toxico for extern
DESCRIPTION
TRANSCRIPT
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Common Toxicology
sukit wipusattayaEmergency Medicine
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Common poison exposure Ramathibodi Poison Center: 2001-2005
กลุ่��ม จํ�านวน %
สารป้�องก�นก�าจํ�ดศั�ตร�พื�ช (pesticides) 9,327 39.9
สารใช�ในบ้�านเร�อน(household products) 4,421 18.9
ยา (pharmaceutical products) 4,397 18.8
สารใช�ในงานอ�ตสาหกรรม (occupational products) 2,527 10.9
พื�ชม�พื ษ(plant toxins/poisonous plants) 977 4.2
ส�ตว"ม�พื ษ (poisonous animals) 621 2.7
รวม 23,368
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Case
PI : 6 “ ” ช�#วโมงก�อน ก นน%ายาลุ่�างห�องน�&า เป้'ดโป้ร ป้ระมาณ 50 ml. หลุ่�งก นม�อาการแสบ้คอมาก แลุ่ะป้วด
ท้�องโดยเฉพืาะบ้ร เวณลุ่ &นป้.#
PE : P 110/min, BP 90/60, RR 24/min, T 37.8 Erythema or soft palate and posterior pharynx, no stridor Lung : clear Abdomen : tender at epigastrium, no guarding or rigidity, normal bowel sound
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Acid
Sulfuric acidHydrochloric acidHydrofluoric acidFormic acid Acetic acid
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Alkali
Sodium hydroxideCalcium hydroxideLithium hydroxideAmmonium hydroxideSodium hypochloriteSodium tripolyphosphate
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determinants of damaging potential
•Volume •Concentration•Physical state•pH
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Alkali burn•Liquefaction necrosis•Protein dissolution, collagen destruction, fat saponification and cell membrane emulsification•Facilitate penetration of the alkali•often injure oropharynx and proximal esophagus
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Liquefaction necrosis
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•Coagulation necrosis •protein precipitation and eschar formation•tend to be protective against deep injury
Acid Ingestion
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Pathology
• Ingestion:
• Squamous epithelium
• Erythema, edema, erosion, ulcer
• Lowest tensile strength of the esophagus: Day 3-14
• Collagen organization and epithelial repair in months
• Shortening and dysmotility
• Increase risk of squamous cell CA x 20-40
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Clinical manifestations
•Drooling --> oropharyngeal injury •Odynophagia ,dysphagia --> esophageal injury•Abdominal pain,GI bleed --> stomach injury •Dysphonia,stridor,resp distress --> laryngotracheal injury •Retrosternal chest pain --> mediastinitis•Signs of complication:
•GI hemorrhage•Laryngeal involvement•Esophageal perforation
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TREATMENT
1. Initial Stabilization
2. Clinical Evaluation
3. Decontamination
4. Diagnostic tests
5. Enhance Elimination
6. Specific antidotes
7. Supportive care
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Initial stabilization
• Personal protective equipment
• Airway: indications for early intubation• Stridor
• Dyspnea
• Oropharyngeal obstruction
• Blind nasotracheal intubation is contraindicated
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Clinical Evaluation
• History
• type and amount of caustic ingested
• intentional or unintentional ingestion
• Physical examination
• determine hemodynamic stability
•etiology of shock (GI bleed , volume deplete)
• examine peritoneal sign & mediastinitis
• examine eye & skin
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Decontamination
• contraindicated• No role of dilution or neutralization
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Diagnostic test
•arterial blood gas•electrolyte•liver function•complete blood count•coagulation profile•calcium & magnesium ( HF acid)•Chest x-ray•EKG
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Enhance elimination
No role of enhance elimination
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Antidote
•Some agents need specific antidote•Hydrofluoric acid •Phenol
: calcium gluconate
: isopropyl alcohol
: ethyleneglycol
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Hydrofluoric acid
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Hydrofluoric acid
Apply 2.5% calcium gluconate gel (10% calcium gluconate 10 ml in KY gel 60 ml ) on skin until pain resolves (usually within 10 minutes)
+
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Supportive care
Endoscopy•Benefits: treatment plan, disposition and prognosis•Timing:
• 4-6 hours post-ingestion: avoid underestimation• Not later than 48 hours post-ingestion
•Indications:• All intentional ingestion • Presence of symptom or sign of corrosive injury
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• Grade 0: Normal• Grade I: Mucosal edema or hyperemia• Grade II: Ulceration
• IIa: superficial ulceration• IIb: deep discrete or superficial ulceration
• Grade III: Necrosis• IIIa: small, scattered areas of necrosis• IIIb: extensive necrosis
Grading of Esophageal injury
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Pathologic severity of injury
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Supportive care
Corticosteroid•Aim: minimizing stricture in second degree (II, IIb) burns with plans for dilation•Controversial issues
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Disposition
• Grade 0 – I can be discharge if tolerate well to eating and drinking
• Grade IIb-III need ICU admission.
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Question
1. ผู้��ป้0วยชาย 30 ป้. chronic alcohol drinking น�&าหน�ก50 kg 30 นาท้�ก�อนมาโรงพืยาบ้าลุ่ ก น paracetamol 10 เม1ด
• ท้�านจํะให�การร�กษาแก�ผู้��ป้0วยอย�างไรต�อไป้
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Acetaminophen
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Paracetamol
Sulfation Glucuronidation CYP2E1
Renal excretion
NAPQI
Reduced glutathione
+
CYP2E1
NAPQI
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Clinical symptoms
Stage I : 0.5-24 hrs nausea, vomiting
Stage II : 24-72 hrs RUQ pain , liver enzyme , bilirubin , prolong PT
Stage III : 72-96 hrsjaundice, hepatic encephalopathy , renal failure
Stage IV : 96 hrs -2 wksrecovery phase
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Diagnosis
1.History of ingestion > 150 mg/kg•Exception
•chronic alcohol•inducible agent : phenytoin, phenobarbital, isoniazid•eating disorder e.g. anorexia nervosa, starvation
2.Serum paracetamol level (normogram)•at 4-24 hr
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Overdose estimation: amount > 150 mg/kg
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Treatment
Paracetamal level
N-acetylcysteine
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NAC therapy : Routes of administration
•Oral : 18 doses over ~70 hours
•140 mg/kg for loading
•70 mg/kg for maintenance every 4 hours x 17 doses
•Vomiting
•Intravenous : ~ 21 hours
•150 mg/kg in 1 hours
• 50 mg/kg in 4 hours
•100 mg/kg in 16 hours
•Anaphylactoid reaction 35
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Management of Anaphylactoid reactions from IV NAC
•Flushing: continue treatment
•Urticaria:
•Diphenhydramine 50 mg IV
•Continue treatment
•Angioedema
•Stop NAC
•Diphenhydramine 50 mg IV
•Restart if no symptoms after 1 hour
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Disposition
Follow up• LFT at 48 hrs , PT• BUN/Cr at day 7
If liver enzyme >1000 •PT , BUN/Cr•NAC 150 mg/kg/day •until clinical improve , PT normal 3
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Case• ผู้��ป้0วยชายอาย� 47 ป้. มาด�วยอาการหมดสต ไม�ค�อยร� �ส3กต�ว
ตรวจํร�างกายพืบ้ RR=8 , BP=80/50 , PR=60 T=36 O2sat = 85% E1V1M5 , pupil 1mm SRTL ,
• lung clear , absent bowel sound , no sweating , DTX=141
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OpioidOpioid
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Opioid
1.Natural derived from opium• Morphine, Codeine
2.Semi-synthetics• Heroin
3.Synthetics• Fentanyl, Meperidine, Methadone
Diphenoxylate (Lomotil)
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Opioid Toxidrome
•CNS depression•Miosis•Respiratory depression
Miosis
hypoventilation
hypothermia
CNS depression
Bradycardia ,hypotension
Ileus
Hyporeflexia
Needle mark
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Treatment
1. Initial Stabilization
2. Clinical Evaluation
3. Decontamination
4. Diagnostic tests
5. Enhance Elimination
6. Specific antidotes
7. Supportive care
urine toxicology
Naloxone
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Initial stabilization
•Airway : oral airway , bag-mask valve , ETT
•Breathing : Improve oxygenation
•Circulation :
• Hypotension : typically orthostatic --> supine , rise legs
•R/O hypoglycemia, hypoxia, hypothermia•cardiac monitoring
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Decontamination
•No role of ipecac syrup
•NG lavage : not necessary
•Activated charcoal 1 gm/kg in moderate
to large dose after ingestion within 1 hr
•Sustained release product (Oxycodone) ,
body packer --> whole-bowel irrigation
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Enhance elimination
•No role of cathartic alone
•Multiple dose activated charcoal may be
useful in Lomotil overdose
•no role of dialysis (due to large volume
distribution)
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Naloxone
•Opioid antagonist : reverses almost all adverse effects mediated through opioid receptors
•Empiric use may assist in diagnosis
•Can administered IV , IM , ETT•Onset of action (iv) 1-2 mins•Duration of action 20-90 mins
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Naloxone
Dosage Minimal resp depression Markly resp depression
Opioid dependent
0.2 mg iv
2 mg iv Non-opioid dependent
0.4 mg iv
Repeat dose q 2-3 min until •respiratory is reversed •maximum dose of 10 mg
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Case
• ผู้��ป้0วยชายอาย� 50 ป้. มาด�วยอาการหมดสต ไม�ค�อยร� �ส3กต�ว• PE : RR=14 , BP=120/80 , PR=60 T=36 O2sat = 92% • a man with drownsiness , hypersalivation• heart : regular• lung : wheezing and rhonchi both lung • abdomen : hyperactive bowel sound • extremities: sweating • E2V2M5 , pupil 1 mm SRTL
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Organophosphate/Carbamate
Organophosphate : parathion, malathion Carbamate : methamyl, methyl carbamate
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Inhibit acetylcholine esterase enzyme
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MnemonicsDUMBELS
D – DiarrheaU – UrinationM – MiosisB – bradycardia,
bronchospasm, bronchorrhea
E – EmesisL – LacrimationS – Salivation
Days of the Week:M – MydriasisT – TachycardiaW – WeaknessH – HypertensionF – Fasciculations
Sign and Symptom
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Treatment
plasma cholinesterase level , gastric content
atropine , 2-PAM
1. Initial Stabilization
2. Clinical Evaluation
3. Decontamination
4. Diagnostic tests
5. Enhance Elimination
6. Specific antidotes
7. Supportive care
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Atropine
•Atropine 0.02 - 0.05 mg/kg (1-3 mg) q 5 min
until
•Control of mucous membrane hypersecretion
•Airway clear
•May require 200 - 500 mg in 1st hr
•Not active at nicotinic sites
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Pralidoxime (2-PAM)
•Pralidoxime 1-2 g bolus (20-50 mg/kg) Then 500 mg/hr (10-25 mg/kg/hr)•Monitor clinical and AChE level
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Paraquat
Trade name:
Gramoxone
Herboxone
Dextron
Color: Blue - green
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Toxicodynamic Mechanism
PQ2+ PQ+
NADP+NADPH
O2 O2
.
PQ reductase
Pentose phosphate pathway
Cell death : (lung , liver , kidney)
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Oropharyngeal ulceration and corrosion
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Ocular injury
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Clinical symptoms
• GI : like corrosive agent
• Cardiovascular : Hypovolemia, shock, dysrhythmias
• Renal : acute tubular necrosis , renal failure
• Hepatobilliary : hepatitis , hepatic necrosis
• Respiratory : mediastinitis, pneumothorax, hemoptysis, pulmonary edema, and hemorrhage, pulmonary fibrosis
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Paraquat Lung
Day 1 Day 28
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Treatment
No oxygen until PaO2<50 , resp distress
lavage , fuller’s earth
urine for paraquat
hemoperfusion
1. Initial Stabilization
2. Clinical Evaluation
3. Decontamination
4. Diagnostic tests
5. Enhance Elimination
6. Specific antidotes
7. Supportive care
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InvestigationsInvestigations
•Serum paraquat level
•Urine paraquat level
•Bedside : 1% Na-dithionate in NaOH 2 ml + urine 10 ml (blue = positive = paraquat 1 ppm)
•BUN, Cr, UA, arterial blood gas, pulmonary function test
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Paraquat
alkaline sodium dithionate
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- antioxidant: Vit C, Vit E, NAC
- Immunosuppressive
Cyclophosphamide 5mg/kg/day IV
Dexamethazone 10 mg IV q 8 hrs
Specific treatment
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Case เด1กผู้��ชาย 5 ป้.
CC. ก นแชมพื�30 นาท้�ก�อนมาโรงพืยาบ้าลุ่PI. 30 นาท้� ก�อนมารพื. ผู้��ป้0วยก นแชมพื�สระผู้มป้ระมาณ 5 อ3ก
หลุ่�งก นม�อาการป้วดชาลุ่ &นเลุ่1กน�อย มารดาพืยายามลุ่�วงคอผู้��ให� อาเจํ�ยน แต�ไม�อาเจํ�ยน จํ3งมารพื. ผู้��ป้0วยร� �ส3กต�วด� ไม�ส�าลุ่�ก ไม�ป้วด
ท้�อง อาการอ�#นป้กต PH. ไม�ม�โรคป้ระจํ�าต�วใดๆ ไม�เคยแพื�ยาใดๆ
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ผู้ลุ่ ตภั�ณฑ์"ท้�าความสะอาด (cleaner)
• ท้�าความสะอาดร�างกาย• สบ้��อาบ้น%า•แชมพื�สระผู้ม
• ท้�าความสะอาดเส�&อผู้�า• ผู้งซั�กฟอก•น�&ายาซั�กผู้�าน�&ายาขจํ�ดคราบ้
• ท้�าความสะอาดอ�#นๆ ท้�#วไป้• น�&ายาลุ่�างจําน•น�&ายาท้�าความสะอาดพื�&น
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Detergent
Surfactant Builder
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Surfactant
•Nonionic surfactant
•Anionic surfactant
•Cationic surfactant
3
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Nonionic surfactant
Condensation products of fatty alcohols + ethylene oxide
• Alkyl phenol polyglycol
• Alkylphenyl polyethoxyethanol
• Alkylpolyethoxylates
• Ethoxylated alcohols
• Nonoxynol
• PEG stearates
Polyalkaline glycol, fatty acid alkanolamide amide
Polyethylene glycol alkyl aryl ethers
• Polyoxyethylene alkyl ethers
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Anionic surfactant
Sodium, potassium, or ammonium salts of fatty acids
• Alkyl sulfonate
• Alkylbenzene sulfonates
• Alkyl sulfate
• Dialkyl sulfosuccinate
• Linear alkylate sulfonate
• Phosphorylated hydrocarbons
• Sulfonated hydrocarbons
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Cationic surfactant
Pyridinium compounds• Cetalkonium chloride
• Cetrimide
• Cetrimonium bromide
• Cetylpyridinium chloride
• Stearalkonium chloride
Quaternary ammonium compoundsBenzalkonium chloride
• Benzethonium chloride
• Quinolinium compound• Dequalinium chloride
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Example• Sodium lauryl ether sulfate 14% w/w
• Sodium lauryl sulfate 6%w/w
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•Sodiumdodecylbenzenesulphonate 6.7%w/w •Nonyl phenol ethoxylated 9% w/w•Sodium lauryl ether sulfate 5% w/w
Example
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•Sodium lauryl ether sulfate 2.12% w/w•Sodium dodecyl benzene sulphonate 14.88% w/w
Example
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Example• C12-C15 alcohol ethoxylated 1.2% w/w
• Sodium lauryl ether sulfate 3.92% w/w
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Example
• Alkoxylated linear alcohol 8%w/w
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•Anionic surfactant -Sodium linearalkyl benzenesulfonate -Polyoxyethylene alkyl ether•Sodium tripolyphosphate•Zeolite•Sodium carboxymethyl cellulose•Fluorescer
Example
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Example•Dialkyl Dimethyl Ammonium Chloride
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Builder
•sodium phosphate
•sodium carbonate
•sodium metasilicate 85
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Symptoms
•Nonionic / Anionic surfactant •mild irritation•mild GI symptoms : N/V , abdominal pain --> dehydrate
•Cationic surfactant• like corrosive agent• upper airway edema , respiratory distress• hypotension, metabolic acidosis, CNS depression
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GASTROINTESTINAL
Nausea, vomiting diarrhea --> metabolic alkalosis
Oral, pharyngeal,esophageal burns
Esophageal stricture
irritation of mucous membranes
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1. ผู้ลุ่ ตภั�ณฑ์"ความสะอาดร�างกาย (toilet articles and cosmetics):
แชมพื�สระผู้ม, สบ้��อาบ้น%า, คร�ม/ โฟมลุ่�างหน�า : nonionic and anionic surfactant
คร�มนวดผู้ม : cationic detergent
2. ผู้ลุ่ ตภั�ณฑ์"ซั�กผู้�า(laundry products):
ผู้งซั�กฟอก, น�&ายาซั�กผู้�า : nonionic and anionic surfactant
น�&ายาป้ร�บ้ผู้�าน��ม : cationic detergent
น�&ายาขจํ�ดคราบ้ไคลุ่ : anionic surfactant
3. ผู้ลุ่ ตภั�ณฑ์"ลุ่�างจําน (dishwashings):
น�&ายาลุ่�างจําน, น�&ายาลุ่�างขวดนม : nonionic and anionic detergent
น�&ายาลุ่�างจําน(เคร�#อง) : cationic detergent
4. น�&ายาท้�าความสะอาดพื�&น (floor cleaners) : nonionic and anionic detergent
5. น�&า ยาท้�าความสะอาดห�องน�า�บ้างส�ตร (toilet cleaners) : nonionic, anionic and cationic
6. น%ายาท้�าความสะอาดเอนกป้ระสงค" (All-purpose cleaner) : nonionic, anionic and
cationic
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TREATMENT
1. Initial Stabilization
2. Clinical Evaluation
3. Decontamination
4. Diagnostic tests
5. Enhance Elimination
6. Specific antidotes
7. Supportive care
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• Nonionic or anionic is generally self-limiting•requiring no treatment•maybe dilute with 120 - 240 ml of water or milk
•Cationic detergent should treat as corrosive agent•Do not induce vomiting•If signs or symptoms of esophageal irritation or burns are present, consider endoscopy •Activated charcoal - unnecessary
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Supportive care
• Treat dermal irritation / burns with standard topical drug
• Dermal hypersensitivity reactions Rx. with systemic / topical corticosteroids / antihistamines
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Summary•No activated charcoal•Nonionic / anionic surfactant•dilution by water/milk•may NG lavage •improve in 24 hr
•Cationic surfactant • treat as corrosive agent --> endoscopic 9
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Case
ผู้��ป้0วยหญิ งไท้ยโสด อาย� 20 ป้. ป้ฏิ เสธโรคป้ระจํ�าต�วCC: พื�นยาไบ้กอน(spray) ฉ�ดย�งเข�าป้าก 3 คร�&ง 5 นาท้�ก�อนมารพื.
PI: 5 นาท้�ก�อนท้ะเลุ่าะก�บ้แฟน จํ3งน�า สเป้รย"ฉ�ดย�งย�# ห�อไบ้กอนส�เหลุ่�องมาฉ�ดเข�าป้าก 3 คร�&ง แฟนน�า
ส�งรพื.ท้�นท้�PE: WNL ม�กลุ่ #นยา บ้ร เวณป้าก
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Pyrethrines & Pyrethroids•Pyrethrins: compounds extracted from chrysanthemums•Pyrethroids: synthetic derivatives of pyrethrins
•greater chemical stability•Type II pyrethroid
•Contain a cyano substituent•More toxic formulation•Potential danger to human
•Common as aerosals in automate insect spray•Less toxic and safer than other compound
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Toxicodynamics
• affect sodium channel in nerve cell• depolarization and hyperexcitability• Type I pyrethroid
• briefer , repetitive nerve discharge
• Type II• longer repetitive nerve discharge• inhibit Cl in GABA receptor --> seizure
• allergic : true IgE-mediated anaphylatic100
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PyrethrinesPyrethrines
• Pyretrum extract• Pyrethrine I• Pyretrhrine II• Cinerin I• Cinerin II• Jasmolin I• Jasmolin II
AllethineBarthrineBioallethrineBioresmethrineCismethrineCymethrineCypermethrineDecamethrineDeltamethrineFenothrinFenvalerateFuramethrinetetramethrin
PyrethroidsPyrethroids
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ยาจํ�ดก�นย�งแลุ่ะผู้ลุ่ ตภั�ณฑ์"ก�นย�งใช�ก�บ้เคร�#องไฟฟ�า
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Mechanism of toxicity
1. Hypersensitivity
•immediate rhinitis and bronchial hyperreactivity
•uncertain mechanisms
2. Increase sodium influx into neurons
• Increase neurotransmitter release
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Clinical manifestation• Allergic and hypersensitivityAllergic and hypersensitivity
• Allergic rhinitisAllergic rhinitis
• Contact dermatitisContact dermatitis
• AsthmaAsthma
• AnaphylactoidAnaphylactoid• Dermal and systemic manifestationsDermal and systemic manifestations
• Abdominal pain, nausea, vomiting within 10 minutes to 1 Abdominal pain, nausea, vomiting within 10 minutes to 1 hourshours
• Paresthesia, numbness: onset hours, duration: less than Paresthesia, numbness: onset hours, duration: less than 24 hours24 hours
• Weakness and muscle fasciculationWeakness and muscle fasciculation
• SeizureSeizure
• In cases of ingestion, beware of hydrocarbon pneumonitisIn cases of ingestion, beware of hydrocarbon pneumonitis105
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Respiratory mildly irritate rhinitis , bronchitis , bronchospasm , asthma
Cardiovascular not direct effect
Nervous type I : T-syndrome (tremor)type II : CS-syndrome ( choreoathetosis salivation seizure)
skin & mucous membrane
allergic contact dermatitisallergic conjunctivitis
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Gastrointestinal salivation , N/V , abdominal pain , diarrhea
Liver effected due to prolong hypoxemia
Genitourinary effected due to prolong hypoxemia
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Decontamination
Respiratory
Remove from sourceadequate ventilation with 100% oxygeninhaled beta-agonist
Skin remove all contaminated clothing ,jewelrywash affected area with water and liquid detergent
Eye irrigate with water at least 20 minsMorgan lenses with ophthamic local anesthetics
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Primary survey and resuscitation
Airway open airway , intubate if necessary
Breathing
adequate oxygenation high flow O2 15 LPM via nonrebreathing reservoir maskBMV in inadequate spontaneous ventilationendotracheal intubation
Circulation
cardiac monitoring , ALCL guidelinestart IV NSS
Disability
assess level of conscious continuallyIV diazepam if seizure despite adequate O2 and glucose
Exposure
undress and decontaminated
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Poisoning treatment paradigm
Alter Absorption
Remove from the poison
Antidote non
Basic continue reassess ABCtreat anaphylactic
Change catabolism
not applicable
Enhance Elimination
not applicable
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Treatment
•Typical GI decontamination•Be careful in case of hydrocarbon media•Treat allergic symptoms with antihistamine•Symptomatic•Observe for 6 hrs and d/c if asymptomatic