Toxicology Table
Transcript of Toxicology Table
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Drug Toxidrome
Acetaminophen
Phase 1 (0-6 hrs): nausea/vomitingPhase 2 (4-24 hrs): clinically silent, LFTs, PT
rise
Phase 3 (18-72 hrs): toxic hepatitis, peaks in
2-3d in pts that recover; otherwise fulminant
liver failure
Phase 4: full recovery of liver function
Anticholinergics
(antimuscarinic)
Mydriasis, dry mouth, dry skin, tachycardia,
slows GI and GU tracts (urinary retention),altered mental status (staring, mumbling,
"picking" at clothes/sheets)
pts look like zombies
Antidepressants
- MAO inhibitors- Tricyclic
antidepressents
MAO inhibitors: HTN rxn with some foods
Tricyclic antidepressants:
- anticholinergic toxidrome + abnormal EKG
(due to Na channel blockade)
SSRIs, SNRIs: serotonin syndrome
- neuromuscular: myoclonus, rigidity
(legs>arms)
- autonomic: tachycardia, hyperthermia,
hyper/hypotension, diaphoresis
- altered mental status: agitation, sz, coma
Antipsychotics
Overdose effects:
- CNS depression, sz, decr BP
- QT prolongation
Adverse effects:
- movement disrder, distonia, parkinsonian-life
effects
neuroleptic malignant syndrome
- muscle rigidity, hyperthermia, autonomic
instability, altered MS/delirium, rhabdo
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Aspirin
Primary respiratory alkalosis
- stimulates brainsteam resp ctr --> breathe
fast
Primary anion gap metabolic acidosisTinnitus
Beta blockers Bradycardia and hypotension
Calcium channel
blockers
Bradycardia and hypotension
- hyperglycemia common
Carbon monoxide
Symptoms of hypoxia
"cherry red" discoloration: usually pre-terminal finding
Cholinesterase
inhibitors
- organophosphate/
carbamates
SLUDGE/DUMBBELS
- diaphoresis, urination, miosis, broncho
- produce a lot of fluid
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Cyanide
Turns off aerobic metabolism
- anion gap metabolic acidosis- elevated serum lactate
- coma: brain needs ATP
- hypotension
Digoxin
Ethanol andsedative-hypnotics
OpioidsMiosis, CNS depression, respiratory
depression
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Rattlesnake
envenomation
3 "flavors" of effects:
1) local tissue injury: progressive pain and
swelling, extends proximally up limb
2) hematologic: decr platelets, fibrinogen,
coagulopathy (incr PT/INR)
- looks like DIC3) Neurologic: paresthesias, metallic taste,
muscle twitching
- usually a minor issue in US snakes
Theophylline
Tachycardia, tremor, vomiting
Severe: seizures
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Toxicokinetics/dynamics Antidote
Activated by liver into toxic
metabolite
Small amount oxidized byCYP450 to N-acetyl-para-
benzoquinoneimine (NAPQI) -
very reactive, short half life
- results in centrilobular
hepatic necrosis
Toxicity occurs when
glutathione stores are depleted
N-acetylcysteine (NAC)
- repletes glutathione
- PO or IV, both are effective;
IV shorter time, but higher
incidence of anaphylactoid
rxns
Supprotive: IV fluid, sedation
Physostigmine: inhibits
AchE
- raises synaptic Ach levels
to overcome blockade
Serotonin syndrome: bzd,?cyproheptadine
alpha adrenergic block --> decr
BP
NMS:
?dantrolene, bromocriptin,
amantadine
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Overdose: 1st order
elimination --> zero order
- half life increases
- primarily renal elimination
1. GI decontamination
(activated charcoal)
2. Maintain urine output:
- IV fluid bolus + infusion
- urine alkalinization (ion
trapping with NaHCO3)
Severe cases: hemodialysis
Supportive, IV fluids,
atropine, vasopressors
glucagon: uses Gs/cAMP,
bypassing blocked beta
receptors
Hyperglycemia: need Ca to
release insulin vesicles
IV
fluids/atropine/vasopressors,Ca salts
both b-blocker and CCB
toxicity:
high dose insulin/ glucose,
mechanical adjuncts, IABP,
bypass
CO poisoning prevents O2
delivery
hyperbaric O2 (controversial)
atropine
- fixes muscarinic effects only
pralidoxime
- regenerates active AChE
- muscarinic and nicotinic
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CN- ion binds Fe3+ in iron-sulfur complex in mitochondria
Traditional antidote kit:
- Amyl nitrite perles (induce
methemoglobinemia)
- sodium nitrite IV
(induce methemoglobinemia)- sodium thiosulfate (helps
normal detox)
Hydroxocobalamin:
- provitamin B12a binds CN --
> Vit B12
Supportive: cardiac
monitoring, IV access,
atropine for bradycardia
digoxin immune Fab:
- ovine Fab antibody
fragments: digifab and
digibind
For benzodiazepines:
- flumazenil: BZD like
structure that competes for
GABAa Cl channel
- not used empiricallybecause it may precipitate
seizures/withdrawal
- primary indication:
iatrogenic toxicity (when
the physician overdoses the
pt)
Naloxone: IV/IM/ETT/neb
- short acting
Also naltrexone (PO),
nalmefene
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Antivenom: CroFab
- ovine produced immune fab
- very expensive!!
Other antivenoms: coralsnake, black widow (IgG
antivenom), bark scorpion
(arizona)
Supportive, charcoal
beta-blockers, hemodialysis
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Notes
Rumack Matthew Nomogram:predicts who is at risk of liver
toxicity
- serum APAP level and time
elapsed since ingestion
- derived from acute, single
ingestion
Common side effects of manymedications: antihistamines, psych
drugs (antidepressants,
antipsychotics), urinary
incontinence drugs
serotonin syndrome: more
common as a drug interation, but
can also occur in overdose
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smoke inhalation/fires, automobile
exhaust
CO binds heme 250x strongerthan O2
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Venomous snakes through
continental US; 6 in california, 3 in
OC
Rattlesnakes: Pit vipers - lens-shaped pupil, heat sensing pit
organ
nearly obsolete therapy for
asthma/COPD, closely related to
caffeine
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Drug Uses Toxidrome
Heavy metals
Lead
Batteries,
ammunition (bullets),
allyows, glass, paint,gasoline
Mutisystem toxic effects via multiple
mechanisms of action
Developing CNS more susceptible:
fetus/children at highest risk
>30ug/dl: neuro-cognitive
- irritability, fatigue, anorexia, sleep
disturbance, ataxia, tremor
>100ug/dl: encephalopathy
- ataxia, stupor, coma, seizure, death
- peripheral: wrist-drop
Hematotoxicity:
- increased RBC fragility
- basophilic stippling
Renal: (decr uric acid excretion) "saturnine
gout"
Reproductive toxicity
CV: HTN
GI: "Lead colic", gingival lead lines
toxic level: 10 ug/dL
Arsenic
Rare therapeutic use
as abx,
promyelocytic
leukemia
Semi-conductor
industry, wood
preservatives,
pesticides, lewisite(CW agent)
Rapid-onset gastroenteritis
Cardiopulmonary and hemotoxicity
Neuro effects: ascending sensory/motor
peripheral neuropathy, encephalopathy
Delay: Mees lines (transverse white nail
lines) indicated period of decr growth
Chronic:
constutional symptoms, anemia,neuropathy, skin lesions, skin/kidney/lung
cancer
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Mercury
dental amalgam,
fish/shellfish
3 flavors:
1) elemental: liquid =
least toxic, vapor iswell absorbed and
dangerous
2) salts: corrosive,
cause hemorrhagic
gastritis, ATN, renal
failure
3) organomercuries:
neurotoxicity
Erethism: neuropsychiatric effects
(shyness, social withdrawal, depression,
explosive anger, blushing)
Classic triad: tremore, neuropsychiatric
disturbance, gingivostomatitis
Acrodynia: painful extremity erythema,
mostly in children
Chelation
Dimercaprol 10% soln in peanutoil - IM injections
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Toxicokinetics/dynamics Antidote
Inhaled, absorbed in GI tract
(children absorb more than adults,
50% vs 10-15%)
- incr absorption with low dietary
calcium, iron deficiency, empty
stomach
Binds RBCs and distributed
throughout bodyClearance: blood/soft tissue (1-2
months), bone (yrs-decades)
Interferes with heme synthesis at
multiple steps: elevated
protoporphyrin levels can be
detected
Terminate further exposure
(determine source),
supportive care (hydration)
Chelation
Encephalopathy: treat
cerebral edema/seizures -
steroids/mannitol/
anticonvulsants- IV CaNaEDTA, IM
dimercaprol
Not encephalopathic:
- succimer: primary agent
(DMSA, chemet)
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Notes
Retained bullets in soft tissues are
generally benign
- may cause more damage to
remove bullet- joints near bone in CSF are more
commonly associated with lead
poisoning
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Avoid some fish inpregnant/lactating women
shark, swordfish, king mackerel,
tilefish