Lecture 3: Toxicity

Lecture 3: Toxicity Drug Effects · drugs can be undesirable (adverse) or therapeutic · therapeutic is the goal · allergies would be considered undesirable, but we treat them differently Pharmacotherapy Across the Lifespan · Different age groups have different concerns when it comes to drug administration and drug effects · Its important to assess for renal function in the elderly and consider that neonates and young infants have lower renal function ↳ drugs will not be metabolized or excreted as efficiently in these age groups ↳ will likely require smaller dosages · Renal function decreases with increasing age, causing 1%/year decline in the elderly Pregnancy & Pharmacotherapy · In pregnancy, the mother has delayed GI emptying so the drugs take longer to absorb, as well as there being less acidity in the Mother's GI · The Mother also has a higher blood volume (up to 50% ) ↳ higher HR = more distribution (↑ CO) ↳ higher GFR ↳ decreased PPB ↳ high blood flow to uterus/fetus · Many drugs are able to cross into the placenta and breast milk, especially if they are smaller, lipophilic, and non-ionized eg. ibuprofen and opioids (with OTC drugs the maternal dose is too much for the baby) · agents that cause fetal malformations are called teratogens · drugs that cause harm to the baby (C & D) should only be given if the benefits outweigh the risk to the fetus/infant ·"X" drugs should NEVER be given, and "N" drugs do not have enough data and thus should not be given either “All Good” “R vs. B” - “Never” Pediatric Pharmacotherapy (0-18 yrs) · calculated per kg of body weight ↳ 2.2 Ib to 1 kg ↳ do not exceed adult recommended dose ↳ note: pediatric blood volume is 80mL/kg · adherence depends on the caregiver who gives child medication · protect from poisoning (keep drugs out of reach etc. ) · Teens are often curious about drugs ↳ menstrual cramps, sports injuries, skin problems ↳ educate on STI's, recreational drug use, drug misuse * Most Common Toxicities: · ASA (aspirin) · Tylenol (acetaminophen) · Opioids ↳ oxycodone, fentanyl, isotonitazene · Benzodiazepines (sedative/hypnotic) · Alcohol (ETOH) · Cocaine · Other (eg. antidepressants) Older Adult Pharmacotherapy · polypharmacy: older adults have too many drugs to the point where they don't remember what drugs they take, why they take them, or what they do · decreased acidity, peristalsis, elimination, GFR · decreased liver and renal function · 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, overuse, misuse) Common Nursing Errors · medication errors: ↳ dose! ↳ crushing of enteric-coated tablets ↳ crushing of sustained-release tablets · Prevention: ↳ Check 10 rights EVERY TIME ↳ eg. drug, patient, dose, route, time, reason... Clinical Procedure in Toxicity (Overdose) · A - airway: patency! · B - breathing: oxygenation & ventilation · C - circulation: organ perfusion (CO, BP) · D - disability: assess for disfunction (VS, pupils, ECG... ) and treat as needed · E - exposure: identify the drug/substance; initiate specific treatment to decrease activity - - - - - Stabilizing the Patient · ABC's · A & B: assess patency, effort, rate ↳ respiration → shallow breathing = breathing (anatomical dead space) ↳ obstruction (eg. vomit) ↳ oxygen supplement? → If you don't have depth this is useless ↳ ET Tube insertion? · C: assess perfusion quality ↳ IV fluids? → ↑ BP by adding more fluids into circulation ↳ drugs? · other VS stabilization (eg. temperature) and monitoring Stabilizing the Patient ① Identify drug/substance · patient's heath history, lab results (urine, blood) · physical assessment, signs & symptoms, using a clinical tool: "toxidromes" · toxidromes: a classic constellation of symptoms and signs ASA (aspirin) · confusion · tachycardia · tachypnea · hyperthermia · diaphoresis · vomiting Acetaminophen (Tylenol) · Abdominal pain · Loss of appetite · Nausea, vomiting · Diaphoresis · Somnolence - - Opioids (Fentanyl, Codeine, Morphine, Oxycodone, Heroin, Isotonitazene... ) · Bradypnea/apnea · Bradycardia · Somnolence/coma · Pupils constricted - Cannabis Toxicity · no antagonists for cannabis toxicity, uncommon in adults (b/c of high TI) but common in children b/c edibles look like candy · route of administration: inhalation, PO ↳ inhalation has more potency · LD50 = route dependent ↳ THC is more agitation + intense, CBD is calming · signs & symptoms: sensory alterations, acute psychosis, seizures, somnolence, VS changes, respiratory depression, motor impairment · Lab: urine toxicology, serum levels · Treatment: supportive fluids, antipsychotics, ventilator etc. - ② Treatment · Clinical tools: ADME · Adsorption (prevent absorption) ↳ binding of a drug to decrease its absorption · ex. Activated Charcoal ↳ binds drug to surface carbons (only works in GI tho) ↳ enteral route ↳ eliminated via stool ch whi for : (Lookin ↳ dose: 0.5-2 g/kg (max. 100g) drugs slides) = ↓ ③ Induce Metabolism · more biotransformation and elimination · Treatment in Tylenol Toxicity ↳ tylenol toxicity depletes liver enzyme (glutathione) ↳ accumulation of phase I active metabolite → hepatotoxicity ↳ treat with NAC (n-acetylcysteine/acetylcysteine) - precursor to glutathione enzyme - induces phase II metabolism of NAPB - - Cocaine (+ stimulants) · Agitation, tremors · Tachycardia · Tachypnea · Diaphoresis · Pupils dilated - Alcohol Poisoning · liver metabolized by alcohol dehydrogenase (depletes Vitamin B) · CNS effects increase the more you drink ↳ GABA binding (high affinity) ↳ lowers glutamate · Inhibits ADH → diuresis (dehydration) · Chronic use leads to tolerance ↳ GABA receptor #'s increase, requiring more alcohol to create same effect · Treatment: Metadoxine, IV fluids ↳ induces alcohol dehydrogenase function (↑metabolism + clearance, zero order kinetics) ④ Increase Elimination · ionized substances are secreted easier → make them ionized · GI tract: ↳ activated charcoal · Renal: ↳ alkalization to induce excretion ↳ sodium bicarbonate (ionizes acidic substance) eg. ASA (aspirin) · Hemodialysis (active removal) ⑤ Antagonism · Antagonism of a specific receptor = cessation of drug action · bad drug cannot bind to exert its effects · eg. Narcan/Naloxone for opioids Signs & Symptoms: · slow or irregular breathing · low body temperature · vomiting · Seizures · unconsciousness → alcohol induced coma -