Exam 1 Flashcards
USP, Functional Groups, Acids and Bases
What is USP 797?
A set of standards required for the compounding of sterile products.
Who designed the USP 797?
US Pharmacopeia
Who needs to follow USP 797?
Anyone who prepares sterile compounds for both humans and animal patients.
What is USP 795?
This outlines the standards for non-sterile preparation like topical creams, suppositories, and more.
What is the main focus of USP 797?
It focuses on keeping things clean and sterile.
What is USP 800?
This outlines that standards for handling and preparing hazardous drugs that can be sterile or non-sterile.
What is the goal of USP 800?
The goal of this is to keep the employees and persons safe while handling hazardous material.
Why does USP 797 matter?
It keeps patients safe, it sets clear standards and expectations for performance, and provides clear guidance on how to ensure that products are truly sterile.
What is the primary engineering control (PEC)?
This is the IV hood where the actual compounding of the sterile product is created.
What is the secondary engineering control (SEC)?
This is the buffer room the houses the IV hood (PEC). This is usually referred to as the sterile compounding room.
What is the anteroom?
This is the room that connects the SEC (sterile compounding room) to the outside world. This is where garbing and handwashing occurs.
What is the ISO?
International Organization of Standardization
What is ISO 5?
This is the required environment inside the IV hood (PEC). It has 3,520 particles per cubic meter.
What is ISO 7?
This is the required environment inside the IV clean room (SEC). It has 352,000 particles per cubic meter.
What is ISO 8?
This is the required environment for some anterooms. It has 3,520,000 particles per cubic meter.
What is ISO 9?
This is the real world with particles over 35 million per cubic meter.
What type if primary engineering controls (IV hood) is used to compound sterile but non-hazardous materials?
Horizontal laminar flow hood
What type if primary engineering controls (IV hood) is used to compounding sterile and hazardous drugs?
Class II biological safety cabinet
What type if primary engineering controls (IV hood) is used to compound hazardous or non-hazardous products?
Restricted access barrier system
What is the ISO level for the SEC room for non-hazardous drugs?
ISO 7
PEC is ISO 5 while the outside is ISO 9
In a non-hazardous IV room setup, how is the pressure between rooms organized?
The SEC and Anteroom are at a positive pressure compared to the outside room. This allows air from the SEC and anteroom to flow out instead of non-sterile air from outside coming in.
In a hazardous IV room setup, how is the pressure between rooms organized?
The SEC where hazardous drugs are compounded has a negative pressure while the anteroom and other rooms are at a positive pressure. This makes sure to trap all the hazardous drug particles in the SEC hazardous IV drug room.
What is an alternative to an SEC room setup that can be utilized by smaller hospitals or surgery centers?
The segregated compounding area
Know the chart on air quality requirements.
What is a category I compounded sterile product (CSP)?
This product was prepared in an ISO 5 environment but was in a segregated compounding area so it was not made in a true IV room.
What is category II compounded sterile products?
This product was prepared in an ISO 5 environment with an ISO 7 cleanroom. This is typically what large hospitals will make.
What is a category III compounded sterile product?
This product is similar to category II but it must undergo additional testing and monitoring.
What are the steps to entering the sterile IV room at UC pharmacy school?
- Shoe cover
- Hair cover, face cover, and mask
- Wash hands
- Don gown
- Use hand sanitizing product
- Gloves
- Spray gloves with 70% IsoP
What is the Bronsted-Lowry definition of an acid?
An acid is any substance that can donate a proton.
What is the Bronsted-Lowry definition of a base?
A base is any substance that can accept a proton.
Do strong or weak acids completely dissociate in water?
Strong acids
What is the Ka value?
This is the acid dissociation constant that is experimentally determined.
What does a large Ka mean?
A large Ka means a stronger acid. This means more of the acid dissociates to create more product and more H+ ions.
What were the 3 strong acids discussed in class?
HCl, H2SO4, and HNO3
What were the 3 strong bases discussed in class?
NaOH, KOH, and Ca(OH)2
What is Kb?
Kb is the base equilibrium constant that is also experimentally determined.
What is pKa?
pKa is the negative base 10 of the acid dissociation constant Ka in solution. The smaller the pKa value, the stronger the acid.
What does a small pKa mean?
A small pKa means a stronger acid!
What acid discussed from the table is the weakest of the weakest acids?
Phenol with a pKa of 9-11.
What acid discussed from the table is the strongest of the weakest acids?
Sulfonic acid with a pKa of 0-1.
What base discussed from the table is the weakest of the weakest bases?
Arylamine with a pKa of 3-5 and a pKb of 9-11.
What base discussed from the table is the strongest of the weakest bases?
Guanidine with a pKa of 12-13 and a pKb of 1-2.
The smaller the pKb, the _____________ the base.
Stronger
The smaller the pKa, the __________ the acid.
Stronger
What are the 12 different organic functional groups that are neutral?
Alkyl alcohol, ether, ester, sulfonic acid ester, amide, diarylamine, nitrile, quaternary ammonium, amine oxide, ketones and aldehydes, thioether, sulfoxide, and sulfones.
What are electron withdrawing groups?
These are groups attached to compounds and they want electrons very badly!
If an electron withdrawing group is attached to a phenol ring, will it make the phenol a stronger or weaker acid?
EWG attached to a phenol ring will make that phenol a stronger acid.
If an electron withdrawing group is attached to a amine, will it make the amine a stronger or weaker base?
EWG attached to an amine will make the amine a weaker base.
What are electrons donating groups?
THese are groups attached to compounds that hate electrons and want to get rid of theirs.
If an electron donating group is attached to a phenol ring, will it make the phenol a stronger or weaker acid?
EDG attached to a phenol ring will make the phenol a weaker acid.
If an electron donating group is attached to an amine, will it make the amine a stronger or weaker base?
EDG attached to an amine will make the amine a stronger base.
Levothyroxine contains a phenol. A phenol is a weak acid. The substitutes attached to the phenol ring is _________. The substituents will make the phenol be a _______ ________.
Iodine
Stronger acid
T or F: Most drugs that bind to their receptors in the body to exert their effects form covalent bonds.
False!!! Most drugs do not form covalent bonds
Thinking of all the different bond types, what is the absolute strongest bond?
Covalent bonds
Rank intermolecular forces from strongest to weakest?
Covalent bonds
Ionic bonds
Ion-dipole bonds
Hydrogen bonds
Dipole-dipole bonds
Van Der Waals
Van der waals interactions are __________ interactions.
Hydrophobic
Are aromatic hydrocarbons like benzene rings neutral, acidic, or basic?
Neutral
What are all the weak acid functional groups?
Ranked from highest to lowest pKa:
Phenol
Sulfonamide
Imide
Alkylthiol
Thiophenol
N-Arylsulfonamide
Sulfonimide
Aryl Carboxylic acid
Sulfonic acid
What are all the weak base functional groups?
Ranked from highest pKb to lowest:
Arylamine
Aromatic amine
Imine
Alkylamines
Amidine
Guanidine
What are all the neutral functional groups?
Amide
Amine oxide
Ether
Diarylamine
Ketones
Aldehydes
Ester
Nitrile
Thioester
Sulfonic acid ester
Quaternary ammonium
Sulfoxide
Sulfone
Do benzene rings act as acids, bases, or are they neutral?
Neutral!
Are benzene rings EWG or EDGs?
Benzene rings act as EWGs
Benzene rings are metabolized via ___________ by CYP450 enzymes into __________ intermediates.
Hydroxylation
Epoxide
Are alcohols acids, bases, or are they neutral?
Neutral!
Are alcohols EWGs or EDGs?
Alcohols act as EDGs
Can alcohol hydrogen bond with other alcohols?
Yes!
Does having hydrogen bonds between molecules increase or decrease the boiling point and water solubility?
Hydrogen bonds increase the boiling point and water solubility for a molecule.
What is special about having an alcohol (-OH) in the middle of the molecule instead of near the end of the molecule as seen in the picture?
Having the OH within the middle of the molecule disrupts the Van Der Waal interactions which decreases the boiling point but increases water solubility as VDW forces are hydrophobic.
In phase 1 metabolism _____ alcohols are converted to ___________ acids via oxidation by oxidases.
Primary
Carboxylic acids
In phase 1 metabolism ______ alcohols are converted to ___________ via oxidation by oxidases.
Secondary
Ketones
Do tertiary alcohols undergo oxidation during phase I metabolism?
No
In phase 2 metabolism _____ alcohols undergo _____________________ via UGT or __________via SULTs and PAPs to form a glucuronide or sulfate.
Primary
Glucuronidation
Sulfonation
What is a phenol?
This is a benzene ring with an alcohol attached.
Do phenols act as acids, bases, or are they neutral?
Phenols act as weak acids meaning they are willing to give up a proton.
Does the pKa of a phenol increase or decrease when a EDG like a methyl is at the meta position?
When an EDG like a methyl is in the meta position on a phenol, it decreases it pKa making it a stronger weak acid compared to the EDG being in the para position.
Does the pKa of a phenol increase or decrease when an EWG like NO2 is at the meta position?
The pKa of a phenol increases when an EWG like NO2 is at the meta position on a phenol. The pKa decreases if an EWG is at the para position.
In order for a molecule to hydrogen bond to other molecules, what must the hydrogen be attached to?
The hydrogen must be attached to an Oxygen, Fluorine, or Nitrogen in order to Hydrogen bond with other molecules.
What are the 3 ways in which phenols are metabolized?
Glucuronidation, sulfonation, and methylation. All increase water solubility for excretion except methylation.
Why does cyclohexanol have the lowest boiling point and water solubility in comparison to other phenols?
Cyclohexanol converts between the chair and boat formation making it difficult for this molecule to Hydrogen bond therefore decreasing the boiling point and water solubility of the molecule.
Do aldehydes and ketones act as acids, bases, or are they neutral?
Neutral!
Can aldehydes and ketones hydrogen bond with themselves?
No, but they can hydrogen bond with water.
What is keto-enol tautomerization?
Keto-enol tautomerization is a chemical reaction where a ketone molecule and an enol molecule interconvert. The keto and enol forms are known as tautomers.
What is the pKa of an enolic -OH?
5
Do long carbon chains on ketones and aldehydes increase or decrease the boiling point and water solubilit?
Long carbon chains are ketones and aldehydes increases the boiling point while decreasing the water solubility.
When alcohols are mixed with aldehydes, what two things can be formed?
Hemiacetals and full acetals
When alcohols are mixed with ketones, what two things can be formed?
Hemiketals and full ketals
Aldehydes are oxidized to ___________ acids during metabolism. Ketones are much less likely to undergo this reaction due to possible carbon-carbon bonds.
Carboxylic acids
Do amines act as acids, bases, or are they neutral?
Amines act as bases meaning they are very willing to accept protons.
Which type of amines (primary, secondary, and tertiary) can hydrogen bond with another version of itself?
Primary and secondary are the only types of amines that can hydrogen bond
Is the boiling point and water solubility higher in tertiary amines compared and primary and secondary amines?
The water solubility and boiling point is lower in tertiary amines compared to primary and secondary as tertiary amines can’t hydrogen bond with other molecules.
Does adding more alkene chains to an amine increase of decrease the boiling point?
Adding more alkyl chains to an amine leads to a higher boiling point due to increased ability for van deer waals interactions. This also leads to a decreased water solubility.
It is known that amines act as bases. If an EWG group is attached to it, does it become a weaker or stronger base?
EWG groups on amines make them weaker bases. This is due to the lone pairs not being as available.
It is known that amines act as bases. If an EDG group is attached to itm does it become a weaker or stronger base?
EDG groups on amines make them stronger bases. This is due to the lone pairs being more available.
T or F: Aromatic amines are weaker bases than alkele amines.
True
What is the order of basicity when it comes to methylamines?
Secondary, primary, then tertiary. Tertiary methyl amines are the weakest bases due to steric hindrance which is blocking the lone pair of electrons.
What is the order of basicity when it comes to ethylamines?
Secondary, tertiary, then primary. The ethyl groups within the ethylamine pumps the lone pair of electrons on tertiary amines so they can overcome steric hinderance.
Is a diarylamine (secondary amine with two benzene rings), an acts, base, or neutral?
Neutral. The EWG properties of the benzene rings are so intense that the lone pair on the nitrogen is no longer accessible.
During metabolism, _______ and _______ amines undergo de-alykation to form ___________.
Secondary and tertiary
N-oxides
During metabolism _______ amines can undergo deamination reactions to form aldehydes or ketones.
Primary
During conjugation reactions of amines, they can undergo glucuronidation, sulfonation, and acetylation. Which one of these conjugation reactions decreases water solubility?
Acetylation decreases water solubility
Do carboxylic acids act as acids, bases, or are they neutral?
Carboxylic acids act as acids
Can carboxylic acids hydrogen bond with other carboxylic acids?
Yes
Are carboxylic acids weaker or stronger acids when compared to phenols?
They are stronger weak acids when compared to phenols due to resonance.
Do EDG, like a methyl, on carboxylic acids make then stronger or weaker acids?
EDG groups make carboxylic acids weaker acids due to the repulsion of charges.
Do EWG, like a benzene ring, on carboxylic acids make then stronger or weaker acids?
EWG groups makes carboxylic acids stronger acids.
Does the length of the alkyl chain attached to a carboxylic acid affect the water solubility of the molecule?
Yes. The longer the alkyl chain attached, the less water soluble the molecule is.
How does the presence of a salt with a carboxylic acid affect its properties?
Salts can have an increased water solubility due to hydrogen bonding and ion-dipole interactions.
What is beta-oxidation?
This is the breakdown of carboxylic acids by clipping off two carbons at a time.
During metabolism, carboxylic acids can undergo glucuronidation or the addition of an amino acid. Which conjugation reaction decreases water solubility?
The addition of the amino acid glycine or glutamate decreases the water solubility of the carboxylic acid.
Can esters hydrogen bond with themselves?
No, but they can hydrogen bond with water.
What is the name of a cyclic ester?
Lactone
Are esters acid, bases, or neutral?
Esters are neutral
How does the boiling point and water solubility change for esters as the alkyl chain gets longer?
As the alkyl chains get longer, the boiling point increases while the water solubility decreases.
How are esters metabolized?
Esters are hydrolyzed by esterases to form carboxylic acids and alcohols.
What is an amide?
This is a carboxylic acid and an amine.
Do amides act as acids, bases, or are they neutral?
Amides are neutral due to resonance
What is a cyclic amide called?
Lactam
Amides are metabolized via __________ to form carboxylic acid and __________. They have a longer half-life compared to esters.
Hydrolysis
Amine
Do amides undergo ion-dipole interactions with water?
Yes!
What are the 3 derivatives of carbonic acids?
Carbonate (diester), carbamate (ester and amide), and urea (diamide)
Are carbonic acid derivatives acids, bases, or neutral?
Neutral
Is Urea stable or unstable?
Urea is fairly stable and is not readily hydrolyzed unlike carbamate and carbonate.
What is the product of hydrolysis of a carbonate?
2 alcohols and 1 CO2
What is the main characteristic present in amidines and guanidines?
Imide bond (C=N)
Do amidines and guanidines act as acids, bases, or are they neutral?
Weak bases due to resonance
Do sulfonic acids act as acids, bases, or are they neutral?
Strong acids due to the SO2 group being EWG.
Do sulfonamides act as acids, bases, or are they neutral?
Weak acids when nitrogen is attached to a hydrogen.
What is unique about sulfonamides?
Nitrogen acts as an acid here and not a base.
Are nitro groups (NO2) acids, bases, or neutral?
Neutral
Are nitro groups EWG or EDGs?
Nitro groups are EWGs when attached.
Are imides basic, acidic, or neutral?
Weakly acidic
What enzyme within bacteria can cleave open Beta-Lactam rings?
Beta-lactamase
Is pyrrole basic, acidic, or neutral?
Pyrrole is neutral as its pKb is 14 and its electrons are tied up in the pi cloud.
Is pyridine basic, acidic, or neutral?
Pyridine is a weak base with a pKb of 10.
What is the function of a 5-FU, decoy molecule for uracil and a derivative of pyrimidine?
It functions to inhibit thymidylate synthetase.
Ionized/charged drug tend to be more ______________.
Hydrophilic
Ionized charged/drugs promote systemic distribution, facilitate contact with membranes and are more readily _________.
Excreted
Unionized/uncharged drugs tend to be more ___________.
Lipophilic
Unionized/uncharged drugs increase passive transport across biological membranes, promote absorption into general circulation from the site of administration, and __________ excretion.
Inhibit
T or F: Resonance stabilized conjugate bases and conjugate acids result in stronger acids and bases respectively.
True
Looking at the periodic table, in which directions does electronegativity increase?
To the right and up
What are the different electronegative groups that want electrons for themselves?
Halogens
Ketones
Amides
Esters
Oximes
Nitro groups
Alkenes
Aromatic rings
What is electronegativity?
This is how much an atom wants an electron. The more electronegative, the more electron withdrawing it is.
T or F: Electronegative halogens make acids weaker acids if attached.
False. Attached halogens make acids stronger acids
T or F: Electropositive groups (EDG) make phenols stronger acids in attached.
False. Electropositive groups (EDGs) make phenols weaker acids.
T or F: The less resonance structures a molecule can undergo allows it to be a stronger acid.
False. The more resonance structures a molecule can undergo allows it to be more stable so it can act as an acid or a base.
What is unique about 1,1-Dicarbonyl?
Due to resonance, the carbon can act as a weak acid and donate its proton.
Amindines are ________ _________ made stronger due to resonance.
Weak bases. The positive charge on the nitrogen can be shared on both nitrogen atoms.
How does intramolecular hydrogen bonding affect the pKa of certain groups?
In this instance, the hydrogen on the phenol and the oxygen on the carboxylic acid are hydrogen bonded. This means that the hydrogen on the phenol is hard to remove making it almost neutral while the hydrogen apart of the carboxylic acid is much less restricted so it has a higher pKa to act as a weak acid.
T or F: Salts have improved water solubility compared to the free acid or base form.
True.
What is the definition of a salt?
A salt is an ionic substance in which the ions are neither proton nor hydroxide.
Which salts always result in a neutral pH solution?
NaCl
KBr
NaNO3
Kl
Salts of strong acids and weak bases produce _____________ solutions.
Acidic
Salts of strong acids and weak bases produce acidic solutions. The anion does not react with water while the cation reacts with water to produce _________________ ions.
Hydronium
Salts of weak acids and strong bases will produce _________ solutions.
Basic
Salts of weak acids and strong bases will produce basic solutions. The cation does not react with water while the anion reacts with water to form _________________ ions.
Hydroxide
What are the salts of the strong acids?
Cl- (chloride)
SO42- (Sulfate)
NO3- (Nitrate)
Will not affect the pH of the solution
What are the salts of the strong bases?
Na+ (sodium)
K+ (potassium)
Ca2+ (calcium)
Will not affect the pH of the solution
A mixture of a salt of a strong acid and a strong base results in a solution ph of _________.
7 (Neutral)
A mixture of a salt of a strong acid and weak base results in a solution pH of ____________.
Less than 7 (acidic)
A mixture of a salt of a weak acid and strong base results in a solution pH of _________.
Greater than 7 (basic)
A salt of a weak acid and a weak base result in a solution pH of __________.
More information on pKa values is needed to determine the pH of the solution.
Is potassium nitrate salt acidic, basic, neutral, or is more information needed?
Potassium nitrate salt results in a neutral solution as potassium is the salt of a strong base and nitrate is the salt of a strong acid. These two things together result in a pH of 7.
Is pyridinium chloride salt acidic, basic, neutral, or is more information needed?
Pyridinium chloride salt results in an acidic solution as chloride is the salt of a strong acid and pyridinium is the salt of a weak base. The two things together result in pH less than 7.
Is sodium budesonide salt acidic, basic, neutral, or is more information needed?
Sodium budesonide salt results in a basic solution. Sodium is the salt of a strong base and budesonide is the salt of a weak base. Together these things result in a basic pH greater than 7.
What is an isomer?
These are compounds with the same number and kinds of atoms but different bonding arrangements. Isomers can exhibit different physical and chemical properties like different solubility, boiling point, and biological effects.
What are steroisomers?
These are compounds with the same number and kinds of atoms, same bonding arrangements, but a different 3-dimensional structure.
What are enantiomers?
These are isomers that are non-superimposable mirror images of each other.
What are diastereoisomers?
Isomers without a mirror image relationship and different 3-dimensional arrangement of atoms in space.
T or F: Enantiomers have the same melting point, boiling point, and water solubility.
True.
T or F: Diastereomers have different physical chemical properties
True
Is pyrrole acidic, basic, or neutral?
Neutral. It has a pkb of 14.
Is pyridine acidic, basic, or neutral?
It is a weak base with a pkb of 10
What 4 atoms are included in a hemiacetal?
1 H
1 C
1 OH
1 OR
What molecule is this and what is its pka?
It is a sulfonamide which has a pka of 9-10
What molecule is this and what is its pka?
It is an imide which has a pka of 9-10
What is the normal pkb for a primary amine?
4-5
What is the normal pkb for a secondary amine
Around 4
What is this molecule and what is its pkb?
It is an imine which has a pkb of 10-11
