Receptor basic, agonists antagonistic Flashcards
What are the effects of adrenaline?
-Many effects on the body including increasing heart rate and contraction
What is bisoprolol and and what is it prescribed for?
-Synthetic drug
-Prescribed to reduce heart rate and contraction
What is the bisoprolol used to treat?
-Used to treat cardiovascular conditions such as angina and heart failure when we want to reduce the effort of the heart
What does bisoprolol reduce the effect of?
-Bisoprolol reduces the effect of adrenaline
What does adrenaline do to the heart?
-Increase heart rate and contraction strength
What does adrenaline do to the lungs?
-Dilates airways
What does adrenaline do to the liver?
-Increases breakdown of glycogen, increasing plasma glucose
What is the importance of enantiomers for adrenaline
-The (+) enantiomer of adrenaline has about 100 fold greater biological than (-) adrenaline
Potency of adrenaline?
-Very high. Adrenaline acts at very low concentrations (bc they act act receptors)
e.g. 10-9M - 10-15M ranges can produce significant increases in heart rate
What are receptors?
-Target molecules with endogenous substances or ‘given’ drugs bind to produce a cellular response
What receptors in the heart does adrenaline stimulate?
-Adrenaline is a physiological hormone, which stimulates the beta-adrenoceptors
Where does bisoprolol act in the heart?
Bisoprolol is a synthetic drug which acts at beta adrenoceptors to prevent the action of adrenaline
What are the general properties of receptors?
-Expressed in different tissues
-High selective targets: Only specific drug structures bind to receptors
-Amplify signals: Small number of drug/receptor interactions initiate significant biological effects
What is the general structure of beta-adrenoceptor?
-Is a large complex protein molecule consisting of transmembrnae domains
What do the transmembrane regions contain in beta-adrenoceptor and what does this allow for?
-Transmembrane regions with hydrophilic and lipophilic amino acids
-Allows the folding of membrane hence creates binding sites
Where else can beta-adrenoreceptors be found?
-liver
-lungs
What are the 4 different types of receptors?
Receptors
-Adrenaline and Bisoprolol act at beta adrenoreceptor
Enzymes
-Ibuprofen acting on cyclooxygenase
Carrier molecules
-Fluoxetine(anti-depressant) acting at serotonin uptake carrier
Ion channels
-Lignocaine (local anaesthetic) acting at Na+ channels
What is an agonist
A drug which binds to a receptor to produce a biological cellular response
-e.g. adrenaline is an agonist that increases heart rate
What is an antagonist?
A drug which binds to a receptor but does NOT produce a biological cellular response
-e.g. Bisoprolol is an antagonist that blocks adrenaline-mediated increases in heart rate
What are drugs classified according to?
Clinical use
- e.g. bisoprolol is used to treat angina hence “anti-anginal drug”
Target receptor
-e.g. bisoprolol binds to beta-adrenoreceptors hence “beta-adrenoreceptor antagonist (beta-blocker)”
What are receptors often classified according to?
-Receptors are often classified according to the agonists and antagonists that act upon them e.g. adrenoceptors: These drugs bind to adrenoceptors, but their differential actions define whether an alpha or beta adrenoceptor is involved
What receptors do blood vessels express?
Alpha adrenoceptors
What is most to least potent on alpha adrenoceptors in blood vessels? What do they do?
Noradrenaline>Adrenaline>Isoprenaline
-Increase constriction
What drugs acts as an antagonist on alpha adrenoceptors?
-Alpha adrenoceptors on blood vessels are blocked by prazosin(not bisoprolol)
What is most to least potent on alpha adrenoceptors in the heart? What do they do?
Isoprenaline>Adrenaline>Noradrenaline
-Increase heart rate
What is the occupation of receptor governed by?
-Occupations of receptor is governed by affinity
What is activation of receptor goverend by?
-Activation governed by efficacy
What is binding of agonist and antagonist assessed by?
Both agonists and antagonists bind to receptors
-How well they bind is assessed by equilibrium constant(KA, Kant)
How is the quality of action produced by an agonist assessed?
How well they produce an action is assessed by effective concentration producing 50% of maximal response(EC50)
- only agonists
In what fashion do agonists and antagonists bind to receptors?
Reversibly -Adrenaline and bisoprolol bind to beta adrenoceptor-then dissociate- this is a continuous ‘off and on’ process
What are the types of binding that occur between receptor and agonist/antagonist?
Hydrogen bonding, Ionic bonding, van der waal’s forces
-Relatively weak therefore reversible binding and good dissociation
Covalent binding
-Stable strong bonds therefore irreversible binding and poor dissociation hence “conformational change”
What governs the reversible binding of agonist to receptor? What is this dependant on?
-Rate of reversible binding of agonist to receptor is governed by law of mass action
-Dependent on concentration of the reactants involved
What does the law of mass predict?
- Low concentration of A and lots of Rfree results in a low rate of AR interactions
- Increase the concentration of A and you increase rate of AR interactions-shifts reaction to right
- Continue increasing concentration of A results in few Rfree, which results in a low rate of AR interaction
When is the equilibrium constant (KA or KANT) reached?
When 50% of receptors are free and 50% are bound by drug
What is KA or KANT for the drug and what does this mean?
-KA or KANT is the concentration of the drug at equilibrium:
-This means that a KA of 50nM means that at this concentration 50% of receptors will be occupied by agonist
What does a small KA or KANT value mean?
Smaller KA or KANT means agonist or antagonist has a greater affinity for receptor(binds more) than an agonist or antagonist with a higher KA or KANT
What does efficacy measure?
-Efficacy measures biological effect like increase in heart rate by adrenaline
What is EC50?
Effective concentration giving 50% biological response
Are affinity and efficacy equal? Why?
Affinity and Efficacy of an agonist are not equal
-You do not need full occupancy to give a maximum response
-The reason why drugs can work at low concentration is because receptors amplify signals, so only a small number of drug-receptor interactions provide biological effects
What happens to response against log(agonist) curve in the presence of a competitive antagonist?
-Presence of a competitive antagonist shift agonist curve to the right
-Same maximal response
What needs to be done to overcome/surmount competitive antagonism?
-Increasing concentration of agonist will out compete or surmount antagonism
What happens to response against log(agonist) curve in the presence of a non competitive antagonist?
-reduce slope and depress maximum
How does non-competitive antagonism work?
-Antagonist binds to a different site than agonist
How does irreversible antagonism work?
-Antagonists binds irreversibly to either agonist or non-agonist binding sites on the receptor through covalent bonds
What impact do both non-competitive/irreversible antagonists have?
-Both non competitive/irreversible antagonists reduce number of receptors
