ABSTRACT
Background: Calcium channel blockers (CCBs) are popular medicines used to treat hypertension, tachyarrhythmias or angina during pregnancy. Lack of adequate safety data has however created an uncertainty in the use of CCBs in pregnancy. Nifedipine has been reportedly associated with a variety of embryotoxic and fetotoxic effects in animals. Therefore, this study was undertaken to establish whether or not the commonly used CCBs (nifedipine and amlodipine) would produce teratogenic effects in rats.Methods: Twenty pregnant rats were randomly assigned to each of the treatment and control groups. Nifedipine and amlodipine were used in three dose levels of 5, 10, 20 mg/kg and 0.5, 1, 2 mg/kg body weight respectively to test its teratogenic effects. The maximum dose of the test drugs used in our study was ten times the maximum recommended human dose. The drugs were administered to the pregnant rats using nasogastric tubes from day 6 through day 15 of pregnancy. The number of live births, stillbirths, litter sizes, crown-rump lengths, birth weights and gross abnormalities of the pups delivered were observed and recorded. Skeletal changes and soft tissue changes were also observed in the pups delivered to treated pregnant rats.Results: It was found that nifedipine and amlodipine did not produce any teratogenic effects in rats at doses 2.5 to 10 times the recommended human dose. None of the pups showed any gross morphological, skeletal or visceral defects.Conclusions: Nifedipine and amlodipine appear to be safe during pregnancy in therapeutic doses.
ABSTRACT
Migraine is ranked by the World Health Organization as the world’s second leading cause of disability. The current state of knowledge suggests that migraine is a neuronal process involving activation and sensitization of the trigeminal nociceptors and the trigeminocervical complex, as well as cortical spreading depression and abnormal brainstem activity. The present non vascular etiological basis has opened a new horizon in the treatment of acute migraine targeting the trigeminal pathways. Lasmiditan, a highly selective 5-HT1F receptor agonist, acts on the trigeminal system without causing vasoconstriction because of its low a?nity for 5-HT1B receptors. The compound belongs to a new class of drugs “ditans” and its mechanism of action is neuronal without evidence of vasoactive effects as seen with triptans. It lowers plasma protein extravasation decreasing the neurogenic inflammation of the dura and suppress neuronal firing within the trigeminal nucleus caudalis. Also, 5HT1F agonists have shown to decrease c-fos activity within trigeminal nucleus thereby reducing the level of synaptic activation. The onset of action of lasmiditan is fast, shows rapid absorption, oral bioavailability of 40% and linear pharmacokinetics. Most common adverse reactions seen are dizziness, paresthesia, somnolence, nausea, fatigue and lethargy with dizziness being the most recurrently reported adverse event. Clinical trials for lasmiditan to date have been positive, and maiden results suggest that lasmiditan may be a new safe and effective option for acute migraine treatment, especially for patients refractory to or unable to tolerate triptans, and/or for patients with pre-existing cardiovascular disease. With Eli Lilly and Co. having already applied for US FDA approval in Nov 2018, lasmiditan may soon be a new addition to the mounting armoury of drugs against migraine.
ABSTRACT
Background: Paracetamol is used for symptomatic treatment of fever and pain with isoniazid and other anti-tubercular drugs in patients of tuberculosis. Literature has conflicting data regarding their interaction. Some studies show that isoniazid increases oxidative metabolism of paracetamol whereas some other suggest that isoniazid has an inhibitory effect. The present study was conducted to find out the possible interaction between paracetamol and isoniazid. Methods: The study was undertaken on Wistar strain of Albino rats. Group I and Group II animals were treated with paracetamol (500 mg/kg) and the combination of paracetamol (500 mg/kg) and isoniazid (30 mg/kg) respectively for 2 months. Blood samples were taken before and during the study for biochemical and histopathological studies of liver and renal functions and plasma paracetamol concentration was also evaluated. Results: Isoniazid decreased the plasma paracetamol concentration without affecting its analgesic activity. However, the hepatotoxic and nephrotoxic effects of paracetamol were found to be further aggravated by isoniazid co-administration. Conclusion: Isoniazid potentiates the hepatotoxic and nephrotoxic effects of paracetamol possibly due to hepatic enzyme induction by isoniazid.