ANTI-INFLAMMATORIES AND ANALGESICS IN PAEDIATRIC DENTISTRY

Analgesics are used to reduce pain, which is the main symptom experienced in dental inflammatory pathologies. Painkillers are among the most used drugs in dentistry, along with anti-inflammatories and antibiotics. A lack of knowledge regarding well-defined prescription protocols has been observed. The aim of this study was to revise and update the prescription of anti-inflammatories and analgesics according to the latest guidelines. We performed electronic research of selected databases: PubMed, Google Scholar, AAPD, from 2010-2020, in order to identify the most frequent anti-inflammatories and analgesics used in paediatric dentistry. Approximately 25% of all adverse drug reactions are the consequences of treatments with anti-inflammatory drugs. This paper focuses on both the correct and wrong prescription of medication in paediatric dentistry, as well as on the short and long-term side-effects of this prescription.


BACKGROUND AND AIMS
The incidence of inflammatory pathologies has increased significantly over the past years, all over the world. The most simple inflammatory processes, up to the most complex diseases that affect multiple systems of the body, are treated, both in adults and children, with anti-inflammatory drugs [1].
Anti-inflammatory drugs are used to either prevent the inflammation, or to reduce it [2]. These synthetic drugs exert their effects through hormonal action, inhibiting the secretion of inflammatory enzymes, proteins and other factors involved in the inflammatory process. They can also promote the anti-inflammatory immune response. Depending on the presence or absence of steroids in their composition, anti-inflammatory drugs can be steroidal or non-steroidal [1].
Steroidal anti-inflammatory drugs were first synthesized to treat inflammatory processes. Their action is extremely strong and fast, the main mechanisms being: anti-inflammatory action (by inhibiting prostaglandin and LT synthesis, inhibiting cytokine production, decreasing the polymorphonuclear response) and immunosuppressive action, by decreasing the number of monocytes and lymphocytes [1].
In the past few years, there was an attempt to limit the use of steroidal anti-inflammatory drugs, due to important side effects such as: a weakened immune system, weight gain, hormonal disorders, muscle aches, nausea, vomiting, abdominal cramps and dilated pupils [1].
Non-steroidal anti-inflammatory drugs are the most commonly prescribed drugs worldwide, for both adults and children [6]. More than 30 million people are using prescribed non-steroidal anti-inflammatory drugs daily [9]. Their widespread use is due to both anti-inflammatory and antipyretic effects [6].

METHODS
The sites accessed for this article were represented by PubMed, Google Scholar, AAPD. We've searched for articles such as: review, clinical protocols, cross-sectional studies, clinical studies, laboratory studies. Other criteria: articles were searched in English and published / revised in the last 10 years (2010-2020).
The keywords used to search the articles were: anti-inflammatory drugs, medication in pediatrics, drugs used in inflammation, steroidal anti-inflammatory drugs, non-steroidal anti-inflammatory drugs, NSAIDs in pediatrics, pain, paracetamol.
Out of a total of 98 articles found, 20 met the criteria of our chosen topic. The other studies were rejected because they lacked in relevance and/or specificity regarding this theme.

INDICATIONS AND CONTRAINDICATIONS
Painkillers are among the most used drugs in dentistry, along with antibiotics. Paracetamol is currently the analgesic of choice worldwide; however, it is marketed in such way that it is not recommended to use it for more than 3 days without consulting a specialist, despite being used in chronic diseases as well. Nevertheless, it is still recommended as a first-line treatment in countries such as the United Kingdom [10].
The selection of the right analgesic is recommended to be tailored to the patient and the specific dental /surgical procedure, taking into consideration a number of factors, such as the complexity and duration of the procedure, psychological factors, and the patient's medical history. Therefore, besides the complexity of the performed medical act, various pathologies such as liver diseases, kidney diseases, haematological disorders, are important factors when we are choosing the proper analgesic (table 1) [11]. The pain management plan is recommended to take into account the patient's previous experiences with medical acts, post-operative treatment, medication allergies and intolerances, cognitive status, preferences for treatment and treatment goals (table 2) [11].
In a study published in 2019, Monisha et al. conclude that dental practitioners are aware that medications should be prescribed depending on the patient's clinical condition. Even so, prescriptions are filled out based on the systemic compli-cations that may occur as a result of certain treatments. Out of a total of 100 dentists, 63% prescribed the medication according to the diagnosis and not the symptomatology itself, while clearly knowing the indications and contraindications of prescribing analgesics and anti-inflammatory drugs. However, all the subjects concluded that there is a need to create awareness programs for a better understanding of medication [12].
There is also a need for understanding the effects of delayed treatment with suboptimal doses of analgesics (table 3) [4].
Studies show that children who underwent dental extractions and those who experienced 12 or more dental interventions will undergo postoperative pain [14]. Unfortunately, when it comes to children, the assessment of pain is subjective. Because of that, various methods have been created that can help with the measurement of the intensity of pain in children, such as FACES pain scale and Wong-Baker FACES scale [8].
When we are doing the anamnesis, besides the severity of pain, it's very important to locate the pain, when it started, how it started, the pattern of the pain, the factors that intensify or ease it, the previous treatments and their effects [11].
Non-steroidal anti-inflammatory drugs are used for various pathologies, in different doses. Accord-ing to The National Institute of Health and Care Excellence (NICE), the treatment with non-steroidal anti-inflammatory drugs for children should be as short as possible, with the lowest possible dosage, in order to avoid and control the side effects [7,15]. To be able to use the lowest possible dosage of non-steroidal anti-inflammatory drugs, WHO recommends combining them with Paracetamol [14]. Therefore, Paracetamol can be used as a single treatment [11], or in combination with anti-inflammatory medication to treat a variety of pediatric conditions [7,14].
Due to the fact that it is very well tolerated by children, Ibuprofen is the only drug in the class of non-steroidal anti-inflammatories that has been approved to treat children under 3 years old [15]. It is also the most widely-used anti-inflammatory drug in paediatric dentistry [2]. Numerous studies have shown the efficacy of Ibuprofen in paediatric pathologies, as well as its high tolerance compared to other non-steroidal anti-inflammatory drugs [15].
In essence, both Ibuprofen and Paracetamol are considered to be equally safe and have a similar degree of tolerance in pediatric pathologies. Kanabar et al. showed in a meta-analysis of 19 studies that there were no significant differences between the two drugs in terms of the incidence of side effects in children [4]. 1,2-2 g/day [2] Jóźwiak-Bebenista M, Nowak JZ Acetaminophen 65 mg/kg/day [2] (maximum 75 mg/kg/ day) [8] 325-650 mg/day [2] or 1000 mg, 3-4 times per day [8] 4 g/day [8]

SIDE EFFECTS
Despite many benefits, there is documented evidence regarding the potential side effects, especially the gastrointestinal ones [6].
Non-steroidal anti-inflammatory drugs were originally created as an alternative to steroidal anti-inflammatory drugs and their numerous side effects. Nevertheless, the NSAIDs' action can affect the cardiovascular, respiratory and central nervous systems, causing adverse reactions such as headaches, tinnitus, irritability, hypertension, nausea, vomiting, hypersensitivity reactions (asthma, angioedema, rash). According to The World Health Organization (WHO), the most common side effects children's experience are: diarrhoea, tinnitus, nausea, headache, constipation, rash, flatulence, abdominal pain, dyspepsia [7,14].
Approximately 25% of all adverse drug reactions are the consequences of treatments with anti-inflammatory drugs [9]. Local manifestations of toxicity in the gastrointestinal tract are represented by mucosal lesions, and systemically, by reducing the mucosa of prostaglandins derived from COX-1 [16]. Most commonly, side effects associated with non-steroidal anti-inflammatory drugs are located in the upper and lower gastrointestinal tract. In addition to lesions in the gastric mucosa, damage may also occur in the mucosa of the small intestine and colon [17]. Among the many complications that can occur are: gastric ulcer, bleeding and intestinal perforation [5,15]. Annually, there are over 100,000 people hospitalized in the United States, and between 7,000 and 10,000 deaths from these complications, most of those patients being in high-risk categories [6].
When it comes to antipyretics, in recent years, the concern about long-term side effects of Paracetamol increased, at first when it came to patients with hypertension, and later in patients with other conditions as well (table 4).
There is clear evidence of an increased risk of gastrointestinal bleeding and of a slight increase in systolic blood pressure (approximately 4 mmHg) in patients receiving acetaminophen. However, the risk of these side effects is dose dependent [10].

SIDE EFFECTS IN CHILDREN
Side effects rarely occur in children and there are limitations regarding the knowledge of the level of their manifestation. Most of the known data are based only on case reports and studies conducted in groups with a small number of patients [17]. In line with these observation, individual assessment remains the simplest tool to control and prevent unwanted side-effects.
A British study conducted for over 10 years illustrated the association of nonsteroidal anti-inflammatory drugs with the death of 12 children out of a total of 390 deaths (0.03%). In 4 of these cases, aspirin is considered the causal factor, children (12-14 years) being diagnosed with Reye's syndrome. Another child who was given ibuprofen developed cerebral oedema, which could also could have been caused by Reye's syndrome. Another 4 children underwent gastrointestinal perforations, in 2 of the cases ibuprofens being considered the causal factor [18].
In another study that was observing children who suffer from rheumatoid arthritis and take a long-term treatment with non-steroidal antiinflammatory drugs, over 75% of patients experienced abdominal pain, gastritis or ulcer [17].
Grimaldi-Bensouda et al. report in a study that 83 of 177 children (46.9%) with upper gastrointestinal bleeding have previously taken non-steroidal anti-inflammatory drugs at least once [19].
There is strong evidence that proves the link between non-steroidal anti-inflammatory drugs and gastrointestinal complications in adults, but much  [20].
Overall, despite the widespread use of ibuprofen and paracetamol, thankfully the rate of severe side effects in children is low. Both drugs are associated with rare specific side effects, which are generally difficult to detect in small studies; these are easier to quantify in larger research groups [4].

CONCLUSIONS
More than 30 million people are using prescribed non-steroidal anti-inflammatory drugs daily. Ibuprofen is considered by the World Health Organisation to be the only safe enough anti-inflammatory to be prescribed to children under 3 years old. However, in the case of short-term treatments (less than 7 days), such as those in pedodontics and dentistry in general, both ibuprofen and paracetamol are considered safe and with a similar tolerance. The continuous education and awareness programs are necessary, for both doctors and general population.