Chem test 4 Erin's Flashcards
this is the study of the interactions between a drug and
organism
pharmacology
the study of how a drug affects the
organism
Pharmacodynamics
the study of how the organism affects the drug
Pharmacokinetics
What is included in pharmacodynamics?
-Site of Action
-Mechanism of Action
-Receptor Binding
-Postreceptor Effects
-Chemical Interactions
What can affect pharmacodynamics?
Disease or Disorder
Age
Drug–Drug interactions
What are the three receptor subtypes?
Enzymes
Ion Channels
Membrane receptors
What are the ways that drugs bind due to chemical interactions (4 total)?
- Electrostatic interactions (intermolecular forces)
- Hydrophobic interactions
- Covalent bonds
- Stereospecific interactions (enantiomers)
how well the drug binds to the receptor
affinity
how well the drug produces its desired effect
efficacy
term used to compare the relative affinity of competing drugs
potency
These concepts help us gain a better understanding of how we are going to administer the drug
absorption, distribution, metabolism, and excretion of drugs from the body
What is the most common type of intermolecular force with drugs?
hydrogen bonding
LD50
lethal dosage to kill 50% of the population given that drug - not done on humans
This method of drug administration is other than the intestine
parenteral
Examples of parenteral drug administration
-intramuscular
-Subcutaneous
-Intravenously
-Inhalation
This determines time to maximal concentration at the receptor to produce peak effect.
Absorption rate
This is how much of the administered drug is actually
absorbed. (typically used for oral administration)
bioavailability
8 factors effecting bioavailability
- Molecular weight of the drug
- Drug formulation
- Drug stability (especially pH sensitivity)
- First pass metabolism (typically in the liver)
- Blood flow
- Gastric emptying (food slows this process)
- Intestinal motility
- Drug interactions
This is the effectiveness of the movement of the drug throughout the body
distribution
What influences distribution? (6 things)
- Blood
- Total body water
- Extracellular fluids
- Lymphatic fluids
- Cerebrospinal fluids
- Protein-binding
What type of properties help determine ability of drug to be
distributed to the desired receptor site.
drug solubility
This is the breakdown of drugs into metabolites
metabolism
What happens to prodrugs during metabolism?
They are converted from inactive form to active form
Cytochrome p450 enzymes like to use this type of reaction to metabolize drugs
REDOX reactions
Common metabolism processes
REDOX reactions, hydrolysis
What things are metabolized via hydrolysis?
esters, amides, and nitriles
What is a downside to metabolism?
Has the potential to lead to the formation of toxic metabolites
Main routes for excretion:
- Kidneys (majority of drugs)
- Feces (unabsorbed drug or metabolites from bile)
- Lungs (inhaled anesthetic drugs)
- Sweat (not very common)
Most drugs fail during the _____ phase
discovery
___% of all drugs fail in clinical testing
90%
Lipinski Rule of 5
-describes drug potential for a new chemical entity (NCE)
-Used as a tool to measure a NCE’s potential bioavailability
Ionized drugs are more ___ soluble
water
Lipinski rule of 5 with drug development is based on
*Hydrogen bond donors (typically amines and alcohols)
* Hydrogen bond acceptors (total number of N, O, and F)
* Molecular weight (MW)
* Calculated Partition Coefficient (cLogP)
Violation of more than one “rule” predicts a NCE is ______
non-orally available
We try to limit molecular weight at
500
Ratio of the solubility of a drug in oil vs water (so it mirrors the cellular membrane)
cLogP
Try to keep the cLogP under __
5
We try to limit the amount of hydrogen bond acceptors (N and O) to __ or less
10
This is where the binding has to occur to elicit a response
active site
Is it easy for low MW drugs with a low cLogP to cross membranes?
Yes
Potential drug compounds must have a mix of ________ and
______ groups
hydrophilic, lipophilic
Structural alerts – certain functional groups that have been linked
to increased toxicity due to their metabolites (5 total) :
- Aromatic anilines
- Nitroaromatics
- Aliphatic halides
- Polycyclic aromatic hydrocarbons
- Thiophenes
Drug efficacy is directly related to ____________
the concentration of the drug at
its site of action.
True or false Drugs must cross membranes throughout the entirety of ADME
true
Absorption of drugs into the bloodstream is dependent on the _____ properties of the drug and the ___ at the site of absorption
acid/base, pH
Why does transport plateau at high drug concentrations?
due to limited number of transport proteins available
Daltons is shorthand for
g/mol
Extremely Small Drugs (< 50 Da)
Bulk Flow (passive transport)
Lipophilic Drugs (50 – 500 Da)
Passive transport
Lewis acid
electron acceptor
Lewis base
electron donor
Bronsted base
proton acceptor
Anything less than 500 g/mol will diffuse by
passive transport
Bronsted acid
proton donor
These acids completely ionize (break apart into ions) when
dissolved in water
strong acids
Strong acid examples
HCl, HBr, HI, HNO3, HClO4, H2SO4
These acids partially ionize when dissolved in water
weak acids
Examples of weak acids
HF, H2CO3, H3PO4, organic acids (carboxylic acids, protonated drugs, etc)
Strong Acids have ____ conjugate bases
weak
Weak Acids have _____ conjugate bases
strong
When we calculate pH we focus on the ____ definition of acid and bases. Why?
Bronsted-Lowry, we are looking at the protons
Conjugate acid and bases are shown on the ___ side of an equation
product
Water can act as
either an acid or base
How it acts depends on what it is being mixed with
Think of acidity as
a sliding scale
You can take two acids and they react together, one will react as an acid one as a base because one is more acidic than the other.
This is the substance formed by the removal of a proton from an acid
conjugate base
This is a chemical compound formed when an acid gives a proton to a base
conjugate acid
When talking about strength of acids we are referring to
if it completely ionizes (strong) or not (weak)
What does ionize mean?
break apart into ions
All of the drugs we are dealing with will be
a weak acid or weak base
These bases completely ionize (break apart into ions) when
dissolved in water
strong base
What does the double arrow “equilibrium” represent
The rate of the forward reaction is equal to the rate of the backwards reaction
Strong base examples
LiOH, NaOH, KOH, Sr(OH)2, Ca(OH)2, Ba(OH)2
These bases partially ionize when dissolved in water
weak bases
What is the Water Constant (KW)? (definition)
measure of the self ionization of water
What is the water constant (#)?
1.00 x 10^-14
The higher the pH the more ___ something is
basic
The higher the pOH the more ___ something is
acidic
The lower the pOH the more ___ something is
basic
When dealing with a strong acid it produces
H3O+
When dealing with a strong base it produces
OH-
When solving for a pH of a base solve for ___ initially then ___
pOH, then subtract it from 14 to get pH
If you get a pH for a base it should always be
> 7.0
if you get a pH for an acid it should always be
<7.0
pH + pOH =
14
pH of 7 =
neutral
Acid strength is actually relative and depends on the ability of the
group to _________
give up a proton.
The larger the KA = the easier it is to ______
remove the proton (more acidic)
The lower the pKA the more ___ something is
acidic
Note the pH scale is logarithmic so a change of 1 actually scales to a
change by a _____
factor of 10
So when you go to a pH of 6 –> 7 you are actually changing it by a factor of 10
If the exponent is negative move your decimal place
to the left
Calculate the pH of the following solution:
1.50 x 10^-3 M HCl
2.82
Steps:
-log [1.50 x 10^-3] = 2.82
Calculate the pH of the following solution:
3.51 x 10^-2 M NaOH
12.55
Steps:
-log[3.51 x 10^-2] = pOH = 1.45
pH = 14 - 1.45 = 12.55
pKA of H2O
16
Water is amphoteric, what does this mean?
can act as either an acid or a base
