processing.... Drugs & Diseases > Pediatrics: Cardiac Disease and Critical Care Medicine Neonatal Abstinence Syndrome Medication Updated: Dec 20, 2017 Author: Ashraf H Hamdan, MD, MBBCh, MSc, MRCP, FAAP; Chief Editor: Santina A Zanelli, MD more...
Share Email Print Feedback Close Facebook Twitter LinkedIn WhatsApp webmd.ads2.defineAd(id: 'ads-pos-421-sfp',pos: 421); Sections Neonatal Abstinence Syndrome Sections Neonatal Abstinence Syndrome Overview Practice Essentials
Background Pathophysiology Etiology Epidemiology Prognosis Show All Presentation History
Physical Examination Show All DDx Workup Approach Considerations
Laboratory Studies Imaging Studies Other Tests Show All Treatment Approach Considerations
Medical Care Consultations Diet Activity Prevention Long-Term Monitoring Show All Medication Medication Summary
Antiepileptic agents Opiates Alpha2 Agonists, Central-Acting Show All Questions & Answers References Medication Medication Summary Medications used in patients with neonatal abstinence syndrome (NAS) should be considered when supportive measures fail to ameliorate the infant's withdrawal. This may be manifested early on as difficulty with feeding, extreme irritability, and poor sleeping. If a scoring system is used, pharmacological treatment is commonly started when the average of 3 scores is 8 or more on the Finnegan scale [41] or 4 or more on the Lipsitz scale.
Long-acting narcotic analgesic. PO bioavailability is 50%, with peak plasma levels obtained in 2-4 hours. Serum half-life ranges from 16-25 hours in neonates and is prolonged in patients with renal failure. Available as PO solutions in 1-mg/mL and 2-mg/mL concentrations containing 8% alcohol and 10-mg/mL alcohol-free solution.
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An analysis of 31 commonly available commercial melatonin supplement products found in grocery stores and pharmacies found melatonin content ranged from 0.37% to 466% of its label claim in more than 71% of the products analyzed. Products with the least variability were tablets and sublingual tablets; liquids had the next lowest variability. Additionally, 8 (26%) of the supplements were found to be contaminated with serotonin at levels of 1 to 75 mcg. No correlation in mislabeling was found with manufacturer or product type.Erland 2017
The melatonin receptor agonists agomelatine (Valdoxan), ramelteon (Rozerem), and tasimelteon (Hetlioz) are available and are being studied in depression and sleep disorders.Esteban-Zubero 2016, Fornaro 2010, Goodwin 2009, Howland 2011, Liu 2012, Spadoni 2011, Tordjman 2017
Melatonin was first discovered and isolated from beef pineal glands in 1958 by Aaron B. Lerner.Tordjman 2017 Early animal studies of melatonin in the mid-1960s revealed its ability to affect sexual function, skin color, and other mammalian functions. It is a mediator of photo-induced antigonadotropic activity in photoperiodic mammals, and it affects thermoregulation and locomotor activity rhythms in birds. Early studies showed that diurnal variations in estrogen secretion in rats could be regulated by changes in melatonin synthesis and release, induced by the daily cycle of light and dark via the efferent limb of the reflex in the sympathetic innervation of the pineal gland. Continual darkness depresses the estrous cycle. Studies in the 1990s led to widely expanded uses of melatonin, including for easing insomnia, combating jet lag, preventing pregnancy (in large doses), protecting cells from free-radical damage, boosting the immune system, preventing cancer, and extending life.Bowman 1980, Webb 1995, Windoholz 1989
Pain perception (eg, heat and cold intolerance) varies throughout the day and night, which may be a reflection of melatonin fluctuations. Melatonin receptors have been identified in spinal cord tissue, where release of brain-derived neurotrophic factor (BDNF), an important mediator and central modulator of pain, has been observed; therefore, it may modulate nociception through decreasing BDNF levels.(Zhu 2017)
In a randomized, double-blind, placebo-controlled clinical study, 105 adults with chronic migraine headache receiving nortriptyline 10 to 25 mg or propranolol 20 to 40 mg at baseline were randomized to receive adjunctive melatonin 3 mg, sodium valproate 200 mg, or placebo for 2 months. Melatonin decreased attack frequency, attack duration, attack severity, and Migraine Disability Assessment scores; effects were similar to sodium valproate but melatonin was associated with greater tolerability.(Ebrahimi-Monfared 2017)
Melatonin has been suggested to exert antioxidant effects through scavenging of free radicals; stimulating antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and catalase; and reducing pro-oxidant expression.(Karaaslan 2015)
Animal models suggest that melatonin is able to scavenge free radicals and reduce oxidative stress associated with brain ischemia in stroke.(Ramos 2017, Watson 2016) In the setting of hemorrhagic stroke, melatonin may act by enhancing autophagy protection, alleviating inflammation, and attenuating oxidative stress.(Ramos 2017)
A meta-synthesis of the literature assessing melatonin and other interventions for insomnia in children with autism spectrum disorder found that melatonin, behavioral interventions, and parent education/education programs were most effective at improving various domains of sleep problems. Melatonin was associated with a strong efficiency at improving sleep latency, sleep duration, bedtime resistance, and cosleeping.(Cuomo 2017)
Because melatonin has been shown to alleviate some autoimmune conditions while exacerbating others, melatonin should be avoided in people with autoimmune diseases.(Dos Santos 2018, Farez 2016, Jahanban-Esfahlan 2017)
Melatonin may be beneficial in breast cancer as it can selectively neutralize estrogen's effects on breast tissue and has demonstrated antiaromatase activity. It also acts as a selective estrogen receptor modulator. Melatonin regulates estradiol production through controlling enzymes involved in its synthesis, thus making it a selective estrogen enzyme modulator. In vitro data have demonstrated that melatonin was able to sensitize human breast cancer cells to ionizing radiation through reducing cell proliferation, inducing cell cycle arrest, down-regulating proteins associated with DNA repair, and increasing p53 mRNA expression. Animal models indicate that melatonin may attenuate radiation-induced adverse effects, making therapy more tolerable. Additionally, a murine model of mammary gland adenocarcinoma found melatonin exerted synergistic antitumor effects.(Griffin 2018, Kubatka 2018, Reiter 2017)
In vitro data demonstrate that physiological doses of melatonin reduced cell numbers in estrogen-dependent BG-1 ovarian adenocarcinoma cell lines. Additionally, melatonin reduced ovarian masses in an animal model. Melatonin may be beneficial in ovarian cancer through its antiproliferative, antioxidant, proapoptotic, and antiangiogenic effects.(Chuffa 2017, Menendez-Menendez 2018)
In vitro and animal studies suggest potential beneficial effects of melatonin use in liver, renal, lung, gastric, colorectal, bone, and melanoma cancers, as well as leiomyosarcoma, leukemia, and glioblastoma.(Li 2017, Reiter 2017)
In addition to their existence in the central and peripheral nervous systems, melatonin receptors have been identified in the cardiovascular system, including in vascular tissues, the left ventricle, and coronary arteries. Metallothionein 1 (MT1) melatonergic receptors mediate arterial vasoconstriction and MT2 melatonergic receptors cause vasodilation. Low levels of serum melatonin have been associated with coronary heart disease, angina, myocardial infarction (MI), and heart failure. Melatonin's effects on lowering blood pressure are complex and extend beyond vasodilatory effects. Melatonin may cause a hypotensive effect through concentration-dependent effects on vascular smooth muscle cells. At lower concentrations, but not higher concentrations, melatonin may cause contractions, which is reflective of what occurs with blood pressure reductions at night when melatonin secretion is high. Melatonin may also reduce blood pressure through reductions in oxidative stress, indirect increases in nitric oxide production, and mediation of blood pressure through central autonomic mechanisms. Melatonin has also been shown to decrease the pulsatility index in the internal carotid artery, reduce platelet aggregation, diminish lipid peroxidation, decrease oxidation of low-density lipoprotein levels, increase high-density lipoprotein levels, and decrease catecholamine levels.(Baker 2018, Jiki 2018, Pandi-Perumal 2017)
Following MI in mice, melatonin inhibited cardiac remodeling and dysfunction through reversal of autophagy inhibition, reduction of apoptosis, and reversal of mitochondrial dysfunction in mice.(Hu 2017)
Animal models suggest that melatonin is able to scavenge free radicals and reduce oxidative stress associated with brain ischemia in stroke. It also has been associated with a reduction in white matter inflammation and cerebral edema. Additionally, melatonin protected against the breakdown of the blood-brain barrier following middle cerebral artery occlusion in animal studies.(Ramos 2017)
In a nested case-control study, low nocturnal melatonin secretion was associated with an elevated risk for MI. Specifically, the greater incidence of MI was noted in women with increased body mass index (BMI).(McMullan 2017)
In a study of intubated adults who had experienced hemorrhagic stroke, melatonin 30 mg per night administered via nasogastric tube significantly reduced the length of stay in the ICU compared with control (8 vs 12 days; P=0.041). Although not statistically significant, melatonin was associated with a shorter duration of mechanical ventilation (4 vs 12 days; P=0.065) and ICU mortality (15% of patients vs 30% of patients; P=0.451).(Dianatkhah 2017) 2ff7e9595c
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