Clinical Toxicology Exam 2 Part 2: Geriatric Issues in Toxicology ; Forensic Toxicology for the Living and the Dead ; Toxicology of Aspirin and NSAIDs

Geriatric Issues in Toxicology

Dr. Swanson

_____% of all deaths and ______% of hospitalizations due to adverse effects that occur in the elderly.

Drug related problem are the _______ leading cause of death in those >65 YO.

____________ of hospital admissions for patients >75 years old linked to drug-related problems.

51% ; 39%

5th

One-third

Contributors to "America's Other Drug Problem"

*** America's Other Drug Problem is the fact that $38.8 billion is associated with DRPs resulting in long-term care admissions. ***

- _______________

- Consequences of _____________ _____________

- __________ __________

- ________________ changes of aging

- ________________ changes of aging

- Effects of _______________ on kinetics and dynamics

- Polypharmacy (Rx and OTC)

- drug-drug interactions

- Adherence issues

- Pharmacokinetics

- Pharmacodynamics

- co-morbidity

Impact of Polypharmacy

- Over ______ of prescription medications are taken by elderly (≥65 YO) and __________ of OTC medications consumed by older people.

- Between 1988 and 2010, the median number of prescription medications used by older people ________ from 2 to ___, and the proportion taking ≥5 medications ________ from 12.8% to _____.

- Approximately _____ of medications prescribed for older people are considered potentially inappropriate per AGS Beers Criteria.

- An estimated 30% of all medications for older people are considered __________.

- 30% ; 40-50%

- doubled ; 2 to 4 ; trilled from 12.8% to 39%

- 25%

- unnecessary

Inappropriate Medications:

Use of medications on the Beers List is associated with:

- Decreased __________ of ________

- Increased risk of _________________

- ______________ of hospitalizations

3 drug classes implicated in approximately 60% of ED visits for older adults (aged ≥65 YO) for adverse drug events:

- _________________

- ______________ agents

- ____________ ___________

===> Although medication justified based on treatment guidelines, inadequate monitoring linked to more side effects.

- quality of life

- hospitalizations

- Prolongation

- Anticoagulants

- Diabetes agents

- Opioid analgesics

Typically Physiologic Changes in Geriatric Patients That Lead to Altered Pharmacokinetics:

Body Composition:

- Diminished _______ _____

- Increased ________ tissue (aka __________ )

Nervous System:

- _________ reaction time

- Diminished _________ --> leads to rigidity, posture changes, and slowed movement

Renal:

- Reduced _______, ________ _________, and ________ _______

Cardiovascular:

- _________ vessel thickness and stiffness

- Reduced compensation to __________ ________

Gastrointestinal:

- Decreased __________ surface and cells

- Reduced ___________/_______ _______/ _________ ____________ (aka ____________ )

- Reduced _________ __________

Hepatic:

- Reduced ______

- ________ _______ (enzyme changes)

- Reduced ________ _______ (aka ______________ )

- muscle mass

- adipose tissue (distribution)

- Increased

- dopamine

- GFR, tubular function, and blood flow

- Increased

- impaired LVF

- absorptive surface and cells

- motility/blood flow/acid secretion (elimination)

- active transport

- size

- Cellular changes

- blood flow (metabolism)

Pharmacokinetic Changes in Aging - Absorption

- There are many age-related structural and physiological changes in the GI tract, yet there is _______ _______ ________ in absence of GI pathology.

- Decreased ____________ __________ with oral administration ( ex. morphine, isosorbide denitrate (Isordil))

- _________ _________ impacts absorption of some medications (ex. furosemide - Lasix)

- The effects on percutaneous, subcutaneous, and intramuscular absorption is largely unknown. However, expect delayed or incomplete absorption in states of ________ _____________.

- minimal clinical significance

- first-pass effect

- Heart failure

- poor perfusion

Pharmacokinetic Changes in Aging - Distribution (volume of distribution)

Altered Lean-to-fat Ratio:

- _______________

- _______________

- _______________

Decreased Total Body Water:

- _______________

Protein Concentration Changes:

- ________________

- ________________

- Digoxin (Lanoxin)

- Acetaminophen

- Alcohol

- Lithium

- Warfarin (Coumadin)

- Phenytoin (Dilantin)

Pharmacokinetic Changes in Aging - Metabolism (clearance)

- Liver size and blood flow decline with age which affects drugs with _______ ____________ metabolism

===> ___________ and ______________

- Some ____________ metabolic pathways diminish with age due to affects on CYP systems ( oxidation, reduction, and hydrolysis)

===> (________, _______, , __________and __________).

- ____________ ( conjugation) metabolic pathways is NOT diminished with age.

===> (________, _______, , __________and __________).

- high-flow dependent metabolism

===> propranolol (Inderal) and verapamil (Calan)

- Phase 1 ; diazepam, alprazolam, flurazepam , chlordiazepoxide (anxiety)

- Phase II ; lorazepam, oxazepam, triazolam (Halcion), temazepam (sleep)

Pharmacokinetic Changes in Aging - Elimination (clearance)

- Most individuals over age 50 lose ______ of _______ function per decade.

- MANY medications dependent on ________ elimination and ALWAYS consult labeling for dosing!

Using Crokroft-Gault equation for estimating CrCl in Elderly:

- ___________ true CrCl in older people who of NORMAL weight

- ___________ true CrCl in older people who are UNDER weight

- Caution when adjusting _________ _________ in the elderly

For eGFR use the __________ equation, yet the same concerns as Crockroft-Gault equation. _______________ is another equation derived estimate of GFR with age as a variable.

- 10% of renal function

- renal elimination

- Underestimate

- Overestimate

- antibiotic doses

MDRD equation ; CKD-EPI

Pharmacodynamic Changes of Aging:

- Alterations in __________ _________

- Alterations in _________ ________

- Enhanced or diminished ___________ ________

- Alterations in Sodium-Potassium ATPase and Calcium channels leads to enhanced toxicity of _________ and _____________

- Changes in homeostatic control mechanisms (baroreceptors) results in increased risk of ___________ ________ _______ from ________________

- Impaired glucose counter-regulation leads to increased risk of ___________ from ______________ agents

- receptor affinity

- receptor number

- post-receptor response

- digoxin and antiarrhythmics

- orthostatic BP changes from anti-hypertensives

- hypoglycemia from anti-diabetic agents

Pharmacodynamic Changes of Aging - Central Nervous System Sensitivity

- ___________ receptor response

- Reduced CNS dopamine ===> increased ____________ ____________

- Reduced serotonin receptor function ===> enhanced sensitivity to _______________

- Altered GABA-benzodiazpeine receptor function ===> increased sensitivity to ____________, __________, __________

- Enhanced

- extrapyramidal symptoms (EPS)

- antidepressants

- benzodiazepines, alcohol, barbiturates

Pharmacodynamic Changes of Aging - Reduced CNS Acetylcholine

- __________ anti-cholinergic drug side effects including: _______, confusion, __________, delirium, ________ _________, __________, and _______ _______ decline (especially in the very old or those with dementia).

- REMEMBER that anticholinergic drugs have ___________ function

Long-term use of anticholingeric drugs results in:

- Increases the risk of dementia up to ______________

- Increases ___________ risk

- Increases __________

- Enhanced ; sedation ; psychosis ; urinary retention ; constipation ; cognitive function decline

- additive function

- 1.5 fold

- hospitalization risk

- mortality

Increased Risk for Pharmacodynamic Response in Older Individuals:

Increased QT-Prolongation:

- Citalopram doses > _________

- Escitalopram doses > __________

Increased Risk of Sudden Death and Stroke:

- ALL ______________ used in elderly patients with dementia

- > 20 mg

- > 10 mg

- anti-psychotics

What is are Prescribing Cascades?

The concept of prescribing a new (chronic) drug to treat symptoms arising from an unrecognized adverse effect. Essentially adding on more and more drugs.

What are 5 factors increasing the risk of Prescribing Cascades?

- Increased age

- Multiple co-morbid conditions

- Multiple drug therapies

- Multiple prescribers

- Patient and caregiver expectations

Management Considerations to Minimize Drug Related Problems:

- Minimize number of _________, attempt _______ ______ _______, and __________ when appropriate

- Maximize _______________ _______________

- _______ therapy to the individual patient and goals of care. Remember that patients are NOT always consistent with guidelines and drugs DO NOT have doses but people do!

- Closely monitor narrow therapeutic index drugs ( _______, _______, ________, and all active ______ drugs, etc.)

- Educate the patient and caregiver

- Review all medications ______________

- Improve ________________ between practitioners, caregivers, and consumers

- Use a ________ __________ for all medication needs and utilize the pharmacist to help manage medications and costs

- Use EXTRA caution during __________ _________ ________ facilities and providers ( __________ )

- Apply __________ _______ principles at end of life (i.e. deprescribing stati

- medications ; gradual dose reduction ; deprescribing

- non-pharmacologic alternatives

- Titrate

- warfarin, insulin, digoxin ; CNS

- annually

- communications

- single pharmacy

- transitions between care (reconciliation)

- palliative care

Forensic Toxicology for the Living and the Dead

Dr. Kemp

Define Forensic Toxicology

The study of the harmful effects of chemicals on living organisms and its application to the law

Human Performance Toxicology:

Behavioral Toxicology:

- Study of human ___________ __________ under the influence of drugs

- Combination of ________, ___________, and __________

- Analyzes the effects of legal and illegal drugs on ______ _________, _________, and _________ (uses 'real life' tests and lab based psychomotor tests)

This form of toxicology established criteria for recognizing effects:

- Predicting/interpreting ___________

- ________ ________ ________

- Drug ____________ __________

The most widely studied drugs are ________ and ____________.

However, potential problems include ________ and _________ issues.

- human psychomotor performance

- psychology, pharmacology, and toxicology

- skills acquisition, learning, and performance

- behaviors

- Field Sobriety Tetss

- Drug Recognition Experts

ethanol and marijuana

assumptions and validity issues

Forensic Drug Testing varies depending on location:

Military:

- "Drug Free Workplace" policy: if you use illegal substances, then you _______ - _______ from service and referred for treatment

Criminal/Civil Justice System:

- _______ population monitoring, _________, __________

- _______/________, Custody, Compliance with court judgements

Private Sector:

- "______ ______ _________" policy

- ___________ screening, __________ testing, __________

- Professional/Amateur _______ or __________

- __________ _______ _______ for patient compliance

Review Slide 8

- lose - barred

- Prison, probation, parole

- DUI/DUID

- "Drug Free Workplace"

- Pre-employment ; For-cause ; Accidents

- sports or Olympics

- Therapeutic Drug Monitoring

Postmortem Toxicology is the ______ form of toxicology. It involves analysis of postmortem ______ and _________, and interpretation of results in context of case to aid in _________ of ______________ or _________ of _______.

Exceptionally complex:

- ________ of drugs or “poisons” and ________ present

- ________ and _________ of specimens

- Complexity of analysis – ___________

- Interpretation of postmortem anatomy/physiology

- Black box of questions – Don’t know what you don’t know

oldest ; fluids and tissues ; determination of contribution or cause of death

- Diversity ; quantity

- Quality and quantity

- extractions

At the Medical Examiner's Office, the pathologist assimilates investigative, pathology, and toxicology information. They provide the medical opinion on two key questions:

- ____________________: natural disease, injuries, drugs/poisons (presence of ; lack of presence)

- ____________________: natural, accident, suicide, homicide, unknown/undetermined

- Cause of Death (COD)

- Manner of Death (MOD)

In Postmortem Toxicology, it is important to remember case diversity:

- _______ ___________/____________

- _____________: Behavior/Impairment

- _____________

- _____________: impairment/medical misadvantages

- ______________: compliance

- Drug intoxication/overdose

- Homicide

- Suicide

- Accident

- Natural

Toxicology: Living Assumptions

The first thing to do is assess the "normal" ADME and if any complications are present:

- _________ __________

- _____________

- Injury: ________ _________ or a ________ in ____________

- Medical Conditions

- Illness

- therapeutic intervention or delay in treatment

Toxicology: Deceased Assumptions

Postmortem ADME: ____ out of 4 can still occur postmortem

- Absorption: _________ ___________

- Distribution: Postmortem ______________

- Metabolism: __________ and ______________

- Excretion: not so much because bladder/bowel evacuation

In postmortem forensic toxicological practices, ___________ is by far the most important and least controlled phenomenon.

3

- Incomplete Distribution

- Redistribution

- Endogenous and Microbial

redistribution

Post-mortem Redistribution is drug movement within the body after death and prior to autopsy.

Influenced by:

- Drug chemistry = _____, _____________, and ________/_________

- Drug PK = _______, _______ ________, ______, and storage deposits

- Distribution Mechanism:

===> Acidification, ________, Blood __________/________

===> PM _________, ______________

This results in artificial __________ of drug concentration in ______ ________ blood specimens.

- pKA, lipophilicity, and size/structure

- transport, protein binding, Vd

===> diffusion ; coagulation/hypostasis

===> circulation and putrefaction

elevation ; centrally collected

Toxicology Specimens:

Antemortem:

- Blood/serum, _______, ______ fluid, _________, __________, ________, and _________

Post-mortem:

- "Blood" from multiple sites ( _______ and __________ )

- _______ ________, urine, _______, ______, and gastric contents

- Others: _______, _______, ________, ________, ______ ______, hair, nails, and ________

- urine, oral fluid, breath, sweat, hair, and nails

- central and peripheral

- Vitreous humor ; liver, brain

- bile, lung, kidney, spleen, skeletal muscle ; bone

True or False

Urine is the specimen of choice for detecting, quantifying, and interpreting drug concentrations.

False ; Blood is the specimen of choice because it gives concentration estimate of the drug and/or metabolites at the site of action.

Drugs may be detected in other specimen types (urine, tissues), but they lack the interpretive value of blood.

In postmortem toxicology, ___________ blood is the preferred blood specimen, because it is the most resistant to postmortem _____________.

femoral blood ; redistribution

Testing Approach within Toxicology

Testing between the living and deceased is largely the same.

- ________ instrumentation

- ________ extractions

- ________ clean-up of specimens

Screening vs. Confirmation

Screening:

- ________ results

- _______ ________ if drugs or drug classes

- May not provide information on ________________ and does not provide ___________

- ______________

Confirmation:

- Greater __________ and __________

- Verifies ________ and __________ specific drug/metabolite

- More expensive than the screening test

- ____________ coupled with ________ _________ (GC/MS or LC/MS)

- Same

- Different

- Different

- Rapid

- Preliminary identification

- specific drug ; amount

- Immunoassay

- sensitivity and specificity

- identify and quantities

- Chromatography + mass spectrometry

Screening with Immunoassay:

- If NEGATIVE, this means NO drug is present

What are alternate considerations?

- Test is NOT sensitive to a specific drug

- Drug levels not high enough to be reported

- Drug not used in recent past

- Sample artificially diluted

- Substances present that interfere with test

Screening with Immunoassay:

- If POSITIVE, this means drug or drug metabolite is present

What are alternate considerations?

A positive result may be due to poor specificity (false positives), such as:

- Interferences: many cross-reacting substances

- Pseudoephedrine/Ephedrine with Methamphetamine

- Dextromethorphan with PCP

It is important to check package inset and check with the lab.

_____ ___________ ( Identifier: __________ ___________ ) and _____ _____________ ( Identifier: _______ _____________ ) is the gold standard for confirmation of the drug.

Gas Chromotagraphy ( Retention Time ) and Mass Spectrum ( Ion "fingerprint" )

Interpretation of Toxicology Testing:

Antemortem:

- Generally, what you see is what you get (e.g. blood or serum concentration ~ observation)

- REMEMBER: this concentration is a _____ _____ in time and _______ is a real thing

Postmortem:

- More convoluted due to post-mortem factors and decomposition

- _______ is a central figure for putting boundaries on interpretation (

===> When was decedent discovered? Last known alive? Observations from that time?

===> How long was the postmortem interval? Sample storage time till analysis?

===> How long does the drug stay in the body (half-life)? Drug stability?

===> How long has the decedent been using the drug (tolerance)?

===> How long was the exposure (route of administration, acute vs. chronic)?

- single point ; tolerance

- TIME

What are the Top 10 Drugs listed in Cause of Death from 2019 - 2023?

- Alprazolam

- Cocaine

- Ethanol

- Fentanyl

- Heroin

- Hydrocodone

- Methamphetamine

- Oxycodone

- Methadone*

- Morphine*

*Gabapentin and Diphenhydramine

Toxicology of Aspirin and NSAIDs

Dr. Edelen

Review Patient Case Throughout the Lecture

Review

What are some products in which aspirin or a derivative of aspirin is commonly found?

- Genuine aspirin

- Chalk flavored products like Pesto Bismol

- Peppermint flavored products like IcyHot or Bengay

- Acetaminophen flavored like Excedrin

- The Plop, Plop, Fizz, Fizz flavored like Aka-Seltzers

- The Wintergreen Flavored like Wintergreen Oil

- Compound W Wart Remover

- Sunscreen

- Acne Products containing salicylic acid

Conversion Factors for Non-aspirin salicylate to Aspirin:

- Methyl Salicylate: mg x ________

- Bismuth Subsalicylate: mg x ________

- Homosalate: mg x _____________

- Octisalate: mg x _________

- 1.39

- 0.5

- 0.7154

- 0.7303

Oil of Wintergreen

- Commercial topical presentations are not less than 98% w/w methyl salicylate.

- One milliliter of 98% methyl salicylate is approximately equivalent to ________ __________ (1,362 mg) ASA in salicylate potency.

- __________________ of Oil of Wintergreen is 6,811 mg of ASA.

- 1.4 grams ASA

- One teaspoonful (5 mL)

Criteria for Medical Evaluation:

- Ingestions of _______ mg/kg or _______ g of aspirin

- Ingestion of greater than a _____ or a ______ of oil wintergreen (98% methyl salicylate) by children younger than 6 years of age

- Ingestion of more than _______ of oil of wintergreen by patients 6 years of age and older

- Patients with significant ________ _________ and signs of toxicity

- 150 mg/kg or 6.5 g

- a lick or a taste

- 4 mL

- topical exposures

Explain the pharmacokinetics of aspirin

Aspirin is a weak acid, so at stomach acid, aspirin is non-ionized and rapidly absorbed. At blood pH (7.4), aspirin becomes ionized and stuck in the blood.

Salicylate Toxicokinetics:

Substantially longer half-lives at toxic concentrations:

- 2 to 4 hours at therapeutic concentrations

- __________ at toxic concentrations

Dosage form influences the absorption rate

- ______________________ may not peak until 4-6 hours post ingestion and in overdose, peak may not be reaches until _______ post ingestion

Delayed absorption of aspirin from pharmacobezoar formation, so consider _______ with _________________.

- 20 hours

- Enteric coated ; 24 hours

whole bowel irrigation with GoLytely

Mechanism of Toxicity of Salicylates:

- Toxic Effect = ________ ________ _______ __________

1. Interference with the ______ ______

2. Uncoupling of __________ __________

- ________ and other organic acids accumulate and produce an ________ _______ ______ ____________ _________ which has a direct effect to stimulate the ________ center in the brain

Salicylate toxicity has a mixed acid-base disturbances with both _____________ and _____________. The actual blood pH reflects whichever process is dominant in the patient at the time.

Much attention is paid to the _________ because it can make the problem worse. This is because more _______ _________ of salicylates occurs in the _________ patient, putting the organ at a even greater energy deficit.

- impairs cellular energy production

1. Krebs cycle

2. oxidative phosphorylation

- Lactate ; elevated anion gap metabolic acidosis ; respiratory

respiratory alkalosis and metabolic acidosis

acidosis ; CNS penetration ; acidotic

Signs and Symptoms of Salicylate Poisoning:

- _________ is the earliest sign and can see at therapeutic levels

- Nausea and vomiting

- __________ and _____________

- Fever, diaphoresis, dehydration

- ______________ ________________ ( _________ )

- Confusion, lethargy, coma

- Hypokalemia

- ________________________

- Acid-base disturbance

- A primary ________ _________ predominates initially

- An _______ _______ ________ ________ begins to develop early in the course

- Tinnitus

- Tachypnea and Hyperpnea (Kussmaul-type breathing)

- Pulmonary edema (ARDS)

- Neuroglycopenia

- respiratory alkalosis

- anion gap metabolic acidosis

Initial Evaluation of Patient in Salicylate Poisoning:

- IMPORTANT: thorough assessment of the ____________ ______ and ________ (Subtle tachypnea or hyperpnea should not be overlooked because if missed, delays may occur in the initiation of appropriate laboratory analysis and management.)

- __________ ________ upon presentation [ DO NOT WAIT] and repeat every __________ until _____ declining levels are seen

- __________ or ________ for pH, pCO2, and HCO3

- respiratory rate and depth

- Salicylate level ; 2-4 hours ; two

- ABGs or VBGs

Management of Salicylate Toxicity:

- ________ _________

- If the patient is intubated, consider setting at a ________ _______ _______ on the vent and ___________ patient. This helps with compensation for the _________ _________.

- There is NO antidote for salicylate toxicity.

The primary toxicity of salicylate is on the _______ and the amount of salicylate in the brain is a function of _____, so ________ enhances penetration of the drug to this location. Stive to create concentration gradients and pH conditions that:

- ______ _______ of salicylate from the _______ and other tissues

- Enhance ________ __________

- Activated charcoal

- higher tidal volume ; hyperventilate ; metabolic acidosis

CNS ; pH ; acidemia

- Favor exit ; CNS

- renal elimination

Treatment of Salicylate Toxicity:

If ASA concentration is > 25 mg/dL, begin ________ __________

- ________ mEq of ________ ________ to 1 L of ____________ + _____ mEq of ___________

If ASA concentration > 75 mg/dL or any neurological deficit

- Begin ____________

Neuroglycopenia:

- ____________ ____________

urinary alkalization

- 100 mEq of sodium bicarbonate to 1 L of D5 1/4NS + 40 mEq of potassion

- dialysis

- Supplement glucose

Explain the 5, 4, 3, 2, 1 idea

5- use D5W

4- 40 mEq of potassium

3- 3 ampules of bicarbonate

2- 2x maintenance IV fluids should be used

1- all in 1 bag

True or False

Excessive IV fluids should be avoided in salicylate toxicity because mechanical stress of prolonged and severe hyperventilation is a significant contributing factor.

True

Explain the pharmacokinetics of aspirin AFTER urinary alkalization

Alkalinized urine greater than 7.4 causes aspirin to be ionized in urine and will be excreted more quickly.

Urinary Alkaliniation transforms _______ ________ drugs to __________ form. Drug is toxic because it cannot transverse biological membranes (aka _____ ________).

Indications: toxicity with....

- ____________

- ____________

- ____________

Method: _________ __________ 1-2 mEq/kg IV, then initiate IV infusion @ 100-150 mL/hr titrating urine pH ___________. Don't forget to add ______________.

weakly acidic drug to ionized form ; ion trapping

- Salicylate

- Barbiturate

- Methotrextate

Sodium bicarbonate ; pH > 7.5 ; potassium

NSAIDs:

MOA:

- Inhibit __________ to prevent the formation of ___________ from __________ _______

- Do NOT _____________ inhibit

- Some agents have higher affinity or elect only for COX-2

Pharmacokinetics:

- Most NSAIDs have extensive _______ ________ (95-99%) and small volumes of _________ of approximately 0.1 to 0.2 L/kg

- _________ absorption of most NSAIDs occurs rapidly and near completely, resulting in bioavailabilities above 80%.

- The plasma elimination half-life in therapeutic dosing varies from as short as 1 to 2 hours for diclofenac and ibuprofen to 50 to 60 hours foroxaprozin and piroxicam.

- cyclooxyrgenase ; prostaglandin from arachidonic acid

- irreversibly

- protein binding ; distribution

- Oral

Toxic Effects of NSAIDs

1. ________ _________

- Most common ADE from NSAID use

- Inhibit prostaglanings responsible for maintaining GI integrity

- Have a ________ __________ or _________ ___________ effect

- Increases the risk of _______ and _________ _________, _______________, and ________________

1. Gastrointestinal (GI) Toxicity

- direct cytotoxic or local irritation effect

- gastric, duodenal ulcers, performations, and hemorrhage

How does Acute Kidney Injury (AKI) occur with NSAIDs?

decreased renal production of prostaglandins leads to vasoconstriction and resultant ischemia

Management of Ibuprofen Overdose:

- Inadvertent ingestions of __________ mg/kg can be observed at HOME due to main symptoms of GI upset, nausea and vomiting

- Metabolic acidosis at _______ mg/kg

- Seizures, coma, death at __________ mg/kg (for a 70 kg adult, would need to ingest 210 of the 200 mg tabs or 53 of the 800 mg tablets)

- <200 mg/kg

- 400 mg/kg

- 600 mg/kg

Management of Ibuprofen Overdose:

- Management is largely _________

- Patients who ingest greater than _______ mg/kg are at high risk for toxicity and require medical evaluation

- GI decontamination with ________ ________ for asymptomatic patients with the potential for large ingestion

- ________ ______ should be corrected and _______ ________ administered for life-threatening metabolic acidosis

- Hypotension should be treated initially with __________ therapy followed by direct-acting ________ if necessary

- supportive

- 400 mg/kg

- activated charcoal

- electrolyte imbalances ; sodium bicarbonate

- IV fluids ; vasopressors

True/False

Checking APAP levels in NSAID overdose is NOT necessary

False ; it is necessary due to co-ingestant risk with subtle/no presenting symptoms because APAP toxicity delayed for first 4 hours