Pharmacokinetics 2

Question 1

Who do you love?

Answer 1

Little One!! hehehehe

Question 2

Lipophilic nature allows:

Answer 2

Passage through biological membranes, access to site of action, BUT hinders excretion

Question 3

What does lipophilic nature hinder

Answer 3

Excretion

Question 4

How are lipophilic compounds largely reabsorbed into systemic circulation?

Answer 4

During passage through renal tubules

Question 5

Drugs and xenobiotics have to be turned into what for elimination from body?

Answer 5

Hydrophilic metabolites

Question 6

What does metabolism/biotransformation do?

Answer 6

Generates more polar (water soluable) metabolites

Question 7

Prodrug is what?

Answer 7

Pharmacologically inactive, converted to active metabolite, and maximizes amount of active species that reach site of action

Question 8

What is the main function of Phase I metabolism?

Answer 8

Prepare the compound for Phase II metabolism

Question 9

Phase I metabolism includes which 5 reactions?

Answer 9

Oxidation, Reduction, Hydrolysis, Hydration, Isomerization

Question 10

Phase I metabolism is responsible for?

Answer 10

Functionalization reactions, converting parent drug to more polar metabolite.

Question 11

Phase I metabolism may result in?

Answer 11

In loss of pharmacological activity, sometimes may be equally of more active than parent.

Question 12

Where are Phase I oxidative enzymes mostly localized?

Answer 12

Almost exclusively localized in the endoplasmic reticulum.

Question 13

Phase II metabolism is

Answer 13

conjugation reactions

Question 14

Phase II enzymes are located?

Answer 14

Predominantly in the cytocol

Question 15

Name the factors affecting drug metabolism

Answer 15

Environmental Determinants, disease factors, age & sex, genetic variation

Question 16

Cytochrome P450 monooxygenase system

Answer 16

Superfamily of heme containing proteins, involved in metabolism of diverse endogenous & exogenous compounds which include (drugs, environemental chemicals, other xenobiotics.

Question 17

Phase I Metabolism Summary..

Answer 17

Final product contains chemical reactive group such as OH, NH2 etc..,functional group can be acted upon by phase II or conjugative enzymes

Question 18

Is it possible for drugs to undergo phase II followed by phase I?

Answer 18

Yes, isoniazid

Question 19

CYP 450s

Answer 19

Basis of nomenclature system is divergent evolution-sequence similarity between the cytochrome P450s.
Categorized into 17 families (CYPs)-sequences >40% identical, identified by Arabic number, CYP1
Further into subfamilies-sequences >55% identical, identified by a letter CYP1A
May have different, individual isoforms-identified by another Arabic number, CYP2D6

Question 20

Phase II (conjugation reactions) are…

Answer 20

Reaction in which a covalent linkage is formed between a functional group on the parent compound or Phase I metabolite and an endogenous substrate.

Question 21

What are examples of endogenous substrates?

Answer 21

Glucuronic acid (glucuronidation)-most common
Sulfate (sulfation)
Acetic Acid (acetylation)
and amino acid ( glutathione conjugation, glycine conjufation)
Alkyl group (methylation)

Question 22

Phase II Metabolism is

Answer 22

where highly polar metabolites are formed (excreted in urine & feces, usually inactive)-exception is morphine 6-glucuronide

• the true detoxification of drugs
• occurs mostly in cytosol
• stereoselective reactions( isomers of many drugs are metabolized differently)