Exam 1 Flashcards
What are the agencies responsible for selection of nonproprietary drug names?
USAN, AMA, APhA, USP, FDA
Define pharmacore
portion of a drug that is responsible for its biological action
Define prototype
representative compound of a drug class that is the standard of comparison for other compounds; ex. IBP is a prototype for NSAIDs
What are the characteristics of an effective drug?
- effectively released from its dosage form
- maintain physical characteristics and long shelf life
- be appealing (via smell, taste, etc)
Define dosage form
final drug product in its final form which includes the active ingredient, excipients and drug delivery system
What are the four categories that dosage form fall under?
- solids
- liquids
- semi-solids
- dispersions
What are the physicochemical characteristics of drugs?
- Physical nature of compound
- Chemical nature of compound
- Solubility
- Acid-base formation
- Stability
- Stereochemistry
- Functional groups
What are two forms of solid compound?
Crystalline form & Amorphous form
What are characteristics of the most stable polymorph?
highest melting point, lowest solubility, maximum stability
Define solution
solute dissolved in a solvent
Define VanderWaal interactions
weakest, between nonpolar portion, temperature dependent; important in lipopihlic substances
Define dipole-dipole interactions
also known as H bonding, partial ionic character leads to permanent dipole,
Define ionic interactions
attraction of oppositely charges atoms, important in inorganic molecules and salts of organic molecules
Define ion-dipole interactions
occurs between ion and dipole, important for dissolving organic salts in water, strong attraction is insensitive to temperature and distance
Define dissolution
process that controls the availability of a drug at the site of action, whereby a compound goes from a solid to solution in a solvent
Define solubility
concentration of a saturated solution of the compound in a given solvent at a given temperature
What is important in monofunctional groups?
intermolecular bonding
What is important in polyfunctional groups?
intramolecular bonding AND intermolecular bonding
What is lipophilicity important for?
- permeability
- drug transport
- binding to plasma proteins
- accumulation in tissues
- recognition by receptor
- specificity
What does the empiric method measure?
Estimates how many carbons a functional group can solubilize and water solubility
What is used in the analytical method for predicting solubility?
partition coefficient
With reference to the partition coefficient, which phase will the lipophilic drugs be more concentrated in?
the n-octanol phase
With respect to the analytical method, what is the value/meaning of LogP?
Concentration of drug in octanol / Concentration of drug in water
With respect to the analytical method, what does a positive and negative pi (π) value mean?
- Positive: lipophilic
- Negative: hydrophilic
What does IMHB stand for?
intramolecular hydrogen bonding
Does intramolecular hydrogen bonding reduce or increase solubility?
reduces
Define water solubility with log P values
- Log P > +0.5 (P > 1) –> water insoluble
- Log P < + 0.5 (P ≤ 1) –> water soluble
Identify undesirable values of log P to be a drug
- Log P < 0 (P < 1) –> too hydrophilic to be a drug
- Log P > 3.5 (P> 3,000) –> too lipophilic to be a drug
What kind of shapes does micelles exist in?
spherical and cylindrical
Brönsted-Lowry definition of acids
any substance that can donate a proton
Brönsted-Lowry definition of bases
any substance that can accept a proton
Strong acid Ka and pKa values
- tend to have high Ka value
- low pKa values
Strength of weak and strong acid’s conjugate base
- strong acid have weak conjugate base
- weak acid has strong conjugate base
Strong base Ka and pKa values
- low Ka value
- high pKa value
What does having a low Ka value mean?
favor accepting protons
What does having a high Ka value mean?
favor donating protons
Why are salts preferred for manufacturing?
they are easier to crystallize, more stable, dissolve faster, and easier to handle
Different salts of the same pharmacore have (same/different) chemical and biological profiles
different
Which is more soluble in water? monovalent salts or multivalent salts
monovalent salts
What are examples of salts of acidic drugs?
sodium, potassium, ammonium, calcium, magnesium, zinc and aluminum salts
What are examples of salts of basic drugs?
hydrochlorides, sulfates, phosphates, gluconates, glucuronates
Salts with what are likely water insoluble?
complex amines and fatty acids
With respect to what they do in the body, how does ionized compounds differ from non-ionized compounds?
they undergo absorption, distribution, metabolism, bind to receptors, and undergo elimination
Stomach pH
1 - 3.5
Small intestine pH
5.5 - 7.5
Lung and blood pH
7.4
Weak base and solubility
- higher solubility at low pH
- high solubility and dissolution in the stomach
- low solubility in the small intestine
Weak acid and solubility
- higher solubility at high pH
- low solubility and dissolution in the stomach
- high solubility and dissolution in the intestines
What are the purposes of buffers?
- control pH
- minimize degradation
- improve patient comfort and compliance
- (sometimes) to improve the efficacy of the drug
Acidic buffer is made of what?
weak acid and salt
Basic buffer is made of what?
weak base and salt
weak acid + strong base ->
gives a weak conjugate base, results in a basic solution
weak base + strong acid ->
gives a weak conjugate acid, results in an acidic solution
For a weak acid, what does it mean when pH > pKa?
ionized (A-) > non-ionized (HA)
For a weak base, what does it mean when pH < pKa?
ionized (BH+) > non-ionized (B)
Percent of ionization based on pH and pKa values (pH of solution, pKa of compound)
- if difference between the two is close to 0, then changes in pH cause changes in % ionization
- if difference is large, there is little change in % ionization
- if compound is weak acid and solution pH is 4 units less than the pKa, completely unionized
- if compound is weak base and solution pH is 4 units above the pKa, completely unionized
What are two excipients commonly found in IR drugs?
disintegrants and surfactants (which increases deaggregation)
Which (IR or CR) has better pharmacodynamics?
CR; it also has better efficacy
What is sustained release?
it is CR but dissolution rate is reduced so that dissolution rate = elimination rate ==> Drug in = Drug out
Can all drugs be formulated into sustained release?
No; it depends on the limitation of the drug’s physicochemical properties
Define shelf life
Time period of consistent performance of a drug when stored under the recommended conditions
What are the accepted levels of degradation?
± 10% of the active ingredient
What are the properties which to consider when determining a drug’s stability?
chemical, microbiological and physical
Define chemical stability
ability of compound to resist changes in amount of active ingredients with time as a result of hydrolysis, oxidation, and photolysis
Define microbiological stability
ability of a drug to resist microbial contamination from the environment and/or from patient use
Define physical stability
ability of a drug to maintain its physical properties over time
What are some examples of physical properties (with respect to Dr. You’s lecture notes)?
dissolution rate, uniformity, appearance, taste, odor
What are the ways in which you can avoid degradation of a drug and maintain its stability?
adding buffers, cosolvents, chelating agents, antioxidants, protective film coating; adapted packaging, formulated as pro drugs
What are the similarities and differences in enantiomers?
similar in physicochemical properties but differ in interactions (ex. binding sites)
What are the different types of isomers?
optically active, enantiomers, geometric
Define enantiomers
non-superimposable mirror images of each other
What does functional groups determine (with respect to properties of a drug)?
- size
- solubility
- acid-base properties
- stereochemistry
- reactivity
Define bioisoterism
Functional groups which have similar spatial and electronic character
Define ionic bonds
the strongest type of non-covalent bond. This results from the attraction of ions with opposite charge
Define ion-dipole bonds
results when there is an attraction between an ion and the partial charge of a dipole of the opposite polarity
Define dipole-dipole bonds
partially positive atom in a dipole is attracted to a partially negative atom in another dipole
Define hydrogen bonding
dipole-dipole interaction where one of the constituents is a hydrogen attached to a heteroatom
Define the hydrophobic effects
when water cage surrounding a hydrophobic region is broken and entropy increases
Define the charge-transfer complexes
lone pair of electrons is “shared” with a neighboring group that has considerable pi character
Acidic buffer pH
pH < 7
Basic buffer pH
pH > 7
How do can dissolution be increased?
- decrease particle size
- increase solubility of weak acids/bases
- decrease concentration in bulk
- decrease diffusion layer thickness
Define chemical isoterism
similarity in physicochemical properties of ions, compound, or elements due to the similar electronic structure
What happens when replacing a group within a bioisostere?
a new compound that retains/enhances/reduces the activity of the parent compound
What are the Lipinski’s Rule of Five?
- Not more than 5 hydrogen bond donors
- Not more than 10 hydrogen bond acceptors
- A molecular mass not greater than 500 daltons (g/mol)
- An octanol-water partition coefficient log P not greater than 5
What are important functional groups in receptor and enzyme binding?
hydroxy, carboxy, amino, ethers, carbonyl groups
What are “Privileged Scaffolds”?
molecular frameworks that are seemingly capable of serving as ligands for a diverse array of receptors
What makes up Phase I in metabolism?
oxidation, reduction, hydrolysis
What makes up Phase II in metabolism?
acetylation, sulfation, glucuronidation, and conjugation with amino acids
