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