Salbutamol/Salmeterol Flashcards
What type of adrenoreceptors does noradrenaline and adrenaline stimulate?
alpha and beta-adrenoreceptors
What type of adrenoreceptors does isoprenaline stimulate?
beta-adrenoreceptors
where are beta1 receptors found?
in the heart
Where are beta2 receptors found?
on bronchial smooth muscle
how do we treat bronchoconstriction without affecting the cardiovascular system?
using drugs that only stimulate beta2 receptors for bronchodilation
how are the airways in asthmatic patients characterised?
- inflammation (swelling and thick mucus production)
2. bronchospasm (bronchoconstriction, narrow airways)
what system causes bronchoconstriction?
the cholinergic system
what system causes bronchodilation?
the adrenergic system
what drug is used as an adrenergic agonist to stimulate bronchodilation?
salbutamol
what drug is used as an inhaled corticosteroid to treat inflammation?
beclometasone
How does inflammation occur?
- Antigen binds to Antibody (IgE)
- A-A complex forms
- Bronchoconstricting mediators (mast cells) arrive at site
- prostaglandin, histamine and leukotrienes released by mast cells
What is used to inhibit the cholinergic system?
anticholinergics
what are noradrenaline and adrenaline classified as?
Catecholamine
where is noradrenaline synthesised?
in neurons of both CNS and autonomic nervous system
how is a transmission terminated?
- stimulated adrenergic neurons release noradrenaline into synaptic cleft producing a characteristic adrenergic response
- presynaptic neurones are taken in causing termination
- some noradrenaline also diffuses away from the receptor and is metabolised by catechol-O-methyltransferase (COMT) or by monoamine oxidase (MAO) in circulatory system or COMT in other tissues
- noradrenaline can also be used again or metabolised by mitochondrial MAO
what are the two types of central nervous systems?
somatic and autonomic
What are the two types of autonomic nervous systems?
sympathetic and parasympathetic
where do drugs target in the release of noradrenaline and its transmission?
- enzymes in noradrenaline biosynthesis
- vesicles carrying noradrenaline
- exocytosis of vesicles with cell membrane
- adrenergic receptors
- transport protein for noradrenaline
- metabolic enzymes
- presynaptic receptors
How do adrenoreceptors affect biological activity?
they release secondary messenger molecules inside the cell after binding to an extracellular agonist
what three bonds does noradrenaline make with adrenoreceptors?
- ionic bonds
- hydrogen bonds
- van der Waals
What type of effect do esters and amides have on beta receptors?
they’re beta-antagonists
What derivative is salbutamol?
a salicylamine derivative
what determines whether the drug is alpha or beta adrenoreceptor selective?
the substituents on the amine group
What three characteristics must the substituents on the benzene ring have to exhibit beta2-receptor activity?
- the phenolic hydroxy group should be in the para position
- the substituent in the meta position should be able to take part in H-bonds
- the ring configurations are resistant to COMT metabolism
how can we increases the time the drug is effective for?
- make resistant to metabolism and low plasma clearance. (change pharmacokinetic properties)
- re-formulate (delayed release instead of IR)
- make it a pro-drug (becomes active when metabolised)
How do LABA’s (Long Acting Beta2-Agonist) work?
- bind in the vicinity of the beta adrenoreceptor for longer
- has 2 sites of interaction (active site and a non-polar region)
which is longer acting salbutamol or salmefamol?
Salmefamol
To obtain a long drug potency what range does the cLogP value have to lie within?
3.3-4.5
To maintain potency, how many carbons should be between N and O and between C and O in the Salbutamol structure?
between N and O = 5-6 carbons
between C and O = 2-4 carbons
(slide 34)
what is the exo-site hypothesis?
the concept that the long side chain of salbutamol (exo-site) interacts with the non-polar region of the cell membrane within the vicinity of the beta receptor.
