Factors Affecting ADME Flashcards
what ages are most sensitive to certain drugs?
very young and very old
why are the very young sensitive to certain drugs?
BBB not fully developed
liver function not fully developed
renal excretion is less
why are the very old sensitive to certain drugs
slower gastric emptying
decreased gastric secretion
inc total body fat
dec muscle mass
dec renal excretion
dec hepatic metabolism
dec renal functions
what diseases modify drug metabolism?
fever-infections-inflammation
liver disease
renal impairment
meningitis, encephalitis
how does fever-infections-inflammation modify drug metabolism?
pro-inflammatory cytokines inc capillary permeability
inc extravascular distribution of drugs, increased Vd
dec Vd by binding to the inflammatory exudates
what types of liver disease modify drug metabolism?
active and inactive cirrhosis
viral and drug induced hepatitis
chronic active hepatitis
how does renal impairment modify drug metabolism?
characterized by dec of creatine clearance, less excretion of drugs
how does meningitis, encephalitis modify drug metabolism?
increased penetration into CNS
Which maintains a higher gastric pH herbivores or non-herbivores?
herbivores higher gastric pH
what type of drugs are more likely to be in an ionized form in a herbivores stomach?
weak acids
what do differences in distribution primarily results from?
differences in fat content
Where will fat soluble drugs exist at higher concentration in target tissues, animals with high or low body fat?
low body fat
what aspect of pharmacokinetics has the greatest species variation?
metabolism
what does the variability in metabolism result from?
liver enzyme function
How do greyhounds handle thobarbituates?
deficits in oxidative enzymes needed for metabolism of thiobarbituates
more sensitive to the drug
what drug causes greyhound to have a prolonged recovery time
prolonged recovery for greyhound dosed with thiopental
what is the implication of thiopental being lipid soluble in greyhounds
they have less body fat so they are more sensitive to the drug
what are cats lacking in regards to phase 2 metabolism?
deficits in glucuronidation enzymes
what are the consequences of cats that have deficits in glucuronidation enzymes?
glutathione depletion -> inc cellular oxidative stress -> hepatotoxicity -> inc Fe3+ to Fe2+ in heme -> dec O2 supply by RBC and hemolysis
what metabolizes several neuromuscular blocking agents?
plasma pseudocholinesterase (succinylcholine and atracurium)
what do excretion rates primarily depends on?
functions of proximal and distal convoluted tubules of the kidney
what do collies lack that effects their drug excretion?
lack MDR1 for P-gp which leads to reduced excretion of several drugs from CNS
what type of drugs are very toxic to collies due to their lack of MDR1 gene? what does this lead to?
avermectins -> CNS depression, ataxia, death
why is xylazine so toxic to sheep?
xylazine acts through a1-adrenergic receptor
sheep have a variant a2-adrenergic receptor in their brain stem
xylazine binding to variant receptor -> hypoxemia, pulmonary edema, and death
what drug causes similar issues as xylazine in sheep and goats?
dexmedetomidine, a2 agonist
order species in most to least sensitive to morphine - cats, horses, dogs
horses, cats, dogs
define allometry
correlation of physiological functions across body sizes
How are drugs with low TI’s dosed to maximize therapeutic effect and minimize side effects across species?
according to body surface area (BSA)
Equation for conversion between BSA and BW in dogs >10kg
Equation for calculating dose based upon absolute surface area
what determine starting doses in clinical trials for interspecies use of drugs?
allometrics
