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FastGrowingAutomatism

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University of St Andrews

Rutter GI

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gastroenterology oral health GI tract medicine

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This chapter covers gastroenterology, focusing on the anatomy of the gastrointestinal tract, history taking, and physical examination. It includes detailed information about conditions affecting the oral cavity, such as mouth ulcers and oral thrush, with specific questions to be asked about ulcers, thereby helping to create a differential diagnosis.

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Chapter 7 Gastroenterology In this chapter Background 161 Dyspepsia 174 General overview of the anatomy of the Diarrhoea 182 gastrointestinal tract 161...

Chapter 7 Gastroenterology In this chapter Background 161 Dyspepsia 174 General overview of the anatomy of the Diarrhoea 182 gastrointestinal tract 161 Constipation 189 History taking and physical examination 162 Irritable bowel syndrome 197 Conditions affecting the oral cavity 162 Haemorrhoids 201 Mouth ulcers 162 Abdominal pain 206 Oral thrush 168 Self-assessment questions 218 Gingivitis 172 Background Stomach The stomach is roughly J-shaped and receives food and fluid The main function of the gastrointestinal (GI) tract is to break from the oesophagus. It empties into the duodenum. It is down food into a suitable energy source to allow normal located slightly left of midline and anterior (below) to the physiological function of cells. The process is complex and rib cage. The lesser curvature of the stomach sits adjacent involves many different organs. Consequently, there are to the liver. many conditions that affect the GI tract, some of which are acute and self-limiting and respond well to over-the- counter (OTC) medication and others that are serious and Liver require referral. The liver is located below the diaphragm and mostly right of midline in the upper right quadrant of the abdomen. The liver General overview of the anatomy performs many functions, including carbohydrate, lipid and protein metabolism and the processing of many medicines. of the gastrointestinal tract It is vital that pharmacists have a sound understanding of GI Gallbladder tract anatomy. Many conditions will present with similar symptoms and from similar locations; for example, abdom- The gallbladder is a pear-shaped sac that lies deep to the liver inal pain, and the pharmacist will need a basic knowledge of and hangs from the lower front margin of the liver. Its func- GI tract anatomy, and in particular of where each organ of tion is to store and concentrate bile made by the liver. the GI tract is located, to facilitate a correct differential diag- nosis (see Fig. 7.15). Pancreas Oral cavity The pancreas lies behind the stomach. It is essential for pro- ducing digestive enzymes transported to the duodenum via The oral cavity is comprised of the cheeks, hard and soft pal- the pancreatic duct and secretion of hormones such as ates and tongue. insulin. 162 Gastroenterology Small intestine The small intestine is where most of the absorption of nutrients and medicines occur. It is comprised of three sections: the duo- denum, the jejunum and the ileum. The duodenum starts at the exit of the stomach and its main roles are to neutralize stom- ach acid and initiate the chemical digestion of chyme (the Hard palate Posterior Soft palate partly digested food from the stomach). The jejunum is a small pillar section that joins the duodenum and ileum. In the ileum, the Anterior Uvula mucosa becomes highly folded to form villi that increase the pillar surface area and facilitate the absorption of soluble molecules. Pharynx Right tonsil Large intestine Tongue The large intestine starts with the caecum, which is where the appendix connects to the gut. This is followed by the colon and ends with the rectum. The role of the large intestine is largely to absorb water and expel waste. History taking and physical examination Fig. 7.1 The oral cavity. A thorough patient history is essential because physical examination of the GI tract in a community pharmacy is gen- 2. Once the presenting problem has been inspected, check erally limited to inspection of the mouth. This should allow the rest of the oral cavity for any further signs or symp- confirmation of the diagnoses for conditions such as mouth toms. It is possible that other parts of the mouth are ulcers and oral thrush. A description of how to examine the affected but have not been noticed by the patient. oral cavity appears in the following section. 3. While inspecting the mouth also check for signs of a healthy mouth; that is, no signs of tooth decay or peri- odontal disease (bleeding gums). Conditions affecting the oral cavity Background Mouth ulcers The process of digestion starts in the oral cavity. The tongue and cheeks position large pieces of food so that the teeth can Background tear and crush food into smaller particles. Saliva moistens, Aphthous ulcers, more commonly known as mouth ulcers, is lubricates and begins the process of digesting carbohydrates a collective term used to describe various different clinical (by secreting amylase enzymes) before swallowing. presentations of superficial, painful oral lesions that occur in recurrent bouts at intervals from a few days to a few The physical examination months. Most patients (80%) who present in a community pharmacy will have minor aphthous ulcers (MAUs). It is The oral cavity (Fig. 7.1) can be easily observed in the phar- the community pharmacist’s role to exclude more serious macy, provided the mouth can be viewed with a good light pathology; for example, systemic causes and carcinoma. source, preferably a pen torch. Before performing the exam- ination, it is important to explain to the patient fully what you are about to do and gain their consent. Steps involved Prevalence and epidemiology in performing an oral examination are detailed as follows: The prevalence and epidemiology of MAUs is poorly under- 1. Examine the area where the lesion(s) and/or pain origi- stood but probably affects 20% of the UK population. They nates from. Look at the size, shape and colour of the occur in all ages, but it has been reported that they are more lesion(s). Note any redness or swelling local to the area. common in women and those under the age of 40. Mouth ulcers 163 Aetiology that the patient will be suffering from MAUs, it is essential that these be differentiated from other causes and referred The cause of MAUs is unknown, although about 40% of peo- ple have a family history of oral ulceration. A number of the- to the GP for further evaluation. A number of ulcer-specific questions should always be asked of the patient (Table 7.2), 7 ories have been put forward to explain why people develop and an inspection of the oral cavity should be performed to MAUs, including a genetic link, stress, trauma, food sensitiv- help aid in the diagnosis. ities, nutritional deficiencies (iron, zinc, and vitamin B12) and infection, but none have so far been proven. Clinical features of minor aphthous ulcers Arriving at a differential diagnosis MAUs are roundish, grey-white in colour, and painful. They There are three main clinical presentations of ulcers: minor, are small, usually less than 1 cm in diameter, and shallow, major, and herpetiform (Table 7.1). Although it is most likely with a raised red rim. Pain is the key presenting symptom and can make eating and drinking difficult, although pain subsides after 3 or 4 days. They rarely occur on the gingival Table 7.1 mucosa and occur singly or in small crops of up to five ulcers. Causes of ulcers and their relative incidence in It normally takes 7 to 14 days for the ulcers to heal, but recur- community pharmacy rence typically occurs after an interval of 1 to 4 months Incidence Cause (Fig. 7.2). Most likely Minor aphthous ulcers (MAUs) Likely Major aphthous ulcers, trauma Conditions to eliminate Unlikely Herpetiform ulcers, herpes simplex, oral Likely causes thrush, medicine-induced, hand, foot, and Major aphthous ulcers mouth disease These account for 10% to 15% of cases and are characterized Very unlikely Oral carcinoma, erythema multiforme, by large (>1 cm in diameter) numerous ulcers, occurring in Behçet syndrome, Crohn’s disease and crops of 10 or more. The ulcers often coalesce to form one ulcerative colitis large ulcer. These ulcers are slower to heal than MAUs, typ- ically taking 3 to 4 weeks and may cause scarring (Fig. 7.3). ? Table 7.2 Specific questions to ask the patient: Mouth ulcers Question Relevance Number of Minor aphthous ulcers (MAUs) occur singly or in small crops. A single large ulcerated area is more indicative of ulcers pathology outside the remit of the community pharmacist. Patients with numerous ulcers are more likely to be suffering from major or herpetiform ulcers rather than MAUs. Location of Ulcers on the side of the cheeks, tongue and inside of the lips are likely to be MAUs. ulcers Ulcers located towards the back of the mouth are more consistent with major or herpetiform ulcers. Size and shape Irregular-shaped ulcers tend to be caused by trauma. If trauma is not the cause, referral is necessary to exclude sinister pathology. If ulcers are large or very small, they are unlikely to be caused by MAUs. Painless ulcers Any patient presenting with a painless ulcer in the oral cavity must be referred. This can indicate sinister pathology such as leukoplakia or carcinoma. Age MAUs in young children (14 days Duration Refer ❶ Only one trial conducted by Truelove and Morris-Owen (1958) 1 cm Yes Major ulcer or dence for antibacterial agents is of poor quality. in diameter Candidiasis ❹ No Products containing anaesthetic or analgesics MAU: symptomatic relief There is very little evidence to support the pain-relieving if pain bothersome effect of anaesthetics or analgesics in MAUs, apart from choline salicylate and benzydamine. However, these prepa- Fig. 7.6 Primer for differential diagnosis of mouth ulcers. rations are clinically effective in other painful oral condi- tions. It is therefore not unreasonable to expect some relief ➊ Minor aphthous ulcers. (MAUs) normally resolve in 7 to of symptoms when using these products to treat MAUs. 14 days. Ulcers that fail to heal within this time need referral to exclude other causes. Choline salicylate ➋ Painless ulcers. These can indicate sinister pathology, especially if the patient is older than 50 years. In Choline salicylate has been shown to exert an analgesic effect addition, it is likely that the ulcer will have been present in a number of small studies. However, only one study by for some time before the patient presented to the Reedy (1970) involving 27 patients evaluated choline salicy- pharmacy. late in the treatment of oral aphthous ulceration. No signifi- ➌ Numerous ulcers. Crops of 5 to 10 or more ulcers are rare in cant differences were found between choline salicylate and MAUs. Referral is necessary to determine the cause. placebo in ulcer resolution, but choline salicylate was found to be significantly superior to placebo in relieving pain. ➍ Major ulcer or candidiasis. See Fig. 7.9 for a primer on the differential diagnosis of oral thrush. Benzydamine Benzydamine mouthwash has been studied in a small, low- Evidence base for over-the-counter medication quality trial for its effect in managing recurrent aphthous sto- matitis. (Taylor 2018) The study found that benzydamine was A wide range of products are used for the temporary relief not significantly different from placebo in terms of ulcer sever- and treatment of mouth ulcers. These products contain cor- ity or ulcer pain. However, nearly 50% of patients preferred ticosteroids, local anaesthetics, antibacterials, astringents benzydamine because of its transient topical analgesic effect. and antiseptics. Protectorants Corticosteroids Pastes that contain gelatin, pectin, and carmellose sodium Topical corticosteroids are recommended as one of the main- stick when in contact with wet mucosal surfaces. These have stays of treatment for patients with MAU; however, most been advocated, but there is a paucity of data to support their products are not available OTC in the UK. efficacy. Mouth ulcers 167 Table 7.3 Practical prescribing: Summary of medicines for ulcers Name of Very common (≥1/10) or Drug interactions Patients in whom Pregnancy and 7 medicine Use in children common (≥1/100) side effects of note care is exercised breastfeeding Corticosteroid >12 years None None None OK Choline >16 years None None None OK salicylate Lidocaine >7 years (Iglu)a Can cause None None OK sensitization reactions Benzocaine >12 years Chlorhexidine >12 years None None None OK Benzydamine >12 years May cause stinging None None OK a Children should not be given products routinely because ulcers are rare in this age group. use include reversible tongue and tooth discolouration, burning HINTS AND TIPS BOX 7.1: ULCERS of the tongue, and taste disturbances. Protectorant Apply after food because food is likely products to rub off these products. Choline salicylate Adults and children older than 16 years should apply the these gels (Bonjela Cool, Bonjela Adult) using a clean finger over the ulcer every 3 hours when needed. It is a safe med- Practical prescribing and product selection icine and can be given to all patient groups. It is not known to interact with any medicines or cause any side effects. Prescribing information relating to the medicines used for ulcers is reviewed in Table 7.3; useful tips relating to patients Local anaesthetics presenting with ulcers are given in Box 7.1. All local anaesthetics have a short duration of action; fre- Hydrocortisone tablets quent dosing is therefore required to maintain the anaes- thetic effect. They are thus best used on an as-needed Each tablet contains 2.5 mg hydrocortisone in the form of the basis, although the upper limit on the number of applications ester hydrocortisone sodium succinate. The dose for adults allowed varies, depending on the concentration of anaes- and children over 12 is one pellet to be dissolved in close thetic included in each product. They appear to be free from proximity to the ulcers four times a day for up to 5 days. any drug interactions, have minimal side effects, and can be It does not interact with any medicines, can be taken by given to most patients. A small percentage of patients might all patient groups, has no side effects, and appears to be safe experience a hypersensitivity reaction with lidocaine (Anbe- in pregnancy and breastfeeding. sol range, Iglu gel, Medijel) or benzocaine (Orajel range); this appears to be more common with benzocaine. Antibacterial agents Chlorhexidine (e.g., Corsodyl) mouthwash is indicated as an aid Benzydamine in the treatment and prevention of gingivitis and in the main- For dosing and administration of the oral rinse, see page 34. tenance of oral hygiene, which includes the management of aphthous ulceration. Ten millilitres of the mouthwash should Protectorants be rinsed around the mouth for about 1 minute twice a day. It can be used by all patient groups, including those who are These can be applied as frequently as required. There are no pregnant and breastfeeding. Side effects associated with its interactions, and they can be used in all patient groups. 168 Gastroenterology (Gonsalves et al., 2007). Prevalence in denture wearers is References even higher. Changes to the normal environment in the oral Browne, R. M., Fox, E. C., & Anderson, R. J. 1. cavity allow C. albicans to proliferate. Reedy, B. L. (1970). A topical salicylate gel in the treatment of oral aphthous ulceration. Practitioner, 204, 846–850. Taylor J. (2018). Oral aphthous ulcers. BMJ Best Practice. Arriving at a differential diagnosis https://bestpractice.bmj.com/topics/en-gb/564. Truelove, S. C., & Morris-Owen, R. M. (1958). Treatment of Oral thrush is not difficult to diagnose, and the role of the aphthous ulceration of the mouth. BMJ, 1, 603-607. pharmacist is to eliminate underlying pathology and exclude risk factors. A number of other conditions need to be consid- Further reading ered (Table 7.4) and asking a number of specific questions of Brocklehurst, P., Tickle, M., Glenny, A. M., et al. (2012). Systemic the patient will aid the differential diagnosis (Table 7.5). After interventions for recurrent aphthous stomatitis (mouth ulcers). Cochrane Database System Rev, (9), CD005411. questioning, the pharmacist should inspect the oral cavity to MacPhee. I. T., Sircus, W., Farmer, E. D., et al. (1968). Use of help confirm the diagnosis. steroids in treatment of aphthous ulceration. BMJ, 2(598), 147–149. Scully, C., Gorsky, M., & Lozada-Nur, F. (2003). The diagnosis and Table 7.4 management of recurrent aphthous stomatitis: A consensus Causes of oral lesions and their relative incidence in approach. Journal of the American Dental Association, 134, community pharmacy 200–207. Incidence Cause Websites Most likely Thrush Behçet’s Syndrome Society: https://behcets.org.uk/ Oral health foundation (formerly the British Dental Health Likely Minor aphthous ulcers, medicine-induced Foundation): https://www.dentalhealth.org/ thrush, ill-fitting dentures Unlikely Lichen planus, underlying medical disorders, such as diabetes, xerostomia (dry mouth), Oral thrush and immunosuppression, major and herpetiform ulcers, herpes simplex Background Very unlikely Leukoplakia, squamous cell carcinoma Oropharyngeal candidiasis (oral thrush) is an opportunistic mucosal infection that is unusual in healthy adults. If oral thrush is suspected in this population, community pharma- cists should determine whether any identifiable risk factors ? Table 7.5 Specific questions to ask the patient: Oral are present. A healthy adult with no risk factors generally thrush requires referral to the doctor. Question Relevance Prevalence and epidemiology Size and Typically patients with oral thrush present shape of with patches. They tend to be irregularly The very young (neonates) and the very old are most likely to lesion shaped and vary in size from small to suffer from oral thrush. It has been reported that 14% of infants large. at 4 weeks and 10% of debilitated older patients suffer from oral thrush. It is associated with underlying pathology such Associated Thrush almost always causes some degree as diabetes, xerostomia (dry mouth) and patients who are pain of discomfort. Painless patches, immunocompromised, or an attributable risk factor such as especially in people >50 years, should be recent antibiotic therapy, inhaled corticosteroids or ill-fitting referred to exclude sinister pathology, such as leukoplakia. dentures is present. Location of Oral thrush often affects the tongue and Aetiology lesions cheeks, although if precipitated by inhaled steroids, the lesions appear on It is reported that Candida albicans is found in the oral cavity the pharynx. of 30% to 60% of healthy people in developed countries Oral thrush 169 Clinical features of oral thrush Denture wearers Wearing dentures, especially if they are not taken out at night, The classic presentation of oral thrush is with creamy white, soft, elevated patches that can be wiped off, revealing under- not kept clean, or do not fit well can predispose people to thrush. 7 lying erythematous mucosa (Fig. 7.7). Burning or irritation is associated with the infection rather than true pain. Lesions Unlikely causes can occur anywhere in the oral cavity but usually affect Lichen planus the tongue, palate, lips and cheeks. Patients sometimes com- Lichen planus is a dermatological condition with lesions sim- plain of malaise and loss of appetite. In neonates, spontane- ilar in appearance to plaque psoriasis. In about 50% of people, ous resolution can occur but can take a few weeks. the oral mucous membranes are affected. The cheeks, gums, or tongue develop white, slightly raised painless lesions that resemble a spider’s web. Other symptoms can include soreness Conditions to eliminate of the mouth and a burning sensation. Occasionally, lichen planus of the mouth occurs without any skin rash. Likely causes Minor aphthous ulcers Underlying medical disorders Mouth ulcers are covered earlier in this chapter; please refer As stated previously, oral thrush is unusual in the adult pop- to this section for the differential diagnosis of these from oral ulation. Patients are at greater risk of developing thrush if thrush. they suffer from medical conditions such as diabetes or xer- ostomia (dry mouth) or are immunocompromised. Medicine-induced thrush Inhaled corticosteroids and antibiotics are often associated Other forms of ulceration with causing thrush. In addition, medicines that cause dry- Major and herpetiform ulcers and herpes simplex are cov- ness of the mouth can also predispose people to thrush. ered in more detail in the mouth ulcer section of this chap- Always take a medicine history to determine whether medi- ter; see these sections for the differential diagnosis from oral cines could be a cause of the symptoms. thrush. Very unlikely causes Leukoplakia Leukoplakia is predominantly a white lesion of the oral mucosa that is a diagnosis based on exclusion (Fig. 7.8). It is often associated with smoking and is a precancerous lesion, Fig. 7.7 Oral candidiasis. From Forbes, C. D., & Jackson, W. F. Fig. 7.8 Leukoplakia. From Forbes, C. D., & Jackson, W. F. (2004). Illustrated pocket guide to clinical medicine (2nd ed.). (2004). Illustrated pocket guide to clinical medicine (2nd ed.). St Louis: Mosby. St Louis: Mosby. 170 Gastroenterology although epidemiological data have suggested that the annual transformation rate to squamous cell carcinoma is approxi- TRIGGER POINTS indicative of referral: Oral thrush mately 1%. Patients present with a symptomless white patch mainly on the buccal mucosa but also on the tongue, which Symptoms/ Possible danger/reason Urgency of develops over a period of weeks. The lesion cannot be wiped signs for referral referral off, unlike oral thrush. Most cases are seen in people over the Diabetic May indicate poor As soon as age of 40 and is more common in men. patients diabetic control practicable Duration > Unlikely to be thrush and 3 weeks needs further Squamous cell carcinoma investigation by a Squamous cell carcinoma is covered in more detail under doctor mouth ulcers and the reader is referred to this section for Immuno- Likely to have severe and Urgent differential diagnosis from oral thrush. compromised extensive involvement; possible Fig. 7.9 will aid the differentiation of thrush from other patients outside community same-day oral lesions. pharmacist’s remit referral Painless lesions Sinister pathology >3 weeks Duration Refer ❶ 1 cm No in diameter Possibly MAU ❷ Good Refer to dentist Dentures No Check sterilization procedure Treat with imidazole Poor History of diabetes or No Antibiotics ❸ patient immunocompromised Treat with imidazole Resolution No No Steroid use ❹ Refer to dentist Yes Treat with imidazole Lesions can be wiped off and/or pain Refer No Fig. 7.9 Primer for the differential diagnosis of oral thrush. ➊ Duration. Any lesion lasting more than 3 weeks must be ➍ Inhaled corticosteroids. High-dose inhaled corticosteroids referred to exclude sinister pathology. can cause oral thrush. Patients should be encouraged to use a ➋ Minor aphthous ulcers (MAUs). See Fig. 7.6 for a primer on spacer and wash their mouth out after inhaler use to the differential diagnosis of mouth ulcers. minimize this problem. ➌ Antibiotics. Broad-spectrum antibiotics, such as amoxicillin and macrolides, can precipitate oral thrush by altering the normal flora of the oral cavity. Oral thrush 171 Evidence base for over-the-counter medication these interactions are except with warfarin. Co-administration of warfarin with miconazole increases warfarin levels mark- Only Daktarin oral gel (miconazole) is available OTC to treat oral thrush. It has proven efficacy and appears to have clin- edly, and the patient’s INR (internationalize normalized ratio) should be monitored closely. The manufacturers advise that 7 ical cure rates between 80% and 90%. In comparative trials, Daktarin should be avoided in pregnancy, but published data Daktarin appears to have superior cure rates than the do not support an association between miconazole and con- prescription-only medication (POM) nystatin (Hoppe & Hahn genital defects. It appears to be safe to use while breastfeeding. 1996; Hoppe, 1997). Practical prescribing and product selection References Gonsalves, W. C., Chi, A., & Neville, B. W. (2007). Common oral Prescribing information relating to Daktarin Oral gel is dis- lesions: Part I. Superficial mucosal lesions. American Family cussed and summarized in Table 7.6; useful tips relating to Physician, 75, 501–507. the application of Daktarin are given in ‘Hints and Tips’ in Hoppe, J. E. (1997). Treatment of oropharyngeal candidiasis in Box 7.2. immunocompetent infants: A randomized multicenter study The dosage of the gel is four times a day in all age groups, of miconazole gel vs. nystatin suspension. The Antifungals although the volume administered varies, depending on the Study Group. The Pediatric Infectious Disease Journal, 16, age of the patient. For those aged between 4 and 24 months, 288–293. 1.25 mL (¼ measuring spoon) of gel should be applied; for Hoppe, J. E., & Hahn, H. (1996). Randomized comparison of two nystatin oral gels with miconazole oral gel for treatment of adults and children older than 2 years, 2.5 mL (½ measuring oral thrush in infants. Antimycotics Study Group. Infection, spoon) of gel is applied. 24, 136–139. It can cause nausea and vomiting, dry mouth and oral discomfort. The manufacturers state that it can interact with Further reading a number of medicines; namely mizolastine, cisapride, triazo- Parvinen, T., Kokko, J., & Yli-Urpo, A. (1994). Miconazole lacquer lam, midazolam, quinidine, pimozide, HMG-CoA reductase compared with gel in treatment of denture stomatitis. inhibitors (statins) and anticoagulants. However, there is a Scandinavian Journal of Dental Research, 102, 361–366. lack of published data to determine how clinically significant Table 7.6 Practical prescribing: Summary of medicine for oral thrush Very common (≥1/10) Drug Patients in Name of or common (≥1/100) interactions whom care is Pregnancy and medicine Use in children side effects of note exercised breastfeeding Daktarin >4 months Nausea and vomiting, Warfarin None OK (unlicensed under 4 months but dry mouth Clinical Knowledge Summaries (CKS) advocates its use to GPs as first-line treatment) HINTS AND TIPS BOX 7.2: DAKTARIN Application of Patients should be advised to hold the gel in the mouth for as long as possible to increase contact Daktarin time between the medicine and the infection. For denture wearers, the dentures should be removed at night and brushed with the gel. Duration of Treatment should be continued for up to 2 days after the symptoms have cleared to prevent relapse treatment and reinfection. Patient acceptability The gel is flavoured orange to make retention in the mouth more acceptable to patients. 172 Gastroenterology Gingivitis ? Table 7.7 Specific questions to ask the patient: Gingivitis Background Question Relevance Gingivitis simply means inflammation of the gums; it is usu- Toothbrushing Overzealous toothbrushing can lead to ally caused by an excess buildup of plaque on the teeth. The technique bleeding gums and gum recession. condition is entirely preventable if regular and correct tooth- Make sure the patient is not ‘overcleaning’ his or her teeth. An brushing is undertaken. electric toothbrush might be helpful for people who apply too much force Prevalence and epidemiology when brushing teeth. It is estimated 50% of the UK population is affected by gum Bleeding gums Gums that bleed without exposure to disease, and more than 85% of people older than 40 years will trauma and is unexplained or experience gingival disease. Men are affected slightly more unprovoked need referral to exclude than women. underlying pathology. Aetiology After toothbrushing, the teeth soon become coated in a mixture of saliva and gingival fluid, known as pellicle. Oral gingivitis-specific questions should always be asked of the bacteria and food particles adhere to this coating and begin patient to aid in the differential diagnosis (Table 7.7). to proliferate, forming plaque; subsequent brushing of the teeth removes this plaque buildup. However, if plaque is Clinical features of gingivitis allowed to build up for 3 or 4 days, bacteria begin to undergo internal calcification, producing calcium phosphate, better Gingivitis is characterized by swelling and reddening of the known as tartar (or calculus). This adheres tightly to the sur- gums, which bleed easily with slight trauma; for example, face of the tooth and retains bacteria in situ. The bacteria when brushing teeth. Plaque might be visible, especially on release enzymes and toxins that invade the gingival mucosa, teeth that are difficult to reach when toothbrushing. Halitosis causing inflammation of the gingiva (gingivitis). If the pla- might also be present. que is not removed, the inflammation travels downwards, involving the periodontal ligament and associated tooth Periodontitis structures (periodontitis). A pocket forms between the tooth If gingivitis is left untreated, it will progress into periodonti- and gum and, over a period of years, the root of the tooth and tis. Symptoms are similar to those of gingivitis but the patient bone are eroded until the tooth becomes loose and is lost. will experience spontaneous bleeding, taste disturbances, This is the main cause of tooth loss in people over 40 years halitosis and difficulty while eating. Periodontal pockets of age. might be visible, and the patient might complain of loose A number of risk factors are associated with gingivitis and teeth. Referral to a dentist is needed for evaluation. periodontitis; these include diabetes mellitus, cigarette smoking, poor nutritional status and poor oral hygiene. Medicine-induced gum bleeding Gingivitis also worsens during pregnancy. Medicines such as warfarin, heparin, and NSAIDs might pro- duce gum bleeding. It is also worth noting that a number of Arriving at a differential diagnosis medicines can cause gum hypertrophy, notably phenytoin and ciclosporin. It has also been seen in patients taking Gingivitis often goes unnoticed because symptoms can be nifedipine. If medicine-induced gum hypertrophy is sus- very mild and painless. This often explains why a routine pected, the patient should have at minimum 1- to 3-month checkup at the dentist reveals more severe gum disease than history of taking the medicine. patients thought they had. A dental history needs to be taken from the patient, in particular details of his or her tooth- Spontaneous bleeding brushing routine and technique, as well as the frequency of visits to the dentist. The mouth should be inspected for A number of conditions can produce spontaneous gum tell-tale signs of gingival inflammation. A number of bleeding; for example, agranulocytosis and leukaemia. Other Gingivitis 173 symptoms should be present, such as progressive fatigue, toothpaste to prevent tooth decay should preferably take weakness and signs of a systemic illness such as fever. In place after eating. Flossing is recommended three times a agranulocytosis, the patient will have a history of taking medicines that decrease granulocyte production. week to access areas that a toothbrush might miss; this is associated with less gum bleeding compared with tooth- 7 brushing alone (Sambunjak et al., 2019). Oral lichen planus A Cochrane review concluded that powered toothbrushes (with rotation oscillation action, where the brush heads This commonly manifests on the gingiva. It presents with rotate in one direction and then in the opposite direction) nonswollen red gingiva with white, plaque-type lesions. are more effective than manual brushing for plaque removal For more information see the oral thrush section. (Yaacob et al., 2014). There is a plethora of oral hygiene products marketed to the TRIGGER POINTS indicative of referral: Gingivitis public. These products should be reserved for established gingi- vitis or those patients who have a poor toothbrushing technique. Symptoms Possible danger Urgency of Mouthwashes contain chlorhexidine, hexetidine and and signs and reason for referral hydrogen peroxide. Of these, chlorhexidine has high-quality referral evidence for reducing dental plaque and gingivitis, regard- Foul taste Suspect As soon as less of its concentration (James et al., 2017). associated periodontitis practicable to with gum a dentist Practical prescribing and product selection bleeding Loose teeth Prescribing information relating to the medicines used for Spontaneous Suspect Immediate gingivitis is discussed and summarized in Table 7.8; useful gum periodontitis or referral to tips relating to products for oral care are given in ‘Hints bleeding more sinister either a dentist and Tips’ in Box 7.3. pathology or doctor All mouthwashes have minimal side effects and can be Signs of Indicator of more As soon as used by all patient groups. They are rinsed around the mouth systemic serious practicable to for 30 to 60 seconds and spat out. illness underlying a doctor pathology Chlorhexidine gluconate mouthwash (e.g., Corsodyl) This is suitable for adults and children older than 12 years, Evidence base for over-the-counter medication with a standard dose of 10 mL twice a day. Although chlor- Put simply, there is no substitute for good oral hygiene. Pre- hexidine is free from side effects, patients should be warned vention of plaque buildup is the key to healthy gums and that prolonged use (>4 weeks) may stain the tongue and teeth. Twice-daily brushing is recommended to maintain oral brown the teeth. This can be reduced or removed by brushing hygiene at adequate levels. Brushing teeth with a fluoride teeth before use. If this fails to remove the staining, it can be Table 7.8 Practical prescribing: Summary of medicines for gingivitis Drug Name of Use in Very common (≥1/10) or interactions of Patients in whom Pregnancy and medicine children common (≥1/100) side effects note care is exercised breastfeeding Chlorhexidine >12 years Staining of teeth and tongue. Mild None None OK irritation Hexetidine >6 years Mild irritation or numbness of tongue Hydrogen >6 years None peroxide 174 Gastroenterology HINTS AND TIPS BOX 7.3: TOOTH PROTECTION Dental flossing A piece of floss about 8 inches long should be wrapped around the ends of the middle fingers of each hand, leaving 2 to 3 inches between the first finger and thumb. The floss should be placed between two teeth and curved into a C shape around one tooth, slid up between the gum and tooth until resistance is felt, and then moved vertically up and down several times to remove plaque. Using fluoride Fluoride does reduce dental caries. Drinking water in some parts of the UK contains measurable concentrations of fluoride. Therefore, fluoride toothpastes or fluoride supplementation is not needed However, most people in Britain require fluoride supplementation, which is normally obtained through toothpaste. Most packs of toothpaste state how many parts per million (ppm) of fluoride the toothpaste contains: 00 ppm is a low level, 1000–1500 ppm is a high level. A low-dose toothpaste should be used for children 50 years, in whom a specific pathological condition becomes more common. Location Dyspepsia is experienced as pain above the umbilicus and centrally located (epigastric area). Pain below the umbilicus will not be due to dyspepsia. Pain experienced behind the sternum (breastbone) is likely to be heartburn. If the patient can point to a specific area of the abdomen, it is unlikely to be dyspepsia. Nature of pain Pain associated with dyspepsia is described as aching or discomfort. Pain described as gnawing, sharp or stabbing is more likely to be ulcer-related. Radiation Pain that radiates to other areas of the body is indicative of more serious pathology, and the patient must be referred. The pain might be cardiovascular in origin, especially if the pain is felt down the inside aspect of the left arm. Severity Pain described as debilitating or severe must be referred to exclude more serious conditions. Associated symptoms Persistent vomiting with or without blood is suggestive of ulceration or even cancer and must be referred. Black and tarry stools indicate a bleed in the gastrointestinal tract and must be referred. Aggravating or relieving Pain shortly after eating (1–3 hours) and relieved by food or antacids are classic symptoms of ulcers. factors Symptoms of dyspepsia are often brought on by certain types of food; for example, caffeine-containing products and spicy food. Social history Bouts of excessive drinking are commonly implicated in dyspepsia. Likewise, eating food on the move or too quickly is often the cause of the symptoms. A person’s lifestyle is often a good clue to whether these are contributing to the symptoms. Risk factors for GORD Stress, smoking, being overweight, and taking medicines that decrease lower oesophageal sphincter tone predispose people to GORD. GORD, Gastro-oesophageal reflux disease. use is associated with a three- to fourfold increase in gastric affect up to 25% of patients. Table 7.11 lists other medicines ulcers. commonly implicated in causing dyspepsia. Duodenal ulcers tend to be more consistent in symptom presentation. Pain occurs 2 to 3 hours after eating, and pain Irritable bowel syndrome that awakens a person at night is highly suggestive of a Patients younger than 50 years who have uncomplicated duodenal ulcer. dyspepsia, lower abdominal pain, and altered bowel habits The peak incidence of duodenal ulcers is between 45 and are likely to have irritable bowel syndrome (IBS). For further 64 years, whereas the incidence of gastric ulcers increases details on IBS, see later in this chapter. with age. If ulcers are suspected, referral to the GP is neces- sary because peptic ulcers can only be conclusively diag- Biliary disease nosed by endoscopy. Acute cholecystitis (inflammation of the gallbladder) and cholelithiasis (presence of gallstones in the bile ducts, also Medicine-induced dyspepsia called biliary colic) typically present with sudden persistent A number of medicines can cause gastric irritation, leading to colicky and severe epigastric pain. Pain usually lasts or provoking GI discomfort, or they can decrease lower oeso- 30 minutes but can last hours; it starts a few hours after a phageal sphincter tone, resulting in reflux. Aspirin and meal, frequently awakening the patient in the early hours NSAIDs are very often associated with dyspepsia and can of the morning. The pain can radiate to the tip of the right Dyspepsia 177 Pain/discomfort in No Consider other GI epigastric region Yes causes of pain 7 ALARM symptoms Yes Refer ❶ No Taking regular Yes Rule out adverse drug reaction, NSAIDs If ADR suspected contact GP No Pain radiates to Yes Refer jaw/neck/arm CVS cause? No Pain wakes Yes Refer patient at night Possible duodenal ulcer No Pain worse when Yes Refer stomach empty Possible gastric ulcer No Heartburn major Yes Reflux: treatment with Treatment failure symptom alginates of 2 weeks No Refer Vague pain with Yes Treatment with antacid for belching/bloating maximum of 2 weeks Treatment failure Fig. 7.10 Primer for the differential diagnosis of dyspepsia. 1, ALARM symptoms. These include anaemia (signs can include tiredness and pale complexion), loss of weight, anorexia, dark stools, difficulty in swallowing and vomiting blood. GI, Gastrointestinal; GP, general practitioner; NSAIDs, nonsteroidal antiinflammtory drugs. scapula (see Fig. 7.18). Fatty foods often aggravate the pain. Oesophageal carcinoma Nausea and vomiting are common. The incidence increases In its early stages, oesophageal carcinoma might go unno- with increasing age and is most common in people older than ticed. Over time, however, because the oesophagus becomes 50 years. It is also more prevalent in women than in men. constricted, patients will complain of difficulty in swallow- ing and experience a sensation of food sticking in the Very unlikely causes oesophagus. As the disease progresses, weight loss becomes prominent, and anaemia may occur. Gastric carcinoma Gastric carcinoma is the third most common GI malignancy Atypical angina after colorectal and pancreatic cancers. However, only 2% Not all cases of angina have the classic textbook presentation of patients who are referred by their GP for an endoscopy of pain in the retrosternal area with radiation to the neck, have malignancy. It is therefore a rare condition, and com- back, or left shoulder that is precipitated by temperature munity pharmacists are extremely unlikely to encounter a changes or exercise. Patients can complain of dyspepsia-like patient with carcinoma. One or more ALARM symptoms symptoms and feel generally unwell. These symptoms might should be present, plus symptoms such as nausea and be brought on by a heavy meal. In such cases, antacids will vomiting. fail to relieve symptoms, and referral is needed. 178 Gastroenterology Table 7.11 pale complexion, Medicines that commonly cause dyspepsia/ shortness of abdominal discomfort breath) Acarbose (1%–10%) Loss of weight Antibiotics (e.g., macrolides, tetracyclines) Anorexia Anticoagulants Recent onset of progressive Angiotensin-converting enzyme (ACE) inhibitors symptoms Alcohol (in excess) Melaena, dysphagia, and Bisphosphonates haematemesis Calcium antagonists Pain described as Suggests As soon as severe, ulceration practicable Iron debilitating or that awakens the Metformin patient at night Metronidazole Persistent vomiting Nitrates Referred pain Possible cardiovascular Oestrogens or biliary cause Orlistat (>10%) Potassium supplements Selective serotonin reuptake inhibitors Sildenafil (1%–10%) Evidence base for over-the-counter medication Steroids The National Institute for Health and Care Excellence (NICE) has issued guidance on the management of dyspepsia and Theophylline GORD in adults in primary care (2014). These guidelines have specific information on pharmacist management of dyspepsia, and specific reference is made to this guidance. Other conditions In accordance with NICE guidelines, the group of patients Coeliac disease, Crohn’s disease, and pancreatitis can exhibit that should be treated by pharmacists are classed as having dyspepsia-like symptoms, although these will not be the ‘uninvestigated dyspepsia’ (i.e., those who have not had major presenting symptoms. Symptoms such as diarrhoea endoscopic investigation). OTC treatment options consist and pain will be much more prominent. of antacids, H2 antagonists, alginates and proton pump Fig. 7.10 will aid in the differentiation of the causes of inhibitors (PPIs). Before treatment is initiated, lifestyle dyspepsia. advice should be given where appropriate. Although there is no strong evidence that dietary changes will lessen dys- pepsia symptoms, a general healthier lifestyle will have TRIGGER POINTS indicative of referral: Dyspepsia wider health benefits. Recommendations should include the following: Symptoms/signs Possible danger/ Urgency of reason for referral Change diet to a lower fat diet. referral Keep alcohol intake to recommended levels. ALARM signs and Symptoms Urgent Stop smoking. symptoms requiring referral to Decrease weight. further GP Reduce caffeine intake. Anaemia (signs investigation include tiredness, It might also be possible to identify factors that precipitate or worsen symptoms. Commonly implicated foods that Dyspepsia 179 precipitate dyspepsia are spicy or fatty foods, caffeine, choc- Proton pump inhibitors olate and alcohol. Bending is also said to worsen symptoms. 7 A number of trials have compared PPIs with H2 antagonists for nonulcer dyspepsia and GORD-like symptoms (Talley Antacids et al., 2002; Sigterman et al., 2013; Pinto-Sanchez et al., Antacids have been used for many decades to treat dyspepsia 2017). Results indicated that PPIs, even at half the standard and have proven efficacy in neutralizing stomach acid. How- POM dose, are generally superior to H2 antagonists in treat- ever, the neutralizing capacity of each antacid varies, ing dyspeptic symptoms. depending on the metal salt used. In addition, the solubility of each metal salt differs, which affects their onset and dura- Summary tion of action. Sodium and potassium salts are the most Antacids will work for most people presenting at the phar- highly soluble, which enables them to have a quicker onset, macy with mild dyspeptic symptoms. They can be used as but are shorter acting. Magnesium and aluminium salts are first-line therapy unless heartburn predominates; then an less soluble, so these have a slower onset, but longer duration alginate or alginate–antacid combination can be used. H2 of action. Calcium salts have the advantage of being quick antagonists appear to be equally as effective as antacids acting and have a prolonged action. but are considerably more expensive. PPIs are most effective It is therefore common for manufacturers to combine two and could be considered first-line, especially for those or more antacid ingredients together to ensure a quick onset patients who suffer from moderate to severe or recurrent (generally sodium salts; e.g., sodium bicarbonate) and pro- symptoms. Like H2 antagonists, they are expensive in com- longed action (aluminium, magnesium or calcium salts). parison to simple antacids and might influence patient choice or the pharmacist’s recommendation. Alginates Alginate products are promoted as first-line treatment for Practical prescribing and product selection patients suffering from GORD. When in contact with gastric acid the alginate precipitates out, forming a spongelike Prescribing information relating to the medicines used for matrix that floats on top of the stomach contents. Alginate dyspepsia is discussed and summarized in Table 7.12. A small preparations are also commonly combined with antacids to number of products are licensed for children younger than help neutralize stomach acid. In clinical trials, alginate- 16 years but should not be recommended because dyspepsia containing products have demonstrated superior symptom symptoms in children are uncommon. control compared with placebo and antacids, although the evidence of greater efficacy is limited. Antacids Most antacids marketed are combination products contain- H2 antagonists ing two, three or even four constituents. The rationale for Just one H2 antagonist is currently available OTC in the UK, combining different salts together appears to be twofold: ranitidine. Cimetidine and famotidine were also available First, to ensure the product has quick onset (containing OTC but have been withdrawn by the manufacturer; nizati- sodium or calcium) and a long duration of action (con- dine has exemption from POM control but currently there is taining aluminium or calcium) no marketed product. Second, to minimize any side effects that might be expe- There is a paucity of publicly available trial data support- rienced from the product ing their use at nonprescription doses. The inhibitory effects of OTC doses of ranitidine on gastric For example, magnesium salts tend to cause diarrhoea, acid have been investigated in healthy volunteers. Trials and aluminium salts tend to cause constipation; however, showed conclusively that ranitidine and its comparator drug if both are combined in the same product, neither side effect famotidine significantly raised intragastric pH compared with is noticed. Useful tips relating to antacids are given in ‘Hints placebo, although antacids (calcium carbonates) had a signif- and Tips’ in Box 7.4. icantly quicker onset of action but with shorter duration. Antacids can affect the absorption of a number of medi- Controlled studies have consistently shown H2 antago- cations via the mechanisms of chelation and adsorption. nists to be superior to placebo (Moayyedi et al., 2006). How- Commonly affected medicines include tetracyclines, quino- ever, the same review found only two head to head studies lones, imidazoles, phenytoin, penicillamine and bispho- comparing H2 antagonists with antacids, and the results sphonates. In addition, the absorption of enteric-coated showed no significant difference in symptom scores. preparations can be affected due to antacids increasing the 180 Gastroenterology Table 7.12 Practical prescribing: Summary of medicines for dyspepsia Very common (≥1/10) Patients in Name of Use in or common (≥1/100) Drug interactions whom care Pregnancy and medicine children side effects of note is exercised breastfeeding Antacids Sodium only >12 years None None Patients with OK heart disease Calcium only Constipation Tetracyclines, None OK quinolones, Magnesium only Diarrhoea imidazoles, Aluminium only Constipation phenytoin, penicillamine and bisphosphonates Alginates >12 yearsa None None Patients with OK heart disease Ranitidine >16 years None None None Experience has shown them to be OK; reported diarrhoea with famotidine during breastfeeding PPIs Omeprazole, >18 years Headache, diarrhoea, Azole antifungals, None Manufacturers advise esomeprazole constipation, nausea clopidogrel, avoidance but limited and vomiting, diazepam, information indicates abdominal pain, fluvoxamine, that maternal PPI doses insomnia, dizziness, cilostazol, produce low levels in dry mouth, rash atazanavir milk and would not be expected to cause any adverse effects in breastfed infants Pantoprazole As for other PPIs, plus fatigue PPIs, Proton pump inhibitors. a Certain products can be given to children but dyspepsia is unusual in children and it might be prudent to refer such patients to their GP. Alginates stomach pH. Most of these interactions are easily overcome by leaving a minimum gap of 1 hour between the respective Products containing alginates (e.g., the Gaviscon range) are doses of each medicine. combination preparations that contain an alginate with ant- Most patient groups can take antacids, although patients acids. They are best given after each main meal and before on salt-restricted diets (e.g., patients with coronary heart dis- bedtime, although they can be taken on an as-needed basis. ease) should ideally avoid sodium-containing antacids. They can be given during pregnancy and breastfeeding and Dyspepsia 181 HINTS AND TIPS BOX 7.4: ANTACIDS Type of formulation? Ideally, antacids should be given in the liquid form because the acid-neutralizing capacity and speed of onset is greater than that of tablet formulations. 7 Overuse of antacids Misuse and chronic use of antacids will result in significant systemic absorption, leading to various unwanted medical conditions. Milk-alkali syndrome has been reported with chronic abuse of calcium-containing antacids, as has osteomalacia with aluminium-containing products. Antacid therapy should ideally not be longer than 2 weeks. If symptoms have not resolved in this time, other treatments and/or evaluation from the GP should be recommended. When is the best time Antacids should be taken after food because gastric emptying is delayed in the presence to take antacids? of food. This allows antacids to exert their effect for up to 3 hours. Salt (sodium) content Be aware that some antacid preparations contain significant amounts of sodium; for example, Gaviscon Advance contains 4.6 mmol of sodium/10 mL. UK Medicines Information (UKMi) has produced a document detailing medicines with high sodium content.a Older adults Avoid constipating products because older adults are prone to constipation. Possible solutions to Simple suggestions such as eating less but eating more often or eating smaller meals might minimize symptoms help control symptoms. Avoid eating late at night and lying flat at night; use a pillow to prop up the person. a Specialist Pharmacy Service. What is the sodium content of medicines? 2019. https://www.sps.nhs.uk/articles/what-is-the-sodium-content-of-medicines-2 to most patient groups but, as with antacids, patients on salt- Omeprazole (Dexcel Heartburn Relief Tablets, restricted diets should ideally avoid sodium-containing algi- Boots Acid Reflux Tablets) nate preparations. They are reported not to cause side effects or interactions with other medicines. This is marketed for the relief of reflux-like symptoms (e.g., heartburn) associated with acid-related dyspepsia. Omeprazole can cause a number of common side effects Ranitidine (>1 in 100; see Table 7.12). Drug interactions with omepra- Sales of ranitidine (e.g., Zantac, Gavilast, Ranicalm) are zole are possible because it is metabolized in the liver by restricted to adults and children older than 16 years. It pos- cytochrome P450 isoenzymes. These include azole antifun- sesses no clinically important drug interactions, and side gals (decreased azole bioavailability), diazepam (enhanced effects are rare. Evidence suggests that it can be used in preg- diazepam side effects), fluvoxamine (increased omeprazole nancy and breastfeeding, although manufacturers advise levels), cilostazol (increased cilostazol levels) and clopidogrel patients to speak to their doctor or pharmacist before taking. (reduced clopidogrel levels). Other interactions listed in the One tablet (75 mg) should be taken straight away but, if manufacturer’s literature include phenytoin and warfarin, symptoms persist, another tablet should be taken 1 hour but their clinical significance appears low. later. The maximum dose is 300 mg (four tablets) in 24 hours. It appears to be safe in pregnancy and excreted in only The General Sales List versions of ranitidine (Zantac 75 Relief small amounts of breast milk; it is not contraindicated when and Ranicalm) cannot be used for the prevention of heart- used as a POM medicine. However, product licences for phar- burn, and the maximum dose is only two (150-mg) tablets macy use state that it should not be recommended. in 24 hours. Esomeprazole (Nexium Control) Nexium Control is indicated for the short-term treatment of Proton pump inhibitors reflux symptoms (e.g., heartburn and acid regurgitation) in These are only available to adults and those aged 18 years adults. The recommended dose is 20 mg (one tablet) once and older. If symptoms have not been controlled within daily with its side effects and cautions in use being the same 2 weeks, the patient should be referred to the doctor. as for omeprazole. 182 Gastroenterology Pantoprazole National Institute for Health and Care Excellence (NICE). (2017). Pantoprazole (Pantoloc Control) has a license for the short- Suspected cancer: Recognition and referral. https://www. term symptomatic treatment of GORD-like symptoms (e.g., nice.org.uk/guidance/ng12. Reilly, T. G., Singh, S., Cottrell, J., et al. (1996). Low-dose heartburn). The dosage is one 20-mg tablet daily. Manufac- famotidine and ranitidine as single post-prandial doses: turers advise avoidance in pregnancy and breastfeeding A three-period placebo-controlled comparative trial. women. However, limited data in breastfeeding indicate that Alimentary Pharmacology & Therapeutics, 10, 749–755. maternal pantoprazole doses of 40 mg daily produce low Smart, H. L., & Atkinson, M. (1990). Comparison of a levels in milk and would not be expected to cause any dimethicone/antacid (Asilone gel) with an alginate/antacid adverse effects in breast-fed infants. Like other PPIs, panto- (Gaviscon liquid) in the management of reflux oesophagitis. prazole is associated with a number of side effects, interac- Journal of the Royal Society of Medicine, 83, 554–556. tions, and cautions. Websites American Gastroenterological Association: https://www. References gastro.org/ Moayyedi, P., Soo, S., Deeks, J., et al. (2006). Pharmacological British Society of Gastroenterology: https://www.bsg.org.uk/ interventions for non-ulcer dyspepsia. Cochrane Database of Gastroenterological Society of Australia: https://www.gesa.org.au/ Systematic Reviews, (4), CD001960. https://doi.org/10.1002/ GutsUK: https://gutscharity.org.uk/ 14651858.CD001960.pub3. New Zealand Society of Gastroenterology: https://nzsg.org.nz/ National Institute for Health and Care Excellence (NICE). (2014). Gastro-oesophageal reflux disease and dyspepsia in adults: Investigation and management. https://www.nice.org.uk/ guidance/cg184. Pinto-Sanchez, M. I., Yuan, Y., Hassan, A., Bercik, P., & Moayyedi, Diarrhoea P. (2017). Proton pump inhibitors for functional dyspepsia. Cochrane Database System Review, (11), CD011194. Talley, N. J., Moore, M. G., Sprogis, A., et al. (2002). Randomised Background controlled trial of pantoprazole versus ranitidine for the treatment of uninvestigated heartburn in primary care. The Diarrhoea can be defined as an increase in frequency of the Medical Journal of Australia, 177(8), 423–427. passage of soft or watery stools relative to the usual bowel Sigterman, K. E., van Pinxteren, B., Bonis, P. A., et al. (2013). habit for that individual. The World Health Organization Short-term treatment with proton pump inhibitors, H2- (2017) defines this as the passage of three or more loose or liq- receptor antagonists and prokinetics for gastro-oesophageal uid stools per day. It is not a disease but a sign of an underlying reflux disease-like symptoms and endoscopy negative reflux problem, such as an infection or gastrointestinal disorder. It disease. Cochrane Database System Review, (5), CD002095. can be classified as acute (14 days), Further reading or chronic (lasting longer than a month). Most patients will Castell, D. O., Dalton, C. B., Becker, D., et al. (1992). Alginic acid present to the pharmacy with a self-diagnosis of acute diar- decreases postprandial upright gastroesophageal reflux. rhoea. It is necessary to confirm this self-diagnosis because Comparison with equal-strength antacid. Digestive Diseases patients’ interpretations of their symptoms might not match and Sciences, 37, 589–593. closely with the medical definition of diarrhoea. Neilson, J. P. (2008). Interventions for heartburn in pregnancy. Cochrane Database System Review, (4), CD007065. Prevalence and epidemiology Drake, D., & Hollander, D. (1981). Neutralizing capacity and cost effectiveness of antacids. Annals of Internal Medicine, 94, The exact prevalence and epidemiology of diarrhoea are not 215–217. well known. This is probably due to the number of patients Feldman, M. (1996). Comparison of the effects of over-the who do not seek care or who self-medicate. However, acute counter famotidine and calcium carbonate antacid on diarrhoea does generate high medical consultation rates. It postprandial gastric acid. A randomized controlled trial. has been reported that children under the age of 5 years have JAMA, 275, 1428–1431. between one and three bouts of diarrhoea per year and adults, Halter, F. (1983). Determination of neutralization capacity of antacids in gastric juice. Zeitschrift für Gastroenterologie, 21, on average, just under one episode of diarrhoea per year. S33–S40. Many of these cases are thought to be food-related. Netzer, P., Brabetz-Hofliger, A., Brundler, R., et al. (1998). Comparison of the effect of the antacid Rennie versus low Aetiology dose H2 receptor antagonists (ranitidine, famotidine) on intragastric acidity. Alimentary Pharmacology & The aetiology of diarrhoea depends on its cause. Acute gastro- Therapeutics, 12, 337–342. enteritis, the most common cause of diarrhoea in all age groups, is usually viral in origin. Commonly implicated viruses Diarrhoea 183 are the rotaviruses (now vaccine preventable) and noroviruses. Table 7.13 Viruses tend to cause diarrhoea by blunting the villi of the Causes of diarrhoea and their relative incidence in upper small intestine, decreasing the absorptive surface. Bac- terial causes of diarrhoea are normally a result of eating con- community pharmacy Incidence Cause 7 taminated food or drink, which cause diarrhoea by a number of mechanisms. For example, enterotoxigenic Escherichia coli Most likely Viral and bacterial infection produces enterotoxins that affect gut function with secretion Likely Medicine-induced and loss of fluids, enteropathogenic E. coli interferes with nor- mal mucosal function, and enteroinvasive E. coli, Shigella, Unlikely Irritable bowel syndrome, giardiasis, faecal and Salmonella spp. cause injury to the mucosa of the small impaction intestine and deeper tissues. Very unlikely Ulcerative colitis, Crohn’s disease, colorectal Other organisms – for example, Staphylococcus aureus cancer, malabsorption syndromes and Bacillus cereus – produce preformed enterotoxins, which on ingestion stimulate the active secretion of electrolytes into the intestinal lumen. Clinical features of acute diarrhoea Arriving at a differential diagnosis Symptoms are normally rapid in onset, with the patient hav- The most common causes of diarrhoea are viral and bacterial ing a history of prior good health. Nausea and vomiting infections (Table 7.13), and the community pharmacist can might be present before or during the bout of acute diarrhoea. appropriately manage the vast majority of cases. The main pri- Abdominal cramping, flatulence and tenderness are also ority is identifying patients that need referral and how quickly often present. If rotavirus is the cause, the patient might also they need to be referred. Dehydration is the main complicating experience viral prodromal symptoms such as cough and factor, especially in the very young and very old. A number of cold. Acute infective diarrhoea is usually watery in nature, diarrhoea-specific questions should always be asked of the with no blood present. Complete resolution of symptoms patient to aid in the differential diagnosis (Table 7.14). should be observed in 2 to 4 days. ? Table 7.14 Specific questions to ask the patient: Diarrhoea Question Relevance Nature of the stools Diarrhoea associated with blood and mucus (dysentery) requires referral to eliminate invasive infection such as Shigella, Campylobacter jejuni, Salmonella, Clostridium difficile and Escherichia coli O157. Bloody stools are also associated with conditions such as inflammatory bowel disease. Periodicity A history of recurrent diarrhoea of no known cause should be referred for further investigation. Duration A person who presents with a history of chronic diarrhoea should be referred. The most frequent causes of chronic diarrhoea are irritable bowel syndrome (IBS), inflammatory disease, and colon cancer. Onset of symptoms Ingestion of bacterial pathogens can give rise to symptoms in a matter of a few hours (toxin-producing bacteria) after eating contaminated food or up to 3 days later. It is therefore important to ask about food consumption over the last few days, establish if anyone else ate the same food, and check the status of his or her health. Timing of diarrhoea Patients who experience diarrhoea first thing in the morning might have underlying pathology such as IBS. Recent change of Changes in diet can cause changes to bowel function; for example, when away on holiday. If the person has diet recently been to a non-Western country, giardiasis is a possibility. Signs of Mild (10%] or common (1%–10%). Adapted from Whittlesea C. Hodson K. Clinical Pharmacy and Therapeutics. 6th ed. London: Churchill Livingston: 2018. soiling as a result of liquid passing around hard stools and suspected in individuals with persistent GI symptoms such mistakenly believe they have diarrhoea. On questioning, as steatorrhoea (fatty, frothy or floating stools in the toilet), the patient might describe the passage of regular, poorly bloating and abdominal pain. Fatigue and weight loss are formed hard stools that are difficult to pass. Referral is also observed. needed because manual removal of the faeces is often required. Colorectal cancer Approximately 40 000 new cases of colorectal cancer are Very unlikely causes registered each year in the UK and represent the second most Ulcerative colitis and Crohn’s disease common cause of cancer deaths. Occurrence is strongly Both conditions are characterized by chronic inflammation related to age, with almost 75% of cases occurring in people at various sites in the GI tract and follow periods of remission aged 65 years and older. Colorectal carcinomas are rare in and relapse. They can affect any age group, although peak patients younger than 40 years, but any middle-aged patient incidence is in those between 20 and 30 years. In mild cases presenting with signs of anaemia (e.g., fatigue, pale skin, of both conditions, bloody diarrhoea is one of the major pre- shortness of breath) and a change in bowel habits should senting symptoms. Patients often have left lower quadrant be viewed with suspicion. Persistent diarrhoea accompanied abdominal pain and suffer from urgency, nocturnal diar- by a feeling that the bowel has not really been emptied is sug- rhoea and early morning rushes. In the acute phase, patients gestive of neoplasm. This is especially true if weight loss is will appear unwell and have malaise. also present. However, weight loss, a classic textbook sign of colon cancer, is common but observed only in the later Malabsorption syndromes stages of the disease. Therefore, a patient is unlikely to have Lactose intolerance is often diagnosed in infants under 1 year noticed a marked weight loss when visiting a pharmacy early old. In addition to more frequent loose bowel movements, in the disease progression. symptoms such as fever, vomiting, perianal excoriation Further information on symptoms that are suggestive and a failure to gain weight might occur. of lower GI tract cancers is provided by NICE (https://cks. Coeliac disease has a bimodal incidence; first, in early nice.org.uk/gastrointesti

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