Sympathomimetic activity, intrinsic

Pindolol (Visken) Has some intrinsic sympathomimetic activity as well as pi and P2 blocking activity. Intrinsic sympathomimetic activity decreases likelihood of rebound hypertension (by dilating large arteries via P2) or bronchospasm. 

Some P-adrenoceptor blockers have intrinsic sympathomimetic activity (ISA) or partial agonist activity (PAA). They activate P-adrenoceptors before blocking them. Theoretically, patients taking P-adrenoceptor blockers with ISA should not have cold extremities because the dmg produces minimal decreases in peripheral blood flow (smaller increases in resistance). In addition, these agents should produce minimal depression of heart rate and cardiac output, either at rest or during exercise (36). 

P-Adrenoceptor blockers for the treatment of hypertension include (/) the cardioselective P -adrenoceptor blockers without intrinsic sympathomimetic activity (ISA), ie, atenolol (Table 3), bisoprolol (Table 3), and metoprolol (Table 1) (2) the cardioselective with ISA, ie, acebutolol (Table 1) (J) the noncardioselective without ISA, ie, propranolol (Table 1) and timolol [26839-75-8] C23H24N4O2S and (4) the noncardioselective with ISA, ie, oxprenolol [6452-71-7] C 3H23N03, and pindolol. 

FIGURE 2-4. Flowchart listing various P-blocking agents separated by P-receptor activity and intrinsic sympathomimetic activity. 

International Verapamil-Trandolapril Study Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria study intrinsic sympathomimetic activity intravenous... 

Esmolol hydrochloride is a competitive p-adrenergic receptor antagonist it is selective for pT adrenoceptors. In contrast to pindolol, esmolol has little intrinsic sympathomimetic activity, and it differs from propranolol in that it lacks membrane stabilizing activity Of all of the p-adrenergic blocking drugs, this compound has the shortest duration of action because it is an ester, it is hydrolyzed rapidly by plasma esterases and must be used by the intravenous route Esmolol is approved only for the treatment of supraventricular arrhythmias... 

Modifying the way in which the aromatic system was linked to the ethanolamine moiety led to the oxypropranolamines as typified by propranolol. It is 10-20 times more potent than pronethalol and shows no intrinsic sympathomimetic activity. 

Thus the "ideal" anti-hypertensive 3-blocking agent should be a moderately long acting cardioselective agent showing little or no intrinsic sympathomimetic activity. 

The side chain and substituents on the amino group critically affect affinity for P-receptors, whereas the aromatic nucleus determines whether the compound possess intrinsic sympathomimetic activity (ISA), that is, acts as a partial agonist (p. 60) or partial antagonist. In the presence of a partial agonist (e.g., pindolol), the ability of a full agonist (e.g., isoprenaline) to elicit a maximal effect would be attenuated, because binding of the full agonist is impeded. names. 

Pharmacology Carvedilol, an antihypertensive agent, is a racemic mixture in which nonselective -adrenoreceptor blocking activity is present in the S(-) enantiomer and -adrenergic blocking activity is present in both R(+) and S(-) enantiomers at equal potency. Carvedilol has no intrinsic sympathomimetic activity. 

INR intOTiational normalized ratio Insuff insufficiency Intravag intravaginal lO intraosseous infusion/injection lOP intraocular pressure ISA intrinsic sympathomimetic activity IT intrathecal... 

Due to the numerous indications for these type of drugs a large number of compounds have been introduced into therapy. Differences between these drugs concern their affinity profile towards the Pi-and j82-adrenoceptors, the lipophilicity and the ability to partially activate the receptor (intrinsic sympathomimetic activity, ISA). One isomer of the racemic mixture of labetalol and carvedilol are a-blocker as well. Although this might be therapeutically useful in the treatment of conditions like hypertension and heart failure, there is no real evidence for a contribution of this property to the overall beneficial effect of these compounds. 

The similarity in structure to (3-agonists is most certainly responsible for the finding that some (3-blockers activate (3-receptors that is, they have some intrinsic sympathomimetic activity. The intrinsic activity of these compounds is generally modest in comparison with an agonist, such as isoproterenol, and they are generally referred to as partial agonists (see Chapter 2). 

Mechanism of Action An antihypertensive that possesses nonselective beta-blocking. Has moderate intrinsic sympathomimetic activity. Therapeutic Effect Reduces cardiac output, decreases blood pressure (BP), increases airway resistance, and decreases myocardial ischemia severity. 

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