Lecture 6: Factors affecting ADME Flashcards
What age groups are more sensitive to certain drugs
Very young and very old
Why do very young individuals react differently to certain drugs
- BBB is not fully developed (opioids)
- Liver function is not fully developed (opioids, chlroamphenicol)
- Renal excretion is less
Why do elderly animals react differently to certain drug
- Slower gastric emptying
- Decreased gastric secretion
3, increase in total body fat - Decrease in muscle mass
- Decrease in renal excretion but no increase in serum creatinine
- Decrease in hepatic metabolism but no decrease in conjugations
- Decrease in renal functions precedes the decline of liver functions
How do fevers, infections and inflammation impact drug metabolism
Pro-inflammatory cytokines increase capillary permeability, resulting in increased extravascular distribution of drugs, increased Vd or decreased Vd by binding to inflammatory exudates
How does liver disease modify drug metabolism
Active and inactive cirrhosis, viral and drug induced hepatitis, and chronic and active hepatitis
Overall: drug is higher in concentration and longer lasting
How does renal impairment impact drug metabolism
Decrease GFR—> can be measured by measuring creatinine clearance
What can be measured to indicate renal impairment
Creatinine- decrease creatinine clearance= renal impairment
How does meningitis, encephalitis impact drug metabolism
Increased penetration into the CNS
What route of administration leads to the greatest species variation in absorption
PO
Herbivores tend to maintain a ___ gastric pH than non-herbivores
Higher
How does a greater gastric pH in herbivores impact absorption of both weak acids and weak bases
Increased pH, more basic environment, therefore weak acids are poorly absorbed because become ionized whereas weak bases are less ionizable and are more readily absorbed
What is the primary cause of differences in drug distribution
Fat content
Fat soluble drugs will exist in higher concentrations in target tissues from animals with ___body fat
Lower- because drugs that migrate into fatty tissues will become inactive
Distribution example: would you expect a mixed breed (more fat content) or greyhound (leaner) to have a greater L/kg dose
Mixed breed because greater fat content would cause more of the drug to enter fatty tissue and less to act on CNS
Which part of pharmacokinetics has the greatest species variability
Metabolism