BULETIN PENAWAR

VOLUME 1/2016 MARCH 2016

Inside this issue:

Management of Major Depressive 2
Disorder
By Cik Lai Siew Yen
Editorial Board Use of Desferal® In The Management of 4
ADVISOR: Thalassemia
 DR SITI NORLINA BINTI
MD SAID
By Cik Andrea Tan Yin Lin
EDITORS:
 EN MOHD SHAFIE B
The Use of Biologic Agents In Psoriasis 6
ZABIDI
By Cik Nur Afiqah Bt Mahrom
 PN NG WANG SING
 PN PATRICIA LIM MING
HUA
Crohn’s Disease 8
 EN TAN CHOR MENG
By Cik Lim Yun Hui
HOSPITAL SULTANAH
AMINAH JOHOR BAHRU
Respiratory MTAC at HSAJB 10
Kementerian Kesihatan Malaysia

Jalan Persiaran Abu Bakar Sultan, By Pn Norhafizah Bt Ab Rahim

80100 Johor Bahru.

Tel: 07-2257000
Fax: 07-2242694
E-mail:

publichsajb@moh.gov.my
 MANAGEMENT OF MAJOR DEPRESSIVE DISORDER
By Lai Siew Yen

Depression is more than just a low mood Diagnosis

Depression is a common mental disorder, characterized by sadness, loss of interest
Assessment of depression consists
or pleasure, feelings of guilt or low self-worth, disturbed sleep or appetite, feelings
of detailed history taking, mental
of tiredness, and poor concentration (WHO 2015)
state examination, physical exami-
nation, and investigations where
indicated.
Prevalance
In Malaysia, there are two diag-
nostic guidelines:
In Malaysia, a cross sectional study reported the prevalence of MDD as 5.6%. -ICD-10 DIAGNOSTIC
GUIDELINES
By the year 2020 major depression is projected to be the second largest contributor to
the global burden of disease, after heart disease. -DSM-IV DIAGNOSTIC
GUIDELINES

Sign and Symptoms

Difficult concentrating
Fatigue, decreased energy
Feeling of hopelessness, helplessness
Causes??
Overeating/ loss of appetite
Loss of interest in activities Brain chemistry (imbalance of neurotransmitters)
Sad, anxious, empty mood Hormones

Insomnia /over sleeping Thoughts of death/suicide Genetic inheritance

Irritability Trauma, Stress
Restlessness
Drugs/Alcohol

Treatment Options

First Generation Antidepressants :

A) Tricyclic Antidepressants (TCA) B) Monoamine Oxidase Inhibitors( MAOI)
 Imipramine, amitriptyline, clomipramine  Moclobemide, Phenelzine

 Older antidepressants
 Works by blocking reabsorption of serotonin and
noradrenaline
 Very effective but the major limitations is their unwanted
side effects
 Side effects include dry mouth, blurred vision, constipation,
urinary retention, sweating, excessive drowsiness and
weight gain
 Block effect of MAO which is an enzyme that break down
serotonin, adrenaline, and dopamine
 Have severe interactions with certain foods, drinks and
medications
 Avoid combining MAOI with food containing tyramine eg:
aged cheese, fermented products
 Avoid using MAOI with SSRI to avoid serotonin syndrome
 Second Generation Antidepressants :
A) Selective Serotonin reuptake inhibitors (SSRIs) B) Serotonin and norepinephrine reuptake inhibitors
Fluoxetine, fluvoxamine, sertraline, paroxetine, citalopram, (SNRIs)
escitalopram Venlafaxine, duloxetine

 First line and most commonly prescribed  Block reuptake of both serotonin and norephinephrine

 Relatively safe and generally cause fewer side effects  Similar side effects with SSRIs

 Helps to increase level of serotonin by blocking their

reuptake
 Side effects: nausea, vomiting, diarrhea, headache, dry
mouth and sexual problems

Others Antidepressants :
Bupropion
 Works by inhibiting reuptake of dopamine, serotonin and norepinephrine
 May be more likely to improve symptoms of fatigue and sleepiness than some of the SSRIs
 Tends to have similar side effects as SSRIs and SNRIs, but is less likely to cause sexual side effects, but can increase risk of seizure

Mirtazapine
 Elevates mood by raising level of serotonin and norephinephrine
 Comparable efficacy to SSRIs
 Generally tolerable side effects profile
 Cause dry mouth, increased appetite, weight gain

Psychotherapy:
A) Cognitive Behavioural Therapy (CBT) B) Interpersonal Therapy (IPT)

 Helps people with depression restructure negative thought patterns
 During CBT a therapist will actively work with a person to uncover
unhealthy patterns of thought
 By addressing these patterns, patient and therapist can work together to
develop constructive ways of thinking thus will produce healthier
thoughts and beliefs
 Belief that psychological symptoms (such as depression) are
often due to difficulties of interacting with others
 Thought process behind therapy is that once a person is
capable of interacting more effectively with those around
them, the psychological symptoms can improve

Brain Stimulation Therapy :

Electroconvulsive Therapy (ECT)
 Considered when medication and psychotherapy are not effective in treating severe symptoms
 Performed under anesthesia in which electrical currents are passed through the brain
 Other more recently include vagus nerver stimulation (VNS), repetitive transcranial magnetic stimulation (r TMS)

REFERENCES
•Alan J. Gelenberg et al.2010.Practice Guideline for The Treatment of Patients with Major Depressive Disorder. Third Edition.American Psychiatric Association.
•Clinical Practice Guideline of Management of Major Depressive Disorder. 2007. Ministry of Health Malaysia.
•Mitchell J et al. 2013. Institute for Clinical Systems Improvement. Adult Depression in Primary Care. Institute for Clinical Systems Improvement.
•National Institute for Health and Care Excellence (NICE).2010.Guideline of The Treatment and Management of Depression in Adults. The British Psychological Society and The Royal
College of Psychiatrists.
•Sidney H. Kennedy et al. 2009. Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. Jour-
nal of Affective Disorders 117 (2009) S1–S2.
•World Health Organisation (WHO). http://www.who.int/topics/depression/en/

D E S F E R A L ®
( D E S F E R R I O X A M I N E )
In this article:
Thalassemia: Types, 4 ducted to diagnose thalas-
Diagnosis, Signs &
Symptoms
Treatment, Prognosis 4 is prevalent in Asian, Afri-
and Complications of
Thalassemia
Haemosiderosis and 5 One in twenty Malaysians
Treatment with Des-
feral®
Dosage, Side Effects 5
References 5
Special points of inter-
est:
 There are 2 main types
of thalassemia: alpha
and beta thalassemia
 Thalassemia patients
who undergo blood
transfusion may experi-
ence iron overload
 Slow subcutaneous infu-
sion is the preferred
method of Desferal®
administration
 The therapeutic index of
Desferal® should be
<0.025 to avoid excessive
chelation.
f De s f e r al®
Use o
me n t o f T ha la s s e mia
Manag e
Thalassemia: Types, Diagnosis, Signs & Symptoms
Thalassemia is an inherited
blood disorder caused when
the body does not make
enough haemoglobin, lead-
ing to malfunction or short
lifespan of red blood cells. It
can, Middle Eastern and
Mediterranean countries.
are estimated to be carriers
of the thalassemia gene.
The 2 main types of thalas-
semia:
1) Alpha thalassemia
2) Beta thalassemia
The severity of thalssemia
in each individual varies
(thalassemia trait, minor,
Treatment, Prognosis and Complications of Thalassemia
Treatment options for
thalassemia patients:
1) Blood transfusion
(especially thalassemia
intermedia and thalas-
semia major patients)
2) Chelation therapy (for
patients who undergo
multiple blood transfu-
sions)
in t h e
By: Andrea Tan Yin Lin
intermedia or major). fatigue, pale appearance,
yellowish-tinge skin colour,
Various tests can be con-
facial bone deformities, slow
growth, dark urine, short-
semia. Examples include:
ness of breath and dizzi-
ness.
1) Full blood count (Mean
corpuscular haemoglo-
Diagram 1: Alpha and beta
bin <27pg and red cell
thalassemia generation
distribution width
>15% may indicate
iron deficiency or
thalassemia)
2) Peripheral blood film
3) Haemoglobin electro-
phoresis
4) HPLC
Some signs and symptoms
of thalassemia include
3) Haematopoietic stem cell Thalassemia can cause com-
therapy (HSCT) plications such as iron over-
load, alloimmunisation and
4) Gene therapy
infections.
The prognosis of patients
with thalassemia depends on
it form of the disease would
be a poorprognosis severity.
A more severe for the pa-
tient.
 Haemosiderosis and treatment with Desferal®
Haemosiderosis is a form of iron over-
load where there is focal iron deposition
in the body but it does not cause tissue
damage.
Treatment of iron overload is carried out
using Desferal® (desferrioxamine). Des-
ferrioxamine is a chelating agent and
forms complexes mainly with ferric iron
and trivalent aluminium ions.
Patients are usually started on desferri-
oxamine after more than 10 units of
blood, and serum ferritin >1000µg/L on
at least 2 occasions measured at least 2
weeks apart.
Desferal® can be administered via:
collected for 6 hours and
checked for iron levels.
Items needed for admin-
istering Desferal® sub-
cutaneously are water for
injection, syringe, nee-
dle, butterfly-type nee-
dle, alcohol swab, infu-
sion pump and Des-
feral®.
Desferal® administration
(refer Diagram 2 on the
right):
1) Draw WFI using sy-
ringe and needle

1) Slow subcutaneous infusion 2) Inject 5mL water

into each Desferal®
2) Intravenous infusion during blood vial
infusion
3) Shake vial
3) Continuous intravenous infusion
7) Swab injection site with alcohol and
4) Draw drug into syringe
4) Intramuscular injection insert butterfly-type needle under
5) Attach syringe to extension tube, the skin of abdomen, arm, upper leg
Desferal® test must be performed be- then attach a butterfly-type needle or thigh.
fore starting treatment. For patients with to the end of the extension tube
normal kidney function, 300mg Des- 8) Fix the needle with tape
feral® is to be injected IM and urine is 6) Place syringe into infusion pump

Dosage, Side effects and Vitamin C

Dosage of Desferal®:
1) Children: 20-40mg/kg/day
2) Adults: up to 50-60mg/kg/day
Adjustment of dose is based on the
therapeutic index, which should be kept
<0.025 (formula shown below). vision or hypotension.
Common side effects of Desferal® in- Patients with iron overload are usually
clude headache, nausea, urticaria, myal- vitamin C deficient. Vitamin C increases
gia, growth retardation, injection site the availability of iron for chelation.
reaction and fever.
Thus, it is recommended to start vitamin
Treatment with C one month after starting Desferal®.
Desferal® may The dose of vitamin C is
rarely cause mu-
cormycosis, loss 1) 50mg/day (children <10 years)
of vision, blurred
2) 100mg/day (older children)

1) Centers for Disease Control and
Prevention (2015), Thalassemia.
http://www.cdc.gov/ncbddd/
thalassemia/treatment.html
2) Thalassemia Foundation of Can-
ada (2015), Frequently Asked
Questions. http://
www.thalassemia.ca/resources/
faq-2/
References
3) MedlinePlus (2014), Thalas-
semia. https://www.nlm.nih.gov/
medlineplus/ency/
article/000587.htm
4) MyTalasemia (2015), About Tha-
lassemia. http://
www.mytalasemia.net.my/
PublicFolder/About.aspx
5) Dr Mohd Ibrahim, H., Dr Hassan,
A., et al (2009), Management of
Transfusion Dependent Thalas-
semia. http://www.moh.gov.my/
attachments/8318.pdf
6) Dr Wong, SL, Dr Ng, HP, et al
(2003), Management of Thalas-
semia. http://www.moh.gov.my/
attachments/727.pdf
7) Desferal® product leaflet
The use of biological agents in psoriasis
By: Nur Afiqah Bt Mahrom

What is psoriasis? Types of psoriasis

 Autoimmune disease which result in painful, scaly, &
1. Plaque
inflamed patches of skin (plaques). 2. Erythrodermic
 Common sites : skin of the scalp, elbows, legs, knees, 3. Pustular
nails , palms/soles, gluteal cleft. 4. Inverse
 psoriatic arthritis involves joints. 5. Guttate

Treatment options Biological agents

 Biologics, biologic therapies, biological response modifiers,
a. Topical therapy
targeted therapies.
b. Phototherapy (UV light therapy)
c. Systemic therapy  Drugs derived from living materials which interfere with
specific parts of the body's immune system .
d. Biological therapy

Risk associated with biological agents

Immunosuppressive Common side effect Caution
 Increase the risk of infection &  Flu-like symptoms Patients who are:
reactivation of tuberculosis  Injection-site reactions  pregnant
(screening for latent tuberculosis  Headache  immune-compromised
is recommended)
 congestive heart failure
 Increase the risk of cancer
(lymphoma, skin cancer)

Biological Agents in psoriasis

 Indication : moderate-to-severe chronic plaque-type psoriasis.

 Mostly are administered subcutaneously.

 Targets the key parts of immune system that drive psoriasis.

When should biological agent be used?

Limited to patients with moderate to severe psoriasis where:

 All other treatments have failed

 Intolerable side effect of other treatment/toxicity occurred.

 Tumour necrosis factor-alpha (TNF-alpha) inhibitors
Block TNF-alpha which signals other cells to cause inflammation reduction in TNF-alpha
and stops the inflammatory cycle.

Infliximab (Remicade®)

 Administered via IV infusions

every 2 weeks for the first 6
weeks of treatment
 Infusions repeated every 8
weeks.

Etanercept (Enbrel®) Adalimumab (Humira®)

Self-injection subcutaneously
Self-injection subcutaneously
usually every other week
once or twice a week

Interleukin (IL-12 and IL-32) Interleukin-17A (IL-17A) inhibitor

inhibitor
Targets cytokines IL-12 & IL- 23
which promote the accumulation of
psoriatic disease-causing T cells &
thus reduces inflammation.
Inhibits IL-17A which is involved in inflamma-
tory & immune response — inhibiting its pro-
inflammatory effects — interrupts the inflam-
matory cycle of psoriasis

Ustekinumab (Stelara®) Secukinumab (Cosentyx)

Given by injection on week Self-injection

zero, week four, then subcutaneously once a week
every three months for the first 5 weeks, then
every 4 weeks

References:
 http://emedicine.medscape.com/article/1943419-overview
 http://dermnetnz.org/treatments/biologics.html
 https://www.psoriasis.org/about-psoriasis/treatments/biologics/resources
 https://www.psoriasis-association.org.uk/pages/view/about-psoriasis/
treatments/biologics
CROHN’S DISEASE
By: Lim Yun Hui

Crohn’s disease is a type of chronic inflammatory bowel disease (IBD). It mostly affects
the ileum and colon, but can also involve any part of gastrointestinal tract, from the
mouth to the anus. There is a unique characteristic about Crohn’s disease: the inflam-
mation parts can ‘skip’, leaving normal area between patches of diseased intestines.

Pathophysiology of Crohn’s Disease:

Beneficial bacteria of GIT are mistaken for harmful invaders, and the immune
system mounts a response. The resulting inflammation does not subside, leading
to chronic inflammation.

Complications of Crohn’s Disease:

Signs and Symptoms:

Small bowel obstruction Diarrhea

Fistulae Abdominal cramping

Anal fissures Weight loss

Malnutrition Feeling tired

Kidney stones Nausea or loss of appetite

Who is at risk of getting
Gall stones Crohn’s disease?
Fever
Joints: arthritis  Evenly affecting males and fe-
males
Liver: fatty liver, primary scle- Anemia
 More common in developed
rosing cholangitis countries
Joint pain or soreness
Eyes: uveitis, episcleritis  More common in urban than rural
areas
Oral ulcers Eyes irritation
 Can develop at any ages, most
commonly presents between
Skin: erythema nodosum, Skin changes that involves ages 20-30 years.
pyoderma gangrenosum red tender bumps under the
skin

Causes of Crohn’s disease:

 Autoimmune response - bacteria or viruses mistakenly trigger immune response to attack the inner lining of
intestines.
 Genes - Runs in family. Up to 20% of patient will have first-degree relatives with the disease.
 Environment - NSAIDs, antibiotics, OCP or high fat diet slightly increases the risk of disease. It is also more
common in developed countries.
* Diet and stress do not cause Crohn’s disease directly, but can aggravate it.
 Smoking
 Special points of interest: Management goals:
● Clinical history: chronicity, acuity and severity of ● There is no cure in Crohn’s dis-
symptoms, smoking, family history of GI disorders, ease; it is a chronic disease that
travel history. patient has to deal throughout their
● Physical examinations: mouth ulcers, abdominal life.
discomfort when pressing on abdomen, masses in
abdomen, rashes, joint swelling and perianal dis- ● To induce and maintain remission
ease. ● To reduce side effects of medica-
● Blood test: complete blood count may show anemia, tions
sedimentation rate and C-reactive protein ● To improve quality of life
(inflammatory markers)
● To prevent complications of
● Endoscopy and biopsy: colonoscopy and upper en-
doscopy
Crohn’s disease

● Chromoendoscopy: look for polyps or pre-

● To prevent hospitalization and
cancerous changes in the setting of colitis. surgery
● Small intestinal imaging: fluoroscopic x-ray, CT
scan or MRI scan.

Managements:
1. Surgery:
 Indications for surgery: perforation of intestine, uncontrollable intestinal bleeding, symptomatic stricture, abscess, fistula
that is symptomatic and cannot be medically managed, toxic megacolon, failure of medical therapy.
 Types of surgery: bowel resection, proctocolectomy and ostomy, stricturoplasty

2. Medical therapy:
 5-aminosalicylates, act topically on the GI tract and exerts anti-inflammatory effects for mild disease - sulfasalazine and
mesalamine
 Corticosteroids, anti-inflammatory and immunosuppressive effects for active flares and moderate to severe disease - predni-
solone, budesonide, hydrocortisone
 Immunomodulators to alter the over active immune system of Crohn’s disease - azathioprine, 6-mercaptopurine, meth-
otrexate
 Anti-tumor Necrosis Factor-alpha (TNF-α) for moderate to severe disease that do not response to standard therapy - inflixi-
mab and adalimumab

3. Bowel rest:
 When symptoms are severe, patient might need to rest the bowel for a few days to several weeks.
 Drink only clear fluid, or have no oral intake. Patient might get IV nutrition.

4. Dietary treatment:
 Patient stops eating normal food and is given a liquid feed as sole source of nutrients.
 When all the symptoms has cleared, normal food is reintroduced to see which one causes the symptoms.
 Exclude food that provoke symptoms, and dietician will check the resulting diet if it is nutrionally adequate and if any
supplements needed.

References:
 Crohn’s and Colitis Foundation of America. What is Crohn’s Disease [Internet]. US: Crohn’s and Colitis Foundation of America; 2016. [Cited
2016 Jan 15]. Available from: http://www.ccfa.org/what-are-crohns-and-colitis/what-is-crohns-disease/
 National Institute of Diabetes and Digestive and Kidneys Diseases. Crohn’s Disease [Internet]. Bethesda: National Institute of Health; 2014. [Cited
2016 Jan 15]. Available from: http://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/crohns-disease/Pages/facts.aspx#8
 Beth Israel Deaconess Medical Center. Crohn’s disease [Internet]. Boston: Beth Israel Deaconess Medical Center; 2016. [Cited 2016 Feb 3]. Avail-
able from: http://www.bidmc.org/Centers-and-Departments/Departments/Digestive-Disease-Center/Services/Inflammatory-Bowel-Disease-
Program/Crohns-Disease.aspx
 RESPIRATORY MTAC at HSAJB
By: Norhafizah Bt Ab Rahim

Respiratory Medication Therapy Adherence Clinic (RMTAC) in Hospital

Sultanah Aminah is a pharmacist-managed clinic in collaboration with

Chest Clinic aimed at improving patient asthma and COPD control by

enhancing compliance and improving inhaler technique. Thus, it

indirectly improves patients’ Quality of Life (QoL). Started in the year

2010 in HSAJB, every Tuesday from 8.00am-1.00pm, RMTAC is a clinical

pharmacy service under the directive and supervision of

Pharmaceutical Services Division which sees the expansion

of clinical role of pharmacists in the out-patient setting.

The clinic is conducted by dedicated pharmacists who help asthma and

COPD patients gain better knowledge and understanding of their

medications, and therefore, improving patients’ adherence to the

medication regimen. Throughout the patients’ visits, the pharmacist does

pharmacotherapy review of the patient, identifies pharmaceutical care

issues, provides solution to drug-related problems, educates patient, and

monitors the therapeutic outcome to ensure therapeutic goal is achieved.

References:
1. Medication Therapy Adherence Clinic: Respiratory 1st Edition 2010, BPF KKM