β2-Selective Adrenergic Receptor Agonists:
-These drugs have selective affinity for β2 receptors more than β1 receptors.
They have the following advantages:
1-They are less potential to activate cardiac β1 receptors, so produce less tachycardia.
2-They are not containing catechol nuclus, so not substrates for COMT enzyme, leading to low rate of metabolism.
3-Enhanced oral bioavailability.
4- Can be used by inhalation,
a-Selective β2 Receptor Agonists used in bronchial asthma:
In the treatment of asthma and COPD, these agents are useful due to:
1-They activate β2 receptor in bronchial smooth muscle which leads to relaxation and decrease airway resistance.
2- Suppress the release of leukotrienes and histamine from mast cells in lung tissue.
3-Enhance mucociliary function and decrease capillary permeability.
i)Short Acting β2 Adrenergic Agonists
-Metaproterenol (orciprenaline).
-Terbutaline (Bricanyl).
-Albuterol (salbutamol).
ii)Long-Acting β2 Adrenergic Agonists
-Salmeterol.
-Formoterol.
-Arformoterol.
b-Selective β2 Receptor Agonists act on the uterus:
Ritodrine: -It is a β2-selective agonist that was developed for use as a uterine relaxant (tocolytic effect).
- Adverse Effects of β2-Selective Agonists
- 1-Tremor,
- 2-Tachycardia .
- 3-Arrhythmias or myocardial ischemia
- B- Selective- α1 Adrenergic Receptor Agonists:
- 1-Direct-acting α1 receptors agonist:
- -Phenylephrine.
- -Methoxamine.
- -Midodrine.
- -Xylometazoline and oxymetazoline
- 2-Direct and indirect-acting α1 receptors agonist:
- -Mephentermine.
- -Metaraminol.
- C- Selective- α2 Adrenergic Receptor Agonists:
- 1-Clonidine and its related drugs.
- 2-α-methyl dopa.
- 3-Guanafesin.
- 4-Guanabenz.
- Clonidine
- Mechanism of action:
- 1-Activation of α2 receptors in the cardiovascular control centers of the CNS;
- 2-Activation of presynaptic α2 receptors that suppress the release of NE, ATP, and NPY in the lower brainstem- region.
- 3- Stimulation of α2 receptor in the kidney leads to inhibit release of renin.
- 4-Activation of imidazoline receptors which regulate vasomotor tone leading to the hypotensive actions.
- Therapeutic Uses
- 1- treatment of hypertension.
- 2- It is useful in reducing diarrhea in diabetic patients with autonomic neuropathy .
- 3-it is used in treating and preparing addicted subjects for withdrawal from narcotics, alcohol,
- 4-it may be useful in patients receiving anesthesia because it may decrease the requirement for anesthetic.
- 5-clonidine and related drugs such as dexmedetomidine selective α2 receptor agonist with sedative properties) in anesthesia include preoperative sedation
- 6-Transdermal administration of clonidine is useful in reducing the incidence of menopausal hot flashes.
- 7-It is used in the differential diagnosis of patients with hypertension and suspected pheochromocytoma.
- Adverse Effects
- 1- Dry mouth and sedation,
- 2- Marked bradycardia,
- 3- Contact dermatitis
- 4-Withdrawal reactions after abrupt discontinuation
- 5-Sexual dysfunction.
- Apraclonidine It is a selective α2 receptor agonist that is used topically to reduce I.O.P. this occurs with no effects on systemic cardiovascular parameters;
- Brimonidine It is a clonidine derivative that is α2-selective agonist. It reduces I.O.P both by decreasing aqueous humor production and by increasing outflow.
- Guanfacine It is an α2 receptor agonist, similar to clonidine, guanfacine lowers blood pressure, but has longer duration of action and its withdrawal syndrome is milder than clonidine withdrawal.
- Guanabenz It is a centrally acting α2 agonist that decreases blood pressure by a mechanism similar to those of clonidine and similar adverse effects.
- α Methyl dopa
It is a centrally acting antihypertensive agent. - Therapeutic uses: In treatment of hypertension especially in:
- 1-Pregnancy where it is safer than other drugs.
- 2-Renal impairment where it increase renal blood flow.
- Side effects:
- 1-Sedation, depression and parkinsonism.
- 2-Hypersensitivity reaction, hepatotoxicity, hemolytic anemia.
- 3-Increase prolactin, leads to galactorrhea and gynecomastia.
- 4- Salt and water retension leading to pseudotolerance.
- 5- Nausea vomiting and dry mouth