M1: Ch4 Drug Metabolism & Excretion

Question 0

Substance absorbed or ingested in food and drink or deliberately as drugs. Inadvertent or accidental exposure. Can provoke biologic responses the depend on conversion of the absorbed substance into an ____________.

Answer 0

Xenobiotics. Active metabolite.

Question 1

Metabolized by same enzymatic pathways and transport systems that are utilized for dietary constituents.

Answer 1

Xenobiotics

Question 2

Xenobiotics: many are ________ that, without metabolism, would not be efficiently eliminated and would accumulate in the body which may lead to possible ________.

Answer 2

Lipophilic. Toxicity.

Question 3

Xenobiotics: most are subjected to metabolic pathways that convert these _________ into more _________ derivatives that are readily eliminated in ______ or _____.

Answer 3

Hydrophobic. Hydrophilic. Urine or Bile.

Question 4

Metabolism & Excretion collectively named as this.

Answer 4

Biotransformation

Question 5

Processes responsible for elimination of drug (parent and metabolite) from the body.

Answer 5

Metabolism & Excretion

Question 6

Frequently but not universally less pharmacologically active.

Answer 6

Metabolite

Question 7

Changes the chemical structure of a drug to produce a drug metabolite

Answer 7

Drug Metabolism

Question 8

Lipophilic drug that has no metabolism and excretion is impossible

Answer 8

Metals & Toxins

Question 9

Drug Disposition: more water soluble = easily ______.

Answer 9

Excretable

Question 10

Phases of Metabolism

Answer 10

Phase I (Redox) & Phase II (Conjugation)

Question 11

As you hydrolyze, it becomes more _______ and then ________.

Answer 11

Polar. Soluble.

Question 12

Convert the parent drug to a more polar metabolite by introducing or unmasking a functional group. Often metabolites is inactive, although in some instances activity is only modified or even enhanced.

Answer 12

Phase I Redox

Question 13

Act by causing the drug molecule to undergo oxidation or more rarely reduction.

Answer 13

Enzymes

Question 14

If Phase I metabolites are sufficiently ________, they may be readily excreted.

Answer 14

Polar

Question 15

Splitting a bond

Answer 15

Hydrolysis

Question 16

Bonds that are cleaved in Phase I

Answer 16

Ester & Amide bonds

Question 17

Undergoes Hydrolysis of the ester bond with the help of Acetylcholinesterase

Answer 17

Acetylcholine

Question 18

Undergoes Hydrolysis of the ester bond with the help of Esterase. It becomes active once metabolize.

Answer 18

Acetylsalicylic acid

Question 19

Bond used by Angiotensin

Answer 19

Peptide/Amide bond

Question 20

A peptidase/amidase that causes hydrolysis to Angiotensin

Answer 20

ACE

Question 21

Angiotensin I is activated to this which is a vasoconstrictor

Answer 21

A2

Question 22

Enzyme used in converting A1 to A2

Answer 22

Angiotensinase

Question 23

Has an amide bond and is an Anesthetic agent

Answer 23

Prilocaine

Question 24

Remove alkyl group then increases polarity

Answer 24

N-Dealkylation

Question 25

Major Reactions involved in Drug Metabolism

Answer 25

Oxidative & Hydrolysis Reactions

Question 26

Oxidative Reactions

Answer 26

N-Deakylation, A-Deakylation, N-Oxidation, Aliphatic hydroxylation, S-Oxidation, Aromatic hydroxylation & Deamination "NANA SAD"

Question 27

Many Phase I products are not eliminated rapidly and undergo a subsequent reaction in which an endogenous substrate is added.

Answer 27

Phase II Conjugation

Question 28

Endogenous substrates. Combine with the newly incorporated functional group to form a highly polar conjugate.

Answer 28

Glucuronic acid, Acetic acid, Glutathionase, Amino acid & Sulfuric acid "GAGAS"

Question 29

Hallmark of Phase II Metabolism

Answer 29

Conjugation/Synthetic Reaction

Question 30

Conjugation Reactions in Phase II

Answer 30

Methylation, Acetylation, Glucuronidation & Sulfation "MAGS"

Question 31

The most important of Phase II Conjugation reactions. Reaction does not proceed spontaneously. Requires its activated form.

Answer 31

Glucuronidation

Question 32

Activated form of glucuronic acid

Answer 32

Glucuronic Acid Uridine Diphosphate

Question 33

Drug that causes Grey baby syndrome

Answer 33

Chloramphenicol

Question 34

When chloramphenicol is given without regard for infant's diminished capacities for hepatic detoxification and renal elimination these will occur

Answer 34

Grey discoloration, Cyanosis, Hypothermia, Acidosis & Vomiting "G CHAV"

Question 35

Immature activity of this enzyme in Grey Baby Syndrome

Answer 35

Glucuronosyl Transferase

Question 36

Xenobiotic Metabolic Enzyme for Phase I

Answer 36

Oxygenases

Question 37

Xenobiotic Metabolic Enzyme for Phase II

Answer 37

Transferases

Question 38

An anticonvulsant used in treatment of epilepsy is virtually insoluble in water

Answer 38

Phenytoin

Question 39

Phase I: Phenytoin ------------> 4-OH-Phenytoin

Answer 39

Cytochrome P450 enzymes

Question 40

Phase II: 4-OH-Phenytoin -------------> 4-glucoronate

Answer 40

UDP glucuronosyltransferase

Question 41

Also terminates the biologic activity

Answer 41

Metabolism

Question 42

May also precede Phase I reactions

Answer 42

Phase II

Question 43

Site of cellular metabolism

Answer 43

Endoplasmic Reticulum

Question 44

Endoplasmic Reticulum: Phase I enzymes

Answer 44

FMOs, Ehs & CYPs "FEC"

Question 45

Endoplasmic Reticulum: Phase II enzymes

Answer 45

Conjugating enzymes, UGTs

Question 46

Enter the cell and embed in the lipid bilayer, where they encounter the Phase I enzymes.

Answer 46

Hydrophobic molecules

Question 47

Once oxidized, drugs are conjugated in the membrane by the

Answer 47

UGTs or by cytosolic transferases

Question 48

Carry out most drug Metabolism, produce conjugate substrates, transported through bile canalicular membrane then gut elimination.

Answer 48

Hepatocytes

Question 49

Enzyme Superfamily is the primary Phase I enzyme system involved in the oxidative metabolism of xenobiotics. Also are responsible for all or part of the metabolism and synthesis of a number of endogenous compounds such as steroid hormones and prostaglandin.

Answer 49

CYP450

Question 50

CYPs are most abundant in the

Answer 50

Liver

Question 51

Is the most abundantly expressed. Metabolism of 50% of clinically used drugs.

Answer 51

CYP3A4

Question 52

Rarely involved in metabolism of therapeutic drugs. Catalyze the metabolic activation of many protoxins and procarcinogens.

Answer 52

CYP1A, CYP1B, CYP2A, CYP2B & CYP2E

Question 53

CYP3A5 whose AA sequence is similar to that of CYP3A4 appears to possess roughly the same substrate specificity characteristics as (not present in all individuals)

Answer 53

CYP3A

Question 54

Hence, patients expressing both CYP3A4 and CYP3A5 have the potential to exhibit ___________ of CYP2A substrates as compared to individuals expressing only the CYP3A4 isoform.

Answer 54

Increased Metabolism

Question 55

Expressed only in the fetus and rapidly disappears following birth. Replaced by CYP3A4 and CYP3A5.

Answer 55

CYP3A7

Question 56

Second most common CYP isoform involved in human drug metabolism; most known for its propensity to exhibit genetic polymorphisms.

Answer 56

CYP2D6

Question 57

Metabolized several clinically important drugs with narrow therapeutic indices.

Answer 57

CYP2C9

Question 58

An antiepileptic agent

Answer 58

Phenytoin

Question 59

An anticoagulant

Answer 59

Warfarin

Question 60

Induce enzyme = _______ drug effect. Inhibit enzyme = ________ drug effect.

Answer 60

Decrease. Increase.

Question 61

General metabolizer

Answer 61

CYP3A4

Question 62

Study of the genetic basis for variation in drug response

Answer 62

Pharmacogenetics

Question 63

Employs tools for surveying the entire genome to assess multigenic determinants of drug response

Answer 63

Pharmacogenomics

Question 64

An individual's response to a given drug depends on a complex interplay among many environmental and genetic factors

Answer 64

Environmental & Genetic factors

Question 65

A variation in the DNA sequence that is present at an allele frequency of 1% or greater in a population

Answer 65

Polymorphism

Question 66

Two major types of sequence variations

Answer 66

Single Nucleotide Polymorphism(SNPs) & Insertions/Deletions(Indels)

Question 67

In Asian, Isoniazid is considered as an _________ which may cause _________.

Answer 67

Rapid Acetylator. Hepatotoxicity.

Question 68

In American, Isoniazid is considered as an _________ which may cause ___________.

Answer 68

Fast Acetylator. Peripheral neuropathy.

Question 69

An anti-arrhythmic drug. Slow acetylators are much more likely to develop SLE like syndrome that has been described as a characteristic and therapy-limiting event associated with this drug. The culprit is polymorphism in __________.

Answer 69

Procainamide. N-acetyltransferase.

Question 70

Are more likely to have complete ulcer healing after therapy with ________(a proton pump inhibitor that reduces gastric acid) than are extensive metabolizers. A positive benefit. 2-3% caucasians & 20-30% asians.

Answer 70

CYP2C19 Polymorphism. Omeprazole.

Question 71

Drugs are transferred from the internal to the external environment. Thru what?

Answer 71

Excretion. Biliary system, Lungs, Intestines & Kidneys "BLIK"

Question 72

Is the primary organ of removal of drugs, especially for those that are water soluble and not volatile.

Answer 72

Kidney

Question 73

Three principal processes that determine the Urinary excretion of a drug

Answer 73

Glomerular filtration, Tubular secretion & Tubular reabsorption (passive-back diffusion) "GTT"

Question 74

Excretion of a weak acid may be accelerated by ______ the urine with _______.

Answer 74

Alkalinizing. Bicarbonate.

Question 75

Excretion of a weak base may be accelerated by ________ the urine with _________.

Answer 75

Acidifying. Ammonium chloride.

Question 76

The rate of urinary drug excretion will depend on its degree of binding protein

Answer 76

Vd

Question 77

The amount of drug that finally appears in the urine will represent a balance of _______, _______ & _______ drug.

Answer 77

Filtered. Reabsorbed. Secreted.

Question 78

Passage of xenobiotics from the blood into the liver normally is not restricted because the endothelium of the hepatic blood sinusoid behaves as a porous membrane. Hence, drugs with molecular weights ___________ those of most protein molecules readily reach the hepatic extracellular fluid from the plasma.

Answer 78

Biliary excretion. Lower than.

Question 79

The physiochemical properties of most drugs are sufficiently favorable for ___________ that the compound will reenter the blood that perfuses the intestine and again to be carried to the liver.

Answer 79

Passive Intestinal Absorption

Question 80

Gases and other volatile substances that enter the body primarily through the respiratory tract can be expected to be excreted by this route. All volatile materials.

Answer 80

Pulmonary excretion

Question 81

Lipid insoluble compounds such as urea and glycerol

Answer 81

Sweat & Saliva

Question 82

More acidic than plasma, basic compounds like alkaloids may be somewhat more concentrated.

Answer 82

Human milk

Question 83

Examples of Alkaloids

Answer 83

Morphine & Codeine

Question 84

pH level of Milk

Answer 84

6.5

Question 85

Other factors of Human milk

Answer 85

Plasma binding, Lipid solubility & Molecular weight "PLM"

Question 86

Main organ for Drug Metabolism

Answer 86

Liver

Question 87

Main organ for Drug Excretion

Answer 87

Kidney