Muscle relaxant Smooth muscles

Elevation of cycHc AMP levels is also known to inhibit the release of inflammatory and contractile mediators from mast cells (42). The good clinical efficacy of P2" goiAsts may be related to this action because some members of this class of dmgs inhibit mediator release at the same concentrations at which they relax smooth muscle (43). In contrast to their effectiveness against immediate bronchoconstriction, P2" gonists do not inhibit the late asthmatic... 

Vasodilators having potassium channel opener activity relax smooth muscle ia low (5—20 mM) K+ coaceatratioa but aot ia high (>80 mAf)K + solutioa, and glibenclamide [10238-21-8] should be able to reverse the iaduced relaxation (242,245—249). They also iacrease potassium efflux. 

NO (nitric oxide) Relaxes smooth muscle of blood epithelium... 

Priapism has been treated with analgesics, antianxiety agents, and vasoconstrictors to force blood out of the corpus cavernosum (e.g., phenylephrine, epinephrine), and vasodilators to relax smooth muscle (e.g., terbutaline, hydralazine). 

N, O-Diacylated or O-alkylated N-hydroxysulfonamides release nitroxyl (HNO) upon hydrolysis or metabolic dealkylation, as determined by gas chromatographic identification of nitrous oxide in the reaction headspace [27-29, 38]. Scheme 7.5 depicts the decomposition of a representative compound (7) to a C-acyl nitroso species that hydrolyzes to yield HNO. Either hydrolysis or metabolism removes the O-acyl or O-alkyl group to give an N-hydroxy species that rapidly decomposes to give a sulfinic acid and an acyl nitroso species. This C-acyl nitroso species (8) hydrolyzes to the carboxylic acid and HNO (Scheme 7.5). These compounds demonstrate the ability to relax smooth muscle preparations in vitro and also inhibit aldehyde dehydrogenase, similar to other HNO donors [27, 29]. 

Methyixanthines relax smooth muscle, and have a bronchodilating effect in the lungs. Theophylline is used as a treatment for asthma. Methyixanthines dilate coronary arteries, increasing cardiac blood flow, but an opposite effect occurs on cerebral blood vessels (see below). 

Vasoactive intestinal Relaxes smooth muscle in blood... 

Figure 19.16 Role of nitric oxide synthase in control of penile erection. Nitric oxide synthase catalyses conversion of arginine to nitric oxide, which then acts to acb vate guanyl cyclase which results in an increase in the concentrab on of cyclic GMP. The latter relaxes smooth muscle in the arterioles that supply blood to the corpora cavernosa in the penis so that blood flow increases and erection results.

Figure 22.4 Injury to endothelial cells can lead to vasospasm. Normal endothelial cells release nitric oxide (NO) which relaxes smooth muscle this is achieved by nitric oxide increasing the concentration of cyclic GMP within smooth muscle fibres and cyclic GMP relaxing the smooth muscle. Injured endothelial cells secrete very little nitric oxide but secrete more endothelin. The latter increases the formation of inositol trisphosphate (IP3), which binds to the sarcoplasmic reticulum (SR) where it stimulates the Ca ion channel. The Ca ion channel in the plasma membrane is also activated. Both effects result in an increase in cytosolic Ca ion concentration, which then stimulates contraction (vasospasm). This reduces the diameter of the lumen of the artery.

Normal endothelial cells produce nitric oxide, which relaxes smooth muscle, whereas damaged cells release less nitric oxide but more of a local hormone, endothelin, which stimulates contraction of smooth muscle (Figure 22.4). 

Figure 22.17 Summary of mechanisms to maintain the ATP/ADP concentration ratio in hypoxic myocardium. A decrease in the ATP/ADP concentration ratio increases the concentrations of AMP and phosphate, which stimulate conversion of glycogen/ glucose to lactic acid and hence ATP generation from glycolysis. The changes also increase the activity of AMP deaminase, which increases the formation and hence the concentration of adenosine. The latter has two major effects, (i) It relaxes smooth muscle in the arterioles, which results in vasodilation that provides more oxygen for aerobic ATP generation (oxidative phosphorylation). (ii) It results in decreased work by the heart (i.e. decrease in contractile activity), (mechanisms given in the text) which decreases ATP utilisation.

Nifedipine is a calcium-channel blocker of the dihydropyridine group. It relaxes smooth muscle and dilates both coronary and peripheral arteries by interfering with the inward displacement of calcium-channel ions through the active cell membrane. Unlike verapamil, nifedipine can be given with beta-blockers. Long-acting formulations of nifedipine are preferred in the long-term treatment of hypertension. 

Alfuzosin is a selective alpha-blocker, which relaxes smooth muscle, thereby increasing urinary flow rate. Because of its alpha-blockade effect, alfuzosin tends to lower the blood pressure and the first dose of the drug may lead to a hypotensive effect. 

Adrenoblocking drugs are classified as a-adrenoblockers, j8-adrenoblockers, and adrenergic neuron blockers depending on the response brought about in the organism. a-Adrenoreceptors cause dilation of peripheral blood vessels, and a few of them relax smooth muscles. 

Hydralazine exhibits an antihypertensive effect by directly relaxing smooth muscles of the vessels. It has an effect on arterial vessels while having a minimal effect on venous vessels. As a result, resistance of peripheral vessels decreases, and blood pressure is reduced (diastolic more than systolic). 

AminophyUine [Bronchodilator/Xanthine Derivative] Uses Asthma, COPD bronchospasm Action Relaxes smooth muscle (bronchi, pulm... 

Uses Viagra ED, Revatio Pulm artery HTN Action X PDE5 (responsible for cGMP breakdown) T cGMP activity to relax smooth muscles T flow to corpus cavemosum and pulm vasculature antiproliferative on pulm artery smooth muscle Dose ED 25-100 mg PO 1 h before sexual activity, max 1 X d if >65 y avoid... 

Papaverine is an opium alkaloid initially isolated in the mid-1800s. It relaxes smooth muscle and is a potent vasodilator. As such it is used to dilate pulmonary and other arteries. It is therefore sometimes of use in the treatment of angina pectoris (usually caused by partial blockage of the coronary artery), heart attacks and bronchial spasms. 

Theophilline is also a minor constituent of tea, but is prepared by direct chemical synthesis for medical use. It functions to relax smooth muscle and, therefore, can be used as a bronchodilator in the treatment of asthma and bronchitis. Aminophylline is a derivative of theophilline (theophylline ethylenediamine), which is often used in place of theophilline due to its greater aqueous solubility. 

Muscarinic antagonists inhibit secretions and relax smooth muscle in the respiratory system. The parasympathetic innervation of respiratory smooth muscle is most abundant in large airways, where it exerts a dominant constrictor action. In agreement with this innervation pattern, muscarinic antagonists produce their greatest bronchodilator effect at large-caliber airways. 

Forskolin, an herbal, relaxes smooth muscle. Injected intracavernosally, forskolin has been of limited use in the treatment of vasculogenic impotence. 

Garlic clearly has antithrombotic properties. Ajoene (an allicin metabolite) and methyl allyl trisulfide inhibit platelet aggregation. Garlic may promote vasodilation by relaxing smooth muscle, and it may reduce low-density lipoprotein (LDL) oxidation. 

Mecfianism of Action An alphaj antagonist that targets receptors around bladder neck and prostate capsule. Therapeutic Effect Relaxes smooth muscle and improves urinary flow and symptoms of prostatic hyperplasia. 

Mechanism of Action A xanthine derivative that acts as a bronchodilator by directly relaxing smooth muscle of the bronchial airways and pulmonary blood vessels. Therapeutic Effect Relieves bronchospasm and increases vital capacity. Pharmacokinetics Rapidly and well absorbed. Protein binding Moderate (to albumin). Extensively metabolized in liver. Partially excreted in urine. Half-life 6-12 hr (varies). 

Mechanism of Action A nitrite vasodilator that relaxes smooth muscles. Reduces afterload and improves vascular supply to the myocardium. Therapeutic Effect Dilates coronary arteries, improves blood flow to ischemic areas within myocardium. Following inhalation, systemic vasodilation occurs. 

Mechanism of Action An antihypertensive that selectively blocks alpha -adrenerglc receptors, decreasing peripheral vascular resistance. Therapeutic Effect Causes peripheral vasodilation and lowers BP. Also relaxes smooth muscle of bladder and prostate. 

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