[1] Pharmacokinetics II (CH2)

Answer 1

refers to the chemical changes that take place to the drug following administration

Question 2

biotransformation usually occurs via __ located in __ that change the physical structure of a drug

Answer 2

biotransformation usually occurs via [enzymes] located in [organs] that change the physical structure of a drug

Question 3

compare the differences between pharmacodynamic vs pharmacokinetic

Answer 3

pharmacodynamic: what the drug does to the body
pharmacokinetic: what the body does to the drug

Answer 4

True, alteration of the drugs structure alters the drugs pharmacologic properties, aiding in removal from the body

Question 5

[T/F]: biotransformation “usually” makes drug inactive or it greatly reduces activity

Answer 5

True, biotransformation usually makes the drug active or greatly reduces its activity

Question 6

what is an example of a drug that is inversely related to biotransformation

Answer 6

“Prodrugs” are activated by the process of biotransformation, NOT reduced

Question 7

mechanisms of drug metabolism can be classified as __ or __. What happens during these classifications?

Answer 7

mechanisms of drug metabolism can be classified as [Phase I] or [Phase 2].
- typically the drug is converted to a more “polar” and water-soluble compound that can be more readily excreted by the kidneys

Answer 8

• sometimes explained as placing or exposing a “handle” on the drug for subsequent Phase II reaction

Answer 9

Oxidation
Reduction
Hydrolysis

Answer 10

Conjugation (usually follows Phase I rxn)

• Conjugation, in this context, is the process of covalently linking drugs or prodrugs to various natural or synthetic molecule carriers for specific applications
• ie. polymers, polypeptides or proteins, lipids, and carbohydrates

Question 11

what is the predominant biotransformation

Answer 11

Oxidation (Phase I)

Question 12

where is the CYP450 family located?

Answer 12

the liver

Question 13

drug-drug interactions often involve…

Answer 13

a drug interfering with metabolism of another by competing for the same CYP450s

Answer 14

either intact drug or metabolite following Phase I may be coupled (conjugated) to an endogenous substance to make it polar
- ex. acetylation, glucuronidation, sulfation

Answer 15

True

Question 16

the primary organ/location for drug metabolism is the …

Answer 16

liver

Question 17

the liver contains an abundant amount of CYP450s… in addition to the liver, what other organs/locations have these enzymes?

Answer 17

lungs, kidneys, skin, epithelial layer of the GI tract

Question 18

we know that the liver is the main organ for biotransformation:
- what would be fair to assume about a damaged or diseased liver in conditions such as hepatitis or cirrhosis?

Answer 18

damage or disease of the liver could lead to reduced metabolism of drugs resulting in prolonged or toxic drug effects

Question 19

enzymes involved with drug metabolism may be induced or inhibited
- what does that mean?

Question 20

what potential situation may result from enzyme induction

Answer 20

pt could develop a tolerance to a drug

- since the drug is being metabolized faster, higher amount needed to exert effect

Question 21

what potential situation may occur from enzyme inhibition?

Answer 21

elevated plasma drug [ ]

- such that higher drug level results in adverse effects

Question 22

what is the “take home message” regarding enzyme induction and inhibition?

Answer 22

health care professionals need to be aware of drug combinations that can yield phenomenon’s

Answer 23

True

Question 24

• Kidneys
• Lungs
• GI Tract

Answer 24

Kidneys: primary route of excretion for most drugs
Lungs: play role in excreting volatile drugs administered via inhalation
GI: minor role for excretion, either reabsorbed or drug is excreted in feces

Question 25

functional unit of the kidney is the __, where each kidney contains about __

Answer 25

functional unit of the kidney is the [nephron], where each kidney contains about [1 million nephrons]

Question 26

the epithelial lining of the kidney tubule is generally impermeable to the polar metabolite of a drug... what happens then?

Answer 26

drug passes through tubule into urine

Question 27

drugs may also be actively secreted into tubule by __ and __ in the __

Answer 27

OATs & OCTs in the Proximal Tubule (PT)

Question 28

recall that filtration occurs at the...

Answer 28

glomerulus

Question 29

the rate in which a drug is eliminated is important in determining...

Answer 29

determining the amount and frequency of drug dosing

Question 30

- if a specific amount of drug is given too frequently, __? | - if dosing interval is too long (pt takes once daily when Rx is every 4 hours), __?

Answer 30

- drug given too frequently = may accumulate to toxic levels | - dosing interval too long = drug may never reach therapeutic levels so no effect

Question 31

what are the 2 primary measurements for base dose and intervals?

Answer 31

clearance & half-life

Question 32

clearance (CL) by organ depends on what 2 things?

Answer 32

blood flow & extraction ratio

Question 33

what is CL defined as?

Answer 33

volume of plasma completely cleared of drug per unit of time - ex. 500mL/min - NOT: mg/min

Question 34

what is the abbreviation of clearance?

Answer 34

CL

Question 35

what is the abbreviation of half-life?

Answer 35

t(1/2)

Question 36

what is half life (t1/2) defined as?

Answer 36

time it takes for the [ ] of a drug in plasma to decrease by one-half

Question 37

Drug X has t1/2 of 2 hours, so 50% of Drug X will be eliminated in ..?

Answer 37

2 hours

Question 38

what is the equation for t1/2?

Answer 38

t1/2 = (log * Vd) / CL

Question 39

since t1/2 is a fxn of Vd and CL, changes in t1/2 may by due to to changes in Vd or CL - what could be a reason as to why this would happen?

Answer 39

disease

Question 40

how many half-life's does it take to reach a steady state [ ] of a drug once started?

Answer 40

5 half-life's

Question 41

how many half-life's does it take to eliminate a drug from the body once dosing in terminated?

Answer 41

5 half-life's

Question 42

what is the goal of dosing schedules?

Answer 42

reach and maintain a certain plasma [ ] of a drug for a therapeutic effect

Question 43

what is the easiest way to reach and maintain a certain plasma [ ] for a drug in order for it to assert its therapeutic effect?

Answer 43

continuous IV infusion | - rate of admin can match the rate of elimination

Question 44

if an interval of drug admin is too long, you may need larger doses. - you tend to see ___ in drug [ ] on a chart

Answer 44

if an interval of drug admin is too long, you may need larger doses. - you tend to see [peaks and valleys] in drug [ ] on a chart

Question 45

if an interval of drug admin is in shorter intervals, lower dosages may be needed. - lower dosages are intended to avoid __ of drug [ ] in plasma

Answer 45

with shorter intervals, lower dosages of drug admin are intended to avoid [large fluctuations] of drug [ ] in plasma

Question 46

graphically compare the drug concentration levels given an IV with the following dosage intervals: - large dosing intervals - shorter dosing intervals

Answer 46

[large]: drug doesn't accumulate or reach a steady state concentration (Css) [shorter]: drug does accumulate and reaches a steady state concentration (Css)

Question 47

list some factors as to why 2 patients who take the same drug may have different beneficial or adverse responses between each other:

Answer 47

genetics, disease, drug interactions, age, diet, sex, etc.

Question 48

[drug metabolism & response]: ultimate goal regarding pharmacogenomics and patient drug admin

Answer 48

ultimate goal: design drug treatment regiment to individual patient depending on genetics

Question 49

[drug metabolism & response]: disease

Answer 49

- altered blood flow / damaged organs can change how the metabolism or excretion of a drug will change [ ] of plasma drug levels - vomiting & diarrhea can impair absorption

Question 50

what considerations should you have regarding drug drug interactions (DDI)?

Answer 50

- DDI could be beneficial (ie. 2 drugs from different classes healthily lower BP) - DDI may be adverse (ie. 2 drugs from different classes both cause depression) - DDI may be neutral/cancel (ie. 1 bronchodilator + 1 bronchoconstrictor)

Question 51

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