June 2013

Make the pharmacist occupation respectable again

News Bringing CMPA to light

Feature Understanding common feeding issues in infants

Spotlight Pharmacists should brush up on oral health advice

Pharmacy Practice Benefits and Risks of hormone replacement therapy in menopause

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News | Pharmacy Today | June 2013 

Make the pharmacist occupation respectable again
By Pank Jit Sin

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he business of running a pharmacy and running a sundry shop is not much different today, with up to 80 percent of floor space in a community pharmacy taken up by daily-use items such as cosmetics, haircare products and groceries. “The pharmacy section is often just a small corner at the back of the shop,” said Rainee Joy, a pharmacist and CEO of Lovy Pharmacy. “What is our focus? We are supposed to provide professional healthcare services, but because of cash-flow constraints, we have to resort to these measures.” Another red-zone practice, said Ms Rainee, is ‘throwing price’ or being known as a ‘discounter’. This practice is so rampant that consumers often discuss which pharmacy has the cheapest prescription medicines and supplements. Beyond discounts, Ms Rainee pointed to the practice of selling medicines without prescription. Apart from being unethical, it is also illegal and could lead to serious repercussions. Ms Rainee also touched upon the issue of pharmacists conducting unlicensed practices. “We have intruded upon the roles of other healthcare professionals such as doctors and pathologists.” Some pharmacists today provide blood pressure measurement in their pharmacy, proceed to diagnose hypertension and subsequently prescribe an antihypertensive agent. Needless to say, such a practice should be stopped, she said.

Instead of resorting to such ‘red-zone’ practices, Ms Rainee suggested pharmacists sell quality professional pharmacy services, and brand themselves as ethical professionals. By upholding the profession, Ms Rainee said wider roles will open up for pharmacists as they will be seen as more than mere ‘licensed drug pushers’ and as legitimate sources of knowledge on drugs and medicines. She also encouraged pharmacists to retail their products within a more standardized price range. By upholding the profession to the highest ethical standards, pharmacists can further justify the delegation of dispensing rights to them. This would, in turn, translate into better profits and sales. On the Lovy Pharmacy business model, Ms Rainee said the pharmacy does not have to resort to selling sundry goods as it works synergistically with BP Diagnostic Centres. Health-conscious individuals who come for screening are directed to the right place ie, either to doctors or pharmacists – all of whom are housed under the same roof. “We work side by side with our diagnostic center, which consists of a diversified team of healthcare professionals including doctors, pharmacists, nurses and nutritionists. Here, the services are provided by the right professionals who have been entrusted with the right roles, without intrusion from other professions.”

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Dietary changes to treat gout

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hile eating or avoiding certain foods may not help all arthritis sufferers, it is important to adjust your diet if you suffer from gout. Gout mainly affects middle-aged men, and is closely linked with the level of uric acid in the body. Uric acid is a by-product of the metabolism of foods rich in purines, and is also made by the body. Excess uric acid is transferred by the kidneys to urine and removed by the body. However, people with gout either produce too much uric acid or their kidneys are unable to dispose of it sufficiently. Uric acid accumulation results in tiny needle-shaped crystals in the joints, causing inflammation and pain. A gout attack can occur overnight, followed by severe pain and joint inflammation that can last five to 10 days. The big toe where it joins the ball of the foot, the instep, ankle, knee, kneecap, wrist, tip of the elbow and fingers can all be affected.

Medical advice should be sought early as an NSAID can be effective as a pain reliever, but the dose should be adequate and the drug should be taken at the first sign of the attack. Drugs such as colchicine or corticosteroids administered as tablets or an injection into the joint can be used for a short period. Medications containing aspirin should be avoided. Drugs such as allopurinol or probenecid will help control uric acid levels and should be taken over a long period of time, even if the patient does not feel ill. Dietary changes recommended are: • avoid or restrict foods high in purines such as offal, sardines, anchovies, shell fish, fish roe, peas, lentils, beans, Marmite and Vegemite • avoid large amounts of red meat • drink alcohol in moderation • drink plenty of non-alcoholic fluids as dehydration can trigger an attack.

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Bringing CMPA to light
By Malvinderjit Kaur Dhillon

CMPA and lactose intolerance
ow’s milk protein allergy (CMPA), the most common form of food allergy among infants in Malaysia, is often referred to as lactose intolerance. In fact, both two very different conditions, says an expert. The terms ‘intolerance’ and ‘allergy’ have been used too loosely and interchangeably, said Amir Hamzah Abdul Latif, president of the Malaysian Society of Allergy and Immunology (MSAI), and a consultant pediatrician and consultant clinical immunologist/allergist. An allergy, as defined and endorsed by the World Allergy Association since 1999, is when there is immune system involvement, said Dr Amir. When a hypersensitivity reaction occurs without an immunological mechanism, it is defined as an intolerance. “Based on the similar signs and symptoms of CMPA and lactose intolerance, one may easily be mistaken for the other. However, the mechanisms involved are very different: this is the major difference. Lactose intolerance involves a non-immunological mechanism which occurs due to lactase deficiency. Due to this, lactose cannot be broken up into its components – glucose and galactose,” said Dr Amir. The amount of cow’s milk involved, as well as the time between exposure and reaction, can be used to differentiate between CMPA and intolerance. In infants with CMPA, a small amount of protein is enough to elicit symptoms. Exposure in CMPA is not limited to consumption of cow’s milk, but also includes smelling or coming into physical contact with it eg, a mother kissing her baby’s

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From L-R: Prof Lee, Dr Amir Hamzah and Dr Chai Pei Fan advocating the guidelines for the management of CMPA in children

cheek after consuming cow’s milk causes the baby’s lips to swell. Intolerance, on the other hand, means a person may be able to tolerate two glasses of milk without a problem, but then start to show symptoms after consuming a third glass. Children with CMPA develop symptoms in several organ systems such as the skin, gastrointestinal (GI) tract and respiratory tract. Symptoms involving the skin include itching, hives or welts, flushing and swelling. GI tract symptoms include itching of the mouth and lips, abdominal pain, vomiting and diarrhea. Respiratory symptoms include sneezing, coughing, wheezing, tightness in the throat and dyspnea. In severe cases, CMPA can also manifest as anaphylaxis, a life-threatening reaction. “Usually, CMPA presents within two hours of exposure to CMP. Lactose intolerance takes longer to present,” said Dr Amir.

Managing CMPA
Lee Way Seah, a professor of pediatrics and a senior consultant pediatrician, highlighted the management guidelines on CMPA in children released last year. The guidelines aim to help healthcare professionals better understand the symptoms and signs of CMPA in

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young children and infants, as well as provide comprehensive advice on how to approach CMPA. “The guidelines are especially helpful as they are based on products available in Malaysia. The overall principle is to promote breastfeeding, as we believe it can help prevent or lower the incidence of CMPA. However, in a situation where the mother is unable to breastfeed, we provide guidelines on products available,” said Prof Lee. He also urged parents to use the allergy risk checklist and to seek medical advice if they notice symptoms of CMPA. The checklist provides healthcare professionals with the medical history of the child and parents. It is provided in a CMPA information leaflet available at healthcare centers.

The panel of experts speaking at the CMPA Awareness Campaign

Right diagnosis for CMPA
Chai Pei Fan, a consultant pediatrician and consultant pediatric gastroenterologist and hepatologist, stressed it is essential for parents to seek the opinion of a GP or specialist to get the right diagnosis and proper advice on what milk substitute to use. In discussing some of the misconceptions parents have about CMPA, he said, “… parents often form their own assumptions and will carry out their own interventions. The common practice is to change from one brand of cow’s milk to another. Another popular choice is soy formula. Sometimes, parents also go for lactose-free formulas as they are not aware that CMPA and lactose intolerance are entirely different problems. Some parents also opt for hypoallergenic (HA) formulas

and it seems to be a logical choice for them to make. However, they need to know that HA formulas are used for prevention. If a parent is unable to exclusively breastfeed and the child has a high risk of developing CMPA, HA formula is an option. But once a child has developed CMPA symptoms, this is not an appropriate formula choice,” he said. The panel of experts stressed that prevention is better than cure. They encouraged mothers to breastfeed if they are able to as this is the best way to prevent CMPA. The experts were speaking at the launch of the CMPA Awareness Campaign organized by MSAI and the Malaysian Paediatric Association (MPA) to help educate parents about CMPA among children. The launch was in conjunction with the recent World Allergy Week 2013.
The guidelines for the management of CMPA in children 2012 can be accessed online at www.allergymsai.org/file_ dir/6296706325048109343baa.pdf

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Probiotics can improve gut health
stressful and busy lifestyle can take its toll on the digestive system. However, probiotics can help many people get gut health back on track. Lifestyle and environmental factors such as stress, pollution and drinking too much caffeine and alcohol can all deplete beneficial bacteria from the body. Probiotics can help with a range of digestive health problems including indigestion, constipation, diarrhea and abdominal cramps. They work by correcting the shortage of good bacteria in the system, Nicola Johns Pharmacy owner Nicola Johns said. Probiotics can also aid digestion because the level of processing in food today can leave it lacking in vitamins and nutrients which aid gut health, she added. However, when it comes to deciding which probiotics are the best to recommend, it is a good idea to look at the research and the studies on different strains, she said. Ms Johns would not recommend a probiotic which had shown resistance to antibiotics, for example. How many probiotics a person takes and how often also depends on the symptoms the patient has, she said. Once or twice a day is sufficient if the probiotic is being taken as a preventative measure. However, if the person is vomiting or is starting to get a cough and cold, it is beneficial to increase the frequency to every few hours – increase the frequency rather than the dose, Ms Johns said.

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Selling probiotics is no longer an uphill battle Selling probiotics has also become easier over the last couple of years as there is increased public awareness, which makes it easier to talk to the patients about them. Previously, it was a major exercise in education. As a result, probiotics are more widely accepted and people are more open to trying them, Ms Johns said. While probiotics are recommended for a wide group of people, patients with autoimmune disorders should check with their specialist on whether it is safe for them, she said. Probiotics – it’s all in the details Pharmacists should also advise patients to be consistent when taking probiotics. It is a good idea to develop a routine around taking them, for example, having them with breakfast and dinner, Healthy Food Guide nutritionist Claire Turnbull said. This will help patients keep on track of their routine and to finish the required course. The course needs to be completed for it to be effective, Ms Turnbull added. It is also important to check the label on the probiotics to see how they are meant to be stored because they have to be kept at the right temperature for them to work, the nutritionist said. While probiotics are beneficial for most people, it is important to seek medical advice if there are significant changes to bowel health, such as blood in the stool, Ms Turnbull said.

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Continuous mission to help Malaysians stop smoking
alaysians can now pledge to support the drive towards a cigarettefree country with the new Pledge to Quit Right campaign. All they need to do to show their support for a cigarette-free Malaysia is to post their pledges on the Pledge to Quit Right board at the Pledge to Quit Right roadshow or on the mobile Pledge to Quit Right board transported by Era FM and My FM radio cruisers. Designed not just for smokers who are committed to quit, this first-of-its-kind pledge drive is also targeted at Malaysians wishing for a smoke-free environment, as well as healthcare professionals who are to be recruited to educate patients and customers on the use of smoking cessation aids through GlaxoSmithKline Consumer Healthcare Sdn Bhd’s comprehensive Quit Right platform. The Pledge to Quit Right campaign – a holistic, quitter-at-heart smoking cessation campaign – continues GSK’s ongoing effort to raise awareness amongst smokers as well as non-smokers on the right way to quit smoking. The campaign also endeavors to help smokers plan how to quit smoking, and learn how to stay away from cigarettes for good, with the provision of helpful advice, nicotine replacement therapy and GSK’s Behavioural Support Programme (BSP). Launched in 2012, the BSP is a free webbased program that empowers smokers to plan and monitor their own quit-smoking journey, aided by daily motivation and advice, reading materials and a community support system with other smokers on the same

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By Saras Ramiya

The Pledge to Quit Right campaign is the first of its kind drive targeted at Malaysians who want a smoke-free environment

journey to increase their chances of success. The BSP also allows users to conveniently share updates of their progress on Facebook and through other channels to enhance support from family and friends in their endeavor. The smoking cessation campaign is into its third year and is supported by the Ministry of Health. “The Ministry is pleased to see GSK’s continuous efforts to help smokers quit smoking and raise awareness on the techniques of smoking cessation, through the Pledge to Quit Right campaign this year,” said Lokman Hakim Sulaiman, Deputy Director General of Health (Public Health). “We are also pleased to be collaborating with [GSK] on some of our own initiatives. I commend GSK for once again participating in the National World No Tobacco Day 2013 celebration event,” said Datuk Dr Lokman. “The Pledge to Quit Right campaign by GSK has seen success in other markets and we are excited to introduce it in Malaysia. Our research shows that many smokers may have the will to quit, but have not taken any concrete steps due to lack of knowledge on smoking cessation methods or fear of failure,” said Soumitra Sen, Asia Area Marketing Director (Wellness), GSK.

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News | Pharmacy Today | June 2013  “Many smokers have thought of quitting, and we want to encourage more of them to journey towards not just trying to quit, but to quit for good using the right methods. With the Pledge to Quit Right campaign, the pledges we’re collecting will spur them on, knowing that the nation is supporting their desire to be cigarette-free.”

“With the Pledge to Quit Right campaign, we are incorporating important elements that improve the rates of success, such as consulting Certified Smoking Cessation Service Providers (CSCSP) at pharmacies, garnering support from family and friends, and using tested systems such as the three-step, 12-week quit smoking plan with NiQuitin, our stop-smoking aid that uses nicotine replacement therapy,” said Mr Sen.

MOH liberalizes pharmacists training scope
By Malvinderjit Kaur Dhillon

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he Ministry of Health (MOH) has relaxed the training scope of provisionally trained pharmacists (PRP) with the aim of increasing the pharmacist-to-people ratio by 2016. The MOH also hopes to increase the number of registered pharmacists in Malaysia, which at January 31 stands at 10,250. This liberalization will allow pharmacy graduates to undergo PRP training at private pharmacy facilities such as private hospitals, in research and development, and community pharmacies. Previously, training was limited to government hospitals and facilities, said Dato’ Eisah Abdul Rahman, MOH’s pharmaceuticals services senior director. Eisah said the decision was made to provide a platform for pharmacists to become involved in the private pharmaceutical sector. Community pharmacies interested in being listed as training facilities for graduates are encouraged to submit their applications to the MOH. This will enable them to receive recognition through accreditation of commu-

nity pharmacy program under the Malaysian Pharmacy Board. Pharmacies wishing to participate in the program will need to ensure their premises meet the rules and regulations set in the Community Pharmacy Benchmarking Guidelines*. The MOH’s liberalization of the training scope of pharmacists comes after the shortening of compulsory training for pharmacists from three years to one year effective 2011. Eisah was speaking at the launch of the 100th Cosway Pharmacy in Kuala Lumpur. Cosway Pharmacy has been selected as a recognized establishment for the training of PRP. Cosway Pharmacy is also giving the opportunity for pharmacists who fulfill the attachment requirement to be trained on managing a pharmacy store. They can then go on to be awarded a free store under the Free Store program.
*The Community Pharmacy Benchmarking Guidelines can be found at www.pharmacy.gov.my/v2/sites/default/files/document-upload/ community-pharmacy-benchmarking-guideline-2011.pdf

PHARMACY TODAY

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De-liver us from NAFLD
on-alcoholic fatty liver disease (NAFLD) is a condition where fat accumulates in the liver of people who drink little or no alcohol. NAFLD is a rather common condition, and for most people, causes no signs or symptoms. Unfortunately, in some people with NAFLD, the accumulated fat may cause inflammation and scarring of the liver. This more serious form of NAFLD is sometimes called non-alcoholic steatohepatitis. At its most severe, it can progress to liver failure. A wide range of diseases, conditions and factors can increase the risk of developing NAFLD. These include certain types of medications; gastric bypass surgery; high cholesterol; high levels of blood triglycerides; malnutrition; metabolic syndrome; obesity; rapid weight loss; toxins and chemicals, such as pesticides; type 2 diabetes; and Wilson’s disease. The best ways to detect NAFLD are liver function blood tests, which measure the liver enzyme markers alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transferase (GGT). Elevated levels of these enzyme markers usually denote a problem with the liver and may help the doctor make a diagnosis. Imaging procedures can be used to diagnose NAFLD. These include ultrasound, computerized tomography (CT) and magnetic resonance imaging (MRI). If there is a suspicion of a more serious form of NAFLD, the doctor may advocate a liver biopsy. The tissue sample is examined in a laboratory to look for signs of inflammation and scarring. A biopsy is typically done using a long needle inserted into the liver to remove liver cells.

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By Leonard Yap

There are currently not many therapeutic options for NAFLD. Lifestyle adjustments are usually prescribed, and these include: • Losing weight. If you are overweight or obese, reduce the number of calories you eat each day and increase your physical activity in order to lose weight • Choose a healthy diet. Eat a healthy diet that’s rich in fruits and vegetables. Reduce the amount of saturated fat in your diet and instead select healthy unsaturated fats, such as those found in fish, olive oil and nuts. Include whole grains in the diet, such as whole-wheat breads and brown rice • Exercise and be more active. Aim for at least 30 minutes of exercise most days of the week. Incorporate more activity in your day • Control your diabetes. Follow your doctor’s instructions to stay in control of your diabetes. Take your medications as directed and closely monitor your blood sugar • Lower your cholesterol • Protect your liver. Avoid things that will put extra stress on your liver. Avoid alcohol and follow the instructions on all medications and over-the-counter drugs

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News | Pharmacy Today | June 2013  into the cell membrane of both normal and damaged liver cells to increase membrane fluidity and active transport cross the membrane. Low-density lipoprotein cholesterol (LDL-C) and total cholesterol levels appear to decrease with the consumption of phospholipids. In addition, phospholipids appear to have antioxidant properties and have been found to reduce inflammation and scarring of the liver.

Nutritional supplements have shown some benefit in protecting the liver and aiding recovery from oxidative damage. Supplements containing polyunsaturated fatty acids, which are also known as essential phospholipids (Essentiale®, sanofi) are vital nutrients which can support the liver. Studies have shown that these essential phospholipids, specifically phosphatidylcholine from soy, are incorporated

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From the research bench to your patient’s bedside – JPOG raises the quality of life of women and children in Asia. Pick up a copy today and start earning CME points. For further details, visit www.jpog.com today.

PTAPR-13/001

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Pediatric & Digestive Health

Feature
Understanding common feeding issues in infants

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ypersensitivity reaction to food is becoming more common. Without a basic understanding and strict use of the various terminologies used to describe these hypersensitivity reactions, healthcare professionals face an uphill task to optimizing patient care in those who are susceptible. The World Allergy Organization recognizes food hypersensitivity as an umbrella term to describe objectively reproducible symptoms as a result of exposure to susceptible food that are otherwise tolerated by normal persons.1 Food hypersensitivity can be further classified into immune-mediated food hypersensitivity (food allergy) or non-immune mediated food hypersensitivity (food intolerance).

Differentiating between food allergy and food intolerance
It is very common for the general public and healthcare professionals alike to use ‘food allergy’ and ‘food intolerance’ interchangeably. There are, however, distinct differences between the two. Essentially, food allergy is a specific form of intolerance to food or a food component that activates the immune system. An allergen is a type protein found in offending food or food component that sets of a chain of immune reactions including the release of histamine in the hypersensitive individual.

In the majority of people, the offending allergen will not elicit such adverse reactions. The release of histamine causes a variety of symptoms that are seen in the following: gastrointestinal system (vomiting, diarrhea), skin (urticaria, atopic dermatitis) and respiratory system (asthma attack, rhinitis).2 An example of the commonest form of food allergy seen in the early years is cow’s milk protein allergy. On the other hand, food intolerance describes feeding problems commonly encountered in infants. Food intolerance involves the body’s metabolism, but not the immune system. Food intolerance occurs when the body is unable to digest food or a food component completely. An example of this is lactose in-

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Pediatric & Digestive Health thriving and are not experiencing any breathing problems during spit ups. Fussiness, excessive crying and colic Fussiness is the inability of infants to settle down or be soothed. Excessive crying is unexplained prolonged crying of healthy infants whose basic needs are met. Colic is a pattern of weeks-long excessive crying and occurs in intervals. Exactly what causes fussiness, excessive crying and colic is unknown, although it is thought that abdominal gas could be a cause. There are many things that can cause abdominal gas and worsen crying in infants: • Swallowing of air during sucking. Infants may swallow excess air during feeding especially if they drink too rapidly, are lying down during feeding or the bottle nipple has holes that are too big. • Swallowing of air when crying. Infants who have been crying intensely for a period of time can swallow in extra air. • l Improper feeding. Certain milk formulas may lead infants to have excessive gas due to intolerance to lactose or milk protein. A change of type of formula may be recommended if the source of colic is due to food hypersensitivity. Constipation Although a normal bowel pattern is desirable and thought to be an indicator of good health, the frequency of infants’ bowel movements vary so much that it is difficult to define constipation in infants. Mild constipation occurs when infants experience difficulty and discomfort in passing hard and dense stools for two or more weeks. Constipation tends to happen when infants are going through dietary transition, for example the change from breastfeeding to infant formula. Constipated infants may have

tolerance, which is the inability of the body to breakdown lactose due to a lack in the enzyme lactase. The symptoms of food intolerance are not dissimilar from food allergy, and usually manifest as gastrointestinal intolerance. It is for this reason that accurate diagnosis to differentiate between the two can only be made by means of a combination of clinical history and dietary investigations followed by food challenge or food reintroduction.2

Symptoms of common feeding issues
Spitting up Spitting up is an effortless return of swallowed formula or breast milk through the mouth or nose after feeding. As infants swallow milk, it glides pass the back of the throat into the stomach, passing through the esophagus. The lower esophageal sphincter is a valve located between the esophagus and the stomach that opens to let milk flow into the stomach and tightens to prevent milk (and stomach contents) from moving back into the esophagus. It is very common for infants to spit up simply because infants cannot sit up during feeding. Spitting up can also happen because infants’ stomachs are quite small and can get quite easily distended by feeding. Also, the lower esophageal sphincter may be immature and unable to keep all of the stomach’s contents in place. Spitting up can be reduced by burping infants after every 1-2 ounces feed to prevent build up of air in the stomach, slower feeding to allow stomach contents more time to empty into the intestines, avoid overfeeding at any one time or stop feeding once the infant seems full, and keeping infants in an upright position for at least 15 minutes after feeding. Spitting up should not be a cause of concern if infants seem content, are in no discomfort,

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Pediatric & Digestive Health in the large intestine, drawing more water into the colon, which results in loose and watery stools. The byproducts of lactose degradation in the large intestine cause the symptoms of gas, bloatedness and abdominal discomfort seen in infants with lactose intolerance. The symptoms of lactose intolerance can be easily mistaken for irritable bowel syndrome. Hence, a careful past medical history and dietary review is important to make the accurate diagnosis. Several tests exist to confirm lactose intolerance and they are as follows: • Hydrogen breath test. This is a noninvasive test that measures the amount of hydrogen in an individual’s breath as an indication of lactose nonabsorption. Under normal circumstances, very little hydrogen is detectable in the breath. In the lactose-intolerant individual, the undigested lactose is fermented in the colon, producing various gases including hydrogen. The hydrogen gas will be partially excreted in the mouth that is detected by the test.3 • Plasma glucose test. The hydrolysis of lactose produces galactose and glucose. Once hydrolyzed, galactose is absorbed into the liver to be converted into glycogen as storage, while glucose enters the bloodstream causing a spike in blood glucose concentration. This spike in blood glucose concentration is not seen in lactose-intolerant individuals and a rise in blood glucose of less 1.5 mmol/L is indicative of lactose intolerance.3 • Stool acidity test. This test can be used in infants and children as it measures the acidity of stool due to lactic acid, fatty acid and glucose, all of which are byproducts of lactose fermentation in the colon. Presence of lactose intolerance is indicated by a high acidity level ie, low pH value.4 Milk protein intolerance Infants with symptoms of milk protein intol-

stomach ache and/or a swollen belly and start to drink less. In formula-fed infants, changing the type of formula may be useful to ease constipation. Ensuring adequate water intake in formula-fed infants may also help to relieve constipation. Diarrhea Diarrhea is frequent and watery bowel movement. Diarrhea is a symptom that is more commonly associated with acute viral gastroenteritis - characterized by sudden onset and lessens in one to several days. In contrast, chronic diarrhea that last for weeks and months in infants is more likely to be due to gastrointestinal intolerance to milk or its components. Prolonged diarrheal episodes can lead to dehydration in infants. Signs of dehydration in infants include urinating less often than usual, irritability, dry mouth, unusual drowsiness or lethargy, and loss of elasticity in skin. Dehydrated infants require medical help immediately. A change in the type of infant formula may be useful in diarrhea that is caused by milk intolerance.

Causes of common feeding issues in infants
Symptoms of common feeding issues in infants are usually gastrointestinal in nature, and can be due to intolerance to lactose or milk protein present in cow’s milk. Lactose intolerance Lactose intolerance simply means the body cannot digest lactose, a natural sugar that is found in milk and dairy products. It is a disaccharide that is hydrolyzed by lactase to yield glucose and galactose. The primary site for lactose digestion and absorption happens in the small intestine, where lactase is produced in the brush borders of the small intestine. Undigested lactose creates an osmotic load

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Pediatric & Digestive Health of that, this survey noted that symptoms of vomiting, inconsolable crying, gas and diarrhea are the top four concerns encountered in infant feeding. These symptoms can be sources of frustration for mothers, causing endless worrying and sleepless nights because their child is not feeling well. It is very common for Malaysian mothers to use traditional methods like gripe water or Chinese medicated oil to relieve symptoms of tummy discomfort in infants. Although these over-the-counter products may offer some relief, the soothing effects are only temporary and do not address the root cause of the problem. Parents are likely to suspect that infant formulas may be the culprit when their infants have prolonged diarrhea, excessive crying, frequent spit ups or refusal to feed.

erance means that their bodies are not tolerating cow’s milk proteins, specifically whey and casein. The reactions due to milk protein intolerance are often delayed, sometimes hours to days after intake of milk. Onset of milk protein intolerance is almost always during infancy and this disorder can sometimes go undiagnosed. Infants with milk protein intolerance typically present with symptoms such as rashes, colic, stomach upset, diarrhea, constipation, gastroesophageal reflux and fussiness. The rashes are usually transient and can appear as tiny bumps on the cheeks and upper arms. Some infants may have chronic redness of cheeks and earlobes. Infants with milk protein intolerance tend to be fussy after feedings as well. Diagnosing milk protein intolerance can be difficult because there are no specific test to confirm the diagnosis. An allergy test may be performed to rule out milk allergy as infants with milk protein intolerance will test negative in such tests. Knowing whether infants have milk protein intolerance, therefore, depends on detailed medical history and physical examination. Questions on whether cow’s milk has been recently introduced to the diet and infant’s bowel habits are useful information in making a diagnosis. Sometimes, blood tests may be required to check if the infant is anemic. More often than not, milk protein intolerance is confirmed after absolute dietary elimination of cow’s milk protein for 3-4 weeks. A clinical improvement of symptoms should be noted during this time.

Parents lacked knowledge on the content of infant formula
It is a natural tendency for parents to consider a switch in infant formula to improve symptoms of tummy discomfort. A study by Nevo et al which looked at infant feeding patterns in the first six months of life found that nearly 50% of parents switched infant formula without consulting a healthcare professional, and the switches were often made in response to a perceived health problem such as regurgitation, vomiting and fussiness.5 Although switching infant formula is the first step towards happy and healthy infants, many parents lack knowledge on what type of infant formula is most suitable. This was revealed in the same study by Nevo that when parents made the switch, most of them chose another cow’s milk-based formula. There were also 12% of parents noted in this study who made more than two switches of infant formula over a span of six months.5 This clearly reflects that parents are unsure

Preventing tummy discomfort in infants
Symptoms of tummy discomfort are very common in infants. According to a survey, up to 84% of Malaysian mothers admit to having feeding difficulties with their infants. On top

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Pediatric & Digestive Health sitivity response when given to infants. These tests include efforts to determine the molecular weight of residual peptide, the amount of immunologically recognizable material present and the ability of the formula to elicit an immune response in preclinical studies. For a formula to be labelled as hypoallergenic, it has to, at minimum, ensure 95% confidence that 90% infants with documented milk hypersensitivity will not react with defined symptoms to the formula under double-blind, placebocontrolled studies.7 Majority of the world’s leading health organizations on child nutrition seem to agree on the suitability of hypoallergenic formula for infants who could be at risk of milk hypersensitivity, especially if they have strong family history, in the first 4-6 months of life.6 However, emerging evidence has shed light on the possible differences between partially and extensively hydrolyzed formulas, suggesting that these formulas could have different therapeutic uses. Essentially, any hypoallergenic formula may be of therapeutic use in infants with tummy discomfort, while specialized formulas such as extensively hydrolyzed formulas should be used in infants with documented cow’s milk protein allergy.8-10 Lactose-free formulas Infants with tummy discomfort are likely to be introduced to a trial of lactose-free formula during the diagnosis process to see if symptoms improve. Lactose-free formulas are usually indicated in infants with primary lactase deficiency, which is the relative or absolute absence of lactase that develops in childhood in different racial groups. Primary lactase deficiency is the commonest cause of lactose malabsorption and lactose intolerance.11 It is recognized that lactose-intolerant individuals have varying degrees of lactase defi-

of the contents of infant formulas, which explains the frequent switches and poor choices for their infants. It is common for parents to think that changing the brands of infant formula will improve tummy discomfort. This perception needs to be changed because specific infant formulas are available for infants with tummy discomfort and parents need to be educated on what are the appropriate choices.

Helping parents make the right choices
A wide variety of infant formulas is available out there in the market and they are described in various terminologies. For lessinformed parents, it can be confusing and overwhelming to discern what is the suitable choice for infants with tummy discomfort. Pharmacists play an important role in advising parents on choices of infant formulas based on available evidence and, more importantly, help to distinguish the minority of infants who may benefit from specialized formulas. Hypoallergenic formulas It is thought that protein peptides in the range of 10 - 70 kD (particularly 10 - 40 kD), found in regular cow’s milk-based infant formula are allergenic. Hence, hypoallergenic formulas are formulas which contain predigested protein that are formed using enzymatic processes to break down large protein peptides into smaller fragments. Depending on the sizes of predigested protein formed, these formulas can be further classified as partially hydrolyzed (containing larger peptide fragments) or extensively hydrolyzed formulas which has smaller peptide fragments.6 Hypoallergenic formulas have to undergo rigorous preclinical formulation and testing to ensure that they do not elicit any hypersen-

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Feature | Pharmacy Today | June 2013 

Pediatric & Digestive Health
Tummy discomfort in infants

ciency and correspondingly, are able to tolerate varying amounts of dietary lactose. However, it may be sensible to consider lactose-free formulas in infants with tummy discomfort, especially if the infant has prolonged tummy discomfort and at risk of malnutrition.11 Soy-based formulas Soy formulas are often marketed as alternative formulas suitable for infants with tummy discomfort. However, it may not be so for most infants. A study by Lothe et al found that symptoms of tummy discomfort did not improve or deteriorated in more than half of infants who had tummy discomfort and given a soy-based formula. These infants went on to be symptom-free when they were given predigested protein formulas.12 The American Academy of Pediatrics (AAP) has specified the use of soy-based formulas in the following conditions: (a) for infants with galactosemia and hereditary lactase deficiency (rare) and (b) in situations in which a strict vegetarian diet is preferred. The AAP also noted that isolated soy protein-based formulas has no proven value in the management of infantile tummy discomfort.13 Soybased formulas may be of value in infants with documented cow’s milk protein allergy who cannot tolerate the palatability of extensively hydrolyzed and/or amino acids formulas.14

Caring for infants with tummy discomfort can be stressful and overwhelming for mothers, especially if they are first-time parents. Tummy discomfort can cause symptoms such as excessive crying, fussiness, colic, gas, constipation and sometimes, diarrhea. Most of the time, tummy discomfort in infants are likely to be due to intolerance to certain components of cow's milk such as lactose and milk proteins. Most parents think that switching the brand of infant formula may help, when they should be educated on the type of infant formula that is suited to resolve the symptoms. Hypoallergenic infant formulas that contain predigested proteins and lactose-free may resolve symptoms of tummy discomfort. Pharmacists can help parents in making the right choices to bring comfort to their infants

References:
1. Johansson SG, et al. J Allergy Clin Immun 2004;113:832-836. 2. European Food Information Council. Food allergy and food intolerance. Available at: www.eufic.org/article/en/expid/ basics-food-allergy-intolerance/. Accessed on: 25 Apr

3. Barreling PM. IeJSME 2012; 6(Suppl 1):S12-S23. 4. Kissous-Hunt M. Advance for NPS & PAS 2012;3(12):16-18. 5. Nevo N, et al. J Pediatr Gastroenterol Nutr 2007;45:234–239. 6. Lowe AJ, et al. Expert Rev Clin Immunol 2013;9(1):31-41. 7. American Academy of Pediatrics.Committee on Nutrition. Pediatrics 2000;106;346-349. 8. Garrison MM, et al. Pediatrics 2000;106;184-190. 9. O'Connor NR. Am Fam Physician 2009;79(7):565-570. 10. Critch J. Paediatri Child Health 2011;16(1):47-49. 11. Heyman MB. Pediatrics 2006;118:1279-1286. 12. Lothe L, et al. Pediatrics 1982;70:7-10. 13. Bhatia J, et al. Pediatrics 2008;121:1062-1068. 14. Vandenplas Y, et al. Arch Dis Child 2007;92:902–908.

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Spotlight | Pharmacy Today | June 2013 

Spotlight
Pharmacists should brush up on oral health advice
With around a third of adult New Zealanders not brushing their teeth twice daily with fluoride toothpaste, pharmacists have an important role to play in spreading the oral health message, Pharmacy Today New Zealand reports

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hile pharmacists should send patients with toothache directly to a dentist, they can also help reinforce good oral hygiene, New Zealand Dental Association (NZDA) chief executive David Crum said in an email to Pharmacy Today. “Pharmacists are within communities, are trusted by communities and should be encouraging the public to seek regular dental care,” Dr Crum said. They should also support public health measures to reduce dental disease such as water fluoridation and, most importantly, encourage customers to adopt simple oral health measures at home. The basics for a healthy mouth are a good, low-sugar diet, twice-daily cleaning with fluoride toothpaste and regular visits to a dentist, Dr Crum said. Further advice on the NZDA website includes flossing daily, quitting smoking and not rinsing after brushing, as this washes the fluoride away.

The Australian Dental Association advocates that pharmacists work with dentists to ensure they give compatible information and are up to date on the latest oral health promotions. Anxiety over visiting a dentist, either due to the cost or fear of pain, combined with pharmacy’s longer opening hours, mean pharmacists are often the first port of call for people experiencing oral health issues, according to the Australian Journal of Pharmacy (AJP). The advice a pharmacist gives can make or break a customer’s future oral health outcomes, the Australian Dental Association’s Peter Alldritt told the AJP. For example, customers buying baby bottles present a good opportunity for pharmacists to remind them to protect their babies’

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Spotlight | Pharmacy Today | June 2013  Often, she will sell a product to treat acute symptoms and a remedy for the root causes. Bleeding gums are often a symptom of low vitamin C, so she may recommend a herbal toothpaste or a pill with Indian gooseberry due to its high vitamin C content. Mouth ulcers can also be due to a vitamin or mineral deficiency, or a sign of stress, for which she may suggest a vitamin B supplement. Bad breath often linked to digestion issues. If a customer comes in complaining of bad breath, the problem is usually related to digestion, and Ms Rama will give advice on diet. The Healthcare Handbook 2012 (p105) recommends mouthwash containing chlorhexidine for bad breath and gingivitis, but cautions prolonged use may stain teeth. Patients with continual bad breath or gingivitis should be sent to a dentist as soon as possible to prevent their teeth eventually falling out, the Healthcare Handbook says. Sufferers of persistent halitosis may also have a non-dental health issue and should see a doctor. Preventative oral health recommendations for children include reinforcing the ‘Breast is best’ message for babies and switching from a bottle to a cup as soon as possible (Healthcare Handbook, p141). Chewing sugar-free gum for adults stimulates saliva production, which buffers against food-acid, remineralizes the mouth and helps clear food from around teeth. The NZ Ministry of Health’s website www. health.govt.nz has a downloadable publication in various languages informing families of the free oral health services for children and covering oral hygiene basics.

teeth by not putting infants into bed with a bottle of milk or juice, Dr Alldritt said.

Fluoride in toothpaste essential for healthy teeth
Fluoride’s power to reduce tooth decay by 2030% outweighs the potential risk that it may leave white spots on children’s teeth, the New Zealand Dental Association website said. However, at the Buller Pharmacy, sales of fluoride tablets are low despite NZ’s West Coast having an unfluoridated water supply, owner Julie Knudsen said. People generally buy toothpaste at the supermarket rather than from her pharmacy, but being located across the road from a dental surgery has increased mouthwash sales, Ms Knudsen said. For ayurvedic-trained central Auckland pharmacist Hansa Rama, when customers come in with oral health issues, it is a good opportunity for complementary selling and relationship building. Some of her advice for treating problems like mouth ulcers and bad breath involves simple home remedies like rinsing with salt and warm water, or applying turmeric or baking soda, Ms Rama said. Providing advice does not create direct sales, but she builds up customer trust and they come back to her with other health issues. Ms Rama also stocks a wide range of herbal toothpaste, generally not available in supermarkets, to alleviate different tooth problems, from discoloration to bleeding gums. Her customers do not seem to mind that these toothpastes usually do not contain fluoride, Ms Rama said.

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Spotlight | Pharmacy Today | June 2013 

PromOat health without the bloat
By Leonard Yap

onsuming oats has long been used as a way to reduce blood cholesterol. But what many people do not know is that to get the desired cholesterol-lowering effects from oats, you need to consume three bowls a day for 60 consecutive days. Dedicated and health-conscious individuals may not find it a pain to religiously consume three bowls of oats every day, but it is a challenge for most other people. Those on hectic schedules have little time for breakfast, let alone keeping up with the three-bowl-aday regimen. Besides having to consume the traditional three bowls of oats, most people cannot tolerate its bland taste or lumpy texture. In addition, consuming that amount of oats may cause bloating or gas in some people, which make eating oats even more of a chore. The options for breakfast in Malaysia abound, and when you compare the Malaysian staples of nasi lemak or roti canai, a bowl of oats just cannot compete. But things have gotten a lot easier with a new form of oats in the market! Kordel’s Active Oat 35™, which contains PromOat™, an oat beta-glucan, provides the three-bowl equivalent with just two spoonfuls. With Active Oat 35 powder, consumers can now more easily reap the full benefits of oats and its cholesterol-lowering properties. So how do oats work? It is believed that oat beta-glucans have a dual-action mechanism

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on the digestive tract. First, it reduces bile acid reabsorption by binding to bile acid in the intestinal tract and to produce more bile acid quickly. Second, it lowers the absorption of dietary fat and cholesterol by expanding and increasing the viscosity of food in the small intestine to form a physical barrier and reduce excessive cholesterol absorption. There have been various studies to access oat beta-glucan’s effects on reducing cholesterol. One study showed that people who took oat beta-glucan had a 10% reduction in low-density lipoprotein cholesterol (LDL-C) after 4 weeks compared to those who did not take it. It also reduced total cholesterol levels by 5%. (Nutr Rev 2011;69(6):299-309) This appeared to confirm findings from a doubleblind, parallel-design, multicenter clinical trial of nearly 400 patients which tested the ability of oat beta-glucan to reduce serum LDL-C. (Am J Clin Nutr 2010;92(4):723-32) So why should we care about LDL-C and total cholesterol levels? High cholesterol levels have become an increasing concern for Malaysians. In 2011, the National Health and Morbidity Survey 2011 (NHMS 2011) found that the percentage of Malaysians suffering from high cholesterol had increased from 20.7% in 2006 to 35.1% in 2011. This translates to a staggering 10 million people, or nearly one-in-three.

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Spotlight | Pharmacy Today | June 2013 

Topical treatments first-line for fungi infections
minor irritation in healthy people, but severe in the sick or those with low immunity, fungal infections are part of the stock and trade of pharmacy. Of those affecting the skin, tinea pedis (or athlete’s foot) is the most common, usually making itself known between the toes and giving a “white and soggy” look, according to the New Zealand Healthcare Handbook 2012. Cracks on the foot and toes may also appear. Fungal infections can usually be treated with topical creams and/or powders, ranging from general sale to pharmacist-only, which can be used as both a preventative and curative. Pharmacy staff should advise customers to bleach their bath areas to prevent spreading the infection, while towels and socks should be washed in hot water and slippers worn in communal changing areas. An antiperspirant for sweaty feet will also help prevent tinea developing, but it needs to be different from the one used under the arms to avoid cross-contamination. Less common, but probably more annoying, is tinea cruris or jock itch. Often going hand in hand with athlete’s foot due to transfer via towels, tinea cruris can cause the groin and inner thigh to turn a reddish brown and to itch intensely. The infection will often have a well-defined border and can spread to the buttocks. Customers should keep the infected area dry and avoid sharing towels. This advice also applies to ringworm (tinea corporis), which usually affects the trunk and limbs, and looks like a circular itchy red patch on the skin.

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It often has a raised edge, some clear skin in the middle and can look similar to other skin conditions like dermatitis. Ringworm is often caught from kittens. Toenail fungal infections can occur on their own or in conjunction with athlete’s foot, while fingernail infections are common in gardeners and people who spend a lot of time with their hands in water. Both make the nail look thick and discolored and it may become brittle, crumble or fall off. Topical nail antifungals usually treat the condition, but occasionally prescription oral medicine is needed. Pharmacy staff should advise customers to wear gloves while gardening, which will also prevent mould infections. Often indistinguishable from tinea infections, mould infections picked up through soil are much harder to treat and need a pharmacist’s attention. Signifiers are inflamed nail beds and failure of previous antifungal treatments. Malassezia infections can affect the scalp and may cause dandruff or create pink, coppery brown or pale patches, usually on the trunk, neck or shoulders. The condition is more common in hot, humid climates or when people sweat a lot. Antidandruff shampoos with selenium sulphide can treat it, or topical antifungal products applied overnight for at least a fortnight. Tea-tree oil and garlic are possible natural treatments. Infections which are large, repeated, oozing, in the nails, scalp or beard, or in any way severe, should be referred to a pharmacist.

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Spotlight | Pharmacy Today | June 2013 

Blood glucose monitoring improves diabetes control
By Leonard Yap

iabetes mellitus (DM) is a degenerative disease affecting beta cells of the pancreas. This may be due to the pancreas not producing sufficient insulin or beta cells not responding to the insulin produced. According to the WHO, about 347 million people worldwide have DM. The classical symptoms of diabetes include frequent urination, increased thirst and hunger. It is important to recognize these symptoms and understand that DM is a disease that affects most organs in the body. Preventing these symptoms from progressing will enhance its management. There are three main types of DM: • Type 1 DM results from the body’s failure to produce insulin, and was previously referred to as insulin-dependent diabetes mellitus or juvenile diabetes. • Type 2 DM (T2DM) results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes combined with an absolute insulin deficiency. T2DM was previously referred to as non insulindependent diabetes mellitus or adult-onset diabetes. • Gestational diabetes occurs when pregnant women without a previous diagnosis of diabetes develop high blood glucose levels. Women who have had gestational diabetes may go on to develop T2DM later in life. Early diagnosis of DM can be accomplished through relatively inexpensive blood testing. Treatment should target lowering blood glu-

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cose and attempting to sensitize ‘ailing’ beta cells to the effects of insulin. Other known risk factors that damage blood vessels, like hypertension, should also be kept under control. Tobacco cessation should also be part of the management strategy. Most people check their blood glucose levels using a personal blood glucose meter. There are many brands available and one such product is the Omron HGM-112 blood glucose monitoring system. It is compact, easy-to-use and pocket-sized system, weighing a mere 25.5 g. You use a disposable lancet contained within the button-activated device to obtain a small drop of blood from your fingertip or palm. The drop of blood on the disposable test strip is then inserted into the meter, which provides a reading after just five seconds. The HGM-112 also has an error indication when expired, damaged or reused strips are used to ensure reading accuracy.

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Spotlight | Pharmacy Today | June 2013 

Eating small meals slowly reduces heartburn
Pharmacy staff are well placed to offer advice and treatment for heartburn; however, some symptoms can be similar to those of a heart attack. Urgent medical help is required for anyone describing pain which radiates through the jaw, neck, shoulders or arm, and gets worse with exercise. For other non-urgent instances, treatments can be offered. Antacids and alginates are commonly used as a first-line treatment. H­ 2 antagonists are pharmacy-only medicines used to block the action of histamine on gastric acid cells to reduce acid release, while proton pump inhibitors reduce gastric acid secretion by a direct action on stomach gastric acid-releasing cells. Patients should also be advised to: • avoid foods known to cause indigestion or heartburn • eat small meals slowly • avoid tight waistbands, bending over or lying down soon after a meal • reduce alcohol intake, lose weight, stop smoking and raise the bed head • see a doctor if symptoms persist for longer than two weeks.

Heartburn is common in pregnancy because the stomach is pushed upwards by the baby. Medications such as iron tablets and antiinflammatories can also aggravate the condition.

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Pharmacy Practice | Pharmacy Today | June 2013 

Pharmacy Practice
Benefits and Risks of hormone replacement therapy in menopause
By Dr Chua Siew Siang B. Pharm (Hons), PhD Department of Pharmacy Faculty of Medicine, University of Malaya Recognised by Academy of Pharmacy

Every mont earn 1 h CPD p oint

ost women reach menopause (the last menstrual period) around the age of 5020. Women are considered as postmenopausal if their menstruation has ceased consecutively for at least a year. As a woman approaches menopause, there is a decline in the production of estrogen and progesterone which are hormones produced by a the ovaries20. A few years before and after reaching menopause, some women may experience a variety of debilitating vasomotor symptoms and vulvovaginal changes termed as the climacteric or menopausal syndrome, which are mainly a consequence of reduction in estrogen production20. These symptoms include hot flushes, night sweats, sleep disturbances, reduction in bone mass, mood swings and vaginal dryness which may differ in severity between individuals and can affect the quality of life and health of women2. To help to alleviate the menopausal symptoms, hormone replacement therapy (HRT) is used in menopause to supplement the body with either estrogen or a combination of estrogen and progesterone. There are some quarters who feel that the term ‘HRT’ is misleading and, therefore, should be substituted with ‘postmenopausal hormone therapy’ to

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avoid the perception that the natural process of menopause, a physiological phase in a woman’s life, is a disease due to hormone deficiency13. However, the term HRT is still very commonly used, and to be consistent in this article we will retain the term HRT. There are two types of HRT: • estrogen-only HRT • combined HRT (estrogen plus progestogen).

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Pharmacy Practice | Pharmacy Today | June 2013  menstruation has ceased or is infrequent) for 28 days, with the addition of another tablet which contains a progestogen for days 17 to 28 of the cycle. Subsequent courses are repeated without any interval22. Globally, there are various pharmaceutical dosage forms of HRT, i.e. tablet, intrauterine device, transdermal patch, implant or injection, cream or gel and vaginal ring, but not all are available in Malaysia19. Side effects of HRT include headache, dizziness, breast tenderness or enlargement, edema, weight gain, changes in libido, unscheduled vaginal bleeding or spotting, vaginal candidiasis, endometrial proliferation, mood swings, gastrointestinal disturbances such as nausea, vomiting, abdominal cramps and bloating, cholestatic jaundice, glucose intolerance, altered lipid profile (which may lead to pancreatitis), thrombosis and increase in blood pressure22.

Estrogens used in HRT include: • conjugated equine estrogen • ethinyl estradiol • 17β-estradiol • estradiol valerate • estradiol hemihydrate • estrone sulphate • esterified estrogens. Ethinyl estradiol is commonly used in oral contraceptives, but is now rarely used in HRT for menopausal women because it has distinct effects on hepatic metabolism4. Progestogens used include4: • micronized progesterone, dydrogesterone and progesterone derivatives such as medrogestrone • pregnanes such as medroxyprogesterone acetate, megestrol acetate and cyproterone acetate • norpregnanes such as trimegestrone, nestorone and promegestone • l estranges (first-generation progestogens) such as norethisterone, norethisterone acetate and lynestrol • gonane progestogens: • second-generation progestogens such as norgestrel and levonorgestrel • third-generation progestogens such as desogestrel, gestodene, norgestimate and dienogest • drospirenone. Most HRTs contain conjugate estrogen or estradiol hemihydrate/valerate, while the progestogen component is usually cyproterone acetate, drospirenone, dydrogesterone, norgestrel, levonorgestrel, norethisterone or medroxyprogesterone. Most of combined HRTs for the alleviation of menopausal symptoms or the prevention of osteoporosis in women with a uterus, consist of estrogen given on the first day of menstruation (or any time if

Benefits of HRT
Basically, HRT is used for the control of menopausal symptoms and to improve the quality of life of affected women. Systematic reviews have shown that HRT is effective for alleviating vasomotor symptoms such as hot flushes and night sweats as well as symptoms associated with vaginal atrophy such as vaginal dryness, pruritus and dyspareunia10,8,21. Trends in the use of HRT in menopausal women have fluctuated like a rollercoaster for the past few decades. Stefanick describes in detail the history and trends in estrogen and progestin use dating back as early as 1889 when French physiologist Charles Edouard BrownSequard self-injected an extract of testicles of dogs and guinea pigs to reverse aging19. In 1899, the Merck Manual featured several treatments for climacteric symptoms, including a product Ovarin® which was de-

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Pharmacy Practice | Pharmacy Today | June 2013  ed equine estrogen 0.625 mg and medroxyprogesterone acetate 2.5 mg) or a matching placebo15. This trial was terminated early after a mean follow-up period of 5.2 years as analysis of the data showed that the health risks of the combined HRT exceeded its benefits15. The initial report of this WHI study stated an increased risk in breast cancer and was publicised in the media which resulted in fear and a negative impact on the use of HRT. Consequently, there was a drastic worldwide decline in the use of HRT, with the cessation of long-term use of HRT in many users and a drop in HRT use rate of 40 to 80%3,10. However, a subsequent report by the WHI study in 2007, which contained more positive results on HRT, stated that there was no significant increase in risks of any clinical outcome in women aged between 50 and 59 years due to the use of HRT3,16. In addition, there was a reduction in total mortality in women of this age group using HRT. The WHI trial of estrogen-only HRT in women with hysterectomy was also terminated earlier due to an increase in risk of stroke1. An extended follow-up of this WHI trial found that the use of estrogen-only HRT for a median of 5.9 years was associated with lower incidence of invasive breast cancer compared with placebo (0.27% versus 0.35% per year; hazard ratio (HR) 0.77, 95% CI 0.62-0.95; p=0.02). This breast cancer risk reduction was only applicable to women without benign breast disease or a family history of breast cancer1. However, the negative impact of HRT created by the initial WHI announcement in 2002 has instilled sufficient fear and anxiety among healthcare providers as well as affected women that the negative reputation of HRT could not be erased completely although more positive effects of HRT were reported in

rived from cow ovaries. However, the first HRT approved by the US FDA in 1941 for the treatment of menopausal symptoms was diethylstilbestrol, while Premarin® (1.25 mg conjugated equine estrogen) was approved in 194219. Use of estrogen increased steadily in the mid-1960s to mid-1970s due to initiation of oral contraceptives in young women, but declined dramatically in 1975 when estrogeninduced endometrial cancer was reported19. However, the use of estrogen climbed again after the emergence of evidence of protective effects of progestogens on estrogen-induced endometrial changes and reports of improved bone mass with conjugated estrogen. Conflicting reports on the effects of estrogen on coronary heart disease occurred around 1985. Consequently, in 1992, the American College of Physicians issued a position statement based on a landmark meta-analysis of observational studies, which recommended that all postmenopausal women should be offered HRT to prevent cardiac problems19. Findings from the Postmenopausal Estrogen-Progestin Interventions (PEPI) trial in 1995 showed favorable lipoprotein changes in estrogen users, and this reinforced the cardioprotective effects of HRT19. In addition, there were reports which suggested that estrogen therapy could prevent bone loss. Consequently, HRT was widely used during the 1990s although there were insufficient randomized controlled trials to support its benefits and also its safety during that time12. By 2001, approximately 15 million US women were using HRT5. The Women’s Health Initiative (WHI) randomized controlled trial on postmenopausal women between the ages of 50 and 79 years in the US involved 16,608 women with an intact uterus who were given either a combined estrogen and progestin (contained conjugat-

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Pharmacy Practice | Pharmacy Today | June 2013  and there was a 50% increased risk of bone fracture associated with a 50% decrease in HRT use, this could then translate into enormous health and economic consequences. Therefore, women who wish to stop HRT should consult their healthcare providers so that alternative treatment for the prevention of osteoporosis and bone fractures could be given6. The systematic review by Marjoribanks and colleagues also found that HRT was not indicated for the prevention of cardiovascular disease or dementia in postmenopausal women aged around 6012. However, if HRT, especially estrogen-only HRT, was started in women under 60 years and closer to the start of menopause, a cardioprotective effect was observed9,12,16. Similarly, a 59% reduction in Alzheimer’s disease was observed if HRT is initiated in early menopause and continued for more than 10 years12,23.

later years. This can be seen from a study in Australia which demonstrated a fall in the prevalence and duration of use of HRT from 28% in women over 50 in the year 2000 to an estimated 10.2% in 200211. Similarly, a drastic drop in HRT use was observed in the US, following the WHI publication in 20025. Some women, especially those with severe symptoms of menopause, but were too afraid to start HRT, may have been inappropriately deprived of the benefits of HRT and some had to suffer unnecessarily3. Consequently, there was an increased use of non-evidence-based complementary medicines for the management of menopausal symptoms although these had not been proven safe and/or more effective than the placebo used in HRT trials14,8,11. Decades ago, it was already known that the incidence of bone fractures was twice as common in postmenopausal women compared to their male contemporaries and, hence, it was suggested that small doses of estrogen should be given to retard the deterioration of bones in postmenopausal women20. A recent systematic review concluded that a reduction in the risk of fracture with the use of HRT was the only beneficial outcome which has strong evidence12. Low-dose estrogen-only HRT is especially beneficial for the prevention of fractures in women if initiated before age 60 years, as menopausal symptoms also occur around this age9. A longitudinal study on 80,955 postmenopausal women aged 60 and on HRT found that after 6.5 years of followup, women who discontinued HRT were at 55% greater risk of hip fracture compared with those who continued using HRT6. Protection from hip fracture in postmenopausal women seemed to tail off within two years of cessation of HRT. If one million women entered menopause each year in the US alone,

Risks of HRT
Controversies over the risks and benefits of HRT have been debated continuously over the past two decades. Risks associated with the use of HRT include: • Endometrial hyperplasia which may lead to endometrial cancer • Breast cancer • Ovarian cancer • Gallbladder disease • Stroke • Thromboembolism. The risks associated with the use of HRT are shown in Table 1. Unopposed estrogen in women with intact uterus is associated with an increase in risks of endometrial hyperplasia at all doses and this may develop into endometrial cancer4. However, the addition of a progestogen in combined HRT reduces such risk in women with an intact uterus4.

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Pharmacy Practice | Pharmacy Today | June 2013  (CHD) was most apparent and significant in the first year of HRT use12,19. The WHI trial found that for postmenopausal women aged 50 to 59, the hazard ratio (HR) for CHD was 0.93 (95% CI, 0.65-1.33) and the absolute excess risk was − 2 per 10,000 person-years, but this protective effect reduced with an increase in the age of women given HRT leading to an increase instead of a reduction in risk among women aged 70 to 7916. The recommendation is that women with menopausal symptoms need to be informed that the symptoms are transient and also the risks and benefits of using HRT. Women should attempt non-pharmacological management first since there is evidence to show that some symptoms may be alleviated with lifestyle modifications such as a healthy and balanced diet, exercise, cessation of smoking, reduction in alcohol intake and reduction of psychosocial stress10,13. A study in five European countries and the US showed that the majority of physicians had not lost confidence in HRT as most of them were of the opinion that the negative publicity of HRT by the media was not justified and that HRT remained an effective treatment for the alleviation of climacteric symptoms and could significantly improve the quality of life of some menopausal women. In addition, most of the physicians believed that the benefits of HRT outweigh its risks, if given appropriately2. Generally, it is agreed that the risk-benefit ratio of HRT depends on the age of the woman, medical profile of the woman, types of HRT, dose of HRT and duration of HRT use2. Although there are potential side effects and risks associated with the use of HRT, these problems may be reduced by tailoring the use of HRT to individual needs and following some general principles4,9,17: • Use the lowest effective dose of HRT • Duration of use should be determined by

Several observational studies have associated a drop in the incidence of breast cancer during the period when there was a decline in the use of HRT6. However, this association was not consistently observed in different studies. On the contrary, reviews of randomized controlled trials of HRT have shown that estrogen-only HRT does not increase the risk of breast cancer9,10,12. An increase in risks of ovarian cancer had been seen mostly in women who have undergone hysterectomy with ovarian conservation and have been on estrogen-only HRT for more than five years9. However, this risk of ovarian cancer increased with the use of estrogen-only HRT in a duration-dependent manner7 and appeared to be attenuated by the presence of progestogens. A systematic review of mainly observational studies indicated that both estrogen-only and combined HRT was associated with an increase in risk of ovarian cancer12. The review also found a statistically significant association between HRT and gallbladder disease. There appeared to be an increase in risk of stroke in women initiated with HRT many years after menopause9,12. However, Rossouw et al reported that the risk of stroke did not vary significantly with age of the woman or time of initiation of the HRT since menopause16. Thromboembolism is the main serious short-term risk associated with the use of HRT especially during the first year or two of use9,12. The risk is highest among those with thrombophilia and/or obesity9. It has been recommended that, if indicated, only low doses of transdermal estrogen-only HRT should be used in women with risk factors for stroke, high risk for venous thromboembolism and for older postmenopausal women18. The elevated risk in coronary heart disease

Summary

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Pharmacy Practice | Pharmacy Today | June 2013  fits such as a reduction in fracture and cardiovascular risks, and possibly also cognitive benefits9,17. These may outweigh the risks which are less likely to occur in women aged below 609,17. Estrogen-only HRT has a more favorable benefit-risk profile than the combination HRT (except for those with an intact uterus and a high risk of endometrial hyperplasia) which appears to be associated with an earlier appearance of increased breast cancer risk. Therefore, the duration of use of estrogenonly HRT is more flexible compared to the combination HRT which should not be used beyond 3 to 5 years17.
Estrogen-only HRT Duration of use (year) AR per 1000 (95% CI) RR (95% CI)

the estimated risks and benefits for each individual • Minimize or eliminate systemic progestogens (by using intrauterine progestogen delivery systems) • Use non-oral routes or local estrogen-only preparations, especially in women with only symptoms of vulvar and vaginal atrophy • Initiate HRT in symptomatic women near menopause. HRT should be initiated as near the time of menopause as possible for symptom control when it will also have other additional beneCombined continuous HRT Events Duration of use (year) AR per 1000 (95% CI)

RR (95% CI)

Coronary (MI or cardiac death) Venous thromboembolism (DVT or PE) Stroke Breast cancer All clinical fractures

1

4 (3 – 7) 22 (18 – 27) 7 (4 – 11) 18 (14 – 23) 23 (19 – 29) 86 (79 – 94)

1.89* (1.15 – 3.1) 7 1.22 (0.98 – 1.52) 4.28* (2.49 – 7.34) 1.38* (1.08 – 1.75) 1.26* (1.02 – 1.56) 0.78* (0.71 – 0.85) 7

38 (32 – 46)

0.94 (0.74 – 1.13)

5.6

1

21 (16 – 28) 32 (25 – 40) 24 (19 – 31) 102 (91 – 112)

1.32* (1 – 1.74) 1.34* (1.07 – 1.68) 0.79 (0.61 – 1.01) 0.73* (0.65 – 0.8)

5.6 5.6 5.6

7 7 7

AR = Absolute risk; CI = Confidence interval; DVT = deep vein thrombosis; HRT = hormone replacement therapy; MI = myocardial infarction; PE = pulmonary embolism; RR = risk ratio
Table 1: Risks of HRT in relatively healthy postmenopausal women12

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Business Managers : Lee Pek Lian, Grace Yeoh, Sumitra Pakry Tel: (603) 7954 2910 Email: enquiry.my@mims.com Designer Production : Razli Rahman, Agnes Chieng, Sam Shum : Edwin Yu

Circulation Executive : Sara Nadarajah Accounting Manager : Christine Goh Published by :  MIMS Medica Sdn Bhd Level 3A, Luther Centre No.6 Jalan Utara, 46200 Petaling Jaya, Selangor, Malaysia Email: enquiry.my@mims.com

Pharmacy Today is published 11 times a year by MIMS Medica, a division of MIMS. Pharmacy Today is on controlled circulation publication to pharmacists in Malaysia. It is also available on subscription to members of allied professions. The price per annum is US$48 (surface mail) and US$60 (overseas airmail); back issues at US$5 per copy. Editorial matter published herein has been prepared by professional editorial staff. Articles ending with PTNZ have been adapted from Pharmacy Today New Zealand. Views expressed are not necessarily those of MIMS Medica. Although great effort has been made in compiling and checking the information given in this publication to ensure that it is accurate, the authors, the publisher and their servants or agents shall not be responsible or in any way liable for the continued currency of the information or for any errors, omissions or inaccuracies in this publication whether arising from negligence or otherwise howsoever, or for any consequences arising therefrom. The inclusion or exclusion of any product does not mean that the publisher advocates or rejects its use either generally or in any particular field or fields. The information contained within should not be relied upon solely for final treatment decisions. © 2013 MIMS Medica. All rights reserved. No part of this publication may be reproduced in any language, stored in or introduced into a retrieval system, or transmitted, in any form or by any means (electronic, mechanical, photocopying, recording or otherwise), without the written consent of the copyright owner. Permission to reprint must be obtained from the publisher. Advertisements are subject to editorial acceptance and have no influence on editorial content or presentation. MIMS Medica does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature. Printed in Malaysia by KHL Printing Co Sdn Bhd. Lot 10 & 12, Jalan Modal 23/2, Seksyen 23, Kawasan MIEL, Fasa 8, 40000 Shah Alam, Selangor Darul Ehsan. PP17931/12/2013(033147) ISSN 1170-1927

Editorial Advisory Board
Dato’ Eisah A. Rahman Datuk Nancy Ho Yip Sook Ying Assoc Prof Dr Mohamad Haniki Nik Mohamed Prof Dr P.T. Thomas Pharmaceutical Services Division, Ministry of Health President, Malaysian Pharmaceutical Society Secretary, Malaysian Pharmaceutical Society Malaysian Academy of Pharmacy Universiti Kebangsaan Malaysia

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