Archived PDF from the original on 21 September Patients so treated should be closely monitored in the hospital. J Intern Med ;45 2: Turn the injection button in the opposite direction to the arrow on the injection button as far as it will go See Figure W. Higher potential for abuse compared to other opioids due to its rapid penetration of the blood-brain barrier. Lowering blood homocysteine with folic acid-based supplements:
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However, it's only been more recently that the focus has shifted to increasing the level of human growth hormones in our bodies. Foreign currency values are for information purposes only and are based on current market exchange rates. You have successfully Logged Out.. New Somatropinne Now Shipping! Our 1 HGH Supplement is better than ever. Experience the benefits of HGH without the injection. Labor Day Holiday Special! Vitamins B6, B12 and folic acid. Am J Obstet Gynecol ; Macrocytic anemia in patients treated with sulfasalazine for rheumatoid arthritis.
Optimization of dietary folate or low-dose folic acid supplements lower homocysteine but do not enhance endothelial function in healthy adults, irrespective of the methylenetetrahydrofolate reductase CT genotype. Calcium supplementation and prevention of pregnancy induced hypertension. J Obstet Gynaecol Res ; Folic acid supplementation and cancer risk: Folic acid supplementation with and without vitamin B6 and revascularization risk: Homocysteine-lowering therapy with folic acid is effective in cardiovascular disease prevention in patients with kidney disease: Folic acid therapy reduces the first stroke risk associated with hypercholesterolemia among hypertensive patients.
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Optimization of folic acid, vitamin B12, and vitamin B6 supplements in pediatric patients with sickle cell disease. Am J Hematol ; The effect of different treatment regimens in reducing fasting and postmethionine-load homocysteine concentrations. Combination of low-dose folic acid and pyridoxine for treatment of hyperhomocysteinaemia in patients with premature arterial disease and their relatives.
A randomized controlled trial examining the addition of folic acid to iron supplementation in the treatment of postpartum anemia. Int J Gynaecol Obstet. Results of a 2-year vitamin B treatment on cognitive performance: Folate, vitamin B12, and risk of ischemic and hemorrhagic stroke: Folic acid and reduction of plasma homocysteine concentrations in older adults: Effect of daily vitamin B and folic acid supplementation on fracture incidence in elderly individuals with an elevated plasma homocysteine concentration: Am J Clin Nutr ; 6: Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: Periconceptional use of folic acid and risk of miscarriage - findings of the Oral Cleft Prevention Program in Brazil.
Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: Multivitamin supplements are effective and inexpensive agents to lower homocysteine levels. Low serum folate concentrations are associated with an excess incidence of acute coronary events: Eur J Clin Nutr ; Low dietary folate intake is associated with an excess incidence of acute coronary events.
Calcium plus vitamin D supplementation and the risk of colorectal cancer. Randomized trial of folic acid supplementation and serum homocysteine levels. High dosage folic acid supplementation, oral cleft recurrence and fetal growth. View abstract Werbach MR. Nutritional strategies for treating chronic fatigue syndrome. Altern Med Rev ;5: The effect of cholestyramine on intestinal absorption. Pharmacokinetic study on the utilisation of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease.
Br J Pharmacol ; The use of folic acid for the prevention of neural tube defects and other congenital anomalies. J Obstet Gynaecol Can ;25 Effects of folic acid and zinc sulfate on male factor subfertility: Long-term improvement in homocysteine levels and arterial endothelial function after 1-year folic acid supplementation.
Folic acid improves arterial endothelial function in adults with hyperhomocysteinemia. Effect of B-group vitamins and antioxidant vitamins on hyperhomocysteinemia: Efficacy of folic acid therapy on the progression of chronic kidney disease: The renal substudy of the China stroke primary prevention trial. J Thromb Thrombolysis ;34 4: Drug interactions in intestinal transport of folic acid and methotrexate. Further evidence for the heterogeneity of folate transport in the human small intestine.
Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: Folic acid improves vascular reactivity in humans: Am J Clin Nutr ;86 3: Trend in prevalence of neural tube defects in Quebec. Reduction in neural-tube defects after folic acid fortification in Canada. J Med ; 2: Preventing the recurrence of neural tube defects in South Carolina. Proc Greenwood Genet Center ; Why do homocysteine-lowering B vitamin and antioxidant E vitamin supplementations appear to be ineffective in the prevention of cardiovascular diseases?
Vitamin B-6 supplementation in elderly men: Psychopharmacology Berl ; 4: Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: A randomized, placebo-controlled, double-blind trial. The effects of folic acid supplements on coagulation status in pregnancy. Folic acid and sulfasalazine for colorectal carcinoma chemoprevention in patients with ulcerative colitis: J Gastroenterol ;12 4: Vitamin requirements for the reduction of homocysteine blood levels in healthy young women [dissertation].
Folic acid and Vitamin B6 supplementation and plasma homocysteine concentrations in healthy young women. Daily low-dose folic acid supplementation does not prevent nitroglycerin-induced nitric oxide synthase dysfunction and tolerance: J Cardiol ;26 9: Effect of homocysteine-lowering therapy on vascular endothelial function and exercise performance in coronary patients with hyperhomocysteinaemia.
Acta Cardiol ;58 5: Disorders of homocysteine metabolism: Proceedings of an international symposium. Fulda, Germany, November Vitamin and mineral supplements in pregnancy and the risk of childhood acute lymphoblastic leukaemia: Dose-dependent effects of folic acid on blood concentrations of homocysteine: Folate improves endothelial function in coronary artery disease: Folic acid improves endothelial function in coronary artery disease via mechanisms largely independent of homocysteine lowering.
Its occurrence, cofactor therapy, and enzymology. Breast Cancer Res Treat. Effect of 3 y of folic acid supplementation on the progression of carotid intima-media thickness and carotid arterial stiffness in older adults. Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: Combined analyses and extended follow-up of two randomized controlled homocysteine-lowering B-vitamin trials.
Homocyst e ine and cardiovascular disease: Plasma and red cell folate values and folate requirements in formula-fed premature infants. A critical evaluation of the relationship between serum vitamin B, folate and total homocysteine with cognitive impairment in the elderly. J Hum Nutr Diet ;17 4: Supplementation with antioxidants and folinic acid for children with Down's syndrome: Diet and risk of dementia: Plasma folate concentrations are positively associated with risk of estrogen receptor beta negative breast cancer in a Swedish nested case control study.
High folate intake is associated with lower breast cancer incidence in postmenopausal women in the Malmo Diet and Cancer cohort. Folate intake, methylenetetrahydrofolate reductase polymorphisms, and breast cancer risk in women from the Malmo Diet and Cancer cohort.
A randomized trial of fluorouracil and folinic acid in patients with metastatic colorectal carcinoma. Health effects of mixed fruit and vegetable concentrates: Effect of oral vitamin B with or without folic acid on cognitive function in older people with mild vitamin B deficiency: Effect of folate intake on health outcomes in pregnancy: Implementation and outcomes of recommended folic acid supplementation in Mexican-American women with prior neural tube defect-affected pregnancies.
Effect of folic acid treatment on carotid intima-media thickness of patients with coronary disease. Int J Cardiol ; 3: Folic acid supplementation and colorectal cancer risk: Colorectal adenomas in a randomized folate trial: Folic acid and prevention of colorectal adenomas: Int J Cancer ; 1: Low folate levels in the cognitive decline of elderly patients and the efficacy of folate as a treatment for improving memory deficits. The prevention of anaemia in pregnancy in primigravidae in the guinea savanna of Nigeria.
Ann Trop Med Parasitol. The prevention of megaloblastic anaemia in pregnancy in Nigeria. Effects of iron and folic acid antenatal supplements on maternal haematology and fetal wellbeing. The value of folic acid supplements in pregnancy. Effect of folic acid supplementation on small-for-gestational-age infants born at term. Effect of homocysteine lowering treatment on cognitive function: Vitamins B 12 , B 6 , and folic acid for cognition in older men.
Vitamins B12, B6, and folic acid for onset of depressive symptoms in older men: Effect of various regimens of vitamin B6 and folic acid on mild hyperhomocysteinaemia in vascular patients. Treatment of mild hyperhomocysteinemia in vascular disease patients. Folic acid treatment in males and females with fragile- X -syndrome.
Am J Med Genet. Womens Health Lond Engl. The effects of antimalarials and folate supplements on haematological indices and red cell folate levels in Gambian children. Influence of folic acid on birthweight and growth of the erythroblastotic infant. Effect of folic acid supplementation. Demographic, lifestyle, and health characteristics and serum B vitamin status are determinants of plasma total homocysteine concentration in the post-folic acid fortification period, J Nutr ; 2: Low-dose aspirin and incidence of colorectal tumors in a randomized trial.
J Natl Cancer Inst. The role of diet and nutrition in cervical carcinogenesis: Effect of folic acid supplementation on biochemical indices in overweight and obese men with type 2 diabetes. Diabetes Res Clin Pract. Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis.
J Med ; Primary chemoprevention of familial adenomatous polyposis with sulindac. The influence of folic acid on the frequency of epileptic attacks. Eur J Clin Pharmacol. Is low folate a risk factor for depression? A meta-analysis and exploration of heterogeneity. Community Health ;61 7: Changes in frequencies of select congenital anomalies since the onset of folic acid fortification in a Canadian birth defect registry.
J Public Health ;99 4: Prenatal multivitamin supplementation and rates of congenital anomalies: J Obstet Gynaecol Can. Prenatal multivitamin supplementation and rates of pediatric cancers: Interactions between homocysteinaemia and conventional risk factors in vascular disease. Eur Heart J ;15 suppl: Folic acid in folate-deficient patients with epilepsy.
Br Med J ;4 Indicators for assessing folate and vitamin B status and for monitoring the efficacy of intervention strategies. Folic acid supplementation and neural tube defect recurrence prevention. The Hordaland Homocysteine Study. Homocysteine, B vitamins, and the incidence of dementia and cognitive impairment: Folic acid supplements in pregnancy and early childhood respiratory health. Treatment and prevention of anemia with ferrous sulfate plus folic acid in children attending daycare centers in Goiania, Goias State, Brazil: Saude Publica ;24 Suppl 2: A controlled trial of stimulant medication in children with the fragile X syndrome.
Multiple-micronutrient supplementation for women during pregnancy. Effect of multiple micronutrient supplementation during pregnancy on maternal and birth outcomes. Public Health ;11 Suppl 3: Folic acid deficiency and abruptio placentae. Metabolic interactions of alcohol and folate. J Nutr ; 8 Suppl: Homocysteine and vascular disease. Indian Heart J ;52 7 Suppl: Concurrent use of folinic acid and methotrexate in rheumatoid arthritis. J Rheumatol ;15 7: Child-bearing, health and social priorities: Improvement in bronchial squamous metaplasia in smokers treated with folate and vitamin B Report of a preliminary randomized, double-blind intervention trial.
B vitamins and the risk of total mortality and cardiovascular disease in end-stage renal disease: Homocysteine as a risk factor for cardiovascular disease in patients treated by dialysis: Am J Kidney Dis. A randomized comparison of routine versus selective iron supplementation during pregnancy. Prevention of preeclampsia by linoleic acid and calcium supplementation: Clin Lab ;52 Hyperhomocysteinemia and endothelial function in young subjects: Clin Cardiol ;25 Colon cancer in Chile before and after the start of the flour fortification program with folic acid.
Eur J Gastroenterol Hepatol. Is high homocysteine level a risk factor for cognitive decline in elderly? A systematic review, meta-analysis, and meta-regression. Folic acid supplementation improves vascular function in amenorrheic runners. Clin J Sport Med ;20 3: High-dose B vitamin supplementation and progression of subclinical atherosclerosis: Growth and recurrence of colorectal polyps: The effect of folinic acid supplementation on homocysteine concentrations in newborns.
Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: Vitamin supplementation and neural tube defects. Homocysteine-lowering trials for prevention of cardiovascular events: Am Heart J ; 2: Relation of abnormal folate metabolism to neuropathy developing during anticonvulsant drug therapy.
J Intern Med ;45 2: Unmetabolized folic acid and total folate concentrations in breast milk are unaffected by low-dose folate supplements. Am J Clin Nutr ;89 1: Effect of B-vitamin therapy on progression of diabetic nephropathy: Benefits of fatty fish on dementia risk are stronger for those without APOE epsilon4.
Folate metabolism polymorphisms influence risk of colorectal adenoma recurrence. Hyperhomocysteinemia in children treated with antiepileptic drugs is normalized by folic acid supplementation. Zinc supplementation during pregnancy: Am J Clin Nutr ;37 4: No effect of vitamin B treatment on cognitive function and depression: Folic acid supplementation for the prevention of recurrence of colorectal adenomas: Folic acid-based intervention in non-ST elevation acute coronary syndromes.
The effect of folic acid, protein energy and multiple micronutrient supplements in pregnancy on stillbirths. Prevalence of severe congenital heart disease after folic acid fortification of grain products: Does a selective cyclooxygenase-2 inhibitor tiracoxib induce clinically sufficient suppression of adenomas in patients with familial adenomatous polyposis?
A randomized double-blind placebo-controlled clinical trial. Int J Clin Oncol. Prophylaxis of anemia in pregnancy. Effect of folic acid supplement on birth weights of infants. Folic acid requirements of Indian pregnant women. Anemia of pregnancy in Liberia, West Africa: Homocysteine increases as folate decreases in plasma of healthy men during short-term dietary folate and methyl group restriction.
J Nutr ; 7: The effect of folic acid fortification on plasma folate and total homocysteine concentrations. Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: The effect of folic acid based homocysteine lowering on cardiovascular events in people with kidney disease: Folic acid supplementation inhibits recurrence of colorectal adenomas: World J Gastroenterol ;14 Subnormal serum folate due to anticonvulsive therapy.
A double-blind study of the effect of folic acid treatment in patients with drug-induced subnormal serum folates. Diminished need for folate measurements among indigent populations in the post folic acid supplementation era.
Lab Med ; 3: Folate intake, markers of folate status and oral clefts: The influence of soy-derived phosphatidylserine on cognition in age-associated memory impairment. Nutr Neurosci ;4 2: Exacerbation of rheumatoid arthritis in patients treated with methotrexate after administration of folinic acid. Dietary intake of selected B vitamins in relation to risk of major cancers in women.
Recent clinical trials of pharmacologic cardiovascular interventions in patients with chronic kidney disease. Rev Recent Clin Trials ;3 2: Cardiovascular disease in patients with chronic kidney disease. A base pair deletion polymorphism in dihydrofolate reductase is associated with increased unmetabolized folic acid in plasma and decreased red blood cell folate. A trial of B vitamins and cognitive function among women at high risk of cardiovascular disease. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids.
Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.
There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs e. In patients who may be susceptible to the intracranial effects of CO2 retention e. Opioids may also obscure the clinical course in a patient with a head injury.
Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis , for worsening symptoms. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low.
Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people. Long term studies in animals to evaluate the carcinogenic potential of hydromorphone have not been conducted. Hydromorphone was positive in the mouse lymphoma assay in the presence of metabolic activation, but was negative in the mouse lymphoma assay in the absence of metabolic activation.
Hydromorphone was not mutagenic in the in vitro bacterial reverse mutation assay Ames assay. Hydromorphone was not clastogenic in either the in vitro human lymphocyte chromosome aberration assay or the in vivo mouse micronucleus assay.
Reduced implantation sites and viable fetuses were noted at 2. In animal reproduction studies, reduced postnatal survival of pups, and decreased were noted following oral treatment of pregnant rats with hydromorphone during gestation and through lactation at doses 0.
In published studies, neural tube defects were noted following subcutaneous injection of hydromorphone to pregnant hamsters at doses 6. No malformations were noted at 4 or Based on animal data, advise pregnant women of the potential risk to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect , loss, or other adverse outcomes. Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.
Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor , vomiting, diarrhea, and failure to gain weight.
The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn.
Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone , must be available for reversal of opioid-induced respiratory depression in the neonate. However, this effect is not consistent and may be offset by an increased rate of cervical dilation , which tends to shorten labor.
Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. Maternal toxicity was noted in all treatment groups reduced food consumption and body weights in the two highest dose groups.
There was no evidence of malformations or embryotoxicity reported. Maternal toxicity was noted in the two highest dose groups reduced food consumption and body weights. The findings cannot be clearly attributed to maternal toxicity. In a published study, CF -1 mice were treated subcutaneously with continuous infusion of 7. Increased pup mortality and decreased pup body weights were noted at 0. Maternal toxicity decreased food consumption and body weight gain was also noted at the two highest doses tested.
Low levels of opioid analgesics have been detected in human milk. Withdrawal symptoms can occur in breastfed infants when maternal administration of hydromorphone is stopped, or when breast-feeding is stopped. Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. Elderly patients aged 65 years or older may have increased sensitivity to hydromorphone. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.
Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration.
Hydromorphone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. The pharmacokinetics of hydromorphone are affected by hepatic impairment.
Due to increased exposure of hydromorphone, patients with moderate hepatic impairment should be started at one-fourth to one-half the recommended starting dose depending on the degree of hepatic dysfunction and closely monitored during dose titration. The pharmacokinetics of hydromorphone in patients with severe hepatic impairment has not been studied. The pharmacokinetics of hydromorphone are affected by renal impairment.
Start patients with renal impairment on one-fourth to one-half the usual starting dose depending on the degree of impairment. In case of overdose, priorities are the reestablishment of a patent airway and protected airway and institution of assisted or controlled ventilation , if needed.
Employ other supportive measures including oxygen and vasopressors in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques. The opioid antagonists, naloxone or nalmefene are specific antidotes to respiratory depression resulting from opioid overdose.
For clinically significant respiratory or circulatory depression secondary to hydromorphone overdose, administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to hydromorphone overdose.
If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product's prescribing information. In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome.
The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be initiated with care and by titration with smaller than usual doses of the antagonist.
Hydromorphone is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of hydromorphone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with morphine.
Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression. The precise mechanism of the analgesic action is unknown.
However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug. Hydromorphone produces respiratory depression by direct effect on brain stem respiratory centers.
The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation.
Hydromorphone causes miosis , even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic e. Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations. Hydromorphone causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased.
Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm, resulting in constipation. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase.
They also stimulate prolactin , growth hormone GH secretion, and pancreatic secretion of insulin and glucagon. Chronic use of opioids may influence the hypothalamic- pituitary -gonadal axis , leading to androgen deficiency that may manifest as low libido , impotence , erectile dysfunction , amenorrhea , or infertility.
The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date [see ADVERSE REACTIONS ].
Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown. Overall, the effects of opioids appear to be modestly immunosuppressive. The minimum effective analgesic concentration will vary widely among patients, especially among patients who have been previously treated with potent agonist opioids.