Receptor Theory Flashcards
What are examples of some drug targets?
Receptors
Enzymes
Carrier molecules
Ion channels
What is a receptor?
Target molecule through which soluble physiological mediators produce their effect
What is required for drug receptor interactions?
Specific chemical structure required
What are kinetic experiments in binding studies?
Where the binding of one or more concs of radioligand is measured at an incrementing series of time points
What are saturation experiments in binding studies?
Where binding of an increasing series of concs of radioligand L
What are competition/modulation experiments in binding studies?
Where the binding of one or more fixed concs of a radioligand is measured at eqm in presence of an incrementing series of cons of a non-labelled compound
What is an agonist?
A substance that interacts with the receptor, + elicits observable biological response. Can be endogenous or exogenous substance
What happens as agonist conc increases?
Response increases
What is ED50?
Effective dose = indicates how much drug is required
What is a partial agonist?
Acts on same receptor as agonists, BUT, regardless of the dose it cannot produce same max biological response as full agonist
What happens to partial agonist as drug conc increases?
Response of agonist increases
What are inverse (negative) agonists?
Acts on same receptor of agonist yet produces an inverse effect
What happens to inverse agonist as drug conc increases?
Response decreases
What is a spare receptor?
Max responses elicited at less than max response occupancy. Receptors which exist in less of those required to produce full effect
What is intrinsic activity?
Value that refers to the ability of complex to produce a response
What is an antagonist?
Inhibits the effect of an agonist BUT has no effect of its own. May compete on the same receptor site that the agonist couples, or may act on allosteric site
What are the different type of antagonists?
Competitive
Non-competitive
Allosteric
Physiological
What is a competitive antagonist?
Binds to same site as agonist in reversible manner
What is a non-competitive antagonist?
Binds to same site as agonist irreversibly
What is an allosteric antagonist?
Antagonist + agonist bind to different site on same receptor
What is a physiological antagonist?
2 drugs have opposite effects through different mechanisms
What does a competitive antagonist do to the curve?
Shift to right
What does a non-competitive antagonist do to the curve?
Shift to right + down
What does a allosteric antagonist do to the curve?
Shift to right
What is a heteroreceptor?
Receptor that regulates synthesis + release of chemical mediators other than its own ligand
What is an auto receptor?
Macromolecule typically found in nerve ending that regulates synthesis + release of own ligand
What is receptor-down regulation?
Agonist, induces a decrease in no. of receptors available for binding
What is receptor-up regulation?
Agonist, induces an increase in no. of receptors available for binding
What is affinity?
The ability of drug to bind to receptor
What happens if a ligand has low affinity?
High conc needed for biological response
What is efficacy?
Measure of max physiological response
What is potency?
Refers to dose of drug required to produce specific effect of given magnitude
What is potency dependent on?
Affinity + efficacy
What happens if it is more potent?
Effect at lower conc
What happens if less potent?
Effect at higher conc
What is the occupation theory?
Receptor theory
Drugs act on independent binding sites + activate them = biological response proportional to amount of drug-receptor complex formed
Response stops = complex dissociation
Drug effect directly proportional to no. of receptors occupied
What is rate theory?
Pharmacological activity directly proportional to rate of dissociation + association, NOT no. of receptors occupied
What is the dissociation + association of an agonist?
BOTH fast
What is the dissociation + association of an antagonist?
Fast association
Slow dissociation
What is the dissociation + association of a partial agonist?
Intermediate association
Intermediate dissociation
What is the induced-fit theory?
As drug approaches receptor, receptor alters conformation of its binding site to produce drug-receptor complex. Binding produce mutual plastic moulding of both ligand + receptor
How many types of macromolecular perturbation theory is there?
2
What is the first type of macromolecular perturbation theory?
Specific conformational perturbation = biological response (agonist)
What is the second type of macromolecular perturbation theory?
Non-specific conformational perturbation = biological response (antagonist)
What is activation aggregation theory?
Drug receptor exists in eqm between activated state (bioactive) + inactive state (bio-inactive); agonist bind to activated state + antagonist to inactivated state
What is 2-state receptor model?
Receptor exists in resting + active state, presence of drug shifts eqm either way
What are chemotherapeutic drugs?
Used to cure diseases + cancer
What are examples of chemotherapeutic drugs?
Sulfa drugs + antibiotics
What are pharmacodynamic drugs?
Used in non-infectious diseases
What are examples of pharmacodynamic drugs?
Sedatives + hallucinogenic
What are examples of miscellaneous agents?
Narcotic analgesics + local anaesthetics
What are the different types of drug mechanisms?
Physical Chemical Drug-receptor interactions Drug-enzyme interactions Drug-channel interactions Miscellaneous
What is a physical mechanism?
Drug does NOT produce chemical reaction or change in cells of body
What is a chemical mechanism?
Drug acts by producing chemical reaction
What is drug-receptor interaction mechanism?
Act on cell membrane + builds complex
What is a ligand?
Substances that bind to receptors
What is an example of a ligand?
Acetyl choline
What is an agonist?
Drugs that bind to receptors = activate receptors
What happens after response increases till peak?
Response decreases even though agonist still bound
What happens once response decreases after peak is met?
Produces relaxation of skeletal muscles by:
Activation of nicotine receptors
Desensitization of receptors in neuromuscular junction
What are drug-enzyme interaction mechanisms?
Same as drug-receptor just enzymes instead
Competitive + non-competitive
What are drug-channel interaction mechanisms?
Same as drug-receptor just involves channels
eg. Na+, K+, Ca2+ + Cl- channels
What are miscellaneous mechanisms?
Drugs don’t act through any mechanism already mentioned
Describe non-specific interactions
Drugs act by physical means outside cell
External surfaces of skin + GI tract
Outside of cell = chemical interactions
What is primary effect?
Desired therapeutic effect
What is secondary effect?
All other effects beside therapeutic - beneficial or harmful
What is local effect?
When drug effect occurs immediate vicinity of application
What is systemic effect?
When drug effect occurs away from site of administration
What are the two modes of action?
Killing foreign organisms
Stimulation + depression
What is killing foreign organisms?
Mode of action
Chemotherapeutic agents kill bacteria, worms + viruses
What is stimulation + depression?
Mode of action
Drugs act stimulating or depressing normal physiological functions
Stimulation = increases rate of activity
Depression = decreases
What is the action of drugs?
Biochemical physiological mechanisms by which the chemical produces a response in living organisms
