Adrenergic antagonist

Source: Wikipedia, the free encyclopedia.
(Redirected from
Antiadrenergic
)
Visual definition of an antagonist, where it compared to agonists and reverse agonists.

An adrenergic antagonist is a drug that inhibits the function of adrenergic receptors. There are five adrenergic receptors, which are divided into two groups. The first group of receptors are the beta (β) adrenergic receptors. There are β1, β2, and β3 receptors. The second group contains the alpha (α) adrenoreceptors. There are only α1 and α2 receptors. Adrenergic receptors are located near the heart, kidneys, lungs, and gastrointestinal tract.[1] There are also α-adreno receptors that are located on vascular smooth muscle.[2]

Antagonists reduce or block the signals of

endogenous ligands
. The α-adrenergic antagonists have different effects from the β-adrenergic antagonists.

Pharmacology

Adrenergic ligands are endogenous proteins that modulate and evoke specific

cardiovascular effects. Adrenergic antagonists reverse the natural cardiovascular effect, based on the type of adrenoreceptor being blocked. For example, if the natural activation of the α1-adrenergic receptor leads to vasoconstriction, an α1-adrenergic antagonist will result in vasodilation.[3]

Some adrenergic antagonists, mostly β antagonists,

passively diffuse from the gastrointestinal tract. From there, they bind to albumin and α1-acid glycoprotein in the plasma, allowing for a wide spread through the body. From there, the lipophilic antagonists are metabolized in the liver and eliminated with urine while the hydrophilic ones are eliminated unchanged.[4]

Mechanisms of action

There are three different types of antagonists.

Competitive

While only a few α-adrenergic antagonists are competitive, all β-adrenergic antagonists are

competitive antagonists.[5][6] Competitive antagonists are a type of reversible antagonists. A competitive antagonist will attach itself to the same binding site of the receptor that the agonist will bind to. Even though it is in activator region, the antagonist will not activate the receptor. This type of binding is reversible as increasing the concentration of agonist will outcompete the concentration of antagonist, resulting in receptor activation.[7]

Adrenergic competitive antagonists are shorter lasting than the other two types of antagonists. While the antagonists for alpha and beta receptors are usually different compounds, there has been recent drug development that effects both types of the adrenoreceptors.

Phentolamine, an adrenergic antagonist

Examples

Two examples of competitive adrenergic antagonists are propranolol and phentolamine. Phentolamine is a competitive and nonselective α-adrenoreceptor antagonist. Propranolol is a β-adrenoreceptor antagonist.[8]

Non-competitive

While competitive antagonists bind to the agonist or ligand binding site of the receptor reversibly,

allosteric site. A receptor's agonist does not bind to its allosteric binding site. The binding of a non-competitive antagonist is irreversible. If the non-competitive antagonist binds to the allosteric site and an agonist binds to the ligand site, the receptor will remain unactivated.[9][10]

An example of an adrenergic non competitive antagonists is phenoxybenzamine. This drug is a non-selective α-adrenergic antagonist, which means it binds to both alpha receptors.[11]

Uncompetitive

There were few if any adrenergic

uncompetitive antagonists. An uncompetitive antagonist is slightly different from the other two types of antagonists. The action of an uncompetitive antagonist is dependent on the receptor's prior activation. This means only after the agonist binds to the receptor can the antagonist block the receptor's function.[12]

Examples

Alpha blockers

Beta blockers

Mixed action

Major effects

Major complications of persistent high blood pressure, which can be attenuated by adrenergic antagonists.

Adrenergic antagonists have inhibitory or opposing effects on the receptors in the adrenergic system. The adrenergic system modulates the

vasculature tone.[14] Administration of an adrenergic antagonist that specifically targets the beta receptors, results in this decrease in blood pressure by slowing or reducing cardiac output.[15]

Medical uses

Adrenergic antagonists are mostly used for cardiovascular disease. The adrenergic antagonists are widely used for lowering blood pressure and relieving hypertension.[16] These antagonists have a been proven to relieve the pain caused by myocardial infarction, and also the infarction size, which correlates with heart rate.[17]

There are few non-cardiovascular uses for adrenergic antagonists. Alpha-adrenergic antagonists are also used for treatment of

ureteric stones, pain and panic disorders, withdrawal, and anesthesia.[18][2]

Limitations

While these adrenergic antagonists are used for treating cardiovascular disease, mainly hypertension, they can evoke harmful cardiac events through prolongation of the QT interval. Some adrenergic antagonists have a diminished ability to reduce stroke compared to placebo drugs.[19][needs update]

Side effects and toxicity

While adrenergic antagonists have been used for years, there are multiple issues with using this class of drug. When overused, adrenergic antagonists can result in bradycardia, hypotension, hyperglycemia and even hypodynamic shock. This is because adrenergic stimulation by agonists results in normal calcium channel regulation. If these adrenergic receptors are blocked too often, there will be an excess in calcium channel inhibition, which causes most of these problems.[20]

See also

References

  1. PMID 18092107
    .
  2. ^
    PMID 25849473
    .
  3. ^ The Pharmacology of Adrenergic Blockade, Nickerson, M. (1949). The pharmacology of adrenergic blockade. Pharmacological Reviews, 1(1), 27–101.
  4. ^ a b c d e f g h i j k l Stereospecific Pharmacokinetics and Pharmacodynamics of Beta-Adrenergic Blockers in Humans, Mehvar, R., & Brocks, D. R. (2001). Stereospecific pharmacokinetics and pharmacodynamics of beta-adrenergic blockers in humans.
  5. PMID 11527109
    .
  6. ISSN 2395-5414
    .
  7. ^ "In Vitro Pharmacology: concentration-response curves]". GlaxoWellcome. Retrieved October 19, 2018.
  8. ^ A review of the animal pharmacology of labtalol, a combined alpha- and beta-adrenoceptor-blocking drug, Brittain, R. T., & Levy, G. P. (1976). A review of the animal pharmacology of labetalol, a combined alpha-and beta-adrenoceptor-blocking drug. British journal of clinical pharmacology, 3(4 Suppl 3), 681–684.
  9. ISBN 978-1-60831-270-2
    .
  10. ISBN 978-0-7817-3762-3
    .
  11. PMID 24829175
    .
  12. ISBN 978-0-12-373989-6
    .
  13. ^
    PMID 28107561
    .
  14. ISBN 978-3-319-13680-6
    .
  15. PMID 27264986
  16. ^ Effects of β-Blockers With and Without Vasodilating Properties on Central Blood Pressure, Pucci, G., Ranalli, M. G., Battista, F., & Schillaci, G. (2015). Effects of β-Blockers With and Without Vasodilating Properties on Central Blood Pressure. Hypertension, HYPERTENSIONAHA-115.
  17. ISBN 978-1-60795-108-7
    .
  18. PMID 27908918
    .
  19. PMID 17253471
    .
  20. PMID 17482022
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Adrenergic_antagonist&oldid=1220573006"