EXAM #1: PHARMACODYNAMICS Flashcards
Generally, what is the pharmacodynamics?
“What the drug does to the body.”
What are the five categories of receptors?
1) Intracellular receptors
2) Receptors with intrinsic enzyme activity
3) Receptors that directly associated with intracellular enzymes
4) Ligand-gated ion channels
5) 7-membrane spanning receptors (GPRC)
What type of ligands bind intracellular receptors?
LIPOPHILLIC ligands e.g.
- Steroids
- Thyroid hormone
- Fat-soluble vitamins
What is the general consequence of ligand binding with an intracellular receptor?
Change in gene transcription
Describe the structure of a receptor with intrinsic enzymatic activity.
- Single membrane spanning domain
- Extracellular domain binds ligand
- Intracellular domain contains enzymatic activity
What is the difference between a receptor with intrinsic enzymatic activity and a receptor that directly associates with intracellular enzymes?
Transmembrane domain associated with an enzyme instead of containing intrinsic activity itself
Describe the general structure of a ligand-gated receptor. What types of substances typically interact with ligand-gated channels?
- Multimeric complex of several transmembrane domains that form a barrel in the membrane
- Hormones and neurotransmitters
What is a 7MSR? What types of signals are propagated through a 7MSR?
“7 Membrane Spanning Receptors” that mediated:
- G-protein coupled signals
- G-protein independent signals
What are estrogen receptors and Vitamin A receptors examples of?
Intracellular receptors
What are epidermal growth factor receptor (EGFR), insulin receptor (IR), and transforming growth factor receptor (TGF-BR) examples of?
Receptor with intrinsic enzymatic activity
What receptor type associates with kinases and proteases including IL-3R, erythropoetin receptor, and the leptin receptor?
Receptors that directly associated with intracellular receptors
What type of receptor is the nicotinic acetylcholine receptor (NAChR)?
Ligand-gated
What type of receptor are the B-adrenergic, odorant, rhodopsin, frizzled, and smoothened receptors?
7MSR or G-protein coupled
What is a typical stimulus for receptor downregulation?
Continued simulation of the receptor
What is a typical stimulus for receptor upregulation?
Continued exposure to an inhibitor
What is Kd?
- Dissociation constant
- Ligand concentration at a point at which 50% of receptors are bound
Write the two different equations for Kd.
N/A
Draw and label a graph of drug concentration (C) vs Receptor-bound drug (B). Be sure to include Kd and Bmax.
N/A
What does Kd represent?
Affinity of a ligand for a receptor
What does a small Kd indicate? What does a large Kd indicate?
Small Kd= high affinity
Large Kd= low affinity
Example from powerpoint.
IP
Draw the dose-response curve on a drug concentration (C) vs. drug effect (E) graph. Be sure to include EC50 and Emax.
N/A
What is the EC50?
Concentration of drug that produces half-maximal effect.
What is potency a comparison of? What is potency conceptually?
- EC50
- Potency is a measurement of relative affinity and effectiveness of two or more drugs.
*****A drug with a LOWER EC50 is MORE potent.
What is efficacy a comparison of? What is efficacy conceptually?
- Emax
- Efficacy is the maximal effect a drug can induce.
*****A drug with a higher maximal effect is more efficacious.
If drug A has a lower EC50 than drug B, what does this indicate about drug B?
Drug A is MORE potent
Are potency and efficacy independent or dependent on each other?
INDEPENDENT
What is an agonist?
A ligand that binds to a receptor AND produces a response
*****Response can be molecular, cellular, or physiological
What is an antagnoist?
A ligand that binds to a receptor and INHIBITS the response produced by the agonist
What is the difference between a competitive and noncompetitive antagonist?
Competitive= agonist and antagonist compete for the same binding site
Noncompetitive= agonist and antagonist bind at DIFFERENT sites
How does a competitive antagonist alter the dose-response curve?
- Shift in the EC50 to the RIGHT
- Emax is stall achievable
How does a noncompetitive antagonist alter the dose-response curve?
Decrease in Emax
**Note that the agnoist’s affinity (EC50) for the receptor may not be changed by the noncompetitive antagonist
How can you overcome the effects of a competitive antagonist?
Administer more agonist
What is a partial agonist?
- Drug that produces a lower than maximal response compared to the agonist i.e. lower Emax/ efficacy
- Binding of the partial agonist also DECREASES binding of the agonist
*****Note that the partial agonist evokes a partial response, whereas a noncompetitive antagonist inhibits a response. BOTH decrease Emax.
How can a partial agonist be used clinically?
- Administration of a partial agonist decreases binding of the full agonist
- A partial agonist can be given to decrease the effect of an endogenous substance (full agonist)
E.g. epinephrine as the endogenous substance, drug as a partial agonist–blunts the normal physiologic response
See ppt. example question on “dose response curve.”
B is most potent (lower ED50)
A, C, and D are equally efficacious (but differ in potency)
See ppt. example question on “dose response curve 2.0”
B and C are competitive inhibitors
D and E are non-competitive inhibitors
What is a quantal dose response curve?
Graph of dose (x) vs. % individuals responding (y)
What is the quantal dose response curve used for?
Describing the:
- Effective dose
- Toxic dose
- Lethal dose
What is the ED50?
“Median Effective Dose”
- Dose at which 50% of individuals exhibit a specific quantal response
What is the TD50?
“Median Toxic Dose”
- Dose at which a specific toxic effect occurs within 50% of the individuals tested
*****Note that this is typically further to the right on the quantal dose-effect curve than the ED50
What is the LD50?
“Median Lethal Dose”
- Dose that is lethal for 50% of individuals tested
What is the TI? What is the TI an indication of?
TI= Therapeutic Index
The TI is a measure of SAFETY
What is the equation for the TI?
TD50/ED50
Is a drug with a large TI, more safe or less safe than a drug with a small TI?
Greater TI= MORE SAFE
Answer the case presentation example on TI?
A= 4,000/100= 40
*Safer
B= 1,000/200= 5
Draw a quantal dose-effect curve representing the TI examples from the ppt.
N/A
What is tolerance?
Decreased drug response following repeated administration
What is sensitization?
“Reverse tolerance”
- Increase in drug response following repeated administration
What does tolerance look like on a dose-response curve? Sensitization?
Tolerance= shift to the right
Sensitization= shift to the left
What are the causes of tolerance?
1) Phamacokinetic changes i.e. a change in metabolism
2) Change in pharmacodynamic parameters i.e. downregulation/ decrease in receptor number
3) Behavioral changes i.e. patient predicts response to drug and mentally compensates for it
What is the additive effect of multi-drug therapy?
Two drugs given together produce an effect consistent with the combined potency of the drugs
What is the synergistic effect of multi-drug therapy?
Two drugs produce a response that is GREATER than the sum of the agent’s potency
