TOXIDROMES

Patricia Evans, M.D.Georgetown University-

Providence Hospital Family Practice Residency

Searching for Clues

HISTORYWhen to suspectApproach to known exposureApproach to unknown exposure

PHYSICAL EXAMINATIONVSEye examSkinNeuro

LABORATORY EXAMAnion gap, acid-base status, osmolar gapBUN/creat, UAECGAbd filmCXRToxicology screen

APPROACH TO TREATMENT

Early and effective decontaminationSupportive therapyAntidotesEnhanced elimination

TOXIC SYNDROMES AND DRUG OVERDOSAGES

Physiologic stimulantsPhysiologic depressantsOther drug overdosages

PHYSIOLOGIC STIMULANTSAnticholinergicsSympathomimetics (ex. cocaine)HallucinogensDrug withdrawalMiscellaneous (thyroid hormones)

ANTICHOLINERGICSANTIHISTAMINESANTIPSYCHOTICSBELLADONNA ALKALOIDSCYCLIC ANTIDEPRESSANTCYCLOBENZAPRINE

PARKINSON’S DZ DRUGSGI/GU ANTISPASMODICSMYDRIATRICSPLANTS/ MUSHROOMS

ANTICHOLINERGICS: ATROPINE

CLINICAL PRESENTATION

“Hot as a hare, dry as a bone, mad as a hatter”Dryness of mouthflushed, hot, dry skindilated and nonreactive pupilstachycardiahallucinations, restlessness

ANTICHOLINERGIC: ATROPINE

TREATMENTGut decontaminationPhysostigmineSupportive care

COCAINECLINICAL PRESENTATION

tachycardia, HTN arrhythmiacan get hypotension and reflex bradycardiaCNS stimulation

COCAINETREATMENT

CNS sedationLabetololTreat hyperthermia?Parlodel or desipramine

HallucinogensStimulation of serotoninergic systemIllusions, visual hallucinations, sweating, tachycardia, pupillary dilatationUsu done in 12 hoursNo true withdrawal state

HallucinogensTreatment

Generally do not require medical treatmentCan use benzodiazepine for agitationReduce stimuliDiscontinuation can result in dysphoria from reduced serotonin activity. SSRI can be used for 3-6 months

PHYSIOLOGIC DEPRESSANTS

CholinergicsNarcoticsSymphatholytics (cyclic antidepressants)Sedative-hypnoticsMiscellaneous (carbon monoxide)

CHOLINERGICSBETHANACOLCARBAMATE INSECTICIDESMYASTHENIA GRAVIS DRUGSEDROPHONIUMPHYSOSTIGMINE

PILOCARPINENICOTINE

CHOLINERGICS: CLINICAL PRESENTATION

DEFECATIONURINATIONMIOSISBRONCHO- CONSTRICTIONBRADYCARDIAEMESISLACRIMATIONSALIVATION

CHOLINERGICSTREATMENT

Gastric decontaminationRespiratory supportAtropinePralidoximeCardiac monitoringTx seizures with benzodiazipine

OPIATESCLINICAL PRESENTATION

Pinpoint pupilsRespiratory depressionBradycardiaHypotensionHypothermiaPulmonary edemaSeizures

OPIATESTREATMENT

AcuteNaloxone

ChronicMethadoneCatapresNaltrexone

OPIATESPOSSIBLE COMPLICATIONS

AspirationPulmonary edemaWithdrawal symptomsNeed for repeated doses

BENZODIAZIPINESCLINICAL PRESENTATIONRespiratory depressionDrowsinessComa

BENZODIAZIPINESTREATMENT

Generally requires no pharmacologic interventionFlumazenil

CYCLIC ANTIDEPRESSANTSCLINICAL PRESENTATION

Most are combination anticholinergic and sympatholyticComaSeizuresHypotensionCardiac dysrhythmias

CYCLIC ANTIDEPRESSANTSTREATMENT

Gastric decontaminationTreat cardiac dysrhythmiasTreat seizures

Carbon Monoxide Poisoning

Most common cause of death by poisoningSymptoms vary:

Mild: HA, mild dyspneaMod: HA, dizziness, N/V,dyspnea, irritabilitySevere: Coma, seizures, CV collapse

Carbon Monoxide Poisoning

Most common cause of death by poisoningSymptoms vary:

Mild: HA, mild dyspneaMod: HA, dizziness, N/V, dyspnea, irritabilitySevere: Coma, seizures, CV collapse

OTHER DRUGSDISSOCIATIVE DRUGSACETOMINOPHENSALICYLATESDIGOXIN

SEROTONIN SYNDROMELITHIUM“CLUB DRUGS”

DISSOCIATIVE DRUGSKetamine, Phenycyclidine (PCP), Phenylcyclohexylpyrolidine (PHP)Acts on all six neurotransmitter systems

Anticholinergic: dry skin, miosisDopamine/norepinephrine:agitation, delusionsOpioid:pain perception alterationsSerotonin: perceptual changesGABA receptor inhibition: excitation

DISSOCIATIVE DRUGSTreatment

HaloperidolPresynaptic dopamine antagonistShifts the dopamine-acetylcholine activity ratio in the limbic systemTherefore can counteract the dopamine stimulation and cholinergic antagonism of the drug

ACETAMINOPHENCLINICAL PRESENTATION

No specific symptoms or signs

ACETAMINOPHENTREATMENT

Gastric decontaminationN-acetylcysteine

SALICYLATESCLINICAL PRESENTATION

Mixed acid-base disturbancesGI: N/V, abdominal painCNS: tinnitus, lethargy seizures, cerebral edema, irritabilityResp: pulmonary edemaCoagulation abnormalities

DIGOXINCLINICAL PRESENTATION

Nausea/vomitingMental status changesCardiovascular symptoms

DIGOXINTREATMENT

Gastric decontaminationFab fragments

SEROTONIN SYNDROMECLINICAL PRESENTATION

Neurobehavioral: mental status changes, agitation, confusion, seizuresAutonomic: hyperthermia, diaphoresis, diarrhea, tachycardia, HTN, salivationNeuromuscular: myoclonus, hyperreflexia, tremor, muscle rigidity

SEROTONIN SYNDROMETREATMENT

Respiratory supportTemperature controlSedativesMuscle relaxants

LITHIUMSymptoms

GI: vomiting, diarrheaNeuro: tremors, confusion, dysarthria, vertigo, choreoathetosis, ataxia, hyperreflexia, seizures, opisthotonis, and comaLabs: decreased anion gap

TreatmentLevels >2.5 meq/LGastric lavageUrinary alkalinization

Not very effective

AminophyllineHemodialysis

>3.5 mEq/L (acute)>2.5 w/ chronic ingestion or renal insufficiency

“CLUB DRUGS”Rave parties increasing in popularityDrugs meant to intensify sensory experience of lights/music, facilitate prolonged dancing

MDMA “Ectasy”Structurally resembles amphetamine (stimulant) and mescaline (hallucinogen)SX: trismus, bruxism, tachycardia, mydriasis, diaphoresis, hyperthermia, hyponatremia, hepatic failure, CV toxicity (tachycardia, HTN)

TreatmentMainly supportiveBenzodiazepinesCalm environmentAvoid beta-blockers

Can result in unopposed alpha effectIf essential consider labetolol

GHB: Date rape drug “Georgia homeboy, liquid ectasy, or

grievous bodily harm”

Developed as anesthetic agent. GABA analogSymptoms

BradycardiaHypothermia hypoventilationSomnolenceVomitingMyoclonic jerking

TreatmentConservative mgmtIntubationCareful exam for sexual assault

Ketamine: “K”, “special K”Developed as an anesthetic, structurally resemble PCPSymptoms

NystagmusTachycardiaHTNvomiting

TreatmentBenzodiazepinesSupportive careIVCan consider urine alkalinization

CLINICAL SCENARIO 1A 48 year old unconscious woman is brought to the hospital. She is convulsing and has an odor of garlic on her breath. She is incontinent for urine and stool. On exam her VS: T99, HR50, RR24, BP146/88. Skin is diaphoretic. She is drooling. Pupils are constricted. Lungs diffuse wheezing.

CLINICAL SCENARIO 1Recognize: Cholinergic poisoningTreatment:

Gastric decomtaminationRespiratory supportCardiac monitoring Atropine followed by pralidoxime Treat seizures with benzodiazepine

CLINICAL SCENARIO 217 year old male presents to the hospital with somnolence, slurred speech, and combative behavior. His younger sister said he showed her a handful of small seeds that he was going to take. On exam his VS: T100, HR120, BP100/60, RR22. Skin is warm and dry. Mucous membranes are dry. Pupils are dilated and not reactive.

CLINICAL SCENARIO 2Recognize: Anticholinergic poisoningTreatment

Supportive carePhysostigmine

Coma

Arrythmias

Severe HTN

Seizures

CLINICAL SCENARIO 326 y/o male presents unresponsive. His friend accompanies him and states he took a handful of pills because he was in pain. On exam his VS: T96, HR40, RR6, BP50/30. Pupils are 3mm.

CLINICAL SCENARIO 3Recognize: Opioid poisoningTreatment

Naloxone

SummaryDon’t panic!!Recognize your cluesLook for the toxidrome syndrome