Receptors: Intro to Pharm Flashcards
What are the principles that are special to and underlie pharmacology?
There are active materials in plants and medicine which cause the effects
Distinct relationship between dose and drug effect
Structure-activity relationship exist
Drugs do not create function they modify it
No drug has a single action
Is drugs-receptor binding cause by a single interaction?
Not normally, it is usually a combination of binding interactions which provides forces needed for a drug-receptor complex
How does an agonist work?
Binds to the receptor and activate it like a key
Initiates a conformational change in receptor and activation of one or more downstream pathways
Compound that binds to a receptor and produced a biological response
How does an antagonist work?
Can fit the lock but can't open it Drugs that bind to receptors but do not activate it Inhibit activation by agonists Block or reverse effects of agonists No effect on their own
What is an allosteric modulator?
Compunds that bind to a seperate site on the receptor from that which normally binds agnoists
Can inc or dec response of natural agonist
What is affinity?
Tendency of a drug to complex with a receptor
What is the affinity constant?
k(aff) = k1/k2
Value which measures the attraction of a drug for a receptor
What is drug selectivity?
Drug must have a molecular conformation which permits binding with a particular receptor surface
Potency
The amount of drug necessary to elicit a response
Uses EC50 values
Expressed as the dose of a drug required to achieve 50% of the desired therapeutic effected
Analogs of active drugs are sought to be;
More potent, better complete absorption, metabolized less quickly, binds less to plasma proteins and less toxic
What are the two types of dose-response curves?
Quantal and grades
Quantal dose-response curve
All or none response
Based on population
Graded does-response curve
Range of responses
Based on individual
Efficacy
The ability of the agonist to cause the receptor to assume an active conformation
Represented by k3
Maximal response a drug can produce
What is a partial agonist?
Dual activity as agonists and antagonists
When bound, only partially able to shift the receptor to activated state
Partially inhibits full response at the same receptor
What does a spare receptor do?
Makes a tissue more sensitive to an agonist without changing its affinity for the receptor
Maximum response by only occupying a weenie bit of a the receptor
What is the therapeutic index?
Measure of drug safety
What is the normal therapeutic index?
LD50/ED50
What is the more realistic estimate of drug safety based on therapeutic index?
LD1/ED99
Margin of safety
What is the protective index of a drug?
ED50/ED50
Undesirable effect/desirable effect
Competitive antagonist
Compete with agonist for the same binding site on a give receptor
Makes agonist less potent and shifts the dose response curve right
Non-competitive antagonist
Occupy the binding site in an irreversible manner
Physiological (functional) antagonism
Response occurs when 2 agonists with opposing effects are administered together
What is an example of physiological antagonism?
Histamine (vasodilation) and norepinephrine (vasoconstriction)
Competitive antagonism
Response that occurs when a receptor antagonist is administered with an agonist
What is an example of competitive antagonism?
Atropine when blocking the effects of acetylcholine (ACh) at a muscarinic receptor
Chemical antagonist
Interacts directly with the drug being antagonized to remove it or to prevent it from binding to its target
What is an example of a chemical antagonist?
Dimercaprol - a chelator of lead and other toxic metals
What is tolerance?
Diminished response to the same dose of a drug over time
What are the mechanisms of tolerance?
Desensitization
Down regulation
Tachyphylaxis
Desensitization
A rapid process involving continuous exposure to a drug altering the receptor so that it cannot produce a response
What is an example of desensitization?
Continuous exposure to beta adrenergic agonist (albuteral for asthma)
Down regulation
Decrease in number of receptors cause by high doses of agonists over prolonged periods
Tachyphylaxis
Rapid development of tolerance
Indirect-acting amines exert their effect by releasing monoamines
What is supersensitivity/hyperactivity?
Enhanced response to a drug that may be due to an increased number of receptors (upreg)
Antagonists or denervation cause up-reg of receptors
Potentiation
Enhancement of the effect of one drug by another which has no effect on its own
Produces a parallel shift of the log-dose response curve to the left
What is an example of potentiation?
Cocaine potentiates response to noreponephrine
Syngergism
Production of a greater response than 2 drugs that act individually
What are two types of down regulation?
The cell type specificity of receptor subtypes
The cell type specificity of receptor-effector coupling
