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Pharmacology > Factors Affecting ADME > Flashcards

Factors Affecting ADME Flashcards

1
Q

what ages are most sensitive to certain drugs?

A

very young and very old

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2
Q

why are the very young sensitive to certain drugs?

A

BBB not fully developed
liver function not fully developed
renal excretion is less

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3
Q

why are the very old sensitive to certain drugs

A

slower gastric emptying
decreased gastric secretion
inc total body fat
dec muscle mass
dec renal excretion
dec hepatic metabolism
dec renal functions

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4
Q

what diseases modify drug metabolism?

A

fever-infections-inflammation
liver disease
renal impairment
meningitis, encephalitis

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5
Q

how does fever-infections-inflammation modify drug metabolism?

A

pro-inflammatory cytokines inc capillary permeability
inc extravascular distribution of drugs, increased Vd
dec Vd by binding to the inflammatory exudates

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6
Q

what types of liver disease modify drug metabolism?

A

active and inactive cirrhosis
viral and drug induced hepatitis
chronic active hepatitis

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7
Q

how does renal impairment modify drug metabolism?

A

characterized by dec of creatine clearance, less excretion of drugs

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8
Q

how does meningitis, encephalitis modify drug metabolism?

A

increased penetration into CNS

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9
Q

Which maintains a higher gastric pH herbivores or non-herbivores?

A

herbivores higher gastric pH

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10
Q

what type of drugs are more likely to be in an ionized form in a herbivores stomach?

A

weak acids

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11
Q

what do differences in distribution primarily results from?

A

differences in fat content

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12
Q

Where will fat soluble drugs exist at higher concentration in target tissues, animals with high or low body fat?

A

low body fat

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13
Q

what aspect of pharmacokinetics has the greatest species variation?

A

metabolism

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14
Q

what does the variability in metabolism result from?

A

liver enzyme function

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15
Q

How do greyhounds handle thobarbituates?

A

deficits in oxidative enzymes needed for metabolism of thiobarbituates
more sensitive to the drug

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16
Q

what drug causes greyhound to have a prolonged recovery time

A

prolonged recovery for greyhound dosed with thiopental

17
Q

what is the implication of thiopental being lipid soluble in greyhounds

A

they have less body fat so they are more sensitive to the drug

18
Q

what are cats lacking in regards to phase 2 metabolism?

A

deficits in glucuronidation enzymes

19
Q

what are the consequences of cats that have deficits in glucuronidation enzymes?

A

glutathione depletion -> inc cellular oxidative stress -> hepatotoxicity -> inc Fe3+ to Fe2+ in heme -> dec O2 supply by RBC and hemolysis

20
Q

what metabolizes several neuromuscular blocking agents?

A

plasma pseudocholinesterase (succinylcholine and atracurium)

21
Q

what do excretion rates primarily depends on?

A

functions of proximal and distal convoluted tubules of the kidney

22
Q

what do collies lack that effects their drug excretion?

A

lack MDR1 for P-gp which leads to reduced excretion of several drugs from CNS

23
Q

what type of drugs are very toxic to collies due to their lack of MDR1 gene? what does this lead to?

A

avermectins -> CNS depression, ataxia, death

24
Q

why is xylazine so toxic to sheep?

A

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

25
Q

what drug causes similar issues as xylazine in sheep and goats?

A

dexmedetomidine, a2 agonist

26
Q

order species in most to least sensitive to morphine - cats, horses, dogs

A

horses, cats, dogs

27
Q

define allometry

A

correlation of physiological functions across body sizes

28
Q

How are drugs with low TI’s dosed to maximize therapeutic effect and minimize side effects across species?

A

according to body surface area (BSA)

29
Q

Equation for conversion between BSA and BW in dogs >10kg

A
30
Q
A
31
Q

Equation for calculating dose based upon absolute surface area

A
32
Q

what determine starting doses in clinical trials for interspecies use of drugs?

A

allometrics

Pharmacology (8 decks)

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