Intro to Pharming Flashcards
What does a lower Kd mean
It means that less drug is needed for activation. It is a measure of affinity/potency
high on rate and low off rate
What is the fold difference between minimal activation (10%) and max activation (90% response)
81 fold or 2 log units
Response Equation
DR Complexes/ Total Receptors = [D] / [D] + Kd
Potency
compares the concentrations of drugs needed to get 50% of maximal effect (EC50)
think a more potent drug is lower on the x acis because less drig is needed for the same effect
Efficacy
the measure of the maximal effect. Not all drugs lead to maximal effect. Ex: a partial agonist you never get maximum activation and is less efficacious
Is efficacy or potency more important?
efficacy is more important because a less potent drug with high effiacy will produce better results than a less efficacious drug with high potency
What are the types of receptors
1) ionotropic receptors (ion channels
2) metabolic teceptors (g proteins, kinases)
3) Transcription factors (alter gene expression- steroid hormones)
Examples where effects may not be proportional to receptor binding
1) complex interactions (cascades of 2nd messengers)
2) spare receptors- only need to activate a small fraction of receptors to get a max response (NMJ)
3) Tolerance/Desensitization- previous exposure to a drug may causes decreased effects
agonists
bind and activate receptors, get a dose response curve
antagonist
bind and dont activate receptor. Flat dose response curve. If given with an agonist, you get a shift dose that leads to a decrease in potency
Partial agonists
binds receptors and induced a partial activation (non-maximal)- lower efficacy
Spare Receptors
excess number of receptors for maximal effect. Only need to activate a fraction to get the maximal response. Causes a dose-response curve to be altered. ED50 is lower than Kd because you will get 50% binded at a lower dose
Dissociation Constant
the measure of affinity/potency (kd)
also the ratio of off rate receptor binding to the on rate
a smaller kd will bind the receptor longer
drugs with a very small kd may act for a longtime
Population curve
similar curve to individual dose response curve but contain frequency distribution that depends on the variability of response in the population that gives the sum of responsers
Therapeutic Index
important for toxicity, tell you that LD50/ED50. Not based on receptor binding but the variation in the population
How might there be changes in receptor window?
-Effects of drug diminished by repeated uses
-Down regulation in the number of receptors
-upregulation: overstimulation leading to an increase number of receptors such as seen in denervation hypersensitivity
-Sick animals (diminished organ failure)
What does parenteral drug admin depend on
1) form of the durg
2) perfusion of site of injection
3) perfusion of target organ (central compartment of peripheral
Pros and Cons of Intravenous administration
Pros: can give irritating solutions due to rapid dilution, can give large volumes
Cons: Dont give oils, suspensions
Bolus
initial high concentration of drug that moves to less perfused organs later. This redistribution decreases the blood concentration
When is steady state reached in constant infusion
4 half lifes
Pros and Cons of subcutaneous administration
Pros: prompt absorption for aqueous solutions, some suspensions, impants
Cons: cant give large volumes or irritants
Pros and Cons of Intramuscular administration
Pros: prompt absorption for aqueous solutions, slow and sustained for repository, moerate volumes, some oily vehicles and irritatns
What method of administration is about as fast as IV
Intraperitoneal
Why is oral absorption variable
Depends onL
1) Form of drug (capsules or those that dissolve)
2) Movement across a membrane/mucosa
3) Absorption from stomach
4) Bioavailability
