Drug Therapy Lifespan

Drug Therapy Lifespan

1. PREGNANCY

   • -Few information about how drugs affect pregnant/breast-feeding women -Can look back in medical records
   • Prescription
   • Placental Drug Transfer
     • -Small, lipid soluble drugs transfer easier -Ionic and polar drugs don't transfer to fetus easily
   • General considerations
     • -Some drugs are feto-toxic -Physiologic changes of pregnancy alters pharmkinetics --> changes from pre-pregnancy dosing
   • Physiological Changes
     • -How will this influence actual dose needed? -Physiological changes during pregnancy and their impact on drug disposition and dosing
     • Absorption
       • -Decreased tone and motility, gut slows, delayed onset of action
     • Distribution
       • -Inc blood volume, total body water --> decreased drug concentrations -Increased Cardiac Output --> increased delivery to tissues -(If taking drug that is highly protein-bound) Decreased serum albumin --> increased free drug 
     • Metabolism and Excretion
       • -Increased  -Shortened duration of drug action
   • Teratogenesis
     • -Less than 1% of birth defects caused by drugs -IDing teratogens very difficult  -Ex: Cardiac problems with Paxil/Prozac 
     • Minimize risk
       • -Avoid unnecessary drug use -Respond to exposure -ID details of exposure -Ultrasound scans
     • 3 Stages of development
       • 1. Conception
         • -Conception to week 2
       • 2. Embryonic period
         • -Weeks 3-8 -Gross malformations produced by teratogens -Retardation, neural tube, neurological
       • 3. Fetal period
         • Week 9-term Functions disrupted with teratogen  -Palate, genatalia 
     • Ex: Fetal Alcohol Syndrome
       • -Behavioral manifestations
     • Ex: Fetal Hydantoin Syndrome
       • -Exposed to dilantin -Depressed nasal bridge -Hypoplasia of phalanges of hands/toes
   • ***FDA Pharm Pregnancy Categories
     • Category A
       • -We have evidence (studies) that there are no risks to developing fetus -Very few
     • Category B
       • -Most drugs -Data from animal (mice) studies, or humans but demonstrated no risk
     • Category C
       • -Animal studies demonstrate risk -No human studies performed
     • Category D
       • -We know that there is a risk -Only used if mother's health is dependent on benefit.  -Benefits may outweigh risk -Woman cannot deliver without this drug
     • Category X
       • -Most significant risk -Animal and human studies demonstrate risk. -Risks outweigh benefits

2. BREAST-FEEDING

   • -Nearly all drugs pass into breast milk -1-2% maternal dose
   • LactMed
     • -National Library of Medicine Drugs and Lactation Database -Drugs to which breastfeeding mothers may be exposed -Maternal and infant level of drugs, possible effects on breastfed infants and on lactation, alternate drugs to consider
   • Decrease Risk to Infant
     • -Take drugs immediately after breast-feeding; postpone next feed for four hours -Avoid drugs that have a long half-life or sustained release -Choose drug that tned to be excluded from breast milk, least likely to affect infant -Avoid hazardous drugs -"Pump and dump" -Awareness of toxic effects on infant: sedation, poor feeding, diarrhea, rash, irritability 
   • Contraindicated
     • -Controlled substances -Antineoplastics/anti-cancer -Immunosupressants -Anti-seizure/psych -Anti-migraine

3. PEDIATRICS

   • -Patients under 16 -Respond differently to drugs than rest of population -More sensitive (immature organ systems), greater individual variation, increased adverse effects 
   • Challengers
     • -2/3 of drugs in peds have never been tested in peds -Ongoing growth and development -Different age groups (under 1 year, 1 and older)
   • <1 Year
     • Absorption
       • -Variable, oral drugs impacted by gastric pH and gastric emptying time; thinner skin --&gt; topical drugs absorption increases&nbsp;
     • Distribution
       • -Distributing drug to target organ -Liver still developing, decreased plasma albumins, increased drug effects -Increased total body water -Immature blood-brain barrier (drug gets to brain easier)
     • Metabolism
       • Decreased --&gt; prolonged/increased drug effect -Immature liver&nbsp;
     • Excretion
       • -Decreased --&gt; prolonged/increased rug effects&nbsp; -Immature kidneys
   • >1 Year old
     • -Most PK parameters similar to adults -Difference: metabolizes drugs faster than adults -Faster until 2 years old, then gradual decline -Sharp decline at puberty -May need to increase dosage or decrease interval between doses&nbsp;
   • Adverse Drug Reactions
     • -Vulnerable to unique adverse effects related to organ immaturity and ongoing growth and development
     • Age-related effects
       • -Glucocorticoids (Ex prednisone) --&gt; Growth suppression -Tetracycline --&gt; discoloration of developing teeth -Fluroquinolones (Ciprofloxacin) --&gt; Tendon rupture&nbsp;
   • Guidelines
     • -Aspirin causes Reyes Syndrome in children -Frequent monitoring of drugs with low therapeutic index -Special dosing considerations&nbsp;
     • Dosing
       • -Based on BSA (Body surface area) larger BSA --&gt; larger dose -Initial dosing is (at best) an approximation -Subsequent doses need to be adjusted
       • BSA Nomogram
       • Calculation
         • (BSA x Average adult dose)/1.73msq
   • Administering
     • -Don't dilute in large volumes -Don't disguise it; honesty, no trickery -Consider developmental level -Allow choices, allow control