Muscle relaxant effects release

Sodium nitroprusside (SNP), which is also known as Nipruss or Nipride to medical practitioners, was the first iron nitrosyl complex, prepared as far back as 1850 by Playfair [40]. The hypotensive property of SNP was first demonstrated by Johnson [41] in 1929. It was shown that application of a moderate dose of SNP reduces the blood pressure of a severely hypertensive patient without any side effect [42]. Since that time considerable research has been carried out to understand the mode of action of nitroprusside and its metabolic fate. SNP is now regarded as a potent vasodilator that causes muscle relaxation by releasing NO which activates the cytosolic isozyme of guanylyl cyclase [43-46]. 

Hydralazine and minoxidil cause direct arteriolar smooth muscle relaxation. Compensatory activation of baroreceptor reflexes results in increased sympathetic outflow from the vasomotor center, producing an increase in heart rate, cardiac output, and renin release. Consequently, the hypotensive effectiveness of direct vasodilators diminishes over time unless the patient is also taking a sympathetic inhibitor and a diuretic. 

Molsidomine (8.159, Fig. 8.18), a very special example of a carbamate prodrug that acts by vascular smooth muscle relaxation, is an anti-angina agent effective mainly in the treatment of myocardial ischemia [207], Molsidomine undergoes enzymatic hydrolysis in the liver to form the imine 8.160 (Fig. 8.18) [208]. This metabolite is inactive and unstable, breaking down spontaneously to the A-nitroso secondary metabolite known as Sinl A (8.161, Fig. 8.18). The latter was found to be active, but there are reasons to believe that it acts by releasing nitrogen monoxide in the form of nitroxyl (HNO), which dissociates to the nitroxide ion NO, i. e., the reduced form of NO. 

Despite the many decades amyl nitrite and glyceryl trinitrate have been used in therapy, it is only in recent years that the molecular mechanism of action of the nitrovasodilators has begun to be understood [3-5]. The drugs act by releasing nitric oxide (NO, a neutral radical usually written simply as NO), which produces smooth muscle relaxation in blood vessels and exhibits a range of other biological effects [6]. Thus, bioactivation to yield NO precedes the main therapeutic effect of nitrovasodilators and would justify their classifica-... 

These compounds competitively inhibit phosphodiesterase, resulting in an increase in cyclic AMP (see Box 14.3) and subsequent release of adrenaline. This leads to the major effects a stimulation of the central nervous system (CNS), a relaxation of bronchial smooth muscle, and induction of diuresis. These effects vary in the three compounds. Caffeine is the best CNS stimulant, and has weak diuretic action. Theobromine has little stimulant action, but has more diuretic activity and also muscle relaxant properties. Theophylline also has low stimulant action and is an effective diuretic, but it relaxes smooth muscle better than caffeine or theobromine. 

Dantrolene is a drug that causes spastic muscle contraction. Unlike other muscle relaxants, it has a direct effect on the contractile mechanism by interfering in the process of calcium ion release from the sarcoplasmic reticulum. This results in a lack of coordination in the mechanism of excitation—contraction of skeletal muscle, which has a greater effect on fast muscle fibers than on slow muscle fibers. Dantrolene is used for controlling the onset of clinical spasticity resulting from serious clinical cases such as wounds, paralysis, cerebral palsy, and disseminated sclerosis. Synonyms of this drug are dantrium and danlen. 

Smooth muscle relaxation, central nervous system (CNS) excitation, and cardiac stimulation are the principal pharmacological effects observed in patients treated with theophylline. The action of theophylline on the respiratory system is easily seen in the asthmatic by the resolution of obstruction and improvement in pulmonary function. Other mechanisms that may contribute to the action of theophylline in asthma include antagonism of adenosine, inhibition of mediator release, increased sympathetic activity, alteration in immune cell function, and reduction in respiratory muscle fatigue. Theophylline also may exert an antiinflammatory effect through its ability to modulate inflammatory mediator release and immune cell function. 

Mecfianism of Action A skeletal muscle relaxant that reduces muscle contraction by interfering with release of calcium ion. Reduces calcium ion concenfrafion. Therapeutic Effect Dissociafes excitation-conf racf ion coupling. Interferes wifh catabolic process associated with malignant hyperthermic crisis. 

Muscle relaxants and antispasmodics methocarbamol (Robaxin), carisoprodol (Soma), chlorzoxazone (Paraflex), metaxalone (Skelaxin), cyclobenzaprine (Flexeril), and oxybutynin (Ditropan) Do not consider the extended-release Ditropan XL Most muscle relaxants and antispasmodic drugs are poorly tolerated by elderly patients, because these cause anticholinergic adverse effects, sedation, and weakness. Additionally, their effectiveness at doses tolerated by elderly patients is questionable. High... 

Activation of endothelial cell muscarinic receptors by acetylcholine (Ach) releases endothelium-derived relaxing factor (nitric oxide), which causes relaxation of vascular smooth muscle precontracted with norepinephrine, 10-8M. Removal of the endothelium by rubbing eliminates the relaxant effect and reveals contraction caused by direct action of Ach on vascular smooth muscle. (NA, noradrenaline [norepinephrine]. Numbers indicate the log concentration applied at the time indicated.)... 

The best-characterized action of the adrenoceptor agonists in the airways is relaxation of airway smooth muscle. Although there is no evidence for direct sympathetic innervation of human airway smooth muscle, ample evidence exists for the presence of adrenoceptors on airway smooth muscle. In general, stimulation of 32 receptors relaxes airway smooth muscle, inhibits mediator release, and causes tachycardia and skeletal muscle tremor as adverse effects. 

Atracurium has several stereoisomers, and the potent isomer cisatracurium has become one of the most commonly used muscle relaxants in clinical practice. Although cisatracurium resembles atracurium, it has less dependence on hepatic inactivation, produces less laudanosine, and is less likely to release histamine. From the clinical perspective, cisatracurium has all the advantages of atracurium with fewer side effects. Therefore, cisatracurium has largely replaced atracurium in clinical practice. 

Release. Certain drugs will increase synaptic activity by directly increasing the release of neurotransmitter from the presynaptic terminal. Amphetamines appear to exert their effects on the CNS primarily by increasing the presynaptic release of catecholamine neurotransmitters (e.g., norepinephrine). Conversely, other compounds may inhibit the synapse by directly decreasing the amount of transmitter released during each action potential. An example is botulinum toxin (Botox), which can be used as a skeletal muscle relaxant because of its ability to impair the release of acetylcholine from the skeletal neuromuscular junction (see Chapter 13). 

The only muscle relaxant available that exerts its effect directly on the skeletal muscle cell is dantrolene sodium (Dantrium).40,102 This drug works by impairing the release of calcium from the sarcoplasmic reticulum within the muscle cell during excitation (Fig. 13 -3).56,89 In response to an action potential, the release of calcium from sarcoplasmic storage sites initiates myofilament cross-bridging and subsequent muscle contraction. By inhibiting this release, dantrolene attenuates muscle contraction and therefore enhances relaxation. 

As indicated earlier, the relaxant effects of the toxin are likewise temporary, and these effects typically diminish within 2 to 3 months after injection.91 The effects apparently wear off because a new presynaptic terminal sprouts from the axon that contains the originally affected presynaptic terminal. This new terminal grows downward, reattaching to the skeletal muscle and creating a new motor end plate with a new source of acetylcholine. The effects of the previous injection are overcome when this new presynaptic terminal begins to function. Another injection will be needed to block the release from this new presynaptic terminal, thus allowing another 2 to 3 months of antispasticity effects. This fact raises the question of how... 

Theophylline may also act as an adenosine antagonist.86 113 Adenosine is thought to bind to specific receptors on the smooth-muscle cells and to stimulate contraction. By blocking this effect, theophylline would facilitate smooth-muscle relaxation. Theophylline may likewise help produce bronchodilation by other mechanisms, such as inhibition of intracellular calcium release and stimulation of catecholamine release.115 In reality, theophylline and similar drugs may induce bronchodilation and help protect the airways through a combination of several mechanisms, but the relative importance of each cellular effect remains to be determined. 

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