Uterus relaxants

C2 0H27NO2 Amine, Ar ethers Uterus relaxant (9) W472... 

While the inhibition of noradrenaline re-uptake exerts predominantly an a-adrenergic effect, a selective jS-adrenergic effect can not be obtained by such an indirect mechanism. All selective /3-sympathomi-metics activate the receptors, P -, P2- or both sub-types, directly. The first pure jS-sympathomimetic in clinical use was isoproterenol which is structurally identical to adrenaline except the methyl-moiety at the N-position in the side-chain is replaced by an isopropyl-group. All effects produced by isoproterenol are due to either P -or 62-adrenoceptor stimulation tachycardia, increased stroke volume, decreased vascular resistance, broncho dilatation and, in pregnancy, uterus relaxation. The metabolic effects of isoproterenol are less pronounced than those of adrenaline. 

Beta-2 receptor Bronchioles bronchodilation Uterus relaxation Prevent bronchospasm Prevent premature labor No significant clinical use... 

LlltUtrln. Lutrexin. A uterus-relaxing factor obtained from the corpus luteum of sow ovaries and standardized for potency in terms of units of activity on the guinea pig uterus. Ref JAm. Med. Assoc. 156, 1252 (1954),... 

S 35 (d id 0 V 1 I Broncnodilation (B), vasoconstriction (a), and decreased secretions (a). Used therapeutically as bronchodilator (Table 5.1). Glycogenolysis and gluconeogenesis (B2), lipolysis (Pl), predominant insulin release (u2) but also T insulin release (P2), T renin secretion (pi) Gut relaxation (a,P2) bladder sphincter contraction (a) uterus contraction in non-pregnant women (a1), uterus relaxation in near-term women (p2). ... 

Heart T heart rate (SA node) t contractility t conduction velocity t automaticity Kidney T renin secretion Trachea and Bronchioles relaxation Pregnant/nonpregnant Uterus relaxation Arterioles (except in skin or brain) and Veins dilation Eye relaxation of ciliary muscle (minimal effect) Urinary Bladder relaxation of detruser muscle (minimal effect). 

The existence of two different adrenergic receptors was first suggested by Ahlquist (1948) Those responses evoked most readily by noradrenaline (norepinephrine), less by adrenaline 7.43), still less by isoprenaline 12.44) and least by A -/-butylnorepinephrine are credited to a-receptors those for which this sequence runs in the reverse direction are credited to jS-receptors. Typical a-responses are constriction of blood-vessels, stimulation of the uterus, relaxation of the intestine. Typical jS-responses are dilatation of blood-vessels, relaxation of the uterus, stimulation of muscle glycogenolysis, production of tachycardia (Levy and Ahlquist, 1961). 

Tocolytics are drugs such as the selective (32-adrenoceptor agonists, e.g. salbutamol or terbutaline, which inhibit both the spontaneous and oxytocin-induced contractions of the pregnant uterus by relaxing... 

Ergonovine and metiiylergonovine may be given orally during die postpartum period to reduce die possibility of postpartum hemorrhage and to prevent relaxation of die uterus. When die patient is to receive eitiier of tiiese drains after delivery, it is important to take die blood pressure, pulse, and respiratory rate before administration. 

The nurse assesses the patient s blood pressure, pulse, and respiratory rate every 30 minutes. The FHR and uterine contractions are assessed every 15 minutes or as ordered by the primary health care provider. Three to four firm uterine contractions should occur every 10 minutes, followed by a palpable relaxation of die uterus. 

Caffeine (10 mM), an agonist for CICR, is unable to produce any rise of Ca2+ or force in myometrium (Taggart Wray 1998, Kupittayanant et al 2001a). These data are also in agreement with earlier force measurements reporting no rise in force (Savineau Mironneau 1990) indeed caffeine relaxes the uterus, due to its inhibitory action on the phosphodiesterase that breaks down cAMP (Arnaudeau et al 1994a). 

Thus the role of the SR in the uterus can be seen to incorporate excitability via Ca2+-activated channels, as well as releasing some Ca2+ to support agonist-induced contractions. As with other smooth muscles it is necessary to consider the spatiotemporal nature of the Ca2+ signals produced, if we are to fully understand the ultimate functional effects on contraction. So far the discussion has focussed on the elevation of the Ca2+ signal with stimulation. We will now consider the equally important process of lowering Ca2+ and its role in relaxation in the uterus. 

The rise in [Ca2+] and MLCK phosphorylation of myosin need to be reversed for relaxation. It is very important to the correct functioning of the uterus that its contractions are phasic and not maintained (tonic), as blood flow falls in the myometrium at the peak of contraction, due to the occlusion of its blood vessels (Larcombe-McDouall et al 1999). Relaxation involves a cessation of voltage-gated... 

Uterus Some relaxation Some relaxation Some relaxation Some relaxation Some relaxation ... 

Parturition is the process by which the mother expels the foetus from the uterus. The process involves a considerable amount of biochemistry. The maintenance of pregnancy requires many conditions, two of which are particularly relevant here (i) inactivity of the muscles of the uterus (myometrium), and (ii) closure of the cervix to provide physical support for the growing foetus. Consequently, prior to parturition there must be a restoration of physical activity of the myometrium, so that contractions can increase intrauterine pressure, which is essential for expulsion. Contractions must, however, be periodic, not continuous, so that blood supply to the foetus is not occluded. There must also be a relaxation of the cervix. 

Ritodrine relaxes the uterine muscle and is therefore indicated to prevent premature labour. Ergometrine, oxytocin and carboprost are all indicated to induce or augment labour by inducing uterine contractions and hence can be used to cause the uterus to contract after delivery. Dinoprostone is mostly used for the induction of labour. 

Uterus Pi Contraction Relaxation (non-pregnant > pregnant) Variable... 

The effect of catecholamines on the human uterus, which can be mediated by a- and /3-adrenoceptors, depends on its functional state. During pregnancy /32-adrenoceptor stimulation decrease the uteral tonus, an effect that can be used therapeutically. /32-Adrenoceptor agonists are in use as tocolytics. In the bladder base and the urethral sphincter a-adrenoceptors are present, mediating a contraction, whereas the /32-adrenoceptors of the bladder wall induce a relaxation of the particular smooth muscles present at these structures. Ejaculation is regulated by a-adrenoceptors. 

Uterine muscle contains both a- and (3-adrenoceptors, which mediate contraction and relaxation, respectively. The response of the human uterus to catecholamines is variable and depends on the endocrine balance of the individual at the time of amine administration (see Chapter 62). During the last stage of pregnancy and during parturition, epinephrine inhibits the uterine muscle, as does isoproterenol norepinephrine contracts the uterus. 

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