Module 4 (Exam II) Flashcards
Describe the two most common reactions pertinent to metabolism.
- Hydrolysis (esters, amides, & nitriles)
- REDOX reactions (CYP450’s in liver)
What are the 4 areas of drug excretion?
- Kidneys
- Feces (via bile)
- Lungs (inhaled anesthetics)
- Sweat (uncommon)
Why do most drugs fail during their discovery phase?
Poor Pharmacokinetics
___% of all drugs fail in clinical testing.
90
What is the Lipinksi rule of 5 utilized for?
- Describes a drug’s potential as a NCE (new chemical entity)
- Measures the NCE’s bioavailability
What metrics comprise the Lipinksi Rule of 5
- ≤ 5 hydrogen bond donors (amines & alcohols)
- ≤ 10 hydrogen bond acceptors (Total: O, N, F)
- MW less than 500g/mol
- cLogP ≤ 5
What is cLogP?
What would an increased cLogP denote?
How about a decreased cLogP?
Calculated Partition Coefficient
↑ = lipophillic. ↓ = hydrophillic
Low MW drugs with a high cLogP can easily cross membranes. T/F?
False, Low MW w/ low cLogP needed to cross membranes.
needs verification
Which 5 functional groups have been linked to increased toxicity due to their metabolites?
- Aromatic Anilines
- Nitroaromatics
- Aliphatic Halides
- Polycyclic Aromatic Hydrocarbons
- Thiophenes
What functional group was linked to testicular cancer in chimney sweeps?
Polycyclic Aromatic Hydrocarbons
Differentiate strong acids & weak acids?
Strong acids completely dissociate in H₂O
Weak acids partially dissociate in H₂O
Strong acids have _____ conjugate bases.
weak
Equilibrium favors the ______ acid.
weaker
Water is amphoteric, meaning what?
It can act as either an acid or a base.
What is molarity?
Mol solute / L solution
What is Molality?
Mol of solute / kg of solvent
What is weight percent?
(mass of solute/ mass of solution) · 100
What is volume percent?
(volume of solute/ volume of solution) · 100
What is a Dalton?
g/mol
What drugs require active transport?
Ionized drugs
What drugs do not require active transport?
- Small drugs (<50 Da) - bulk flow
- Lipophillic drugs (50 - 500 Da) - passive transport.
What forces allow a drug to bind to its active site?
Intermolecular forces
Shorter bond length means ______ strength.
more
What are the intermolecular forces in order of weakest to strongest?
- Van-Der-Waals
- Dipole-Dipole
- Hydrogen Bonding
- Ion-Dipole
- Electrostatic
- Covalent bonds
What characterizes van der Waals forces?
- Two non-polar molecules
- Most common intermolecular force
What characterizes dipole-dipole forces?
- Occurs in all polar molecules
- Strength depends on individual dipoles
What characterizes hydrogen-bonding forces?
- Specialized Dipole-Dipole between an H-bond donor and H-bond acceptor.
What are the strongest Hydrogen-bond acceptors?
- O, N, & F
What is the most important intermolecular force pertaining to drug-receptor binding?
- Hydrogen bonding
What characterizes an Ion-Dipole force?
- Interaction between a full formal charge (ex. Na⁺) and a dipole (ex. H₂O)
What characterizes electrostatic interaction forces?
- Cation & Anion interacting
