Drug Toxicity and Patient Response

Toxicity Overview

• Toxicity is an important aspect of drug effects to consider
• Assessing the body's response to a drug involves evaluating its Clinical factors, Administration method, Pharmacokinetics, and Pharmacodynamics
• Undesirable drug effects are classified as non-deleterious (side effects) or deleterious (toxic) with the therapeutic index providing important information
• Multiple factors influence a patient's response to a drug
• Side effects and toxicity cause responses like nausea
• Consider patient history when assessing toxicity levels

Factors Influencing Patient Response

• Dosage should be calculated per weight for pediatric patients (0-18 years)
• Side effects can be an indicator of toxicity, with nausea being a common after its effects
• Health history is relevant, along with the dose information, assessing the amount of drug taken
• Alterations to the blood-brain barrier (BBB) require dosage adjustments to prevent the drug from entering the central nervous system (CNS)
• Neonates' kidneys don't function fully until age 2 with their organ function still maturation until age 20

Genetic and Lifespan Considerations

• Genetic differences affect Absorption, Distribution, Metabolism, and Excretion (ADME), influencing drug response based on gender, ethnicity, and race
• Liver enzyme polymorphisms influences toxicity, like reduced CYP2D6 enzyme activity elevates toxicity risk
• Special safety considerations that account for lifespan stages are important, especially considering toxicity risks

Pregnancy & Pharmacotherapy

• Altered GI function during pregnancy delays gastric emptying and drug absorption and decreased acidity
• Increase in patients blood volume impacts a drugs effectiveness
• Higher blood volume dilutes drugs, and higher GFR increases elimination
• Most drugs are likely going to enter the placenta and breastmilk
• High Vd drugs show particular A&D characteristics
• Breastfeeding contraindications apply to drugs like Ibuprofen and Opioids

Pediatric Pharmacotherapy

• Dosing gets calculated by body mass and weight
• Caregiver-dependent administration requires education and caution to prevent poisoning
• Teens are curious and need education on STIs and recreational drug use
• Neonates and young infants have lower liver and renal function
• Monitor organ function e.g. creatinine clearance, liver enzymes, urine volume

Older Adults

• Organ function decreases
• Decreased peristalsis, acidity, and elimination
• Renal function declines (1% per year)
• Lower albumin increases risk for dehydration
• Communication is essential for proper use of many potentially addicting drugs
• Polypharmacy, or using many drugs to maintain a state of wellness, e.g. use of 10 or more prescribed
• Polypharmacy use increases amount of potential side effects, increasing additional use of more medications
• Doctors restart treatment frequently in a polypharmacy setting

Common Toxicities & Errors

• Common toxicities include accidental overdoses from accessible drugs
• Frequent substances involves ASA, Tylenol, Opioids, Benzodiazepines, Alcohol, THC, and Cocaine
• Common nursing errors include dose errors, crushing enteric-coated tablets, late charting, and rushing,
• Crushing enteric coated tablets could result in severe drug interactions or adverse effects

Stabilization & Treatment

• Stabilize and analyze in toxicity cases with the ABCDE approach: Airway, Breathing, Circulation, Disability, Exposure
• Assess various factors like patency, perfusion quality (LOC, pulses, skin, BP), and dysfunctions e.g. apnea, seizures, and cardiac arrhythmias
• Identify the drug/substance and initiate focused treatment
• Identify the drug or substance from the patient's history, physical assessment, and lab toxicology
• Utilize the 'toxidromes' to identify from signs and symptoms:
  • ASA symptoms include Confusion, Tachycardia, Tachypnea, Hyperthermia, Diaphoresis, and Vomiting
  • Acetaminophen symptoms include Abdominal pain, Loss of appetite, Nausea/vomiting, Diaphoresis, and Somnolence.
  • Opioid symptoms include Bradypnea/Apnea, Bradycardia, Somnolence/Coma, and constricted Pupils
  • Cocaine symptoms include Agitation, tremors, Tachycardia, Tachypnea, Hyperthermia, Diaphoresis, and dilated Pupils

Cannabis Toxicity

• Cannabis toxicity presents variable neurocognitive effects
• VS changes (tachycardia, hypertension), seizures, nausea/vomiting and acute psychosis
• Routes of administration titration to effect: inhalation (15-30 min onset, 50% bioavailability), PO (1-2 hr onset, 20% bioavailability)
• THC causes CNS and VS instability, interacts in CBD receptors
• Treatment is largely supportive

Treatment Options

• Stabilization with supportive care:
  • Addresses disabilities like benzodiazepines for seizures, antihypertensives for hypertension, and antipsychotics for psychosis
• Clinical tools include algorithms to identify and treat specific medication effects
• Utilizes the ADME processes to address toxic components
• Adsorption involves binding the drug to decrease absorption
• Activated charcoal binds drugs which are then eliminated via bowel movements
• Induce metabolism can eliminate a number of active substances
• NAC increases glutathionine metabolism for phase II
• Increase elimination through the GI tract (activated charcoal), kidneys (alkalization and bicarbonate), or blood (hemodialysis)

Intoxication Treatments

• Antagonism uses a specific receptor to counteract drug action
• Tx reverses toxicity with opioid receptor antagonists e.g. Narcan to treat opioid toxicity
• Flumazenil (IV) treats benzodiazepine toxicity
• Tx drug: metadoxine, administered IV, and may include alcohol dehydrogenase metabolism and IV fluids
• Consider alcohol metabolizion and effects on bodily functions
• ETOH intoxication can result in Bradypnea/Apnea, Hypothermia, Emesis, Seizures, and a loss of consciousness
• CNS is also impacted and changes in levels of chloride through agonists create depressant-like effects

Overview of drug toxicity, including factors influencing patient response. Dosage considerations for pediatric patients and the relevance of health history are discussed. Side effects as indicators of toxicity and alterations to the blood-brain barrier are also addressed.