toxicology

Sensitisers
These provoke an immune response (sensitisation) resulting in asthma, rhinitis, allergic dermatitis e.g.
diisocyanates, glutaraldehyde, nickel
effects
LADME
Routes of elimination of toxic substances / or their metabolites
elimination usually follows 1.order principles
Lungs - especially fat soluble vapours e.g. - alcohols, or gases such as carbon monoxide
Kidneys - especially water soluble substances
Metabolism/ biotransformation of toxic substances Water soluble metabolites are then more easily excreted by the kidney. biotransformation does not
necessarily result in less toxic compunds.
non-polar and therefore not water soluble organic compounds tend to be oxidised within the liver
Distribution within the body
chemicals appear to distribute into the body as a single compartiment
Thus for example water soluble compounds of lead are found (amongst other places) in the red blood
cells, while fat soluble ones concentrate in the central nervous system (CNS).
Absorption into the body
fat soluble liquids are readily absorbed through the skin and fat soluble vapours are readily absorbed
through the lungs. organic solvents such as hexane, toluene, trichlorethylene and many others.
general management
dialysis
Haemodialysis: This may be useful in severe poisonings with dialysable drugs (low PB, small molecules)
that have small Vd and meaningful enhancement in Cl, e.g. lithium. Drugs for which haemodialysis is
the method of choice in severe poisonings Salicylates Phenobarbitone Lithium Methanol Ethanol
Ethylene glycol
forced diuresis and urinary pH manipulation
acidic diuresis: amphetamine, quinidine, alkaloids, phencyclidine
alkaline diuresis: ASA, SA, phenobarbital, barbiturate
whole bowel irrigation if charcoal lacks efficacy
activated charcoal, adults 25-100g
Drug characteristicsa low PB, small Vd, low Cl drugs
contraindicate
not for children>1 year
not absorbed metals, ethanol, ethylene glycol, organic solvents, acids and alkalis
side-effects black stool and constipation
dosage drugs with enterophepatic circulation every 6h
digitalis
phenothiazines
TCA
phenobarbital
theophylline
carbamazepine
gastri lavage
aspiration of gastric contents. water is instilled and aspirated
contraindication
risk of GI perforation or if they are combative
acid, alkali or petroleum (hydrocarbons)
emesis
sirup of ipecacuanha, no longer recommended
contraindication
with emesis after ingestion
acid, alkali, sharp objects, petroleum, substances rapid onset
with CNS depression/seizures
children under 6 months
SPECIFIC ANTIDOTES
alcohol fomepizole
atropine poisoning physostigmine
cheese reaction phentolamine
nitrites methylene blue
heparin protaminsulfate
warfarin
warfarin last 5 days
vit.K and fresh frozen plasma
mercury, arsenic, gold dimercaprol
iron deferoxamine
cyanide nitrites and thiosulfate
calcium blocker calciumchloride and glucagon
paracetamol n-acetylcysteine
organophosphate atropine and pralidoxime
digoxin digoxin-specific Fab antibodies
ethylene glycol and methanol ethanol
isoniazide pyridoxine
theophylline esmolol
benzodiazepines flumazenil
b-blockers glucagon
carbon monoxide 100% oxygen
opiods naloxone
INSECTICIDES
herbicides
chlorophenoxyacetic acid
treatment GL
signs of toxicity coma, muscle hypotonia, dermatitis
paraquate
treatment
supportive therapies and hemodialysis
GL
signs of toxicity
pulmonary impairment
GI irritation
botanical insecticides nicotine, rotenone, pyrethrum
organophosphates
treatment
Atropine antagonizes AChPralidoxine reactivatesacetylcholinesterases
airway management
GL if ingested
signs of toxicity
muscarinic: nv, abdominal cramps, sweating etc
nicotinic: fasiculations, weakness, hypertension, tachycardia
irreversible inhibit acetylcholinesterase n and m synapses
chlorinated hydrocarbons (DDT)
not available anymore
block inactivation of nerve membranes in Na channel
AIR POLLUTANTS
hydrocarbons
bone marrow suppression with pancytopenia
benene, toluene, carbon tetrachloride: CNS depressants
ozone
chronic: emphysema, bronchitis...
acute: irritation and dryness of mucous membranes
nitrogen dioxide irritation of lung, eyes, nose, throat
sulfur dioxide
pulmonary edema
epistaxis
conjunctival and bronchial irritation
carbon monoxide
signs of toxicity
syncope
confusion, coma
headache
causes tissue hypoxia because hemoglobin affinity is higher than for oxygen
HEAVY METALS
mercury
treatment
dimercaprol, penicillamine or succimer
GL
signs of toxicity
chronic loosening of teeth, gingivitis, stomatitis
acute
tremor, excitability, delirium
chest pain and sob
GI distress
normally through inhalation
lead
treatment
EDTA, dimercaprol, penicillamine or succimer
GL
signs of toxicity
Lead poisoning: presentation ABCDEFG:
Anemia Basophilic stripping Colicky pain Diarrhea Encephalopathy Foot drop Gum (lead line)
both abdominal pain, anemia
alduts: ataxia, memory loss
children: mental retardation
arsenic
treatment
hemodialysis
dimercaprol or penicillamine
GL
signs of toxicity
chronic
skin changes
polyneuritis
acute
sweet garlicky odor
acute tubular necrosis and oliguria
hemolysis and bone marrow depression
seizure and coma
hypotension and arrhythmia
GI distress
interferes with oxidative phosphorylation
CHELATORS
Succimer
side-effects
GI distress
rash
increase hepatic transaminase levels
oral congener of dimercaprol for childhood lead intoxication
Deferoxamine
side-effects
rapid infusion: histamine release and hypotensive shock
severe oagulapathies
hepatic and renal dysfunction
neurotoxicity
competes very poorly for heme iron
iron parenterally
Penicilllamine
side-effects
thrombocytopenia resembling penicillin hypersensitivity
rash, fever, leukopenia
orally
rheumatoid arthritis and cystinuria
copper (Wilson's disease), lead, arsenic, mercury, gold
Dimercaprol
contraindicated
peanut oil allergy
G-6-PD deficiency
iron: toxic complex
mercury, arsenic, lead, cadmium im
EDTA
calcium disodium salt, since sodium salt causes hypocalemia
side-effect: reversible nephrotoxicity
lead iv or im
DRUGS/CHEMICALS
electrolytes
Fe
treatment deferoxamine, GL, maybe whole-bowel irrigation
NV, diarrhea, bleeding up to metabolic acidosis, renal and hepatic failure, selpsis, pulmonary edema
K treatment 10% calcium chloride, sodium bicarbonate, glucose and insulin. sodium polystyrene
sulfonate , maybe hemodialysis
cardiac dysrhythmias(bradycardia) peripheral weakness
Mg
treatment 10% calcium chloride, maybe hemodialysis
more than 10mEq/L severe
mild: lethargy and weakness severe:respiratory paralysis and heart block (prolonged intervals)
antidepr
SSRIs
treatment
ECG montioring, maybe use of cyproheptadine to manage serotonin syndrome
GL
mild effects
TCA
treatment
sodium bicarbonate to maintain arterial pH of 7.45-7.55
supportive therapy:maybe phyostigmine for anticholinergic effects
phenytoin for seizures
noradr, dopamine, phenyleph. for hypotension
AC
GL
signs
problem:enterohepatic recirc., highly bound, t1/2 24h
mild: anticholinergic side-effects / severe: CNS depression with seizures, hypotension, cardiotoxicity
theophylline
treatment
b-blockers for tachycardia and hypotension
hemodilaysis
AC
GL
NV, tachypnea, tachycardia, hypotension normal levels 10-20mg/L
salicylates
treatment
severe: hemodialysis
saline diuresis and alkalinization
AC
GL
early:respiratory alkalosis, late: metabolic acidosis control serum levels
NV, tinnitus, hyperthermia, coagulopathy, hypoglycemia, acute renal failure, come
opiods
treatment short-acting naloxone, continuous infusion
miosis, mental status, bradycardia, respiratory dep., hypothermia
lithium
between 1.5-3 and over mEq/l
treatment
sodium polysterene sulfonate monitor K levels
iv fluid
GL
lethargy, dysarthria, delirium, seizures
isoniazid
treatment
pyridoxine (B6) and diazepam for seizures
AC
GL
NV, dizziness and lethargy, hepatic injury, seizures, coma
alcohols
DATA alcohols metabolism
ethanol
metabolised to acetaldehyde and then via acetaldehyde dehydrogenase (inhibited by disulfiram) to
acetic acid in body to CO2 and H2O
isopropyl alcohol
treatment
iv fluid and bicarbonate for acidosis
GL
NV, abdominal pain, atxia, respiratory depression
methanol
methanol is metabolised into formic acid and ormaldehyd
treatment as ethyleneglycol
NV, abominal pain, ataxia and seizures, coma, acidosis methanol may cause blindness
ethylene glycole
metabolized in oxalic acid
treatment
fomepizole is inhibitor of alcohol dehydrogenase
sodium bicarbonate to correct acidosis
vit. b6, b1, folic acid
hemodialysis if renal failure
ethanol
NV, abominal pain, ataxia and seizures, coma, acidosis renal failure with pulmonary edema
cyanide
treatments
oxygen
Na thiosulphate: CN "SCN Amyl NO2: metHb "CNmetHb Dicobalt edetate: chelation
sodium bicarbonae and hydroxycobalamin
amyl nitrit for inhalation, sodium nitrite and thiosulfate iv
cyanide binds to methemoglobin, dissociates from cyt.oxid.
induce methemoglobinemia
GL
inhiibits cytochrome oxidase- decrease aerobic energy production
respiratore distress
tachycardia, hypertension, arrhythmias
NV
calcium channel blockers
treatment
calcium chloride 10% push, maybe dextrose ???
phosphodieesterase inhibitors: amrinone, vasopressors for hypotension
administer glucagon, atropin or cardia pacing for bradycardia
GL
bradycardia, hypotension, CNS depression, constipation
benzodiazepines
treatment
flumazenil , receptor antagonist may cause seizures with stimulants cave with TCA comb
AC
GL
weakness and ataxia, severe: coma and respiratory depression
b-blockers
treatment
iv fluids and vasopressors for hypotension
administer glucagon (patients may become hypoglycaemic), atropin or cardiac pacing for bradycardia
GL
NV , hypotension, bradycardia, CNS depression
paracetamol
treatment
cave anaphylactic reactions 20%
for adults more than 10g and children 200mg/kg
N-acetylcysteine if indicated by Rumack-Matthew nomogram loading dose 140, maintenance 70
activated charcoal administration (AC)
gastric lavage within 2 h (GL)
apparent after 1-2d : nausea, vomiting, anorexia and diaphoresis final:abdominal pain,hepatic failure,coma