Prevalence of Alzheimer's disease according to anticholinesterase drug usage from 2012 to 2017 in the state of Paraná, Brazil

Introduction: Alzheimer's disease (AD) is a public health problem in Brazil due to the growing number of older adults in this population. Knowing the prevalence of AD in the Paraná state is essential to improve patients’ quality of life. The objective of the study was to estimate AD prevalence in the state of Paraná, based on the prescription of anticholinesterases, from 2012 to 2017. Methods: Patients diagnosed with AD, aged 60 years or over, who used Brazil’s Unified Public Health System (SUS) and received AD medication from the Department of Pharmaceutical Assistance of the state of Paraná, from 2012 to 2017, were the target population of the present study. The medication data were collected from the Computerized system management and Monitoring of Exceptional Drugs (SISMEDEX), and the population’s data were collected from the Brazilian Institute of Geography and Statistics (IBGE). Results: The sample consisted of 52,687 patients, and the median prevalence of AD in the established period for the state was 642.6/100,000 inhabitants (0.64%). In all ages and macro-regions, women showed the highest prevalence rates. The median prevalence for women in the established period was 755.4/100,000 inhabitants (0.75%). Among men, the median prevalence was 510.2/100,000 inhabitants (0.51%). In the temporal analysis of prevalence, between 2012 and 2017, a reduction of 23% was found in the state rate. The prevalence rate of Paraná for AD is nine times lower than the Brazilian average. Conclusions: Paraná’s prevalence rate for AD is lower than the rates of Brazil and the world, suggesting that AD is underdiagnosed in most municipalities of this state.

ATORVASTATIN ADSORPTION STUDIES ON CHITOSANS IN AN in vitro PHARMACEUTICAL MODEL

During the pharmacological therapy of specific diseases, drugs are used which, with other preparations or foods, can create connections, in many cases changing or even blocking their action. On the other hand, the use of unsuitable polymers as excipients may result in drug-polymer incompatibilities. Interactions consisting mainly of the occurrence of the adsorption phenomenon and on the formation of complex bonds that reduce the effect of the drugs are of particular importance. The aim of the study was to investigate whether the active substance atorvastatin is incompatible with dietary supplements containing chitosan. The phenomenon of the adsorption of the drug was examined using a static model of a pharmaceutical gastrointestinal tract, in the concentration range generally ingested in a single dose. Measurement results of the amount of bound drug were used to determine the average percentage of adsorbed drug dose. The results of the study prove that the anticholinesterase drug is adsorbed on chitosan in the pH ranges used, and that the binding capacity depends on the chitosan variety, which indirectly affects the reaction of the environment. It was observed that the average size of sorption depending on the chitosan variety ranged from 38% to 86%. The fact that the lowest value of adsorption was at pH 6.4 can be explained by the chemical properties of chitosan, which shows a charge only at pH >6.7. Under such conditions, the phenomenon of electrostatic adsorption may occur in relation to the healing substances of weak acids. At a pH above 7.6, corresponding to the intestinal fluid-filled intestine, the mean sorption for the highest dose of chitosan was from 38–86%. The increase in the adsorbed amount of anticholinesterase drugs on the polymer along with the increase in pH from 7.6 to 8.0 can be explained by the chitosan swelling properties, which increase with an increase in the pH. As a result, the specific surface area of the polymer and its sorption capacity increase. Based on the above considerations, it can be concluded that there is an antagonistic interaction between the drug and the polymer studied, which involves the adsorption of a drug from this group on the polymer (chitosan) and a decrease in its bioavailability.

Atrio-ventricular Block Following Neostigmine-Glycopyrrolate Reversal in Non-heart Transplant Patients: Case Report

Neostigmine is the anticholinesterase drug most commonly used to reverse blockade or speed up recovery from neuromuscular blockade from nondepolarizing neuromuscular blocking drugs. Because of its cardiac muscarinic effects, prior or simultaneous administration of glycopyrrolate or atropine is usually recommended. There have been a few case reports of bradycardia, atrio-ventricular (AV) block, and cardiac arrest following neostigmine/glycopyrrolate administration to reverse neuromuscular block affecting several patients. In this report, we describe a case of 21-year-old with a history of seizure disorder and developmental delay that presented for dental surgery under general anesthesia and developed type I AV block following the simultaneous administration of neostigmine and glycopyrrolate to reverse a nondepolarizing neuromuscular block with rocuronium at the end of his surgery. We suggest that the chronic use of antiepileptic drugs in this patient in combination with neostigmine and glycopyrrolate lead to AV block in this patient. We also review similar cases reported in the literature and suggest an explanation for this observed phenomenon.

Mary Broadfoot Walker: 83 years since a historical discovery

ABSTRACT Mary Broadfoot Walker was a Scottish physician who, in 1935, described in great detail the effect of an anticholinesterase drug (physostigmine) on the signs and symptoms of myasthenia gravis. An original five-minutes movie is available online and the skepticism of her contemporary British medical doctors is understandable when the drastic effect of the treatment is shown in this movie. What Mary Walker taught us, more than eight decades ago, about myasthenia gravis continues to be the basis of a pharmacological diagnostic test and treatment of this disease.

Neuromidin Attenuates Neuropathic Pain in the Streptozocin-Induced Diabetes Model in Rats

Neuromidin Attenuates Neuropathic Pain in the Streptozocin-Induced Diabetes Model in Rats Diabetic neuropathy, which affects all peripheral nerves and may cause dramatic pain, is one of the most severe pathologies associated with hyperglycaemia, damage in the blood vessels, and inflammation in nerves. Anticonvulsants and antidepressants are still the most commonly used options to manage diabetic neuropathy. However, to improve clinical benefit in the treatment of diabetic neuropathies, as well as to minimize side effects, search for a new type of drugs to protect/treat neuropathic pain is still important. The aim of this study was to investigate neuromidin (ipidacrine, amiridin, NIK-247), an anticholinesterase drug of tetrahydroaminoacridine series, in the streptozocin (STZ)-induced diabetic neuropathic pain model in rats. Neuromidin was administered per os at daily doses 0.3, 1.0 and 3.0 mg/kg for ten days. The dynamics in the development of hyperalgesia (pain threshold) was measured by algesimeter for five weeks. The data obtained show that neuromidin considerably protects the development of peripheral neuropathic pain caused by STZ. The most active dose was the lowest—0.3 mg/kg. Neuromidin did not affect STZ-hyperglycemia, nor the weight gain in animal groups. Neuromidin per se at the doses 0.3 and 1.0 mg/kg showed a short-term analgesic activity. The cholinergic mechanism of neuromidin may be considered as essential in attenuating of diabetic neuropathic pain; other mechanisms remain to be elucidated.

Bites by coral snakes (Micrurus spp.) in Campinas, State of São Paulo, Southeastern Brazil

Coral snakes (Micrurus spp.) are the main representatives of the Elapidae in South America. However, bites by these snakes are uncommon. We retrospectively reviewed the data from 11 individuals bitten by coral snakes over a 20-year period; four were confirmed (snake brought for identification) and seven were highly suspected (neuromuscular manifestations) cases of elapid envenoming. The cases were classified as dry-bite (n = 1, caused by M. lemniscatus; did not receive antivenom), mild (n = 2, local manifestations with no acute myasthenic syndrome; M. frontalis and Micrurus spp.), moderate (n = 5, mild myasthenia) or severe (n = 3, important myasthenia; one of them caused by M. frontalis). The main clinical features upon admission were paresthesia (local, n = 9; generalized, n = 2), local pain (n = 8), palpebral ptosis (n = 8), weakness (n = 4) and inability to stand up (n = 3). No patient developed respiratory failure. Antivenom was used in ten cases, with mild early reactions occurring in three. An anticholinesterase drug was administered in the three severe cases, with a good response in two. No deaths were observed. Despite the high toxicity of coral snake venoms, the prognosis following envenoming is good. In serious bites by M. frontalis or M. lemniscatus, the venom of which acts postsynaptically, anticholinesterases may be useful as an ancillary measure if antivenom is unavailable, if there is a delay in obtaining a sufficient amount, or in those patients given the highest recommended doses of antivenom without improvement of the paralysis or with delayed recovery.