(6) DSA | Intro to Pharmacodynamics (Konorev) Flashcards
Define:
Pharmacokinetics
Effect of the BODY on drugs
ADME
- Absorption
- Distribution
- Metabolism
- Elimination
Define:
Pharmacodynamics
Effects of DRUGS on the body
- Drug receptors
- Dose-response curves
- Mechanisms of drug actions
Define:
A Receptor
A specific molecule in a biological system that plays a regulatory role
The receptor interacts with a drug and initiates the biochemical events leading to drug effects
Define:
Inert binding site
A compontnet of the biologic system to which a drug binds without changing any function
Define:
Ligand
A ligand is a molecule, such as a hormone or a drug, which binds to a receptor
Describe the “lock and key” model of ligand receptor interaction
Types of Drug-receptor interactions
Describe: Covalent bonds
Irreversible
Drug removal/receptor reactivation requires re-synthesis of the receptor or enzymatic removal of the drug
Types of Drug-receptor interactions
Describe: Non-covalent bonds
Reversible
Most drugs bind to receptors via non-covalent bonds
Rank the following types of bonds from WEAKEST to STRONGEST
Hydrophobic interactions
Ionic bonds
Hydrogen bonds
Weakest = Hydrophobic interactions
Middlest :) = Hydrogen bonds
Strongest = Ionic bonds
What are the three parameters that describe the interaction of a drug with a receptor?
- Affinity
- Selectivity
- Intrinsic activity
What is affinity of a drug?
What does high vs low affinity mean?
The affinity of a drug for a receptor describes how readily and tightly that drug binds to its receptor
High affinity= good drug-receptor interaction; LESS drug needed to produce a response
Low affinity= poor drug-receptor interaction; MORE drug needed to produce a response
What is the parameter that describes the affinity?
KD
(equilibrium dissociation constant)
Define KD
What are the units?
Drug concentration at which 50% of the drug receptor binding sites are occupied by the drug
Molar concentration
What does a LOW KD mean?
The lower the KD …
The higher the affinity of a drug for a receptor
What does a high KD mean?
The higher the KD …
The LOWER the affinity of a drug for a receptor
What is the equation for calculating KD?
[L] = ligand
[R]= receptor
[LR] = ligand-receptor complex
What is drug selectivity?
A property of a drug determined by its affinities at various binding sites
*A MORE selective drug would affect fewer targets over a specific concentration range
What is instrinsic activity?
The ability of a drug to change a receptor function and produce a physiological response upon its binding to a receptor
What is an agonist?
Bind the receptor and stabilize it in a particular conformation (usually the active conformation) producing a physiological response
*HAS intrinsic activity
What is an antagonist?
Bind to the receptor but do NOT CHANGE ITS FUNCTION
However, they prevent activation of the receptor in the presence of an agonist
**DO NOT have intrinsic activity
What are the three types of agonists?
Full agonists
Partial agonists
Inverse agonists
What do full agonists do?
FULLY activate receptors
Produce max. pharmacological effect when all receptors are occupied
Maximal intrinsic activity
What do partial agonists do?
PARTIALLY activate the receptor upon binding
Produce a sub-maximal pharmacological effect when all receptors are occupied
What do inverse agonists do?
Produce an effect OPPOSITE to a full or partial agonist
- Decrease receptor signaling
- Intrinsic activity is present and related to the inhibition of receptor function
Graphically, depict the response levels of
Full agonist
Partial agonist
Antagonist
Inverse agonist
What are the three types of antagonism?
Pharmacologic
Chemical
Physiologic
Describe:
Pharmacologic antagonism
aka Receptor antagonism
Action at the same receptor as endogenous ligands or agonist drugs
Describe:
Chemical antagonism
When chemical antagonist makes the other drug unavailable
Describe:
Physiologic antagonism
Occurs between endogenous pathways regulated by different receptors
Describe a:
Competitive antagonist
COMPETES with endogenous chemicals or agonist drugs for binding of the receptor
Describe a:
Non-competitive antagonist
What subtypes does this include?
Receptor inactivation is not surmountable
Irreversible antagonists= irreversibly bind to and occlude the agonist site on the receptor by forming covalent bonds
Allosteric antagonists = bind to a site other than the agonist site to prevent or reduce agonist binding or activation of the receptor
Describe the agonist effect (E) vs agonist concentration (EC) relationships graphically for:
Competitive antagonism
Noncompetitive antagonism
What is a dose-response curve?
Graphic representation of the relationship between a drug and its effects
When you plot drug dose arithmetically on the x-axis vs drug effect on the y-axis, you get a ___________
Hyperbolic curve
When you present the dose-response curve as graphing the logarithm of the drug dose vs the respone, you’ll get a __________
Sigmoidal curve
What is the:
Emax
ED50
Within a dose-response curve?
Emax= the maximal effect thta can be produced by the drug
ED50 = Effective dose, the dose that produces 50% of it’s maximal effect
What questions does a graded response answer?
“How much?”
What questions does a quantal response answer?
[All or none; yes-no; “binary” responses]
“Does the response occur or not?”
“In how many?”
Describe what a non-cumulative quantal dose response curve looks like:
What information does it include?
Number or % of individuals responding at a dose of a drug and ONLY AT THAT DOSE
Describe what a cumulative quantal dose response curve would look like:
What information is contained here?
Number or % of individuals responding at a dose of a drug AND at all doses loer than that dose
Define:
ED50
TD50
LD50
ED50= median effective dose
TD50= median toxic dose
LD50 = median lethal dose
How do you claculate the therpeutic index?
What does a HIGH TI mean?
Therapeutic Index (TI) : TD50/ED50
**The higher the TI, the SAFER the drug
Define:
Therapeutic window
The range of doses of a drug or of its concentration in a bodily system that provides for the safe and effective therapy
Define:
Potency
The amout of drug required to produce specific pharmacological effect
Define:
Efficacy
The maximal pharmacological effect that a drug can produce
What are the major classes of drug targets?
Membrane receptors
Nuclear receptors
Ion channels
Transport proteins
Enzymes
What do protein kinases do?
Modify protein by covalently attaching a phosphate group to an amino acid residue
What are the effects of the following G protein subclasses?
Gs
Gi
Gq
G12/13
Gs = activates all isoforms of adenylyl cyclase
Gi = inhibits adenylyl cyclase
Gq = activates phospholipase C
G12/13 = activates Rho GTPases
Note: didn’t include the rest of the DSA info because it’s all biochem review
