L6: Factors affecting ADME Flashcards
How does very young age affect drugs
- BBB not fully developed
- liver function not fully developed
- renal excretion is less
how does fever/infection/inflammation affect drug metabolsim
- pro inflammatory cytokines increase capillary permeability
- increased extravascular distribution of drugs (increased Vd)
- decreased Vd by binding to inflammatory exudates
why are weak acid drugs more likely to be in an ionized form in an herbivores stomach
herbivores have a higher gastric pH
what is the main cause for the differences in redistribution b/w species and breeds
fat content
fat soluble drugs will exist at _______ concentrations in tissues from animals w/ low body fat
higher
metabolism variability results from differences in what between species
liver enzyme function
greyhounds have deficits in ______ enzymes needed for the metabolism of thiobarbituates
oxidative
leads to prolonged recovery time in greyhounds dosed w/ thiopental
cats have deficits in _____ which is an enzyme needed for phase II metabolism
Glucuronidation
excretion rates primarily depend on the function of what
proximal and distal convoluted tubules of the kidney
Collies (and some other breeds) lack the multidrug resistant gene (MDR1) for the protein P glycoprotein, what does this have an effect on
reduced excretion of several drugs, especially avermectins from CNS
What makes collies and some other breeds susceptible to acute avermectin toxicity (associated w/ CNS depression, ataxia, death)
lack of multidrug resitance gene (MDR1) for protein P glycoprotein
Xylazine is a ____ that acts through _____ receptors
sedative that acts through alpha2 adrenergic receptors
in sheep, xylazine causes what
hypoxemia, pulmonary edema and death
what is allometry
correlation b/w physiological functions across body sizes
to maximize therapeutic effect and minimize side effects, drugs w/ low Therapeutic indexes are dose according to…
BSA (body surface area)
