Special Populations Flashcards
Pharmacokinetics
How the body changes the drug
Changes in ADME
Pharmacodynamics
Drug response caused by drug-receptor interactions
6 factors that influence hepatic and renal effects on pharmacokinetics
Organ size Tissue composition Blood flow Enzyme activities Transport activities Protein binding
Ganciclovir
Antiviral used to treat cytomegalovirus
Eliminated primarily through kidney excretion
ACE inhibitors in diabetes
Renoprotective
Diabetics have high afferent flow that causes higher pressure in the glomerulus and results in protein secretion
Dilating the efferent arteriole reduces the pressure in the glomerulus
How do ACE inhibitors work
Angiotensin 2 receptor blockers
Results in efferent arteriole dilation
Decreases pressure in the glomerulus
ACE inhibitors and chronic kidney disease
People with CKD often have lowered afferent flow, so dilation of the efferent vessel drops the pressure even further
Can lead to renal failure
What classification is used for liver function?
Child-Pugh classification and scoring
Total score is classified as mild, moderate or severe
The amount of drug removed by the liver is dependent on what?
Hepatic blood flow
Hepatic impairment -> decreased blood flow -> decreased metabolism
Cirrhosis
Complication of liver disease
Commonly caused by long term alcohol abuse and hep B/C
Loss of liver cells and permanent scarring
Liver function greatly decreased
Chlormethiazole
Has high hepatic extraction ratio
Oral bioavaliability is increased in cirrhosis
Used to treat and prevent symptoms of acute alcohol withdrawal
Alcohol use can lead to overdose
4 physiological changes that occur during pregnancy
Increased GFR
Altered hepatic metabolism
GI motility slows
Changes in drug volume of distribution
Other changes in respirator rate, BP, plasma albumin changes, HR, etc
All of these changes affect pharmacokinetics
Teratogenic
An agent that can disturb the development of embryo or fetus
Tetracycline
Antibiotic
Causes permanent discolouration of teeth in infants and children when used during pregnancy
Due to an uptake in iron during bone development
Thalidomide
Sedative used for morning sickness in the 50s
Withdrawn from market due to teratogenicity and neuropathy
Midazolam
Used for procedural sedation or trouble sleeping
Cleared primarily by CYP3A4
Greater activity in females leading to greater clearance of the drug
Long QT syndrome
Prolonged QT interval
Many people have no signs or symptoms, but it can lead to fainting, seizures, and sudden death
Women have a higher risk of drug induced Long QT syndrome
What are 2 explanations for the sex difference in Long QT syndrome?
Females have longer baseline QT interval
Women have more K cardiac channels
Differences in distributions of 1. Extracellular body water 2. Body fat 3. Proteins in children vs adults
- Children have higher percentage of extracellular body water (hydrophilic drugs may distribute more)
- Differences in body fat affect hydrophobic drug distribution
- Children have a lower proportion of proteins (protein binding is lower which changes drug distribution)
How does renal elimination change during development?
Normal as a newborn, increases until 5 years old, and then begins to decline
Hepatic elimination in children
Slower elimination rates and increased half-life in newborns
Toddlers tend to have higher metabolic activity than adults
Gray baby syndrome
Adverse event occurring in newborn infants following IV administration of chloramphenicol (antimicrobial)
2 causes of gray baby syndrome
Reduced glucuronidation of chloramphenicol
Reduced renal elimination of chloramphenicol
Reye’s syndrome
Rare adverse event associated with giving aspirin to children who have viral infections
Death in 20-40% of instances of Reye’s syndrome
Causes swelling in the liver and brain
Exact cause is unknown
Changes in geriatrics (7)
Reduction in hepatic mass and blood flow Change in plasma protein composition Reduction in renal mass and GFR Increase in body fat Decrease in plasma volume Decrease in total body water Decrease in extracellular body fluid
Effects of pregnancy on amoxicillin and why this happens
Concentration is decreased during pregnancy
Because of the increased GFR
