Clinical Pearls is designed with the 3 qualities of physician-learners in mind. There has been a dramatic de-cline in the use of quinine over the past several years. Results: One month after treatment with orphenadrine; the frequency of muscle cramps decreased significantly to 0.6 AE 0.74 per week compared to 12.53 AE 6.01 at baseline (p < 0.001), the duration of muscle cramps decreased from 1 min to 0.1 min after treatment (p < 0.001). Despite the fact that the adverse effects of QU on the gastrointestinal, cardiovascu-lar, central nervous and haematological systems have been well reported 4 ' 5 , there is still a dearth of publications on the effects of QU on the male reproductive system. Compared with placebo, the use of quinine was associated with an increased incidence of side effects, particularly tinnitus. Vitamin B complex. Other drugs are also available such as verapamil and gabapentine. To evaluate the efficacy and safety of gabapentin in the treatment of muscle cramps, we engaged an open-label trial with a group of 30 patients with frequent (> 5 cramps/week), stable, long-lasting cramps, associated with different diseases. Quinine sulfate, but not vitamin E, is superior to placebo in the treatment of nocturnal leg cramps. Results: Our results showed a significant (p < 0.01) elevation of MDA levels in the testicular homogenates of rats treated with QU only compared with those of the control group and those treated with a combination of QU and AA. Experimental models and observational studies suggest that vitamin E supplementation may prevent cardiovascular disease and cancer. Hyodo T, Taira T, Takemura T, et al. Efficacy of quinine versus vitamin E, Treatment of nocturnal leg cramps: A crossover trial of quinine vs vitamin E, Pharmacokinetics of quinine in young and elderly subjects, Nocturnal Cramps, Quinine, and Thrombocytopenia, Quinine-induced disseminated intravascular coagulation, Placebo-controlled trial of quinine therapy for nocturnal leg cramps, Verapamil vs quinine in recumbent nocturnal leg cramps in the elderly, Randomised double-blind trial of quinine sulphate for nocturnal leg cramp, Nocturnal leg cramps (systremma): A progress report on response to vitamin E, Orphenadrine citrate (Norflex) for the treatment of "restless legs" and related syndromes, Quinine-induced purpura. Quinine significantly increased Fluo3-fluorescence, DCF fluorescence and ceramide abundance. Vitamin D deficiency was seen in 66% of the study cohort, but the serum 25-(OH) vitamin D levels were not significantly different between patients with and without cramps (18.0±8.9 ng/mL vs 19.6±9.5 ng/mL, P=.49). In patients with severe symptoms, a trial of 4-6 weeks' treatment with quinine is probably still justified, but the efficacy of treatment should be monitored, for example using a sleep and cramp diary. also provides integrated problem-solving during construction of heterocycles. While you do get some ECGC from drinking green tea, the stuff in the supplement pills is equal to dozens of cups of tea. Frequency, duration of muscle cramps, and pain score improved significantly after 1 month of orphenadrine therapy in comparison to placebo. Limited evidence supports treating nocturnal leg cramps with exercise and stretching, or with medications such as magnesium, calcium channel blockers, carisoprodol, or vitamin B12. Tablets. Antihypertensive drug treatment was given to 26% of the intervention group and 20% of the control group participants after 10 years. The exact mechanism is Prescribing physicians must closely monitor the risks and benefits in individual patients. High-dosage (> or =400 IU/d) trials were often small and were performed in patients with chronic diseases. Quinine-induced thrombocytopenia has been extensively studied and several in vitro tests have been described. 2012;Hallegraeff et al. For six months a 20-year-old white girl has taken quinine sulfate intermittently for nocturnal leg cramping. You can forcefully stretch the cramped muscle and gently massage it to help it relax. Stimulation of Erythrocyte Cell Membrane Scrambling by Quinine, Management of essential muscle cramps in elderly subjects, Prevalence and Morbidity Associated with Muscle Cramps in Patients with Cirrhosis, Therapeutic Activity and Safety of Vitamin K 2-7 in Muscle Cramps: An Interventional Case-Series, Parasomnias and Movement Disorders of Sleep, Calambres nocturnos: una queja frecuente en atención primaria. With discontinuation of the quinine, the patient's symptoms resolved within 48 hours and the liver enzyme concentrations declined within 72 hours. At the 1 month control (mean dosage, 825 +/- 35 mg), almost every patient had responded to treatment and two thirds experienced a total remission of symptoms. For persons who find this ineffective and whose quality of life is significantly affected, a trial of quinine is warranted. There have been a few other suggested treatments with quinine, nifedipine, vitamin E, biotin and other orally administered drugs, which have been reported to prevent cramping in patients undergoing HD [4][5][6][7][8][9][10]. Papaverine is an alkaloid isolated Sympathetic nervous system response to volume stress is more marked in patients with frequent hemodialysis-associated skeletal muscle cramps than in most patients who cramp infrequently. The pain score improved significantly from a score of 8/10 to 0/10 (p < 0.001). The purpose of this study was to evaluate the effects of orphenadrine citrate (Norflex) in the syndrome of “restless legs” and nocturnal leg cramps. The exact mechanism is unknown, but the cramps are probably caused by muscle fatigue and nerve dysfunction rather than electrolyte or other abnormalities. In addition, the age and sex profiles of patients given quinine and the proportion of these patients concurrently prescribed other drugs associated with leg cramps were determined in a sample of practices. However, elderly subjects excreted 16.6 +/- 3.7% of the dose as unchanged quinine in the urine and this was significantly greater (P less than 0.005) than the amount excreted by the young (11.2 +/- 2.5%). The pooled all-cause mortality risk difference in high-dosage vitamin E trials was 39 per 10,000 persons (95% CI, 3 to 74 per 10,000 persons; P = 0.035). product (±)-Scholarisine II selectively inhibited the inducible COX-2 rather than COX-1, and also markedly inhibited 5-LOX, comparable to positive controls. Forty-two patients completed the 4-month study. The recurrent, painful tightening usually occurs in the calf muscles and can cause severe insomnia. Dec. 12, 2006 -- The FDA is telling people not to use the malaria drug quinine for leg cramps, citing potentially deadly side effects.. The pathophysiologic and clinical features of each of these diagnoses are described. Quinine sulphate is usually the sole drug prescribed, even though firm evidence for its efficacy is not available. IntroductionPatients with lumbar spine disease sometimes complain of nocturnal leg cramps. Compared to placebo, quinine reduced cramp numbers over a 2-week period by 28% (absolute difference of about 2.5 cramps). There is moderate quality evidence that with use up to 60 days, the incidence of serious adverse events is not significantly greater than for placebo in the identified trials, but because serious adverse events can be rarely fatal, in some countries prescription of quinine is severely restricted.Evidence from single trials suggests that theophylline combined with quinine improves cramps more than quinine alone, and the effects of xylocaine injections into gastrocnemius are not significantly different to quinine across all outcomes. Low or moderate quality evidence shows no significant difference between quinine and vitamin E or quinine and quinine-vitamin E mixture. A 48 hours exposure of human erythrocytes to quinine (≥ 50 µM) significantly increased the percentage of annexin-V-binding cells without significantly affecting forward scatter. I read with some interest the article by McGee,1 regarding muscle cramps. 5) Quinine is the best-studied drug for nocturnal leg cramps and has been found effective … Teamwork and skillful airway management prevented this patient's demise. Overdoses of quinine have been reported elsewhere to cause potentially fatal adverse effects, but in the included trials there was no significant difference in major adverse events compared with placebo (RD 0%, 95% CI -1% to 2%). The significance of these symptoms ranges from benign conditions, such as benign cramp-fasciculation syndrome, to devastating neurological conditions like motor neuron disorders. • Quinine is effective in reducing the frequency of nocturnal leg cramps by about 25% in ambulatory patients. On 27 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE. Q. Gabapentin was effective in reducing the frequency and severity of muscle cramps and associated sleep disturbances (clinical outcome measures) within the first 2 weeks of medication at 600 mg/d. ethers and other functional groups. Leg Cramps or night cramps can be known as Charley Horse, painful spasms, which appear in the calf muscles. Introduction: Muscle cramps are common and may occur at any age, particularly among the elderly population. The licensed dose for the treatment and prevention of nocturnal leg cramps in adults is 200–300 mg at night for Vipan1 attributed skin and mucous membrane purpura of four patients to quinine. Are there any alternatives to quinine for leg cramps? An antimalarial medicine. Further, a dosage of 200 to 300 mg of quinine every night has not been shown to cause significant side effects. Vitamin K 2-7 (100µg/Capsule/ Day) was given orally for 3 months. A total of 150 adult patients with cirrhosis were enrolled consecutively. Quinine Sulfate for Leg Cramps: Does It Work? Heterocycle synthesis BSMA presents clinically with slowly progressive, amyotrophic quadruparesis, bulbar involvement, wasting, fasciculations, and gynecomastia. • Quinine should only be considered when cramps are very painful or frequent; when other treatable causes of cramp have been ruled out and where non-pharmacological measures have not worked (e.g. Results: If you have an underlying condition that’s causing leg cramps, treating that condition can often treat the cramps … Prescribing of quinine and cramp inducing drugs in general practice, Private sector to fund new wave of NHS hospitals, Quinine-induced hemolytic uremic syndrome, Quinine Hypersensitivity Simulating Sepsis, Quinine-induced immune thrombocytopenic purpura followed by hemolytic uremic syndrome, Quinine-induced blindness during attempted heroin withdrawal, Gabapentin Treatment for Muscle Cramps: An Open-Label Trial, Magnesium for the treatment of nocturnal leg cramps: A crossover randomized trial. Testicular specimens were also processed for histology under light microscopy. First, we physicians enjoy learning from cases. The side effects were few, such as dry mouth, drowsiness, and nausea, with no significant difference between their occurrences in the two groups. The aim of present study was to determine changes in the testicular levels of malonyldialdehyde (MDA) secondary to QU and ascorbic acid (AA). • Quinine is effective in reducing the frequency of nocturnal leg cramps by about 25% in ambulatory patients. Before establishing the diagnosis of essential cramps, it is important to exclude cramps of endocrine or metabolic origin as well as the restless leg syndrome. 2010; 63(5):287-291). Efficacy trials for quinine in leg cramps have numerous design flaws that have resulted in poor quality data, producing both positive and negative findings. Pregnant women should not be prescribed quinine to treat leg cramps. 2002;Hinoshita et al. In the U.S., there have been about 100 quinine-caused deaths over the last 40 years, according to the FDA, and hundreds of permanent injuries. His treatment involve a combination of nutritional counselling, botanical medicine, eastern medicine (acupuncture), nutraceutical supplementation and hands on physical medicine. They were followed up in the fourth month for recurrence of any cramps. Due to the large size of the groups and because they formed a random population sample, it was assumed that they had similar characteristics at the start of the trial. The parasomnias include a spectrum of abnormal emotions, movements, behaviors, sensory perceptions, dream mentation, and autonomic activity. ?teborg, Sweden, Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality, Prevention of muscle cramps in hemodialysis patients by quinine sulfate, Intravascular Coagulation Induced by Quinine: Unexpected Hazard of ‘Bitter Lemon’, A controlled clinical trial of chlormezanone, orphenadrine, orphenadrine/paracetamol and placebo in the treatment of painful skeletal muscle spasms, Hemolytic-Uremic Syndrome Associated with Ingestion of Quinine, Dialysis leg cramps. Several authors have addressed this subject and have proposed newer classifications to describe the cramping syndromes. 3 investigators independently abstracted study reports. Quinine sulfate, an antimalarial drug, is widely used as an effective therapy for idiopathic leg cramps. There is solid evidence that quinine and quinine derivatives are effective in reducing the frequency of muscle cramps, although the magnitude of benefit is small. Patients kept the record of frequency, duration and intensity of their cramps during the baseline period of 7 days and throughout the study. But this works! Quinine for night-time leg cramps no longer recommended Since the 1940s, doctors have been prescribing quinine for leg cramps because there are no other reliable treatments. Muscle cramps markedly affect the quality of life in cirrhotic patients with no available highly effective treatment. The person should be admitted to hospital if the cramps are severe and they have other concerning symptoms (for example anuria, altered consciousness, or hyper- or hypopyrexia). Conclusion: Orphenadrine is safe and effective in treatment of muscle cramps in patients with liver cirrhosis. During the 2 weeks patients used quinine, there was no statistically significant reduction in mean leg cramp number (quinine 3.5 vs placebo 4.2, P = 0.48), mean leg cramp duration (quinine 152 seconds vs placebo 163 seconds, P = 0.89), or patient ratings of severity using a 1 (low) to 10 (high) scale (quinine = 4.2 vs placebo = 4.0, P = 0.83). However, several trials of high-dosage vitamin E supplementation showed non-statistically significant increases in total mortality. Quinine is moderately effective in decreasing the frequency and intensity of muscle cramps, but it is also associated with an increase in minor adverse effects. We also searched for ongoing trials in November 2014. No specific cause can be identified; therefore, therapy is mostly symptomatic. These men were, however, subjected to health examinations and treatment as well as general health advice. To report a case of quinine-induced hepatotoxicity presenting within 24 hours following the ingestion of the first dose. Therefore, patients will likely continue to request quinine, and some physicians will continue to prescribe it, as there are few alternative treatments for nocturnal muscle cramps. The cause of his bleeding was a severe thrombocytopoaenia, induced by chronic ingestion of quinine. Side effects were recorded. FDA-Inspected Facility. Physiological methods may be useful for preventing cramps in some people, but there have been no controlled trials of these approaches. Given the possible serious side effects of treatment with quinine, the benefits and risks in patients taking this drug should be closely monitored. There is low quality evidence that quinine (200 mg to 500 mg daily) significantly reduces cramp number and cramp days and moderate quality evidence that quinine reduces cramp intensity. Because of this article, I casually began to prescribe the vitamin in the doses recommended—300 international units (IU) a day—first to patients complaining of leg cramps and other types of idiopathic cramps, and then sometimes to patients with pain in the neck and lower part of the back. A dose-response analysis showed a statistically significant relationship between vitamin E dosage and all-cause mortality, with increased risk of dosages greater than 150 IU/d. 3) Diphenhydramine (Benadryl) 12.5 mg to 50 mg nightly (available over the counter). Compared with placebo the decrease in the mean number of muscle cramps (16.1 or 58%) in the active drug treatment group during the medication period was highly significant (Wilcoxon test p = 0.004). Recently, it was found to be dangerous. heterocycles synthesis. Used for. These events typically occur during entry into sleep from wakefulness, or during arousals from sleep, and are often augmented by the sleep state. Although the mechanisms that underlie idiopathic RLS or PLMD are not fully understood, there is currently substantial evidence that dopaminergic dysfunction is likely involved in both conditions. The investigators of the original publications were contacted if required information was not available. Further research into these alternatives, as well other pharmacological and non-pharmacological treatments, is thus warranted.There is no evidence to judge optimal dosage or duration of quinine treatment. Objective To study, the safety, tolerability and therapeutic activity of Vitamin K 2-7(MK7) in a series of patients with idiopathic muscle cramps-systremma Material and Method An open-labelled ambulant trial was conducted in 19 patients presenting with muscle cramps. Four hundred patients with painful muscle spasm caused by five common musculoskeletal diseases were included in a double-blind controlled trial of chlormezanone, orphenadrine, orphenadrine/paracetomol and placebo. This study compared the efficacy and safety of quinine sulfate, vitamin E, and placebo in the treatment of nocturnal leg cramps. Multiple quinine-dependent antibodies have been characterized in the patient's serum. However, the simple expedient of increasing the nightly dose of quinine may carry the concomitant risk of cinchonism. Check if it's leg cramps. Data are available supporting the potential efficacy of verapamil, gabapentin, carisoprodol, and orphenadrine in the general population, and vitamin E in the dialysis population. However, we have speculated in our previous studies that a disruption of the balance between pro-oxidants and anti-oxidants of the testis may be involved. Materials and methods: Thirty adult male Sprague-Dawley rats were used and were randomly di-vided into 3 groups of 10 rats each. passive stretching exercises). The generalizability of the findings to healthy adults is uncertain. The Consultant pharmacist: the journal of the American Society of Consultant Pharmacists, Treatment of nocturnal leg cramps by blockade of the medial branch of the deep peroneal nerve after lumbar spine surgery, Differentiating nocturnal leg cramps and restless legs syndrome. The small amounts of quinine found in tonic water are not enough to help treat diseases or symptoms like leg cramps. Publication bias is present in the reporting of the efficacy of quinine for this indication, as almost all published studies reported larger estimates of its efficacy than did unpublished studies. There are of course other causes of nocturnal leg cramps. Though we have previ-ously demonstrated that QU is toxic to the testes of the rat 6 -7 , the mechanism of this destruction was yet to be determined. The dose was substantial–200 to 300 mg. The pain score improved significantly from a score of 8/10 to 0/10 (p < 0.001). Nighttime leg cramps have been an ongoing problem, so I bought a bottle of tonic water. A total of 107 general ambulatory patients who suffered from regular nocturnal leg cramps from six clinical trials. Methods: Treatment with quinine reduced the number of nights with cramps by 27.4% (24.0% to 30.8%) compared with placebo. There were 11,598 deaths (4.2 per 100 person-years) among the 44,699 participants who took quinine compared with 26,753 deaths (3.2 per 100 … Longer lengths of follow-up in future trials will help determine the duration of action following cessation of quinine as well as long-term adverse events. 2001;Roffe et al. Several double-blind, randomized, placebo-controlled studies have questioned the effectiveness of quinine in leg cramps; whereas other studies have shown significantly more benefit with use of quinine in reducing the frequency and severity of cramps compared with placebo or vitamin E. The mechanism of this beneficial effect is obscure, however. Atthe2001AnnualConferenceoftheAmerican College of Physicians, a new teaching format to aid physician learning, Clinical Pearls, was introduced. Quinine is an anti-malarial natural, Access scientific knowledge from anywhere. vasodilator. The intervention group were given advice on diet, both individually and in groups, the type of advice depending upon serum cholesterol level. In 2011, an estimated 51,800 patients re- ... Quinine, cramps Created Date: The 95% confidence interval for the difference between the number of leg cramps after vitamin E versus quinine treatment (95% confidence interval, -3.8, +3.2) suggests similar efficacy. Since quinine is not without the potential for side effects and drug interactions, clinicians need to carefully consider the likelihood of modest benefit associated with quinine against the potential for side effects and drug-drug interactions. Despite this experience, the patient continued to deny that quinine was the cause of his problem and that he had failed in his obligations to advise the dentist of his drug history. Objective: 2000;Khajehdehi et al. Parasomnias are undesirable emotional or physical events that accompany sleep. The severity of each cramp was less in about two-thirds of patients (63.4%; n = 26) in the block group and was unchanged in one-third (31.7%; n = 13).Conclusions A pharmacist suggested I check with you. Main results: interesting electronic, mechanical or biological properties. The results from 23 clinical trials involving 1,586 people, show that taking quinine at an average dose of 300mg per day (range 200–500 mg/day) was more effective than placebo for stopping leg muscle cramps. Of the 29 patients completing the study, 16 received quinine and 13 vitamin E. During placebo washout, the vitamin E group had a mean of 10.4 leg cramps per month, and the quinine group had a mean of 10.9. Alternative treatments for Nocturnal Leg Cramps The following products are considered to be alternative treatments or natural remedies for Nocturnal Leg Cramps. With respect to the use of quinine for the treatment of nocturnal leg cramps, to determine whether the findings of a previously performed meta-analysis of published data are altered with the addition of unpublished data, and whether publication bias is present in this area. I would agree with Ayres and Mihan that the medication is almost universally effective on idiopathic nocturnal leg cramps. Using these classifications when evaluating patients helps differentiate among the different causes and helps the clinician focus on the specific disorder underlying the muscle cramps. Quinine is no longer recommended to treat leg cramps. An uncontrolled study suggested that calf-stretching exercises could prevent nocturnal leg cramps (night cramps) but these findings have never been confirmed. The intervention group contained 10,000 men and the control group 20,000 men. Tonic Water with Quinine to Ward Off Nighttime Leg Cramps: A. A severity of pain index showed a statistically significant decrease for both groups. It There was also a reduction in the duration as well as severity recorded as 0-3 on VAS as compared to the baseline 2-9 in the Group A. The study was conducted at the Veterans Affairs Medical Center, White River Junction, Vt. However, a trial of quinine may be considered in certain circumstances if self-care measures fail and leg cramps are frequent and affecting the person's quality of life. For cramps - start a course of Magnesium supplements (Magtein has worked great for me! 'Quinine [originally designed to treat malaria] is an alternative medicine prescribed for leg cramps,' says Mr Dajani. One participant suffered from thrombocytopenia (0.12% risk) on quinine.A quinine-vitamin E combination, vitamin E alone, and xylocaine injections into gastrocnemius were not significantly different to quinine across all outcomes, including adverse effects. Administering quinine for leg cramps is effective to some extent but the side effects are severe and, at times, life-threatening. There may be a lot of confusion as to whether quinine and leg cramps go together, but I think a bit of tonic water in your diet is an easy way to find out if quinine works for you. Quinine sulfate at a dose of 200–300 mg at night has been used for many years to treat nocturnal leg cramps. 1999;Serrao et al. The main outcome was the number of nocturnal leg cramps, and the secondary outcomes were duration, severity, and sleep disorders caused by those cramps. There are those who are so sensitive that even a little bit of quinine could prove life threatening. Orphenadrine reduced the frequency of nocturnal leg cramps associated with pain to 39% of the frequency reported by patients when they were receiving placebo. Gabapentin significantly increased the CTF, returning it to normal values. Serum cholesterol, blood pressure and smoking decreased among men in both groups, and only slightly more in the intervention group. from the opium poppy and is a smooth muscle relaxant and a coronary They can happen at any time, but most people have them at night or when resting. Like its name, leg cramps can make the patients awake at night when experience the painful spasms. Nocturnal leg cramps are associated with vascular disease, lumbar canal stenosis, cirrhosis, hemodialysis, pregnancy, and other medical conditions. Vitamin K 2-7 was well tolerated clinically and found to be safe on the organ function in all the patients. Type of medicine. I was at the breaking point with the pain, now I can still work, walk and sleep a full night without pain. That is why it is essential to perform a thorough history and physical examination when evaluating a patient with suspected muscle disease. Chloroquine is a completely synthetic anti-malarial drug that has the Since quinine is not a primary drug in any other condition, further studies of drugs with similar pharmacological actions may thus improve our management of this painful complaint. Data collection and analysis: Pregnant and lactating mothers are also prescribed calcium and potassium supplements [25].
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