Name that Structure
What is this compound that was used in South American poison arrows?
What is Tubocurare.
What substance was used as a solubility agent in elixir sulfanilamide that led to the death of 105 children?
What is diethylene glycol.
Two separate agonists are used together: one agonist raises blood pressure and the other decreases blood pressure. What type of antagonism is this?
What is Functional Antagonism.
Provide definitions for potency and EC50 and what is their relationship RELATIVELY?
Potency - Amount of drug needed to produce an effect (determined by [drug])
EC50 - Plasma concentration required for 50% of a biological response
RELATIVELY if potency is HIGH, EC50 would be low --> (Less total drug is needed to produce a therapeutic response)
Summarize how they measured Ki experimentally
Radio ligand:
Will eventually occupy all of ligand (100%)
* Amount of drug required to bind 50% of receptor = Kd or Ki (how well a drug binds to receptor aka affinity) --> VERY $$$
What is this compound that is also known as Deadly Nightshade/Belladona?
What is Atropine.,
The Harris-Kefauver amendments to the Food and Drug Cosmetic Act required proof what two things?
What are safety and efficacy.
An agonist binds to a different site than that endogenous or natural ligand and causes an alteration to the orthosteric binding side. What type of agonist is this?
What is Allosteroic Agonist.
Define and describe the main differences between pseudo-irreversible and irreversible noncompetitive antagonism
Pseudo – Very very slowly dissociating antagonist (does come off, but very slowly) Does not fully inactivate the receptor FOREVER
Irreversible – Antagonist that binds to receptors and NEVER come off (almost like cell death / permanent inactivation of a receptor) COVALENT MODIFICATION (chemical)
What is the difference between EC50 and ED50?
EC50 - Effective concentration to achieve a 50% RESPONSE in a system
ED50 - Effective DOSE to achieve a desired response in 50% of the GENERAL POPULATION aka median effective dose
What is this compound and what flower does it come from?
What is Morphine and poppies.
What year was legislation passed to protect against mislabeling or interstate transfer of adulterated food and drugs?
What is 1906.
All partial agonists are, BY DEFINITION, what?
What is Partial Antagonists.
What is the relationship between Ki and the rightward shift if agonist concentration is held constant?
The higher affinity of the antagonist, the further there is a rightward shift of the graph. The LOWER Ki, the higher affinity for the antagonist or [I]. Plug in variables if needed
What do LD50 and ED50 determine? What does it mean if these values are very close? What does it mean if these values are juristically different?
LD50 / ED50 = Therapeutic index = RATIO that is relative.
IF LD50 and ED50 are CLOSE, this would result in a small therapeutic index and a hard to dose drug
If LD50 and ED50 are very different, this results in a LARGE therapeutic index and a lot of wiggle room with dose of drug
What is this compound that was used as a chemical warfare agent in WW2, and what type of treatment was it later discovered to be?
What is Nitrogen Mustard and chemotherapy.
What phase of clinical trials is dosage range tested and determined?
What is Phase II.
What type of agonists can lower the response of a drug below baseline or its constitutive activity?
What is Inverse Agonists.
What are PAM and NAM and how do the % of maximal effect curves compared to Log [L] differ?
PAM – Positive allosteric modulator
“enhances affinity”, we need LESS drug to get to EC50!
NAM – Negative allosteric modulator
Can NOT force the response to zero compared to irreversible antagonists
How does TI and TW differ?
TI - A RATIO (regarding drug dose) between lethal dose and effective pharmacological dose
TW - a RANGE of SS concentrations that produces a therapeutic repones while minimizing toxicity
What are the following structures, in order from left to right?
What are Caffeine, Ephedrine, Ergotamine
A patient approaches you and tells you that they have been taking Ozempic for 3 months. They also tell you that they are experiencing supposed side effects of Ozempic that are not commonly listed in the drug’s monograph. As the pharmacist, you report the side effects to the FDA. What phase of the clinical trial is this considered?
What is Phase IV.
A drug modifies dopamine so it is no longer the same structure and can no longer bind to dopamine receptors. What type of antagonism is this?
What is Chemical Antagonism.
Draw a graph with % maximal effect as y-axis and Log [L] as x-axis under circumstances of competitive antagonism, as an inhibitor is added to the system. How will this effect the EC50? What is the key difference between a partial agonist and a competitive antagonist?
Partial agonist - Competes with full agonist, but only reduces response relatively (may lower overall biological response)
Competitive antagonist - Reduce response to zero if no increase in agonist!
What is the difference between an effector molecule and a secondary messenger?
Provide one example that Dr. Roman gave in class
Secondary Messenger - Small molecules (ions)
**Ion Channel and cell becomes more negative; Membrane of cell may be an effector in this instance. --> If Ca+ enters a cell and this may have an impact on many other effectors (ex. E2, E3, and E4)
*Scaffolding proteins - Change shape and function of cell --> Bring other effectors closer! Enhances effect of secondary messengers* (Bring E2, E3, and E4 closer to Ca)