Lecture 9 - Pharmacology Across the Lifespan

‭Drug Therapy: Pregnancy‬ ‭●‬ ‭⅔ of pregnant patients take at least one medication during pregnancy‬ ‭●‬ ‭Some drugs have to be taken despite risk of placental transfer‬ ‭○‬ ‭Ex. a mother with asthma needs bronchodilators to adequately ventilate, with that‬ ‭oxygen being needed by the infant as well‬ ‭○‬ ‭Data regarding adverse fetal effects is retrospective; suspected correlation but not‬ ‭definitively causative‬ ‭Physiologic Changes During Pregnancy Impact Drug Response‬ ‭●‬ ‭Increased blood volume = increased glomerular filtration rate‬ ‭○‬ ‭Doubled by third trimester‬ ‭○‬ ‭Drugs can be excreted more quickly; more is needed for expected effect‬ ‭●‬ ‭Hepatic metabolism increases‬ ‭○‬ ‭Can be made inactive more quickly‬ ‭○‬ ‭Facilitates elimination; decreased duration‬ ‭●‬ ‭Decreased GI motility‬ ‭○‬ ‭Increased time for absorption; may have increased effect‬ ‭○‬ ‭Timing of absorption affect onset‬ ‭Other Factors‬ ‭●‬ ‭Placental drug transfer‬ ‭○‬ ‭Lipid-soluble drugs easily pass‬ ‭●‬ ‭Adverse reactions during pregnancy‬ ‭○‬ ‭Can adversely affect both pregnant‬ ‭patient and fetus‬ ‭○‬ ‭Neonatal abstinence syndrome:‬ ‭Drug-dependent neonate‬ ‭■‬ ‭Irritability, vomiting, shrill crying‬ ‭Risk of Drug Therapy During Pregnancy‬ ‭●‬ ‭Teratogenesis:‬‭Fetal anomalies that‬ ‭occur in response to exposure to a‬ ‭teratogen (ex. thalidomide)‬ ‭●‬ ‭Exposure may result in:‬ ‭○‬ ‭Termination of early pregnancy‬ ‭○‬ ‭Gross physical malformations (ex.‬ ‭Limb abnormalities, cleft palate,‬ ‭hydrocephalus)‬ ‭○‬ ‭Neurobehavioral and metabolic‬ ‭anomalies‬ ‭Teratogenesis and Stage of Development‬ ‭●‬ ‭3 stages of fetal development:‬ ‭○‬ ‭Conception (pre-implantation): Weeks 1-2‬ ‭■‬ ‭Drug exposure → pregnancy termination or no effect‬ ‭○‬ ‭Embryonic period: Weeks 3-8‬ ‭■‬ ‭Drug exposure → altered internal organ development, limb abnormalities‬ ‭○‬ ‭Fetal period: Week 9-delivery‬ ‭■‬ ‭Drug exposure → neurodevelopmental and functional effects‬ ‭Teratogenesis: Nurse’s Role‬ ‭●‬ ‭Minimize risk‬ ‭○‬ ‭Ask about pregnancy or chance of pregnancy (birth control)‬ ‭○‬ ‭Most people find out about their pregnancy around 5-6 weeks‬ ‭●‬ ‭Educate about risk‬ ‭○‬ ‭Avoid unnecessary drug use‬ ‭■‬ ‭Know when drug use began‬ ‭○‬ ‭< 1% of birth defects are caused by drugs‬ ‭○‬ ‭Assure patient about benefits vs. risk‬ ‭●‬ ‭Mitigate risk‬ ‭○‬ ‭Identify when drug was taken‬ ‭○‬ ‭Emotional support‬ ‭FDA Pregnancy Risk Factors‬ ‭●‬ ‭A:‬‭Safest‬‭; studies in pregnant women show no increased‬‭risk for fetal anomalies‬ ‭●‬ ‭B:‬‭Animal‬‭studies indicate‬‭no fetal risk‬‭but there‬‭are no adequate human studies to‬ ‭substantiate this; animal studies show adverse fetal outcome, but human studies do not‬ ‭●‬ ‭C:‬‭Animal‬‭studies show‬‭adverse‬‭effect, but no adequate‬‭human studies in pregnant‬ ‭women; animal studies haven’t been done nor are there adequate human studies‬ ‭●‬ ‭D: Adequate studies in‬‭pregnant‬‭women‬‭show demonstrated‬‭risk‬‭to fetus, but benefit‬ ‭may outweigh risk‬ ‭●‬ ‭X: Most‬‭dangerous‬‭and known to cause fetal harm; contraindicated‬‭during pregnancy‬ ‭Drug Therapy: Breast-Feeding‬ ‭●‬ ‭Drugs can be excreted in breast milk‬ ‭●‬ ‭To decrease risk to the infant, educate patient to:‬ ‭○‬ ‭Take drugs immediately‬‭after‬‭breast-feeding‬ ‭○‬ ‭Avoid drugs that have long half-lives (ex. Sustained-release drugs)‬ ‭○‬ ‭Choose drugs that tend to be excluded from milk and least likely to affect infant‬ ‭○‬ ‭Avoid drugs that are known to be hazardous‬ ‭○‬ ‭Discuss alcohol use‬ ‭Briggs Drugs in Pregnancy and Lactation‬ ‭●‬ ‭Lists 1,400 most prescribed drugs in pregnancy and lactation as well as their effects‬ ‭Drug Therapy in Pediatric Patients‬ ‭●‬ ‭Pediatric patients respond differently to drugs than the rest of the population‬ ‭○‬ ‭More sensitive than adults to do pharmacokinetic and pharmacodynamic traits‬ ‭○‬ ‭Increased overall risk of adverse effects‬ ‭●‬ ‭Ongoing growth and development‬ ‭●‬ ‭Greater individual variation‬ ‭●‬ ‭Unique therapeutic differences based on age grouping‬ ‭○‬ ‭Neonates (< 28 days)‬ ‭○‬ ‭Pre-mature infants (< 36 weeks gestation)‬ ‭○‬ ‭Full-term infants (36-40 weeks gestation)‬ ‭○‬ ‭Infants (5 weeks-1 year)‬ ‭○‬ ‭Children (1-12 years)‬ ‭○‬ ‭Adolescence (13-18 years)‬ ‭●‬ ‭Less than a month/year tends to be highly vulnerable‬ ‭●‬ ‭Knowledge of drug therapy in pediatrics is limited‬ ‭○‬ ‭⅓ of drugs used in pediatrics have never been tested in pediatric patients‬ ‭Promotion of Research Among Pediatric Population‬ ‭●‬ ‭Best Pharmaceuticals for Children Act (2002)‬ ‭●‬ ‭Pediatric Research Equity Act (2003)‬ ‭●‬ ‭Research found that many drugs:‬ ‭○‬ ‭20% were ineffective in children‬ ‭○‬ ‭30% caused unanticipated side effects‬ ‭○‬ ‭20% required dosages different from those used in adults‬ ‭●‬ ‭Resulted in over 400 drugs being re-labeled out of what has been testing‬ ‭Drug Therapy: Neonates and Infants‬ ‭●‬ ‭Neonates/infants experience more intense and prolonged drug responses due to immature:‬ ‭○‬ ‭Drug absorption‬ ‭ ‬ ‭Protein binding‬ ○ ‭○‬ ‭Blood-brain barrier‬ ‭○‬ ‭Hepatic drug metabolism‬ ‭○‬ ‭Renal drug excretion‬ ‭ ‬ ‭Increased sensitivity not just due to‬ ● ‭smaller body size‬ ‭Absorption: Neonates/Infants‬ ‭●‬ ‭Oral administration:‬ ‭○‬ ‭Gastric emptying‬ ‭unpredictable until 6-8‬ ‭months old‬ ‭■‬ ‭Quick emptying and should be absorbed in stomach → less absorption‬ ‭■‬ ‭Slow emptying and should be absorbed in SI → slower absorption‬ ‭○‬ ‭Gastric acidity is low until 24 months‬ ‭■‬ ‭Why small babies spit up more often‬ ‭■‬ ‭A drug can depend on a particular pH to be absorbed‬ ‭●‬ ‭Instramuscular administration:‬ ‭○‬ ‭Slow and erratic absorption in neonates‬ ‭■‬ ‭Administration of hepatitis B after birth‬ ‭○‬ ‭Absorption more rapid in infancy than adulthood‬ ‭●‬ ‭Transdermal administration:‬ ‭○‬ ‭Enhanced in infants‬ ‭○‬ ‭Increased risk for toxicity (ex. Sunscreen not recommended)‬ ‭Distribution: Neonates/Infants‬ ‭●‬ ‭Protein binding:‬ ‭○‬ ‭Limited serum albumin in infants (more free drug)‬ ‭○‬ ‭Competition for binding sites‬ ‭○‬ ‭Adult protein binding capacity at 10-12 months old‬ ‭●‬ ‭Blood-brain barrier:‬ ‭○‬ ‭Not fully developed at birth‬ ‭○‬ ‭May readily cross and have greater neurological effects‬ ‭Metabolism: Neonates/Infants‬ ‭●‬ ‭Drug-metabolizing capacity is low in newborns (less blood flow)‬ ‭●‬ ‭Drug metabolized by liver should have dosages reduced‬ ‭●‬ ‭Complete liver maturation by 1 year of age‬ ‭Excretion: Neonates/Infants‬ ‭‬ L ● ‭ ower renal blood flow, glomerular filtration, and active tubular secretion‬ ‭●‬ ‭Increased risk for accumulation‬ ‭●‬ ‭Adult renal capacity by 1 year of age‬ ‭Pharmacokinetics: Age 1 Year and Older‬ ‭●‬ ‭Most pharmacokinetic parameters are like adults except:‬ ‭○‬ ‭Children generally metabolize drugs faster than adults‬ ‭○‬ ‭Peak metabolism around 2 years of age‬ ‭●‬ ‭Increased dosage or reduction in dosing interval may be needed‬ ‭Nursing Action: Pediatric Patients‬ ‭●‬ ‭Considerations:‬ ‭○‬ ‭Dosage size and timing‬ ‭■‬ ‭Usually difficult to give frequent doses‬ ‭○‬ ‭Route and technique of administration‬ ‭■‬ ‭Liquid formulation (volume)‬ ‭■‬ ‭Taste/flavoring‬ ‭○‬ ‭Drug storage‬ ‭■‬ ‭Most not stable for longer than 2 weeks‬ ‭■‬ ‭Refrigeration‬ ‭●‬ ‭Provide patient education in writing (tired parents)‬ ‭●‬ ‭Demonstration techniques should be included as appropriate‬ ‭●‬ ‭Monitor for ADRs‬ ‭Calculating Pediatric Doses‬ ‭●‬ ‭Often done when a drug has not been tested in pediatric populations‬ ‭●‬ ‭Calculate‬‭BSA‬‭(m‬‭2‬‭):‬‭𝐵𝑆𝐴‬ = ‭𝑏𝑜𝑑𝑦‬‭‬‭𝑤𝑒𝑖𝑔ℎ𝑡‬‭‬(‭𝑘𝑔‬)‭‬‭𝑥‭‬‬‭ℎ𝑒𝑖𝑔ℎ𝑡‬‭(‬ ‭𝑐𝑚‬) ‭3600‬ ‭●‬ ‭Calculate‬‭dose‬‭: Pediatric dose‬= ‭‬ ‭or‬ ‭𝑏𝑜𝑑𝑦‬‭‬‭𝑤𝑒𝑖𝑔ℎ𝑡‬‭‬(‭𝑙𝑏‬)‭‬‭𝑥‭‬‬‭ℎ𝑒𝑖𝑔ℎ𝑡‬‭‬(‭𝑖𝑛‬) ‭3131‬ ‭2‬ ‭𝑐ℎ𝑖𝑙𝑑‬‭'‭𝑠‬ ‭‬‬‭𝐵𝑆𝐴‬‭‬(‭𝑚‬ )‭‭𝑥 ‬ ‬‭‭𝑎 ‬ 𝑑𝑢𝑙𝑡‬‭‬‭𝑑𝑜𝑠𝑎𝑔𝑒‬ ‭2‬ ‭1‬.‭73‬‭‬‭𝑚‬ ‭Drug Therapy in Older Adults‬ ‭●‬ ‭Disproportionately high prescription drug use exists in the older adult population‬ ‭○‬ ‭12% of population but take 30% of prescription drugs (overuse)‬ ‭●‬ ‭More sensitive to drugs and have a wider variation in response‬ ‭●‬ ‭Experience more ADRs and drug-drug interactions‬ ‭Older Adults Considerations‬ ‭●‬ ‭Changes in pharmacokinetics‬ ‭●‬ ‭Multiple illnesses with higher complexities/severities‬ ‭●‬ ‭Multiple-drug therapy‬ ‭●‬ ‭Poor adherence‬ ‭Older Adults‬ ‭●‬ ‭Individualization of treatment is essential‬ ‭●‬ ‭Each patient must be monitored for therapeutic‬ ‭and adverse responses‬ ‭○‬ ‭Beers criteria:‬‭Identifies drugs with‬ ‭significant risk of ADRs in older adults‬ ‭■‬ ‭Know risk:benefit ratio‬ ‭○‬ ‭STOPP:‬‭Screening tool for potentially‬ ‭inappropriate prescriptions‬ ‭■‬ ‭One provider may not be aware‬ ‭of drugs prescribed by another‬ ‭●‬ ‭Consider adherence‬ ‭●‬ ‭Goals of drug treatment: Reduce symptoms and improve quality of life‬ ‭Absorption: Older Adults‬ ‭●‬ ‭Percentage of drug absorbed doesn’t change‬ ‭●‬ ‭The rate of absorption may slow with age‬ ‭○‬ ‭Delayed gastric emptying‬ ‭○‬ ‭Reduced splanchnic blood flow‬ ‭Distribution: Older Adults‬ ‭●‬ ‭Increased percentage of body fat‬ ‭○‬ ‭Storage for lipid-soluble drugs‬ ‭○‬ ‭Decreased plasma levels of drugs (thus, response)‬ ‭●‬ ‭Decreased total body water‬ ‭●‬ ‭Decreased percentage of lean body mass‬ ‭○‬ ‭Water-soluble drugs are distributed in a smaller volume, greater concentration‬ ‭●‬ ‭Reduced concentration of serum albumin‬ ‭○‬ ‭Higher risk for malnutrition‬ ‭Metabolism: Older Adults‬ ‭●‬ ‭Reduced hepatic blood flow, reduced liver mass, and decreased activity of some hepatic‬ ‭enzymes (P450) occur‬ ‭●‬ ‭The half-lives of some drugs may increase‬ ‭●‬ ‭Responses to oral drugs may be enhanced‬ ‭●‬ ‭Liver function should be assessed routinely‬ ‭Excretion: Older Adults‬ ‭●‬ ‭Renal function undergoes progressive decline beginning in early adulthood‬ ‭○‬ ‭Not getting rid of drugs as quickly‬ ‭○‬ ‭Creatnine clearance:‬ ‭■‬ ‭Measure of serum creatinine is based on lean body mass‬ ‭■‬ ‭Can be arbitrarily lower; no longer a good measurement of renal function‬ ‭●‬ ‭Drug accumulation from reduced renal excretion is the most important cause of ADRs‬ ‭ADRs: Older Adults‬ ‭●‬ ‭7 times more likely in the elderly‬ ‭●‬ ‭Account for 30% of hospital admissions‬ ‭●‬ ‭Account for 50% of all medication-related deaths‬ ‭●‬ ‭Symptoms can be non-specific‬ ‭Predisposing ADR Factors‬ ‭●‬ ‭Drug accumulation secondary to reduced renal function‬ ‭●‬ ‭Polypharmacy‬ ‭‬ ● ‭●‬ ‭●‬ ‭●‬ ‭●‬ ‭ reater severity of illness‬ G ‭Comorbidities‬ ‭Drugs with low therapeutic index‬ ‭Altered pharmacokinetics‬ ‭Poor adherence‬ ‭Measures to Reduce ADRs‬ ‭●‬ ‭Obtain a thorough drug history (drug reconciliation)‬ ‭●‬ ‭Consider pharmacokinetic changes‬ ‭○‬ ‭Consider need for lower drug dose due to decreased metabolism and excretion‬ ‭●‬ ‭Monitor the patient’s response and plasma drug levels‬ ‭○‬ ‭LFTs, creatnine clearance, plasma drug levels‬ ‭●‬ ‭Use the simplest regimen possible‬ ‭○‬ ‭Ex. extended release‬ ‭●‬ ‭Monitor for drug-drug interactions‬ ‭●‬ ‭Encourage the patient to dispose of old medications‬ ‭Individual Drug Response: Adherence‬ ‭●‬ ‭30-60% of people do not adhere to their prescribed medication regimen‬ ‭●‬ ‭Reasons include:‬ ‭○‬ ‭Cost‬ ‭○‬ ‭Knowledge‬ ‭○‬ ‭Psychological state‬ ‭■‬ ‭Ex. dementia, forgetfulness‬ ‭○‬ ‭Continuance of unnecessary drug‬ ‭○‬ ‭Reliance on caregiver‬ ‭○‬ ‭Impairment (dexterity, visual)‬ ‭○‬ ‭Side effects‬ ‭○‬ ‭Complicated drug regimen (polypharmacy)‬ ‭●‬ ‭Common factor in ADRs and inconsistent drug response‬ ‭●‬ ‭Two types:‬ ‭○‬ ‭Intentional non-adherence: Active decision to not take prescribed drugs‬ ‭■‬ ‭Also due to lack of knowledge or education from provider‬ ‭■‬ ‭Hesitancy to ask provider for clarification‬ ‭○‬ ‭Unintentional non-adherence:‬ ‭■‬ ‭Forgetfulness‬ ‭■‬ ‭Inability to pay for drugs‬ ‭■‬ ‭Impairment (dexterity, visual, cognitive)‬ ‭■‬ ‭Complex medication regimen‬ ‭■‬ ‭Living alone‬ ‭ ‬ ‭Low health literacy‬ ■ ‭How to Address Nonadherence‬ ‭●‬ ‭Discuss goals of care‬ ‭●‬ ‭Simplified drug regiments‬ ‭●‬ ‭Clear and concise verbal and written instructions‬ ‭○‬ ‭Ex. medication box‬ ‭●‬ ‭Appropriate dosage form (easily taken)‬ ‭●‬ ‭Clearly labeled and easy-to-open containers‬ ‭●‬ ‭Daily reminders‬ ‭●‬ ‭Support system‬