Although hepatitis B vaccine reliably induces immunity to hepatitis B virus, the expense of intramuscular (im) vaccination with this product has limited its use. To determine if a smaller, less expensive, intradermal (id) dose of hepatitis B vaccine would be an effective alternative, we compared the response of antibody to hepatitis B surface antigen (anti-HBs) following im vaccination to that following id vaccination. Volunteers who were seronegative for antibody to hepatitis B core antigen were enrolled in the study and received either im or id vaccine. A total of 108 subjects received three 1-mL im injections of hepatitis B vaccine, and another 110 subjects received four 0.1-mL id injections of the vaccine. Similar rates of seroconversion occurred; greater than or equal to 10 mIU of anti-HBs/mL was noted following either three im or three id vaccinations. Furthermore, 2 years after initiation of vaccination, the serum concentration of anti-HBs for id vaccine recipients was similar to that for im vaccine recipients.

Adult↗

PubMedDate not supplied

Hemodynamic profile of a new antihypertensive agent D,L-3-[2-(3-t-butylamino-2-hydroxypropoxy)phenyl]-6-hydrazinopyridazine (SK&F 92657).

The properties of a new antihypertensive agent, SK&F 92657, D,L-3-[2-(3-t-butylamino-2-hydroxypropoxy)phenyl]-6-hydrazinopyridazine, have been studied. The compound, given intravenously, subcutaneously, or orally, caused a sustained fall in systemic blood pressure of conscious genetically hypertensive rats, normotensive cats, and renal hypertensive dogs. The fall in blood pressure of genetically hypertensive rats was maintained during 52 days of chronic dosing with no development of tolerance. The hemodynamic effects and mechanism of action of SK&F 92657 were investigated in anesthetized cats and dogs using a variety of techniques. Blood pressure was lowered by a direct vasodilator effect on precapillary blood vessels (arteries, arterioles), particularly in the renal, coronary, and skeletal muscle vasculatures, giving an overall decrease in total peripheral resistance with no significant change in cardiac output. In contrast, SK&F 92657 had no significant effect on capacitance blood vessel (veins, venules) tone or on vascular reactivity to vasoconstrictors and consequently did not cause postural hypotension. The beta-adrenoceptor-blocking actions of the drug prevented reflex increases in heart rate and cardiac output, except in the conscious dog, where vagal control of heart rate was predominant. It was also concluded that SK&F 92657 was not acting by alpha-adrenoceptor blockade, ganglion blockade, or inhibition of angiotensin II responses. A "central" action was unlikely, as SK&F 92657 caused vasodilatation in denervated autoperfused vascular beds.

Animals↗

PubMedDate not supplied

Studies on the autonomic nervous system with SK&F 92657, a new antihypertensive agent causing direct arterial vasodilatation and beta-adrenoceptor blockade.

The beta-adrenoceptor-blocking properties of SK&F 92657, D,L-3-[2-(3-t-butylamino-2-hydroxypropoxy)phenyl]-6-hydrazinopyridazine, were studied in both in vivo and in vitro. The pA2 against isoprenaline tachycardia (beta 1 effect) in isolated guinea pig right atria was 7.16 (6.14-7.87). In contrast, histamine-induced tachycardia was unaffected by SK&F 92657. The pA2 against isoprenaline relaxation of guinea pig tracheal muscle (beta 2 effect) was 7.03 (6.28-7.61). In vivo ED50's against isoprenaline tachycardia (beta 1) and vasodilation (beta 2) in anesthetized cats were 5.7 x 10(-8) and 6.2 x 10(-8) mol/kg, i.v., respectively. Increases in heart rate caused either by activation of autonomic reflexes or by stimulation of efferent cardiac sympathetic nerves were also antagonized by SK&F 92657. The beta-adrenoceptor blockade caused by SK&F 92657 was shown to be competitive both in vivo an vitro and to be equally effective on beta 1- and beta 2-receptor populations. SK&F 92657 was a weak partial agonist in vivo and had only minimal local anesthetic activity. The compound had no direct effect on the functioning of the autonomic nervous system, apart from beta-blockade, but reflexes maintaining homeostasis were reduced because (1) SK&F 92657 is a beta-adrenoceptor antagonist preventing reflex increases in heart rate and cardiac output, and (2) it is a potent vasodilator counteracting reflex vasoconstriction. Postural reflexes were unaffected because SK&F 92657 selectively dilates arterial blood vessels.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Pharmacological properties of the stereoisomers of prizidilol: their use in analysis of reflex tachycardia and blood pressure control in normotensive cats, rats, and dogs.

Prizidilol, a combined vasodilator/beta-adrenoceptor antagonist, has two optical isomers. The pharmacological activities of these isomers have been established and heart rate/blood pressure responses to both isomers have been determined. Both the R and S isomers elicited similar blood pressure lowering and vasodilator activity in anaesthetised normotensive rats. S-Prizidilol was a substantially more potent beta-adrenoceptor antagonist in vitro and in vivo than R-prizidilol. Neither optical isomer showed any specificity for either beta 1- or beta 2-adrenoceptors. In conscious rats both isomers lowered blood pressure similarly with only marginal differences in heart rate. In conscious cats the importance of increased sympathetic drive in reflex tachycardia was emphasised by the incidence of tachycardia after R-prizidilol but not after S-prizidilol when administered at equieffective blood pressure lowering doses. In conscious dogs both isomers caused tachycardia although S-prizidilol tended to cause the greater fall in blood pressure.

Adrenergic beta-Antagonists↗