Toxicity

Drug effects

undesirable therapeutic

Non-deleterious Deleterious
(side effects) TOXIC

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Factors influencing patient response

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e.g. special safety considerations across the
lifespan (be aware of toxicity risks)
 Pregnancy & pharmacotherapy
• Altered GI fx maternal concentration & high Vd is drug
characteristic dependent:
• Delayed GI emptying
Smaller
• Drugs take longer to absorb
Lipophilic
• Decreased acidity Non-ionized
• Decreased acidity
• Higher blood volume (up by 50%)
• Higher HR = more distribution
• Higher GFR
• Decreased PPB
• High blood flow to uterus
• Most drugs cross into placenta & breastmilk
• Breastfeeding contraindications, e.g.: Ibuprofen, Opioids, …
Pediatric pharmacotherapy
(0-18 yrs of age)
• Calculated by body mass
• Per kg of body weight
• Note: remember pediatric blood volume (80 mL/kg of body weight)
• Adherence depends on the caregiver
• Education!
• Protect from poisoning (Adam’s text: pg. 58)
• Teens – curious about drugs
• Tx focus: menstrual cramps, sports injuries, skin problems
• Factual conversations
• Educate on STIs, recreational drug use, drug misuse (sharing?)
Renal dysfunction?

Pediatrics: neonates & young infants have lower renal function

Aging: renal function decreases with increasing age, causing 1%/year

decline in the elderly

Renal disease affects 2.2 million Canadians (2018 statistic)

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Older adult pharmacotherapy
• Decreased peristalsis, acidity, elimination, GFR
• Decreased liver fx
• Lower albumin (affects PPB)
• Decreased CO (affects distribution)
• Lower total body water due to lower muscle mass & alterations in metabolism
• Risk for dehydration (affects plasma volume; decreases GFR = toxicity risk)
• Communication !
• Adherence (understanding, cognitive ability to remember – underuse, misuse,
overuse,…)
• Polypharmacy
Most common toxicities
• ASA (Aspirin)
• Tylenol (Acetaminophen)

• Opioids
• Oxycodone, Fentanyl, Isotonitazene
• Benzodiazepines (sedative/hypnotic)
• Alcohol (ETOH)
• Cocaine
• Other e.g.
• Antidepressants
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Medication errors!
• Common nursing errors
• Dose!
• Crushing of enteric-coated tablets
• Crushing of sustained-release tablets

• Prevention:
• Check the 10 rights every time
• E.g. drug, patient, dose, route, time, reason, …

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Clinical procedure in toxicity (overdose)

Airway – patency!!!
Breathing – oxygenation & ventilation
Circulation – organ perfusion (CO, BP)

Disability – assess for dysfunction (VS, pupils, ECG,…) & treat as needed
• e.g. coma, seizures, cardiac arrhythmias

Exposure: identify the drug/substance; initiate treatment to decrease activity

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Stabilizing the patient
• ABC’s
• A&B: assess patency, effort, rate
• Obstruction?
• Oxygen supplement?
• ET tube insertion?
• C: assess perfusion quality
• IV fluids?
• Drugs?
• Other VS stabilization, e.g. temperature
• Monitoring
1. Identify drug/substance
Patient’s Health History; Lab results (urine, blood)

Physical assessment, S&S, using a clinical tool: ‘toxidromes’

• ASA Acetaminophen
• Confusion • Abdominal pain
• Tachycardia • Loss of appetite
• Tachypnea • Nausea/vomiting
• Hyperthermia • Diaphoresis
• Diaphoresis • Somnolence
• Vomiting

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Toxidromes cont.

• Opioids (Fentanyl, Codeine, • Cocaine (+ stimulants)

Morphine, Oxycodone, Heroin, • Agitation, tremors
Isotonitazene, ….) • Tachycardia
• Bradypnea/Apnea • Tachypnea
• Bradycardia • Hyperthermia
• Somnolence/Coma • Diaphoresis
• Pupils constricted • Pupils dilated

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Stabilizing patient: tx of cannabis toxicity
Cannabis toxicity
• Route of admin: inhalation, PO
• inhalation – higher overall potency
• LD50=route dependent • Lab:
• THC & CBD • urine toxicology (positive or negative)
• THC causes more CNS & VS instability • serum levels

• S&S: intensified
• sensory alterations
• acute psychosis • Tx: supportive
• seizures Tx of disabilities
• LOC changes (somnolence) e.g. seizures tx with benzodiazepines
• VS changes (tachycardia, hypotension) e.g. hypertension tx with antihypertensives
• respiratory depression e.g. respiratory depression tx with ET
• motor impairment e.g. psychosis tx with antipsychotics
 2. Treatment
clinical tool: Algorithms
utilize ADME

Adsorption

• ‘binding of drug, to decrease its

absorption’
• Activated charcoal
• Binds drug to surface carbons
• Enteral route of administration
• Eliminated via stool
• Dose: 0.5-2 g/kg (max. 100 g)

• e.g. Tylenol, ASA, Benzodiazepines

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 Induce metabolism
• e.g. Tx in Tylenol toxicity
• Tylenol toxicity depletes liver enzyme
• Glutathione
• Accumulation of phase I active
metabolite => hepatotoxicity

• Tx: NAC (n-acetylcysteine/acetylcysteine))

• is a Glutathione enzyme substance
• increases Glutathione liver enzyme
for Phase II metabolism of NAPB

• IV, PO
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Algorithm e.g:

• https://emedicine.medscape.com/article/820200-treatment
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637612/

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 Alcohol
• Liver metabolized by alcohol
dehydrogenase
• depletes Vitamin B
• CNS effects proportionate to drug
dose
• GABA binding (high affinity)
• Lowers Glutamate
• Inhibits ADH => diuresis
• dehydration
• Chronic use: tolerance
• GABA receptor #s increase,
requiring more & more alcohol to
create the same effect
• Tx: Metadoxine, IV
• Induces alcohol dehydrogenase fx
• IV fluids
Homework:
• Review the main functions of the liver
• Brainstorm what occurs to these functions when the liver is
compromised
Increase elimination

GI tract:
• activated charcoal
• intestinal elimination of charcoal-bound drug

Renal:
• alkalization to induce excretion
• Sodium Bicarbonate
• ionizes an acidic substance
• E.g. ASA
• IV dose: 100-150 mEq Sodium Bicarbonate
• Hemodialysis
• Active removal
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Antagonism
• Antagonism of a specific receptor = cessation of drug action
• E.g. Narcan (naloxone)
• Tx: opioids

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