Pharmokinetics chapter 1

Question 1

pharmokinetics

Answer 1

what the body does to a drug

Question 2

four pharmokinetic properties

Answer 2

absorption, distribution, metabolism, elimiation

Question 3

oral administration

Answer 3

absorption is variable,

advantages: safest, convenient, economical
disadvantages: limited absorption of some drugs, food, patient compliance necessary, drugs metabolized sometimes

Question 4

IV admin.

Answer 4

absorption not required

advantages: immediate effect, ideal for large volumes, suitable for irritating substance, emergencies, titration possible, good for high MW proteins
disadvantages: oily substances not good, bolus may be bad, most must be slowly injected, strict aseptics

Question 5

subcutaneous admin.

Answer 5

absorption depends on drug diluents. aqueous is prompt and depot is slow

advantages: suitable for slow release and for poorly soluble suspensions
disadvantages: pain or necrosis, has to be in small volumes

Question 6

intramuscular admin

Answer 6

absorption same as subcutaneous

advantages: suitable for moderate drug vol., oily and irritating substances, and for self administering patients
disadvantages: affects creatine kinase test, painful, and can cause intramuscular hemorrhage

Question 7

transdermal admin. (patch)

Answer 7

absorption is slow and sustained

advantages: bypasses first pass metab., convenient, painless, ideal for lipophilic , drugs w/ poor bioavailability, and drugs that are quickly eliminated
disadvantages: allergies, drug must be highly lipophilic, delay of delivery, limited to drugs taken in small doses

Question 8

rectal admin

Answer 8

absorption is erratic and variable

advantages: partially bypasses first pass effect, and stomach
disadvantges: irritation of rectum

Question 9

inhalation admin.

Answer 9

systemic absorption may occur and is not always desirable

adavntages: rapid, titration possible, fewer systemic side effects, good for respiratory problems
disadvantages: addictive, regulation is difficult

Question 10

sublingual admin.

Answer 10

absorption depends on drug

advantages: bypasses first pass, stomach acid destruction,stability maintained because of pH of saliva, immediate effect
disadvantage: limted to certain drug type and small doses,, may lose part of drug if swallowed

Question 11

Weak acid and. Weak base uncharged form

Answer 11

HA B

Question 12

PKa

Answer 12

Measure of strength of interaction between a compound with a proton. Lower pKa means more acidic and vice versa

Question 13

Distribution equilibrium

Answer 13

Permeable form of drug achieve equal concentration in all body water spaces

Question 14

Why intestine absorption is favored over stomach

Answer 14

Blood flow, surface area, p glycoproteins (high amounts equal slow absorption), contact time, pH

Question 15

Bioavailability

Answer 15

Rate and extent which drug reaches systemic circulation. IV is 100%. AUC measures extent of absorption

Question 16

Factors that influence bioavailability

Answer 16

First pass hepatic metabolism, solubility of drug (largely lip ophicleide but soluble in aqueous solution is best), chemical instability in certain pH or enzymes, nature of drug formulation

Question 17

Bioequivalence

Answer 17

Two drugs are bio equivalent if same bioavailability and similar times to achieve peak blood conc.

Question 18

Therapeutic equivalence

Answer 18

Two drugs that have same dosage form, active ingredient, same route of admin., similar clinical and safety profile

Question 19

Drug distribution

Answer 19

Reversible leaves blood to interstitial, depends on CO,BF,cap. Perm., tissue vol., binding of drug, and lipophilicity of drug

Question 20

Cap perm.

Answer 20

Dependent slit junctions between endothelial cells. Liver has a lot. Brain has none

Question 21

Binding of drugs to plasma and tissue proteins

Answer 21

Binding to plasma proteins makes it non diffusable and slows rate of transfer out of vasculature. Conversely binding to tissue proteins may cause toxicity or prolong actions .

Question 22

Volume of distribution

Answer 22

Vd=amount of drug in body/C0 (concentration at time zero) fluid volume that is required to contain the entire drug in the body at the same concentration measured in plasma. Vd=dose/C0

Question 23

Plasma compartment

Answer 23

High MW or protein bound. Low VD

Question 24

Extra cellular fluid

Answer 24

Low MW but hydrophilic can pass through slit junction to interstitial fluid but can’t pass through cell membrane.

Question 25

Total body water

Answer 25

Low MW and lipophilic. Can go anywhere

Question 26

Effect of Vd on half life

Answer 26

Increases in Vd increases half life because they are unavailable to excretory organs

Question 27

Half life

Answer 27

Time it takes to reduce the plasma drug conc to half. .693 Vd/CL

Question 28

Three major routes of elimination

Answer 28

Urinary,biliary,hepatic

Question 29

Clearance

Answer 29

CL=.693 x (Vd/t1/2)

Question 30

First order kinetics

Answer 30

Rate of dug metabolism and elimination is directly proportional to concentration of free drug. Constant fraction of drug is metabolized over time. v=(Vmax [C])/Km

Question 31

Zero order kinetics

Answer 31

v=Vmax concentration is higher than michaelis constant so does not depend on concentration. Constant amount is metabolized over time

Question 32

Kidney metabolism

Answer 32

Cannot efficiently eliminate lipophilic drugs that readily cross cell membranes back to distal convoluted tubules so they are metabolized into hydrophilic substance in the liver via phase 1 and 2

Question 33

Phase 1

Answer 33

Convert lipophilic drugs into more polar molecules by introducing or unmasking polar functional group such as OH or NH2. Mostly catalyze do by cytochrome P450 in the liver and GI tract

Question 34

C P450 isoforms all CYP family and contributions to drug bio transformation

Answer 34

3A4/5,2A6,2B6,2E1,2C19,1A2(11%),

2C8/9(16%)2D6(19%)

Question 35

Phase 2

Answer 35

If a drug is still too lipophilic to be excreted than it enters phase 2 and a subsequent conjugation occurs.

Question 36

CLtotal =

Answer 36

CL hepatic, CL lungs, CL renal, CL other

Question 37

Increase in drug half life Is caused by

Answer 37

Diminished renal or hepatic BF, decreased ability to extract drug from plasma, decreased metabolism

Question 38

Steady state concentration

Answer 38

Reached when rate of drug elimination is equal to to drug administration rate. Steady state plasma concentration is proportional to infusion rate. If infusion rate is doubled than steady state concentration is doubled. Time needed to achieve steady state does not change.

Question 39

Time required to reach steady state concentration

Answer 39

Rate constant to reach steady state is same as elimination. Thus 50% at t1/2. 75 at 2 half life. 87.5 at 3 half life. 90 at 3.3 half lives. So drug reaches steady state in about four to five half lives. Half life is sole determinant of rate drug reaches steady state and is only affected by factors that affect half life. When infusion stops concentration washes out at same rate to zero

Question 40

Dosing rate

Answer 40

(Target C plasma)(CL)/F

Question 41

Loading dose

Answer 41

VDx(desired steady state plasma concentration)/F(absorbed bioavailability) in IV infusion it is 100 so it is ignored. Loading dose is useful for drugs with long half lives

Question 42

four mechanisms of drug absorption

Answer 42

passive diffusion, facilitated diffusion, active transport, endocytosis and exocytosis (for large molecules)

Question 43

factors influencing absorption

Answer 43

pH,