SABA/ LABA Flashcards
What are The Adrenergic Binding Sites?
catechol OH’S- 2 serine residues
benzene ring- pi stacking interaction with phenylalanine( or any benzene amino acid)
OH- with h bonding
NH3+ -ionically with aspartate( or a generally negatively charged amino acid)
what does the introduction of an isopropyl subunit do?
introduces beta selectivity
what is different in alpha and beta adrenoceptors?
in beta adrenoceptors there is a hydrophobic pocket that the isopropyl substituent is attracted to
in alpha- there is not
how do you increase selectivity and potency?
Adding a methyl group on the a carbon promotes binding to a2-receptor
what effect does adding a distant hydrogen bonding group?
significantly increases potency, while retaining b-selectivity
how can adrenergic agonists be used?
Adrenaline, used in cardiac emergencies and to combat anaphylactic reactions (eg bee stings / penicillin). Lack of specificity limits other uses.
•Ephedrine, found in ma-huang and many non-prescription preparations.
•Bronchodilatory, vasopressor and cardiac stimulatory effects.
•Able to act as CNS stimulant due to relative lipophilicity.
what is Dobutamine used for?
b1 agonist. Treatment for cardiogenic shock.
what is Clonidine used for?
a2 agonist. Treatment for hypertension
what are Oxymetazoline & Xylometazoline used for?
a1 agonists. Vaoconstrictors, topical uses in treatment of nasal congestion and bloodshot eyes.
what are some metaolic problems associated with LABA/SABA?
•Isoprenaline used as asthma treatment, but b1activity produced cardiovascular side-effects
.•Extra substitution in isoetharine gave b2 selectivity.
•Short duration of action due to catechol-O-methyl transferase activity.
Why is salbutamol more clinically effective that Soterenol?
it has an extension of the catechol ring on the OH- therefore not a target for COMT anymore, so it will not be metabolised by it
which is the more active form of salbutamol?
R-salbutamol 68x more active than S.
•Pure R-form, levalbuterol later marketed (chiral switching).
what is another way of dealing with COMt?
Not structurally a catechol, so is not a good catechol-O-methyl transferase substrate
what is another use for terbutaline ?
As well as an asthma treatment, terbutaline is used clinically for the prevention of pre-term labour
what effect does Extending a chain to polar unit ?added
increases potency
