Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key


Play button


Play button




Click to flip

160 Cards in this Set

  • Front
  • Back
Most drugs are lipophilic or hydrophilic?
How does the body ('bag of chemicals') get rid of foreign chemicals?
Makes them water soluble
What is a xenobiotic?
exogenous chemical (ex. pesticide on food, lipstick, etc)
During metabolism what is the difference between an enzyme and a co-enzyme?
Enzymes do not change.

Coenzymes change (give or take).
Are enzymes always reqd during metabolism?
What are the sources of elimination from the body for a xenobiotic or lipophilic drug after it metabolizes into metabolites?
1. URINE (Main source of elim)

2. bile

3. sweat

4. saliva

5. lungs

6. milk
What 3 general things does drug metabolism lead to?
1. Termination of drug action

2. Bioactivation of drug

3. Drug intrxns
In what 3 ways might a drug action be terminated?
1. Bioinactivation

2. Detoxification

3. Elimination
In what 2 ways might a drug be bioactivated?
1. Prodrugs (inactive until metabolized)

2. Active metabolites (some drugs are active with active metabolites...ex) longer t1/2...different drug-drug intrxns)
What is the most important site for drug metabolism?
List 8 sites of drug metabolism?

2. intestine

3. kidney

4. lung

5. adrenal glands

6. brain

7. skin

8. placenta and fetus
How might the intestine be involved in drug metabolism?
1. Digestive secretions (esterases, lipases, etc)

2. Intestinal wall (ex. sulfotransferases)

3. Bacterial flora in the intestine have their own enzymes (ex. reductase)
All sites of drug metabolism contain what?
A polar molecule is hydrophilic or hydrophobic?
Explain a situation that might occur between a drug and a placent/fetus?
Most drugs can pass through the placenta because they are lipophilic.

Once through they may become a hydrophilic metabolite that can't leave and could build up to toxic concentrations.
Phase I rxns are aka what?
Functionalization rxns
Phase I (Functionalization rxns) could be referred to as "? rxns".
"little rxns"...putting a little group on or off
List 3 phase I rxns?
1. Oxidative rxns

2. Reductive rxns

3. Hydrolytic rxns
Phase II rxns could be referred to as "? rxns".
Big rxns...putting something big and H2O soluble on molecule to help excrete it.
List 5 types of Phase II rxns?
1. Glucuronic acid conjugation

2. Sulfate conjugation

3. Glycine, glutamine and AA conjugations

4. Acetylation

5. Methylation
Do drugs undergo only phase I or phase II rxns but not both?
Drugs may undergo Phase I, Phase II, or both.

MOST drugs undergo BOTH.
Covalent bonds share electrons in what way?
What does arrow pushing show?
The movement of only electrons
What is the purpose of a Phase I rxn?
To make a compound more polar to ultimately enhance excretion.

1. Enhance excretion (more h2o soluble)

2. Prepare for phase II rxns (add functional group "handle")
How might a phase I rxn make a compound more excretable?
Add a hydroxyl group (more water soluble)
Why would you add a 'handle' to a compound through a phase I rxn?
Because Phase II rxns require a handle to attach their 'big group' to.
What is the most common phase I rxn?
oxidative biotransformations

What enzyme systems carry out oxidative biotransformations (oxidation)?
Mixed Function Oxidases, Monoxygenases, or Cyp450.
A mixed function oxidase system involves what enzyme?
Cytochrome P450
What are the two parts of a mixed function oxidase system (P450)
1. Apoprotein

2. Protoporphyrin
What does the apoprotein part of an MFO bind to?
part that binds to drug
What does the protoporphyrin part of an MFO bind to?
It has the heme part, has iron, binds Oxygen
Are apoproteins or protoporhyrins responsible for the variety of cyps observed?
apoprotein (aa sequence)
Why are drugs specific to different binding sites?
Because of different AA sequences...most variable being at the substrate binding site.
Where is cytochrome P-450 found?
1. LIVER (high concentrations)

2. kidney

3. intestine

4. skin

5. placenta

6. adrenal cortex
Why could cytochrome P-450 be called a versatile enzme?
It is capable of oxidizing many substrates. This may be due to the multiple forms of the enzyme. The apoprotein portion vary in their tertiary structure. This may account for differences in substrate binding.
Describe a reduction?
Rxn that effects a molecule by:

Increases hydrogen content


Decreases Oxygen, Nitrogen, Halogen content
Describe an oxidation?
Rxn that effects a molecule by:

Decreasing the hydrogen content


Increasing the oxygen, nitrogen, or halogen
Why would the oxidation of aromatic moieties be a huge part of drug metabolism?
Because most drugs have aromatic (phenyl) rings...only one point of substitution.
For monosubstituted benzene rings hydroxylation occurs at what position?
Para(primarily...but can also be ortho or meta)
Most phenolic metabolites undergo what?
Further phase II rxns (remember oxidation is phase handle for phase II)
Hydroxylation of a compound does what to it?
oxidizes it
Substituents on an aromatic ring may influence the ease of hydroxylation.

Aromatic hydroxylation rxns proceed most readily in ? rings.
Hydroxylation rxns proceed most readily in activated (electron rich) rings.
Which aromatic rings are slow or resistant to hydroxylation?
Those containing electron withdrawing groups. (deactivated)
List 4 electron withdrawing groups?
1. Cl

2. -N+R3


For compounds with 2 aromatic rings what occurs with hydroxylation?
Usually only at on ring.

An example would be phenytoin.

Usually occurs preferentially in the more electron-rich in a ring with e-donors or without e-withdrawers.
What is an arene oxide?
unstable electrophilic compound.

intermediat formed during oxidation of aromatic rings
Arene oxides are ? and ? ?.
Electrophilic and Chemically reactive.

(electron loving so it has a positive charge)
Arenes can undergo what 3 COMPETING rxns?
1. Formation of arenols

2. Formation of trans-dihydrols

3. Formationn of glutathione adducts (phase II)

(also may react with nucleophilic functional groups on DNA, RNA, and other macromolecules. Can cause toxicity)
An arenol is a ? product of an arene oxide.
Hydroxylated product (OH)
The formation of trans-dihydrodiols from an arene oxide requires what enzyme?
Epoxide hydrolase
A glutathione adduct is formed from an arene oxide via what enzyme?
Glutathione S-transferase (transfers glutathione via sulfur)
The formation of a glutathione adduct is a detoxification pathway for what?
For electrophiles (changes them to nucleophile?)
Most drugs are nucleophiles or electrophiles?
What macromolecule adducts may be involved with arene oxide rxns?
DNA, RNA, proteins.
What is a NIH shift?
Phase I

Rearrangement of an arene oxide to an arenol.
NIH shifts occur with ? as well as with ?.
With substituents as well as with hydrogen.
Primary alcohols are often further oxidized to ? and ? ?.
Often further oxidized to aldehydes and carboxylic acids.
What is a benzylic carbon?
C on benzene ring
Alkyl side chains are often metabolized on the ? or ? carbon.
Terminal or Penultimate carbon.
The 2 types of side chain oxidations?
1. w (omega)

2. w-1 (omega minus 1)
Which carbon is the penultimate carbon?
The next to last C in a chain.
Pentobarbital undergoes what kind of side chain oxidation?
w-1 (penultimate)
Secobarbital undergoes what kind of side chain oxidation?
w (terminal)
Cyclohexane rings have no ? bonds.
No double bonds...(chair)
Cyclohexane rings usually undergo what kind of oxidations?
3-hydroxylation or 4-hydroxylation

(on C3 or C4)

Either one would give both a cis and a trans product
Concerning cyclohexane ring oxidation acetohexamide is metabolized to what?
The trans 4-hydroxyacetohexamide.
Alkene hydroxylation leads to what?
Epoxide formation
Alkene epoxides are more or less stable than arene oxides?
More stable.
Like arene epoxides alkene hydroxylation products (epoxides) are susceptible to what?
Enzymatic hydration by epoxide hydrolase to form 1,2 dihydrodiols...also GSH transferase rxns.
What is N-oxidation?
Direct oxidation on a Nitrogen atom.
N-oxidation usually occurs with what?
Secondary or tertiary amines.

(and primary aromatic rings)
What is N-dealkylation?
Removes N substituents such as methyl, ethyl, n-propyl, isopropyl, n-butyl, allyl, benzyl and other having an alpha-proton.

Usually occurs on the smaller alkyl group first.
Tertiary amines are dealkylated to secondary amines faster than what?
Faster than secondary amines are dealkylated to primary amines.
During N-dealkylation, oxidation occurs on which carbon?
The carbon alpha to (next to) the nitrogen.
Nitrogen wants how many bonds?
Nitrogen with 2 bonds has what charge?
Nitrogen with 4 bonds has what charge?
So N-dealkylation subtracts a what?
alkyl group
What is deamination?
Removing nitrogen from drugs...same mxm as n-dealkylation.
In deamination oxidation occurs on which carbon?
Carbon alpha to (next to) the nitrogen.
Deamination requires alpha carbon ? first, forming the ?, followed by ?.
Requires alpha carbon oxidation first, forming the carbinolamine, followed by CN cleavage.
Propanolol has how many alpha carbons?
What is O-dealkylation?
Similar mxm as N-dealkylation.

Hydroxylation on the carbon attached to the oxygen followed by C-O cleavage to give the alcohol and the aldehyde or ketone.
People allergic to morphine can't take codeine for what reason?
Because it converts to morphine via O-dealkylation.

If you are missing the O-demethylase enzyme than you won't be allergic but it won't be effective anyway.
List 3 phase I rxns that involve the oxidation of carbon-sulfur systems.
1. Oxidative S-dealkylation

2. Desulfuration

3. S-oxidation
What is S-dealkylation?
The removal of the aklyl group from the sulfur
What is a desulfuration rxn?
Conversion of C=S to C=O
What is S-oxidation catalyzed by?
Catalyzed by flavin monooxygenase and CYP450
What is a chiral center?
C...4 different substituents
Can a carbon with a dbl bd be chiral?
What does the prefix azo- refer to?
Where are esterases found in the body?
"everywhere"...a lot of drugs have esters in them
What are the two most important rxns in this course?
1. Ester hydrolysis

2. Amides Hydrolysis
What enzyme is responsible for ester hydrolysis?
What enzyme is available for amide hydrolysis?
Esters hydrolyzed by esterases produce what kind of products?
1. Carboxylic acids

2. Alcohols

3. Phenols
Amides hydrolyzed by amidases produce what kind of products?
If a carbon atom is partially positive what does it mean?
It is an electrophile. It means the e-s are pulled away from the molecule toward surrounding molecules (like Oxygen).

It will be seeked out by nucleophile.
What does an enzyme do to a rxn?
speeds it up (the rxn would occur with or without it)
Carbon desires how many bonds?
Oxygen desires how many bonds?
2 (or one and 2 e-s)

Electrophiles get ?, they never do what.
Electrophiles get attacked they never do the attacking (remember during arrow pushing)
Where is a bad place to store an ester med. Why?
Warm, damp places. Because it gives them hydrogen to react with.

(ex. ASA)
Water is a strong what?
Is an ester or amide more stable?
amides are more stable (undergo hydrolysis less frequently). longer t1/2.
Nitrogen is electron ?.
Phase II rxns could also be referred to as what?
Conjugation rxns (big rxns)
Phase II rxns are essentially doing what to a drug?
"Puts a big H20-soluble compound on drugs"
Phase II rxns act on what?
Parent drug or phase I metabolite
Can a phase II occur without a phase I?
yes, as long as there is a chemical handle on the compound
What is the most common Phase II rxn in an adult's body?

Used to get rid of drugs.
Where is there lots of glucoronic acid available?
In the liver.
What is the glucorinadation rxn?
Rxn is the direct condensation of the drug with the active form of glucoronic acid (uridine diphosphate glucuronic acid)(UDPGA)(a coenzyme)
List 6 'handles'. The reqt for a phase II rxn?
1. -OH

2. -COOH

3. -NH2

4. -NR2

5. -SH

6. C-H
Glucoronidation transfers what to a drug?
Glucoronic acid
Glucorination is an SN1 or SN2 rxn?
What does glucorinadation cause a molecules configuration to do?
Causes inversion.

alpha link to beta link
Will an oxygen on a ring break during glucorindation?
What kind of rxn is a sulfate conjugation?
A phase II rxn.
List some functional groups that undergo sulfate conjugation.
1. Alcohols

2. arylamines

3. N-hydroxy compounds

4. PHENOLS (primary one)
Often sulfate conjugation and what can occur on the same substrate?
Where is the only place where sulfate conjugation predominates?
phenol hydroxyls


IN CHILDREN (vs. glucorinidation in adults)
What enzyme is involved in sulfate conjugation?
What is the co-enzyme involved in sulfate conjugation?
3' phosphoadenosine-5' phosphosulfate (PAPS)(limited supply)
Unlike glucorinidation, sulfate conjugation has a what?
For albuterol deamination to occur what must be present?
Alpha C next to N with an alpha proton
What is reqd for glucorinidation?
What kind of rxn is AA conjugation?
Phase II
AA conjugation of CARBOXYLIC ACIDS leads to what?
Amide bond formation
What AAs can be added to a drug?
almost any of them

1. GLYCINE (smallest and most abundant)(predominates)

2. glutamine, arginine, asparaginine, histidine, lysine, glutamate, aspartate, alanine and serine.
What is absolutely reqd as a handle for AA conjugation?
Carboxylic acids (COOH)
For an AA conjugation to occur what must happen first? Where can this occur?
The drug must first get activated by ATP and Coenzyme A (CoA) to form an acyl-CoA complex.

The rxn occurs in the mitochondria of liver and kidney cells.
AA acids conjugations req 2 seperate what?
2 seperate enzymes and co-enzymes
The AA acid is always attached by it's what?
AA conjugation is a ? rxn.
Detoxifying (COOH is reqd so molecule is already water soluble)
If there is no COOH on a molecule than what is reqd for an AA conjugation?
Phase I rxn first
What is the nucleophile in AA conjugation?
nitrogen of AA
List two phase I rxns that could give a COOH to a molecule so it could undergo AA conjugation?
1. Deamination

2. Oxidation
What enzyme is reqd for the co-enzyme glycine in AA conjugation rxn?
Glycine N-acyltransferase
Does acetylation make things more water soluble?
No...just detoxifies
N-acetylation is what type of rxn?
Phase II
What does N-acetylation rxn put on a molecule?
Puts acetyl group on a nitrogen.
In N-acetylation what kind of group is converted?
IN N-acetylation a primary amine is converted to what?
Converted to an UNCHARGED amide...which is less soluble (but detoxified)
The extent of N-acetylation is dependent upon what?
Genetically determined.

Three phenotypes:

1. Homozygous fast

2. Homozygous slow

3. Heterozygous (intermediate) acetylators
What does glutathione conjugation break down to?
Mercapturic acid (synthesizes it)
Describe glutathione conjugation and mercapturic acid synthesis?
1. ELECTROPHILIC drugs/xenobiotics react with GSH to form S-substituted GSH adducts.

2. GSH is a tripeptide (lamda-glutamyl-cysteinyl-glycine) (cysteine has the sulfur...the nucleophile to attack the electrophile drug)

3. Usually not eliminated, undergoes further transformation to N-acetylcysteine products called mercapturic acids...less toxic compounds.
Electrophilic drugs can be very what? Why?
Toxic. Because they can be attacked by nucleophile DNA and proteins.
What happens to mercapturic acid?
eliminated in urine
Drug is the ?phile...GSH is the ?phile.
Drug = electrophile

GSH = nucleophile
Methylation is what type of rxn?
Phase II
Are methyl groups polar?
What does methylation put on a molecule?
What is the major role of methylation?
Major role is in the biosynthesis of endogenous compounds-more polar compounds?
What is O-methylation?
methyl on oxygen
What is O-methylation catalyzed by?
What is COMT?

O-methylation specific for catechol metabolism.

extremely important enzyme
What is N-methylation?
Methyl on nitrogen

Methylation of primary and secondary amines.
What is S-methylation?
Methyl on sulfur

Thiols are generally toxic...this detoxifies them