Safety of paracetamol during pregnancy: literature review

Paracetamol (acetaminophen) is the drug of choice in pregnant women as an antipyretic and analgesic agent for various clinical conditions. However, long-term paracetamol administration during pregnancy was found to be associated with disorders in children, such as attention deficit hyperactivity disorder (RR = 1.32, 95% CI 1.18–1.45, I2 = 61%); autism spectrum disorders (RR = 1.23, 95% CI 1.13–1.32, I2 = 17%); hyperactivity disorder (RR = 1.24, 95% CI 1.02–1.46, I2 = 95%), and behavioral disorders (RR = 1.28, 95% CI 1.05–1.52, I2 = 94%). Studies conducted so far failed to identify the effect of paracetamol dose in different trimesters of pregnancy on the development of long-term functional disorders of the central nervous system in children. Further studies are needed to assess the importance of social factors and the environment and their contribution to the development of functional disorders of the central nervous system in children. Key words: acetaminophen, safety, pregnancy, neuropsychiatric development of children, paracetamol

Dissolution Behaviours of Acetaminophen and Ibuprofen Tablet Influenced By L–HPC 21, 22, and Sodium Starch Glycolate as Disintegrant

The dissolution of tablets is one of a drug absorption determinant. Disintegrant agent has play an important role on determining the dissolution of tablets. In this experiment, the dissolution behaviours of Acetaminophen and Ibuprofen Tablet was studied using various disintegrant agent such as Low substituted – Hydroxypropyl Cellulose (L–HPC) 21, L–HPC 22 and Sodium Starch Glycolate (SSG) as comparator. Those disintegrant agents were used at three concentration (6%, 7% and 8%) for every tablets formula. Tablets were made by wet granulation method and pressed using single punch 13 mm flat E. Korsch machine. Evaluation of each tablets quality were conducted include for uniformity of weight and size (diameter and thickness), hardness, friability, disintegration time and dissolution. Physically standards from tablets were in good condition, the standards of the weight and thickness uniformity, hardness and friability met the requirement. The dissolution profile on Acetaminophen Tablets showed that only tablet with 6 % L–HPC 21 did not meet the requirement of FI V (Q = 80%, 30 minutes), but on Ibuprofen Tablets where met the requirement of FI V (Q = 80%, 60 minutes) only tablet with 8% L– HPC 21, 7% and 8% SSG. The conclusion of the study was the L–HPC has more disintegrant character at hydrophilic active ingredients. Key words: Acetaminophen Tablet, Ibuprofen Tablet, SSG, L-HPC 21 and 22, Dissolution Profile

Liver Failure in the Critical Care Setting

Acute liver failure (ALF) can be challenging to manage due to the effect of liver failure on other organs and the severity of illness that ensues. Both the practicing surgeon and the intensivist should be aware of the manifestations, workup, and management implications as ALF is not uncommon to many intensive care settings. ALF precipitates a severe multiorgan dysfunction syndrome in a majority of cases, with high rates of complications and an elevated risk of death. Management requires a systemic approach in addition to the collaboration of a multidisciplinary team with an emphasis on early recognition, prompt management of complications, and timely transfer to a transplant center. In the absence of spontaneous recovery, transplantation is the only definitive management option and may not always be feasible or immediately available. The continuing search to develop alternatives is essential. Key words: acetaminophen, acute liver failure, cerebral edema, coagulopathy, hepatitis, jaundice, N-acetylcysteine, transplantation

Acute Liver Failure

Acute liver failure (ALF) can be challenging to manage due to the effect of liver failure on other organs and the severity of illness that ensues. Both the practicing surgeon and the intensivist should be aware of the manifestations, workup, and management implications as ALF is not uncommon to many intensive care settings. ALF precipitates a severe multiorgan dysfunction syndrome in a majority of cases, with high rates of complications and an elevated risk of death. Management requires a systemic approach in addition to the collaboration of a multidisciplinary team with an emphasis on early recognition, prompt management of complications, and timely transfer to a transplant center. In the absence of spontaneous recovery, transplantation is the only definitive management option and may not always be feasible or immediately available. The continuing search to develop alternatives is essential. Key words: acetaminophen, acute liver failure, cerebral edema, coagulopathy, hepatitis, jaundice, N-acetylcysteine, transplantation

Potential Analgesic Mechanisms of Acetaminophen

Despite nearing the end of the decade of pain research, the analgesic mechanisms of one of the most widely used and popular analgesics remains uncertain. Acetaminophen (APAP) (paracetamol [PARA]) has been used clinically for over a half of a century and although clinicians seem to be comfortable with its benefits, risks, and limitations, they still remain in the dark as to precisely what is providing its pain relief. What does seem clearer is that the predominant mechanisms of APAP’s analgesic effects are in the central nervous system (CNS). Although, which central effects are largely responsible for APAP’s effects on pain continue to be uncertain. Perhaps, the most accepted theory is that of APAP’s positive effects on the serotonergic descending inhibitory pathways. However, interactions with opioidergic systems, eicosanoid systems, and/or nitric oxide containing pathways may be involved as well. Furthermore, endocannabinoid signaling may play a role in APAP’s activation of the serotonergic descending inhibitory pathways. A greater understanding of APAP’s analgesic mechanisms may promote optimal utilization of analgesic polypharmacy. Key words: Acetaminophen (APAP), paracetamol (PARA), pain, analgesia, mechanisms of action, serotonin, opioids, endocannabinoids