Lectures 1-5 Flashcards
Enhanced digestive elimination
Osmotic purgatives
SORBITOL 70%, 240 ML t 1.3h MAGNESIUM CITRAT 20-30g sol 10% t 4h MAGNESIUM SULPHATE sol 10% 15-20g t 17h
Enterohepatic recirculation compounds
Chloralhydrat Phenotyasines Colchicine Phenitoyn Digitoxin Salicylates Digoxin Isoniaside
Drug removal
Ph modification
Forced diuresis
Repetead activated charcoal
Extracorporeal techniques: haemodyalisis,
haemoperfusion, plasmapheresis, exchange
transfusion
Hyperoxibarism
ACID DIURESIS
-> phencyclidine, amphetamine overdose
optimal urine pH < 5.5
ascorbic acid 0.5-2.0 g iv
NH4Cl 75mg/kg/24 h, po/iv (2%)
ALKALINE DIURESIS
-> salicylate, barbiturate overdose
optimal urine pH >7.5
bicarbonate 1-2 mEq/kg
acetazolamide 500 mg
- Unless managed carefully, potential for fluid overload, electrolyte abnormalities
FORCED DIURESIS
Fluids overload
- Diuretics: furosemide, manitol
- Urinary flow: 3-5 ml/kg/h
- Indications: barbiturates, salicylates,
amphetamines - Unless managed carefully, potential for
fluid overload, electrolyte abnormalities
HEMODIALYSIS
Severe poisoning with:
(MW<500, high solubility, low binding plasmatic albumines)
- salicylate
- lithium
- alcohols: methanol, isopropranolol, ethylene glycol
- phenobarbitone
- chloralhidrat
HEMOPERFUSION
Severe poisoning with:
- short acting barbiturates
- sedatives and hipnothics
- phenitoyn
- choramphenicol
- salicylate
- paraquat
Antidote for Paracetamol
Acetylcysteine
Antidote for ethanol
NO antidote ‼️
Antidote for Organophosphates
Diazepam, Atropine
Antidote for benzodiazepines
Flumazenil
Antidote for Arsenic
Dimercaprol
Antidote for iron
Deferoxamine
Antidote for beta adrenergic agonists
Beta blockers
Antidote for Cyanide
Amyl Nitrite
Drug induced hyperthermia
Dantrolene
Antidote for HF, fluorides, oxalates
Calcium gluconate
Antidote for beta blocker
Glucagon
Antidote for ethylene glycol
4 methylpyrazole
Antidote for Methaemoglobinemia
Methylene blue
Antidote for Opiates
Naloxone
Antidote for Organophosphorus insecticides
Obidoxime
Antidote for Carbon monoxide, Cyanide
Oxygen
Antidote for Organophosphorus compounds
Pralidoxime
Antidote for central anticholinergic syndrome
Physostigmine
Antidote for Isoniazid, Hydralazine
Pyridoxine
Antidote for Copper
Penicillamine
Antidote for Cyanide
Sodium nitrite, Sodium Thiosulfate
Antidote for Heparin
Protamine Sulfate
Antidote for Salicylate, tricyclic antidepressants
Sodium Bicarbonate
Emetics
Apomorphine, Ipecacuanha
Alkalinize blood and urine
Sodium Bicarbonate
Cathartics and sol for whole gut lavage
Sorbitol, Mannitol
Magnesium citrate, mag sulfate
Bicarbonates, Sodium Sulfates
…
Prevents absorbtion in gut:
Activated charcoal (for adsorbable poison) Starch (for iodine)
Prevents skin absorbtion/damage
Calcium gluconate gel - for hydrofluoric acid
Polyethylene glycol - for phenol
Anti-foaming agent
Dimethicone (soaps, shampoos)
Dystonia
Benztropine
Medication for: Psychotic with severe agitation
Chlorpromazine
Medication for: Acute allergic reaction, mucosal edema, laryngeal edema, bronhoconstriction
Corticosteroids
Medication for: Convulsions, Anxiety, excitation, muscular hypertonia
Diazepam
Medication for: myocardial depression
Dobutamine, Dopamine
Medication for: Anaphylactic shock, cardiac arrest
Epinephrine
Medication for: fluid retention, left ventricular failure
Furosemide
Medication for: Hypoglycemia
Glucose
Medication for: hallucinations and psychotic states
Haloperidol
Medication for: Hypercoagulability
Heparin
Medication for cardiac arrhythmia
Magnesium sulfate
Medication for Cerebral edema, fluid retention
Mannitol
Medication for hypoxia
Oxygen
Medication for bronchoconstriction systemic/ inhaled
Salbutamol
Medication for acidosis, some cardiac disturbances
Sodium bicarbonate
Toxicological screen
Spot urine test, color test
Thin layer chromatography
- rapid 2 to 4 hours
- urine or plasma
- not for volatiles, alcohols, metals, cyanide, salicylates
Gas and high-pressure chromatography
- for any specimen
- for confirmation
Mass spectrometry
-high specific/sensitive but expensive
ICU admission criteria
Intubation when:
Ventil failure
Airway protection
Therapy induced hypocapnia/alkalosis
CNS: seizures, coma, GCS < 9
CVS: arrhythmia, AV block long QRS, hypotension
Large ingested dose: high blood levels = poor outcome
Drugs associated with SEIZURES:
P - Pesticides, Propoxyphene
L - Lead, Lithium, Lindane, Local anesthetics
A - Antidepressant, Anticonvulsants,
Antihistamines,Antipsychotics, Abstinence
S - Salicylates, Sympatomimetics, Strychnine, Solvents
T - Theophylline, Tricyclic antidepressants, Thallium, Tobacco(nicotine)
I - Insulin, Insecticides, INH
C - Camphor, Cocaine, Cyanide, Chloroquine
Odor: Acetone
Acetone, isopropanol,metabolic acidosis
Odor: Airplane Glue
Toluene, aromatic hydrocarbon inhalation
Odor: alcohol
Ethanol ( no ethylene glycol or vodka)
Odor: Ammonia
Ammonia or Uremia
Odor: bitter Almonds
Cyanide
Odor: Coal gas
Carbon monoxide = odorless but mix with illuminating gas for detection
Odor: Disinfectants
Phenol, Creosote
Odor: Formaldehyde
Formaldehyde, Methanol
Odor: Garlic
Arsenic, Parathion, Yellow Phosphorus, Se, Zn
Odor: Pears
Chloral hydrate, Paraldehyde
Odor: Rotten Eggs
Disulfiram, Hydrogen Sulfide, hepatic failure
Odor: Shoe polish
Nitrobenzene
Anticholinergic syndromes
Cause:
antihistamines antiparkinsonian atropine antipsychotic agents antidepressant agents mydriatic agents skeletal muscle relaxants Amanita muscaria
Common signs:
delirium with mumbling speech incoordination and ataxia respiratory failure coma tachycardia hypertension dry, flushed skin dilated pupils myoclonus slightly elevated temperature urinary retention decreased bowel sounds seizures dysrhythmias
Sympathomimetic Syndromes
Cause:
cocaine amphetamine methamphetamine ephedrine pseudoephedrine phenylpropanolamine
Common signs:
delusions paranoia tachycardia hypertension hyperpyrexia diaphoresis piloerection mydriasis hyperreflexia seizures hypotension dysrhytmias – severe cases
Cholinergic Syndromes
Cause:
organophosphate and carbamate insecticides
physostigmine
edrophonium
some mushrooms
Common signs:
confusion central nervous system depression weakness salivation lacrimation urinary/fecal incontinence gastrointestinal cramping emesis diaphoresis muscle fasciculations pulmonary edema miosis bradycardia / tachycardia seizures
Opiate, Sedative or Ethanol Intoxication
Cause:
narcotics barbiturates benzodiazepines ethchlorvynol glutethimide methyprylon meprobamate ethanol clonidine
Common signs:
coma respiratory depression miosis hypotension bradycardia hypothermia pulmonary edema decreased bowel sounds hyporeflexia seizures may occur (propoxyphene)
Normal Anion Gap
3-11
High Anion Gap induced by:
- metabolic acidosis
- dehydration / loss of fluid
- infusions of salts of organic acids (lactate, acetate, citrate)
- reduced unmeasured cations (K, Ca, Mg)
- alkalemia
- systematic underestimation of serum chloride
- laboratory error
Low Anion Gap induced by:
- volume expansion with free water
- systematic underestimation of serum sodium (hyperNa, hyperviscosity)
- systematic overestimation of serum chloride
- raised unmeasured cations
- acidemia from a respiratory or hyperchloremic metabolic acidosis
- laboratory error
Osmolal Gap
M – C > 10 mOsm/kg H2O
laboratory error
decreased serum water content
↓M subst not used in equation
M normal and C ↓
decrease in serum water associated with
hyperproteinemias and hyperlipidemias
M↑ and C normal/↓ gap= unmeasured osmoles
sorbitol ethanol mannitol methanol glycerin ethylene glycol isoniazid ether diatrizoate sodium acetone
Specific Antidote in (~5% acute poisonings):
NALOXONE + GLUCOSE 5%
Patients having CNS
First priority:
Airways, Breathing
- ventilation
- oxygenation
Obstruction:
mucosa edema, secretions, foreign body,
defectuos position of tongue
Symptoms:
cyanosis, tahipneea, dyspnea, diaphoresis,
altered mental status
Second Priority:
CIRCULATION
Shock: ↓level of consciousness ↓BP peripheral vasoconstriction metabolic acidosis oliguria
Mechanism:
↓contractility
hypovolemia
preload, afterload
Third priority:
DISABILITY
CNS
- pupils
- coma
IV Decontamination
REED classification
Conscious level Pain response Reflex response Respiration Circulation \_\_\_\_\_\_\_\_\_\_
0 asleep arousable intact normal normal I comatose withdraws intact normal normal II comatose none intact normal normal III comatose none absent normal normal IV comatose none absent cyanosis shock
Absorbtion prevention
Internal decontamination
Dilution: caustics, corrosive
-> 300ml milk or water
CI: neutralization reactions
Emetics
Ipecac syrup 10-30 ml, apomorphine,
pharyngeal stimulation
Must have: awake patient with gag reflex
__________
Absolute contraindications:
- unprotected airway (altered mental status)
- strong acids/alkalis
- petroleum derivates
- children<6m
- seizures
- hematemesis
Gastric lavage
Saline solutions: 200-250 ml, 1min, drainage
Useful early after ingestion 4-6h
Doubtful efficacy after this but may be useful for slow absorbed agents
Indications: \_\_\_\_\_\_\_\_\_\_\_ CI emesis analgesics antidepressants alcohols: meth, EG others: digoxin, theophilline
Contraindications: \_\_\_\_\_\_\_\_\_\_\_\_ strong acid/alkalis petroleum derivates bleeding
Activated charcoal
50-100 g immediately following lavage , then 50g q4h
Mechanism: adsorbtion !!!!
Repeted dose effctive for: \_\_\_\_\_\_\_\_\_\_\_\_\_\_ benzo, barbiturates narcotics tricyclics phenothiazines salicylates digoxin digitoxin atropine
Inefective for: \_\_\_\_\_\_\_\_\_\_\_\_ most heavy metals pesticides cyanide alcohol strong acid/alkalis
Contraindications: \_\_\_\_\_\_\_\_\_\_\_\_ unprotected airway strong acid/alkali petroleum derivates
Barbiturates
- Hypnotic and sedative agents
- Induction of anesthesia
- Treatm of epilepsy
Mechanism of toxic:
depression of neuronal activity
GABA mediated synaptic inhibition
depression of central sympathetic tone
↓ cardiac contractility
Toxic dose:
(drug, route, rate, individual tolerance)
toxicity= 5-10 x hypnotic dose
Clinical presentation:
A. lethargy, slurred speech, nystagmus, ataxia
hypotension, coma, resp arrest
B. Hypothermia - deep coma + hypotension/bradycardia
Barbiturates Diagnosis
Diagnosis :
history of ingestion
epileptic patient with stupor or coma
skin bullae –no specific
serum level: 60-80 mg/l -> coma
electrolytes, glucose, ABG, BUN, creatinine
Barbiturates Treatment
Treatment:
A. airway, assist ventilation
coma, hypotermia, hypotension
B. no specific antidote
C. Decontamination:
prehospital: activated charcoal, ipeca (min)
hospital: activated charcoal, gastric lavage
D. Enhanced elimination:
- alkalinization of the urine
- repeat-dose activated charcoal
- hemoperfusion
Benzodiazepines
Mechanism of Toxicity:
GABA med synaptic inhibition
Inhib other neuronal syst
-> depression of spinal reflexes / RAS
Benzodiazepines
Toxic dose:
Oral overdose:
Diazepam 15-20 x therap dose
Rapid iv - Respiratory arrest
Benzodiazepines
Clinical:
lethargy, slurred speech, ataxia, coma, resp arrest
hyporeflexia, midposition or small pupils
hypothermia
complications ! short acting/other depressant
Benzodiazepines
Diagnosis
History ingestion or injection
Dif Diagnosis
Reverse with Flumazenil
Benzodiazepines
Treatment
A. Emergency and supportive measures:
airway, assist ventilation
coma, hypotermia, hypotension
B. Specific drugs and antidotes:
FLUMAZENIL iv 0,1 – 0,2 mg, repetead as
needed < 3mg
C. Decontamination:
prehospital: activated charcoal, ipeca (min)
hospital: activated charcoal, gastric lavage
D. Enhanced elimination:
no role for diuresis, dialysis, etc.
Cyclic Antidepressants
Mechanism of toxicity
CV mechanism:
- anticholinergic effects => tachycardia , mild hypertension
- peripheral α adrenergic blockade =>vasodilation
- effect quinidinelike => myocardial depression, conduction disturbances
CNS mechanism:
- anticholinergic toxicity
- inh reuptake of norepinephrine/serotonin
- relevant pharmacokinetics
1. slow absorbtion
2. active metabolites
3. binding to body tissues and plasma proteins
Cyclic Antidepressants
Toxic dose
Toxic dose:
narrow therapeutic index: intoxication
10-20 mg/kg potentially life-threatening
Cyclic Antidepressants
Clinical
3 major syndromes:
A. Anticholinergic:
sedation, delirium, coma, dilated pupils, dry skin, ↓sweating, tachycardia, ↓ bowel sounds, urinary retention
B. Cardiovascular:
abnormal cardiac conduction, arrhythmias, hipotension
C. Seizures:
recurrent/ persistent hyperthermia, rhabdomyolysis, brain damage,multisystem failure, death
D. Death:
ventricular fibrillation, intractable, cardiogenic shock, status epilepticus with hyperthermia
Cyclic Antidepressants
Diagnosis
Diagnosis
any patient with lethargy, coma, seizures,
QRS ↑
QRS ↑> 0,12 = severe poisoning
A. specific levels:
______
terapeutic c% = 300 ng/ml
serious poisoning = 1000 ng/ml or greater
B. other useful lab studies:
electrolytes, glucose, BUN, creatinine, cont EKG monitoring, x-ray, ABG
CYCLIC ANTIDEPRESSANTS
Treatment
A. Emergency and supportive measures:
- airway and assist ventilation;
- coma, seizures, hyperthermia, hypotension, arrhythmias
- neuromuscular blocker
- continuos monitor Temperature, vital signs, ECG
B. Specific drugs and antidotes:
sodium bicarbonate 1-2 mEq/kg iv
-> pH 7.45-7.55
C. Decontamination
- prehospital : activated charcoal
! not emesis - hospital : activated charcoal
gastric lavage
D. Enhanced elimination :
dialysis/ hemoperfusion not efective
PHENOTHIAZINES
Mechanism of toxicity
CV mechanism:
- anticholinergic effects => tachycardia, mild hypertension
- peripheral α adrenergic blockade => vasodilation => hypotension
- effect quinidinelike => myocardial depression, conduction disturbances
CNS mechanism:
- anticholinergic toxicity => CNS depression
- α adrenergic blockade => miosis
- central dopamine receptor blockade => extrapyramidal dystonic reactions
- distrubances of temperature regulation => poikilothermy
- low seizure threshold => mech unknown
PHENOTHIAZINES
Toxic Dose
high toxic-therapeutic index
extrapiramidal reactions, anticholinergic side effects, orthostatic hypotension =>
therapeutic doses
PHENOTHIAZINES
Clinical
A. Mild intoxication:
sedation, small pupils, orthostatic hypotension.
Aach manifestions:dry mouth, absence of sweating, tachycardia, urinary retention
B. Severe intoxication:
coma, seizures, respiratory arrest, QT ↑,
hypo/hyperthermia
C. Extrapyramidal distonic effects:
torticollis, jaw muscle spasm, rigidity, bradykinesia
D. Chronic => neuroleptic malignant syndrom: rigidity, hyperthermia, sweating, lactic acidosis, rhabdomyolysis
PHENOTHIAZINES
Diagnosis
History of ingestion
sedation, small pupils, hBP, QT ↑
A. specific levels: Q not available, only qualitative
B. other useful lab studies: electrolytes, glucose, BUN, creatinine, CPK, cont EKG monitoring, chest and abdominal x-ray, ABG
PHENOTHIAZINES
Treatment
A. Emergency and supportive measures:
- airway and assist ventilation; supplemental O2
- coma, seizures, hyperthermia, hypotension, arrhythmias
- continuos monitor Temp, vital signs, ECG
B. Specific drugs and antidotes:
no specific antidote
C. Decontamination
- prehospital : activated charcoal
- hospital : activated charcoal, gastric lavage ?
D. Enhanced elimination :
dialysis/ hemoperfusion not efective
OPIOIDS
Mechanism of toxicity
*stimulates specific opiate receptors in CNS
=> sedation,
=> respiratory depression -> resp.failure -> apneea -> death
- noncardiogenic pulmonary edema
OPIOIDS
Toxic dose
Depend on:
compound, route, tolerance, rate of adm
OPIOIDS
Clinical
A. mild/moderate overdose:
lethargy, small pupils (pinpoint size), TA↓,
flaccid muscles, bowel sounds ↓
B. higher dose:
respiratory depression, apnea, pulmonary edema
C. seizures: not common
OPIOIDS
Diagnosis
pinponts pupils, respiratory and CNS depression
-> quickly awakens after adm of Naloxone
signs of iv drug abuse
Screening
Lab: electrolytes, glucose, ABG, x-ray
Which iv injected drug can induce non-cardiogenic pulmonary edema and resp distress?
iv injected HEROIN
also salicylates and cocaine
OPIOIDS
Complications
ARDS Aspiration pneumonia Lezional APE Postinject venous thrombosis Necrosis after inject paravenous Hepatitis B, C HIV Abcess Rabdomiolisis Renal insuf
Sindrom de intrerupere - OPIOIDS
INTENTIONALE (pentru obtinerea drogului)
la 6 – 8 ore DUPA INTRERUPERE
maxim : 36 – 72 ORE
NEINTENTIONALE la 8-12 ORE: ↑ 24 ORE ULTERIOR STABILE
LACRIMATIE, RINOREE, CASCAT, PERSPIRATIE
SOMN AGITAT, TREZIRE DEZAGREABILA
MIDRIAZA, ANOREXIE, AGITATIE, IRITABILITATE, TREMOR
Pentru MORFINA, HEROINA: max 36 – 48 ore
-> 72 ore
↓ 5 – 10 ZILE
MAXIM:
INSOMNIE, ANOREXIE INTENSA, AGITATIE EXTREMA, ANXIETATE, LACRIMATIE, RINOREE, DEPRESIE, GREATA, VOMA, SPASM INTESTINAL, DIAREE, TAHICARDIE, HTA, DURERI SI CRAMPE MUSCULARE, SCADERE IN GREUTATE, DESHIDRATARE, CETOZA, TULB. ACIDO-BAZICE
Sindrom de intrerupere
Tratament
INSOMNIA: NITRAZEPAM, FLURAZEPAM, CLORALHIDRAT
ANXIETATEA: CLORDIAZEPOXID 10 mg x 4 / zi
CRAMPE DIGESTIVE: PROPANTELINA
PREPARAT DE BELLADONA
GREATA: PROCLORPERAZINA (METOCLOPRAMID)
PREVENIREA SINDR. DE ABSTINENTA:
CLONIDINA 0,1 mg x 3/zi
PREFERABIL INTRASPITALICESC
ACETAMINOPHEN
Toxic dose
Toxic dose acute ingestion:
children > 140 mg/kg
adults > 6g; lethal 13-25 g
Rapid absorbtion: 1-4 h ; T1/2: 2-3 h
ACETAMINOPHEN
Mechanism of toxicity
Mechanism of toxicity:
acetaminophen -P-450- toxic metabolit (hepatotoxic) NAPQI
-glutathione- detoxified
=liver injury
ACETAMINOPHEN
Clinical
Clinical presentation
(depend upon the time after ingestion)
A. Early (0-24 h) - anorexia, nausea, vomiting , diaphoresis
B. After 24-48 h (latent) -transaminase level ↑
- PT ↑
C. Hepatic phase - acute hepatic failure -> encephalopathy -> death
D. Recovery phase: normalise hepatic tests (after 5 days)
Acetaminophen
Diagnosis
Diagnosis
- serum acetaminophen level
- history
A. Specific levels : 4 h postingestion
B. Other useful lab studies: electrolytes, glucose, BUN, crea, transaminases, PT
Acetaminophen
Treatment
Decontamination
1. prehospital : activated charcoal
emesis (4-6 h)
2. hospital : activated charcoal
Enhanced elimination :
hemoperfusion
Specific drugs and antidotes: N-acetylcysteine
140 mg/kg orally
70 mg/kg q4 h 17 doses
- replates glutathion
- adverse effects: vomiting
SALICYLATES
Mechanism of toxicity
Mechanism of toxic:
► central stimulation of the respiratory center->
hyperventilation => respiratory alkalosis
► intracellular effects: Inhib of Krebs enzymes & uncoupling of oxidative phosphorylation
=> metabolic acidosis
► alteration in capillary integrity
► alteration of platelet function
► increase in glycolysis => hypoglycemia
SALICYLATES
Toxic dose
Toxic dose:
therapeutic single dose 10 mg/kg
- acute ingestion:
150-200 mg/kg mild intoxication
300-500 mg/kg severe intoxication - chronic intoxication:
100mg/kg/d for 2 or more days
SALICYLATES
Clinical
Clinical presentation
A. Acute ingestion:
vomiting, epigastric pain, hyperventilation, tinnitus, lethargy, respiratory alkalosis + metabolic acidosis
coma, seizures, hypoglycemia, hyperthermia,
dehydration, arrhythmias (K ↓)
pulmonary edema, CV collapse
B. Chronic intoxication:
confusion, dehydration, metabolic acidosis
mortality rates > acute ingestion
cerebral and pulmonary edema
SALICYLATES
Diagnosis
history of acute ingestion
typical signs and symptoms
qualitative: colorimetric;
lab studies:
anion gap calculation, glucose, BUN, PT, ABG, chest X-ray
SALICYLATES
Treatment
A. Emergency and supportive measures:
airway, assist ventilation, supplemental oxygen , X ray
coma, seizures, pulmonary edema, hyperthermia
metabolic acidosis: sodium bicarbonate 1-2 mEq
replace fluid and electrolyte deficits
monitoring
B. Specific drugs and antidotes: no antidote
C. Decontamination:
prehospital: activated charcoal, ipeca induced emesis (30 min)
hospital: activated charcoal, gastric lavage
D. enhanced elimination: 1. urinary alkalinization : sodium bicarbonate -> pH 7.5 alkalemia is not a CI 2. hemodialysis, hemoperfusion 3. repeat dose activated charcoal
IZONIAZID
Mechanism of toxicity
Mechanism of toxicity:
PYRIDOXINKINASE
PYRIDOXINE PYRIDOXALPHOSPHAT
Acute overdose: competition with pyridoxal 5-phosphate
↓ GABA
inh lactat>piruvat => lactic acidosis
Peripheral neuritis
IZONIAZID
Toxic dose
Toxic dose acute: min 1.5g
6g = severe toxicity => death
3mg/kg epileptics => status epilepticus
IZONIAZID
Clinical
Clinical presentation
slurred speech, ataxia, coma, seizures (30-60 min), metabolic acidosis, hemolysis tahicardia, cianosis, hTA, colaps oliguria -> anuria midriasis, nistagmus, toxic psihosis, hyperpirexia
IZONIAZID
Diagnosis
Diagnosis :
history of ingestion
clinical presentation
! Acute onset seizures + acidosis
IZONIAZID
Treatment
Treatment
A. Emergency and supportive measures:
airway, assist ventilation
coma, seizures, metabolic acidosis (NAHCO
B. Specific drugs and antidotes: pyridoxine eq INH
C. Decontamination:
prehospital: activated charcoal, -> ! Not emesis
hospital: activated charcoal, gastric lavage
D. Enhanced elimination:
forced diuresis, dialysis
IZONIAZID
Intoxication Outcome -> End Result
Blocking pyridoxinkinaza.
Hepatic necrosis
Tubular necrosis
Inh GABA => Metabolic Acidosis
Classes of Pesticides
Insecticides (kill insects) • Organochlorines • Organophosphates • Carbamates • Synthetic Pyrethroids Herbicides (kill plants) Rodenticides (kill rodents) Fungicides (kill fungus) Fumigants (kill whatever)
ORGANOPHOSPHATES
Mechanism of toxicity
A.inhibit acetylcholinesterase -> accumulation of acetylcholine
muscarinic R – cholinergic effector cells
nicotinic R – skeletal NM junctions, autonomic ganglia
CNS
B. Absorbtion:
inhalation
ingestion
skin contact
- highly lipophilic
ORGANOPHOSPHATES
Clinical
Toxic dose: wide spectrum, rate, metabolism
Clinical presentation: 1-2 h after exposure
M: vomiting, diarrhea, abd cramping, bronhospasm, miosis, bradycardia, salivation,
sweating -> dehydration -> shock
N: muscle fasciculations, tremor, weakness, resp muscle paralysis
CNS: agitation, seizures, coma, tremor
delayed peripheral neuropathy
ORGANOPHOSPHATES
Diagnosis
Diagnosis:
history of exposure
characteristic sign
solvent odor
Specific levels: ↓PChE, ↓AChE (more reliable)
ORGANOPHOSPHATES
Classification
a. Latent poisoning:
Plasma chol activity >50%
No clinical manifestations
b. Mild poisoning: Fatigue, headache, dizziness N,V,D, abd cramps Sweating, salivation Plasma chol activity 20-50%
-> Atropine 1mg sc, good prognosis !!!
c. Moderate poisoning:
Miosis, fasciculations
Generalized weakness, unable to walk, difficulty speaking
Plasma chol activity 20-50%
-> Atropine 1-5mg iv q5min
d. Severe poisoning:
Miosis, fasciculations, coma, flaccid paralysis, no light reflex, profuse sweating, salivation,
bronchorrhea,
Plasma chol activitity Atropine 1-5 mg iv q5min
fatal if untreated !!!!!!
ORGANOPHOSPHATES
Treatment
A. Emergency and supportive measures:
airway, assist ventilation, ! sudden resp arrest
coma, seizures, 6-8 h observation
B. Specific drugs and antidotes:
ATROPINE, PRALIDOXIME
atropine: 0.5-2 mg iv, repeated (persistent wheezing, bronchorrhea) , HR>60 bpm
pralidoxime: regenerate enzyme activity
1-2 g iv bolus, cont infusion, most effective first 24 h
C. Decontamination: skin: remove, wash exposed areas ingestion: preH: activated charcoal, ipeca H: activated charcoal, cathartic , gastric lavage
D. Enhanced elimination:
dialysis/ hemoperfusion not generally indicated
ETHANOL
Mechanism of toxicity
A. CNS depression
additive effect
B. hypoglycemia
C. predisposition to trauma, hypothermia, metab derangements
ETHANOL
Toxic dose
Toxic dose: 5-8 g/kg
Individual degree of tolerance:
300 mg/dl coma for novice drinkers
500 – 600 mg/dl awakeness – chronic alcoholics
Absorbtion:
20% stomach; 80% intestin
usual 30-60 min (80-90%)
food delayed abs 4-6 h
ETHANOL
Clinical
Clinical presentation:
sensitivity: frontal> occipital> cerebellum
*moderate intoxication:
euphoria, mild incoordination, ataxia, nystagmus, impaired
judgment and reflexes, aggressive behavior, hypoglycemia
- deep intoxication:
coma, respiratory depression, pulmonary aspiration, TA↓,
small pupils , HR↓ - alcohol withdrawal
- tremulousness, anxiety, SNS overactivity, convulsions -> delirium
- other problems
- substitutes ingestion
ETHANOL
Diagnosis
history of ingestion
smell
nistagmus, ataxia, altered mental status, hypoglicemia
may acompany : head trauma, meningitis, hypothermia
other drug intoxication
rough correlation blood levels – clinical presentation
other lab studies
ETHANOL
Treatment
A. Emergency and supportive measures:
airway (prevent aspiration), intubate, assist ventilation
glucose, thiamine, treat coma, seizures,
corect hypothermia with gradual rewarming
B. Specific drugs and antidotes: no antidote
C. Decontamination:
ipeca, gastric lavage not indicated
prehospital: ipeca (min)
hospital: gastric lavage (30 min), activated charcoal if + other toxin
D. enhanced elimination:
hemodialysis (rarely needed)
hemoperfusion, forced diuresis not effective
ETHANOL
Antidote for poisoning by:
Methanol
Ethylene glycol
Diethylene glycol
- Inhibits metabolic activation by alcohol dehydrogenase (ADH)
Alcohol withdrawal effects
- Tremor
- Nausea
- Irritability
- Agitation
- Tachycardia
- Hypertension
- Seizures
- Hallucinations
METHANOL
Mechanism of toxicity & Toxic dose
Mechanism of toxicity:
methanol -> formaldehyde -> formic acid (systemic acidosis) formate -> blindness
Toxic dose:
fatal min oral dose: 30 ml 40%
10 ml sol 40% - blindness
METHANOL
Clinical
A. first few hours:
inebriation, gastritis, not acidosis, ↑OG
B. after a latent period (up to 30h):
severe metabolic acidosis,
visual disturbances, blindness, seizures, coma, death
visual disturbances: “ like standing in a snowfield”
fundoscopic exam:
optic disk hyperemia, venous engorgement,
papilledema
METHANOL
Diagnosis
history of ingestion
symptoms
lab findings, AG, OG
a. Specific levels:
serum methanol > 20 mg/dl =toxic latent period
Elevated serum formate: better measure of toxicity
b. Other useful lab studies:
electrolytes, glucose, BUN, creatinine, serum osmolality, osmolar gap, ABG, lactate level
METHANOL
Treatment
A. Emergency and supportive measures:
airway , intubate, assist ventilation
treat coma, seizures
metabolic acidosis : SODIUM BICARBONATE
B. Specific drugs and antidotes:
ETHANOL
history of significant methanol ingestion, OG>5mosm/l
metabolic acidosis,
methanol c% >20 mg/dl -> c% ethanol 100-150 mg%
FOLIC ACID enhance formate -> CO2 + water ; 50mg iv q4h
4-METHYLPYRAZOLE – INH adh, experimental
C. Decontamination:
preH: ipeca,
H: gastric lavage , activated charcoal = not efficiently
D. enhanced elimination:
hemodialysis , τ↓ 3-6 h
ind: methanol poisoning with significant metabolic acidosis
OG>10mosm/l
ETHYLENE GLYCOL
Mechanism of toxicity & toxic dose
Ethylene glycol -> glycoaldehyde
glycolic / glyoxylic / oxalic acids -> metab acidosis
Oxalate + Ca -> calcium oxalate crystals (insoluble) -> tissue injury
Toxic dose: 100 ml
ETHYLENE GLYCOL
Clinical
- first 3-4 h:
≈ethanol, OG↑, no acidosis; gastritis with vomiting - after 4-12 h:
anion gap acidosis, hyperventilation, convulsions, coma, cardiac conduction disturbances, arrhythmias, renal failure (reversible), pulmonary /cerebral edema, hCa
ETHYLENE GLYCOL
Diagnosis
history of antifreeze ingestion
typical symptoms, OG ↑, AG ↑
oxalate crystals (urine)
ethylene glycol level
50 mg/dl -> serious intoxications
Other lab studies:
electrolytes, glucose, BUN, creatinine, calcium,
transaminases,osmolality, ABG, ECG
ETHYLENE GLYCOL
Treatment
A. Emergency and supportive measures:
airway ,intubate, assist ventilation
treat coma, seizures, cardiac arrhytmias, metabolic acidosis
-> treat hypocalcemia: CALCIUM GLUCONATE iv
B. Specific drugs and antidotes: ETHANOL
(prevent metabolism of EG to its toxic metabolites: pyridoxine, folate, thiamine)
C. Decontamination:
ipeca, gastric lavage not indicated
prehospital: ipeca (min)
hospital: gastric lavage (30 min), activated charcoal not efficiently
D. enhanced elimination:
hemodialysis ind: OG>10 mosm/l, intoxication+renal failure
c%>20 – 50 mg/dl
HYDROCARBONS
Mechanism of toxicity & toxic dose
Used: petroleum, plastic, agricultural chemical
industries as solvents, degreasers, fuels, pesticides
Mechanism of toxic:
- pulmonary aspiration
- sistemic intox: ingestion, inhalation, skin absorbtion
- simple petroleum distillates: poorly absorbed
- aromatic / halogenated HC, alcohols, ethers,ketones: serious systemic toxicity
Toxic dose:
pulmonary aspiration: few ml -> chemical pneumonitis
ingestion: 10-20 ml (camphor, CCl4)
HYDROCARBONS
Clinical
A. pulmonary aspiration:
coughing, choking, gagging, tachipneea, wheezing, severe chemical pneumonitis, sec bacterial infection, respiratory complications
B. ingestion:
abrupt nausea, vomiting, hemorrhagic gastroenteritis
C. systemic toxicity:
confusion, ataxia, lethargy, headache, syncope, coma, respiratory arrest, cardiac arrhythmias
D. skin/eye contact:
irritation, burns, corneal injury
HYDROCARBONS
Diagnosis
A. aspiration :
history of exposure, respiratory symptoms ,<4-6h
chest X-ray, ABG
B. systemic intoxication:
history of ingestions/inhalation
systemic clinical manifestation
Specific level: not available
HYDROCARBONS
Treatment
A. Emergency and supportive measures: 1. general: BLS for all symptomatic patients airway , supplemental O2, assist ventilation monitor ABG, chest X-ray, ECG
- pulm aspiration:
observation 4-6 h
coughing on arrival= aspiration
! Do not use steroids ! - ingestion: 5-10 ml – systemic toxicity rare
B. Specific drugs and antidotes: no specific antidote
(acetylcysteine –CCl4,)
C. Decontamination:
Inh: move the victim to fresh air, O2
Skin /eyes: remove, wash
Ingestions: do not induse emesis, activated charcoal, cathartic
D. Enhanced elimination: no role
HYDROGEN SULFIDE
Mechanism of toxicity & toxic dose
= Highly toxic, flammable, colorless gas, heavier than air
• industrial processes, petroleum, mines, carbon disulfide production, hot asphalt
Mechanism of toxic:
inh cytocrom oxidase system -> cellular asphyxia
rapidly absorbed -> symptoms immediately
= mucous membrane irritant
Toxic dose: •rotten egg odor=0.025ppm •recomm workplace limit=10ppm •resp tract irritation, olfactory nerve paralysis =50-100 ppm •dangerous for life =300 ppm •fatal= 600-800 ppm
HYDROGEN SULFIDE
Clinical
A. irritant effect:
upper airway irritation, burning eyes, blepharospasm;
skin exposure: painful dermatitis, pneumonitis, noncardiogenic pulmonary edema
B. Acute systemic effect:
headache, nausea, vomiting, dizziness,
confusion, seizures, coma
-> massive exposure: immediate CV collapse, respiratory arrest, death
HYDROGEN SULFIDE
Diagnosis
Diagnostic:
hystory of exposure
progressive airway irritation and cellular asphyxia
smell: rotten eggs ‼️
N. olfact. Paralysis
serum levels : not available
HYDROGEN SULFIDE
Treatment
A. Emergency and supportive measures:
airway , high-flow humidified O2, assist ventilation
treat coma, seizures, hypotension
corect hypothermia with gradual rewarming
B. Specific drugs and antidotes:
nitrites -> methemoglobinemia: sulfide
ion -> sulfhemoglobin (less toxic)
C. Decontamination:
remove from exposure, supplem O2
D. enhanced elimination: no role
hyperbaric oxigen therapy: no scientific evidence
CARBON MONOXIDE
Mechanism of toxicity + Toxic dose & Sources
SOURCES:
- smoke inhalation in fires
- auto exhaust fumes
- poorly or faulty ventilated charcoal
- kerosene, cigarette smoke
• Mechanism of toxic:
cellular hypoxia and ischemia
► CO affinity= 250 x O2 curve
► inhibit cytochrom oxidase SaO2↓
• T1/2 COHb = 3 – 4 h IN ATMOSPERIC air
= 30 – 40 min ATMOSFERA O2 100%
= 15 – 20 min O2 HIPERBARR (2,5 ATM)
► sensitivity of the brain
► Hb F fetal=2 x maternal levels
• Toxic dose:
limit accepted = 25ppm
dangerous = 1500 ppm (0.15%)
mins 1000 ppm SaCO 50%
CARBON MONOXIDE
Clinical
Clinical presentation: brain and heart
A. Headache, dizziness, nausea / angina, myocardial infarction, impaired thinking, syncope, coma, convulsions, cardiac arrhythmias, hipotension,
=> death
Concentration | COHb | Symptoms
ppm % :
< 35 | 5 none, mild headache 50 | 10 slight headache, dyspnea on vigorous exertion 100 | 20 throbbing headache, dyspnea with moderate exertion 200 | 30 severe headache, irritability, fatigue 300-500 | 40-50 headache, tachycardia, confusion, lethargy, collapse 800-1200 | 60-70 coma, convulsion 1900 | 80 rapidly fatal
B. Neurologic sequelae :
parkinson, persistent vegetative state,
personality and memory disorders
C. Pregnancy -> fetal death
CARBON MONOXIDE
Diagnosis
Diagnosis – history of exposure, - no specific findings - cherry red skin coloration + bright red venous blood - ABG, pulse oximetry
A. Specific levels: CoHb
B. lab studies:
electrolytes, glucose, BUN, creatinine, ECG
CARBON MONOXIDE
Treatment
• Treatment
A. Emergency and supportive measures:
airway, assist ventilation, early intubation if smoke inhalation
coma, seizures
monitoring EKG
B. Specific drugs and antidotes: OXIGEN (100%) ↓τ C
C. Decontamination:
remove from exposure / suppl O2
D. Enhanced elimination:
HYPERBARIC OXYGEN 100% -> 2-3 atm ‼️
CYANIDE
Source & Toxic dose
• Sources: -industry, chemical lab, plants - burns: polyurethane, polyacrylonitryl, silk, wool - drugs: nitroprusside
• Toxic dose: – INHALED: 100 ppm (in 1 hour) 300 ppm MINUTE – INGESTED: 50 mg LETAL (HCN) 200- 300 mg KCN
- ABSORBTION : rapidly
- ELIMINATION : metabolic
CYANIDE
Mechanism of toxicity
• Mechanism:
CN-(+ Fe3+) blocks cytochrome oxidase -> impairing oxidative phosphorylation, anaerobic metabolism, lactic acid generation -> metabolic acidosis
CYANIDE
Clinical
CLINIC:
– coma, convulsions -> metabolic acidosis -> shock -> respiratory failure -> DEATH (few min)
– Early effects:
cellular hypoxia -> headache,anxiety, tachycardia, hyperpnea, mild HTA, palpitations
– Later effects:
nausea, vomiting,tachi/bradi, hTA, seizures,
coma, apneea, mydriasis, cardiac dysrhytmias, heart blocks, asystole
! Absence of cyanosis sugests CN-
CYANIDE
Diagnosis
DIAGNOSTIC:
severe metabolic acidosis red venous blood bitter almond odor ‼️ <- typical coma with rapidly onset, ‼️ absence of Cyanosis tachypnea
CYANIDE
Treatment
• SUPPORTIVE TREATM:
- assisted ventilation, OXYGEN 100%
- correct acidosis
• DECONTAMINATION:
- AFTER ANTIDOTE ADM !
- < 2h: Lavage, ACTIVATED CHARCOAL
• ENHANCE ELIM
- HEMODIALYSIS, HEMOPERFUSION – NO ❌
- HYPERBARIC O2
ANTIDOTES:
‼️NITRITES →Methaemoglobinemia
MeHb-Fe3+ +CN-CITOCROMOXIDAZA →MeHb-CN + CITOCROMOXIDAZA
METHEMOGLOBINE →40%
___________
- AMYL NITRITE - FIRST EMERGENCY‼️‼️
- SODIUM NITRITE 3% 10 ml i.v. SLOW (~ 20% MeHb)
• THIOSULFATE: sol. 25% 50 ml i.v. SLOW;
Repeted cca. 1 h NITRITE + THIOSULFATE - half doses
- HYDROXYCOBALAMIN
- CoEDTA (KELOCYANOR)
- monitoring 2 – 3 days
- MeHb 40%
- TREAT ACIDOSIS !!!
IRON
Mechanism of toxicity & toxic dose
• Mechanism of toxicity:
- direct corrosive effect -> hemorrhagic necrosis /perforation
- absorbed iron => cellular dysfunction -> lactic acidosis and necrosis
• Toxic dose:
acute lethal dose 150-200 mg/kg ❗️
lowest LD 600 mg
20-30 mg/kg -> vomiting, abd pain, diarrhea
> 60 mg/kg = potentially lethal
IRON
• Clinical presentation:
A. shortly after ingestion: vomiting, diarrhea (bloody)
massive fluid loss -> shock, renal failure, -> death
B. apparent improvement over 12 hours
C. coma, shock, seizures, coagulophaty, hepatic failure, YE sepsis, death
D. pyloric stricture, other intestinal obstruction
• Diagnosis: history of exposure vomiting diarrhea hTA L↑ Gluc↑>150 mg/dl
IRON
Treatment
A. Emergency and supportive measures:
airway, assist ventilation, hypovolemia, shock
coma, seizures, metabolic acidosis
B. Specific drugs and antidotes: DEFEROXAMINE ‼️
pink red color = chelated deferoxamine-iron complex
C. Decontamination:
prehospital: ipeca –emesis
hospital: emesis, gastric lavage, x-ray
❌activated charcoal does NOT adsorb iron‼️
D. Enhanced elimination:
hemodyalisis, hemoperfusion not effective
ARSENIC
Mechanism of toxicity & Toxic dose
Mechanism of toxic:
interacting with sulfhydryl groups (trivalent)
substituting for phosphate (pentavalent)
A. soluble comp. – greatest risk
B. inorganic dusts – skin, mucous memb., resp and GIT
C. human carcinogen
• Toxic dose:
A.inorganic acute 100-300 mg As+3 chronic 20-60 μg/kg/d B. organic less toxic - marine organisms
ARSENIC
Clinical
Clinical presentation
A. acute exposure:
- GIT effects: nausea, vomiting, abd pain, watery diarrhea
- cardiopulm effects: congestive cardiomyopathy, pulm edema, ↑QT
- neurologic effects: delirium, encephalopathy, coma
- others: Aldrich-Mees lines, hair loss, leukopenia
B. chronic intoxication:
fatigue, gastroenteritis, anemia, leukopenia
- skin lesions
- cancer – chronic inhalation -> lung cancer
- chronic ingestion ->lung, liver, kidney, bladder
ARSENIC
Diagnosis
Diagnosis:
history of exposure + typical presentation
garlic odor ‼️
X-ray
specific levels : n <1 ppm
ARSENIC
Treatment
A. Emergency and supportive measures:
airway, assist ventilation
coma, shock, arrythmias, hypotension
B. Specific drugs and antidotes:
BAL (DIMERCAPROL‼️) 3-5 mg/kg/im 4-6 h
C. Decontamination:
prehospital: activated charcoal, ipeca (min)
hospital: activated charcoal, gastric lavage
D. enhanced elimination:
hemodialysis
LEAD
What is it ?
Lead acetate (Pb (C2H3 O2)2· 3H2O)
• White, crystalline substance
• Sugar of lead has a sweet taste
• Paint
Lead tetraethyl (Pb(C2H 5)4)
• antiknock compound added to gasoline
• air pollution
LEAD
Mechanism of toxicity
Mechanisms Of Lead Toxicity
- Inhibition of enzymatic processes
- Lead-Calcium Interactions
- Lead-Protein Interactions
- Lead-Dopamine Interactions
- Lead-Opioid Interactions
LEAD
Health effects
Health Effects
- Encephalopathy
- Colic
- Frank Anemia
- Hemoglobin Synthesis
- Peripheral Neuropathies
- Infertility (MEN)
- Systolic Blood Pressure (MEN)
- Nerve Conduction Velocity
- Erythrocyte Protoporphyrin
- DEVELOPMENTAL TOXICITY❗️
- IQ, Memory, Learning
- Growth
LEAD
Half life
- 25 DAYS – BLOOD
- 40 DAYS – SOFT TISSUE
- 20 YEARS – BONE
LEAD
Clinical
A.acute ingestion:
abdominal pain, anemia, toxic hepatitis
B.chronic intox:
fatigue, irritability, anorexia, insomnia, weight loss, arthralgias, myalgias, hypertension
-GI: nausea, constipation/diarrhea, crampy abd pain (lead colic)
-CNS: impaired concentration, headache, ↓ visual-motor coordination, ataxia, delirium,
convulsion, coma, ↓ intelligence, decreased growth
- peripheral motor neuropathy: upper extremities, extensor muscle weakness
- hematologic: anemia (normochromic,microcytic), hemolysis
-nephrotoxic: acute tubular dysfunction, (Fanconi-like aminoaciduria),
chronic interstitial fibrosis, hyperuricemia
-adverse reproductive outcomes: aberrant sperm production, decreased gestational age
LEAD
Diagnosis
Diagnosis: symtomatology
– multisystem findings: abd pain, headache,
anemia
– child with: delirium, convulsions, neurobehevioral deficits
– whole blood level
– Urinary lead excretion; n<50 microg/d
LEAD
Treatment
A. Emergency and supportive measures:
treat seizures, coma, adequate fluids (avoid overhydration) increased ICP -> corticosteroids
B. Specific drugs and antidotes: CHELATORS
encephalopathy: CALCIUM EDTA
C. Decontamination:
ipeca (min) ,gastric lavage , activated charcoal, cathartics
D. enhanced elimination:
no role
ETHANOL METABOLISM
Which enzyme transforms Ethanol in Acetaldehyde?
ADH – Alcohol Dehydrogenase
ETHANOL METABOLISM
Which Enzyme transforms Acetaldehyde in Acetate?
ALDH – Acetaldehyde Dehydrogenase
Antidote for Methanol, Ethylene Glycol
Ethanol
Antidote for LEAD
Edetate calcium disodium CaNa2-EDTA
