Prazosin release

Cumulative Fraction Prazosin Release Prazosin (mg/Day/lOOmg Particles)... 

High Performance Liquid Chromatographic (HPLC) Analysis. A Waters HPLC system (two Waters 501 pumps, automated gradient controller, 712 WISP, and 745 Data module) with a Shimadzu RF-535 fluorescence detector or a Waters 484 UV detector, and a 0.5 pm filter and a Rainin 30 x 4.6 mm Spheri-5 RP-18 guard column followed by a Waters 30 x 3.9 cm (10 pm particle size) p-Bondapak C18 column was used. The mobile phase consisted of a 45% aqueous solution (composed of 0.25% triethylamine, 0.9% phosphoric acid, and 0.01% sodium octyl sulfate) and 55% methanol for prazosin analysis or 40% aqueous solution and 60% methanol for naltrexone. The flow rate was 1.0 mL/min. Prazosin was measured by a fluorescence detector at 384 nm after excitation at 340 nm (8) and in vitro release samples of naltrexone were analyzed by UV detection at 254 nm. 

Figure 7. In Vitro Release Profile of PHPG-Prazosin Conjugate (Loading 23.9%w/w).

Figure 8. In Vitro Cumulative Fraction Release of Prazosin from PHPG-Prazosin Conjugate.

The major circulating hormones that influence vascular smooth muscle tone are the catecholamines epinephrine and norepinephrine. These hormones are released from the adrenal medulla in response to sympathetic nervous stimulation. In humans, 80% of catecholamine secretion is epinephrine and 20% is norepinephrine. Stimulation of cy-adrenergic receptors causes vasoconstriction. The selective a,-adrenergic receptor antagonist, prazosin, is effective in management of hypertension because it causes arterial and venous smooth muscle to relax. 

Phenoxybenzamine and phentolamine, in addition to blocking postsynaptic a-receptors, also block aj-receptors on nerves and therefore can enhance the release of norepinephrine. When norepinephrine exerts a postsynaptic action by means of -adrenoceptors (e.g., cardiac stimulation, renin release), blockade of presy-naptic a2-receptors by phenoxybenzamine and phentolamine may actually potentiate the responses. Prazosin blocks responses mediated by postsynaptic aj-receptors but has no effect on the presynaptic a2-receptors. Thus,... 

B. The adrenoceptors that epinephrine acts on to affect heart rate, renin release, bronchiolar tone, and glycogenolysis are (3-receptors. Prazosin is an a-antagonist so would not antagonize epinephrine at those receptors. The radial smooth muscle in the iris has a-receptors that when activated, contract the radial muscle which dilates the pupil. This action is antagonized by prazosin. 

Phenoxybenzamine and phentolamine have been available for a number of years and are sometimes referred to as classical a-blockers. The frequency of their use for the treatment of primary hypertension has greatly diminished in recent years because of the development of drugs such as prazosin that are relatively selective for tti-receptors. ai-Receptor-selective antagonists will not potentiate the release of norepinephrine from sympathetic nerves. Thus, the stimulation of the heart and renin release, actions that limit the usefulness of classical a-blockers, are less with aj-selective antagonists. 

Phenoxybenzamine binds covalently to receptors, causing irreversible blockade of long duration (14-48 hours or longer). It is somewhat selective for Ki receptors but less so than prazosin (Table 10-1). The drug also inhibits reuptake of released norepinephrine by presynaptic adrenergic nerve terminals. Phenoxybenzamine blocks histamine (Hi), acetylcholine, and serotonin receptors as well as receptors (see Chapter 16). 

Prazosin, oxazosin and terazosin (see p. 73) produce a competitive block of oci adrenoceptors. They decrease peripheral vascular resistance and lower arterial blood pressure by causing the relaxation of both arterial and venous smooth muscle. These drugs cause only minimal changes in cardiac output, renal blood flow, and glomerular filtration rate. Therefore, long-term tachycardia and increased renin release do not occur. Postural hypotension may occur in some individuals. Prazosin is used to treat mild to moderate hypertension and is prescribed in combination with propranolol or a diuretic for additive effects. Reflex tachycardia and first dose syncope are almost universal adverse effects. Concomitant use of a p-blocker may be necessary to blunt the short-term effect of reflex tachycardia. 

Alpress LP (prazosin) once-daily extended-release tablet for the treatment of hypertension. 

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