TOXICOLOGY
Treatment Tidbits...
Four Contraindications to inducing vomiting or Gastric
lavage:
Caustics -- to avoid further damage
Convulsants -- further stress could initiate
convulsions in someone who has
ingested convulsants
Coma -- to avoid aspiration
Solvents or Petroleum -- to avoid aspiration
Further absorption preventions:
Ipecac
Apomorphine
Gastric lavage
Activated charcoal
Cathartics
Elimination enhancement drugs:
HCO3 -- to alkalinize the urine
NH4Cl -- to acidify the urine
ascorbic acid -- to acidify the urine
Dialysis -- works on non-protein bound toxins
Hemoperfusion -- good poisions that are
highly protein-bound
Classes of Antagonists:
Functional -- two chemicals have opposite
actions on the same system
Chemical -- one chemical neutralizes the
other
Dispositional -- one drug alters the excretion,
absorption, (etc..) of the other
Receptor -- one drug blocks the toxin at the
site of it’s action
Common Drug/toxin
Antidote
Anticholinergics
Physostigmine
-blockers
Glucagon
Benzodiazepines
Flumazenil
Ca2+ channel blockers
Calcium
Carbon monoxide
Oxygen
Cyanide
Nitrite & thiosulfate
Digitalis
specific Ab’s
Ethylene glycol
Ethanol
Isoniazid
Pyridoxine
Lead
EDTA
Methanol
Ethanol
Opioids
Naloxone
Organophosphates
or carbamates
Atropine & 2-PAM
TCAs
Bicarbonate
Amphetamines
Ascorbic acid
Iron
Deferoxamine
Nickel
Dithiocarbamate
Heavy Metals
Lead:
* only 10% of an ingested source is absorbed
whereas 90% of inhaled lead is absorbed
* t1/2 in soft tissue = 1-2 months; in bone it
is = 20-30 years!
* most common means of exposure is from
paint or water from lead pipes
Lead poisoning symptoms:
anorexia
GI pain -- relieved by calcium gluconate
wristdrop/muscle fatigue
lead encephalopathy
defective Heme synthesis
proteinuria
hematuria
‘lead lines’
* Pb inhibits -Aminolevulinate dehydratase
and Ferrochelatase
Diagnosing Pb poisoning:
* measure the accumulation of substrates
ALA -- in the urine
coproporphyrin -- in the urine
zinc protoprophyrin -- in the RBCs
* Average blood Pb = 5g/dL
* above 10g/dL poses risk of developmental
problems in children
* Adults below 30g/dL will have defective
heme synthesis, but show NO symptoms
Pb Chelators:
CaNa2 EDTA -- most often combined w/ BAL
BAL (dimercaprol)
D-penicillamine
Succimer
Mercury:
mercury vapor (elemental Hg)
mercury salts
organic mercurials -- methylmercury is the
most common and dangerous of these
Toxicities:
* Elemental Hg: relatively nontoxic when
ingested – stays in droplets; however, can
be readily absorbed by inhalation
* Inorganic Hg salts: are absorbed by the GI;
high concentrations in the kidneys
* Organic Hg: 90% absorbed from GI;
distributes more evenly throughout the
body, and will enter the CNS;
methylmercury will also cross the placenta!
* t1/2 of methylmercury is about 2 months
* only a blood level of 4g/ml is enough to
cause death!
Symptoms of Hg poisoning:
* Elemental Hg: tremors, dperession,
insomnia, shyness, irritability, and uncont-
rolled blushing
* Hg salts: ashen-gray oral mucosa, GI pain,
vomiting; after absorption the target organ
is the kidney
* Organic Hg: methylHg is a neurotoxicant;
at low doses—paresthesias, visual defects,
and ataxia
Diagnosis of Hg poisoning:
good history
quantify Hg amounts in: blood, urine & hair
* distribution of Hg between RBCs and
plasma indicates if the poisoning is due
to organic or inorganic mercurials
Treatment of Hg poisoning:
Elemental and Inorganic:
Immediately terminate exposure
(if possible), gastric lavage
Chelators are given for large exposures
Penicillamine is used for lower exposures
Organic Hg:
DO NOT use BAL - it increases the levels
of Hg in the brain!
Non-absorbable polythiol resins are used
to ehance the fecal excretion of CH3Hg
Arsenic:
Combines with lipoic acid and blocks Krebb’s
cycle
Initially distributes to the liver and kidney, but
because of its affinity for sulfhydryl groups
it collects in the skin, hair and nails
As will cross the placenta
Arsine is a toxic gas; produces different
effects than other As compounds
Toxic effects of As:
Increased capillary permeability
Gangrene in extremities
Capillary damage in the intestines; leads
to ‘rice water’ stools
Glomerular first, then tubular injury
More chronic exposure leads to hyperkeratosis
and hyperpigmentation
Peripheral neuropathy is common
Can cause squamous & basal cell Ca. as
well as lung cancer
* GI symptoms are first observed after acute
As poisoning: stomach pain, vomiting,
diarrhea—death usually occurs after 24 hrs
* Chronic signs are: Mee’s lines in the fingernails, garlic
breath, and aplastic anemia
As poisoning treatment:
Prevention of further exposure
Chelators (BAL, succimer, etc..)