volume 1/2019 july 2019 penawar - hsajb.moh.gov.myhsajb.moh.gov.my/versibaru/uploads/farmasi/buletin...

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


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


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


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


• Clobetasone butyrate 0.05% cream/ointment

Class 4 (Mild)



• 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].


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.


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.

5. Salama, A., Levin, Y., Jha, P., & Alweis, R. Ventricular fibrillation due to overdose of loperamide, the "poor man's methadone". Journal of community hospital internal medicine perspectives.2017;7(4), 222-226.

6. Wolters Kluwer Clinical Drug Information, Inc. (Lexi-Drugs). Wolters Kluwer Clinical Drug Information, Inc.; version 4.4.0, April 19,

At a very high dose:



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.

volume 1/2019 july 2019 penawar - hsajb.moh.gov.myhsajb.moh.gov.my/versibaru/uploads/farmasi/buletin...

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