Active transport

Diffusion

Elderly

Neonate

Nomogram

Pediatric

Polypharmacy

Three factors that contribute to the safety or potential harm of drugtherapy during pregnancy

1. Drug properties- impact drug transfer to the fetus include the drug's chemistry, dosage, and concurrently administered drugs.
2. Fetal gestational age- an important factor in determining the potential for harmful drug effects to the fetus. The fetus is at greatest risk for drug-induced developmental defects during the first trimester of pregnancy. During the last trimester the greatest percentage of maternally absorbed drug gets the fetus.
3. Maternal factors- Any change in the mother's physiology that could impact the pharmacokinetic characteristics of drugs can affect the amount of drug to which the fetus may be exposed.

Pregnancy safety categories

• Category A- Studies indicate no risk to human fetus.
• Category B- Studies indicate no risk to animal fetus; information for humans is not available.
• Category C- Adverse effects reported in animal fetus; information for humans is not available.
• Category D- Possible fetal risk in humans reported; however, consideration of potential benefit vs. risk may, in selected cases, warrant use of these drugs in pregnant women.
• Category X- Fetal abnormalities reported and positive evidence of fetal risk in human available from animal and/or human studies. These drugs should not be used in pregnant women.

Pharmacokinetic changes in the neonate and pediatric patient

• Absorption
• Gastric pH is less acidic because acid-producing cells in the stomach are immature until approximately 1 to 2 years of age.
• Gastric emptying is slowed because of slow irregular peristalsis.
• First-pass elimination by the liver is reduced because of the immaturity of the liver amd reduced levels of microsomal enzymes
• Intramuscular absorption is faster and irregular.
• Distribution
• Total body water is 70% to 80% in full-term infants, 85% in premature newborns, and 64%in children 1 to 12 years of age.
• Fat content is lower in young patients because of greater total body water.
• Protein binding is decreased because of decreased production of protein by the immature liver.
• More drugs enter the brain because of an immature blood-brain barrier.
• Metabolism
• Levels of microsomal enzymes are decreased because the immature liver has not yet started producing enough.
• Older children may have increased metabolism and require higher dosages once hepatic enzymes are produced.
• Many variables affect metabolism in premature infants, infants, and children, including the status of liver enzyme production, genetic differences, and substances to which the mother was exposed during pregnancy.
• Excretion
• Glomerular filtration rate and tubular secretion and resorption are all decreased in young patients because of kidney immaturity.
• Perfusion to the kidneys may be decreased, which results in reduced renal function, concentrating ability, and excretion of drugs.

Prescribing cascade

Pharmacokinetic changes the Elderly Patient

• Absorpton
• Gastric pH is less acidic because of a gradual reduction in the production of hydrochloric acid in the stomach.
• Gastric emptying is slowed because of a decline in smooth muscle tone and motor activity.
• Movement throughout the gastrointestinal (GI) tract is slower because of decreased muscle tone and motor activity.
• Blood flow to the GI tract is reduced by 40% to 50% because of decreased cardiac output and decreased perfusion.
• The absorptive surface area is decreased because the aging process blunts and flattens villi.
• Distribution
• In adults 40 to 60 years of age, total body water is 55% in males and 47% in females; in those over 60 years of age, total body water is 52% in males and 46% in females.
• Fat content is increased because of decreased lean body mass.
• Protein (albumin) binding sites are reduced because of decreased production of proteins by the aging liver and reduced protein intake.
• Metabolism
• The leves of microsomal enzymes are decreased because the capacity of the aging liver to produce them is reduced.
• Liver blood flow is reduced by approximately 1.5% per year after 25 years of age, which decreases hepatic metabolism.
• Excretion
• Glomerular filtration rate is decreased by 40% to 50%, primarily because of decreased blood flow.
• The number of intact nephrons is decreased.