Basic Principles III

Question 1

70 kg person

Answer 1

• 3 L in plasma
• 9L in interstitial space
• 28 L intracellular
• Vd is volume drug should go in- so if it diffuses only in plasma- 3L, plasma and interstitial- 12L, and total is 40 L

Question 2

volume of distribution

Answer 2

• important pharmacokinetic parameter
• can be experimentally determined
• Vd= dose/cp (cp=dose/vd)
• administration of a drug causes a certain plasma concentration
• cp 1/alpha to vd
• cp increases, Vd decreases
• cp decreases, Vd increases ( can diffuse to more volume)

Question 3

vd

Answer 3

• L/kg
• doses in average adults are estimated in volunteer trials
• weights for kids used for dosing
• body surface area used in chemo

Question 4

apparent volume

Answer 4

• drug can get trapped by plasma volume- vd should be 12 but is only 3
• high degree of tissue binding creates a reservoir- should only be 28 but is over 40
• might need to give stimulus dose

Question 5

distribution

Answer 5

• vi is plasma- dynamic flux
• admin and elimination to and from Vi
• Vi also in flux with Vt- total Vd
• distribution into Vt and then back into Vi and leaves in elimination
• therefore two half lives- 1st into Vt, second for elimination

Question 6

factors affecting distribution

Answer 6

1. blood flow- will distribute first to more vascular organs with higher blood flow
2. ability of drug to enter a fluid space- pH, binding, transport, lipid solubility
3. time after admin- equilibrium with various compartments may take a long time to achieve
4. redistribution- drug may have to distribute from initial compartments to the target tissue
5. size of the patient- Vd can vary with size- many drugs dosed on the basis of weight or body surface area, especially for Peds or chemo

Question 7

thiopental

Answer 7

• drug used for anesthesia

- goes to brain first and then redistributes to other organs

Question 8

placenta and distribution

Answer 8

• no barrier to drugs that are less than 1000 in molecular weight, which is most drugs
• fetal liver and kidney are immature
• PDR and other references
• safety ratings A-X
• B is humans ok, rats bad
• C is rat tested not human
• D is if abs needed
• X is teratogenic

Question 9

teratogenic effects

Answer 9

-esp in 1st trimester, abnormal tissue differentiation

Question 10

toxic effects

Answer 10

• may be chronic or acute
• chronic: addiction, birth weight, specific organ abnormalities
• acute: respiratory depression, hyperbilirubinemia, vascular problems

Question 11

blood brain barrier

Answer 11

• an anatomical protective barrier, created by the existence of tight junctions between the cap endo cells and choroid plexus cells in ventricles
• to enter CNS drug must be lipid soluble or transported by a carrier mediated mechanism
• have to give L dopa to get across and then get changed to dopamine

Question 12

caffeine example

Answer 12

LOOK IN NOTES FOR MATH

-get Vd into liters, then cp=dose/Vd

Question 13

consequences of barrier in brain

Answer 13

• can affect apparent drug potency
• may need to use lipid soluble precursors of the active drug
• will create special problems in treating overdoses of lipid soluble or electrolyte drugs
• may necessitate direct injection of certain drugs into the CNS

Question 14

weak acid drug in brain

Answer 14

• diffuses as HA then gets stuck in brain as A-
• must add bicarb to increase pH of plasma to draw acid back out
• use when overdose on aspirin or barbituates

Question 15

weak base drug and brain

Answer 15

• diffuses as RNH2 and gets stuck as RNH3+

- must increase acidity and decrease pH to cause PNH2 and H to combine outside the brain and draw more RNH2 out

Question 16

protein binding of drugs

Answer 16

• only free drug can interact with receptor
• to albumin, other plasma proteins, or tissue sites
• can change apparent Vd- larger if tissue binding occurs, smaller if plasma protein binding occurs
• can result in unexpected drug tox- act as reservoirs of active drugs (antibiotics and neuropathy)
• drug storage-may need to fill the storage sites before enough free drug is available to interact with receptor-loading dose
• short term-protein binding
• long term-lipid binding or bone
• albumin binds hydrophilic stuff
• plasma concentration reported is both bound and free- free is the only one doing anything

Question 17

displacement of drugs

Answer 17

• normally have equilibrium of one drug and its receptor so effect is desirable
• if adding another drug, may compete for same binding spot and cause too much free drug of the other kind- too much effect
• drug displacement=more free drug at receptor=greater pharmacologic response