Cardiovascular Drugs Flashcards
Adrenergic receptors or adrenoceptors
have two types and these are also have subtypes.
What are they?
Remember these receptors are G-protein coupled receptors
Alpha and Beta
Alpha 1, 2 Beta 1,2,3
Alpha 1A, 1B, 1delta, 2A, 2B, 2C
How do adrenoreceptors work via signal transduction?
Alpha 1: Generates inositol triphosphate and diacylglycerol
Alpha 2: Inhibits generatition of cyclic AMP
Beta 1, 2, 3: Generate cyclic AMP
Distribution and effects of adrenoreceptors.
Activating alpha generally contracts smooth muscle (except gut)
Activating Beta 2 relaxes smooth muscle
Beta 2 predominate in the airways/bronchial smooth muscle. Agonists of this receptor
are potential anti-asthmatic agents.
Beta 3: Predominant receptor in fat cells
Activation results in fat metabolism
Activating Beta 1 contracts cardiac muscle
predominate in the heart.
Antagonists of this receptor are potential cardiovascular drugs
Chemical messengers Noradrenaline neurotransmitter and Adrenaline hormone
bind to all adrenoceptors. They show no selectivity.
Remember General structure of catecholamines (Catechol and Alkylamine)
Explain the Transmission process
1) Vesicle containing noradrenaline on presynapse fuse and release transmitter into the cleft.
2) Then it binds to receptor on post synapse or target cell creating a new signal.
3) Neurotransmitter departs receptor and is reabsorbed by active transport via transport proteins.
4) Neurotransmitter is repackaged or
metabolized to use again.
Presynaptic receptors control the release of noradrenaline via presynaptic control.
This prevents overstimulation and ensures balanced neurotransmission.
Prostaglandins, acetylcholine and noradrenaline affect release
Active cholinergic nervous system inhibits adrenergic activity
Drug targets in the transmission process.
Enzymes in the biosynthesis of noradrenaline
Exocytosis of vesicles with cell membrane
Vesicles carrying noradrenaline
Adrenergic receptor
Transport protein for noradrenaline
Metabolic enzymes
Presynaptic receptors
ß-Blockers are adrenergic antagonists.
Examples of Beta blockers.
First generation beta blockers are non-selective (blocks Beta 1, 2). Give example.
Second generation Beta blockers are designed to be _______________. Give example.
Explain the benefits but why it is still not used.
Propranolol, Practolol, Acebutolol, Atenolol Metoprolol, Betaxolol
Propranolol is first gen. So cannot be used with asthmatic patients because antagonizing beta 2 causes bronchoconstriction.
Beta 1 selective e.g Practolol . It is More polar and less CNS SE.
Treats angina and hypertension but Withdrawn due to serious SE
You can convert an agonist to a partial agonist to _________
How does this work?
Give an example.
How to convert an agonist to an antagonist?
weakly activate receptors and block natural messenger. Adding hydrophobic groups increases van der Waals interactions, altering receptor binding dynamics. Structure binds but produces a different induced fit.
Isoprenaline (agonist) converted to dichloroisoprenaline or Pronethalol (partial agonists)
Add extra binding groups to convert an agonist to an antagonist.
Phenol groups are not required for antagonist activity
β2-Agonists are adrenergic agonists.
Give the natural example, its use and cons.
Give examples of the drugs.
Natural messenger Adrenaline used for severe anaphylactic shock. fast but short acting, cardiovascular SE. But unsuitable for long term medication.
Isoprenaline, Isoetharine, R-Soterenol, Salbutamol (Albuterol), Levalbuterol, Salmefamol, Salmeterol
1) Isoprenaline
2) Isoetharine
3) R-Soterenol
4) Salbutamol (Albuterol)
5) Levalbuterol
6) Salmefamol
7) Salmeterol
1) Selective for Beta adrenoceptors but not for subtypes due to bulky isopropyl group. Cardiovascular SE
2) Beta 2 selective due to ethyl group. Short lasting as it is metabolized by catechol-O-methyltransferase
3) Beta 2 due to sulfonamide group. Long lasting but not used clnically.
4) Beta 2 due to Hydroxymethylene group. As potent as isoprenaline but 2000 times less effect on heart. Not recognized by COMT. Treats asthma using a racemate by inhalation
5) R-Enantiomer of salbutamol. 68 times more active than S
6) 1.5 times more active than salbutamol
Longer duration due to N-Arylalkyl group added.
7) Longer lasting for nocturnal asthma. 2x more active than salbutamol.
