Clinical Toxicology

about ___ of poisonings occur in adults

30%

almost ___ of poisonings occur in children < 6 y/o (40% in children < 3 y/o)

50%

where do most toxic exposures occur?

at the patient's own residence

do most patients require an ER visit?

no, most (75%) are managed on-site w/ assistance from a poison information center

what is the national poison control hotline number?

1-800-222-1222

in an overdose, the expected duration of action & AEs are much ______ than you would expect to see at therapeutic doses

longer

1 multiple choice option

will t/12 & duration of action information apply in a dramatic overdose situation where the body's ability to metabolize & excrete is profoundly overwhelmed?

no

1 multiple choice option

what will overwhelming the body w/ substance lead to?

- slowed & impaired oral absorption

- often hypoperfusion of organs (such as, liver & kidney)

- saturated metabolism & renal clearance

- alterations in protein binding, distribution patterns, etc

what is the general treatment of poisonings?

ABCDEFG

- airway

- breathing

- decontamination

- D.O.N.T

- enhanced elimination

- focused therapy (ex: antidotes)

- get toxicology help/support (contact poison control center)

decontamination for inhaled poison =

fresh air

decontamination for poison on skin =

remove clothing, wash w/ plain soap & shampoo hair

decontamination for poison in eye =

flush w/ 1L (each eye) of saline or water x 15 min

decontamination for swallowed poison =

give 2-4 oz water immediately

what is D.O.N.T?

sometimes considered initial drug therapy for toxic patient w/ altered mental status of unknown origin

- dextrose

- oxygen

- naloxone

- thiamine

dextrose 25-50 g IV

administer if hypoglycemic

oxygen @ 100%

administer if hypoxic

- useful for CO, hydrogen sulfide, & asphyxiants

naloxone 0.4-2 mg IV

administer if opioid toxicity suspected

- reverses opioids/heroin

- watch for immediate & intense withdrawal sx

thiamine 100 mg IV

administer if pt is severely malnourished

- prevents Wernicke's encephalopathy

how are poisonings diagnosed?

- H&P

- toxidrome recognition

- diagnostic tests

what treatments may we use for decontamination?

- syrup of ipecac

- gastric lavage

- activated charcoal

- whole bowel irrigation

which method is most commonly used for decontamination?

activated charcoal

what is the MOA of syrup of ipecac?

derived from ipecec root

- induces vomiting by locally irritating the gastric mucosa & by directly stimulating chemo-receptor trigger zone of CNS

is syrup of ipecac a reliable way to remove toxins from the stomach?

no, theoretically it would only be used for recent ingestions (<1 hr)

although years ago it was recommended that every household keep a bottle of syrup of ipecac for emergency use, is this still recommended?

NO

what are the possible complications of syrup of ipecac?

- aspiration

- persistent/uncontrollable vomiting

- lethargy

- may delay other txs (such as, activated charcoal, whole bowel irrigation, or oral antidotes)

when is syrup of ipecac contraindicated?

in ingestion of caustic material, hydrocarbons, seizures, or if unconscious

how may syrup of ipecac be misused?

in bulimia nervosa or for weight loss

_________________ is only recommended if life-threatening quantities of substances have been ingested & only if ingested w/i 1 hr of presentation to ER

gastric lavage

when doing gastric lavage, _________________ if patient is unconscious or lacks gag reflex

intubate first

what are possible complications of gastric lavage?

- aspiration

- laryngospasm

- perforation injury to esophagus & stomach

- electrolyte imbalance

what is the MOA of activated charcoal?

binds w/ substances in GI tract to prevent oral absorption

what is the preferred method of decontamination for most poisons?

activated charcoal

activated charcoal is most effective when administered ______ after the ingestion

early

what are the possible complications of activated charcoal?

- emesis

- aspiration

- constipation

- bowel obstruction

- perforation

what is ileus?

loss of peristalsis without structural obstruction resulting in intolerance of oral intake

when is activated charcoal contraindicated?

in pts w/ ileus

generally only the 1st dose of activated charcoal should contain ___________.

cathartics

- ex: sorbitol or magnesium citrate

what agent is used for whole-bowel irrigation?

polyethylene glycol electrolyte solution (GoLytely, Colyte)

there is limited efficacy for decontamination by whole-bowel irrigation. when is it the most useful?

- when ingestion occurred hours ago

- sustained release formulations

- lead

- iron

- lithium

- "body packers"

when is whole-bowel irrigation contraindicated?

- bowel obstruction

- bowel perforation

- GI bleeding

- ileus

what are the methods for enhancement of elimination?

- multiple doses of activated charcoal

- dialysis

- diuresis

when may multiple-doses of activated charcoal be helpful for enhancement of elimination?

for drugs that undergo enterohepatic recirculation

examples of drugs that undergo enterohepatic recirculation:

- theophylline

- phenobarbital

- carbamazepine

- diazepam

- digoxin

- TCAs (desipramine, nortriptyline, amitriptyline)

when multi-dose activated charcoal is used, only the _____ dose should contain a cathartic

1st

when may dialysis be helpful for enhancement of elimination?

- methanol

- ethylene glycol

- lithium

- salicylates

- ethanol

- theophylline

when may diuresis be helpful for enhancement of elimination?

for some renally cleared drugs

____________________ may help alkalinize the urine to enhance clearance of acidic poisons

sodium bicarbonate

mental status w/ sympathomimetic CNS stimulant OD:

- hyper alert

- agitation

- hallucinations

- paranoia

mental status w/ anticholinergic OD:

- hyper vigilance

- agitation

- hallucinations

- delirium w/ mumbling speech

- coma

mental status w/ hallucinogenic OD:

- hallucinations

- perceptual distortions

- depersonalization

- synesthesia

- agitation

mental status w/ opioid OD:

- CNS depression

- coma

mental status w/ sedative-hypnotic OD:

- CNS depression

- confusion

- stupor

- coma

mental status w/ cholinergic OD:

- confusion

- coma

mental status w/ serotonin syndrome:

- confusion

- agitation

- coma

vital signs w/ sympathomimetic CNS stimulant OD:

- hyperthermia

- tachycardia

- HTN

- widened pulse pressure

- tachypnea

- hyperpnea

vital signs w/ anticholinergic, hallucinogenic OD, or serotonin syndrome:

- hyperthermia

- tachycardia

- hypertension

- tachypnea

vital signs w/ opioid or sedative/hypnotic OD:

- hypothermia

- bradycardia

- hypotension

- apnea

- bradypnea

vital signs w/ cholinergic OD:

- bradycardia

- hypertension or hypotension

- tachypnea or bradypnea

other manifestations w/ sympathomimetic CNS stimulant OD:

- mydriasis

- diaphoresis

- tremors

- tremors

- hyperreflexia

- seizures

other manifestations w/ anticholinergic OD:

- mydriasis

- dry flushed skin

- unable to sweat

- dry mucous membranes

- decreased bowel sounds

- urinary retention

- myoclonus

- choreothetosis

- picking behavior

- seizures

TCAs may cause..

myrdriasis or miosis

other manifestations w/ hallucinogenic OD:

- mydriasis

- nystagmus

other manifestations w/ opioid OD:

- miosis

- hyporeflexia

- pulmonary edema

- needle marks

other manifestations w/ sedative/hypnotic OD:

- miosis

- hyporeflexia

other manifestations w/ cholinergic OD:

- miosis

- salivation

- urinary & fecal incontinence

- diarrhea

- emesis

- diaphoresis

- lacrimation

- GI cramps

- bronchoconstriction

- muscle fasiculations

- weakness

- seizures

other manifestations w/ serotonin syndrome OD:

- mydriasis

- tremor

- myoclonus

- hyperreflexia

- clonus

- diaphoresis

- flushing

- trismus

- rigidity

- diarrhea

examples of toxic sympathomimetic CNS stimulants:

- cocaine

- amphetamines

- bath salts

- pseudoephedrine

- ephedrine

- theophylline

- caffeine

- nicotine

examples of anticholinergics:

- antihistamines

- TCAs

- cyclobenzaprine & other SMRs

- antipsychotics

- anticholinergic PDs

- atropine

- antispasmodics

- phenothiazines

- scopolamine

- drugs to treat urinary incontinence

- belladonna alkaloids (jimson weed)

examples of hallucinogenics:

- phencyclidine

- LSD

- mesacaline

- psilocybin

- MDMA (ectasy)

- ketamine

examples of opioids:

- heroin

- morphine

- methadone

- oxycodone

- codeine

- hydromorphone

- diphenoxylate

examples of sedative-hypnotics:

- benzos

- barbiturates

- carisoprodol

- zolpidem

- anticonvulsants

- alcohol

examples of cholinergics:

- organophosphate & carbamate insecticides

- nerve gas

- nicotine

- pilocarpine

- physotigmine

- edrophonium

- bethanechol

- urecholine

- toxic mushrooms

examples of meds that may cause serotonin syndrome:

- MOA-Is

- SSRIs

- SNRIs

- TCAs

- meperidine

- dextromethorphan

- LSD

- MDMA (ectasy)

- ketamine

how is sympathomimetic CNS stimulant OD treated?

symptomatically (control agitation & other signs of sympathetic excess; maintain adequate fluid hydration)

- benzos (for agitation, & to treat/prevent seizures)

what can HTN unresponsive to benzos in sympathomimetic/CNS stimulant OD tx be treated w/?

phentolamine & nitroprusside

- BB should not be used w/o a vasodilator (or BP may worsen)

how is anticholinergic OD treated?

symptomatically (identify & dc drugs w/ anticholinergic SEs

- agitation/seizures = benzos

- do NOT give physotigmine unless directed by poison center

why is IV sodium bicarbonate helpful in tx of anticholinergic OD?

bc this type of OD may result in blockage of sodium channels & cardiac dysrhymias

what is physotigmine?

direct acting cholinergic agonist

how is hallucinogenic OD treated?

symptomatically

- obtain serum acetaminophen levels

tramadol toxicity may include:

seizures

methadone toxicity may include:

QT prolongation

how is opioid OD treated?

naloxone

what is naxloxone?

pure opioid antagonist w/ a fast onset of action (1-2 mins)

what is the initial dose of naloxone?

0.2-4 mg, depending on the situation & drug resource

- give q2-3 mins up to 10 mg

- if reversal does not occur after 10 mg, consider another diagnosis

if the patient is in cardiac arrest, ________ IV naloxone can be given

2-4 mg

the higher the dose of naloxone, the more likely __________________________ may occur

immediate withdrawal sx

naxloxone effects last about _________, shorter than most opioids

1-4 hrs

do NOT give __________ for sedative-hypnotic OD treatment

flumazenil

single substance overdoses of benzos are ______ fatal

rarely

- however, when mixed w/ other respiratory depressants (such as, opioids) they can be fatal

what is flumazenil (Romazicon)?

GABA blocker

does flumazenil reduce sedation or respiratory depression better?

sedation

1 multiple choice option

why is re-dosing often required w/ flumazenil?

bc it has a shorter t1/2 than most benzos

when is flumazenil contraindicated?

- hx of seizure disorders

- ingestion of seizuregenic agents (such as, TCAs & many others)

how is cholinergic OD treated?

- atropine (short t1/2, will require repeated, high dose or continuous infusion x several days to wks)

- pralidoxime (antidote; breaks bond between poison & AChE; most likely only effective if used w/i 36-72 hrs)

- benzos (diazepam; to treat/prevent seizures caused by excessive acetylcholine)

how is serotonin syndrome treated?

- benzos (for agitation & correct mild increases in BP & HR)

- cyproheptadine (antidote, if needed)

what is cyproheptadine?

antihistamine + serotonin blocker (specifically 5-HT1A & 5-HT2A)

- may result in sedation & hypotension

why should physostigmine NOT be given in tx of anticholinergic OD unless directed by the poison control center?

although it theoretically should reverse anticholinergic effects, it is assoc. w/ lowering seizure threshold

- thus, should NOT be routinely used

why should flumazenil NOT be used in tx of sedative-hyponotic OD?

only an antidote for benzos specifically

- is assoc. w/ lowering seizure threshold, thus should not be routinely used, esp. for single-substance benzo ODs

symptomatic/supportive care of hypotension:

- initially: IV fluids

- if ineffective: give IV vasopressor (norepi, phenylephrine, epi)

symptomatic/supportive care of hypertension:

- agitated patient: benzos

- shorter acting drugs perferred to accommodate changing status/vitals

- avoid monotherapy w/ a BB in cocaine & other sympathomimetic toxicity