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EDITORIAL BOARD ADVISOR: PN HJH ROHAYAH BINTI ABD. GHANI
BULETIN
JULY 2019 VOLUME 1/2019
PENAWAR
HOSPITAL SULTANAH AMINAH JOHOR BAHRU KEMENTERIAN KESIHATAN MALAYSIA JALAN PERSIARAN ABU BAKAR SULTAN, 80100 JOHOR BAHRU
TEL: 07-2257000 FAX: 07-2242694 EMAIL: [email protected]
EDITORS: EN TAN CHEE CHIN PN NG WANG SING CIK ZANARIAH BT ABU BAKAR PN LI SHIN GIE
HOSPITAL SULTANAH AMINAH JOHOR BAHRU
UPDATES ON CLINICAL PRACTICE GUIDELINES
MANAGEMENT OF HYPERTENSION (5TH EDITION)
2018
PAGE 2-5
ATOPIC ECZEMA PAGE 6-7
LOPERAMIDE TOXICITY PAGE 8-9
LAPORAN SAMBUTAN TAHUN BARU CINA DAN HARI
LAHIR BULAN JAN-MAC
PAGE 10
Updates on CPG Management of Hypertension 2018
Risk stratification
Patients with hypertension should be risk stratified as many of them have more than one cardiovascular risk
factor. Each additional risk factor increases cardiovascular risk substantially. Hence, overall global cardio-
vascular risk of a patient should be done.
Risk stratification table has been used to stratify the risk of developing major cardiovascular events,
including stroke, myocardial infarction and total mortality.
Classification of clinic blood pressure levels in adults
1. For patients with a systolic blood pressure (SBP) of 130—139 mmHg and/or diastolic blood pressure (DBP)
of 85—89 mmHg, the term of “High Normal” is no longer being used. It has changed to “At risk”.
2. The SBP and DBP under classification of “Normal” has been changed from <130 mmHg and < 85 mmHg
to 120—129 mmHg and/or 80—84 mmHg, respectively.
Diagnosis and Initial Assessment
• Assess initial BP measurement results and global CV risk before deciding on the appropriate follow-up
required. Patients need to be reevaluated at subsequent visits as recommended below. (NEW)
In the latest CPG Hypertension, a new
risk stratification has been added,
which is Intermediate risk.
For patients who are categorized under low or
intermediate risk, the appropriate management
is to advise the patient to first have a healthy
living.
For those who are categorized under medium/
high/very high risk, healthy living is encouraged
and drug treatment should be initiated at the
same time.
Drugs Starting dose Recommended maximum daily dose
2013 2018 2013 2018
Enalapril 2.5mg OD 10mg OD 20mg BD 40mg daily
Perindopril 2mg OD 4mg OD 8mg OD 8mg OD
Telmisartan 20mg OD 40mg OD 80mg OD 80mg OD
Valsartan 80mg OD 80mg OD 160mg OD 320mg OD
Hydrochlorothiazide (HCTZ) 12.5mg OD 12.5mg OD 50mg OD 25mg OD
Amiloride/HCTZ 5mg/50mg I tab OD 1 tab OD 2 tabs OD 1 tab OD
Bisoprolol 5mg OD 5mg OD* 10mg OD 20mg/day
Nifedipine 10mg TID 5mg TID 20mg TID 20mg TID
Diltiazem 30mg TID 90mg BD 120mg TID 180mg BD
Verapamil SR 240mg OD 120mg OD 240mg OD 480mg OD
JABATAN FARMASI, HOSPITAL SULTANAH AMINAH JOHOR BAHRU
Prepared by: Lai Shu Yee & Tay Zee Kie
Initial BP
Recommended follow-up Systolic
(mmHg) Diastolic
(mmHg)
<120 and < 80 Recheck in one year
120 —139 and 80—89 Assess global CV risk & recheck within 3—6 months
140 —159 and/or 90—99 Assess global CV risk & confirm within 2 months
160 —179 and/or 100—109 Assess global CV risk & evaluate within 1 month and treat if confirmed
180 —209 and/or 110—119 Assess global CV risk & evaluate within 1 week and treat if confirmed
≥ 210 and/or ≥ 120 Assess global CV risk & initiate treatment after repeated measurement during the same
PAGE 2
*CrCl < 40ml/min: 2.5mg/day
Comparison be-
tween 2013 and
2018 guidelines on
changes of starting
dose and recom-
mended maximum
daily dose of anti
- h y p e r t e n s i v e
agents:
• Definition: severe increase in BP which is not associated with acute end organ
damage/complication, including patients with grade III or IV retinal changes.
• Patients MAY BE admitted depending on the response in terms of BP reduction
after resting in quiet room for 2 hours. (NEW)
• For patients whose BP responded (reduction of 10—20 mmHg SBP) after
adequate rest (after 2 hours), they can be discharged with a hypertensive urgen-
cy discharge plan.
• Combination oral therapy should be initiated when a patient’s SBP is not reduced
after a 2-hour rest. The goal of treatment is to reduce BP by around 25% within 24
hours but not lower than 160/100 mmHg.
Disease Target BP
Diabetes Mellitus
General target: <140/80 mmHg Younger patients & those at higher risk of CVD: <130/80 mmHg Diabetics with CKD: < 130/80 mmHg
Non-diabetic chronic kidney disease
Patients with proteinuria of < 1g/24 hr: <140/90 mmHg Patients with proteinuria of ≥ 1g/24 hr: <130/80 mmHg In patient >50 years, GFR> 20 ml/min/1.73m2 and proteinuria <1g/
day, lower SBP < 120mmHg using Automated Self-measured Office
BP to reduce cardiovascular event.
Renovascular hypertension Diabetic: <140/80 mmHg Younger patients: <130/80 mmHg
Coronary heart disease
Left ventricular hypertrophy (LVH)
<130/<80 mmHg
Heart failure
Atrial fibrillation
Peripheral arterial disease
<140/<90 mmHg
Drugs Dose
Adults Children
Labetalol
20 mg injected slowly for at least 2 min;
followed by 40-80 mg every 10 min. Max: 200
mg.
1 month - 11 years: IV 0.25-0.5mg/kg (Max
20mg); IVI 0.5-1.0 mg/kg/hr initially.
Maintenance: 0.25-3.0 mg/kg/hr.
Nitroglycerine Initial: 5-25 mcg/min. Usual range: 10-200 mcg/
min; up to 400 mcg/min in some cases. -
Isosorbide
Dinitrate
IV infusion 2 – 20 mg/hr, titrate based on target
BP. -
Hydralazine
Initial: 5-10 mg via slow injection, may repeat
after 20- 30 min. Alternatively, as a continuous
infusion, initial dose of 0.2-0.3 mg/min.
Maintenance: 0.05-0.15 mg/min.
1 month - 11 years: IV 0.1-0.5 mg/kg (Max 10
mg) may be repeated after 4-6 hr; IVI 12.5–50
mcg/kg/hr Max 3 mg/kg/day.
Nicardipine
Slow IVI at an initial rate of 5 mg/hr. Increase
infusion rate as necessary, up to max 15 mg/hr.
Consider reducing to 3 mg/hr after response is
achieved.
IV bolus 0.5-5 mcg/kg over 1 minute.
IVI 1- 4 mcg/kg/min.
Esmolol
Loading dose of 80 mg over 15-30 sec, followed
by an infusion of 150 μg/kg/min, may increase
to 300 μg/kg/min if necessary.
IV bolus 250-500 mcg/kg over 1 min; IVI
50-200 mcg/kg/min for 4 min. May repeat
sequence.
Sodium
Nitroprusside
Initial: 0.3-1.5 μg/kg/min, adjust gradually as
needed. Usual: 0.5-6 μg/kg/min. Max rate: 8 μg/
kg/min, discontinue if there is no response after
10 mins. May continue for a few hours if there is
response.
IV 0.25-0.5 mcg/kg/min, may be repeatedly
double at interval of 15-20 min.
Max 6 mcg/kg/min.
JABATAN FARMASI, HOSPITAL SULTANAH AMINAH JOHOR BAHRU PAGE 3
HYPERTENSIVE EMERGENCY
HYPERTENSIVE URGENCY
Treatment Options for Hypertensive Emergency
Patients SHOULD BE admitted AND BP needs to be reduced rapidly.
Oral Treatment for Hypertensive Urgencies
Definition: severe elevation of blood pressure associated with new or progressive end organ damage
complication.
4th edition drug use 5th edition drug use
Ischaemic Stroke SBP≤220 or DBP≤120: Defer therapy SBP>220 or DBP>121-140: a) Labetalol 10-20mg IV over 1-2mins. Max 300mg. b) Nicardipine. IVI 5mg/hr, max 15mg/hr. c) Captoril 6.25-12.5mg PO or IM. DBP>140 a) Nitroprusside 0.5mcg/kg/min with continuous BP
monitoring. b) Nitroglycerin 5mgIV, follow 1-4mg/hr.
Ischaemic Stroke SBP≤220 or DBP≤120: Defer therapy SBP>220 or DBP>120: a) Labetalol 20mg inject slowly followed by 40-80mg
every 10mins. Max 200mg. b) Nitoglycerin. Initially 5-25mcg/min, up to 400mcg/
min. c) Nicardipine. IVI 5mg/hr, max 15mg/hr. d) Sodium nitroprusside. 0.3-1.5mcg/kg/min, max
8mcg/kg/min.
Haemorrhagic Stroke SBP<180 and DBP>105: Defer therapy SBP180-230 or DBP105-140: a) Labetalol 5-100mg IV by intermittent bolus doses
of 10-40mg. b) Esmolol 500mcg/kg load dose, maintenance
50-200mcg/kg/min. c) Enalapril 0.625-1.2mg IV.
Haemorrhagic Stroke
SBP 150-220: Avoid lower SBP <140.
SBP>220: Consider aggressive BP lowering within 6 hr
with continuous IVI.
HYPERTENSION AND STROKE
• This group of patients need to be assessed comprehensively to confirm hypertension including frailty,
mobility, function, cognition, nutrition, postural hypotension and falls. (NEW)
• Treating the older adult to a target SBP of <150 mmHg to improve all cardiovascular outcomes. There is
some evidence that targeting a SBP of <140 mmHg may be beneficial, especially in reducing risk of
stroke whilst a recent trial supports even stricter targets (SBP <130 mmHg). (NEW)
CONSIDERATION IN OLDER ADULTS(NEW)
Ischaemic Stroke (IS)
◦Do not lower SBP <180 mmHg in the first 2 weeks in acute ischaemic stroke patients unless hypertensive
emergencies co-exist. (NEW)
Haemorrhagic Stroke (HS)
◦Do not lower SBP to <140 mmHg in patients presenting within 6 hours of haemoraghic stroke (HS) and BP
of <220 mmHg. (NEW)
◦Lower BP to <130/80 mmHg for secondary prevention in lacunar stroke. (NEW)
◦The drug of choice for acute phase for IS and HS are labetalol, nitroglycerine, nicardipine and sodium
nitroprusside.
Multiple comorbidities
SBP of 140-160 mmHg is associated with better mortality outcomes in older adults with impaired physical or
cognitive functioning. Lower targets (SBP <120 mmHg and DBP<70 mmHg) may increase the risk of death
and cardiac events in older high-risk individuals.
Polypharmacy and Adverse Drug Reactions
Shown to be related to poor outcomes including postural hypotension, falls, electrolyte disturbances, heart
failure, hospitalisation and mortality. De-prescribing should be considered in the presence of ADRs as
there is evidence that de-prescribing does not result in an increase in mortality in older adults.
Postural Hypotension and Falls
Both uncontrolled hypertension, especially isolated systolic hypertension and aggressive BP treatment
have been associated with postural hypotension. Less strict BP targets may therefore be acceptable in the
very elderly, the frail, those with multi-morbidities and previous fallers .
Cognition
Hypertension predisposes mainly to development of vascular cognitive impairment but has also been
found to be a risk factor for Alzheimer’ pathology.
Frailty
The trial showed benefit of treating hypertension in adults >80 years of age and did not find any effect of
frailty on the benefit of hypertensive treatment.
HYPERTENSION IN ELDERLY >65 YEARS OLD
JABATAN FARMASI, HOSPITAL SULTANAH AMINAH JOHOR BAHRU PAGE 4
Hypertension in pregnancy (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg
• Avoid RAS blockers in all women of childbearing potential unless adequate precaution has been taken against
pregnancy. (NEW)
• The absence of a mercury sphygmomanometer, an automated blood pressure measuring device can be used
provided it is calibrated. (NEW)
• In an acute hypertensive crisis, use IV labetalol or continuous infusion of 1-2mg/minute. IV hydralazine (bolus or infu-
sion) is an alternative but do not use it as first line treatment. (NEW)
• Provide low dose calcium supplementation (500-1000 mg daily) from early pregnancy and commence aspirin
(100-150 mg and taken at bedtime) from 12-16 weeks and continue until delivery in pregnant women with one or
more high risk factors or two or more moderate risk factors for pre-eclampsia. (NEW)
Treatment is recommended when BP is consistently above the 99th percentile. There are few published case
series that used diuretics, ACEI, β-blockers and CCB.
The diagnosis of hypertension in children and adolescents is made when the auscultated BP values on three
repeated and different visits are greater than the 95th percentile for age, sex, and height of the patient, or is
≥130/90mmHg.
If the patient BP is symptomatic or >30 mmHg above the 95th percentile (or >180/120mmHg in an
adolescent), send to an emergency department.
Once pharmacologic therapy is initiated, BP must be reduced to <90th percentile (Systolic and Diastolic) and
<130/80 mmHg in adolescents ≥13 years old. (NEW)
In children and adolescent with CKD, lower BP to <50th percentile. (NEW)
Resistant hypertension is defined as uncontrolled hypertension (>140/90 mmHg) with good medication
adherence while on three or four anti-hypertensive agents (including a diuretic) in adequate doses.
Refractory has been proposed to be used on patients whose BP are not controlled after ≥5 antihypertensives.
Treat patients with at least 3 drugs (inclusive of a diuretic) before diagnosing resistant hypertension.
Consider drug non-adherence and secondary hypertension before diagnosing resistant hypertension. (NEW)
A fourth drug should be added to the combination of RAS blocker, CCB and diuretic.
The result of studies confirmed that spironolactone is the drug of choice as the fourth drug in resistant
hypertension. (NEW)
4th edition drug use 5th edition drug use
Labetalol
In IV bolus: 20mg then 40 mg 10–15 minutes later, then 80
mg every 10–15 minutes, up to 220 mg; or continuous IV
infusion of 1–2 mg/minute until BP stabilizes, then stop or
reduce to 0.5mg/minute.
Labetalol
In IV bolus: 20mg then 40mg 10-20mins later, then 80mg
every 10-15mins up to 200mg; or continuous IV infusion of
1–2 mg/minute until BP stabilizes, then stop or reduce to
0.5mg/minute.
Hydralazine
5 mg IV bolus or IM, then 5–10 mg every 20–40 minutes up
to 30mg, or IV infusion of 0.5-10 mg per hour.
Hydralazine
Initial: 5-10 mg via slow inj, may repeat after 20-30 min.
Alternatively, as a continuous infusion, initial dose of 0.2-
0.3 mg/min.
Maintenance: 0.05-0.15 mg/min.
HYPERTENSION IN WOMEN
HYPERTENSION IN NEONATES, CHILDREN AND ADOLESCENTS
RESISTANT AND REFRACTORY HYPERTENSION
JABATAN FARMASI, HOSPITAL SULTANAH AMINAH JOHOR BAHRU PAGE 5
Comparison of drugs used in acute hypertensive crisis between 4th and 5th edition of Malaysian CPG
on Management of Hypertension:
What is Atopic Eczema?
• Also known as atopic dermatitis
• Episodic disease of flares and remission
• Complex, chronic and recurrent inflammatory
itchy skin disorder
• Start in early childhood and persist into adulthood
• Various clinical manifestations according to
different age groups
Atopic Eczema
Types of Atopic Eczema
Acute Chronic
Papulo-vesicular eruption Erythema Weeping Oedema
Excoriation
Lichenification Dry skin
Do you know? Atopic Eczema is often aggravated by factors including: aeroallergen (house dust), physical irritants (nylon or wool, soaps, detergents, chemical reagents), environmental factors (climate and air pollution, warm and high sun exposures), food and microbial colonization or infection. Therefore, identification and management of aggravating factors is important in managing atopic eczema.
Atopic Eczema is often associated with:
• Skin infection
• Atopic disease
• Contact Dermatitis
• Food allergy
• Psychological and psychosocial dysfunction
• Cardiovascular Disease
Management of Atopic Eczema
• I n v e s t i g a t o r ’ s G l o b a l
Assessment (IGA) is a com-monly used tool to assess severity of atopic eczema
• Atopic eczema is then
managed with the algorithm below:
Investigator’s Global Assessment1
Score Description
0 = Clear No inflammatory signs of atopic eczema
1 = Almost Clear Just perceptible erythema, and just perceptible papulation/infiltration
2 = Mild Disease Mild erythema, and mild papulation/infiltration
3 = Moderate Disease Moderate erythema, and moderate papulation/infiltration
4 = Severe Disease Severe erythema, and severe papulation/infiltration
5 = Very Severe Disease Severe erythema, and severe papulation/infiltration with ooz-ing/crusting Adjunct therapy:
• Topical/oral antibiotics/
antiviral/antifungal for bac-terial, viral or fungal infec-tions
• Oral sedating antihistamines
for sleep disturbance
• Topical antiseptics to reduce
Staphylococcus aureus coloni-sation
• Psychological intervention
JABATAN FARMASI, HOSPITAL SULTANAH AMINAH JOHOR BAHRU PAGE 6
Prepared by: Lim Roucen
Algorithm on Treatment of Atopic Eczema
Emollient
Improves the epidermal barrier function and dryness
Reduction in pruritus, severity and rate of flare
Enhance effectiveness of TCS and have steroid-sparing property
Topical Corticosteroids (TCS)
Anti-inflammatory and immunosuppressant effects, use concomitantly with emollients
Inhibiting fibroblast proliferation and collagen synthesis, and local vasoconstriction
During acute flares, short course of moderate to very potent
TCS can be considered for rapid control
Discontinuation of TCS gradually to avoid rebound
After resolution, proactive therapy to maintain remission
Eg. Mild TCS application intermittently once/twice a week
Topical Calcineurin Inhibitors (TCI)
Useful in: 1. Recalcitrance to steroids 2. Sensitive areas: face, anogenital, skin folds 3. Steroid-induced atrophy 4. Prevent long term uninterrupted topical steroid use
Advantage: does not cause skin atrophy
BLACK BOX WARNING RARE CASES OF MALIGNANCY (EG: SKIN CANCER AND LYMPHOMA) HAVE BEEN REPORTED IN PATIENTS TREATED WITH TCI
Usual dose: twice daily application
Proactive Maintenance Therapy with 2-3 times weekly for 40
-52 weeks is able to prevent, delay and reduce mild to severe AE flares.
Wet Wrap Therapy
Consists of two layer of tubular bandage or garments with inner wet and outer dry layers
Applied over moisturizer alone or in combination with TCS
Selecting Steroid Vehicle
Site Potency of TCS Vechicle
Face Low and medium potency Creams
Intertriginous areas
Low and medium potency Creams
Trunk and ex-tremities
Moderate to potent Creams, Ointment, spray, foam
Palms and soles Potent to superpotent Ointment
Scalp Moderate to high Solution, lotion, foam, gel, shampoo
Potency of Corticosteroid (UK Classification)
Class & Potency
Drug
Class 1 (Very Potent)
• Clobetasol propionate 0.05% cream/ointment
Class 2 (Potent)
•Betamethasone dipropionate 0.05% cream/ointment
• Betamethasone valerate 0.1% cream/ointment • Fluticasone propionate 0.05% cream • Mometasone furoate 0.1% cream/ointment • Triamcinolone acetonide 0.1% cream
Class 3 (Moderate)
• Betamethasone valerate 1 in 2 dilution (0.05%) cream/ointment
• Betamethasone valerate 1 in 4 dilution (0.025%) cream/ointment
• Clobetasone butyrate 0.05% cream/ointment
Class 4 (Mild)
• Betamethasone valerate 1 in 8 dilution (0.0125%) cream/ointment
• Betamethasone valerate 1 in 10 dilution (0.01%) cream/ointment
• Hydrocortisone acetate 1% cream/ointment
Fingertip Unit
One fingertip unit (FTU) is the amount of cream squeezed along index finger from tip to the first joint. 1 FTU = 0.5 g (covers the size of two palms of adult)
Non-pharmacological Therapy
Complementary feeding — reduce risk with early introduction at age of 4-5 months but this requires stronger evidence to proof
Probiotic — reduce incidence when given to healthy infant and pregnant mother
Prebiotic — expressed breast milk or infant formula with prebiotic reduce incidence
Bathing — avoid extreme temperature and bath less than 10 minutes
Systemic Therapy
Systemic Corticosteroid 5-60mg OD
Azathioprine 1-3mg/kg/d
Paediatric: 1-4mg/kg/d
Cyclosporin A 150-300mg/d
Paediatric 3-6mg/kg/d
Methotrexate 7.5-25mg once weekly,
Paediatric: 0.2-0.7mg/kg/week
Mycophenolate Mofetil 1.0-1.5g orally twice daily
Paediatric: 1200mg/m2 daily
(30-50mg/kg/d)
Dupilumab Initially: S/C 600mg in 2 divided dose
Maintenance: S/C 300mg once every
other week
Omalizumab S/C 150 or 300mg every 4 weeks
Infliximab IV 5mg/kg at 0, 2, and 6 weeks,
followed by 5mg/kg every 8 weeks
REFERENCES:
1.Clinical Practice Guideline: Management of Atopic Eczema. (2018).
Ministry of Health Malaysia.
2.Atopic Dermatitis. (2018). Emedicine.medscape.com [online] Availa-
ble at: https://emedicine.medscape.com/article/1049085-overview
[Accessed 30 Nov. 2018].
3.Guidelines of care for the management of atopic dermatitis. (2013).
American Academy of Dermatology.
4. Ference & Last. Choosing Topical Corticosteroids. American Family Physician. 2009 Jan 15;79(2): 135-140.
5.Topical steroid. DermNet New Zealand [online]. 2018. Available at: https://www.dermnetnz.org/topics/topical-steroid/ [Accessed 30 Nov
2018].
JABATAN FARMASI, HOSPITAL SULTANAH AMINAH JOHOR BAHRU PAGE 7
LOPERAMIDE TOXICITY Prepared by: Nur Amirah Abdul Aziz
Loperamide is a phenylpiperidine (pethidine) derivative structurally related to haloperidol and diphenoxylate which used to
relieve symptoms of diarrhoea. It is a prescription medicine which is safe and effective when used as directed.
Binds to the mu-opioid receptors in the gut
Inhibits the release of acetylcholine and prostaglandin
Reduce propulsive peristalsis
Increase intestinal transit time
THERAPEUTIC DOSE
Acute diarrhoea:
Adult: Initially 4mg, followed by 2 mg after each
loose stool (MAX: 16mg/day)
Paediatric:
2-5 years (13-20kg): MAX 3mg/day
6-8 years (20-30kg): MAX 4mg/day
9-11 years (>30kg): MAX 6mg/day
>12 years: refer to adult dosing
Contraindicated: Below 2 years old
LOPERAMIDE TOXICITY IN PAEDIATRICS
When given at supratherapeutic dose:
There is high tendency that loperamide might cross the blood brain barrier (BBB) causing central nervous system
(CNS) depression leading to respiratory depression.
Respiratory depression is mediated via mu-opioid peptide receptors at the respiratory centres in the brainstem.
Respiratory rate falls more than the tidal volume and the sensitivity of the brain stem to carbon dioxide is reduced.
There is greater variability of response among paediatrics and they are also prone to toxicity.
LOPERAMIDE MISUSE AND ABUSE
In a very high dose:
Produce euphoric effect (opioid-like high) through activation of
central dopamine reward pathway.
The effects of loperamide at high doses are similar to the centrally
acting opioid.
Speculated to be able to ameliorate opioid withdrawal symptoms.
Information on this use is shared publicly through
unregulated internet forums and blogs without additional
caution regarding adverse effects.
However, no clinical studies have been done on using
loperamide for this purpose.
Many co-ingested loperamide with CYP3A4 Inhibitors and
P-glycoprotein inhibitors to achieve euphoric effect.
Among the documented CYP3A4 Inhibitors include cimetidine,
omeprazole, itraconazole and for P-glycoprotein inhibitors include
gemfibrozil and quinidine.
Both of these interactions may increase loperamide plasma
concentrations up to 4-fold and prolongs its elimination half-life to
approximately 36.9 hours.
OLD BELIEFS OF LOPERAMIDE Loperamide was initially believed to have a low abuse and misuse potential because of:
• Its poor bioavailability (~2% after oral ingestion).
• Extensive first pass metabolism by CYP3A4 and CYP2C8–reduces the ability to achieve dangerous drug concentrations
systemically when taken at therapeutic doses.
• Inability for direct penetration through the BBB in the CNS due to the effects of the P-glycoprotein (P-gp) efflux
transporter which limit the availability of loperamide that can cross BBB.
ONLY APPLICABLE AT THERAPEUTIC DOSE
STATISTICS OF LOPERAMIDE TOXICITY
Based on the reports by National Poison Database System US, the number of
intentional loperamide exposures is more than doubled between 2010 and 2015.
15.34% fatal incidence following loperamide toxicity due to misuse/ abuse/
dependence/ withdrawal (Based on loperamide ADRs reported to European Medi-
cine Agency).
It has been linked to “poor man’s methadone” with average daily intake of 70 mg
and some receiving up to several hundred milligrams per day.
JABATAN FARMASI, HOSPITAL SULTANAH AMINAH JOHOR BAHRU PAGE 8
MECHANISM OF ACTION FOR ANTI-DIARRHEAL
4. SUPPORTIVE CARE
Cardiac arrest
Cardiopulmonary resuscitation
Cardioversion or defibrillation for shockable
rhythm
Polymorphic ventricular tachycardia
Intravenous sodium bicarbonate (1-2mEq/kg) and
magnesium sulfate (1-2g IV bolus over 5-10 min,
then 1g/hr IV infusion for 4 hrs)
QT prolongation
Intravenous isoproterenol 2-20mcg/min
Transvenous pacing
Reverse any electrolyte abnormalities
CLINICAL PRESENTATIONS OF LOPERAMIDE TOXICITY
MILD TO MODERATE TOXICITY
Drowsiness
Vomiting
Abdominal pain
Miosis
Seizure-like activity
SEVERE TOXICITY
CNS depression
Respiratory depression-lead to
apnea and respiratory acidosis
Cardiotoxicity
CARDIOTOXICITY
The main concern as commonly lead to
death
Presenting rhythms vary, but include:
Ventricular tachycardia
Ventricular fibrillation
Asystole
Loperamide inhibits:
Cardiac sodium channel
Human ether-a-go-go (hERG) potassium
channel [very high inhibitory action]
Prolong action potential duration
Delays
depolarization
Delays
repolarization
QRS prolongation
QT prolongation
1. DECONTAMINATION
Within 2 to 4 hours after a large
overdose, activated charcoal can
be given to adsorb the
loperamide.
Loperamide levels are reduced nine-fold when
activated charcoal is given.
For acute poisoning: 50g to 100g followed by 25g to
50g every 4 hours.
2. ENHANCING ELIMINATION
As a lipophilic, highly protein-bound (97%) drug,
loperamide would not be appreciably cleared by
hemodialysis.
A trial of intravenous lipid emulsion may be considered
in patients who remain severely unstable despite optimal
care.
Dosing should be individualized and should proceed
with the recognition that intravenous lipid emulsion may
be ineffective and is not devoid of risk.
Loperamide is slowly eliminated in the setting of
toxicity and prolonged infusions of intravenous lipid
emulsion are generally best.
3. ANTIDOTE
In the presence of respiratory depression
or degrees of somnolence that might
impair airway protection.
Naloxone (opioid receptor antagonist)
should be administered in addition to
supportive care.
Given the possibility of opioid withdrawal,
lowest effective dose (0.01 to 0.4mg)
should be used.
IV Naloxone may be given at repeated doses at
interval of 2-3 minutes due to loperamide’s slow elim-
ination.
MANAGEMENT OF LOPERAMIDE TOXICITY
REFERENCES
1. Wu PE, Juurlink DN. Clinical Review: Loperamide Toxicity. Ann Emerg Med. 2017;70(2):245-252
2.Miller H, Panahi L, Ttapia D, Tran A, Bowman JD. Loperamide misuse and abuse. J Am Pharm Assoc 2017 Mar - Apr;57(2S):S45-S50
3. Schifano F, Chiappini S. Is there such a thing as a 'lope' dope? Analysis of loperamide-related European Medicines Agency (EMA) pharma-covigilance database reports.2018. PLoS ONE 13(10): e0204443.
4. Venkatmurthy M, Balaji M D, Sneha M. A rare case of Loperamide toxicity in a neonate. Int J Pediatr Res.2016;3(7):547-549.
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At a very high dose:
JABATAN FARMASI, HOSPITAL SULTANAH AMINAH JOHOR BAHRU PAGE 9
JABATAN FARMASI, HOSPITAL SULTANAH AMINAH JOHOR BAHRU PAGE 10
LAPORAN SAMBUTAN TAHUN BARU CINA DAN
HARI LAHIR BULAN JAN-MAC
Pada 24 Februari 2019 yang lalu, Jawatankuasa Kebajikan dan Sosial Jabatan Farmasi telah menganjurkan Majlis Sambutan Tahun Baru Cina. Sambutan ini telah diadakan di ruang tengah Unit Farmasi Logistik, Hospital Sultanah Aminah Johor Bahru . Sambutan ini bertujuan untuk meraikan staf yang berbangsa Cina di Jabatan Farmasi dan juga hari lahir staf yang lahir antara bulan Januari hingga Mac.
Dengan adanya sambutan ini, warga Jabatan Farmasi dapat meraikan perayaan bersama-sama dan secara tidak langsung dapat mengeratkan silaturrahim bersama rakan sekerja. Tepat jam 12.45 tengah hari maj-lis dimulakan dengan ketibaan Puan Hjh Rohayah binti Abd Ghani selaku penasihat Jawatankuasa Kebajikan Dan Sosial Jabatan Farmasi.
Majlis dimulakan dengan bacaan doa dan disusuli dengan ucapan daripada Puan Hjh Rohayah binti Abd Ghani. Majlis ini dimeriahkan lagi dengan acara memotong kek bagi staf yang menyambut hari lahir pada bulan Januari, Februari dan Mac. Mereka yang terlibat telah menerima cenderahati daripada pihak jawatankuasa. Majlis kali ini juga dimeriahkan dengan satu cabutan bertuah bagi setiap staf yang menyambut hari lahir antara bulan Januari dan Mac. Tidak lupa juga penyampaian hadiah kepada staf yang ditukarkan ke tempat baru, staf yang telah melahirkan cahaya mata dan staf yang telah mendirikan rumahtangga.
Majlis diakhiri dengan jamuan makan tengahari yang disertai oleh semua anggota yang hadir. Secara keseluruhannya, sambutan Tahun Baru Cina Jabatan Farmasi berjalan dengan lancar dan meriah.