Chapter 1 Flashcards
Explain the difference between poisons and toxins
Poisons are non-biologic substances such as cadmium, arsenic, and lead
Toxins are biological substances such as a puffer fish or certain mushrooms
What are some differences between a competitive inhibitor and Allosteric inhibitors?
Competitive inhibitors: compete at the active site; surmountable at low dose; insurmountable in high doses.
Allosteric inhibitors: binds to site other than active site; always insurmountable.
Describe the relationship between specificity and bond strength
Specificity and bond strength are inversely related. The stronger the bond, the less specific the fit has to be.
How does Kd affect a ligand’s/drug’s affinity for a receptor?
An increasing kd means more receptors are occupied. Therefore, there is a decreased affinity for the receptor.
It takes a higher concentration of the drug to achieve desired effect.
How can a partial agonist act as an antagonist?
Partial agonists act as antagonists IN THE PRESENCE OF A FULL AGONIST.
Reason: when the partial agonist binds to the active site it has a lesser effect than the full agonist would have.
What is physiologic antagonism?
Physiological antagonism occurs when a substance produces effects that counteract those of another substance WITHOUT binding to the same receptor.
Example: Histamine is a physiologic antagonist to epinephrine. Epi acts on alpha-1 receptors, causing vasoconstriction and increased arterial pressure. Histamine acts on H2 receptors, reducing vasoconstriction and BP.
Why is Kd not the same as EC50?
Kd = dissociation constant
EC50 = maximal effective concentration
Sometimes only a few receptors are bound, yet maximum effect occurs. Also, consider if there were only 1 receptor available.
Kd and EC50 are independent of each other.
Does physiologic antagonism happen on the allosteric site or the orthosteric site of the same receptor?
Neither. For example, Epi binds to a beta-receptor to increase HR, while acetylcholine binds to muscarinic receptors to slow HR. The antagonistic effect is achieved using different receptors altogether
When thinking about competitive inhibition, what does it mean when the curve “shifts to the right”?
With competitive inhibition, the antagonist will bind and inhibit the agonist response. However, when more of an agonist is given, the same response will occur as if the antagonist wasn’t present. This causes the graph to shift to the right. The further right the graph shifts, the more agonist is needed to elicit the same response as when no antagonist is present.
When the curve “shifts to the right”, how does that affect the maximum effect of a drug?
Shifting the curve to the right does NOT change the maximum effect at all. The maximum effect will always remain the same. The only thing that changes is the amount of agonist needed to achieve the same effect.
What occurs when a partial agonist and full agonist are given simultaneously?
When given simultaneously, the partial agonist will outcompete the full agonist. Overall, we will see less of an effect because the partial agonist is taking over and acting like an antagonist.
What does the Emax represent and what can change this value?
The point at which maximum effect from the drug is achieved.
By changing the drug itself, we can change the value. However, giving more of a specific drug will not change the Emax; it will start to have a toxic effect on the body.
What is the difference between pharmacodynamics and pharmacokinetics?
Dynamics= the drug’s effect on the body
Kinetics= the body’s effect on the drug, involves ADME: absorption, distribution, metabolism, excretion
What are (3) ways modern pharmacology regulates drugs?
- Adherence to scientific principles and testing
- Evaluation of therapeutic claims
- Control of worthless medications (snake oil!)
Are allosteric inhibitors competitive or non competitive? Why?
Non competitive because they are not binding to the active site that others are trying to bind to, there is nothing to compete for.
Which curve on the graph (Fig 1-2) represents the effect of a competitive inhibitor?
A+B (orange)
A higher dose is required (Right shift) to achieve the same response of the agonist acting alone
How does an allosteric inhibitor lower the ability for agonists to bind?
It decreases the availability of the orthosteric site (changing it’s shape)
What is the constitutive activity and how do you influence it?
The basal activity between receptors fluctuating between their active and inactive forms. This is influenced by giving drugs. Agonists increase the activity, while inverse agonists decrease it.
Albumin can help enhance the pharmacokinetic properties of a drug, explain HOW it can do this:
Albumin acts as a drug carrier, allowing drugs to bind with it as the receptor sites become saturated on the cell’s surface. Albumin acts as a transporter, eventually delivering the drug to its targeted receptor site. Drug carriers, such as albumin, can make the active site of a receptor more or less available for drug binding.
Describe how a drug can overcome an irreversible competitive inhibitor:
With low doses of a competitive inhibitor, a drug can overcome this with a larger dose. However, with a high dose of a competitive inhibitor when covalently bonded to a receptor site, the only way for a drug to overcome this is to wait for new receptor sites to be created and bind with those.
