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32 Cards in this Set

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body fat
muscle
liver
kidney
bone
What are some "other storage sites" for distribution of drug?
other storage sites
often requires more drug

may be redistributed to and from storage sites

low vascularity of adipose causes it to saturate more slowly...may pull drug from brain, etc.
Kg
Distribution of dose given per ____ of body weight.
Metabolism
aka biotransformation
Metabolism
The chemical alterations of a drug by the body.
Metabolism
-usually done by liver (also blood enzymes, intestinal mucosa, skin, lung, etc.)

Smooth ER or microsomal fraction acts to oxidize drug, reduce drug or conjugate drug with other molecule.

(cytochrome P450 group most common: note that it is inducible)

-usually changed to less active chemical

-if changed to more active form, that form is ususally later metabolized again to a less active form.
-often new chemical is more ionized and, therefore, more readily eliminated (not reabsorbed)
liver
skin
Smooth
conjugate
inducible
less
eliminated
-usually done by ______(also blood enzymes, intestinal mucosa, _____, lung, etc.)

_______ ER or microsomal fraction acts to oxidize drug, reduce drug or ________ drug with other molecule.

(cytochrome P450 group most common: note that it is __________)

-usually changed to ____ active chemical

-if changed to more active form, that form is ususally later metabolized again to a less active form.
-often new chemical is more ionized and, therefore, more readily __________(not reabsorbed)
Pathology
Age
Genetic
Drug exposure
What are some "special patient considerations" for metabolism?
hepatic
renal
cardiovascular
What is the pathology that you need to look for before inducing P450 system?
Age

Special patient considerations

P450 system (metabolism)
Infants: immature enzyme systems

aged: degenerating enzyme systems
Genetic
(special patient considerations)
(metabolism)
Some individuals are more or less able to metabolize a drug.
Drug exposure

(special patient considerations)

metabolism
may depress or activate liver

- other prescribed medications may affect biotransformation
-alcohol and tobacco use both induce the P450 system
-currently prescribed drug may enventually cause "metabolic" tolerance
Tolerance
effectiveness of a dose decreases (more required to maintain effect).
biotransformation
induce
metabolic
may depress or activate liver

- other prescribed medications may affect ______________
-alcohol and tobacco use both ______ the P450 system
-currently prescribed drug may enventually cause "__________" tolerance
Excretion
Drug eliminated from the body.
Possible routes of Excretion
kidney
bile to feces (note: enterohepatic circulation possible)
sweat glands
saliva
lungs
mother's milk
acidic
Milk is more ______ than plasma so it ionizes or "traps" alkaline drugs.
cumulative effects
For any drug, knowing excretion rate is important if to avoid ___________ _______.
Renal excretion rate
______ _________ _____ for drugs depends upon health of kidneys and: filtration, secretion, and reabsorption.
kidneys

filtration
secretion
reabsorption
What does renal excretion rate depend on?
filtration
depends upon good circulation (GFR)

concentration of unbound drug in plasma
secretion
often by active transport and carrier mediated

depends upon drug

maturity of the individual (infants, aged etc)
reabsorption
often passive

fat soluble vs. water soluble

size and shape of water soluble molecule

ionization and the effects of pH
Clearance
ml/min or L/hr

calculated volume of fluid in the body

This calculation is more informative than simply measuring the amount removed because it compensates for plasma concentration.
renal clearance
Physiologist refers to "______ _________" - how effective is the kidney.
total clearance
Pharmacologist refer to "_____ __________" = metabolic + renal + other excretion.
clinicians
In practice, ________ use "renal clearance" to estimate individual patient renal function.
Physiological state of the patient

Pathological state

"Receptor" or "cellular" tolerance
What does the ability of the active site to respond to a given concentration surrounding the receptors depend on?
Physiological state of the patient
-diurnal rhythms (sleeping pill)

-hormonal preparation
Pathological state

(The active site response differs)
digitalis works better on failing heart

aspirin decreases body temperature only if elevated.
"Receptor" or "cellular" tolerance
"down regulation" at receptor level

In addition to increased biotransformation, sometimes the body acquires capacity to function "normally" even when blood concentration of a drug is still high.

*Receptor # may change.
*Internal responses (perhaps in second messenger system) may change
* Leads to physical dependence on the drug.
receptor
blood concentration
physical
"down regulation" at ________ level

In addition to increased biotransformation, sometimes the body acquires capacity to function "normally" even when _____ __________ of a drug is still high.

*Receptor # may change.
*Internal responses (perhaps in second messenger system) may change
* Leads to ________ dependence on the drug.