Pharmacology Flashcards
Occupation of a receptor by a drug always results in acitvation of the receptor.
True or false.
False - it may or may not
What is receptor activation?
It means that the receptor is affected by the bound molecule in such a way as to elicit a tissue response.
Distinguish between binding and activation.
Binding of ligand to receptor does not always result in activation. Binding and activation represent two distinct steps in the generation of receptor mediated tissue response by an agonist.
What is an antagonist?
Something that binds to the receptor without causing activation of the receptor and thereby prevents an agonist from binding
What is potency?
How is this depicted on a dose-response curve?
A measure of the amount of drug necessary to cause a biological effect
By the [Drug] at 50% response. A drug with higher potency will reach 50% response with less [Drug].
What is EC50?
The drug concentration that produces 50% of the maximum possible response in a graded dose-response curve. It is a measure of potency.
What is efficacy? What does it depend on?
How is this represented on a dose-response curve?
The ability of a drug to elicit a response when it interacts with a receptor. It is dependent on the number of drug-receptor complexes formed and the efficiency of coupling of receptor activation to cellular response.
The amount of response that is ellicited. If a drug reaches 100% response, it is 100% efficacious. If another drug reaches 80% response it is less efficacous than the drug that reached 100%.
What is a partial agonist?
They have intermediate levels of efficacy such that even when 100% of the receptors are occupied the tissue response is submaximal.
What 2 things influence potency?
Affinity and efficacy
What is a competitive antagonist?
How is this displayed on a dose-response curve?
How are its effects overcome?
When both the agonist and antagonist bind to the same site on the receptor, they are said to be competitive. Competitive antagonists prevent an agonist from binding to its receptor and maintain the receptor in its inactive conformation.
Recognized by a righward shift of the graph. Slopes remain parallel and the agonist will always reach 100% response but will take longer.
Effects overcome by adding more agonist.
What is an irreversible antagonist?
Does adding more agonist overcome the effects of an irreversible antagonist?
What would the dose-response curve look like?
Causes a downward shift of the maximum response because they bind to the receptor permanently and make it so the receptor is no longer funtional.
No
Competitive antagonism reduces an agonist’s ________
Irreversible antagonism reduces an agonist’s ________
Potency
Efficacy
What is a quantal response?
What are they useful for determining?
- A dose-response relationship that is of the influence of the magnitude of the dose on the proportion of a population that responds
- Doses to which most of the population responds
What is the therapeutic index?
The ratio of a drug’s toxic dose to its therapeutic dose. A safe drug has a high therapeutic index.
What would a dose-response curve look like for a drug with a narrow therapeutic index?
What would a dose-response curve look like for a drug with a wider therapeutic index?
What 3 things affect how well a drug interacts with its receptor?
Size
Chirality
Shape
What is Kd for a receptor?
The concentration of drug at which 50% of the receptors are bound
What is Bmax for a receptor?
The maximal number of receptors bound. It is a measure of the amount of drug required to saturate a population of receptors and a measure of the number of receptors present in the sample.
What does it mean if the EC50 < Kd for the receptor?
1) The duration of the activation of the effectory may be much greater than the duration of the drug-receptor interaction
2) The actual number of receptors may exceed the number of effector molecule available (spare receptors)
Spare receptors increase the _____ to the agonist b/c the likelihood of drug-receptor inteaction increases in proportion to the number of receptors available.
Sensitivity
What is the orthosteric site of a receptor?
What are allosteric sites of a receptor?
Where agonists and competitive antagonists bind
Where other drugs/molecules can bind to influence receptor function in various ways
Describe the process of extracellular and intracellular densitization of ion channels.
Extracellular: A conformational change in the receptor results in tight binding of the agonist molecule without opening of the ion channel. This process is rapid and pronounced.
Intracellular: phosphorylation of intracellular regions is another means that can induce desensitization, but it is slower than extracellular route.
Is binding of ligand to the receptor always required to activate the receptor?
Not always - there are some examples of receptors that have appreciable levels of activity when no ligand is bound - constitutively active.
What is an inverse agonist?
A drug that reduces the level of constitutive activation of receptors.
Most of the receptor antagonists in clinical use are actually _____?
Inverse agonists
Chemical antagonism
Uncommon situation where two substances combine in solution and the effect of the active drug is lost
Pharmacokinetic Antagonism
Situation where the antagonist reduces the concentration of the active drug at its site of action by either (1) increasing rate of degradation or (2) reducing the rate of absorption
Non-competitive antagonism
How does the dose-response curve appear as a result?
- Antagonist blocks a point downstream from the receptor, and affects the chain of events that leads to the response by the agonist
- Slope and maximum of agonist are reduced, also possible to see rightwards shift
Physiological antagonism
Interaction of 2 drugs whose opposing actions in the body cancel each other out
What is a synonym for desensitization?
Tachyphylaxis
Describe desensitization of GPCRs
Phosphorylation of intracellular component of GPCR interferes with ability to activate second messenger cascade. Termed uncoupling.
Describe the affect of prolonged exposure to agonists.
A gradual decrease in the number of receptors expressed on the cell surface is seen as a result of internalization of the receptors. These internalized receptors are taken up by endocytosis of patches of the membrane due to receptor phosphorylation.
What is receptor exhaustion?
When a receptor becomes desensitized due to depletion of an essential intermediate substance.
How can the body adapt to a drug’s effects?
A drug’s effects may become lessened, possibly due to altered gene expression resulting in changes in the levels of various regulatory molecules but little known about the mechanisms involved.
What are targets for drug binding?
Receptors
Enzymes
Carriers
Ion channels
What is the pharmacological definition of a receptor?
A protein molecule whose function is to recognize and respond to endogenous chemical signals.
What are the major types of bonds between drugs and receptors?
Covalent
Electrostatic
Hydrophobic
Hydrophobic bonds are most important for interactions between highly lipid soluble drugs with what targets?
Lipids of cell membranes and internal walls of receptor pockets
Drugs that bind to strong bonds to their receptors are generally more selective than drugs that bind by means of weak bonds.
True/False
False - drugs that bind via weak bonds are more selective. Although the bonds are weaker, the precision of the fit between the drug and its receptor must be much higher in order for that drug to still induce a response. As such, very few receptor types are likley to provide such a tight fit and generate effects.
How does drug size affect drug-receptor interactions?
Drugs generally 100 - 1000 Daltons in size.
Lower limit sets requirement for specificity.
Upper limit sets requirement for movement throughout body (can’t be too large or won’t diffuse to tissues).
How does chirality influence drug receptor interactions?
Most drugs are chiral molecules but in most cases one of the enantiomers that are possible is more potent than the other. Enzymes are usually stereoselective and tend to metabolize only a specific enantiomer of a drug –> duration of action of one enantiomer may be very different than that of the other.
- Histamine is formed from the amino acid _____ and exerts its effects on ________ located on cell surfaces.
- Histamine is an _____ and a _______.
- It regulates what physiologic pathways?
- Histidine; GPCRs
- Autacoid (acts like local hormone); neurotransmitter
- Immune, slee/wake, vestibular system
- Histamine signaling through H1 receptors ____ the permeability of capillaries.
- Histamine signaling through H1 receptors ____ the sensory nerve endings that mediate pain and itching.
- These signals what kind of response?
- Increases
- Stimulates
- Immune –> fluid leaving capillaries leads to runny nose/watery eyes
Histamine signaling through H1 receptors promotes the release of what 2 hormones in the CNS?
Epinephrine
Norepinephrine
______ is an antagonist of all H1 receptors.
Diphenhydramine
____ is an antagonist of only peripheral H1 receptors and it cannot cross the blood/brain barrier to enter the CNS.
Fexofenadine
____ is an antagonist against all H2 receptors.
Cimetidine
