatment is supportive and aimed at maintaining
adequate ventilation whilst supporting cardiovasculardepression
Flumazenil (specific benzodiazepine antidote) is notlicensed (in the UK) for routine use in benzodiazepineoverdoses
Flumazenil may induce seizures; particularly dangerouswhere tricyclic antidepressants have been taken
Flumazenil, may however, be used in the differentialdiagnosis of unclear cases of multiple overdoses but expertadvice is ESSENTIAL.
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PHARMACOLOGY
TCAs have several important cellular effects,
including inhibition of:- Presynaptic neurotransmitter reuptake
- Cardiac fast sodium channels
- Central and peripheral muscarinic acetylcholinereceptors
- Peripheral alpha-1 adrenergic receptors- Histamine (H1) receptors
- CNS GABA-A receptors
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Arrhythmias
- widening of PR, QRS, and QT intervals;
heart block; VF/VT
Hypotension
Anticholinergic toxicity
- hyperthermia, flushing, dilated pupils,
intestinal ileus, urinary retention, sinustachycardia
Confusion, delirium, hallucinations
Seizures
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History
Blood/urine toxicology screen
Levels not clinically useful
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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 fluidresuscitation and bicarbonate infusion
Benzodiazepines for seizures
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Carbon monoxide (CO) intoxication is one of the most
common causes of accidental and intentional poisoning Atmospheric composition
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Pathophysiology
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CO is colourless, odourless, nonirritant toxicgas
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
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High level of clinical suspicion
Serum COHb level
Exhaled breath COHb level
Measured by spectrophotometry
Pulse oximetry cannot distinguish betweenHbO2 and COHb
Comprehensive neurological andneuropsychological assessment
CO Neuropsychological Screening Battery CT brain to exclude other conditions
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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 latecomplications and mortality
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Irritant Poisons
Definition:
Those agents that set up an inflammatory process at the site ofapplication 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
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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 indeposition of greyish-blue metallic silver in the pigment
layer of the skin
Treatment:
1. Gastric lavage with NaCl to precipitate silver2. Administration of demulcents, e.g., milk and egg
white which combines with sliver as proteinate
3. Administration of cathartics and cleansing enemas
Poisoning by Iodine
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Poisoning by Iodine
Iodine is used in medicine as antiseptic and disinfectant
Ingestion of iodine causes gastric pain, vomiting (brown-stained vomitus), diarrhea (bloody stool), collapse and
nephritis.
Inhalation of iodine causes inflammation of respiratory
tract, cough, and pulmonary edema.
Iodine produces inflammation, desquamation and
corros ion of mucous membranes
Treatment:1. Gastric lavage with water or 1-1.5% solution of sodium
thiosulphate
2. Administration of starch solution and demulcents,
e.g., milk and egg white
Poisoning by Bromine
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Poisoning by Bromine
Exposure to bromine vapor causes lacrimation,
pharyngitis, salivation, cough, pulmonary edema and
ulceration of eyelids and cornea pain, vomiting (brown-
stained vomitus), diarrhea (bloody stool)
Bromine produces yellow brown discoloration of the skin,
feeling of heat and ulcer
Treatment:
1. Transferring the patient to fresh air
2. Administration of oxygen
3. Treat bronchospasms and pulmonary edema byaminophylline I.V.
Poisoning by Hydrogen Peroxide
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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 bythe 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 tissuecatalase, 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 dilute
2. Use gastric tube to prevent increased pressure
Poisoning by Sulphuric Acid
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Poisoning by Sulphuric Acid
Treatment:
Skin Contact
a. Remove acid by flooding with water for at least 15 minutesb.Do not use chemical antidotes
c. Treat damaged areas as for thermal burns
Ingestion
1. 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 saline
4. Give morphine sulphate to relieve pain
5. Treat asphyxia by maintaining an adequate airway6. If perforation of the stomach or esophagus is suspected
Inhalation
a. Give artificial respiration
b.Treat bacterial pneumonia with organism specific chemotherapy
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Common chemical
Rapidly acting
Blood Agents is a misnomer
No direct effect in blood
Where is cyanide found?Occurs naturally in foods (some fruits, lima beans)Cyanide salts used in industry
(e.g. ore extraction)Produced in smoke of burning plastics/syntheticsElectroplatingMetal polishingSmells like bitter almonds
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Inhibits cellular respiration Cytochrome a-a3
Tissues cannot utilize oxygen
Arterialization of venous blood
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Pulmonary Dyspnea
Tachypnea Pulmonary edema Apnea
Gastrointestinal Nausea, vomiting Caustic effects
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Clinical picture
Lactic acidosis
ABG:
metabolic acidosis
ABG sample
Parameter Finding
PO2 Normal
Calc O2 Sat Normal
Venous O2 Sat Increased
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Remove from source
Oxygen
Cyanide antidote kit
Cyanide kit causes methemoglobinemia
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Amyl nitrite perle until IVestablished
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)
Cyanide antidote kit
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A systematic approach has proven to be themost efficacious way to treat critically illpoisoned patients.
Categorization of the poisoned patientsclinical appearance into a toxic syndromeallows the clinician to initiate effectivetreatment without knowing the specific
poison involved. More research is needed to develop new and
more effective treatments for poisoning.
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