Year : 2018 | Volume
: 16 | Issue : 2 | Page : 78--80
DRUG DIALOGUES – Medication news and new medications
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. DRUG DIALOGUES – Medication news and new medications.Curr Med Issues 2018;16:78-80
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. DRUG DIALOGUES – Medication news and new medications. Curr Med Issues [serial online] 2018 [cited 2020 Aug 5 ];16:78-80
Available from: http://www.cmijournal.org/text.asp?2018/16/2/78/234844
Source: CMC Pharmacy Bulletin, a publication of the Pharmacy Service (DISH), CMC, Vellore.
Hydroxychloroquine is not useful in hand osteoarthritis
A study published in the Annals of Internal Medicine has shown that using hydroxychloroquine has no significant effect on osteoarthritic pain.
There is anecdotal evidence that the slow-acting anti-inflammatory treatment hydroxychloroquine, used to treat rheumatoid arthritis, could also be effective in osteoarthritis. However, data on this are limited.
In the Annals of Internal Medicine [online, 20 Feb 2018], researchers carried out a 12-month randomized trial involving 248 patients with hand osteoarthritis and moderate-to-severe pain who were assigned to 200 - 400mg hydroxychloroquine or placebo, in addition to ongoing usual care.
At six months, the team found that the average hand pain score over the prior two weeks was 5.66 out of 10 in the active treatment group, compared with 5.49 in the placebo group, a non-significant difference.
The results therefore, do not provide evidence to support the use of hydroxychloroquine in hand osteoarthritis, the researchers concluded.
Kingsbury S, Tharnanathan P, Keding A et al. Hydroxychloroquine effectiveness in reducing symptoms of hand osteoarthritis. Ann Int Med 2018;168(6):385–395.
Tramadol declared psychotropic drug
Tramadol has been recently declared a “psychotropic substance” according to the gazette released by the central government of India on 26th April 2018. This abrupt announcement follows the Narcotics Control Bureau (NCB) saying tramadol was being smuggled across international borders, and had possible supply links to one of the global terror groups.
The finance ministry has brought the drug under the control of the Narcotic Drugs and Psychotropic Substances (NDPS) Act and accordingly, the sale of tramadol in the country will now be closely monitored like other opioids including morphine and fentanyl.
Tramadol hydrochloride is a synthetic opioid analgesic. It also has noradrenergic and serotonergic properties that may contribute to its analgesic activity. The drug is also known as ‘fighter drug’ as it is believed to increase performance. Source: The Gazette of India, part II - section 3 - subsection (ii); 26 April 2018
Novel drug rapidly reduces menopausal hot flushes
In a placebo controlled trial reported in Menopause [online, 12 March 2018], researchers explored the efficacy of a neurokinin 3 receptor antagonist known as MLE4901 on hot flushes in 37 women aged 40 - 60 years with vasomotor symptoms.
The team found that by day 3 of treatment, hot flush frequency had reduced in the active treatment group by 51 percentage points compared with placebo. Women who received MLE4901 also reported significant reductions in hot flush severity, interference with daily life, and improvements in sleep and concentration by day 3. These effects were sustained throughout the four-week study period.
The researchers concluded that the results indicate neurokinin 3 receptor antagonism has a rapid effect on vasomotor symptoms of menopause and could provide an effective alternative to oestrogen therapy.
Reference: Prague J, Roberts R, Comninos A et al. Neurokinin 3 receptor antagonism rapidly improves vasomotor symptoms with sustained duration of action. Menopause 2018.
Could steroids reduce death from septic shock?
In a research paper published in the New England Journal of Medicine [online, 19 Jan 2018], researchers randomly assigned 3800 patients with septic shock who were undergoing mechanical ventilation to continuous infusion of hydrocortisone 200 mg/day or placebo for seven days, or until death or discharge from intensive care.
After 90 days, they found there was no significant difference between the hydrocortisone and placebo groups in terms of rate of death from any cause (27.9% and 28.8%, respectively). However, patients in the hydrocortisone group had faster resolution of shock, spent less time in intensive care and were less likely to receive a blood transfusion, compared with those in the placebo group.
The team said that the results indicate that there may be some benefits to glucocorticoids for septic shock, but these do not extend to lowering 90-day mortality.
Venkatesh B, Finfer S, Cohen J, et al. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med 2018.
Pharmacotherapy Refresher – Drugs used in Angina / Myocardial ischemia
Myocardial ischemia is one of the more common causes of chest pain in adults. Classic angina pectoris is described as a pressure, heaviness, tightness, or constriction in the centre or left of the chest that is precipitated by exertion and relieved by rest. There are three classes of anti-ischemic drugs commonly used in the management of angina pectoris: beta blockers, calcium channel blockers and nitrates. Often, a combination of these agents is used for control of symptoms. Nitro-glycerine was the first medication used in 1879 by William Murrell for the treatment of angina pectoris and in its immediate release forms, still remains first-line drug therapy for many patients.
NITRATES (Nitroglycerine, isosorbide mononitrate, isosorbide dinitrate)
Nitrates dilate veins, arteries, and coronary arteries by relaxing vascular smooth musclesNitrates, usually in the form of sublingual preparation, are the first-line therapy for the treatment of acute anginal symptomsTolerance has been a major problem with the use of nitrates as chronic antianginal therapyAn adequate nitrate-free interval (around 8 to 10 hours) may pre-vent nitrate tolerance; however, arguably rebound angina may occur during the nitrate-free intervalCombined nitrate-hydralazine therapy in heart failure patients may attenuate nitrate toleranceNitrates are contraindicated in patients who have taken sildenafil or tadalafil within 24 hours
Beta blockers relieve anginal symptoms by reducing both heart rate and contractilityAll types of beta blockers appear to be equally effectiveBeta blockers are the only antianginal drugs proven to prevent reinfarction and to improve survival in patients who have sustained a myocardial infarction
CALCIUM CHANNEL BLOCKERS
Calcium channel blockers are used in combination with beta blockers when initial treatment with beta blockers fail or contraindicatedLong-acting diltiazem, verapamil or a 2nd generation dihydropyridine (amlodipine) are preferred
Reference: www.uptodate.com [accessed online, 18 May 2018]
Angina pectoris and the history of nitroglycerine
Do you know the story behind the classic drug nitroglycerine that is placed under the tongue to mitigate acute chest pain? During the 1800s, brandy was the standard remedy for anginal pain! Here's how nitroglycerine transfigured as a lifesaver. Frederick Guthrie, an English Chemist in 1859 observed a sudden throbbing of the arteries of the neck followed by a flushing of neck, temples and forehead and an acceleration in the action of the heart when he held a paper moistened with only two drops of amyl nitrite (synthesized in 1844 by Antonie Balard). For this reason, Guthrie proposed that the compound could be used as a resuscitative in drowning, suffocation and protracted fainting, although he would not have known that amyl nitrite, in fact, causes a fall in blood pressure. On this milieu, Thomas Lauder Brunton, a Scottish physician at his young age predicted the potential use of nitrate-containing compound for therapeutic purposes. He used to submit himself to Dr. Gamgee for experiments upon the effect of amyl nitrite on his own pulse, from which he made sphygmographic tracings, and these experiments naturally rendered him thoroughly conversant with its physiological action on the pulse. In 1867, Brunton published a paper in the Lancet with his observations on angina pectoris. Up to then, the standard remedy for angina was brandy, ether or chloroform.
At one instance, Brunton noted a 26-year old man who had been regularly admitted to the wards due to severe anginal pain every night. He had tried every remedy in vain, but Brunton asked the patient to stay one day longer and promised him that he would try one experiment and if he fails he would go out next day. Brunton applied 5 to 10 drops of amyl nitrite on a cloth and gave it to the patient to inhale. The effect took place within 30 to 60 seconds, the pain almost instantaneously disappeared. He also noted the nitrate tolerance during this course. But it was not until 1903 that the suggestion was made by Francois Franck that amyl nitrite was a coronary vasodilator. Brunton was then looking for compounds that had a slower but more lasting action than amyl nitrite and it was then he knew of the work of nitroglycerine performed by the homeopath Constantin Hering, 30 years earlier and started experimenting on this compound. But, Brunton hesitated to give nitroglycerine to his patients because of awful headache it caused. However, in 1878, Dr. Murrell, a London doctor, successfully treated an angina patient with nitroglycerine. Within 4 years, nitroglycerine was hailed as the remedy par excellence for angina pectoris. These experiences led to the inclusion of nitroglycerine in the British Pharmacopoeia. Over 100 years in clinical use, nitroglycerine is still pivotal in the management of anginal pain. Thanks to Brunton, Constantin, Murrell and others.
Marsh Neville, Marsh Alexander. A Short History Of Nitroglycerine And Nitric Oxide In Pharmacology And Physiology. Clin Exp Pharmacol Physiol. 2001 Dec 24;27(4):313–9.
Topiramate induced oral cleft is dose dependent
Topiramate is known to increase the risk of oral clefts when taken by pregnant women with epilepsy. However, it is unknown if lower doses confer the same risk. Researchers studied data on 1360101 mother-infant pairs, including 2425 pairs exposed to topiramate during the first trimester. They found that the risk of oral clefts was 4.1 per 1000 live births in the topiramate group compared with 1.1 per 1000 live births in the unexposed group (RR 2.90). Restricting the study to women with epilepsy, they found that the risk of oral clefts was 12.3 per 1000 infants born to mothers who took topiramate (RR 8.30). By contrast, in women taking topiramate for other indications, such as bipolar disorders, the risk of oral clefts was 2.1 per 1000 exposed infants (RR 1.45). Reporting in Neurology [online, 27 Dec 2017], the researchers said the findings indicated that larger doses of topiramate taken for epilepsy may confer a higher risk or oral clefts.
Hernandez-Diaz S, Huy-brechts KF, Desai RJ et al. Topiramate use early in pregnancy and the risk of oral clefts. Neurology 2018.
Salbutamol may delay pregnancy
Asthmatic women who only use short-acting treatment are more likely to have difficulty conceiving compared with women who rely on longer-acting medication to manage their condition, according to a research published in the European Respiratory Journal.
Researchers discovered that asthmatic women using short-acting beta-agonists took 20% longer to conceive than women on longer acting treatments, and were also 30% more likely to have taken longer than 12 months to get pregnant.
But they found that there was no difference in fertility between women using long-acting asthma treatments and non-asthmatic women.
The findings were based on an analysis of 5617 women from the UK, Australia, New Zealand and Ireland who had never given birth before. Some 1106 (19.7%) re-ported doctor-diagnosed asthma and of those, 656 (11.7%) were identified as current asthmatics and 450 (8%) were former asthmatics.
The researchers found that, com-pared with non-asthmatics, current asthmatics managed with SABAs had a 15% lower chance of conceiving per cycle (OR 0.85; 95% CI 0.75 - 0.96). There were no differences in the fertility of former asthmatics (OR 1.00; 95% CI 0.89 - 1.13) or current asthmatics using ICS with or without LABAs (OR 0.98; 95% CI 0.84 - 1.15).
Compared to non-asthmatics, subfertility, which was defined as taking longer than a year to conceive, increased among women using SABAs (OR 1.30; 95% CI 0.93 - 1.81) but not for women with former asthma (OR 0.89; 95% CI 0.62 - 1.28) or current asthma patients using ICS with or without LABAs (OR 1.08; 95% CI 0.69 - 1.71).
Although the exact mechanism is not known, the researchers suggested that asthma may reduce uterine blood supply or increase infiltration of inflammatory cells into the uterine mucosal layer, impairing implantation.
Grzeskowiak L, Smithers L, Grieger J et al. Asthma treatment impacts time to pregnancy: evidence from the international SCOPE study. Europ Resp J 2018; 51:1702035.
Source: CMC Pharmacy Bulletin, a publication of the Pharmacy Service (DISH), CMC, Vellore