toxicology table

7/30/2019 Toxicology Table

1/20

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


2/20

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


3/20

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


4/20

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


5/20

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


6/20

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


7/20

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


8/20

Antivenom: CroFab

- ovine produced immune fab

- very expensive!!

Other antivenoms: coralsnake, black widow (IgG

antivenom), bark scorpion

(arizona)

Supportive, charcoal

beta-blockers, hemodialysis


9/20

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


10/20

smoke inhalation/fires, automobile

exhaust

CO binds heme 250x strongerthan O2


11/20


12/20

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


13/20

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


14/20

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


15/20


16/20

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)


17/20


18/20


19/20

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


20/20

Avoid some fish inpregnant/lactating women

shark, swordfish, king mackerel,

tilefish

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