Pharmacokinetics

Question 1

when do drugs reach their peak effect?

Answer 1

not instantaneously, takes time (lag period)

Question 2

what are 3 important considerations for routes of administration?

Answer 2

1. convenience (oral vs injection)
2. bioavailability (efficiency of absorption in gut)
3. processing (hepatic portal circ.)

Question 3

what are 3 aspects of pharmacokinetics that alter a drugs effect?

Answer 3

Absorption, distribution, excretion

Question 4

first pass metabolism

Answer 4

loss of drug ingested orally during its first pass through hepatic circ. into liver, before entering systemic circ. (affects bioavailability)

Question 5

what is the extraction ratio?

Answer 5

clearance (liver) / blood flow (inverse of bioavailability)

Question 6

clearance

Answer 6

V of blood that can be rid of a certain drug over a period of time (better processing in liver = higher clearance = higher extraction ratio)

Question 7

5 factors of oral route of administration

Answer 7

most common and convenient, absorption is slow, affected by food intake, influenced by “first pass metabolism”

Question 8

4 factors of intravenous route of administration

Answer 8

direct into circ., most rapid onset, requires expertise, high control over circulating level

Question 9

3 factors of intramuscular/subcutaneous

Answer 9

painful, rate of absorption depends on blood flow, depot preparations (slow dissolving) for sustained release

Question 10

2 factors of inhalation route of administration

Answer 10

absorption through epithelium in lungs, rapid onset

Question 11

2 factors of sublingual (dissolve under tongue) route of administration

Answer 11

rapid, bypasses “first pass metabolism” effects despite taken orally

Question 12

4 factors of transdermal (ointment/patch) route of administration

Answer 12

convenient, slow absorption, sustained exposure, no “first pass metabolism”

Question 13

what is bioavailability?

Answer 13

fraction of unprocessed drug that reaches systemic circ. after administration

Question 14

what 4 routes of administration has the highest % of bioavailability?

Answer 14

intravenous (100), intramuscular and subcutaneous (75-100), transdermal (80-100)

Question 15

what are 2 key factors for drug distribution?

Answer 15

1. binding to plasma proteins

2. drug accumulation in tissues

Question 16

how is drug distribution affected by binding to plasma proteins?

Answer 16

drugs circulate in an equil. btwn free and bound, only the free fraction is pharmacologically active

Question 17

what 2 factors affect drug accumulation in tissues?

Answer 17

lipophilic drugs easily accumulate in tissues, highly perfused tissues accumulate more easily

Question 18

what is the volume of distribution?

Answer 18

relative comparison of how well different drugs are distributed in body (not specific V)

Question 19

what is the volume of distribution equation?

Answer 19

V of dist. = total amount in body / [drug] (in blood, plasma, serum, or unbound)

Question 20

what drugs have a VOD close to blood V? ex?

Answer 20

drugs restricted to circ./plasma (highly bound to plasma proteins); heparin

Question 21

what drugs can be distributed into ECF?

Answer 21

poorly lipid-soluble drugs

Question 22

what drugs can distribute throughout entire body water?

Answer 22

drugs that can be transported into cells

Question 23

what drugs have the highest VOD?

Answer 23

lipophilic drugs (accumulated in fat)

Question 24

rank the types of drugs from smallest to largest VOD, what are the general VOD / 70 kg?

Answer 24

restricted to circ./plasma (~3.5 L), poorly lipid soluble (~14 L), distribute throughout entire body water (>35 L), lipophilic (?)

Question 25

how does distribution affect elimination of a drug?

Answer 25

[drug] decr w/ exponential decay kinetics (elimination rate/slope depends on [drug])

Question 26

What is the difference between multiple compartment distribution systems without an elimination pathway vs with?

Answer 26

Without an elimination pathway, the concentration briefly peaks then decr and levels off once distributed evenly throughout body. With an elimination pathway, the graph does not level off as the drug is eliminated but decr slower than single-compartment bcse distribution decr effective conc. in blood/drug has to return from extra vascular V to blood (incr lifetime)

Question 27

How are drugs eliminated?

Answer 27

Metabolism in the liver (biotransformation) and excretion (kidney/gut)

Question 28

What is phase 1 and phase 2 of liver metabolism of drugs?

Answer 28

• don’t necessarily occur sequentially
  1: mixed function oxidase system (CYP family enzymes) ie. hydroxylation, dehydrogenation, etc
  2: addition of large polar adducts to parent compound or phase 1 product to make it easier to excrete

Question 29

What is the most abundant/important CYP enzyme?

Answer 29

CYP3A4

Question 30

Can >1 CYP enzyme modify a drug?

Answer 30

Yes

Question 31

What is hepatotoxicity?

Answer 31

Toxic/reactive intermediates formed by biotransformation

Question 32

How are drugs excreted through feces?

Answer 32

Biotransformed drugs incorporated into bile & phase 2 modifications make drug more polar and less prone to reabsorption in digestive tract

Question 33

How are drugs excreted through urine?

Answer 33

Drug passes through glomerular filtration in kidneys, hard to be reabsorbed so excreted

Question 34

How is drug elimination usually described?

Answer 34

Half-life (exponential decay - rate vs conc.)

Question 35

What does “capacity-limited elimination” mean?

Answer 35

[drug] has saturated enzymes so rate of elimination is constant (does not depend on [drug])