Exam 4 Flashcards
What is drug affinity?
How well the drug binds to the receptor
What is drug efficacy?
How well the drug produces the desired effect
What is drug potency?
Compares the relative affinity of a drug to a receptor compared to other drugs
Drug must out compete the native ligand to induce an effect
Where do most drugs fail during development?
- Most drugs fail during the discovery phase
- ~90% of all drugs fail in clinical testing (1:10,000 success rate)
What is the Lipinski Rule of 5?
- Tool used to measure a new chemical entity (NCE) bioavailability
Rules:
1. < 10 hydrogen bond donors (NH, OH) or acceptors (N, O)
2. < 500 Da molecular weight
3. < 5 Calculated partition coefficient (cLogP)
4. Not more than 1 toxicophore
Violation of more than one rule predicts the NCE non-orally available
What do hydrogen bonds bind to on a receptor?
Polar, acidic, and basic groups
Determine the various intermolecular forces for Dibucaine?
What are the structural alert drugs and there strucure?
Napthelene is the only polycyclic aromatic that is ok
Thiophenes are bad due to sulfur oxidation
NAP AT night
What is the measure of a dalton?
What is considered a “small” drug?
- Da = g/mol
- 500 da or less
Define an acid and base (Bronsted-Lowry)?
- Acid - proton donor
- Base - proton acceptor
Determine the acid, base, conjugate acid, and conjugate base of the following reaction?
Determine the acid, base, conjugate acid, and conjugate base of the following reaction?
Define amphoteric and what compound has this property?
Amphoteric means a compound can act as an acid or a base like water
What defines a strong acid? weak acid?
What are the strong acids?
Stong acids completely ionize in water
Weak acids partially ionize in water
Bring Clean ClOthes If NOt Swimming
What defines a strong base? weak base?
What are the strong bases?
Strong bases completely ionize in water
Weak bases partially ionize in water
LiNK BaCS
What do the equilibrium arrows favor in a reaction?
Favors the formation of a weaker acid
What is the pH equal to for strong acids and bases?
Strong acids: pH = -log[H3O+]
Strong bases: pH= 14 - -log[OH-]
Calculate the pH of 1.50 x 10^-3 M HCl?
pH = 2.82
Calculate the pH of 2.62 x 10^-5 M HCl?
pH = 4.58
Calculate the pH of 3.51 x 10^-2 M NaOH?
pH = 12.55
Calculate the pH of 5.25 x 10^-6 M Ca(OH)2?
pH = 9.02
What should you consider when looking at a change in pH?
The pH scale is logarithmic and a change of 1 is actually a change by a factor of 10
What ist the true view of the strength of an acid?
The ability of the acid to give up its proton
Stong acids readily give up their proton
How do we determine how readily an acid will give up its proton?
What does this information mean?
- By its Ka (acid-dissociation constant), = [products]/[reactants]
- The larger the Ka the easier it is to remove the proton and therefore more acidic
What is the range for pH and pKa?
What is the pKa of water?
- pH = 0-14
- pKa = -20 - 60+
- pKa H20 = 16
How do you calculate the pH of a weak acid?
Weak acids do not dissociate completely so we must calculate the pH of the equilibrium concentration
Complete the ICE table and then plug the numbers into the Ka formula ([products]/[reactants]).
This gives you [H30+], then take -log to obtain pH.
How do you calculate the pH of a weak base?
The same method as weak acid calculations
Remember, this calculation gives you [OH-], so you must take the -log[OH-] to get pOH and subtract that number from 14 to obtain the pH
What is the pH of 1.20 M soulution of acetic acid (weak acid, Ka= 1.4 x 10^-5)?
pH = 2.39
What is the pH of 0.00250 M solution of morphine (weak base, Kb= 1.6x10^-6)?
pH = 9.80
What is a buffer?
Solutions that contain a weak acid and its conjugate base or a weak base and its conjugate acid
Buffers resist change in pH when strong acids or bases are added up until buffering capacity is exceeded.
What are the 3 main buffering systems in the body?
- Bicarbonate
- Phosphate
- Protein
What is Le Chatelier’s Principle?
When a system is at equilibrium is disturbed, the system will adjust to reestablish that equilibrium.
What is the bicarbonate buffering system equation?
What anesthetic is a weak base?
What is important about this property?
- Most local anesthetics
- Drugs with a pKa closer to normal pH are usually lipid soluble and unionized, this allows this to better cross the axonal membrane and initate their effects
How do you determine % ionization?
(ionized ion/total ions) x 100