TPW Sept-Oct 2022

“Digital technologies are on the way to INTERVIEW
help dermatologists to diagnose and
treat skin diseases more efficiently”

Prof. Dr. M A Hasanat As an eminent endocrinologist of our
Professor and Chairman country, would you please describe the
Department of Endocrinology and prevalence of Diabetes in Bangladesh?
Metabolism, BSMMU, Dhaka
According to the International Diabetes Federation
(IDF), the prevalence of diabetes in Bangladesh is 12.5%.
In 2021, the IDF ranked Bangladesh 8th of the countries
with the highest number of adults (20–79 years) with dia-
betes (13.1 million cases), and it is anticipated that Bang-
ladesh will be ranked 7th in 2045. It is also observed that
the prevalence of diabetes in young (<30 years) is rapidly
increasing in our population.

When does Insulin therapy need to be
started for patients with Diabetes?

Insulin is the only treatment option in several forms
of diabetes like type 1 diabetes and diabetes with acute
complications. Insulin is also the preferred option in the
management of diabetes in pregnancy. In the manage-
ment of type 2 diabetes, insulin may be needed right
from the diagnosis if the patients have typical symptoms
with substantially elevated HbA1c. A type 2 diabetes pa-
tient may also need insulin if the glycemic target is not
achieved by using one or more oral antidiabetic drugs.

Nocturnal hypoglycemia has always been a
nightmare for Insulin users. What other adverse
effects should the patients on insulin therapy
be aware of? How could this be avoided?

The main adverse effect of insulin is nothing but hypo-
glycemia. However, it can be prevented by proper patient
education and careful selection of an insulin regimen.
Precipitating factors of hypoglycemia include missed or
delayed meals, unaccustomed exercise, and errors in in-
sulin injection technique or dosage calculation. As an an-
abolic hormone, insulin may also lead to weight gain. The
other less common adverse effects of insulin are insulin
allergy, lipohypertrophy, and lipoatrophy.

Is there any relationship between Diabetes
and vitamin or mineral deficiencies?

Minerals and trace element deficiencies are related to
widespread human health problems. Deficiencies and,
in a few cases, excess of essential trace elements may
lead to imbalances in glucose homeostasis and insulin
resistance. The serum or tissue contents of certain ele-
ments, such as copper, manganese, iron, and selenium,
may be higher in diabetic patients than in non-diabetic

THE PHARMA WORLD 51

controls. Although the majority of dia- About 50% of women with advanced countries? In terms
betic patients do not have micronutri- gestational diabetes go on to of diabetes care in our country,
ent deficiencies, zinc, chromium, and develop type 2 diabetes. What what in your opinion, has been
magnesium deficiencies have been can be done to prevent it? the greatest development
identified in a subgroup of patients. over the last few years?
At our university, we have conduct-
Diabetes is considered the “Mother ed several studies on gestational dia- Bangladesh emphasized diabetes
of all diseases” as it affects betes and the persistence of postpar- management prior than most other
many other systems in the body. tum abnormal glucose tolerance. We countries of the world. However, we
How is diabetic kidney disease have observed an alarming frequency have a lot of areas for improvement.
(DKD) managed when the patient of GDM and a high rate of persistence The current provision of treatment for
has hypertension as well? as well. It is vital to create awareness our diabetic population is still inad-
for routine pre-pregnancy and ante- equate. Most of our patients are not
In early diabetic kidney disease natal checkups for glycemic status. In achieving their glycemic targets and we
(DKD), it is essential to prevent dis- mothers with GDM, postpartum fol- are unable to prevent the complications
ease progression by strictly control- low-up and screening are also neces- of diabetes. These are imposing a huge
ling diabetes and hypertension. There sary. The promotion of a healthy life- challenge for the health economy. We
are a few drugs like SGLT2 inhibitors style and the provision of universal have world-class endocrinologists and
and GLP-1 analogs that might be in- screening is of utmost importance to almost all newer antidiabetic drugs are
dicated to halt the progression of reduce the burden of this condition. available in our country. But we have
DKD. Management of hypertension is not yet succeeded in providing treat-
vital, and ACE or ARBs are preferable Where does Bangladesh stand as ment facilities to the underprivileged.
in presence of albuminuria. Manage- far as diabetes treatment, patient The government and non-government
ment of advanced DKD needs a multi- care, and patient education are organizations should come forward to
disciplinary effort. concerned, compared to the fight this ongoing epidemic of diabetes.

52 THE PHARMA WORLD

The Discoverers of Insulin HISTORY MAKER

In the early 1920s Frederick Banting and Charles with food intake sometimes as low as 500 calo-
Best discovered insulin under the directorship ries per day, had its consequences, as slow star-
of John Macleod at the University of Toronto. vation, like diabetes, drained patients of their
With the help of James Collip insulin was pu- strength and energy, leaving them semi-invalids.
rified, making it available for the successful
treatment of diabetes. Banting and Macleod In 1921 researchers at the University of To-
earned a Nobel Prize for their work in 1923. ronto began a series of experiments that would
ultimately lead to the isolation and commercial
At the turn of the 20th century a strict low- production of insulin—a pancreatic hormone
calorie, no-carbohydrate diet was the only ef- essential for metabolizing carbohydrates—and
fective treatment for diabetes. But this method, the successful treatment of diabetes.

QUOTABLE Insulin is not a cure for
diabetes; it is a treatment. It
QUOTE enables the diabetic to burn
sufficient carbohydrates,
Man may be the captain of so that proteins and fats
his fate, but he is also the may be added to the diet
victim of his blood sugar. in sufficient quantities
to provide energy for the
— Wilfrid G. Oakley economic burdens of life.

— Sir Frederick Grant

THE PHARMA WORLD 53



Type 2 Diabetes ARTICLE
can be prevented

Dr. Shahjada Selim

What is type 2 diabetes? you need to do involve having a healthier life-
style. So if you make these changes, you will get
If you have diabetes, your blood sugar levels other health benefits as well. You may lower your
are too high. With type 2 diabetes, this happens risk of other diseases, and you will probably feel
because your body does not make enough insu- better and have more energy. The changes are:
lin, or it does not use insulin well (this is called l Losing weight and keeping it off. Weight con-
insulin resistance). If you are at risk for type 2
diabetes, you might be able to prevent or delay trol is an important part of diabetes preven-
developing it. tion. You may be able to prevent or delay
diabetes by losing 5 to 10% of your current
Who is at risk for type 2 diabetes? weight. For example, if you weigh 200 pounds,
your goal would be to lose between 10 to 20
Many people are at risk for type 2 diabetes. The pounds. And once you lose the weight, it is
chances of getting it depend on a combination important that you don›t gain it back.
of risk factors such as genetics and lifestyle. The l Following a healthy eating plan. It is impor-
risk factors include: tant to reduce the amount of calories you eat
l Having prediabetes, which means you have and drink each day, so you can lose weight
and keep it off. To do that, your diet should
blood sugar levels that are higher than include smaller portions and less fat and
normal but not high enough to be called sugar. You should also eat a variety of foods
diabetes from each food group, including plenty of
l Being overweight or having obesity whole grains, fruits, and vegetables. It›s also
l Being age 45 or older a good idea to limit red meat, and avoid pro-
l A family history of diabetes cessed meats.
l Having high blood pressure l Get regular exercise. Exercise has many health
l Having a low level of HDL (good) cholesterol benefits, including helping you to lose weight
or a high level of triglycerides and lower your blood sugar levels. These
l A history of diabetes in pregnancy both lower your risk of type 2 diabetes. Try to
l Having given birth to a baby weighing 9 get at least 30 minutes of physical activity 5
pounds or more days a week. If you have not been active, talk
l An inactive lifestyle with your health care professional to figure
l A history of heart disease or stroke out which types of exercise are best for you.
l Having depression You can start slowly and work up to your goal.
l Having polycystic ovary syndrome (PCOS) l Don›t smoke. Smoking can contribute to in-
l Having acanthosis nigricans, a skin condition sulin resistance, which can lead to type 2 dia-
in which your skin becomes dark and thick, betes. If you already smoke, try to quit.
especially around your neck or armpits l Talk to your health care provider to see wheth-
l Smoking er there is anything else you can do to delay or
to prevent type 2 diabetes. If you are at high
How can I prevent or delay risk, your provider may suggest that you take
getting type 2 diabetes? one of a few types of diabetes medicines.

If you are at risk for diabetes, you may be able to The writer is an Associate Professor, Department of
prevent or delay getting it. Most of the things that Endocrinology & Metabolism, BSMMU, Dhaka

THE PHARMA WORLD 55



“We urge our population to INTERVIEW
diagnose diabetes early
and follow a good lifestyle”

do not develop any symptoms early on. Many a time peo-
ple don’t even know they have diabetes; this condition
remains unrecognized and undiagnosed for a long time
in around 50% of the cases. These patients present with
many complications later. With diabetes there are risks
for renal failure, heart failure, brain stroke, ulcer in the
feet or even amputation. Sexual dysfunction is another
major consequence of diabetes. All these reasons are why
diabetes has been rightly coined “Mother of All Diseases.”

Prof. Dr. Indrajit Prasad When does Insulin therapy need to be
Professor & Head started for patients with Diabetes?
Department of Endocrinology
Dhaka Medical College & Hospital Usually there’s no deficiency of insulin in the body of a
patient with type-2 diabetes initially. As the disease pro-
As a renowned endocrinologist gresses, the insulin level begins to drop. The secretory ca-
of Bangladesh, would you pacity goes down day by day. When Diabetes has crossed
please describe the prevalence 6 years of its age, around 5th year of its diagnosis, 50% of
of Diabetes in our country? the patients become dependent on insulin, the other half
can remain on oral agents. In a few cases, where diabetes
The prevalence of diabetes in is very high— around 20 mmol/L or 30 mmol/L random
Bangladesh is increasing day by day. blood glucose or when the patients present with major
Even few years ago, around 2017 or complications like heart attack, brain stroke, renal failure,
2018, the prevalence was 8%. Now it we can start insulin very early from the beginning. In spe-
has increased to 12%. Previously, the cial situation like gestational diabetes, when the patient
adult population with diabetes was becomes pregnant, we start insulin right away.
84 Lakh; now it rose to 1 Crore 31 Lakh
in a matter of a few years. Nowadays we are seeing many young
patients with type 2 diabetes as well. Will the
Why diabetes is called the management be the same for them as well?
mother of all diseases?
If the blood glucose level is very high, then they can start
You have rightly mentioned that with insulin. But, if it is on the lower side, e.g., 11 mmol/L or
diabetes is the mother of all diseases. 12 mmol/L, then oral antidiabetic agents will suffice. What-
Most cases of diabetes in our country ever the case, we have to look at the rational for prescrib-
is type-2 diabetes mellitus. Type-2 di- ing any treatment. The first and most important solution is
abetes, in most cases, is asymptomat- lifestyle modification, dietary modification, doing physical
ic. So, patients with type-2 diabetes exercises and adequate sleep. Importance Quality sleep is
most often ignored, but you need at least six hours of sleep
to control diabetes, increase longevity of the heart and
overall to ensure a good health.

Nocturnal hypoglycemia has always been a
nightmare for Insulin users. What other adverse
effects should the patients on insulin therapy
be aware of? How could these be avoided?

There are two medications that cause hypoglycaemia,
one is insulin and the other being sulfonylurea. So, why

THE PHARMA WORLD 57

does the nocturnal hypoglycaemia healthcare services, you know! The doctors, monitor blood glucose at
develop? When there’s a timing mis- advancement is in terms of increased home, and follow a good lifestyle.
match between the medications and awareness, diagnosis, and treatment
intake of food, the patient can de- and also in form of pharmaceutical While there’s no cure for diabetes,
velop nocturnal hypoglycaemia. So, advancement— we can produce many what is your advice to patients for
we always recommend taking bedtime medications locally, which we had to im- prevention and control of diabetes?
snacks to avoid nocturnal hypoglycae- port from abroad previously; whichever
mia or early morning hypoglycaemia. medicine is available in advanced coun- This is the most important question
tries like Europe and America, it is avail- in this session I believe. The thing is our
There are other medications related able here in Bangladesh. We can now country is a middle-income country.
to nocturnal hypoglycaemia. As medi- ensure our patients that they need not So, what should be our policy? Is it to
cal science is advancing rapidly, we are go abroad for any kind of endocrine or develop big centers for dialysis or big
moving from conventional insulin to diabetes treatment; we have all the mo- center for angiogram, cardiothoracic
modern analog insulin, which can help dalities, investigations, medications and surgery, by-pass surgery? Not at all.
avoid the nocturnal hypoglycaemia. You treatment readily available right here. The best strategy would be a protec-
know around 40% of the nocturnal hy- tive one, a preventive one. This would
poglycaemia incidences can be avoided Most advanced investigations for be the most cost-effective as well. If a
by simply changing to modern insulin. Diabetes like C-peptide, GAD65 (au- patient walks daily- at least five days a
toantibodies to distinguish between week, takes a healthy diet, sleeps well,
Diabetes is an increasingly type 1 and type 2 diabetes) are avail- and reduce 5–7% of the body weight,
prevalent disease amongst the able in Bangladesh. Managements he can prevent diabetes. Diabetes is
population. Has there been marked like oral hypoglycaemic medications very preventable. That’s why I urge the
improvement in its management like metformin, sulfonylureas, SGLT-2 people to start walking before they de-
and treatment over the last few inhibitors and  conventional insulin, velop diabetes, but unfortunately, the
years in our country compared modern analog insulin, once daily, reality is reverse. We want to aware our
to advanced countries? even once weekly basal insulin like population, educate our population
IGF-1  receptor agonists are all acces- and motivate our population to follow
Thank you very much. This is a very sible in our country. healthy lifestyle, that way 80% of dia-
important subject. Bangladesh has betes incidence can be prevented.
emerged like a tiger with regards to We just urge our population to di-
agnose diabetes early, come to the

58 THE PHARMA WORLD

A behavior-based AMR approach may AMR
assist with vaccination efforts

To address AMR in multiple global contexts, the WHO has released the Tailoring Antimi-
crobial Resistance Program (TAP) to assist Member States to achieve higher levels of vac-
cination uptake. The TAP is an in-depth, stepwise guide that public health officials can use
to develop context-appropriate public health plans to tackle AMR. This behavior insights
approach may also help to provide more actionable methods for AMR containment, as guid-
ance measures at the national level are often well-structured but poorly implemented. TAP
will motivate countries to invest additional time, human resources, and funding to adjust
AMR-prevention strategies to meet their needs.

Rapid detection of Teixobactin promising
resistant Gram-negative to treat MDR infections
bacteria can prevent
inappropriate early Teixobactin, a novel antibiotic with a unique
antibiotic treatment structure and lack of detectable resistance
targeting the bacterial cell wall. Other mem-
Scientists call for faster diagnosis and brane-acting antibiotics have the potential to
treatment of antibiotic-resistant Gram-neg- damage human cells as well, causing unde-
ative bacteria (GNB), particularly those that sirable toxicity, but Teixobactin only destroys
exhibit difficult-to-treat resistance (DTR) or membranes that contain lipid II, a precursor
resistance to all fluoroquinolones and all of peptidoglycan, which is absent in eukary-
beta-lactam categories, including carbap- otes. Teixobactin holds great potential for the
enems. Studies have shown that antibiotic development of better drug candidates.
resistance mechanisms in GNB have re-
sulted in delayed antibiotic therapy, worse Alarmingly high MDR
health outcomes, and increased mortality. bacteria among VAP
Scientists emphasize the importance of un-
derstanding individuals’ infection risk by Among COVID-19 patients in invasive me-
DTR-GNB, improving diagnosis and identi- chanical ventilation in the ICU over 6 months,
fication of specific resistance mechanisms, VAP was prevalent in 33% patients and an in-
and de-escalating an initially broad-spec- cidence rate of 13.48 episodes per 1,000 days.
trum regimen to targeted therapy to reduce Carbapenem resistance was observed in 41.4%
the frequency of inappropriate early antibi- of P. aeruginosa isolates, which attributed to
otic treatment. 52.4% of the cohort receiving broad-spectrum
antibiotics before their ICU admission.

High rates Researchers profiled organisms and antimicrobial resistance
of AMR in of pathogens causing EOS in infants in a prospective, obser-
very preterm vational cohort study involving 32 newborn intensive care
infants with units (ICUs) and 108 cases of EOS in very preterm infants (born
early onset at less than 32 weeks of gestation) in China between January
sepsis (EOS) 2018 to December 2020. The study found that very preterm
infants were at much greater risk for EOS than more mature
infants, with the incidence of EOS highest in infants with a
gestational age of 23–28 weeks (35.8%) and lowest among
those with a gestational age of 31–32 weeks (13.5%). Escheri-
chia coli (n=44, 40.7%) and Klebsiella (n=10, 9.3%) spp. were
the predominant organisms, and both showed high resist-
ance rates to ampicillin and third-generation cephalosporins.

THE PHARMA WORLD 59



“Strict glycemic control from INTERVIEW
the start eliminates many
complications later in life”

Prof. Dr. Feroz Amin What are the available treatment options and
Professor & Head what factors should be considered regarding
Dept. of Endocrinology the best option for an individual?
BIRDEM General Hospital & Ibrahim
Medical College Main focus of diabetes management is Diet, Exercise,
Discipline and Drugs, (oral or Insulin). Diabetes is a meta-
As a renowned physician of bolic disorder in which either insulin is absent or it’s
Bangladesh, would you please not working properly. 50 % of the insulin producing cells,
describe the prevalence of called beta cell is already lost when diabetes is detected
Diabetes in our country? the first time and in the course of time, even more cell is
lost so there will be less insulin production and drug will
At present, the total number of not act. Patients with Type 1 DM, detected at a younger
diabetic persons globally is nearly 537 age, have lost all insulin due to autoimmune reaction; so,
million with a prevalence of 10.5% in they must start insulin from day one for survival. Lack of
the adult population (20 to 79 years). physical activities, obesity, unhealthy foods etc. are the
China and India hold the 1st and 2nd main factors for development of type 2 DM. In Bangla-
positions respectively having 140.9 desh, most of the modern insulins and medications are
and 74.2 million of total cases of dia- available. Choice of insulin depends on patient glucose
betes. It is estimated that this current status, fluctuation, complications and costs. Bolus insulin
number of diabetic persons is pro- will cover the rise of post meal glucose and Basal insulin
jected to reach 643 million by 2030, will take care of Fasting glucose. Some insulin is a combi-
and 783 million by 2045. nation of both bolus and basal. Oral drugs can be added
in Type 2 DM but not in type 1 DM. Some oral drugs will
In Bangladesh the total number sensitize insulin action, few others act on beta cell for
of diabetic people is nearly 13.1 mil- more insulin release, but no drugs are able to produce
lion, with prevalence being 12.5% in new beta cell. In the course of the time when all the beta
the adult population (20 to 79 years). cells has been destroyed/ exhausted, insulin remains as
Bangladesh at present is in 8th posi- the only option. GLP 1 analogue, injectable agent is avail-
tion in the world by the total number able as weekly dose, not alternative of insulin, but they
of people with diabetes. By 2045, it is can help dying beta cell to survive longer to release insu-
projected to move to the 7th position, lin and action potentiation.
with 22.3 million people with T2DM.
Factors to consider for best option of an individual—
diabetes management depends on glucose level, symp-
toms, BMI , infection, weight loss, surgery, pregnancy,
heart & kidney status and also on persons economic
status. If no contraindication, every patient should be
on metformin along with life style modifications . Second
drug either SGLT 2 or DDP4 inhibitor or Sulphonylurea,
even GLP1 or insulin depends on various factors as men-
tioned earlier . It should be always remembered that in
any acute condition or high glucose value , insulin is the
number one and only choice.

Diabetes is considered the “Mother of all diseases”
as it affects other systems in the body as well.
How is diabetic kidney disease (DKD) managed
when the patient has hypertension as well?

More than 50% diabetic patients have one or more

THE PHARMA WORLD 61

complications at the time of presen- cemia as well as fluctuation of glu- Early use of insulin regimen in drug
tation. And if blood glucose is not well cose is more common in premixed in- failure cases and good glycemic con-
maintained they will develop more sulin compared to Basal Insulin. So if trol can prevent many microvascular
complications and die soon. Diabe- needed, changing of insulin regimen & macrovascular complications. Pe-
tes affects all the organs from head and bed time snacks are advocated in riodic eye & foot examination, home
to toe. these groups of patients. monitoring blood glucose as well as
regular follow up investigations has
Chronic complications of diabetes Why diabetic neuropathy been advocated for diabetic patients.
encompass a wide spectrum of micro- is considered a “forgotten
vascular (nephropathy, retinopathy, complication”? what symptoms Where does Bangladesh stand
and neuropathy) and macrovascular should patients look out for? What as far as diabetes treatment,
(coronary artery disease, cerebrovas- are the main challenges related patient care and patient education
cular disease, and peripheral vascular to the symptomatic treatment of is concerned, compared to
disease) disorders. Every person with painful diabetic neuropathy? the advanced countries?
diabetes should be screened periodi-
cally for chronic complications. Diabetic neuropathy is the most Though Bangladesh is a middle in-
common microvascular complica- come country, but still most of our pa-
Very well Control of blood glucose, tion and some time may present with tients are not able take medications
blood pressure and blood lipids spe- burning sensations, severe pain, ab- or even consultation due to poor so-
cifically LDL , along with other factors normal sensation and in severe case, cioeconomic background. A total of
like exercise , diet form the corner- loss of sensation. Patient may develop 62% of people with diabetes usually
stone of prevention and control of neuropathic ulcer and even foot loss. sought treatment and get advice from
diabetic complications. So early diagnosis, regular neurologi- private facilities and only 26.9% from
cal examination is mandatory. Tight government facilities.
Serum creatinine, eGFR and urine blood glucose control like pre-meal,
albumin excretion should be used for (F, BL, BD) 5- 6 mmol/L and post meal Most of the recent medications,
screening diabetic nephropathy. (2hrs after ABF , AL , AD ) 8 -10 mmol modern insulin’s are available in our
/L is mandatory for prevention and country, but those are costly and pa-
ACE inhibitors or ARB-s are drugs delay of any micro vascular complica- tients are not willing to continue or
of choice for hypertension in preven- tions . The most challenges related to start. Diabetic Association of Bangla-
tion or delay of nephropathy. Min- any painful neuropathy is unrespon- desh under the guidance of national
eralocorticoid receptor blocker like siveness of prescribed medications. Professor A K Azad Khan is taking
spirolactone , eplerenone and recent- There are many drugs that has been care of many patients with affordable
ly finerenone have been advocated in advocated but with little outcome, costs in different centers of the coun-
different guidelines for DKD patients but tight glycemic control ultimately try. In fact diabetic guidebook which
if not hyperkalemia . make the patient better . is unique in comparison to other
countries, emphasize diabetic educa-
SGLT 2 inhibitors, GLP1 analogue Diabetes treatment and approaches tion and dietary advice where patient
are more preferable in DKD patients have changed a lot in recent data are available from beginning to
for glucose control. years. What have been the major at present.
developments in your opinion?
Nocturnal hypoglycemia has As diabetic education is the main
always been a nightmare for Diabetes treatment has changed a focus of glucose management, BIR-
Insulin users. What other adverse lot, importantly, strict glycemic con- DEM Hospital also appointed diabe-
effects should the patients on trol from the start eliminates many tes educators, along with physicians
insulin therapy be aware of? complications later in life. In any and nurses. Due to huge load of
How could these be avoided? acute condition or sudden rise of glu- patients and lack of man power, nec-
cose, initiation of insulin should not essary outcome is still not achieved
Hypoglycemia is the most common be delayed. compared to developed countries.
complication in diabetic patients Most of the developed countries bear
treated with Oral Hypoglycaemic Diabetic education is needed for the cost of investigations, treatment
Agents or Insulin. Most common fac- patient empowerment, dose ad- by government or insurance, which is
tors related to hypoglycemia is missed justment, regular home monitor- not possible in our country and that
meal or sudden heavy exercises. If ing. Metformin, SGLT 2 inhibitor, GLP causes delay of expected outcome. At
Insulin treated patients overdose in 1 analogue have been advocated in present, prevention of Diabetes and
administration at night, missed food guideline as initial treatment protocol its complications is the most impor-
or eat less at dinner time, nocturnal as these groups of medications have tant focusing point and so Govern-
hypoglycemia will develop. pleiotropic effect for prevention of ment as well as Diabetic Shamity is
cardiovascular and renal outcomes. taking more steps on that account.
Patient will wake up with drenching
sweating, palpitations, headache, and
in severe case, drowsiness or even
unconsciousness. Nocturnal hypogly-

62 THE PHARMA WORLD

Valacyclovir: Potential risk of drug Levothyroxine DRUG SAFETY

reaction with eosinophilia and and ciprofloxacin:

systemic symptoms (DRESS) Increased risk of

Health Canada has announced that the product safety information hypothyroidism
for valacyclovir containing products will be updated to include
the potential risk of drug reaction with eosinophilia and systemic The Medsafe has announced
symptoms (DRESS). DRESS is a rare, but serious, and potentially that the product informa-
life-threatening drug reaction that includes fever, rash, elevated tion for levothyroxine and
white blood cell count, and can affect one or more organs. Valacy- ciprofloxacin are being up-
clovir is indicated for the treatment of cold sores (herpes labialis), dated to include information
shingles (herpes zoster) and treatment, suppression or reduction on the drug-drug interaction
of the transmission of genital herpes. Health Canada reviewed between levothyroxine and
information provided by the manufacturer of Valtrex®, data from ciprofloxacin and the risk of
the Canada Vigilance database, and the published literature. hypothyroidism. The Cen-
tre for Adverse Reactions

Monitoring (CARM) received

a report of hypothyroidism

Benzodiazepines: Topiramate: symptoms in a patient taking
levothyroxine and a course of

risk of dependence neurodevelopmental ciprofloxacin. The symptoms
and withdrawal disorders in-utero improved upon stopping cip-
rofloxacin and increasing the
The Medsafe has reminded Recently, a study based on levothyroxine dose tempo-
prescribers of the recent up- data from a Nordic registry rarily. In addition, a search
date to the product infor- that investigated the risk of in the literature identified a
mation for benzodiazepines neurodevelopmental disor- case report and study that re-
regarding the potential risks ders associated with several ported or suggested this in-
of abuse, dependence and anti-epileptic drugs, includ- teraction. It is recommended
withdrawal, even when taken ing topiramate was published. that health-care profession-
at recommended dosages. The study conclusions suggest als should instruct patients
New Zealand dispensing a possible increase in the risk to separate the administra-
data shows that diazepam of autism spectrum disorders, tion times of these two con-
and lorazepam are the most intellectual disability and comitant medicines by leav-
dispensed benzodiazepines. child neurodevelopmental ing at least a six-hour gap
Between August 1969 and disorders with the exposure to between administration of
March 2022, there were 23 topiramate during pregnancy. both medicines.
case reports of withdrawal

and/or dependence with

the use of benzodiazepines.

Clonazepam (nine cases) was

the most frequently reported Dexamethasone, betamethasone:

benzodiazepine, followed by Risk of phaeochromocytoma crisis
lorazepam (five), diazepam
(three) and triazolam (three). The MHLW and the PMDA have announced that the product
Health-care professionals are information for dexamethasone and betamethasone contain-
advised to counsel patients ing products should be revised to include the risk of phaeo-
about the risks of benzodiaz- chromocytoma crisis. Cases of phaeochromocytoma crisis
epines when initiating treat- reported with the use of dexamethasone (oral dosage form
ment, regularly review the and injections) and betamethasone (injections) in Japan and
ongoing need for treatment, overseas were evaluated. Several cases were assessed to have
and gradually taper benzo- a possible causal relationship between the drug and event. If a
diazepines following con- marked elevation in blood pressure is observed following ad-
tinuous or high-dose use to ministration of these drugs, health-care professionals should
reduce the risk of withdrawal consider the possible occurrence of phaeochromocytoma cri-
reactions. sis and take appropriate measures.

THE PHARMA WORLD 63

Diagnosing and prescribing through
the pharmacovigilance lens

PHARMACOVIGILANCE n Arshia Bhandari one in five women taking valproate in the EU are
unaware of the risks of taking it when pregnant.
The primary purpose of pharmacovigilance  is In 2018, the Pharmacovigilance Risk Assessment
risk mitigation, prevention and management of Committee (PRAC) of the European Medicines
adverse drug reactions. A major impediment to Agency recommended new measures to prevent
achieving this purpose is lack of effective com- valproate exposure in pregnancy.
munication about signals, adverse drug reac-
tions (ADRs), and drug interactions to health MANY PHYSICIANS FAIL TO RECOGNISE  the
care professionals and patients. Even when the connection between medications and illness,
communication occurs, it is important that the and patients are needlessly prescribed medi-
information is sufficiently absorbed and used cations to treat symptoms without dealing with
by clinicians, and reaches patients. the root cause. Understanding adverse drug
reactions and drug interactions should be an
For example, from 1998 to 2000, terfenadine, essential diagnostic tool in clinical practice, es-
mibefradil, astemizole, and cisapride were re- pecially in patients with chronic conditions or
moved from the US market or restricted in their on multiple medications. Pharmacovigilance
use since their co-prescription with interact- needs to transform from a reactive to a proac-
ing drugs had resulted in deaths. Each one had tive process.
value in the pharmaceutical marketplace and
for patients. However, they continued to be pre- So is misdiagnosis of an adverse drug reac-
scribed in an unsafe manner, even after warn- tion as a new ailment by a clinician a human
ings from the manufacturer and the FDA. Conse- error or rather a lapse in the system? With the
quently, the risk associated with their continued amount of data on adverse drug reactions and
widespread availability could not be justified. drug interactions, is it possible for clinicians to
keep track of all adverse events and interac-
Similarly, valproate, a drug prescribed for ep- tions and be conversant with latest research?
ilepsy and bipolar disorder is contraindicated Can this be resolved through a systems ap-
in pregnancy and in patients with child-bearing proach, by bringing in technology and expertise
potential. Despite warnings and communica- from pharmacology and pharmacovigilance for
tions to health care professionals and patients, clinical decisions?

64 THE PHARMA WORLD

FROM THE TECHNOLOGY PERSPEC- New online courses to support
TIVE, drug interaction trackers such pharmacovigilance activities
as Epocrates and The Medical Letter around the world
can be powerful aids. Searches in da-
tabases such as VigiAccess can also The need for strong pharmacovigi- important and complex topic in phar-
inform health professionals of emerg- lance systems is greater than ever, macovigilance and aims to better pre-
ing signals, and serve as a starting and UMC’s Education & Training team pare assessors for evaluation of such
point in identifying similar events have been hard at work developing cases. It is also the first fruit of UMC’s
in patients. Medication and adverse new courses to provide staff at phar- cooperation with the Council for In-
event review by pharmacologists dur- macovigilance centres with relevant ternational Organizations of Medical
ing hospital rounds can help make knowledge they can use in their day- Sciences (CIOMS), working together
the right diagnosis and spot ADRs. to-day activities monitoring the safety with external experts from the CIOMS
Hands-on experience with pharma- of medicinal products. To that effect, Working Group.
covigilance data in ADR monitoring UMC has released seven new courses
centres during internships and medi- in 2022, including: UMC’s course offering also covers other
cal training could also assist future important aspects of pharmacovigi-
clinicians to appreciate the signifi- • VigiFlow introduction lance, including regulation and com-
cance of pharmacovigilance in clinical • VigiLyze introduction munication. To support WHO in its work
assessment. • Drug-induced liver injury to strengthen regulatory systems world-
• Collecting high-quality ADR reports wide, UMC collaborated with external
ANOTHER IMPORTANT AREA  is pa- • Pharmacovigilance management experts to produce an introduction to
tient engagement and empowerment. medicinal product vigilance as a regu-
Patients have access to online tools, systems and terminologies latory function. Though this course was
symptom checkers, drug interaction • Regulatory aspects of pharma- developed for staff of national regula-
trackers, and drug information web- tory authorities in low- and middle-
sites, with information on ADRs and covigilance income countries looking to strengthen
drug dosages. However, there is still • Essentials of pharmacovigilance their pharmacovigilance capacity, it may
resistance in the medical fraternity to be of interest to other groups as well.
patients armed with knowledge. When communications Lastly, our essentials of pharmacovigi-
patients come with limited knowledge lance communications course shows
and with information from inauthen- Together these courses introduce key the value of good communication and
tic sources, it becomes a challenge for strategies, concepts, terminology, and how it’s done. With this course, anyone
the consulting clinician. A paternalis- tools for effective collection, han- can learn the basics of effective com-
tic approach towards patient engage- dling, and analysis of adverse event munication to help spread the word on
ment in healthcare decisions erodes reports. To give some insight, the in- important topics in medicines safety.
patients’ trust and confidence in their troductory courses to VigiFlow and
clinicians, and compromises patient Vigi-Lyze were designed to guide new All courses are a mix of theory, inter-
safety. Listening to patients’ concerns users through the main functionali- active exercises, knowledge checks,
and providing them with the right in- ties of these systems, such as enter- and reflective exercises. To access
formation can be helpful in reaching ing and sharing reports on adverse these, and our many other courses,
the right diagnosis. events in VigiFlow and qualitative and visit UMC’s online learning platform
quantitative workflows in VigiLyze. Ex- at learning.who-umc.org.
Patient awareness campaigns perienced users can expect more ad-
by national authorities and patient vanced courses soon.
safety organisations help build pa-
tient engagement. However, true pa- The course on drug-induced liver
tient centricity can only be achieved injury, also known as DILI, covers an
when their opinions are respected
and considered as an aid in diagno-
sis. Authentic and reliable sources
of information for patients are vital,
and physicians can help interested
patients find the right information
sources to lead them to appropriate
decisions regarding their treatment.  

The Writer is a Pharmacovigilance
consultant & medical writer Founder
PhVFit.

THE PHARMA WORLD 65



“Diabetes management can be improved INTERVIEW
by Increasing knowledge of the patients
and positive lifestyle modifications”

Prof. Dr. Khwaja Nazim Uddin As a renowned physician of Bangladesh, would
Professor and Hon. Senior Consultant you please describe the prevalence of Diabetes in
of Medicine our country and what is the global scenario?
BIRDEM and Ibrahim Medical
College, Dhaka The prevalence of Diabetes is increasing in our country.
Now, one in eleven of the world’s adult population is living
with Diabetes. According to the statistic of 2017, 425 million
people are suffering from Diabetes. In Bangladesh, so far,
more than 1 crore people are suffering from Diabetes. In case
of densely populated countries like India, Brazil, Saudi Ara-
bia, America, almost 12% people are suffering from Diabetes.
Main difficultly is 1 in 2 persons are undiagnosed. Almost 70%
Diabetic patients’ blood glucose levels remain untested.

D​ iabetes is not a disease of rich people anymore. Low in-
come group is equally vulnerable. 1 in 6 women are having
high sugar during their pregnancy. Children are also getting
Diabetes registered day by day. Another major concern is
Type-2 Diabetes in young adults. Type-2 Diabetes is treated
with tablets and Type-1 is treated with insulin.

What are the available treatment options and
what factors should be considered regarding
the best option for an individual?

Diabetes is mainly treated in 3 ways, firstly, lifestyle chang-
es; lifestyle changes by maintaining proper diet and physical
exercise, secondly, education and monitoring and thirdly, by
Drugs. You can treat hypertension by medicine only. But you
cannot treat Diabetes with only medicine.

T​here are 2 types of medication we all know. One is tablet,
another is injection. Now, initial medication is metformin. It de-
pends on the blood sugar level. This is not only the fasting blood
glucose or the glucose level after breakfast. It is the average of
3 months’ blood sugar level. It’s also called HbA1c (Hemoglobin
A1c). If someone has an HbA1c level of 6.5, fasting blood glucose
level of 7 or more and after breakfast 11.1 or more, then he is Dia-
betic and needs Metformin. Other oral agents include pioglita-
zone; DPP 4 inhibitors like sitagliptin, linagliptin; GLP-1 Analogues
like liraglutide and SGLT-2 Inhibitors like gliclazide, glimepiride.

R​ egarding insulin, doctors don’t want to give insulin. Pa-
tients also don’t like to take it. But, whenever needed, you
have to take it. In case of insulin deficiency, insulin is the only
effective medication and if indicated, early initiation is best.

Diabetes is considered the “Mother of all diseases”
as it affects other systems in the body as well.
How is diabetic kidney disease (DKD) managed
when the patient has hypertension as well?

Diabetes causes major microvascular complications such
as nephropathy, retinopathy, and neuropathy. The macrovas-

THE PHARMA WORLD 67

cular complications caused by diabe- may further cause severe hypokalemia, tor agonists (GLP-1 RAs) and various
tes manifest as high blood pressure, particularly in patients with a normal combinations are making blood sugar
accelerated atherosclerosis, ischemic or low serum potassium concentration. control easier and with fewer side ef-
heart disease, increased risk of cer- This can lead to arrhythmias, cardiac ar- fects.  Insulin has also come a long way
ebrovascular disease, kidney failure, rest and respiratory muscle weakness. since it was first discovered. There are
and severe peripheral vascular dis- variety of formulations, including rap-
ease Peripheral. So, you can see that Why diabetic neuropathy id-acting, long-lasting, and premixed
its impact is so harmful on the vital is considered a “forgotten formulas, and can be delivered via
systems that it is regarded as a moth- complication”? What symptoms syringes, pens or automated pumps.
er of all diseases. should patients look out for? What There are continuous glucose moni-
are the main challenges related tors now available as well for better
Nocturnal hypoglycemia has to the symptomatic treatment of management of diabetes.
always been a nightmare for painful diabetic neuropathy?
Insulin users. What other adverse Where does Bangladesh stand
effects should the patients on This is partly because it is very dif- as far as diabetes treatment,
insulin therapy be aware of? ficult to treat and because of a lack of patient care and patient education
How could these be avoided? awareness of the patients. Some pa- is concerned, compared to
tients remain unaware of their condi- the advanced countries?
When somebody is having the tion because early symptoms may be
deadly experience of hypoglycemia, very subtle and Not all patients expe- Diabetes has become a national
he or she will naturally oppose to take rience pain and numbness. health concern in Bangladesh; how-
insulin. The patient himself along ever, treatment and control are still
with his relatives should know how to Patients should keep alert to de- quite low as education and aware-
treat it. They should know the symp- tect any tingling and numbness, loss ness among the population is low,
toms. Initially, he gets hungry and of ability to feel pain  and changes especially in the rural area.  Diabetic
then starts sweating. After observing in temperature, loss of coordination Associations of Bangladesh (BADAS)
these symptoms, patients should im- and burning or shooting pains. Some is playing a great role in this regard.
mediately take sugar or any kind of patients may have renal impairment BADAS is educating patients through
fine sweetener or glucose. double vision, eye pain or paralysis Leaflet, posters, training tools like
on one side of the face (Bell’s palsy). video programs and animations. They
To prevent it, patients should bal- have taken several Health educa-
ance their meal time and medica- Diabetes treatment and approaches tion programmes like distance learn-
tions. There are many new insulins have changed a lot in recent ing course with a view to develop
and combinations which offer less years. What have been the major manpower in the field of diabetes
nocturnal hypoglycemia and better developments in your opinion? throughout the country.  Diabetes
post-dinner glucose control. management can be improved by in-
A lot has changed in recent years in creasing knowledge of the patients
Another adverse effect which is not the  management  and  treatment  of and positive lifestyle modifications to
widely talked about is that insulin low- diabetes. Newer agents like sodium- reduce comorbidities and complica-
ers the potassium level in patients. Dia- glucose cotransporter-2 (SGLT2) inhib- tions.
betic patients frequently develop elec- itors, Glucagon-like peptide-1 recep-
trolyte disorders. So, insulin therapy

FAST  More than 13,000 new patients are  Approximately 537 million adults (20-79
diagnosed with breast cancer in the years) are living with diabetes as of 2021.
FACTS country every year, out of which 6,783
women die.  The total number of people living with
diabetes is projected to rise to 643
 The cost of treating dengue at million by 2030 and 783 million by 2045.
government hospitals often reaches Tk.
20,000-25,000. In private hospital the cost  3 in 4 adults with diabetes live in low-
is much higher and middle-income countries

 Bangladesh ranks lowest in South  Almost 1 in 2 (240 million) adults living
Asia in terms of health allocation as a with diabetes are undiagnosed
proportion of GDP. Currently, we have to
pay 72% of our medical expenses out of  More than 1.2 million children and
our own pockets. adolescents (0-19 years) are living with
type 1 diabetes

68 THE PHARMA WORLD

‘Bionic Pancreas’ could make life easier Robotic drug capsules TECHNOLOGY
for people with type 1 Diabetes can deliver drugs to gut

A new technology dubbed the “bionic pancreas” may One reason that it’s so difficult to de-
beat standard treatment in helping people with type liver large protein or nucleic acid drugs
1 diabetes control their blood sugar levels, a clinical like insulin, GLP1 receptor agonists and
trial has found. The researchers reported that adults most biologics orally is that these drugs
and children with type 1 diabetes who used the bionic can’t pass through the mucus barrier that
pancreas for three months saw their average blood lines the digestive tract. So, these must
sugar levels decline — without an increase in poten- be injected or administered in a hospi-
tially dangerous blood sugar lows. The device, called tal. A new drug capsule developed by a
the iLet Bionic Pancreas, is under review by the USFDA. collaborated effort of NIH & MIT may one
If approved, it would be the most automated system day be able to replace those injections.
for managing type 1 diabetes — tracking blood sugar The “RoboCap” capsule, which is about
levels and delivering insulin with minimal patient in- the size of a multivitamin, carries its drug
put. Patients using the bionic pancreas saw a decline payload in a small reservoir at one end
in their A1c from an average of 7.9% to 7.3%, while the and carries the tunnelling features in its
comparison (conventional treatment) group showed main body and surface. The capsule is
no change. Patients using the bionic pancreas also coated with gelatin that can be tuned to
spent more time with their blood sugar levels in the dissolve at a specific pH. When the coat-
target range — an extra 2.5 hours per day, on average. ing dissolves, the change in pH triggers a
tiny motor inside the RoboCap capsule to
start spinning and tunnel into the mucus,
displacing it to allow better absorption of
the drug. In tests in animals, the research-
ers found that they could deliver 20 to
40 times more drug than a conventional
capsule and if approved, this would pave
the way to better precision medicine.

Machine learning algorithm can predict diabetes from ECG

A machine learning algorithm can detect  dia- validation, and independent test sets. The clas-

betes and prediabetes from electrocardiogram sifier that used the signal-processed ECG as
(ECG) features. Scientists combined noninvasive input and predicted membership of no diabe-

ECG with machine learning to detect diabetes tes, prediabetes, or type 2 diabetes classes was
and prediabetes using data from 1,262 individu- trained using extreme gradient boosting (XG-
als and 10,461 time-aligned heartbeats recorded Boost). The Algorithm predicted the classes in
digitally. The dataset was divided into training, the independent test set with 97.1 percent preci-
sion, 96.2 percent recall, 96.8 percent accuracy,
and 96.6 percent F1 score. “In theory, our study Source: Science Daily
provides a relatively inexpensive, noninvasive

and accurate alternative which can be used as
a gatekeeper to effectively detect diabetes and

prediabetes early in its course,” the authors
write. “Nevertheless, adoption of this algorithm
into routine practice will need robust validation
on external, independent datasets.”

THE PHARMA WORLD 69



“Bangladesh is still lagging behind the
target of ideal management of diabetes”

Prof. Dr. Mir Mosarraf Hossain have additional benefits beyond gly- diabetic persons. In addition to that,
Professor & Head, cemic control, eg SGLT² inhibitors albuminuria and radiologic changes
Dept. of Endocrinology have a positive impact on cardiac & in renal structure are included in the
Sir Salimullah Medical College Mitford renal function. However, Metformin diagnosis of CKD, but a renal biopsy
Hospital, Dhaka Still remains the first-line drug for can confirm the diagnosis of diabetic
Type 2 diabetic subjects as per rec- nephropathy (DN).
As an eminent endocrinologist of ommendations of most organizations.
the country, would you please tell Regarding the treatment of DN,
us about your valuable observation Do people with diabetes need good glycemic control, BP control, and
regarding the prevalence of to change their medicines over correction of dyslipidemia are impor-
Diabetes in Bangladesh? How does time? What factors should be tant. In addition, cessation of smoking
it compare to the global scenario? considered in choosing the best and weight reduction in overweight or
option for an individual? obese persons are also important. 
Regrettably, Bangladesh was in the
8th position in the world ranking in Yes, some drugs may not be effec- About 50% of women with
accordance with diabetic population. tive and safe for lifelong use. Athero- gestational diabetes go on to
According to the International Diabe- sclerotic Cardiovascular disease (AS- develop type 2 diabetes. What
tes Federation (IDF) atlas, 131 million CVD), heart failure, and chronic kidney can be done to prevent it?
people, in 20-79 age group, were suf- diseases should be taken into consid-
fering from diabetes in 2021. Which eration regarding starting & Changing Lifestyle changes which dietary ad-
is alarming and higher than ever an- antidiabetic medications.  vice and increased physical activities
ticipated before. The number diabetic resulting in achieving and maintain-
persons are increasing more in South Nocturnal hypoglycemia has ing ideal body weight can reduce the
East Asia (SEA) including Bangladesh always been a nightmare for risk of developing type 2 diabetes. 
in comparison to western Countries. Insulin users. What other adverse
It’s apprehended that the rate of in- effects should the patients on Where does Bangladesh stand as
crement will be 68% in SEA, whereas, insulin therapy be aware of? far as diabetes treatment, patient
it will be 24% in USA & 13% in Europe. How could this be avoided? care, and patient education is
concerned, compared to the
Antidiabetic combinations In addition to hypoglycemia, weight advanced countries?
are available nowadays, gain is another adverse effect of insu-
making it easier to manage lin treatment. In addition to that, some Despite utmost efforts, Bangladesh
diabetes. How about the safety problems including infection may oc- is still lagging behind the target of
and efficacy compared to cur at the injection site if proper in- ideal management of diabetes. More
conventional oral agents? structions are not followed. Allergic than 62% of diabetic subjects are un-
reactions are very rare nowadays with diagnosed and half of the diagnosed
Undoubtedly it is safe as far as hy- the use of human insulin and newer patients go to qualified physicians
poglycemia and weight gain are con- analogues. Proper education regarding and half of them follow adequate
cerned. Regarding efficacy, it is almost insulin use, educating diabetic people management plans. Less than 10%
similar to older drugs & some drugs about the symptoms of hypoglycemia, of diabetic subjects achieve target
and frequent self-blood glucose moni- HbA1c in Bangladesh. Bangladesh’s
toring with dose adjustments can be government has taken necessary
very effective in avoiding hypoglyce- measures to provide oral anti-diabet-
mia. Moreover, insulin analogues have ic medications at the grassroots level
relatively less risk of hypoglycemia.  and hopefully, it will have positive
impacts on diabetes management.
What is the most important We need more expert manpower like
marker for diabetic nephropathy? Endocrinologists, medical educators,
What are the challenges in and dieticians to achieve the goals of
treating diabetic nephropathy? diabetes management. We are abso-
lutely optimistic that with the com-
Decreased glomerular filtration bined efforts of all, we can provide
rate (GFR) is important in the diagno- standard services that will be parallel
sis of chronic kidney disease (CKD) in to the developed countries.

THE PHARMA WORLD 71

ARTICLE Rational use of
Medicine: Special
focus on Antibiotics

Dr. Khandaker Sagir Ahmed, M. Pharm, PhD
Director (Retd), Directorate General of Drug Administration

The concept of rational use of medicine is ticularly for childhood infections and chronic
an old one, dating back as far as 300B.C, diseases, such as hypertension, diabetes, epi-
when the Greek physician Herophilus said lepsy and mental disorders. Inappropriate use
that “Medicines are nothing in themselves if not and over-use of medicines waste resources
properly used but in the very hands of God when often out-of-pocket payments by patients and
they are employed with reason and prudence’’. result in significant patient harm in terms of
poor patient outcomes and adverse drug reac-
Rational use of medicine occurs when “ Pa- tions. Furthermore, over-use of antimicrobials
tients receive medication appropriate to their is leading to increased antimicrobial resistance
clinical needs in doses that meet their own in- and non-sterile injections to the transmission of
dividual requirements for an adequate period of hepatitis, HIV/AIDS and other blood-borne dis-
time and at the lowest cost to them and their eases. Finally, irrational over-use of medicines
community” (WHO 1985). can stimulate inappropriate patient demand,
and lead to reduced access and attendance
The definition implies that rational use of rates due to medicine stock-outs and loss of pa-
drugs, especially rational prescribing should tient confidence in the health system. Globally,
meet following criteria’s: about 8% of the total health expenditure or 500
Billion US Dollar can be saved with more ration-
l Appropriate indication: the decision to pre- al use of medicine.
scribe drug(s) is entirely based on medical
rationale and that drug therapy is an effec- Promoting Rational Use of Medicines:
tive and safe treatment. Twelve core interventions to promote more
rational use of medicines like –
l Appropriate drug: the selection of drugs 1. A mandated multi-disciplinary national
is based on efficacy, safety, suitability and
cost considerations. body to coordinate medicine use policies
2. Clinical guidelines
l Appropriate patient: no contraindications 3. Essential medicines list based on treat-
exist and the likelihood of adverse reac-
tions is minimal, and the drug is acceptable ments of choice
to the patient. 4. Drugs and therapeutics committees in

l Appropriate information: Patients should districts and hospitals
be provided with relevant, accurate, impor- 5. Problem-based pharmacotherapy training
tant and clear information regarding his or
her condition and the medications that are in undergraduate curricula
prescribed. 6. Continuing in-service medical education

l Appropriate monitoring: the anticipated as a licensure requirement
and unexpected effects of medications 7. Supervision, audit and feedback
should be appropriately monitored. 8. Independent information on medicines
9. Public education about medicines
According to WHO, medicines accounts for 30% 10. Avoidance of perverse financial incen-
of health expenditure for many countries of the
world. In Bangladesh, the total budget for Health tives
is less than 1% of GDP for last two decades. Lack 11. Appropriate and enforced regulation
of access to medicines and inappropriate doses 12. Sufficient government expenditure to
result in serious morbidity and mortality, par-
ensure availability of medicines and staff

72 THE PHARMA WORLD

According to the WHO report, the irrational use of an- every condition. If the doctor does not prescribe an-
tibiotic was 50% while the misuse and overuse was up to tibiotics do not deny that you are sick.
100% in the upper respiratory tract infections. In a survey l Antibiotica should be used only by the prescription
carried out in USA showed that51% of the patients hav- of a registered physician according to the dose, dura-
ing urinary tract infections and cold received antibiotics tion and instruction of the physician should followed
found that 20% of the antibiotics prescribed were irration- strictly.
al. Irrational use of antibiotics is harmful for both patient l In viral infection antibiotic is unnecessary.
and society. Irrational use of Resistant Antibiotics are one l The physician instructions should be carefully fol-
of the ten cause of mortality and morbidity around the lowed in the selecti on of antibiotic.
world.
Reasons for irrational use of antibiotic:
Strategy of the administration of antibiotics: l Very short consultation time - does not allow proper
1. Patients with serious bacterial infections. The num- diagnosis.
l Prescription of antibiotics for non-bacterial infec-
ber of white cells increases. tions. Physician prescribe antibiotics to patients with
2. Based on the clinical picture, laboratory tests can non-bacterial infections.
l Polypharmacy - Too many medicines are prescribed
identify the anatomical location of the infection. per patient.
3. Patients who develop an infection during their hos- l Antibiotic injections are used where oral formula-
tions would be more appropriate.
pital stay empiric antimicrobial therapy. l Prolonged prophylactic therapy.
4. The remarkable ability of the micro-organisms to l Prolonged empiric antimicrobial treatment without
clear evidence of infection.
adapt to any environment is that each new patho- l Failure to narrow antimicrobial therapy when a caus-
genic is resistant to antibiotics administered in the ative organism is identified.
previous period. l Prescriptions do not follow clinical guidelines
5. Patients with meningitis should not be administered l Patients self-medicate inappropriately
antibiotics which do not pass the blood brain bar- l Patients do not adhere to prescribed treatment
rier, such as the first generation cephalosporin, gen-
tamicin, and clindamycin. Antimicrobial Resistance:
6. The foreign body infections, prosthetic valves, pros- The legacy of the past decades in terms of antibiotic use
thetic joints, pacemakers, it is almost impossible to has added to the development of bacterial resistance to-
eradicate without removing the foreign body. wards multiple drugs.
7. In acute infection, patients with neutropenia, have
an increased mortality from sepsis and appropriate Antimicrobial resistance is rising dangerously high level
direct intravenous therapy (taking the appropriate in all parts of the world. New resistance mechanisms are
cultures) with broad spectrum bactericidal antibiot- emergimg and spreading globally threatening one ability
ics at high doses. to treat common infections eg. pneumonia, blood poison-
8. Older people metabolize and excrete antibiotics at a ing, tuberculosis, gonorrhea and food-borne disease are
slower pace. Therefore, there should be longer inter- commonly hander and sometimes impossible to treat as
vals between the doses of antibiotics. antibiotic becomes less effective.

Health professionals also need to bear in mind the follow- The consequences of AMR on health and healthcare sys-
ing basic rules for the rational management of antibiotics. tems are extraordinary. It has been estimated that millions
of drugs resistant infection cost 67 million deaths worldwide
a) Too many antibiotics together may act synergistically each year. The burden of death from AMR could reach up to
rather than competitively. The majority of infections 10 million each year globally by 2050 unless action is taken.
can be treated with an antibiotic. In case of polymi-
crobial infection. eg. intraventricular brain abscesses The increasingly wide spread antibiotic resistance rep-
and infections of the lower limbs of diabetic patients resent as WHO has said “A slow Tsunami that threatens to
combination antibiotic therapy is preferred. wipe out a century of medical practice”.

b) The use of many antibiotics results in more side ef- Antimicrobial resistance happens when germs like bac-
fects; adverse reactions to antibiotics are common. teria and fungi develop the ability to defeat the drugs de-
When a patient taking many antibiotics had an al- signed to kill them. That means the germs are not killed
lergic reaction, then all antibiotics are suspect and and continue to grow. Resistant infections can be difficult,
cannot reuse. and sometimes impossible, to treat.

c) The use of many antibiotics increases the risk of in- AMR is one of the three major cause of public health
fection with resistant micro-organisms. problems. Bacteria and fungi do not have to be resistant
to every antibiotic or antifungals to be dangerous. AMR is
One should not: a serious threat to public health.
l Make people take antibiotics on their own initiative
if not prescribed by the doctor.
l The prescription of antibiotics is not necessary in

THE PHARMA WORLD 73

Antimicrobial resistant infection that requires the use – Only use antibiotic when prescribed by a certified
of second- and third-line treatment can harm patients by health professional.
causing serious side-effects such as organ failure and pro-
long care and recovery sometimes for month. – Never demand antibiotics if health workers say it is
not needed.
Many medical advances are dependent on the ability to
fight infections using antibiotic including joint replacement, – Follow health workers advice when using antibiotics.
organ transplant, cancer therapy, and treatment of chronic – Never share or use leftover antibiotics
diseases like diabetes asthma and rheumatoid arthritis. – prevent infections by regularly washing hands, pre-

In some cases, these infections have no treatment op- paring food, avoiding close contact with sick people,
portunity. The analysis of 204 countries and territories, practicing safer sex and keeping vacation up to date
published in the Lancet, reveals that AMR is now a leading Policy makers
cause of death worldwide higher than HIV/AIDS or Malaria.
It shows that many hundreds of thousands of deaths now To prevent and control the spread of antibiotics resist-
occur due to common, previously treatable infections eg. ance, policy makers can:
lower respiratory and blood stream infections.
– Ensure a robust national action plan to tackle anti-
Superbug and super resistance: biotic resistance is in place.
The term superbugs refer to microorganisms with
heightened morbidity and mortality due to multiple muta- – Improve surveillance of antibiotic resistance infections
tions conferring high levels of resistance to the antibiotic – Strengthen policies, programs and implementations
classes specifically recommended for their treatment. Su-
perbugs are strains of bacteria that are resistant to most of infection prevention and control measures
of the antibiotics and other medicines commonly used to – Regulate and promote the appropriate use and
treat infections. A few examples of superbugs include re-
sistant bacteria that can cause pneumonia, urinary tract disposal of quality medicine
infections and skin infections. – make information available on the impact of antibi-

Some of the most significant Superbugs are: otic resistance
1. Methicillin resistant Staphylococcus aureus (MRSA)
2. Carbapenem resistant Enterobacteriaceae (CRE) Health professionals
3. Extended spectrum B-Lactamase (ESBL) To prevent and control the spread of antibiotic resistance,
4. Vancomycin resistant enterococcus (VRE) health professionals can:
5. Multi-drug resistant Pseudomonas aeruginosa
6. Multi-drug resistant Acinetobacter Pan-drug resist- Prevent infections by ensuring your hands, instruments,
ant Klebsiella pneumonia and environment are clean.

In recent years some superbugs such as vancomycin re- Only prescribe and dispense antibiotics when they are
sistant enterococci bacteria remain unaffected even by needed, according to current guidelines.
this antibiotic of last result.
Report antibiotic-resistant infections to surveillance teams.
The growing number of antibiotic resistant pathogens Talk to your patients about how to take antibiotics cor-
place a significant burden on healthcare systems and have rectly, antibiotic resistance and the dangers of misuse.
important global economic costs. It results in high mor- Talk to your patients about preventing infections (for
tality and morbidity rates and increased treatment costs, example, vaccination, hand washing, safer sex, and cover-
diagnostic uncertainties and lack of trust in medicine. ing nose and mouth when sneezing).

Antimicrobial resistant superbugs could be responsi- Healthcare industry
ble for up to 80% of death in intensive care units (ICUs) To prevent and control the spread of antibiotic resistance,
of Bangladesh (Prof. Sayedur Rahman, Chairman of Phar- the health industry can:
macology Department of BSMMU, 2018). One-third of the
infections in patients with Cirrhosis is Estimated to be due Invest in research and development of new antibiotics,
to Multi-drug resistant Bacteria. vaccines, diagnostics and other tools.

Prevention and Control: Agriculture sector
Antibiotic resistance is accelerated by the misuse and To prevent and control the spread of antibiotic resistance,
overuse of antibiotic as well as poor infection prevention the agriculture sector can:
and control. Steps can be taken at all level of society to
reduce the impact and limit the spread of resistance. Only give antibiotics to animals under veterinary super-
vision.
Individuals: To prevent and control the spread of Antibi-
otics resistance individuals can: Not use antibiotics for growth promotion or to prevent
diseases in healthy animals.

Vaccinate animals to reduce the need for antibiotics
and use alternatives to antibiotics when available.

Promote and apply good practices at all steps of pro-
duction and processing of foods from animal and plant
sources.

Improve biosecurity on farms and prevent infections
through improved hygienic care.

74 THE PHARMA WORLD

Conclusion achieve future goals. Government and private authority
Rational Use of Medicine is a useful component in delivering should work together in different aspects of decision mak-
quality healthcare services and patient treatment. Irrational ing, rules and regulations and policy making. Mass people
use of medicine specially antibiotics pose a great threat to should refrain from self-medication, should change their at-
public health worldwide. To address this comprehensively, titude and behavior towards medical interventions. A strict
multisectoral and multi stakeholders’ efforts are needed. control should be there to maintain drug flow promotion
Based on the strategy of ONE HEALTH, for this, critical aware- and Drug approval by the Regulatory authority.
ness of the problem across the sectors and professionals,
high level political, inter and intra ministerial co-ordination References
among relevant sectors and enforce mint of regulatory re- Promoting the rational Use of medicines: core components,
gime are urgently warranted. National Drug policy 2016 of September 2002, WHO Geneva.
Bangladesh suggest that medicine distribution and utiliza- * Rational for Antibiotics -Guidelines,
tion in retail and hospitals should be under the supervision Mangesh Tiwasksr, Tanuja Manohar, chapter-2
of qualified Pharmacists. But reality is that a smaller number * Strategies for the Rational use of Antimicrobials, division of
of graduate pharmacists is working in retail pharmacies or
Government Hospital of Bangladesh except very few pri- drug management and policies. WHO Geneva.
vate hospitals. pharmacists have crucial in Health system in * Antimicrobials resistance, WHO fact sheet, Sep-2015, WHO Geneva.
maintaining the Rational and safe use of medicine as they * MOHIUDDIN A, Managing Rational use of drugs in Bangladesh,
are expert in patient management and medications. Without
giving them proper authorization, Health sector can never Pharma Tutor,6,11Nov2018,30-35
* Abid et. Al To determine the rational use of Antibiotics, IJRANSS,

vol 1, issue 2 July 2013, 61-68.
Tackling AMR in Bangladesh’ A scoping view of policies and prac-
tice in human, animal and environment sectors.
Roksana Haque, Sayed Masud Ahmed, Shekh Hasan
ncbi.nlm.nih.gov

5

13

4

5 Source: National Jewish Health
2

THE PHARMA WORLD 75

Adangerous
epidemic
is on the rise!

CONTROL

DIABETES
epidemic

Courtesy by,

“Weight reduction, healthy diet and exercise INTERVIEW
can prevent about 65% of type-2 diabetes”

Why is diabetes called the mother of all diseases?

Diabetes is called mother of all disease because, diabetes
mellitus is a hypo-immune state. So it gives shelter to many
of the diseases. Any infections can occur easily.

Prof. Dr. M.A. Mannan Do people with diabetes need to change their
medicines over time? What investigations should
Professor and Head, Dept. of Endocrinology a diabetic patient undergo regularly?
Anwer Khan Modern Medical College
& Hospital Diabetic patients need time to time update of their treat-
ment regimen (medicine or advices) according to their condi-
Former Head tion of blood sugar, blood pressure, lipid profile and other
Department of Endocrinology and states of their body.
Diabetelogy, Dhaka Medical College
Nocturnal hypoglycemia has always been a
As a renowned physician of nightmare for Insulin users. What other adverse
Bangladesh, would you please effects should the patients on insulin therapy
describe the prevalence of may face? How could these be avoided?
Diabetes in our country?
Patient with insulin therapy may develop hypoglycemia
The prevalence of diabetes is 9.2% which is very dangerous for the patient especially when it de-
(95%CI, 8.7-9.7%) with comparable es- velops at night. It is preventable by giving some advise to the
timates for men: 8.8%, 95% CI 8.1-9.6 patient like re-adjust of insulin dose at night or additional
and women: 9.6%, 95% CI 8.9-10.3. food before going to bed. Other causes of nocturnal hypogly-
the age standardized diabetes preva- cemia should be evaluated by history, clinical examination
lence higher in urban (11.8%, 95%CI, and investigations and treatment given accordingly.
10.9-12.7) than in rural residents (7.9%,
95%CI, 7.3-8.5) and prediabetes was What is the most important marker for
13.3% (95%CI 12.7-13.9) (men: 13.0%, diabetic nephropathy? What are the challenges
women: 13.6%). Among people with in treating diabetic nephropathy?
diabetes, 61.5% were unaware that
they had diabetes. 35.2% took treat- The important marker of diabetic neuropathy- simply
ment regularly and only 30.4% of urine examination, albumin, creatine, ratio (ACR) and Ultra-
them had controlled diabetes. Fac- sonography (USG) of both kidneys in which we can predict the
tors associated with an increased stage of diabetic nephropathy and accordingly we can take
prevalence of having diabetes were early measurement and prevent the development of chronic
increasing with age, overweight, un- kidney disease (CKD).
healthy food, rapid urbanization, obe-
sity, hypertension and stressful con- While there’s no cure for diabetes and prevention is better
dition etc. Diabetes and prediabetes there cure, what is your advice to prevent & control it?
affect a substantial proportion (over
one-quarter) of the Bangladeshi adult From very beginning prevention of diabetes: 1. Proper nu-
population. Continuing surveillance trition of the pregnant mother, 2. Avoid over weight, 3. Healthy
and effective prevention and control diet, 4. Exercise, 5. Children should be kept away from mobile,
measures, focusing on obesity, weight facebook, laptop, computer, also from fast food, ice-cream,
reduction, exercise, healthy food and burger, pizza etc and encourage playing, and 6. Education re-
hypertension management are ur- garding the development of diabetes and grow awareness in
gently needed.(collected-june-2022) the mass media- radio, television, newspaper. Thus it helps
prevention of diabetes.

3DEMM is the basic theme of diabetes management: D Di-
cipline, D Diet, D Drug, E Educaion, M Motivation M Monitoring

Remarks: weight reduction and healthy diet, exercise can
prevent about 65% of type-2 diabetes.

THE PHARMA WORLD 77



“Diabetes education is the most important INTERVIEW
cornerstone of diabetes management”

Dr. Faria Afsana Do people with diabetes need to change their medicines
Associate professor over time? What factors should be considered in
Dept of Endocrinology, BIRDEM and choosing the best option for an individual?
Ibrahim Medical College, Dhaka
Throughout the journey of diabetes, the patients require
As an eminent endocrinologist of change of medications throughout their lifetime. Several
the country, would you please tell factors are considered for this change. Starting with single
us about your valuable observation medicine, they require addition and change of many other
regarding the prevalence of agents of a different mode of action according to blood
Diabetes in Bangladesh? How does sugar level, presence of any comorbidity, and side effects
it compare to the global scenario? of that particular medicine. Any type of acute illness, any
chronic complication, pregnancy, and lactation requires a
The prevalence of diabetes in shift from oral drugs to insulin.
Bangladesh is increasing and the es-
timated prevalence is almost ten mil- What is the most important marker for
lion people. The global prevalence diabetic nephropathy? What are the challenges
of diabetes is 537 million as of 2021. in treating diabetic nephropathy?
As the global prevalence is increas-
ing same is observed in Bangladesh Loss of appetite, nausea, swelling of the foot and body,
also. Bangladesh is now at the eighth worsening blood pressure control, protein in the urine, lack
position according to the number of of concentration and unexplained requirement of reduc-
adults (20–79 years) with diabetes. tion of insulin or oral antidiabetic medication dose are
the symptoms of diabetic nephropathy. Blood urea nitro-
Antidiabetic combinations gen, serum creatinine, estimated glomerular filtration rate
are available nowadays, (GFR), proteinuria, albuminuria and ultrasonography of
making it easier to manage kidney are tests to diagnose diabetic nephropathy. Good
diabetes. How about the safety control of diabetes and hypertension is the key to preven-
and efficacy compared to tion of diabetic kidney disease. Avoiding Smoking and Pain
conventional oral agents? killers (NSAID) also keep the kidney healthy.

There are many advancements in About 50% of women with gestational diabetes go on to
treatment nowadays and with the in- develop type 2 diabetes. What can be done to prevent it?
vention of many antidiabetic agents,
the formulations are also chang- GDM prevention is very important as by preventing GDM
ing. Combination of two antidiabetic we can prevent future risk of the development of diabetes
drugs in a single pill with different for both mother and foetus. Overweight and obesity, hy-
mode of action are available. As dia- pertension, dyslipidaemia are all modifiable risk factors of
betic patients need to take several GDM. Risk factor reduction is the mainstay of GDM preven-
medications, so this type of combi- tion. Normalization of body weight through a healthy diet
nation is helpful for reducing the pill and physical activity can help in GDM prevention.
burden as well as being cost-effective.
Where does Bangladesh stand as far as diabetes
treatment, patient care and patient education is
concerned, compared to the advanced countries?

Considering the provision of diabetes care, Bangladesh
Diabetic Shomity is the greatest diabetes healthcare pro-
vider network, having BIRDEM as the biggest tertiary care
diabetes hospital in the Southeast Asian region. But ac-
cess to diabetes care is still not at reach of every people
throughout the country, considering the continuing in-
crease in the diabetic population. The hopeful thing is that
most of the modern antidiabetic agents are available if
Bangladesh though few are much more expensive. Diabetes
education is the most important cornerstone of diabetes
management, but unfortunately, still not at the reach of all
diabetic people in Bangladesh. Hopefully proper training of
physicians and patients can help to achieve the glycemic
target of Bangladeshi diabetic population.

THE PHARMA WORLD 79



“Health education can impact INTERVIEW
treatment outcome and prevent
many complications and hazards”

Dr Nazmul Kabir Qureshi As a renowned physician of Bangladesh,
Consultant (Endocrinology & Medicine) would you please describe the prevalence
Director, NHN Uttara Executive Centre of Diabetes in our country?
Bangladesh Diabetic Somity (BADAS)
Treasurer, Bangladesh Endocrine According to IDF, in 2021, globally approximately 537 mil-
Society (BES), Dhaka lion adults, aged between 20-79 years, were living with dia-
betes. The number of people living with diabetes is project-
ed to rise to 643 million by the year 2030 and 783 million by
the year 2045. Most of this burden impacts middle-income
or low middle-income countries like Bangladesh. Now,
every 3 of 4 adults with diabetes live in low- and middle-
income countries. Number of undiagnosed diabetes cases
are almost equal to the current number of diagnosed cases.
That means, 1 in 2 (240 million) adults living with diabetes
are undiagnosed. More than 1.2 million children and adoles-
cents (aged 0-19 years) are living with type 1 diabetes and 1
in 6 live births (21 million) are affected by diabetes during
pregnancy. Another, 541 million adults are at increased risk
of developing type 2 diabetes.

Currently, prevalence rate of diabetes in Bangladesh is
12.5% for the age group 20-79 years that is 1 in 8 person have
diabetes in our country. According to IDF, during the year
2021 approximately 13.1 million people ( aged 20-79 years)
were living with diabetes in Bangladesh. The number was
8.4 million during 2011 for the same age group, which in-
dicates the progressive increase in prevalence of diabetes
in our country. While, proportion of undiagnosed diabetes
case is 44.4%.

What are the available treatment options and
what factors should be considered regarding
the best option for an individual?

In the management of diabetes diet and exercise are the
most important components for all patients. Insulin is the
only pharmacotherapy for Type 1 Diabetes. For type 2 dia-
betes, various classes of medications including sulfony-
lureas, meglitinides, biguanides, thiazolidinediones (TZDs),
α-glucosidase inhibitor, glucagon-like peptide-1 (GLP-1) re-
ceptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors,
sodium glucose transporter 2 inhibitor (SGLT2i) and insulin
can be used. For hyperglycemia in pregnancy, insulin (con-
ventional and approved analogue insulins) is the pharma-
cological option.

For choosing the best treatment option, apart from type
of diabetes, presence of complications or comorbidities
such as ASCVD, CKD, and heart failure has an important role.
Other factors which are considered during choosing treat-
ment options are: degree of hyperglycemia, BMI, pregnancy,

THE PHARMA WORLD 81



lactation, emergency, acute illness, life expectancy, socio- autonomic over activity and neuroglycopenia. Nocturnal
economic condition, caregiver support, risk of hypoglyce- hypoglycemia occurs any time during night, usually be-
mia, patient’s preference, etc. tween 2 and 4 am. There are three levels of hypoglycemia
as level 1: blood glucose <3.9-3.0 mmol/L, level 2: blood
Diabetes is considered the “Mother of all diseases” glucose <3.0 mmol/L and level 3: hypoglycemia associated
as it affects other systems in the body as well. with altered mental and/or physical status requiring assis-
How is diabetic kidney disease (DKD) managed tance. Common causes of hypoglycemia are taking excess
when the patient has hypertension as well? dose of insulin, excess intake of antidiabetic medications,
especially insulin secretagogues, delay, omission or undue
Diabetes, hypertension, or a combination of both, cause reduction of a meal, excessive exercise, severe renal or he-
80% of end-stage renal disease globally. More than 50% patic impairment, alcohol intake, etc.
diabetic patients have one or more complications at the
time of presentation. A study in 2019 found that among Typical symptoms of hypoglycemia include, anxiety, sweat-
microvascular complications, nephropathy was prevalent ing, blurred vision, dizziness, fast heartbeat, headache, hun-
among 34.2% of patients. ger, irritability, shakiness, weakness/fatigue, confusion etc.

Diabetic Kidney Disease (DKD) is a specific form of mi- Level 1 and 2 hypoglycemia are treated by the person
cro-angiopathy of the kidney which is characterized by him/herself or by a family member by oral intake of 15
persistent albuminuria and progressive renal insufficiency gm glucose or equivalent food, e.g. a glass of soft drink or
(declining e -GFR) with or without hypertension. It is caused fruit juice or snacks or meal (if it is due). These measures
by damage to small blood vessels in the kidneys leading are usually adequate to raise blood glucose to reasonably
to the kidneys becoming less efficient. Kidney disease is safe limit (5.5 mmol/L). Modification in ongoing treatment
much more common in people with diabetes than in those should be considered. Level 3 hypoglycemia is treated with
without diabetes. Both diabetes and CKD are strongly as- 100 ml of 25% dextrose given intravenously under medical
sociated with cardiovascular disease (CVD) and therefore, supervision at hospital setting.
the major component in their management is control of
CVD risk factors such as hypertension and high blood glu- To prevent Nocturnal hypoglycemia, a few measures
cose (hyperglycemia). Managing DKD has got two major should be taken e.g.; reduction of evening dose of insulin,
component: comprehensive assessment and treatment. changing time of evening insulin dose with dinner time,
Comprehensive assessment includes: assessing anaemia, taking bed time snacks, blood glucose monitoring after din-
blood pressure, pedal edema during each visit, assessing ner and mid-night to adjust dose of insulin or oral drugs.
urinary albumin excretion (UAE) and e-GFR/CCr estimation,
blood urea, creatinine, total protein, serum albumin, elec- Why is diabetic neuropathy considered a “forgotten
trolytes, uric acid, Ca++, PO4 estimation as required, Serum complication”? what symptoms should patients look
creatinine and e-GFR should be assessed at least annually, out for? What are the main challenges related to the
Monitoring of other urinary complications e.g. UTI (includ- symptomatic treatment of painful diabetic neuropathy?
ing asymptomatic), bladder dysfunction (autonomic blad-
der) etc, monitoring by sonography - kidney size, progres- Diabetes can cause damage to the nerves throughout
sive increase in echogenicity of cortex and renal biopsy the body when blood glucose is too high. Diabetic neu-
when indicated. ropathy is an impairment of normal activities of the nerves
throughout the body and can alter autonomic, motor and
Treatment protocol includes: achieving Good glycemic sensory functions. 
control is mandatory. Evidence suggests that SGLT2 inhibi-
tors and GLP RA are beneficial, if not contraindicated. Con- Types of neuropathy are: somatic – sensory, motor, cra-
trol of hypertension is very important because uncontrolled nial (focal neuropathy) and autonomic – gastroparesis, hy-
hypertension causes rapid progression of diabetic nephrop- poglycemia unawareness, postural hypotension, erectile
athy. Target of BP is <130/80 mm of Hg. ACE inhibitors and dysfunction etc.
ARBs are drugs of first choice, while these two drugs must
not be combined. Protein intake up to 0.8 gm/kg/day of Peripheral neuropathy is the most common form of dia-
body weight is allowed. Fluid and electrolyte balance should betic neuropathy, affecting the outer nerves of the limbs,
be maintained. Iron and Renal replacement therapy (dialysis particularly those of the feet. This can lead to pain, tingling
and renal transplantation) are done when indicated. (painful neuropathy), and loss of feeling. Loss of feeling is
particularly important because it can allow injuries to go
Nocturnal hypoglycemia has always been a unnoticed, leading to serious infections and possible am-
nightmare for Insulin users. What other adverse putations.
effects should the patients on insulin therapy
be aware of? How could these be avoided? Painful diabetic neuropathy is difficult to treat. Main-
taining glycemic control is mainstay. For burning pain,
Hypoglycemia is defined biochemically as blood glucose antidepressants e.g. duloxetine, tricyclic anti-depressants
level below 3.9 mmol/L (70 mg/dL) with clinical features of etc. or anticonvulsants are often used. Gabapentin, prega-
balin, or topical capsaicin etc. are also used. For lancinat-
ing pain, anticonvulsants e.g. carbamazepine, phenytoin or
valproate are used. For painful cramps quinine sulfate is
an option. Aldose reductase inhibitors may be used. Other

THE PHARMA WORLD 83

contributing factors e.g. alcohol, cord lesions, vitamin defi- Where does Bangladesh stand as far as diabetes
ciency, renal failure etc. should be addressed. treatment, patient care and patient education is
concerned, compared to the advanced countries?
Diabetes treatment and approaches have
changed a lot in recent years. What have been Bangladesh is a densely populated low middle-income
the major developments in your opinion? country with high prevalence of type 2 diabetes. Its popula-
tion is also affected by gestational diabetes and at a low
Diabetes treatment approach has changed recently a lot. prevalence of type 1 diabetes. Rate of pre-diabetes is also
Both microvascular and macrovascular complications are very high here. Most of its population are Muslim. Preva-
common morbidities for a patient with diabetes. However, lence of diabetes is high among adult population who are
macrovascular complications namely, coronary artery dis- backbone of its economy. Hence, impact of prevalence of
ease and stroke and among microvascular disease, diabetic diabetes is multi-dimensional. Health service of this coun-
kidney disease are major causes of hospital admission and try is not insurance covered while most people here have to
death. In recent years, with the innovation of two important depend on overburdened Govt health service. Hence, im-
molecules, sodium glucose co-transporter inhibitors (SGLT-2 portance of patient education about prevention onset of
i) and GLP – 1RA, treatment protocol has seen a paradigm diabetes, diabetes management, managing special popula-
shift. These two molecules can significantly reduce cardio- tion (like during pregnancy) or special situations (like Ram-
vascular events and can significantly reduce hospital admis- adan, poor or remote setting) is enormous and cost-effec-
sion and mortality rate. Also, both the drugs help in preserv- tive. This population cannot be dealt with diabetes burden
ing renal function. Both the drugs help in reducing obesity only with treatment approach. Health education can impact
and insulin resistance as well. Thus, for patients having type treatment outcome and prevent many complications and
2 diabetes mellitus, is has been emphasized to assess for hazards of persons with diabetes. Bangladesh Diabetic
risks factors of these complications and if found or if the Somity (private sector) and Government has been working
patient have established cardiovascular disease or DKD, hand in hand for a very long time to deliver comprehen-
then these two drugs (SGLT 2i / GLP – 1RA) should be used sive diabetes care to its population where patient educa-
right after metformin (if not contraindicated). Treatment ap- tion sector has received an engaging role. Hence, I must say,
proach now also focus hugely in maintaining normal BMI and compared to many developed country, Bangladesh is doing
preventive strategies have gained enormous importance in much better in delivering patient education service through
comprehensive care for diabetic patients of all ages. various commendable protocols and projects.

M MYTH: No one in my family has diabetes, so I won’t get the disease.
REALITY: It’s true that having a parent or sibling with diabetes increases your risk
VRS for getting diabetes. In fact, family history is a risk factor for both type 1 diabe-
tes and type 2 diabetes. However, many people with diabetes have no close fam-
MYTH VS ily members with diabetes. Lifestyle choices and certain conditions can increase
REALITY your risk for type 2 diabetes. These include obesity, polycystic ovary disease, ges-
tational diabetes, being age 45 or older etc.

MYTH: I can stop taking diabetes medicines once my blood sugar is under control.
REALITY: Some people with type 2 diabetes, are able to control their blood sugar
without medicine by losing weight, eating a healthy diet, and getting regular exer-
cise. But diabetes is a progressive disease, and over time, even if you are doing all
you can to stay healthy, you may need medicine to keep your blood sugar within
your target range.

MYTH: Patients on Insulin Have More Serious Diabetes than Those on Oral Medications 
REALITY: Patients with type 1 diabetes are not able to produce insulin due to an
immune disorder affecting the pancreas. Therefore, oral medications that stimu-
late the production of insulin by the pancreas are not suitable. Such patients
require insulin injections to control their blood glucose level. For patients with
type 2 diabetes, initial treatment may involve only oral medications or insulin in-
jections. Some patients may require a combination of both treatments to achieve
optimal control of their blood glucose levels.

84 THE PHARMA WORLD

Fasting Diet Could Help Folks pants, who didn’t experience any significant in- HEALTH TIPS
with Type 2 Diabetes crease in  hypoglycaemia  or other serious side
effects when they fasted.
Intermittent fasting might help people
with type 2 diabetes better control their
blood sugar levels, a new study has found.
Time-restricted eating pattern also pro-
vided lower 24-hour blood sugar levels
and consistently lower morning fasting
glucose. For this study, the participants
spent three weeks on intermittent fast-
ing diet, and then another three weeks
eating as they normally would whenever
they liked. Participants who restricted
their eating to within a daily 10-hour win-
dow wound up with blood sugar levels in
the normal range for about three hours
longer than when they ate whenever
they pleased, the researchers reported.
Importantly, the eating window was easy
to adopt and proved safe for the partici-

Late bedtimes could raise your When compared with folks who go to bed early and
odds for Diabetes, Heart Trouble wake with the sun, night owls are more likely to be
insulin-resistant, a new study finds. When the body
doesn’t respond well to the hormone insulin, the ex-
cess sugar build-up in the bloodstream eventually
leads to type 2 diabetes. What’s more, “night owls”
get less exercise and burn less fat than “early birds,”
allowing fat to build up in the bloodstream, which
can set the stage for heart disease. Also, poorly timed
sleep is compounded when you don’t get enough
sleep. So, what can be done to fix this? Night owls
should gradually shift their bedtime to wake up early.
Getting outside when the sun is shining can also help
prompt your body’s circadian system to reset.

Evening exercise can reduce
insulin resistance by 25%

A new study published showed working out in the control were when high-intensity exercise was per-
afternoon and evening helps countering the resist- formed in the afternoon rather than in the morn-
ance better than in the morning. Researchers found ing. “However, in our study we examined habitual
that compared to spreading activity throughout MVPA which mostly comprised of brisk walking and
the day, exercising in the afternoon was linked to cycling” the lead study author explains.
an 18% reduction in insulin resistance and doing
so in the evening with a 25% reduction. They also
found that time spent doing moderate to vigorous
physical activity (MVPA) reduced both liver fat con-
tent and insulin resistance. Previous studies also
showed showed most beneficial effects on glucose

THE PHARMA WORLD 85

Big Studies Test Effectiveness
of Common Diabetes Meds

Vitamin D supplements Two common  diabetes  medications point, versus 72% of glimepiride
won’t help prevent seem to outperform two others when patients and 77% of sitagliptin pa-
Diabetes it comes to controlling blood sugar tients. On average, patients on the
levels. The trial  consisted of more former group had about six extra
While vitamin D may have other ben- than 5,000 people with type 2 dia- months in target range, compared to
efits, preventing type 2 diabetes in high- betes who were randomly assigned the sitagliptin group.
risk adults does not appear to be one to add one of four treatments: insu-
of them. A new  Japanese trial  found no lin glargine, a long-acting synthetic
significant difference between study insulin; liraglutide; glimepiride, a
participants who used a vitamin supple- sulfonylurea; or sitagliptin, a DPP-4
ment and those who took a placebo. For inhibitor. Over five years, patients
the study, researchers compared indi- on insulin or liraglutide were most
viduals with impaired glucose tolerance successful at keeping their A1C on
to participants who received a placebo. target. Around 67% saw their blood
They were tested for diabetes every three sugar go above that target at some
months over three years. About 12.5% of
the eldecalcitol group developed dia- Could a Common Diabetes Drug
betes compared to 14% of the placebo Ease Bipolar Disorder?
group. In diabetic patients, blood sugar
levels returned to normal in about 23% A half-century-old diabetes drug ap- their insulin resistance decreased,
of the eldecalcitol group and 20% of the pears to help treat bipolar disorder by said the lead researcher of the new
others. “Although eldecalcitol did not reversing patients’ insulin resistance, study. For the clinical trial, researchers
significantly reduce the incidence of dia- according to a small-scale clinical trial. randomly assigned patients with both
betes among people with prediabetes, Bipolar patients who responded to the insulin resistance and bipolar disor-
the results suggested the potential for a drug  metformin  experienced an im- der to take metformin for half a year.
beneficial effect of eldecalcitol on people provement in their mood disorder as Patients on metformin responded to
with insufficient insulin secretion,” the re- the drug, and no longer were insulin
searchers said. resistant by 14 weeks, the study found.
Those patients also experienced sig-
nificant improvements on standard
tests used to assess symptoms of bi-
polar disorder. Researchers think in-
sulin resistance might do something
to the blood-brain barrier – that influ-
ences bipolar disorder.

Could Herpes Viruses Help
Drive Type 2 Diabetes?

Two herpes viruses – herpes simplex 2 and cytomegalovirus – might
add to the list of risks for Type 2 diabetes. In a new study, researchers
found that adults who tested positive for either virus were more likely
to develop prediabetes over the next seven years which often pre-
cedes full-blown type 2 diabetes. If the viruses, themselves, do affect
blood sugar control, the researchers speculate it might be related to
modulations in immune activity. That, in turn, might affect the endo-
crine system that helps regulate blood sugar. The findings are based
on those who had normal blood sugar levels to start. Most also had
antibodies to more than one type of herpes virus, an indicator of past
infection. Over seven years, people with HSV-2 had a 59% higher risk
of prediabetes, and those with CMV had a 33% higher risk compared
to people without those infections.

86 THE PHARMA WORLD

Vision Damage May When Diabetes Strikes, Eye RESEARCH UPDATE
Begin Long Before Type 2 Exams Can Save Your Sight
Diabetes Is Diagnosed
Could an annual eye exam save your sight if
Nerve damage is a common side effect of type you have  diabetes? Most definitely, one vision
2 diabetes  and it might start in the eyes long expert says. With diabetes, the blood vessels in
before the condition is ever diagnosed, new the retina often become leaky, and this can trig-
research suggests. Researchers found that the ger swelling of the macula – the part of the retina
amount of damage to the corneal nerves rose in at the back of the eye that is responsible for cen-
tandem with the amount of impairment to glu- tral vision.
cose metabolism. People with prediabetes had
corneal nerve damage that was 8% higher than Pregnant women with  gestational diabe-
those with no diabetes. Meanwhile, those with tes are also at risk for diabetic retinopathy and
diabetes had corneal nerve damage that was should be seen multiple times throughout their
8% higher than those with prediabetes and 14% pregnancy. As well as getting an annual dilated
higher than those with neither condition, the eye exam, diabetes patients should follow the
findings showed. Nerve damage also rose with ABCs to manage diabetes and lower their risk for
higher blood sugar levels and with the length of vision loss and other potential complications:
time a person had diabetes. That included high-
er HbA1c levels (the average blood sugar level A stands for the hemoglobin A1C test, which
over several months), and blood sugar levels tracks whether blood sugar levels are under
two hours after a meal. control. For those with diabetes, the target is
below 6.5%.

B stands for blood pressure.
C stands for cholesterol, which should be be-
low 200 mg/dL.
By managing their ABCs and getting an an-
nual eye exam, most patients with diabetes can
retain good vision.

Certain Painkillers Raise
Heart Failure Risk in People
with Type 2 Diabetes

People with  type 2 diabetes  might face a substantially in-
creased risk of  heart failure  if they take  ibuprofen  or some
other type of nonsteroidal anti-inflammatory drug (NSAID), a
new study indicates. Short-term  NSAID  use increased risk of
hospitalization for  heart failure  by 43% among over 331,000
people in Denmark who had type 2 diabetes but no previous
heart problems, according to research. NSAIDs increased the
risk of heart failure even more in type 2 diabetics who were 80
or older (78%) or who had high blood sugar levels (68%), the
results showed. Those who’d never used an NSAID before had
the worst reaction, with their heart failure risk nearly tripling.

THE PHARMA WORLD 87

ARTICLE Quality: In Terms of
Making Medicines

Mohammad Habibur Rahman

Introduction maceutical industries. Pharmaceutical quality
system is very unique and it is vigilantly outlined
The desire for quality is a part of human na- by the regulatory authorities.
ture. It is the key to success in every aspect of
life, unless otherwise there is any exception. In Definitions of quality
case of medicines quality is an absolute neces-
sity. The term medicine by default refers to the Some words are simple, easy to define, and
quality medicine by anyone who is buying or have just the one generally accepted mean-
taking it. Quality can never be an optional extra, ing, or perhaps a few closely related shades of
it is central and very heart when we talk about meaning. “Quality” is not one of those words.
medicine. The need for quality medicines is es- The term is much more complicated than it ap-
sentially the same for developed, developing pears. The definition of quality depends on the
and underdeveloped countries. role of the people defining it. There are many
definitions of quality available in the dictionar-
Medicines versus other products ies and literatures. But there is no single defini-
tion which can satisfy everyone or can give idea
Medicinal products are different from other about quality of a medicinal product.
manufactured products. When we obtain most
other things we need (it could be the most com- A number of the dictionary definitions are
plex in feature or structure and of the highest relevant to persons rather than objects, which
in cost) we can check on their quality before we include character, disposition, capacity, ability,
buy. If anything turns out to be defective, we skill, trait, rank or position in society etc. On the
may often take it back. If a person is the unfor- other hand, in relation to objects, rather than
tunate patient, he/she cannot take the product persons, dictionary definitions include nature,
back for a refund if he/she is dead. People tak- property, attribute, superiority, high grade, de-
ing medications have very little chance of recog- gree or level of excellence etc.
nizing whether anything is wrong with the medi-
cine, which may lead to harmful consequences. Definitions by quality experts
People take medicines very much on the basis
of trust. According to Frank O. Taylor, “Noth- Many quality experts, in other words, qual-
ing of so great importance to human welfare is ity gurus, made significant contributions to the
used more completely on faith than a medicinal field of quality. We can take a look at the defini-
product”. They trust the doctor who prescribed tions of three most contributing quality experts
it and the pharmacist or the professional who on the earth, e.g. Philip B. Crosby, W. Edwards
dispensed it. Ultimately, they all trust those who Deming and Joseph M. Juran. All three experts
manufactured it. For this reason, ensuring qual- had unforgettable contributions in establishing
ity of medicinal products by the manufacturer immeasurably dependable quality systems of
is a regulatory requirement all over the world. Japan. They are also respectfully remembered
It is note-worthy that due to special nature of because of their many influential books on
medicinal products, quality system of no other quality and management.
industries is sufficient for practicing in the phar-
Philip Bayard Crosby was an American busi-
nessman and author who contributed to man-

88 THE PHARMA WORLD

agement theory and quality management practices. He respective of dosage form. A medicinal product is fit for
defined quality as “Conformance to requirements”. This use only when it is:
definition assumes that the specifications have already
been developed and the next thing to look for is conform- l The right product (identity)
ance to these specifications. But it needs sincere efforts l The right strength
from cross-functional experts in setting specifications of l Free from contamination (purity)
medicinal products. The specifications of medicinal prod- l In no way deteriorated, gone off or broken down
ucts may significantly vary based on their route of admin- l Right container
istration, dosage form, technology etc. l Correctly labelled
l Properly sealed in its container
William Edwards Deming was an American statistician,
professor, author, lecturer and consultant who is best In a nut-shell, a medicinal product is “fit” for its use
known for the “Plan-Do-Check-Act” cycle popularly named only when it can be administered to a patient in the secure
after him. He defined quality as “Meeting and exceeding knowledge and confidence that it will have the desired ef-
the customer’s need and expectations”. This definition pro- fects and not cause harm or damages, in any way, through
vides a means to assess quality using a relative measure. faults in manufacturing.
This definition does not help in case of a medicine because
customers generally do not know what properties they It requires paying attention to subsection 210.1(b) of the
should expect in it. 21 CFR (Code of Federal Regulations, US-FDA), part 210. It
states, the failure to comply with any regulation (set forth in
Joseph Moses Juran was a Romanian-born American the 21 CFR, parts 210 and 211) in the manufacture, process-
management consultant and engineer. He is principally ing, packing, or holding of a drug shall render such drug to
remembered as an evangelist for quality and quality man- be adulterated and such drug, as well as the person who
agement. He defined quality as “Fitness for use”. This defi- is responsible for the failure to comply, shall be subject to
nition stresses the importance of the customer who will regulatory action. It indicates that it is not enough to be a
use the product. But it does not help understand how a drug product fit for its use, even, if it perfectly meets the
medicinal product would be “fit” for its use. finished product specifications in the quality control labo-
ratory. It must comply with each and every pre-established
Quality of medicinal products requirement in the manufacturing, processing, packing, or
holding.
Surprising enough, none of the above definition is of a
perfect-match in the context of medicinal products. But How quality of medicines can be ensured
John Sharp (former principal inspector of UK-MHRA, who
alone compiled and edited the first three editions of UK- According to the famous United States marine William A.
MHRA guidelines and authored several unparalleled books Foster, “Quality is never an accident; it is always the result
on pharmaceutical quality) has adopted the definition of of high intention, sincere effort, intelligent direction and
quality given by Juran (i.e. fitness for use) and so wisely skillful execution; it represents the wise choice of many al-
correlated this definition with the expectations of pharma- ternatives.” This immensely powerful definition inevitably
ceutical regulatory authorities. indicates Good Manufacturing Practice (GMP) which is the
inescapable key to quality of medicinal products.
According to the expectations of the influencing regu-
latory authorities e.g. UK-MHRA, TGA-Australia, MCC-South According to the UK-MHRA guideline, “GMP is that part of
Africa and WHO, safety and efficacy must be ensured along Quality Management which ensures that products are con-
with the quality of a medicinal product. John Sharp clari- sistently produced and controlled to the quality standards
fies, if the quality of a medicinal product is measured by appropriate to their intended use and as required by the
its fitness for use, then safety and efficacy are not separate Marketing Authorization, Clinical Trial Authorization or prod-
from quality but are integral part of it. If a medicinal prod- uct specification”. Same or similar definitions exist in all the
uct is unsafe and/or not efficacious, then it is not to be fit prominent regulatory guidelines, with an exception that 21
for use. Thus, quality must include safety and efficacy. CFR and ICH Q10 do not contain any definition of GMP.

On the other hand, US-FDA, which is considered as GMP describes a set of principles and procedures which
the most stringent regulatory authority, has the expecta- when followed helps ensure that medicinal products are
tions to provide assurance that the drug product has the of desired quality. Quite simply, GMP is all about the things
safety, identity, strength and purity along with its quality. we have to do and care we have to take, to ensure the qual-
Similarly, in this case, quality must include safety, identity, ity of medicinal products.
strength and purity as the integral part of it.
It is said by Abraham Lincoln, the sixteenth president of
However, what makes the medicinal product fit for its the United States, “When I do good, I feel good. When I do
use? bad, I feel bad. That’s my religion”. Likewise, good practice
i.e. GMP should not be less than religion to the people en-
John Sharp suggested the properties which make a gaged with pharmaceutical industries, irrespective of their
medicinal product fit for its use and those properties can role.
straightforwardly be applied to any medicinal product, ir-

THE PHARMA WORLD 89

Conclusion REFERENCES

Bangladesh pharmaceutical industries have exemplary 1. Badr Eldin, Ahmed. Quality: General Concepts and Definitions,
achievements in the context of quality through the rec- Sigma Pharmaceutical Corp., Egypt
ognition of the prestigious global regulatory authorities.
The first ever ice breaking was done by Square, making 2. Immel, B. K. (2005). A Brief History of the GMPs, Regulatory
the impossible dream possible, (the dream of its Honor- Compliance Newsletter, The GMP Labeling System.
able Founder Chairman, The Legendary Leader, Samson
H. Chowdhury), through the accreditation of UK-MHRA in 3. Medicines Control Council, Department of Health, Republic of
February 2007. Since then, within only fifteen years, several South Africa, Guide to Good Manufacturing Practice for Medicines
pharmaceutical manufacturers achieved high-status many in South Africa, 1 November 2010.
accreditations such as US-FDA, UK-MHRA, TGA-Australia,
MCC-South Africa, WHO and so on. This is nothing but the 4. Oxford Advanced Learner’s Dictionary of Current English, Fifth
result of amalgamation of the vision of some extra ordi- Edition, Oxford University Press
nary initiators, leadership, commitment, team work, learn-
ing, dedication, determination etc. towards quality. Still, 5. Pharmaceutical Quality System Q10, ICH Harmonized Tripartite
we have a long way to go retaining the achievements what Guideline, 4 June 2008
we already have.
6. PIC/S Pharmaceutical Inspection Co-operation Scheme, Guide
Sir Winston Churchill, Prime Minister of the United King- to Good Manufacturing Practice for Medicinal Products, Part I, 15
dom for two terms and Nobel Laureate in literature, said, January 2009.
“If you have important point to make, don’t try to be subtle
or clever. Use a pile driver. Hit the point once. Then come 7. Quality assurance of pharmaceuticals: a compendium of
back and hit it again. Then hit a third time with a tremen- guidelines and related materials. Vol. 2, Good manufacturing
dous whack”. Top management of pharmaceutical indus- practices and inspection. (2nd ed.). World Health Organization,
tries should constantly focus on quality and inspire per- 2007.
sonnel to make it clear that following GMP is the only way
their company does business in today’s competitive world. 8. Rules and Guidance for Pharmaceutical Manufacturers and
According to Juran, “It is important that top management Distributors 2014. Compiled by the Inspection and Standards
be quality minded. In the absence of sincere manifesta- Division of the Medicines and Healthcare products Regulatory
tion of interest at the top, little will happen below.” Quality Agency (MHRA), UK.
is the business of doing business, especially, in terms of
making medicines. There must have a voice of quality. 9. Sharp, J. (2000). Quality Assurance in the Manufacture of
Medicines and other Healthcare Products. Published by the
Pharmaceutical Press, 1 Lambeth High Street, London SE1 7JN.

10. Sharp, J. (2005). Good Pharmaceutical Manufacturing Practice:
Rationale and Compliance, CRC Press, www.crcpress.com

11. Therapeutic Goods Administration, Australian Code of Good
Manufacturing Practice for Medicinal Products, 16 August 2002.

12. Tirupathi R. Chandrupatla. Quality Concepts, Cambridge University
Press, 978-0-521-51522-1 - Quality and Reliability in Engineering.

13. US Food and Drug Administration (FDA), 21 Code of Federal
Regulations, Part 211, Current Good Manufacturing Practice for
Finished Pharmaceuticals, Revised as of April 1, 2013.

The Author is Deputy Manager, Quality Assurance at Healthcare Phar-
maceuticals Ltd., Rajendrapur, Gazipur.

FAST  1 in 6 live births (21 million) are of long-term accumulated damage to
affected by diabetes during pregnancy the small blood vessels in the retina.
FACTS Close to 1 million people are blind due
 Women with gestational diabetes are to diabetes 
at an increased risk of complications
during pregnancy and at delivery.  Diabetes is among the leading causes
These women and possibly their of kidney failure 
children are also at increased risk of
 People with diabetes are more likely
type 2 diabetes in the future. to have poor outcomes for several
infectious diseases, including COVID-19.
 Adults with diabetes have a two- to
three-fold increased risk of heart  Losing just 7% of your bodyweight — 15
attacks and strokes pounds for a 200-pound individual
— can decrease the risk of diabetes by
 Combined with reduced blood flow, 58%.
neuropathy (nerve damage) in the feet
increases the chance of foot ulcers,  Type 2 diabetes accounts for
infection and eventual need for limb approximately 90% to 95% of all
amputation. diagnosed cases of diabetes; type 1
diabetes accounts for approximately
 Diabetic retinopathy occurs as a result 5-10%.

90 THE PHARMA WORLD

FACTS on Examples of these include time to heal and there is an increased
Fungal infection:  The yeast-like risk for infection.
FINGER TIPS
fungus Candida albicans is often re- Acquired reactive perforating col-
Diabetes Rash sponsible for these infections. lagenosis (ARPC): This is usually seen
in patients with kidney disease. The
People with diabetes have a high- Necrobiosis lipoidica diabeticorum rash is usually red itchy bumps. Treat-
er risk of skin rashes. High blood (NLD): This lower leg rash is more com- ment can consist of topical steroids,
sugar (hyperglycemia) is often to mon in women. NLD causes raised, steroid injections to the rash and oth-
blame.   Itching is often a symptom red, shiny patches with a yellow cent- er medications
of diabetic polyneuropathy, which is er. It can cause pain and itching.
a condition that develops when  dia- Treatment and Prevention
betes leads to nerve damage. Dry, ir- Eruptive xanthomatosis: More com- The best thing you can do to prevent
ritated, or itchy skin is more likely to mon in people with  type 1 diabetes. skin problems is to keep blood sugar
become infected, and people with High cholesterol and fat levels increase levels within the range. Proper skin
diabetes may not be able to fight off the risk of eruptive xanthomatosis. care can prevent skin problems:
infections as successfully as those
who do not have the condition. Blisters (bullosis diabetico- Check your skin daily for signs of
rum):  Painless  blisters  may form on rashes, redness, infections or sores.
Causes of Diabetic skin conditions the backs of hands and feet and on
Sometimes an underlying skin con- the legs and forearms. This rare con- Use warm (not hot) water and
dition can cause itching. People with dition most often affects people who moisturizing soap in the shower.
diabetes can get certain skin condi- have diabetes-related neuropathy.
tions and infections more easily than Pat skin dry with a towel (don’t
people who do not have diabetes. Digital sclerosis: Some people with rub), making sure to dry in between
Type 1 diabetes develop hardened, fingers, toes and skin folds.
thick, waxy skin on the backs of their
hands. The finger joints stiffen, mak- Apply fragrance-free moisturiz-
ing movement difficult. ers after showering while skin is still
damp and soft. Look for creams and
Diabetes Foot Syndrome:  These ointments (not lotions) with ceramide
are ulcers that develop from trauma to help skin retain moisture.
to the skin. The ulcers can take a long
Apply creams containing 10% to
GLOSSARY OF 25%  urea  (an emollient) to cracked,
DIABETES TERMS dry heels at bedtime.

Acetone:  A chemical formed in the blood when the body Glycosylated haemoglobin A1c (HbA1c): Haemoglobin to which
breaks down fat instead of sugar for energy; if acetone forms, glucose is bound. Glycosylated haemoglobin is tested to de-
it usually means the cells are starved. Commonly, the body’s termine the average level of blood glucose over the past two
production of acetone is known as “ketosis.” It occurs when to three months.
there is an absolute or relative deficiency in insulin so sugars
cannot get into cells for energy. Macrovascular complications: Damage to major blood vessels
due to poor blood glucose control which can lead to a heart
Acidosis:  Too much acid in the body, usually from the pro- attack or stroke.
duction of ketones like acetone, when cells are starved; for
a person with diabetes, the most common type of acidosis is Microvascular complications: Damage to tiny blood vessels
called “ketoacidosis.” due to poor blood glucose control which can lead to retinopa-
thy or cataracts, nephropathy, and neuropathy.
Albuminuria:  When kidneys become damaged, they start to
leak protein in the urine. Albuminuria occurs in about 30%- Monogenic diabetes: A less common type of diabetes, which
45% of people who have had type 1 diabetes for at least 10 arises as a result of a genetic mutation.  Examples include
years, increasing the risk of developing end-stage kidney dis- Maturity-Onset Diabetes of the Young (MODY) and Neonatal
ease and cardiovascular disease. Diabetes Mellitus. 

Autonomic neuropathy: Nerve damage to the part of the nerv- Oral glucose tolerance test: The oral glucose tolerance test is
ous system that we cannot consciously control; these nerves one way that diabetes is diagnosed. It measures the blood
control our  digestive system, blood vessels, urinary system, glucose level five times over a period of three hours after you
skin, and sex organs. drink a high glucose mixture.

Background retinopathy: This is the mildest form of eye disease Pre-diabetes: Pre-diabetes, also called glucose intolerance, is
caused by diabetes; it can be associated with normal vision. when a person has high blood glucose levels, but they aren’t
high enough yet to be diagnosed as diabetes. Insulin resist-
Brittle diabetes:  When a person›s blood sugar level often ance (when the body doesn’t use insulin as well as it should)
shifts very quickly from high to low and from low to high. is another pre-diabetes sign.

THE PHARMA WORLD 91

INSIGHT Nanotherapy: A new hope
for diabetic patients

Researchers have opened new paths to cell and tissue
transplantation in pancreas by using nanoparticles to
deliver immunosuppressant drug

Islet transplantation has emerged over the presenting cells (APCs) that allow for more tar-
past few decades as a potential cure for type geted, controlled immunosuppression.
1 diabetes. However, transplantation efforts
have faced setbacks as the immune system con- Using nanoparticles also enabled the team
tinues to eventually reject new islets. Current to deliver rapamycin through a subcutaneous
immunosuppressive drugs offer inadequate injection, which they discovered uses a differ-
protection for transplanted cells and tissues ent metabolic pathway to avoid extensive drug
and are plagued by undesirable side effects. loss that occurs in the liver following oral ad-
ministration. This route of administration re-
Now, researchers at Northwestern University quires significantly less rapamycin to be effec-
developed a nanoparticle delivery system for tive — about half the standard dose.
a common immunosuppressant drug that in-
creases the potential of pancreatic islet trans- Common immunosuppressants, such as ra-
plantation as a viable long-term treatment for pamycin, don’t currently work to protect the is-
Type I diabetes lets adequately, at least at safe doses. The side-
effects of such drugs can be difficult to live with,
Following a transplant, immune cells, called including reduced immune protection against
T cells, will reject newly introduced foreign cells infections such as COVID-19. “To avoid the broad
and tissues. Immunosuppressants are used effects of rapamycin during treatment, the drug
to inhibit this effect but can also impact the is typically given at low dosages and via specific
body’s ability to fight other infections by shut- routes of administration, mainly orally,” said
ting down T cells across the body. But the team a researcher involved in the study. “But in the
formulated the nanocarrier and drug mixture to case of a transplant, you have to give enough
have a more specific effect. Instead of directly rapamycin to systemically suppress T cells,
modulating T cells — the most common thera- which can have significant side effects like hair
peutic target of rapamycin — the nanoparticle loss, mouth sores and an overall weakened im-
would be designed to target and modify antigen mune system.”

92 THE PHARMA WORLD

The team found the diabetes types of immune cells?” said Evan
Scott, Associate Professor of Bio-
was eradicated for the length of medical Engineering at Northwest-
ern University. “By changing the cell
their 100-day trial in the mice; types that are targeted, we actually
changed the way that immunosup-
but the treatment should last pression was achieved. We are
changing it – by repurposing the bi-
the transplant’s lifespan. The ochemical pathway of a drug, in this
case mTOR inhibition by rapamycin,
team also demonstrated the we are generating a totally different
cellular response.”
population of mice treated with
The team tested the hypothesis
the nano-delivered drug had on mice, introducing diabetes to
the population before treating them
a “robust immune response” with a combination of islet trans-
plantation and rapamycin, delivered
compared to mice given via the standard Rapamune® oral
regimen and their nanocarrier for-
standard treatments of the drug. mulation. Beginning the day before
transplantation, mice were given in-
To address this, the Northwestern jections of the altered drug and con-
University researchers used nano- tinued injections every three days
particles to specifically target rapa- for two weeks.
mycin to antigen presenting cells of
the immune system, rather than the The team found the diabe-
T cells it usually affects. This results tes was eradicated for the length
in a more controlled immunosup- of their 100-day trial in the mice;
pression that appears to balance but the treatment should last the
protection for transplanted pancre- transplant’s lifespan. The team also
atic islets with a reasonable safety demonstrated the population of
profile.    mice treated with the nano-deliv-
ered drug had a “robust immune
“We wondered, can rapamycin be response” compared to mice given
re-engineered to avoid non-specific standard treatments of the drug.
suppression of T cells and instead
stimulate a tolerogenic pathway Source: Northwestern University
by delivering the drug to different

THE PHARMA WORLD 93



The Global Diabetes Pen Market Estimated to FORECAST
Surpass Approximately 31.5 Billion by 2027

The Global Diabetes Pen Market to witness terms of reusing the same pen if a prescription
growing  demand for Diabetes Pen, which for the insulin type changes.
is primarily attributed to the factors such
as the increasing prevalence of lifestyle disor- In May 2022, Eli Lilly entered into agreements
ders, such as diabetes and obesity, increasing with four companies DexCom, Inc., Glooko Inc.,
awareness regarding the ease-of-use of diabe- myDiabby Healthcare  and  Roche  – to advance
tes pens, the improvement in patient adher- connected solutions and streamline care for
ence and compliance to the treatment regimen, diabetic patients living outside of the United
and technologically advanced products such as States. These companies offer unique diabe-
smart insulin pens, are expected to drive the Di- tes management platforms which will be com-
abetes Pen Market. patible with  Lilly’s Tempo Pen™  (approved in
several global markets) and Tempo Smart But-
According to the latest report published by ton™ (currently in late-stage development).
DelveInsight  global Diabetes Pen Market is ex-
pected to witness appreciable growth in prod- Recent Developments in
uct demand owing to various reasons, one of the Diabetes Pen Market report
the major factors influencing the growth of the
Diabetes Pen Market is the advantages offered In May 2022, Medtronic plc received the CE (Con-
by diabetes pens over conventional syringe and formité Européenne) Mark approval for their In-
vials mode of insulin administration is further Pen smart insulin pen for expanded functional-
expected to boost the market growth. ity as multiple daily injections (MDI).

Diabetes Pen Market Insight In May 2022, Eli Lilly entered into agreements
with four companies DexCom, Inc., Glooko Inc.,
Among all the regions, APAC is expected to wit- myDiabby Healthcare, and Roche – to advance
ness the fastest growth in the revenue in the di- connected solutions and streamline care for
abetes pens market during the forecast period.  diabetic patients living outside of the United
The reasons for this fast growth can be correlat- States. These companies offer unique diabetes
ed to the large patient population in the region, management platforms which will be compat-
rising disposable income, and increasing focus ible with Lilly’s Tempo Pen™ (approved in sev-
of the market players in improving their market eral global markets) and Tempo Smart Button™
access in the APAC region. (currently in late-stage development).

According to DelveInisght estimates, in the In  May 2022, Bigfoot Medical  received 510k
product segment of the Diabetes Pen market, approval from the US Food and Drug Adminis-
the reusable Diabetes Pen category is expected tration for their first-of-its-kind Bigfoot Unity™
to account for the larger market share during Diabetes Management System. It features con-
the forecast period. Reusable Diabetes Pens nected smartpen caps that recommend insulin
offer advantages such as greater flexibility in doses for people using multiple daily injection
(MDI) therapy.

Source: DelveInsight

THE PHARMA WORLD 95

FDA UPDATE Combination of tremelimumab and durvalumab
for Unresectable Hepatocellular Carcinoma

AstraZeneca’s Imjudo (tremelimumab) in combination with Imfinzi (durvalumab) has been
approved in the US for the treatment of adult patients with unresectable hepatocellular
carcinoma (HCC), the most common type of liver cancer. The novel dose and schedule of
the combination, which includes a single dose of the anti-CTLA-4 antibody Imjudo 300mg
added to the anti-PD-L1 antibody Imfinzi 1500mg followed by Imfinzi every four weeks
is called the STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab). The
USFDA approval was based on positive results from the HIMALAYA Phase III trial, where
patients experienced a 22% reduction in the risk of death versus sorafenib.

FDA Approves bevacizumab- FDA Approves terlipressin
adcd, a Biosimilar to Avastin for the Treatment of
Hepatorenal Syndrome
Vegzelma (bevacizumab-adcd), a recombinant hu-
manized monoclonal antibody which binds to vascu- Mallinckrodt  plc announced that the
lar endothelial growth factor (VEGF), is Celltrion’s third USFDA approved Terlivaz (terlipressin)
oncology biosimilar to receive approval from the US- for injection. Terlivaz is the first and
FDA. Vegzelma was approved for the treatment of six only FDA-approved product indicated
types of cancer: metastatic colorectal cancer; recur- to improve kidney function in adults
rent or metastatic non-squamous non-small cell lung with hepatorenal syndrome (HRS)
cancer (nsNSCLC); recurrent glioblastoma; metastatic with rapid reduction in kidney func-
renal cell carcinoma; persistent, recurrent, or meta- tion,  an acute and life-threatening
static cervical cancer; and epithelial ovarian, fallopian condition requiring hospitalization.
tube, or primary peritoneal cancer. Most common ad- The FDA approval was based, in part,
verse reactions are epistaxis, headache, hypertension, on results from the Phase 3 CONFIRM
rhinitis, proteinuria, taste alteration, dry skin, hemor- trial,  which showed terlipressin to
rhage, lacrimation disorder, back pain, exfoliative der- improve kidney function and lessen
matitis and fetal harm in pregnant women. the associated need for renal replace-
ment therapy, such as dialysis.
Sodium thiosulfate injection for
Cisplatin Associated Ototoxicity Spectrum’s Rolvedon
Injection approved
Fennec Pharmaceuticals’ Pedmark (sodium thiosul- for Chemotherapy-
fate injection) is the First and Only FDA-Approved Induced Neutropenia
Therapy Indicated to Reduce the Risk of Ototoxicity
Associated with Cisplatin in Pediatric Patients one Rolvedon™ (eflapegrastim-xnst)  is
month of age and older with Localized, Non-Meta- the first novel Long-Acting GCSF (LA-
static Solid Tumors. The FDA approval of Pedmark GCSF) product approved in over 20
was based upon safety and efficacy data from two years. eflapegrastim-xnst is indi-
pivotal open-label, randomized Phase 3 trials. The cated to decrease the incidence of
most common adverse reaction is hypokalemia. infection, as manifested by febrile
neutropenia, in adult patients with
Aprepitant for the Prevention of PONV non-myeloid malignancies receiv-
ing myelosuppressive anti-cancer
Heron Therapeutics’ Aponvie (Aprepitant) is the first and only intravenous (IV) drugs associated with clinically sig-
formulation of a substance P/neurokinin-1 (NK1) receptor antagonist indicated nificant incidence of febrile neutro-
for postoperative nausea and vomiting (PONV). Delivered via a single 30-sec- penia. Rolvedon is contraindicated
ond IV injection, Aponvie has demonstrated rapid achievement of therapeutic in patients with a history of serious
drug levels ideally suited for the surgical setting. The FDA approval were results allergic reactions to eflapegrastim,
from two double-blind clinical studies comparing oral aprepitant to current pegfilgrastim or filgrastim products.
standard of care, IV ondansetron, demonstrating that aprepitant was more in Reactions may include anaphylaxis.
preventing vomiting during the 48 hours following open abdominal surgery.

96 THE PHARMA WORLD

FDA APPROVALS

Brand Name Generic Name Manufacturer Date of Treatment
Approval

Imjudo Injection Tremelimumab-actl AstraZeneca Oct 21, 2022 Treatment of adult patients
with unresectable hepato-
cellular carcinoma (uHCC).

Furoscix Injection Furosemide scPharmaceuticals, Inc. Oct 07, 2022 Treatment of congestion due
to fluid overload in adults
with NYHA Class II/III chronic
heart failure

Lytgobi Tablets Futibatinib Taiho Oncology, Inc Sep 30, 2022 Treatment for Cholangiocar-
cinoma

Relyvrio) - formerly Sodium Phenylbu- Amylyx Pharmaceuti- Sep 29, 2022 Treatment for Amyotrophic
AMX0035 tyrate & Taurursodiol cals, Inc. Lateral Sclerosis

Iheezo Ophthalmic Gel Chloroprocaine Harrow Sep 27, 2022 Treatment for Ocular Surface
Hydrochloride Anesthesia

Vegzelma Injection Bevacizumab-adcd Celltrion, Inc. Sep 27, 2022 Treatment for Colorectal
Cancer, Non-Small Cell Lung
Cancer, Glioblastoma Multi-
forme, Renal Cell Carcinoma,
Cervical Cancer, Ovarian Can-
cer, Fallopian Tube Cancer,
Peritoneal Cancer

Omlonti Ophthalmic Omidenepag Iso- Santen Inc. Sep 22, 2022 Treatment for Glaucoma/
Solution propyl Intraocular Hypertension

Pedmark Sodium Thiosulfate Fennec Pharmaceuticals Sep 20, 2022 Treatment for prevention of
Inc. Cisplatin-Induced Ototoxicity

Skysona Suspension for Elivaldogene Auto- Bluebird bio, Inc. Sep 18, 2022 Treatment for Cerebral Adre-
Intravenous Infusion temcel noleukodystrophy

Aponvie Injection - Aprepitant Heron Therapeutics, Inc. Sep 16, 2022 Indicated for the prevention
formerly HTX-019 of postoperative nausea and
vomiting (PONV).

Terlivaz for Injection Terlipressin Mallinckrodt plc Sep 14, 2022 Treatment for Hepatorenal
Syndrome Type 1

Sotyktu Tablets Deucravacitinib Bristol-Myers Squibb Sep 09, 2022 Treatment for Plaque Pso-
Company riasis

Daxxify Lyophilized Daxibotulinumtoxi- Revance Therapeutics, Sep 07, 2022 Treatment for Glabellar
Powder for Injection Lines
nA-lanm Inc

Spevigo Injection Spesolimab-sbzo Boehringer Ingelheim Sep 01, 2022 Treatment for Generalized
Pharmaceuticals, Inc. Pustular Psoriasis

Stimufend Injection Pegfilgrastim-fpgk Fresenius Kabi USA, LLC Sep 01, 2022 Treatment for Neutropenia As-
sociated with Chemotherapy

THE PHARMA WORLD 97



Duvelisib Possible increased risk of death

and serious adverse effects

The US FDA has warned that results from a or small lymphocytic lymphoma who have re-
clinical trial show a possible increased risk of ceived at least two prior therapies that did not
death with duvelisib (Copiktra®) compared to work or stopped working. The US FDA is notify-
alternative medicines to treat leukemia and a ing the public of these risks and is continuing
lymphoma. The trial also found duvelisib was to evaluate the safety of duvelisib. It is recom-
associated with a higher risk of serious ad- mended that Health-care professionals should

verse effects, including infections, diarrhea, consider the risks and benefits of continuing
inflammation of the intestines and lungs, skin duvelisib in the context of other available treat-

reactions, and high liver enzyme levels in the ments, and to advise patients receiving duvel-
blood. Duvelisib is indicated for the treatment isib of the possible increased risk of death and
of adults with chronic lymphocytic leukemia higher risk of serious adverse events.

Metformin Risk of reduced Mefenamic acid, doxycycline RED ALERT
vitamin B12 levels Risk of fixed drug eruption

The MHRA has announced that the product in- The Central Drugs Standard Control Organi-
formation for metformin containing medicines zation (CDSCO) has approved the recom-
have been updated to state that vitamin B12 de- mendation to revise the prescribing infor-
ficiency is a common adverse drug reaction of mation leaflet (PIL) for mefenamic acid and
metformin and may affect up to 1 in 10 people doxycycline to include fixed drug eruption
who take it. Vitamin B12 deficiency is a known as an adverse drug reaction. Mefenamic
adverse drug reaction of metformin, and the cur- acid is indicated for the treatment of rheu-
rent literature has suggested that the frequency matoid arthritis, osteoarthritis, dysmenor-
of this adverse drug reaction is higher than pre- rhea, mild to moderate pain, inflamma-
viously thought. The risk of this adverse reaction tion, fever and dental pain. Doxycycline is
increases with an increase in metformin dose used as a broad-spectrum antibiotic. The
and treatment duration, and in patients with risk National Coordination Centre – Pharma-
factors known to cause vitamin B12 deficiency. covigilance Programme of India (NCC-PvPI),
Health-care professionals are advised to test vi- Indian Pharmacopoeia Commission (IPC)
tamin B12 levels in those presenting with anae- reviewed 23 case reports of fixed drug erup-
mia or neuropathy, and that periodic vitamin tion with use of mefenamic acid and 94 cas-
B12 monitoring should be considered in patients es with the use of doxycycline, and found a
with risk factors for vitamin B12 deficiency. strong causal relationship between each of
the two drugs and the event.

First-generation The TGA has warned that first-generation oral sedating antihista-
oral sedating mines, including those available over-the-counter (OTC), should not
Antihistamines be used for the treatment of cough, cold and flu symptoms in children
Risk of serious under six years and for any indication in children under two years of
harm in children age. First-generation oral sedating antihistamines include products
containing diphenydramine and pheniramine. These medicines can
cause children serious harm, or even death, and there is little if any
evidence that they are effective in treating cough, cold and flu symp-
toms. Warnings on use in children have been introduced in the label-
ling since 2020. Up until 24 May 2022, 226 cases reporting the use of
first-generation oral sedating antihistamines in newborns, infants and
children were received by TGA. The reports included a range of adverse
events, including hypersensitivity reactions, vomiting, hallucination,
tremor and abnormal movement.

THE PHARMA WORLD 99