HM Medical Clinic

Pharmacy Bulletin
September 2015 Edition (Volume 2/2015)
Look Alike
Sound Alike
Sound Alike
Drug Names
Errors Reporting
In Hospital
Page 8-10 Product
Infarction (MI)
& Thrombolytic
Page 14-17
Page 18-21
Patent Ductus
Puan Nazariah Bt. Haron Arteriosus
Editorital Board: Cik Salmi Abdul Razak Page 22-25
Puan Nadiah Mohamed Khazin Encik Ho Lip Yong Cik Chong Ee Ping Encik Chang Kang Wei Cik Thevashantini A/P Kasinathan

On 25th April 2015, the Aseptic Unit of Pharmacy Department of Hospital Putrajaya organized Aseptic Dispensing Course 2015 which was held in Seminar Room, Hospital Putrajaya. The objectives of this event is to increase understanding on handling the cleanroom based on Good Preparation Practice (GPP) as well as to give exposure on Aseptic Techniques. Aseptic technique is the term used for all procedures and techniques performed to keep a sterile product from becoming contaminated. Aseptic technique is a means of manipulating sterile products without contaminating them. Proper use of a cleanroom and strict aseptic technique are the most important factors in preventing the contamination of sterile products. This event was officiated by Puan Nazariah Bt. Haron, Chief Pharmacist of Hospital Putrajaya, which was followed by the first topic on Overview of Good Preparation Practice (GPP) by Pharmacist U54 from Nuclear Pharmacy Department, National Cancer Institute (NCI), Mr. Suharzelim Abu Bakar. Other topics that were presented in this course were, Premises & equipment: Maintenance & Monitoring, Good Documentation Practice (GDP): What you do?, and Personnel Requirement in GPP Personnel Hygiene: Do's and Don't's in cleanroom. The participants were exposed on spill management and also aseptic techniques as well as procedure of cleaning a cleanroom. These hands-on are essential to educate the participants what are the steps and precautions need to be taken in the event of accidental cytotoxic spillage, and also to gain experience on proper techniques and procedure in aseptic in order to prevent contamination of sterile products. This workshop ended with satisfaction from the participants on the whole program. They also enjoyed and benefited a lot especially during the hands-on session.

Therapeutic drug monitoring (TDM) is commonly used during treatment and for diagnostic purposes with known concentrations of drugs in body fluids, usually plasma. The selection of drugs for therapeutic drug monitoring is important as the concentrations of many drugs are not clearly related to their effects. For selected drugs, therapeutic drug monitoring aims to enhance drug efficacy, reduce toxicity or assist with diagnosis. The drug concentration is complementary to and not a substitute for clinical judgment so it is important to treat the individual patient and not the laboratory value. Drug concentrations may be used as surrogates for drug effects so therapeutic drug monitoring may assist with dose individualization. On 30th May 2015, a workshop entitled "Clinical Pharmacokinetic Workshop 2015" was organised by Clinical Pharmacy Unit from the Pharmacy Department of Putrajaya Hospital in collaboration with Bahagian Perkhidmatan Farmasi Jabatan Kesihatan Wilayah Persekutuan Kuala Lumpur & Putrajaya. The event was held in Auditorium of Putrajaya Hospital (HPJ) and was attended mostly by pharmacists of Putrajaya Hospital, and also pharmacist Hospital Rehabilitasi Cheras (HRC) and Institut Kanser Negara (IKN). The speaker invited for this workshop was Associate Professor Dr. Mohd Bin Makmor Bakry, Head of Community and Industry Network from National University of Malaysia (UKM), a renowned expert in Clinical Pharmacokinetic. The objectives of this workshop are to provide updates on latest Therapeutic Drug Monitoring (TDM) practice and to enhance skills in developing appropriate TDM dosing recommendations for patients.

The event was started with a 30 minutes pre-test in order to assess basic knowledge of pharmacists followed by a welcoming speech from Puan Nazariah Bt. Haron, Chief Pharmacist of Putrajaya Hospital. Topics presented by the speaker include Introduction to Clinical Pharmacokinetic, Clinical Pharmacokinetics of Digoxin, Clinical Pharmacokinetics of Antiepileptics, Clinical Pharmacokinetics Pharmacokinetics of Immunosuppressants & Methotrexate, and Clinical Pharmacokinetics of Theophylline. All these topics are specially designed based on the available TDM test done in Pharmacy Department of Putrajaya Hospital. The workshop was closed with a price giving ceremony, where Ms. Pavithira a/p Nagamuthu (PRP) was rewarded with a gift as she scored highest in a post-test that was conducted immediately after the talk ended. In conclusion, all participants had a fruitful day with a better understanding of clinical pharmacokinetics. Hopefully, through this workshop, all pharmacists will be able to handle situations when dealing with TDM. PHARMACY BULLETIN, VOL 2/2015 SEPTEMBER 2015
Drug Names
Confused Drug Names
Chloramphenicol EYE Drops
Chloramphenicol EAR Drops
(Dydrogesterone) (Estradiol/Dydrogesterone) DULoxetine
Femoston CONTI
Gliclazide MR
(Neomycin, Polymyxin B and Dexamethasone (Dexamethasone Opthalmic Drops) Ophthalmic Suspension) Magnesium TRISILICATE
Magnesium SULPHATE
Metformin XR
Olanzapine (ZYPREXA)
Olanzapine (ZYDIS)
Potassium CITRATE
Potassium CHLORIDE
(Estradiol Valerate/Norgestrel) (Estradiol Valerate) AMIsulpride
TRANEXamic Acid
MEFENamic Acid
Trimetazidine MR
Wrong Medication Dispensed
Phenytoin Overdose
On 21/5/2015, at outpatient pharmacy, a 68 On 15/5/2015, an 11 years old girl was years old woman was prescribed with Gutt. discharged from ward with incorrect dose of Fusidic Acid for right eye conjunctivitis. phenytoin. The intended dose of Phenytoin However, the medication was wrongly filled Syrup for the patient was 90mg BD (3mg/kg as Fusidic Acid Cream and was dispensed to BD). Despite there was discussion done the patient. Patient brought home the between doctor and T DM pharmacist, doctor medication and applied once into the eyes. wrongly prescribed Phenytoin syrup 180mg Subsequently, patient called pharmacy and BD (6mg/kg BD, patient BW: 30kg) for 1 omplained uncomfortable sensation after week to the patient. Without thorough using the medication. Then, patient returned checking on TDM note entered by TDM to ref pharmacy and patient was immediately pharmacist, on-call pharmacist prepared the erred to ophthalmologist for further medication after calling doctor to reconfirm the intended dose. Eventually, pharmacist dispensed the medication according to doctor's discharged summary. After few days, ward pharmacist detect this error and immediately called the patient's parent if patient having any 1. Emphasize adherence to standard unusual signs and symptoms. working procedure for effective counter- checking and always dispense medications according to doctor's 1. Emphasize to all doctors and pharmacists 2. To place an Alert Tag on the medication to always check and refer to TDM notes bins of both fusidic acid eye drop and entered by TDM pharmacist before fusidic acid cream to prevent confusion. prescribing and screening any medications 3. A request to change the unit of intake on which required TDM monitoring. label for eye drops to "TITIS" instead of 2. Inexperienced houseman doctor or trainee the current unit "SAPU". pharmacists should always reconfirm any ambiguous medication dose with more experienced medical officers or pharmacists. PHARMACY BULLETIN, VOL 2/2015 SEPTEMBER 2015
Wrong patient wrong medication
Wrong Medication Dispensed via UMP
In in-patient pharmacy, during filling of On 25/4/2015, Telmisartan 80mg/ wards medication trolley on 14/5/2015 by Hydrochlorothiazide 12.5mg tablet was new trainee pharmacist, medication labels initially wrongly filled and dispensed to from 3 different patients was wrongly pasted patient via UMP services to patient taking on the Cumulative Medical Record (CMR) partial prescription medications. However, sheet of a patient. Consequently, the actual intended medication was medications intended for 4 different patients Telmisartan 80mg/ Amlodipine 5mg were filled, counterchecked and dispensed instead. Unfortunately, patient had taken the to the patient. However, the other 3 patients wrong medication for 1 week and then who the medication labels was wrongly notified the pharmacist. pasted did not get their medications. The error was only detected the next day when pharmacist screening CMR files. Due to the fact that Telmisartan/ HCTZ and Amlodipine have similar packaging, there is a high risk of filling 1. Inpatient pharmacy department to revise error. Therefore, to minimize possibility of the orientation module by ensure more error Look Alike Sound Alike tag should be experienced pharmacist to assist, guide labeled at both drug bins. Besides, tallman and supervise trainee pharmacists until lettering should be used on the label of the they are competent to perform task drug bin to minimize error. 2. Emphasize to all pharmacists importance to comply with standard working procedures while doing any tasks given to prevent medication errors. PHARMACY BULLETIN, VOL 2/2015 SEPTEMBER 2015
Wrong Medication Dispensed
During peak hour in outpatient pharmacy on 27/3/2015, calcium carbonate label was mistakenly filled with calcium lactate tablets. Then, the medications was counterchecked and dispensed to patient by pharmacist. The dose given to patient was 2 tablets TDS. Without knowing the medication given was incorrect, the patient had taken 72 tablets of calcium lactate. The incidence was discovered by ward pharmacist during medication history taking when patient was admitted to ward for community acquired pneumonia on 5/5/2015. 1. Therefore, to minimize medication errors, improvement on working procedure were done where at least two pharmacists will be assigned to countercheck dispensed medications during peak hours. PHARMACY BULLETIN, VOL 2/2015 SEPTEMBER 2015
Product Complaint #1
On 23/2/2015, it was reported that the packaging and label of Loxin Injection (Dopamine hydrochloride BP 40mg/mL Injection) had been changed by the company. The new packaging and labels of Dopamine hydrochloride BP 40mg/mL Injection become very similar to the packaging and labels of Noradrenaline Above: Outer Packaging for Loxin Injection (Dopamine Hydrochloride BP 40mg/mL)
4mg/4mL Injection. Staff nurse who was Below: Outer Packaging for Cardiamed Injection (Noradrenaline 4mg/4mL)
aware of the changes then filed in a complaint on the changes as the highly similarity in both labels can cause confusion and increase the risk of medication errors as these medications were commonly used during emergency conditions. The complaint was forwarded to National Pharmaceutical Control Bureau (NPCB), the manufacturer was then notified and advised to revise on the packaging and labels of both of the medications. Subsequently, manufacturer Above: Ampoule Label for Loxin Injection (Dopamine Hydrochloride BP 40mg/mL)
agreed to amend the label for Loxin Below: Ampoule Label for Cardiamed Injection (Noradrenaline 4mg/4mL)
Injection to avoid confusion. Product Complain #2
named N3 Beauty Care Toner 2 and N3 Beauty Care Cream. However, the On April 2015, it was reported that a patient hypopigmented patch did not improve even developed hypopigmented patch over after patient change the products and application site after started using Polla completely stopped all the products. Whitening Cream in early March. Therefore, a report was filed to investigate Subsequently, patient had stopped using the the possibility of presence of whitening product and started on two new products PHARMACY BULLETIN, VOL 2/2015 SEPTEMBER 2015
agent, mercury or adulterants in all three claimed he is unable to control the quantity of drops when applying the medication. Consequently, this causes wastage and Upon investigation, all three products were possible risk of long term effects. Patient found to be un-notified cosmetic products also worried this problem may affect the and Polla Whitening Cream was found to efficacy of the medication as he claimed it contain mercury in the product. However, was not as effective as before. However, for the others two products, additional investigation done by National products were requested for sampling Pharmaceutical Control Bureau (BPFK) on the same batch eye drops conclude that there was neither defect nor deviation from the machines, processes Product Complain #3
as well as the effectiveness. The test On March 2014, the sample did not reveal any difficulty in manufacturing date and controlling quantity of expiry date on the drops dispensed. packaging of Rinz Besides, manufacturer Normal Saline Eye advised counseling to Drops were found be given to patient, so difficult to be read. After that only minimal investigation, it was found that the root cause when applying the of the problem was due to wear and tear of addition, manufacturer embossing digits used to will revised on the print the details. design of eye drop "bottle tip" so that it Subsequently, corrective measures which allows better drop control for patient. will be done by the manufacturer are to purchase a new embossing digits machine to replace the old machine and take all necessary preventive measures such as Product Complain #5
personnel training to prevent reoccurrence On October 2014, bottles of Zinc cream were found to have disintegrate to 2 layers (water and cream layer) and were not homogenous. The manufacturer had done Product Complain #4
investigation on the issues and concluded that the problem arise due to incompatibility On May 2014, patient who was prescribed of the cream with the packaging bottle jar with Latanoprost 0.005% w/v eyedrop which result in changes in the texture of zinc PHARMACY BULLETIN, VOL 2/2015 SEPTEMBER 2015
cream. Additional contributing factor could be exposure of the product to extreme high temperature ( 40°C). Therefore, manufacturer had stopped the production of zinc cream until the problems can be overcome. Product Complain #6
bronchopneumonia. For both of the cases, Patient was prescribed with IV Meropenem despite after at least 5 days of treatment, at a dose of 40mg/kg TDS for the treatment patient's condition remained clinically ill of sepsis. However, after 7 days of with spiking temperature, elevated white cell treatment, patient's condition remained count and C-reactive protein. However, both critically ill and blood tests suggest patients' condition improved once antibiotic worsening of infection, blood culture and therapy was converted to similar medication sensitivity remained positive and C-reactive from the same class (Ceftriaxione and protein is still elevated. After investigation Cefepime injection). Overall, Cefuroxime was done by manufacturer, results revealed injection did not show good efficacy in that the batch of medications affected was treating both of these patients. As this was produced up to standard and the quality and the first case reported to National specification of the medications was Pharmaceutical Control Bureau (BPFK) on Cefuroxime injection, BPFK conducted laboratory tests on the sample from same batch of medication reported. However, the Product Complain #7
results confirmed that the affected batch of medications fulfilled the required quality On December 2015, doctor reported 2 cases specification. Therefore, BPFK concluded of ineffectiveness of Cefuroxime injection in the possibility of external factors diminish the treatment of partially treated the efficacy of the medications. PHARMACY BULLETIN, VOL 2/2015 SEPTEMBER 2015
The annual incidence of SLE averages 5 cases per 100,000 populations in United States. The Centers for Disease Control and Prevention (CDC) estimates a range between 1.8 and 7.6 per 100,000 persons per year in the continental United States [1]. In Malaysia, it is estimated that more than 10,000 people
have been diagnosed with SLE over the past 30 years. However, this number may be only the tip of the iceberg. The Malaysian SLE Association believes that there are many more SLE sufferers in Malaysia who have not been diagnosed [2]. More than 90% of cases of SLE occur in women, frequently starting at childbearing age within the range of 15 to 50 years old [3] DEFINITION:
Systemic Lupus Erythematosus (SLE) is a chronic, auto-immune disease of unknown cause wher e the patient's body makes large quantities of blood proteins called anti-bodies that react against the person's own tissues [2]. The word "systemic" means the disease can affect many parts of the HISTORY:
The term ‘lupus' (Latin for ‘wolf') was first discovered by Dr.Cazenave in 1851 when he noticed red rashe s on a patient's face that looked like wolf bites. He named the rash Discoid Lupus Erythematosus (DLE). In 1885, Sir William Osler recognised that many people with lupus had a disease involving not only the skin but many other organs or systems. He named the disease Systemic Lupus Erythematosus (SLE) [2]. PHARMACY BULLETIN, VOL 2/2015 SEPTEMBER 2015
Immune responses against endogenous nuclear antigens are characteristic of SLE. Autoantigens releas ed by apoptotic cells (UV-related and/or spontaneous) are presented by dendritic cells to T cells lea ding to their activation. Activated T cells in turn help B cells to produce antibodies to these self- constituents by secreting cytokines such as interleuki n 10 (IL10) and IL23 and by cell surface molecules such as CD40L and CTLA-4. In addition to this antigen-driven T cell-dependent production of autoa ntibodies, recent data support T cell- independent mechanisms of B cell stimulation via combine d B cell antigen receptor (BCR) and TLR signaling. Immune reactants such as immune complexes amplify and sustain the inflammatory response. The pathogenesis of SLE involves a multitude of cells and molecules that participate in apoptosis, innate ad adaptive immune responses [4]. Ultraviolet rays (UV rays) from fluorescent light sensitive to the TRIGGER

Emotional stress or physical stress PHARMACY BULLETIN, VOL 2/2015 SEPTEMBER 2015
Management of SLE depends on their symptoms and severity. Used to treat pain, sw elling and fever associated with lupus. Example: Naproxen sodium and Ibuprofen.
Common side effects of NSAIDs can include stomach upset, heartburn, diarrhoea, and fluid retention Help control lupus. Example: Hydroxychloroquine
Antimalarial drug
Side effects of anti- malarials can include stomach upset and, extremely rare, damage to the retina of the eye. Counter the inflammation of lupus. Example: Prednisolone/ Prednisone
Short-term side effect s of corticosteroids include swelling, increased appetite, and weight gain. Long-term side effects of corticosteroids include osteoporosis, high blood pressure, hig h cholesterol, diabetes, damage to the arteries, infections, and cataracts. Suppress the immune system may be helpful in serious cases of lupus. Example: Azathioprine, Mycophenolate, Leflunomide, Belimumab
Side effects may include nausea, vomiting, hair loss, bladder pr decreased fertility, and increased risk of cancer and infection.

Centers for Disease Control and Prevention. Systemic Systemic lupus erythematosus (SLE) is an lupus erythematosus (SLE or lupus). Available at autoimmune disease in which the body's Accessed: 23 June 2015. immune system mistakenly attacks healthy Malaysia SLE Association. Available at tissue. It can affect the skin, joints, kidneys, brain, and other organs. More than 90% of cases of SLE occur in women, frequently Ginzler E, Tayar J. Systemic lupus erythematosus (lupus). Updated: January 2012. Available at starting at childbearing age. Management of SLE often depends on the individual Accessed: March 15, 2012. patient's disease severity and disease Medscape. Systemic Lupus Erythematous.Available at Accessed: 23 June 2015. 5.Foundation of America.Lupus.Available common-triggers-for-a-lupus-flare.Accessed: 23 June 2015. PHARMACY BULLETIN, VOL 2/2015 SEPTEMBER 2015
Myocardial Infarction (MI) & Thrombolytic Agents
Cardiovascular Disease (CVD) is a medical spectrum of heart diseases ranging from ST segment elevation myocardial infarction (STEMI), non-STEMI to unstable angina depending on the degree of the disease. In Malaysia, CVD remained to be the major cause of mortality in year 2013 which accounted for approximate 25% of all death in both public and private hospitals nationwide. [1] Therefore, up till today, a total of 12 Clinical Practice Guidelines (CPGs) had been published by MOH to guide healthcare professionals in the management of CVD. Besides, study showed that the in-hospital and 30-day mortality following STEMI is as high as 10% and 14% respectively. [2] STEMI is a medical emergency condition where clinical diagnosis is done based on the presence of myocardial injury or necrosis as indicated by Imaging evidence of new loss of viable abnormalities in serum cardiac bio-markers myocardium or new regional wall in addition to one of the following criteria motion abnormality • Identification of an intracoronary (IC) • Clinical history consistent with chest thrombus by angiograpy or autopsy pain of ischaemic origin Due to the severity and urgency of the • Electro-cardiogram (ECG) changes of disease, appropriate treatments must be ST segment elevation or presumed Left given as promptly as possible from time of Bundle Branch Block (LBBB) onset as most deaths occur during pre- PHARMACY BULLETIN, VOL 2/2015 SEPTEMBER 2015
hospital phase. According to guideline, pain In Hospital Putrajaya, Streptokinase is management and reperfusion therapy is the the most generally used agent for acute core management for patient with acute myocardial infarction despite it is less STEMI. Two main approaches of effective in term of reducing mortality rate reperfusion therapy are primary in compared to fibrin specific agent such as percutaneous coronary intervention (PCI) Tenecteplase.[4,5] This is because according and fibrinolytic therapy. to Malaysia Ministry of Health Drug Ideally, PCI is the preferred choice of Formulary, Tenecteplase should be reserved reperfusion strategy if both options are for treatment where Streptokinase is readily available. However, unfortunately, contraindicated or patient with prior PCI is not readily available at all health care Streptokinase exposure. Streptokinase is centers, so fibrinolytic agents will be the antigenic and will induce production of choice of therapy in the absent of PCI antibody by the recipients, therefore, services with the condition time from onset reducing the efficacy of the agent if it is re- to treatment is less than 3 hours. [2] If administered after 5 days of first fibrinolytic agent is indicated, it should be administered within 30 minutes from arrival On the other hand, being a new fibrinolytic agent, Tenecteplase has the Currently, there are four fibrinolytic advantage of fibrin specific action, agents available in Malaysia Ministry of resistance to plasminogen activator Health Drug Formulary, namely inhibitor-1 (PAI-1), longer duration of Streptokinase, Urokinase, Alteplase, and action and cause more rapid perfusion of the Tenecteplase. However, among the four occledded artery. In addition, Tenecteplase medicines, only three are available in can be administered as a single bolus dose Hospital Putrajaya where Alteplase is not over 5 seconds in compared to older agents which require infusion up to 1 hour. Streptokinase and Urokinase are All in all, usage of Tenecteplase is considered the older generation of limited by its higher cost and indication fibrinolytic agents while Tenecteplase is the stated in the drug formulary despite it being newer agent. The older agents had few more effective than Streptokinase in clinical disadvantages over the newer one treatment of acute myocardial infarction. such as low specificity for fibrin, allergenic Therefore, it is necessary to formulate a (particularly Streptokinase) and short half proper guideline or criteria on the selection life.[2,3] On the other hand, newer agents of fibrinolytic agent to prevent any delay in have overcome all the insufficiency of treatment of acute myocardial infarction. In aforementioned agents with increased fibrin conclusion, time is the essence in the specificity, increase resistance to inhibition management of acute myocardial infarction of plasminogen activators, longer duration as timely administration of fibrinolytic of action and rapid reperfusion. However, therapy gives significant impact on the drawback of the newer agents is due to it has high cost.[2,3] HPJ PHARMACY BULLETIN, VOL 2/2015 SEPTEMBER 2015
The table below summarizes a comparison between Tenecteplase and Streptokinase. [2,6,7] Fibrinolytic Agents
Older Fibrinolytic Agent
Newer Fibrinolytic Agent
Streptokinase 1,500,000IU Injection Tenecteplase 10,000IU (50mg) Injection Tissue Plasminogen Activator Indication in
Acute myocardial infarction, acute Acute myocardial reinfarction where pulmonary embolism streptokinase is contraindicated due to previous streptokinase induced antibodies. [Indicated when antibodies was given more than 5 days and less than 12 months] Mechanism of Action
Initiates activation of endogenous Promotes initiation of fibrinolysis by fibrinolytic system upon binding to binding to fibrin and converts plasminogen, producing complex that plasminogen to plasmin possess activator properties and accelerate the transformation of plasminogen into the proteolytic and fibrinolytic plasmin Myocardial Infarction :
Single bolus dose (over 5 seconds) of not
1.5mega units over 30 – 60 minutes. exceed 50mg, based on patient body Pulmonary embolism:
 < 60kg: 30mg 250,000 units by IV infusion over 30  60 to < 70kg: 35mg minutes, then 100,000 units every hour for  70 to < 80kg: 40mg up to 12 – 72 hours with monitoring of  80 to < 90kg: 45mg clotting factors  > 90kg: 50mg Contraindication &
1) Risk of Intracranial Haemorrhage 2) Risk of Bleeding Precaution
 History of intracranial  Active bleeding (excluding  Ischaemic stroke within 3 months  Significant head trauma within 3  Structural cerebral vascular lesion  Suspected aortic dissection Streptokinase should not be use in patient who is hemodynamically unstable and with hypotension (BP < 90/60 mmHg). Transient fall in blood pressure is common during intravenous infusion of Streptokinase. Ionotropic support should be given prior to fibrinolytic therapy. Elimination Half Life
Elimination Half life: 80 mins Elimination Half life: 90 to 130 mins Fibrin Specificity
Antigenic Effects
Systemic Fibrinogen
1. Health Facts 2013. Malaysia: Health Information Centre, Planning and Development Division, Ministry Of Health Malaysia, 2013. 2. Clinical Practice Guidelines: Management of Acute ST Segment Elevation Myocardial Infarction (STEMI) 2014 – (3rd Edition) 3. Dundar Y, Hill R, Dickson R, Walley T. Comparative Efficacy of Thrombolytics in Acute Myocardial Infarction: A Systemic Review. The Association of Physician, 2003; 103-113. 4. National Institute for Health and Care Excellence (NICE). Guidance on the Use of Drugs for Early Thrombolysis in the Treatment of Acute Myocardial Infarction. 2002. 5. Armstrong PW, Collen D. Fibrinolysis for acute myocardial infarction: current status and new horizons for pharmacological reperfusion, part 1. Circulation 2001; 103: 2862-6 6. Dana WJ, Fuller MA, Corbett AH, Gonzales JP, editors et. al. Drug information Handbook (Lexicomp). 24th ed. p. 1996-97. 7. Glickman, S. W., Cairns, C. B., Chen, A. Y., Peterson, E. D., & Roe, M. T. (2010). Delays in fibrinolysis as primary reperfusion therapy for acute ST-segment elevation myocardial infarction. American heart journal, 159(6), 998–1004.e2. PHARMACY BULLETIN, VOL 2/2015 SEPTEMBER 2015
Patent Ductus Arteriosus (PDA)
The ductus arteriosus (DA) is a blood vessel shunting of blood and undesirable that connects two major arteries which are pulmonary, renal and gastrointestinal the aorta and the pulmonary artery. DA is effects, including pulmonary edema and important for fetus because baby lungs are hemorrhage, congestive vascular accidents, not functioning while in the amniotic fluid. necrotizing enterocolitis (NEC), feeding The baby gets nutrition and oxygen directly intolerance, poor weight gain, from the mother's placenta, so DA divers bronchopulmonary dysplasia (BPD) and blood away from the lungs to protect lungs death. Therefore, once the diagnosis against circulatory overload. confirmed, appropriate treatment should be In term baby, the ductus usually given to prevent the morbidities. undergoes constriction and functional Conservative medical management, closure within the first day of life so that the pharmacological therapy or surgical ligation right ventricular output passes through the is the treatment option available. For lungs to facilitate proper gas exchange since pharmacological therapy, NSAID the DA is no longer needed. Patent Ductus (indomethacin, ibuprofen) is the common Arteriosus (PDA) is failure in closure of the drug choice for PDA. However, recently patent ductus that causing poorly some of the studies show that high dose of oxygenated blood flow in the wrong paracetamol seems have some positive direction. PDA is a cardiovascular response for PDA treatment. Both NSAID abnormality which is commonly happen in and paracetamol causing the closure of the preterm infant that the closure is delayed ductus by inhibit the prostaglandin or does not occur. Failure of the PDA to close leads to hemodynamically significant left to right PHARMACY BULLETIN, VOL 2/2015 SEPTEMBER 2015
Both NSAID and paracetamol causes prostaglandin F2α, prostaglandin E2, the closure of ducts by inhibiting the prostaglandin I2 and thromboxane A2. The prostaglandin H2 synthetase (PGHS) enzyme production of arachidonic is inhibited by which is responsible for the production of NSAID through COX binding site while prostaglandin. PGHS enzyme has two paracetamol inhibits the coversion of PGG2 binding sites which are cyclooxygenase to PGH2. Prostaglandin reduction results in (COX) and the peroxidase (POX) site. The muscular constriction of the COX binding site converts arachidonic acid arteriosus with profound hypoxia in the to prostaglandin G2 (PGG2) by oxidation. ductal vasa vasorum. This causes topical The POX binding site then converts PGG2 to angiogenesis, neo-intima formation and prostaglandin H2. The prostaglandins H2 apoptosis. Together with platelet (PGH2) later will be synthesized to recruitment, this will result in obstruction, fibrosis and anatomic closure. PHARMACY BULLETIN, VOL 2/2015 SEPTEMBER 2015
Pharmacotherapy Treatment For PDA
Paracetamol Syrup
(of label use)
Drug class
Nonsteroidal Anti- Nonsteroidal Anti- inflammatory Drug (NSAID) inflammatory Drug Mechanism
COX inhibitors block the conversion of arachidonic acid Paracetamol inhibit prostglandins of Action
to various prostaglandins that are involved in maintaining production by inhibit the POX the patency of the ductus arteriosus in the fetus. IV or oral Indomethacin IV or oral Ibuprofen 15mg/kg per dose every 6 hours 0.2mg/kg/day daily dose for 10mg/kg first dose, 5mg/kg second and third doses, administered by syringe pump over 15 minutes at 24 hour Advantages Decrease cerebral blood
Less COX 1 inhibition resulting in less free of the adverse effects consumption to a great vasoconstrictive side generally associated with degree than ibuprofen. This effects on gastrointestinal, traditional associated with a cerebral and renal NSAID in preterm neonates, preventative effect in the including peripheral occurrence of IVH vasoconstriction, gastrointestinal oliguria, impaired platelet aggregation, and/or hyperbilirubinemia. - Stronger COX 1 - No preventative effect No safety profile yet especially advantages
inhibition, resulting in the occurrence of Intraventricular gastrointestinal, cerebral haemorrhage (IVH) and renal side ef ects. - Increase the risk of - Indomethacin more profoundly decreases renal blood flow, resulting in significant oliguria and an increase in serum creatinine levels. - Increase the risk of bilirubin encephalopathy PHARMACY BULLETIN, VOL 2/2015 SEPTEMBER 2015
Paracetamol Syrup
(of label use)
- Infant is proven or - Infant is proven or indications
suspected to have suspected to have infection that is infection that is - Bleeding, especially - Bleeding, especially active gastrointestinal or active gastrointestinal or intracranial. - Platelet count: < 60 - Platelet count: < 60 x - NEC or suspected NEC - NEC or suspected NEC - Duct dependant - Duct dependant congenital heart disease congenital heart - Impaired renal function: creatinine > 140 μmol/L, - Impaired renal function: blood urea >14 mmol/L. creatinine > 140 μmol/L, blood urea >14 Pharmaco- - Half-life elimination 4.5
- Half- life elimination in - Half-life elimination neonates 7 hours; prolonged in premature infant (highly hours (range:4 to 10 hours) variable between - Rapid onset of action - Onset of action 30 studies) 23 to 75 hours - Acetaminophen mainly - Onset of action 30 to metabolite in hepatic. - Indomethacin significant - Ibuprofen metabolite in hepatic via oxidation. Cathy Hammerman, Alona Bin-Nun, Einat Markovitch, Michael S. Schimmel, Michael Kaplan et al. Ductal Closure With Paracetamol: A Surprising New Approach to Patent Ductus Arteriosus Treatment. American Academy of Pediatrics 2013; 1-6. Ramesh Agarwal, Ashok K Deorari, Vinod K Paul. Patent Ductus Arteriosus in Preterm Neonates. Department of Pediatrics All India Institute of Medical Sciences 2007; 1-16. KC Sekar and KE Corff. Treatment of patent ductus arteriosus: indomethacin or ibuprofen? Journal of Perinatology 2008; 28:1-3 Karel Allegaert, Brian Anderson,Sinno Simons, Bart van Overmeire. Paracetamol to induce ductus arteriosus closure: is it valid? 2013; 1-6. Charles F, Lora L., Morton P, Leonard L, et al. Drug Information Handbook, 24th Edition, 2015 - 2016; 32-6, 1032-36, 1067-70 7. Frank Shann. Drug Doses. Intensive Care Unit Royal Children's Hospital, Australia. 6th edition, 2014. p. 50, 52. Paediatric Protocols for Malaysian Hospital 3rd Edition, 2012. p. 133. Ohlsson A, Shah PS. (2015) Paracetamol (acetaminophen) for patent ductus arteriosus in preterm and low-birth-weight infants [online] March 2015. Available from: [Accessed:7 July 2015] OXFORD HANDBOOK OF NEONATOLOGY 2012. p. 191. 10. Dani C. Ibuprofen and paracetamol for patent ductus arteriosus. J Pediatr Neonat Individual Med. 2014;3(2):e030226. doi:


Microsoft word - decamp et al final manuscript revised lp edits revised wd.doc

Childhoods Today, Volume 10, Issue 1, 2016 Motivation is Key: The Differing Predictors of Adolescents' Nonmedical Use of Prescription Drugs Whitney DeCamp, Western Michigan University; James Herzig, Western Michigan University; Brooke O'Neil, Western Michigan University; Daniel O'Connel , University of The nonmedical use of prescription drugs (NMUPD) persists as a problem

Kno c he nmarke rkrankung e n Priv.-Do z. Dr. Ro land Re pp Me dizinis c he Klinik V Klinikum Bambe rg Was will ic h Ihne n e rzähle n … • Funktion des Knochenmarks • Welche Symptome werden durch ein gestörtes Knochenmark verursacht? • Was sind die häufigsten Erkrankungen des Knochenmarks? • Wie werden diese Erkrankungen