Question

how exactly ISA drugs work while they are partial agonist?

please explain in details.

Answer 1

Ans) Intrinsic Sympathomimetic Activity (Partial Agonist Activity)

- Certain β-blockers have an intrinsic sympathomimetic activity (partial agonist activity) at β1-adrenergicreceptor sites, β2-adrenergic receptor sites, or both.

- In a β-blocker, this property is identified as a slight cardiac stimulation that can be blocked by propranolol.

- The β-blockers with this property partially activate the β-adrenergic receptor in addition to preventing the access of natural or synthetic catecholamines to the receptor.

- Dichloroisoprenaline, the first β-adrenergic receptor-blocking drugto be synthesized, exerted such marked partial agonist activity that it was unsuitable for clinical use.

- However, compounds with less partial agonist activity are effective β-blockers.

- The partial agonist effects of β-blockers such aspindolol differ from those of agonists epinephrine andisoproterenol in that the maximum pharmacologic response that can be obtained is low, although the affinity for the receptor is high.

- In the treatment of patients with arrhythmias, angina pectoris of effort, and hypertension, drugs with mild to moderate partial agonist activity appear to be as efficacious as β-blockers that lack this property.

- It is still debated whether the presence of partial agonist activity in a β-blocker constitutes an overall advantage or disadvantage in cardiactherapy.

- Drugs with partial agonist activity cause less slowing of the heart rate at rest than do propranolol and metoprolol, although the increments in heart rate with exercise are similarly blunted.

- These β-blockers reduceperipheral vascular resistance and may cause less depression or AV conduction than drugs that lack these properties.

- Some investigators claim that partial agonist activity in a β-blocker protects against myocardial depression, adverse lipid changes, bronchial asthma, and peripheral vascular complications, such as those caused by propranolol.