Exam1Lec2Pharmacokinetics

Question 1

What is first pass effect?

Answer 1

Combined action of bacterial and liver enzyme on drugs before reaching systemic circulation. Drug is not 100% absorbed

a phenomenon in which a drug gets metabolized at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the systemic circulation.

drug administered orally, gi tract, portal vein, liver for bio transformation

Question 2

Explain the significance of absorption

Answer 2

When a drug is administered orally it goes through the liver/portal vein which is the main detoxification center(like a gate) and then it can reach other organs through the plasma compartment such as the brain, kidney, and heart. IV bypasses absorption (going through liver, GI, etc) and going straight into the plasma compartment whihc can reach other organs

Question 3

What are the factors that influence drug distribution?

Answer 3

Blood flow, lipid solubility of drug, molecular size, protein binding

Question 4

How does blood flow affect drug distribution?

Answer 4

The most higly perfused organs recieve most of the drug during the first few minutes after absorption. Delivery of drug to musle , viscera, skin and fat is slower

ex: giving propofol, within a few seconds it can reach the brain

Question 5

What is the most impt factor for drug distribution?

Answer 5

Blood flow

Question 6

How does lipid solubility of drug affect drug distribution?

Answer 6

Lipid insoluble drugs that crosses the membrane poorly are restricted in their distribution and hence in their site of action.

propofol and thiopentol can easily cross the BBB cell membrane b/c its very lipophilic

Question 7

How does Molecular size influence drug distribution?

Answer 7

Extremely large drugs are mainly confined to the plasma compartment

Ex: heparin is an anticoagulant that stays trapped in plasma compartment, it cant go through non brain capillaries

Question 8

How does protein binding affect drug distribution?

Answer 8

distribution may be limited to drug binding to plasma proteins. Only unbound drugs cross the cell memebrane. ACIDIC drugs bind to serum albumin. Basic drugs bind alpha-one glycoprotein.

Question 9

Free drug is free to

Answer 9

1. leave plasma compartment
2. transported into hepatocytes for biotransformation
3. go through glomelur filtration in kidneys for secretion
4. be actively transported into bile

Question 10

What are the drug reservoirs?

Answer 10

Plasma proteins, fat, bone, cellular reservoirs

Question 11

Many drugs bind to plasma proteins. Is this reversible?

Answer 11

Yes

but whatver stays bound is less destined to be eliminated

Question 12

A drug is always ____ % bound to plasma proteins

Answer 12

90

Question 13

Fat can act as a drug reservoir for what type of drugs?

Answer 13

Highly lipophilic drugs

high lipid water coefficient

Ex: thiopental.

Question 14

How do drugs accumulate in the bone?

Answer 14

By absorption onto the bone-crystal surface and eventual incorporation into the crystal lattice

Ex: tetracycline and lead

Question 15

Drugs accumulate in the muscle or other at ____

Answer 15

higher concentrations than in EC fluids

Ex: antimalarial agent quinacrine in the liver (high affinity for hepatocytes, you dont have much in plasma comp)

Question 16

The BBB has____ fenestrations

Answer 16

NO

Question 17

True or False, blood-brain barrier is adaptive

Answer 17

True. Note that BBB has very tight junctions b/w epithelial cells, only very hydrophobic drugs can cross cell membrane and reach CNS.

Think about that if you have so much drug concentration it can be toxic.

Question 18

Why would we create different maneuvers to increase the permeability of the BBB?

Answer 18

We want more drugs to be able to go through to enhance the efficacy of chemotherapuetic agents used to treat specific infections or tumors localized in the brain.

Question 19

How can drugs move through non-brain capillaries?

Answer 19

Drugs can move through fenestrations (openings) by bulk flow

Question 20

How can drugs move thorugh brain capillaries?

Answer 20

Drugs cross the cell membrane by passive diffusioln or carrier mediated diffusion.

Question 21

Is placenta a drug barrier? Why or why not?

Answer 21

NO because the fetus is to at least some extent exposed to essentially all drugs taken by the mother

Question 22

What is biotransformation?

Answer 22

Process of which drugs are enzymatically altered in the LIVER and eventually excreted by the kidneys.

Question 23

Biotransformation ____ water solubility of drugs

Answer 23

increases

Question 24

What is elimination?

Answer 24

Process by which the drugs are enzymatically altered (biotransf) in LIVER mainly and then eventually excreted by the kidneys.

COMBO of biotrans and excr

Question 25

Biotransformation can result in?

Answer 25

1. inactive metabolite 2. metabolite that retain similar activity 3. altered activity 4. bioactivated metabolites (Pro-drug)

Question 26

what is the term for loss of effect of drug given orally?

Answer 26

first pass effect

Question 27

Prodrug

Answer 27

a drug administered in an inactive form (no pharmacological activity) and is designed that when it undergoes biotransformation its converted to its active form.

Question 28

What are the two main reactions of biotransformation?

Answer 28

Phase 1 and Phase 2

Question 29

What are phase 1 reactions?

Answer 29

Mainly DEGRADATIVE resulting in inactivation, change in activity, or conversion of inactice cmpd (prodrug) to active drug

Question 30

What are the main phase 1 reactions?

Answer 30

Oxidation (most impt), reduction, hydrolysis

Question 31

Pharmokinetics vs Pharmaodynamic

Answer 31

Pharmaokinteics is studying what the body does to the drug vs pharmodynamic is studying what the drug does to the body.

Question 32

What are phase 2 reactions?

Answer 32

Mainly involved in COUPLING of the drug or frequently its polar metabolite from the phase 1 reaction to an endogenous substrate (ex: glucuronate)

Question 33

What are the main phase 2 reactions?

Answer 33

Conjugation/transferases

Question 34

enzyme system most responsible for oxidation reactions is ____ which is found in _____ mainly in ____

Answer 34

Cp450 (CYP) system, microsomal fraction (SER), liver then lung and kindey

Question 35

Cytochrome P450 system consists of two components. What are they and what do they require?

Answer 35

CytochromeP450 oxidoreductase Cytochrome P450 it requires molecular oxygen and NADPH

Question 36

CYP is a family of ____ with ____

Answer 36

isoenzymes with overlapping specificities ## Footnote 2 enzymes can deal with the same drug and a single enzymes can deal with different cmpds.

Question 37

What is a key step in oxidation?

Answer 37

Insertion of O2 producing a non-stable intermediate which breaks down to yield the final product

Question 38

What are the main reactions catalyzed by oxidation?

Answer 38

1. dealkylation: removal of alkyl group (CH3) 2. hydroxylation: adding a hydroxyl group 3. sulfoxide: adding oxygen to sulfur group 4. N-oxidation: adding oxygen to N 5. deamination: removal of amine group

Question 39

Non-microsomal oxidation system enzymes are

Answer 39

Alcohol dehydrogenase Aldehyde dehydrogenase ## Footnote non-microsomal enzymes are located in the cytosol

Question 40

Hydrolysis reactions are carried out by which enzymes?

Answer 40

1.Esterases: break down ester grp and hydrolyze ester linkage 2.Amidases: break down amide grp 3.Peptidases" break down peptide grp ## Footnote these enzymes are mainly found in the liver, plasma, and GI tracr

Question 41

Reduction reaction enzymes can catalyze the reduction of what?

Answer 41

Nitro groups, azo, carbonyl groups. ## Footnote These enzymes are reductases and can be found in the ER, cytosol of the liver, and other tissues