Special Populations Flashcards
Who is considered special populations?
Children, elderly, pregnant and breastfeeding, obese, dialysis, ECMO, cooling
What does scaling adult doses to infants based on body weight or surface area not account for?
Developmental changes that affect drug disposition and tissue/organ sensitivity
By basing only or weight or surface area can result in ineffective treatment or toxicity
What makes drug research in children so difficult?
Different ethics, population, parents, formulations, groups and outcome measures
Smaller blood volume, fewer draws
Why are most drugs prescribed to pediatrics off-label?
There is a lack of appropriate safety and efficacy date and shortage of child-friendly formulations (oral solid multiparticulate formulations in development)
What may drug clearance increase with?
Weight, height, age, body surface area and creatinine clearance
How does gastric pH change throughout life?
At birth, gastric pH is 6-8 but it rapidly falls within 3-5 hours to adult values (pH 1-5)
How do gastric secretions change with age?
HCl production increases with age.
Gastrin production decreases with age.
Volume increases
Approach adult values by age 2
How does gastric emptying time change with age?
In the neonatal period, gastric emptying rate is variable and unpredictable, partially dependent on type of formula.
Approaches adult values within 6 to 8 months
How does splanchnic blood flow change with age?
Changes in the first 2-3 weeks of life may influence absorption rates by altering the concentration gradient across the intestinal mucosa
How does biliary function change with age?
The rate of synthesis, pool size and intestinal transport of bile acids are reduced in neonates
Lipase activity is present by 34-36 weeks of gestation and increases rapidly up to 9 months old.
What is involved in intestinal drug metabolism?
Efflux transporter P-glycoprotein (multidrug resistance protein-1)
How does barrier thickness affect drug absorption?
Skin layer is thinner in newborns, so topical application can be quicker
How does skin hydration change throughout life?
Hydration will lead to better absorption. Better in newborns.
How does diffusional surface area differ in newborns?
Surface area to weight is much higher, giving quicker absorption
How does regional blood flow differ in newborns?
The muscle mass to body mass ratio is lower with reduced skeletal muscle blood flow and inefficient muscular contractions reduce drug dispersion and absorption
May be offset by high density of skeletal muscle capillaries
How does metabolism change with age?
Metabolic routes mature at different rates
How do DME vary with age?
CYP 2C9 is very very low as a neonate then increase at birth.
SULT 1E1 decreases at birth and with age.
How does degree of protein binding differ in newborns?
A reduction in total quantity of plasma proteins, increasing free drug and drug availability
Higher concentrations of free fatty acids and unconjugated bilirubin compete for binding to the protein, leaving more free drug.
What happens when drugs compete with and displace bilirubin from albumin?
Ampicillin, Diazepam, Phenytoin, Sulfonamides can increase a neonate’s risk for developing kernicterus
How can hyperbilirubinemia affect drug protein binding?
Can reduce the protein binding of ampicillin, penicillin and phenobarbital
How does body composition differ in newborns?
The amount of water in the body is higher than in adults, thus hydrophilic drugs have a higher volume of distribution and lipophilic have a lower
Skin and brain, mostly everything else are a much higher percentage of body weight
How does the permeability of cell membranes differ in newborns?
The blood brain barrier is much less efficient, leading to more CNS side effects but also to better permeability
How does receptor ontogeny work?
Expression tends to follow a general maturation pattern from birth to adult levels but the time course varies widely
Abundance does not often equate directly to pharmacological response
How does transporter ontogeny work?
Expression pattern follows a general maturation pattern
Alterations in expression are more readily translated into clearance