Toxicity Overview - Symptoms, Treatment, and Drugs

Toxicity All images are used for educational purposes only, not for further distribution.  Drug effects undesirable therapeutic Non-deleterious Deleterious (side effects) TOXIC...

Toxicity All images are used for educational purposes only, not for further distribution.  Drug effects undesirable therapeutic Non-deleterious Deleterious (side effects) TOXIC H. Schaefer MN Factors influencing patient response Helena Schaefer MN 3  Genetic differences affecting ADME genetic polymorphisms in liver enzymes: e.g. decreased CYP2D6 enzyme = reduced metabolism of specific drugs, risk of toxicity + reduced metabolism of prodrugs (e.g. Codeine) risk of low efficacy e.g. special safety considerations across the lifespan (be aware of toxicity risks) Pregnancy & pharmacotherapy Altered GI fx Delayed GI emptying Drugs take longer to absorb Decreased acidity Decreased acidity Higher blood volume (up by 50%) => blood flow to placenta Higher HR Decreased PPB Higher GFR Most drugs cross into placenta & into breastmilk e.g. high Vd drugs; A&D characteristics? breastfeeding contraindications, e.g.: Ibuprofen, Opioids, … Pediatric pharmacotherapy (0-18 yrs of age) Calculated by body mass Per kg of body weight Note: remember paediatric blood volume (80 mL/kg of body weight) Caregiver-dependent Education Protect from poisoning (Adam’s text: pg. 58) Teens – curious Tx focus: menstrual cramps, sports injuries, skin problems Factual conversations Educate on STIs, recreational drug use Organ fx neonates & young infants have lower liver & renal function check organ fx (e.g. creatinine clearance; liver enzymes; urine volume/hr; …) Older adult pharmacotherapy Decreased organ fx GI: decreased peristalsis, acidity, elimination Renal: decreased GFR (1%/year decline in the elderly) Lung: shallower resps 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 Toxicities: most common ASA (Aspirin) Tylenol (Acetaminophen) Opioids Oxycodone, Fentanyl Benzodiazepines Xanax (alprazolam), Valium (diazepam) Alcohol (ETOH) THC Cocaine H. Schaefer MN Medication errors! Common nursing errors Dose errors Crushing of enteric-coated tablets or sustained-release tablets Late charting Rushing (not checking all the rights, every time) H. Schaefer MN  Clinical procedure in toxicity (overdose): ‘stabilize & analyze’ A & B assess patency, effort, rate, colour ET tube insertion? O2 ? C assess perfusion quality e.g. LOC, pulses, skin, BP IV fluids? Sympathomimetics ? D assess for dysfunctions & treat as needed e.g. apnea, seizures, cardiac arrhythmias, hyperthermia E identify the drug/substance & initiate treatment H. Schaefer MN 1. Identify drug/substance Patient’s Health History Lab toxicology (urine, serum) Physical assessment of S&S, using a clinical tool: ‘toxidromes’ ASA Acetaminophen Confusion Abdominal pain Tachycardia Loss of appetite Tachypnea Nausea/vomiting Hyperthermia Diaphoresis Diaphoresis Somnolence Vomiting H. Schaefer MN  Toxidromes cont. Opioids (Fentanyl, Codeine, Cocaine (& other stimulants) Morphine, Oxycodone, Heroin, ….) Agitation, tremors Bradypnea/Apnea Tachycardia Bradycardia Tachypnea Somnolence/Coma Hyperthermia Pupils constricted Diaphoresis Pupils dilated H. Schaefer MN Cannabis toxicity & toxidrome: Neurocognitive effects, variable presentation: VS changes (tachycardia, hypertension) seizures nausea/vomiting acute psychosis LOC changes: agitation; coma Route of admin: inhalation – 15-30 min onset, bioavailability 50% PO - 1-2 hr onset (variable), bioavailability 20% THC & CBD THC causes CNS & VS instability CBD modulates effect of THC at receptors Tx: supportive  2. Treatment clinical tool: Algorithms utilization of ADME stabilize patient with supportive tx e.g. Tx of disabilities: seizures tx with benzodiazepines hypertension tx with antihypertensives respiratory depression tx with intubation psychosis tx with antipsychotics  Adsorption ‘binding of drug, to decrease its absorption’ e.g. Tx of toxicities: Tylenol, ASA, Benzodiazepines Tx drug: Activated charcoal Binds drug to surface carbons Enteral route of administration Eliminated via stool H. Schaefer MN  Induce metabolism e.g. Tx of Tylenol toxicity Tylenol toxicity depletes liver enzyme Glutathione hepatotoxic NAPB causes liver failure Tx drug: NAC (n-acetylcysteine/acetylcysteine)) is a Glutathione enzyme precursor enhances phase II metabolism IV, PO H. Schaefer MN  Algorithm e.g: Details are FYI, critical thinking is testable https://emedicine.medscape.com/article/820200-treatment https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637612/ H. Schaefer MN Homework, testable: Review the main functions of the liver Brainstorm what occurs to these functions when the liver is compromised Homework, testable: Review the main functions of the liver Brainstorm what occurs to these functions when the liver is compromised Increase elimination 1. via the GI tract activated charcoal increases GI elimination of charcoal-bound drug 2. via the kidneys alkalization to induce acidic drug excretion Tx drug: Sodium Bicarbonate ionizes an acidic substance E.g. Tx of ASA toxicity 3. Via blood: Hemodialysis active removal from blood H. Schaefer MN Antagonism Antagonism of a specific receptor = cessation of drug action Tx of opioid toxicity opioid receptor antagonist Tx Drug: Narcan (Naloxone), IV Tx: benzodiazepine toxicity GABA receptor antagonist Tx Drug: Flumazenil, IV H. Schaefer MN