Several components are used to aid in the prevention of muscle cramps. These include:

• Magnesium. An essential mineral that helps regulate muscle contraction and can prevent cramps.
• Potassium. Important for muscle and nerve function, its deficiency can lead to muscle cramps.
• Calcium. Crucial for muscle contraction, adequate intake can help prevent cramps.
• Vitamin E. Known for its antioxidant properties, it can help reduce muscle cramps.
• Water. Maintaining proper hydration is crucial for preventing cramps, as dehydration can cause electrolyte imbalances.
• Sodium. An important electrolyte for fluid balance and muscle function, its deficiency can cause cramps.
• Vitamin D. Helps with calcium absorption and can contribute to muscle health.
• Omega-3 Fatty Acids. Have anti-inflammatory properties that can help reduce the risk of muscle cramps.

Components that may contribute to or exacerbate muscle cramps.

• Dehydration. Inadequate fluid intake can lead to muscle cramps.
• Electrolyte imbalances. Low levels of potassium, calcium, or magnesium can cause cramps.
• Excess sodium. High sodium intake can disrupt water and electrolyte balance.
• Caffeine. Excessive consumption can lead to dehydration and muscle cramps.
• Alcohol. Can cause dehydration and electrolyte imbalances..
• Excessive physical exercise. Overuse of muscles can lead to cramps.
• Vitamin D deficiency. Can affect calcium absorption and muscle function.

Studies

Miller TM, Layzer RB. Muscle cramps. Muscle Nerve. 2005 Oct;32(4):431-42. doi: 10.1002/mus.20341. PMID: 15902691.

Abstract. Muscle cramps are a common problem characterized by a sudden, painful, involuntary contraction of muscle. These true cramps, which originate from peripheral nerves, may be distinguished from other muscle pain or spasm. Medical history, physical examination, and a limited laboratory screen help to determine the various causes of muscle cramps. Despite the "benign" nature of cramps, many patients find the symptom very uncomfortable. Treatment options are guided both by experience and by a limited number of therapeutic trials. Quinine sulfate is an effective medication, but the side-effect profile is worrisome, and other membrane-stabilizing drugs are probably just as effective. Patients will benefit from further studies to better define the pathophysiology of muscle cramps and to find more effective medications with fewer side-effects.

Katzberg HD. Neurogenic muscle cramps. J Neurol. 2015 Aug;262(8):1814-21. doi: 10.1007/s00415-015-7659-x. 

Abstract. Muscle cramps are sustained, painful contractions of muscle and are prevalent in patients with and without medical conditions. The objective of this review is to present updates on the mechanism, investigation and treatment of neurogenic muscle cramps. PubMed and Embase databases were queried between January 1980 and July 2014 for English-language human studies. The American Academy of Neurology classification of studies (classes I-IV) was used to assess levels of evidence. Mechanical disruption, ephaptic transmission, disruption of sensory afferents and persistent inward currents have been implicated in the pathogenesis of neurogenic cramps. Investigations are directed toward identifying physiological triggers or medical conditions predisposing to cramps. Although cramps can be self-limiting, disabling or sustained muscle cramps should prompt investigation for underlying medical conditions. Lifestyle modifications, treatment of underlying conditions, stretching, B-complex vitamins, diltiezam, mexiletine, carbamazepine, tetrahydrocannabinoid, leveteracitam and quinine sulfate have shown evidence for treatment.

Maughan RJ, Shirreffs SM. Muscle Cramping During Exercise: Causes, Solutions, and Questions Remaining. Sports Med. 2019 Dec;49(Suppl 2):115-124. doi: 10.1007/s40279-019-01162-1. 

Abstract. Muscle cramp is a temporary but intense and painful involuntary contraction of skeletal muscle that can occur in many different situations. The causes of, and cures for, the cramps that occur during or soon after exercise remain uncertain, although there is evidence that some cases may be associated with disturbances of water and salt balance, while others appear to involve sustained abnormal spinal reflex activity secondary to fatigue of the affected muscles. Evidence in favour of a role for dyshydration comes largely from medical records obtained in large industrial settings, although it is supported by one large-scale intervention trial and by field trials involving small numbers of athletes. Cramp is notoriously unpredictable, making laboratory studies difficult, but experimental models involving electrical stimulation or intense voluntary contractions of small muscles held in a shortened position can induce cramp in many, although not all, individuals. These studies show that dehydration has no effect on the stimulation frequency required to initiate cramping and confirm a role for spinal pathways, but their relevance to the spontaneous cramps that occur during exercise is questionable. There is a long history of folk remedies for treatment or prevention of cramps; some may reduce the likelihood of some forms of cramping and reduce its intensity and duration, but none are consistently effective. It seems likely that there are different types of cramp that are initiated by different mechanisms; if this is the case, the search for a single strategy for prevention or treatment is unlikely to succeed.

Stephens HE, Joyce NC, Oskarsson B. National Study of Muscle Cramps in ALS in the USA. Amyotroph Lateral Scler Frontotemporal Degener. 2017 Feb;18(1-2):32-36. doi: 10.1080/21678421.2016.1245755. Epub 2016 Dec 15. Erratum in: Amyotroph Lateral Scler Frontotemporal Degener. 2017 Aug;18(5-6):470. 

Abstract. The objective of this study was to describe muscle cramps in an US sample of amyotrophic lateral sclerosis (ALS) patients. Utilizing an anonymous web based questionnaire we queried ALS patients regarding the severity, frequency, time-course, treatment of muscle cramps and their relationship to pain. The survey had 282 respondents with 92% reporting that they had cramps. For 20% of the sample, cramps were stated to be the presenting ALS symptom. Cramp severity was rated at a mean of 5.2/10 and the mean cramp frequency was 5.3 cramps per day. Cramp intensity and frequency did not correlate with duration or severity of ALS. Pain as measured with the Patient Reported Outcome Measurement Information System (PROMIS) pain scales was not statistically different from the US general population. Cramp severity and frequency significantly and positively correlated with the PROMIS pain scales. Patients with more severe cramps were more likely to use prescription medications for their cramps compared to patients with milder symptoms. Treatments directed at cramps were tried by 57%. In conclusion, cramps are a common symptom in ALS and it does not correlate with disease duration or severity. The severity of cramps is on average moderate and many patients try treatments.

Maquirriain J, Merello M. The athlete with muscular cramps: clinical approach. J Am Acad Orthop Surg. 2007 Jul;15(7):425-31. doi: 10.5435/00124635-200707000-00007. 

Abstract. Muscle cramps are involuntary, painful, spasmodic contractions of the skeletal muscle. Although cramps are a common clinical complaint, their etiology and management have not been well established. Exercise-associated muscle cramps occur during or immediately following exercise, and they are associated with muscular fatigue and shortened muscle contraction. The main challenges for treating physicians are to identify whether the complaint represents a true muscle cramp as well as to rule out the presence of an underlying serious clinical condition. Muscle cramps may be a symptom of any of several conditions, including radiculopathies, Parkinson's disease, hypothyroidism, diabetes mellitus, vascular problems, electrolyte disorders, and metabolic myopathies. Cramps also may occur as a side effect of certain drugs (eg, lipid-lowering agents, antihypertensives, beta-agonists, insulin, oral contraceptives, alcohol). Most athletes who experience exercise-associated muscle cramps are healthy individuals without systemic illness. Therapy should focus on preventing premature fatigue by means of appropriate nutrition and adequate training.

Schwellnus MP. Muscle cramping in the marathon : aetiology and risk factors. Sports Med. 2007;37(4-5):364-7. doi: 10.2165/00007256-200737040-00023.

Abstract. Skeletal muscle cramps are commonly encountered in marathon runners by medical staff. However, the aetiology, and therefore management, of this condition is not well understood. Exercise-associated muscle cramping (EAMC) is defined as an involuntary, painful contraction of skeletal muscle during or immediately after exercise. In early anecdotal reports, cramps were associated with profuse sweating, together with changes in serum electrolyte concentrations. No mechanism explains how such imbalances in serum electrolytes result in localised muscle cramping. The 'muscle fatigue' hypothesis suggests that EAMC is the result of an abnormality of neuromuscular control at the spinal level in response to fatiguing exercise and is based on evidence from epidemiological studies, animal experimental data on spinal reflex activity during fatigue and electromyogram data recorded during bouts of acute cramping after fatiguing exercise. The development of premature muscle fatigue appears to explain the onset of EAMC.

Hensley JG. Leg cramps and restless legs syndrome during pregnancy. J Midwifery Womens Health. 2009 May-Jun;54(3):211-8. doi: 10.1016/j.jmwh.2009.01.003.

Abstract. Sleep disturbance during pregnancy can result in excessive daytime sleepiness, diminished daytime performance, inability to concentrate, irritability, and the potential for an increased length of labor and increased risk of operative birth. Sleep disturbance may be the result of a sleep disorder, such as leg cramps, a common yet benign disorder, or restless legs syndrome, a sensorimotor disorder. Both disrupt sleep, are distressing to the pregnant woman, and mimic one another and other serious disorders. During pregnancy, up to 30% of women can be affected by leg cramps, and up to 26% can be affected by restless legs syndrome.

Several components are used to aid in oral hygiene and anti-plaque prevention. These include:

• Chlorhexidine. A powerful antiseptic used in various oral hygiene products, such as mouthwashes and gels. Chlorhexidine is effective in reducing bacterial plaque and preventing gingivitis. It is known for its ability to adhere to oral surfaces and provide prolonged antibacterial action.
• Lysozyme. A protein with antibacterial properties, naturally found in saliva, breast milk, and other body fluids. In the context of oral hygiene, lysozyme helps reduce harmful bacteria and can contribute to maintaining a healthy balance of oral flora (2).
• Sesame Seed Oil (Sesamum indicum seed oil). Extracted from sesame seeds, this oil is known for its antibacterial and anti-inflammatory properties. It has been used in the practice of oil pulling, which helps reduce plaque and improve oral health. Sesame seed oil can also help strengthen gums and reduce dryness in the mouth (3).
• Cetylpyridinium chloride (CPC). An antiseptic that reduces plaque and tartar, as well as combats bacteria that cause bad breath (4).
• Peppermint essential oil ozone-enhancing agent in the control of microorganisms causing oral diseases in medicine (5).
• Alexidine. An effective antiseptic against a wide range of microorganisms. Alexidine is similar to chlorhexidine but with a lesser tendency to cause staining on teeth. It is used in some mouthwashes and oral hygiene products for its antibacterial action.
• Delmopinol. This compound helps prevent the formation of plaque and tartar. It works by interfering with the formation of bacterial biofilm on the surface of the teeth, thereby facilitating the removal of plaque during brushing. Delmopinol is often found in mouthwashes.
• Hexetidine. An oral antiseptic used to treat various mouth conditions, such as gingivitis, mouth ulcers, and bad breath. Hexetidine has antibacterial and antifungal properties and is effective in reducing plaque and improving oral health.

The most effective components according to the scientific literature are in green.

Several components or factors can contribute to or exacerbate plaque formation and gingivitis. These include:

• Poor oral hygiene. Failure to regularly remove plaque and tartar through brushing and flossing can lead to plaque buildup and the development of gingivitis.
• Diet high in sugars and carbohydrates. Sugars and carbohydrates can be metabolized by mouth bacteria, producing acids that promote plaque formation.

• Smoking and tobacco use. Smoking can compromise gum health and increase the risk of gingivitis and periodontal diseases.
• Hormonal changes. Hormonal fluctuations, such as those during pregnancy or puberty, can make gums more susceptible to inflammation.
• Systemic diseases. Conditions like diabetes can affect gum health and increase the risk of gingivitis.
• Medications. Some medications can impact oral health, causing dry mouth or promoting excessive growth of gum tissue.
• Genetics. Genetic predisposition can play a role in susceptibility to gingivitis and periodontal diseases.
• Stress. Stress can negatively affect the immune system and increase the risk of gum problems.

References_____________________________________________________________________

(1) König J, Storcks V, Kocher T, Bössmann K, Plagmann HC. Anti-plaque effect of tempered 0.2% chlorhexidine rinse: an in vivo study. J Clin Periodontol. 2002 Mar;29(3):207-10. doi: 10.1034/j.1600-051x.2002.290304.x. PMID: 11940138.

Abstract. Objectives: The aim of this in vivo study was to compare the anti-plaque effect of warm and cold chlorhexidine gluconate irrigation on matured human plaque. Methods: In a split-mouth design, the antibacterial effect of 47 degrees C "warm" 0.2% chlorhexidine solution was compared with that of 18 degrees C "cold" rinse at the same concentration on newly-formed supragingival plaque that had been left undisturbed for 72 h. Before and 1 h after a 1-min rinse procedure, plaque was sampled from 10 test persons and vitality determined using vital fluorescence technique. Results: Cold and warm 0.2% chlorhexidine solution reduced plaque vitality significantly from 99.63% to 77.81% (p=0.014) and from 98.98% to 51.77% (p<0.001), respectively. Rinsing with warm chlorhexidine solution reduced plaque vitality to a significantly greater degree (p=0.003) than did cold chlorhexidine. Conclusion: In this study, warm 0.2% chlorhexidine rinse showed a significantly more intensive anti-plaque effect than cold chlorhexidine solution at the same concentration.

(2) Golac-Guzina, N., Novaković, Z., Sarajlić, Z., Šukalo, A., Džananović, J., Glamočlija, U., Kapo, B., Čordalija, V. and Mehić, M., 2019. Comparative study of the efficacy of the lysozyme, benzydamine and chlorhexidine oral spray in the treatment of acute tonsillopharyngitis-results of a pilot study. Acta Medica Academica, 48(2), pp.140-146.

Abstract. Objective. Lysozyme is a natural antimicrobial and immunomodullatory enzyme, which is produced as a host response to infectious agents. The objective of this study was to compare the efficacy and safety of lysozyme-based versus benzydamine and chlorhexidine-based oral spray in patients with an acute tonsillopharyngitis associaated with a common cold. Patients and Methods. A prospective two-arm pilot study (lysozyme/cetylpyridinium/lidocaine spray versus: benzydamine spray—arm 1; chlorhexidine/lidocaine spray—arm 2) was conducted in the primary health care unit. Efficacy was evaluated by the patient’s self-assessment of pain, difficulty in swallowing and the throat swelling, by using the visual analog scale (VAS) at baseline and three follow-up visits. Safety was evaluated by the assessment of the frequency and severity of adverse effects. Results. Lysozyme-based spray reduced pain faster than benzydamine-based spray and slower than chlorhexidine-based spray. Lysozyme-based and chlorhexidine-based sprays similarly reduced difficulty in swallowing, but were faster than benzydamine-based spray. Similar effects on the reduction of throat swelling were seen in all treated groups. All tested products showed proper safety and were well tolerated, with no serious adverse events reported. Conclusions. The lysozyme-based oral spray was shown to be effective and safe in the reduction of pain, difficulty in swallowing and throat swelling in patients with acute tonsillopharyngitis associated with a common cold. Lysozyme-based oral spray (containing natural compound with advantages of influencing immune system and preventing recurrences) had similar activity to benzydamine and chlorhexidine-based oral antiseptic sprays. 

(3) Chandraprakash, R., Shivamurthy, R., Rangaraju, V. M., & Babu, H. M. Evaluation of Cocos nucifera and Sesamum indicum in comparison with Chlorhexidine on gingivitis-A double blind Clinico-Immunological study. International Journal of Ayurvedic Medicine, 12(3), 618-622.

Abstract. Background: Myriad of synthetic products has been used in chemical plaque control. There is a constant search for cost effective herbal products with minimal adverse effect to substitute synthetic compounds. The objective of this study was to evaluate the anti-inflammatory properties of Cocos nucifera and Sesamum indicum and compare their effect with commercially available chlorhexidine on gingivitis. Methods: In this double blind, randomized, control clinical trial, a total of 45 samples from patients aged between 18 to 35 years reporting to the institution, diagnosed with gingivitis were selected and randomly divided into Group-A (Scaling + Cocos Nuciferamouthwash), Group-B (Scaling + Sesamum Indicum mouthwash) and Group C (Scaling + Chlorhexidine mouthwash). Clinical (Plaque index, Gingival index and Sulcus bleeding index), and Immunological (Interleukin-6) parameters were assessed at baseline and 45th day following scaling. Saliva samples were collected and stored at -200C till they were subjected to enzyme-linked immunosorbent assay (ELISA) analysis. Inferential statistics done were analysis of variance, paired t test, post hock Scheffe test and Chi- square test by using SPSS software (22.0). Results: In Clinical parameters, group B (p˂0.001) showed statistical significant reduction compared to group A and group C. In Immunological parameter group A (p˂0.001) showed statistical significant reduction in Interleukin-6 compared to group B and group C (p=0.126 & p=0.196 respectively). Conclusion: Cocos nucifera and Sesamum indicum mouth washes effectively decreased plaque formation and could be used as an adjunct to scaling in treating plaque induced gingivitis. 

(4) Van der Weijden FA, Van der Sluijs E, Ciancio SG, Slot DE. Can Chemical Mouthwash Agents Achieve Plaque/Gingivitis Control? Dent Clin North Am. 2015 Oct;59(4):799-829. doi: 10.1016/j.cden.2015.06.002.

Abstract. Also note that structured abstracts are not allowed per journal style: What is the effect of a mouthwash containing various active chemical ingredients on plaque control and managing gingivitis in adults based on evidence gathered from existing systematic reviews? The summarized evidence suggests that mouthwashes containing chlorhexidine(CHX) and essential oils (EO) had a large effect supported by a strong body of evidence. Also there was strong evidence for a moderate effect of cetylpyridinium chloride(CPC). Evidence suggests that a CHX mouthwash is the first choice, the most reliable alternative is EO. No difference between CHX and EO with respect to gingivitis was observed.

(5) Floare AD, Dumitrescu R, Alexa VT, Balean O, Szuhanek C, Obistioiu D, Cocan I, Neacsu AG, Popescu I, Fratila AD, Galuscan A. Enhancing the Antimicrobial Effect of Ozone with Mentha piperita Essential Oil. Molecules. 2023 Feb 21;28(5):2032. doi: 10.3390/molecules28052032. 

Abstract. This study aimed to obtain and analyse Mentha piperita essential oil (MpEO) for the prospect of being used as an enhancement agent for the antimicrobial potential of ozone against gram-positive and gram-negative bacteria and fungi. The research was done for different exposure times, and it gained time–dose relationships and time–effect correlations. Mentha piperita (Mp) essential oil (MpEO) was obtained via hydrodistillation and further analysed by using GC-MS. The broth microdilution assay was used to determine the strain inhibition/strain mass growth by using spectrophotometric optical density reading (OD). The bacterial/mycelium growth rates (BGR/MGR) and the bacterial/mycelium inhibition rates (BIR/MIR) after ozone treatment in the presence and absence of MpEO on the ATTC strains were calculated; the minimum inhibition concentration (MIC) and statistical interpretations of the time–dose relationship and specific t-test correlations were determined. The effect of ozone on the following tested strains at maximum efficiency was observed after 55 s of single ozone exposure, in order of effect strength: S. aureus > P. aeruginosa > E. coli > C. albicans > S. mutans. For ozone with the addition of 2% MpEO (MIC), maximum efficacy was recorded at 5 s for these strains, in order of effect strength: C. albicans > E. coli > P. aeruginosa > S. aureus > S. mutans. The results suggest a new development and affinity regarding the cell membrane of the different microorganisms tested. In conclusion, the use of ozone, combined with MpEO, is sustained as an alternative therapy in plaque biofilm and suggested as helpful in controlling oral disease-causing microorganisms in medicine.

Several components are used for their antipyretic action, that is, to reduce fever. A few examples:

• Paracetamol (Acetaminophen). Commonly used to reduce fever and relieve mild pain (1).
• Ibuprofen . A nonsteroidal anti-inflammatory drug (NSAID) that reduces fever and relieves pain (2).
• Aspirin (acetylsalicylic acid). In addition to its anti-inflammatory and analgesic properties, it is effective in reducing fever (3).
• Diclofenac sodium, used to reduce fever, especially in cases of inflammation (4).

Components or factors that can contribute to or exacerbate fever. A few examples:

• Bacterial or viral infections. These are the most common causes of fever, as the body raises its temperature to fight the infection.
• Inflammations. Inflammatory processes can trigger fever as an immune response.
• Vaccinations. Can cause a temporary fever as a reaction of the immune system.
• Autoimmune diseases. Conditions like rheumatoid arthritis can cause fever due to chronic inflammation.
• Dehydration. Can disrupt the body's temperature regulation and lead to fever.
• Heat or cold overload. Exposure to high ambient temperatures or excessive temperature differences can cause fever.

The reports  provided on Tiiips website are for informational purposes only and should not replace medical advice. Always consult a healthcare professional before making health-related decisions.

References_____________________________________________________________________

(1) Tan E, Braithwaite I, McKinlay CJD, Dalziel SR. Comparison of Acetaminophen (Paracetamol) With Ibuprofen for Treatment of Fever or Pain in Children Younger Than 2 Years: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020 Oct 1;3(10):e2022398. doi: 10.1001/jamanetworkopen.2020.22398. PMID: 33125495; PMCID: PMC7599455.

Abstract. Importance: Acetaminophen (paracetamol) and ibuprofen are the most widely prescribed and available over-the-counter medications for management of fever and pain in children. Despite the common use of these medications, treatment recommendations for young children remain divergent. Objective: To compare acetaminophen with ibuprofen for the short-term treatment of fever or pain in children younger than 2 years....Conclusions and relevance: In this study, use of ibuprofen vs acetaminophen for the treatment of fever or pain in children younger than 2 years was associated with reduced temperature and less pain within the first 24 hours of treatment, with equivalent safety.

(2) Rainsford KD. Ibuprofen: pharmacology, efficacy and safety. Inflammopharmacology. 2009 Dec;17(6):275-342. doi: 10.1007/s10787-009-0016-x. Epub 2009 Nov 21. 

Abstract. Objectives: This review attempts to bring together information from a large number of recent studies on the clinical uses, safety and pharmacological properties of ibuprofen. Ibuprofen is widely used in many countries for the relief of symptoms of pain, inflammation and fever. The evidence for modes of action of ibuprofen are considered in relation to its actions in controlling inflammation, pain and fever, as well as the adverse effects of the drug....Conclusions: This assessment of the safety and benefits of ibuprofen can be summarized thus: (1) Ibuprofen at OTC doses has low possibilities of serious GI events, and little prospect of developing renal and associated CV events. Ibuprofen OTC does not represent a risk for developing liver injury especially the irreversible liver damage observed with paracetamol and the occasional liver reactions from aspirin. (2) The pharmacokinetic properties of ibuprofen, especially the short plasma half-life of elimination, lack of development of pathologically related metabolites (e.g. covalent modification of liver proteins by the quinine-imine metabolite of paracetamol or irreversible acetylation of biomolecules by aspirin) are support for the view that these pharmacokinetic and notably metabolic effects of ibuprofen favour its low toxic potential. (3) The multiple actions of ibuprofen in controlling inflammation combine with moderate inhibition of COX-1 and COX-2 and low residence time of the drug in the body may account for the low GI, CV and renal risks from ibuprofen, especially at OTC doses.

(3) Lanas A, McCarthy D, Voelker M, Brueckner A, Senn S, Baron JA. Short-term acetylsalicylic acid (aspirin) use for pain, fever, or colds - gastrointestinal adverse effects: a meta-analysis of randomized clinical trials. Drugs R D. 2011 Sep 1;11(3):277-88. doi: 10.2165/11593880-000000000-00000. 

Abstract. Background and aim: Acetylsalicylic acid (ASA [aspirin]) is a commonly used over-the-counter drug for the treatment of pain, fever, or colds, but data on the safety of this use are very limited. The aim of this study was to provide data on the safety of this treatment pattern, which is of interest to clinicians, regulators, and the public.....Conclusion: Short-term, mostly single-dose exposure to ASA for the treatment of pain, fever, or colds was associated with a small but significant increase in the risk of dyspepsia relative to placebo. No serious GI complications were reported.

(4) Bettini R, Grossi E, Rapazzini P, Giardina G. Diclofenac sodium versus acetylsalicylic acid: a randomized study in febrile patients. J Int Med Res. 1986;14(2):95-100. doi: 10.1177/030006058601400208. 

Abstract. One hundred and twenty adult patients with high temperatures (greater than or equal to 38 degrees C) brought about by influenza viruses or other conditions were randomly treated with two different antipyretics: a) a 25 mg sodium diclofenac tablet (Novapirina) every 12 hours for 2 consecutive days; b) a 500 mg tablet of acetylsalicylic acid (Aspirin) every 8 hours for 2 consecutive days. Antipyretic action (assessed at 6 hours following the first administration) was found to be equally rapid and consistent in both cases but significantly longer-lasting in the Novapirina-treated group than the Aspirin-treated group (p less than 0.01). Mean temperature changes over the 48 hours of observation and the over-all judgement on the antipyretic effect expressed at the end of each day of treatment were similar for both groups and good in all cases. The antiphlogistic-painkilling properties of both drugs were found to be effective in improving the symptomatology accompanying the high temperature during the course of the bout of influenza. The effectiveness/tolerability ratio was found to be satisfactory for both groups: only one case of gastric intolerance to Novapirina was recorded and five cases of gastric intolerance to Aspirin.

Antihistamines are used medicinally to treat allergies, colds, insomnia, and coughs and can be taken with or without a prescription. They can be classified into three categories: sedative, less sedative, and nonsedative based on measurements of antihistamine receptor occupancy in the human brain and depending on the level of penetration into the central nervous system. (1).

They have a long history. First-generation antihistamines (e.g., chlorpheniramine, promethazine, diphenhydramine, hydroxyzine), many of which can be purchased without a prescription, could cause adverse reactions such as drowsiness, tachycardia, decreased cognition, urinary retention, thirst, and more. Second-generation antihistamines have been put on the market since 1979 to overcome the contraindications and adverse reactions that first-generation antihistamines could cause and rarely lead to severe toxicity (2).

Neuronal histamine, a biogenic monoamine, is found throughout the body with high concentrations in the gastrointestinal tract, lungs, and skin and acts as a neurotransmitter, reverse agonist, through activation of H1, H2, H3 receptors, H4 (G protein-coupled receptor (GPCR) family, consisting of 7 transmembrane-spanning helices) in the brain that have influence on various mechanisms both immunological and physiological such as intestinal and vascular smooth muscle and brain (3), gastric secretion, inflammation, vasodilation.

The relationship between histamine and migraine has been debated for decades. Since the 1940s, antihistamines have been considered to play a primary role in the management of vertigo. In 2019, intravenous cetirizine was approved for the treatment of acute urticaria, and compared with intravenous diphenhydramine, cetirizine has fewer contraindications and lower risk on elderly patients (4).

References_____________________________________________________________________

(1) Yanai K, Yoshikawa T, Yanai A, Nakamura T, Iida T, Leurs R, Tashiro M. The clinical pharmacology of non-sedating antihistamines. Pharmacol Ther. 2017 Oct;178:148-156. doi: 10.1016/j.pharmthera.2017.04.004.

(2) Jensen LL, Rømsing J, Dalhoff K. A Danish Survey of Antihistamine Use and Poisoning Patterns. Basic Clin Pharmacol Toxicol. 2017 Jan;120(1):64-70. doi: 10.1111/bcpt.12632.

(3) Hill SJ. Multiple histamine receptors: properties and functional characteristics. Biochem Soc Trans. 1992 Feb;20(1):122-5. doi: 10.1042/bst0200122. 

(4) Blaiss MS, Bernstein JA, Kessler A, Pines JM, Camargo CA Jr, Fulgham P, Haumschild R, Rupp K, Tyler T, Moellman J. The Role of Cetirizine in the Changing Landscape of IV Antihistamines: A Narrative Review. Adv Ther. 2021 Dec 4. doi: 10.1007/s12325-021-01999-x.

Other major studies

Zappia CD, Monczor F. Therapeutic utility of glucocorticoids and antihistamines cotreatment. Rationale and perspectives. Pharmacol Res Perspect. 2019 Dec;7(6):e00530. doi: 10.1002/prp2.530.

Abstract. We hypothesize that the existence of this synergistic effect could contribute in reducing the glucocorticoids clinical doses, ineffective by itself but effective in combination with an antihistamine. This could result in a therapeutic advantage as the glucocorticoid-desired effects may be reinforced by the addition of an antihistamine and, as a consequence of the dose reduction, glucocorticoid-related adverse effects could be reduced or at least mitigated.

Fukui H, Mizuguchi H, Kitamura Y, Takeda N. Patho-Pharmacological Research of Anti-allergic Natural Products Targeting Antihistamine-Sensitive and -Insensitive Allergic Mechanisms. Curr Top Behav Neurosci. 2021 Oct 14. doi: 10.1007/7854_2021_255.

Abstract.  Combination therapy using medicines suppressing both H1R gene expression and IL-9 gene expression is promising for outstanding alleviation of allergic disease. Multifactorial diseases involving H1R gene expression may be treated by the combination therapy with antihistamine and complementary drugs, and diseases involving PKCδ signaling may be treated by drugs targeting Hsp90.

Antibiotics, antibacterial agents that inhibit the growth of harmful bacteria in a host and kill them, were introduced into medicine in the mid-1900s with the expectation of curing all bacterial infections. Penicillin seemed to be the magic remedy that destroyed bacteria. Unfortunately, in the 1960s Kislak and others discovered that a strain of Streptococcus pneumoniae was resistant to penicillin. From then on, it was discovered that more bacteria were demonstrating resistance to antibiotics and their resistance increased in almost every country. Bacteria have demonstrated abilities to modify themselves to resist antibiotic action. Antibiotics are used to fight bacterial infections and are ineffective for viral infections.

This study finds that antibiotic resistance is a global and growing problem that is not counterbalanced by the development of new therapeutic agents. The prevalence of antibiotic resistance is particularly high in intensive care units with frequently reported outbreaks of multidrug-resistant organisms. This study provides an overview of selective oropharyngeal and digestive tract decontamination, methicillin-resistant Staphylococcus aureus decolonization, and antibiotic rotation as strategies to modulate antibiotic resistance in the intensive care unit (1).

Is there such a thing as an ideal antibiotic? The efficacy of all antibacterial agents is rapidly being eroded due to resistance. This viewpoint provides an overview of today's antibiotics, the challenges, and the potential pathway toward the discovery and development of new (ideal) antibiotics (2).

Another danger to human health is the unnecessary use of antibiotics, which is a widely recognized threat to global health, development, and sustainability (3).

Some commonly used antibiotics:

• ciprofloxacin
• streptomycin
• tetracycline
• levofloxacin
• fluoroquinolones
• aminoglycosides
• beta-lactams

References_________________________________________________________________

(1) Plantinga NL, Wittekamp BH, van Duijn PJ, Bonten MJ. Fighting antibiotic resistance in the intensive care unit using antibiotics. Future Microbiol. 2015;10(3):391-406. doi: 10.2217/fmb.14.146. 

(2) Singh SB, Young K, Silver LL. What is an "ideal" antibiotic? Discovery challenges and path forward. Biochem Pharmacol. 2017 Jun 1;133:63-73. doi: 10.1016/j.bcp.2017.01.003.

(3) Machowska A, Stålsby Lundborg C. Drivers of Irrational Use of Antibiotics in Europe. Int J Environ Res Public Health. 2018 Dec 23;16(1):27. doi: 10.3390/ijerph16010027. 

Intense or harmful stimuli cause pain, an unpleasant sensation, sensory, emotional, multidimensional, often also associated with tissue damage that, however, warns us that something is wrong with our body and asks us to take action. 

Over the centuries, many remedies for pain have been used, many forms of therapy. Medicinal plants were the first to be used to mitigate pain: from Papaver somniferum is extracted morphine, considered the prototype of opioid analgesics, which however has rather serious side effects.

From Alliaceae, Apiaceae, Asteraceae, Lamiaceae, Myrtaceae, Poaceae and Rutaceae it is possible to extract essential oils of medicinal value and suitable for industrial production.

These essential oils have many pharmacological properties: antitumor, anxiolytic, hypnotic, anticonvulsant.

There are 43 natural bioactive ingredients that have demonstrated analgesic properties, among which 62.8% were monoterpenes, 18.6% sesquiterpenes and other constituents as described in this study and including: linalool, menthol, eugenol, limonene, α-Santalol which is a sesquiterpenoid isolated from the root of Saussurea (Santelum album L.) an "oriental incense" used for meditation and sedation. and others (2).

There is also a whole series of chemical compounds including. 

• paracetamol, a non-steroidal drug, which is almost unanimously considered to have no anti-inflammatory activity and does not produce gastrointestinal damage or unpleasant cardiorenal effects (3).
• ibuprofen with side effects, associated mild adverse events. Minimal renal effects. Characteristics described in this study whose authors also believe that ibuprofen possesses a good safety profile and has provided evidence of efficacy for mild to moderate pain of various origins in children (4).

For more acute pain, opioids are used but can cause dependence, while most analgesics are associated with serious side effects, such as FANS (Nonsteroidal Anti-inflammatory Drugs) can cause gastrointestinal disorders (5).

References_____________________________________________________________________

(1) Almeida RN, Navarro DS, Barbosa-Filho JM. Plants with central analgesic activity. Phytomedicine. 2001 Jul;8(4):310-22. doi: 10.1078/0944-7113-00050.

(2) de Sousa DP. Analgesic-like activity of essential oils constituents. Molecules. 2011 Mar 7;16(3):2233-52. doi: 10.3390/molecules16032233. 

(3) Bertolini A, Ferrari A, Ottani A, Guerzoni S, Tacchi R, Leone S. Paracetamol: new vistas of an old drug. CNS Drug Rev. 2006 Fall-Winter;12(3-4):250-75. doi: 10.1111/j.1527-3458.2006.00250.x. 

(4) Barbagallo M, Sacerdote P. Ibuprofen in the treatment of children's inflammatory pain: a clinical and pharmacological overview. Minerva Pediatr. 2019 Feb;71(1):82-99. doi: 10.23736/S0026-4946.18.05453-1. 

(5) Ruchita, Sucheta, Nanda S, Pathak D. Analgesic Prodrugs for Combating their Side-Effects: Rational Approach. Curr Drug Deliv. 2017;14(1):16-26. doi: 10.2174/1567201813666160504100705. 

In recent years, there has been an increase in allergic diseases such as dermatitis, asthma, and allergic rhinitis. This comes not only from environmental factors, but also from the critical chemical compounds that we frequently find everywhere, in soaps, deodorants and even in medicinal tablets and drops. All of this has contributed to mortality and morbidity worldwide.

Chirality plays an important role in pharmacokinetics and pharmacodynamics of various pharmaceutical agents. The importance of stereoisomeric purity in the pharmacologic industry has increased during the past decade as demonstrated by the increased number of studies that examined the in vivo and in vitro effects produced by changes in stereoconfiguration of pharmaceutical agents. This review highlights such effects in certain frequently used medications used in the treatment of asthma and various allergic and immunologic disorders (1).

Allergy, IgE-mediated inflammatory disorders including allergic rhinitis, asthma, and conjunctivitis, affects billions of people worldwide. Conventional means of allergy management include allergen avoidance, pharmacotherapy, and emerging therapies. Among them, chemotherapeutant intake via oral, intravenous, and intranasal routes is always the most common mean. Although current pharmacotherapy exhibit splendid anti-allergic effects, short in situ retention, low bioavailability, and systemic side effects are inevitable. Nowadays, nanoplatforms have provided alternative therapeutic options to obviate the existing weakness via enhancing the solubility of hydrophobic therapeutic agents, achieving in situ drug accumulation, exhibiting controlled and long-time drug release at lesion areas, and providing multi-functional therapeutic strategies. Herein, we highlight the clinical therapeutic strategies and deal with characteristics of the nanoplatform design in allergy interventions via intratracheal, gastrointestinal, intravenous, and ocular paths. The promising therapeutic utilization in a variety of allergic disorders is discussed, and recent perspectives on the feasible advances of nanoplatforms in allergy management are also exploited (2).

Components that help in antiallergic action are substances that can contribute to reducing or preventing allergic reactions. Here are some examples

• Antihistamines. Medications like cetirizine and loratadine can relieve allergic symptoms by blocking the action of histamine.
• Nasal Corticosteroids. Such as fluticasone and mometasone, reduce inflammation in the nasal passages.
• Montelukast. A leukotriene antagonist that can help control allergic reactions, especially in cases of allergic asthma.
• Omega-3 Fatty Acids. Found in fatty fish and flaxseeds, they can reduce inflammation associated with allergies.
• Probiotics. Help strengthen the immune system and can reduce sensitivity to allergies.

• Vitamin C. An antioxidant that can help reduce allergy symptoms.
• Quercetin. A flavonoid found in fruits and vegetables that may have antihistamine properties.
• Green Tea. Contains antioxidants that can help reduce allergic inflammation.
• Bromelain. An enzyme found in pineapple that can reduce nasal and respiratory inflammation.
• Chamomile. Has anti-inflammatory properties and can help soothe allergic reactions.

The reports  provided on Tiiips website are for informational purposes only and should not replace medical advice. Always consult a healthcare professional before making health-related decisions.

Components that can contribute to or exacerbate allergies include various factors that can increase sensitivity or allergic reactivity. Here are some examples

• Pollen. The presence of pollen in the air can trigger seasonal allergic reactions.
• Dust Mites. Tiny organisms in household dust that can cause allergies.
• Animal Dander. Dander or hairs from pets can be common allergens.
• Molds. Mold spores in the environment can cause allergic reactions.
• Specific Foods. Foods like peanuts, tree nuts, milk, eggs, and seafood can trigger food allergies.
• Environmental Pollutants. Substances like cigarette smoke and exhaust gases can aggravate respiratory allergies.
• Chemicals and Fragrances. Chemicals in detergents, cosmetics, and perfumes can trigger allergic reactions.
• Latex. Latex can cause allergic reactions in some people.
• Climate Changes. Changes in temperature and humidity can affect the spread of allergens.

Compendium of the most significant studies

Hogan Ii RB, Hogan Iii RB, Cannon T, Rappai M, Studdard J, Paul D, Dooley TP. Dual-histamine receptor blockade with cetirizine - famotidine reduces pulmonary symptoms in COVID-19 patients. Pulm Pharmacol Ther. 2020 Aug;63:101942. doi: 10.1016/j.pupt.2020.101942.

Li QS, Wang YQ, Liang YR, Lu JL. The anti-allergic potential of tea: a review of its components, mechanisms and risks. Food Funct. 2021 Jan 7;12(1):57-69. doi: 10.1039/d0fo02091e.

Shams MH, Jafari R, Eskandari N, Masjedi M, Kheirandish F, Ganjalikhani Hakemi M, Ghasemi R, Varzi AM, Sohrabi SM, Baharvand PA, Safari M. Anti-allergic effects of vitamin E in allergic diseases: An updated review. Int Immunopharmacol. 2021 Jan;90:107196. doi: 10.1016/j.intimp.2020.107196. 

Nieto A, Nieto M, Mazón Á. The clinical evidence of second-generation H1-antihistamines in the treatment of allergic rhinitis and urticaria in children over 2 years with a special focus on rupatadine. Expert Opin Pharmacother. 2021 Mar;22(4):511-519. doi: 10.1080/14656566.2020.1830970.

Zhang W, Tang R, Ba G, Li M, Lin H. Anti-allergic and anti-inflammatory effects of resveratrol via inhibiting TXNIP-oxidative stress pathway in a mouse model of allergic rhinitis. World Allergy Organ J. 2020 Oct 22;13(10):100473. doi: 10.1016/j.waojou.2020.100473.

Sandner G, Heckmann M, Weghuber J. Immunomodulatory Activities of Selected Essential Oils. Biomolecules. 2020 Aug 3;10(8):1139. doi: 10.3390/biom10081139.

Jafarinia M, Sadat Hosseini M, Kasiri N, Fazel N, Fathi F, Ganjalikhani Hakemi M, Eskandari N. Quercetin with the potential effect on allergic diseases. Allergy Asthma Clin Immunol. 2020 May 14;16:36. doi: 10.1186/s13223-020-00434-0.

References_______________________________________________________________________

(1) Bielory L, Leonov A. Stereoconfiguration of antiallergic and immunologic drugs. Ann Allergy Asthma Immunol. 2008 Jan;100(1):1-8; quiz 8-11, 36. doi: 10.1016/S1081-1206(10)60396-1.

(2) Fan PS, Sun MJ, Qin D, Yuan CS, Chen XG, Liu Y. Nanosystems as curative platforms for allergic disorder management. J Mater Chem B. 2021 Feb 25;9(7):1729-1744. doi: 10.1039/d0tb02590a.