Exam1Lec3Pharmacokinetics

Question 1

The phase 2 reactions are mainly involved in ____ of drug

Answer 1

coupling

Question 2

What is coupling of drug?

Answer 2

Takes drug and conjugates to an enfogenous drug by the use of transferases

ex: glucuronic acid (the most common conjugation rxm, e.g morphine)

Question 3

What groups can be added to drug for conjugation reaction?

Answer 3

1. Sulfate
2. Acetyl
3. Methyl
4. Glutathione, glycine

Question 4

most conjugates are ____ and unable to cross plasma membrane making them ____

Answer 4

highly polar/water soluble

pharmacologically inactive

Question 5

What are the names of the different types of conjufation (phase 2) rxns?

Answer 5

glucoronidation
methylation
acetylation
sulfation
GSH (reduced glutathione)
Amino acids

Question 6

The word “transferase” is associated with what?

Answer 6

Conjugation/phase 2 rxns

Question 7

What are the factors influencing Drug Metabolism?

Answer 7

“DPAGEER”

Drug dosage
Physiologic/disease state
Age
Genetic variation
Enzyme induction
Enzyme Inhibition
Route of Drug Administration

Question 8

Explain how physiologic/disease state can influence drug metabolism

Answer 8

1. Any disease that affects liver fxn influences a drug’s hepatic clearance.
2. Congestive heart failure can decr hepatic blood flow and distribution of drugs ( if blood flow is reduced to liver, then % of biotransf is effected)
3. Liver is the center of serum albumin, so alteration
   in albumin production can alter the ratio of bound to unbound drug

remeber albumin binds drugs

Question 9

Explain how genetic variation can influence drug metabolism.

Answer 9

There is a great variation in the activity of N-acetyl transferase enzyme among different population.

the proportion of drugs metabolized by the major cytochrome P450 enzyme (know about CP450 CYP2D6 is a polymorphic drug-metabolizing enzyme)

Question 10

If you are a fast acetylator, do you have more or less drug concentration in blood? Do you have more or less tranferase?

Answer 10

Less drug
less transferase

Question 11

If you are a slow acetylator, do you have more or less drug concentration in blood? Do you have more or less tranferase?

Answer 11

more drug
more transferase

Question 12

How does dosage influence drug metabolism?

Answer 12

as drug dosage increases = drug [ ] may saturate metabolic enzyme

ex: high dosage of acetaminophen causing hepatic cell death

Question 13

How does age influence drug metabolism?

Answer 13

In young children, drugs may be more active. This is b/c the lack complete development of Phase 1 and II enzymes.

older children: some drugs less active than in adult (liver larger=more biotransf=less drugs active bc undergoes biotrans faster)

In older ppl, metabolizing enzymes decline.

Question 14

How can the route of drug administration influence drug metabolism?

Answer 14

First pass effect: combined action of bacterial enzyme w/ intestine and liver on the drug taken orally.

Think: there are lots of enzymes in the intestine and liver, and this can destroy drug

Question 15

Explain how enzyme induction can influence drug administration

Answer 15

Phenobarbital and Rifampin act as enzyme inducers

wil be on exam

Question 16

How does Phenobarbital and Rifampin act as enzyme inducers

Answer 16

increase synthesis or decrease degradation of drug metabolizing enzymes

will be on exam
with enzyme induction, the second drug you take can. be metababolized at much faster rate (reduce, half life)

Question 17

In cigarette smokers, polycyclic aromatic hydrocarbon appear to induce ____

Answer 17

N-demethylation (Phase I oxidation rxn)

so cig smokers have lower plasma lvs of drugs than non-smokers

Question 18

Enzyme induction can produce a condition known as ____

Answer 18

pharmacokinetic tolerance

drugs can block certain enzymes that are involved in metabolizing other drugs

Question 19

Explain how enzyme inhibition can influence drug metabolism.

Answer 19

some drugs can. decr the metabolism of other drugs. This inhibition can occur by destruction of drug-metabolizing enzymes by inhibitiin of enzyme synthesis

phenytoin is increased by co-admin of chloramphenicol (enzyme inhibitor)

Question 20

What are the three Renal excretion processes?

Answer 20

excretion of drugs and metabolites in the urine involve:

Glomerular filtration (+) (GFR)

Active tubular seceretion (+) (fixed capacity)

Passive tubular reabsorption (-) (pH effect)

Question 21

What is Glomerular filtration

Answer 21

Free drug enters glomerular fltration to enter urine

note: when drug is bound to plasma protein, it doesn’t enter filtration

you see free drug in urine because when its bound, it doest not go through glumerular filtration

Question 22

What is Active tubular secretion?

Answer 22

some drugs get actively secreted into urine

on exam: fixed capacity: you have many transporters that can do many things, but it will reach vmax

Question 23

What is Passive tubular reabsorption?

Answer 23

unionized form of drug can get readily reabsorbed in systemic circulation

take blood from urine and put back into systemic circulation

Question 24

What is biliary excetion?

Answer 24

Enterohepatic recirculation (biliary cycling)

Transport system analagous to those found in kidney actively secrete drugs into bile

transport drug into bile through active transport, then get reabsopbed from GI tract.

Question 25

Biliary excretion favors compounds with molecular weight ____

Answer 25

greater than 300

Question 26

Conjugated drugs can be ____ to the free drug by _____ and ____ into circulation

Answer 26

hydrolyzed
intestinal bacteria
reabsorbed

Question 27

enterohepatic recirculation ____ elimination of drugs and ____ duration of action

Answer 27

reduces
prolongs

keeps drug in body for long time

know this

Question 28

milk is ___ and ___ drug will get trapped

Answer 28

acidic
basic

impt for nursing infant and as a residue in dairy products

Question 29

True or false, Drugs can be excreted from the lungs?

Answer 29

True (anesthetic gases, alcohol)

breath analyzer ex

Question 30

What is clinical pharmacokinetics?

Answer 30

process of using drug [ ], pharmacodynamics principles to optimize drug therapy in individuals

Question 31

What is bioavailability?

Answer 31

percentage of the dose which reaches systemic circulation

Question 32

IV drugs have a bioavailability of ___

Answer 32

1

Question 33

Apparent volume of distribution

Answer 33

amount of drug in the body to the serum [ ] (L or ml)

If the volume distributiion is large, that tells us that the drug is in the body but not the plasma

Question 34

Clearance & half-life

Answer 34

C= rate of drug removal (how much of the drug is removed per unit time ml/min)

H= time it takes for [ ] of drug in plasma to decrease by 50% (unit of time)