ISSN 1391-0736

The Sri LankaPrescriber

The Sri Lanka Prescriber is sponsored bythe State Pharmaceuticals Corporation of Sri Lanka

as a service to the medical profession.

December 2012; Volume 20, No. 4

Prescribing for the elderly 1

How to communicate instructions on taking medicinesto your hearing disabled patient 4

Hypertensive disorders of pregnancy 8

Self-assessment questions 14

CONTENTS

The Sri Lanka

PrescriberEditorsProfessor Gita Fernando MBBS, FRCP, FCCP

Professor Colvin Goonaratna MBBS, FRCP, FRCPE, FCCP, PhD, DSc

Professor Laal Jayakody MBBS, MRCP, PhD

Editorial BoardChinta Abayawardana Diploma in Pharmacy

Dr Anuja Abayadeera MBBS, FRCA, MD

Dr Nanda Amarasekara MBBS, MD, FRCP, FCCP, FRACP

Dr Shamya de Silva MBBS, DCH, MD

Dr Priyadarshani Galappatthy MBBS, MD, MRCP, DMT

Dr Chamari Weeraratne MBBS, MD

Dr A M O Peiris BDS, FDSRCPS, FFDRCS

Dr Hemamali Perera MBBS, MRCPsych, MD

Professor Harshalal Seneviratne MBBS, FRCOG, DM

Professor Anura Weerasinghe MBBS, MD, FRCP, DCH, DTM&H, PhD, FCCP

Copies of the Sri Lanka Prescriber and inquiries from M. P. Kuruppu,Deputy General Manager, Marketing, and Ms Anusha Gunatilleke,Manager Promotions and Publicity (Telephone 2338102), StatePharmaceuticals Corporation, P. O. Box 1757, 75, Sir BaronJayathilake Mawatha, Colombo 1.Price per copy Rs 50.00 (students Rs 25.00). Personal callers mayalso obtain copies from the Departments of Pharmacology atthe Medical Faculties in Colombo, Galle and Sri Jayewardenepura.

Published byDepartment of PharmacologyFaculty of Medicine271, Kynsey Road, Colombo 8, Sri Lanka.Telephone: + 94 11 2695300 Ext 315E-mail: phrm_cmb@hotmail.comandState Pharmaceuticals Corporation75, Sir Baron Jayathilake Mawatha, Colombo 1.Telephones + 94 11 2320356-9Fax: + 94 11 447118E-mail: prmanager@spc.lk Web site: www.spc.lk

Printed byAnanda Press82/5, Sir Ratnajothi Saravanamuttu Mawatha,Colombo 13.Telephone: + 94 11 2435975E-mail: anpress@sltnet.lk

(Secretary to Board and member)

Cover picture

(About 1886)

The French retail pharmacist, Stanislas Limousin,introduced many devices to Pharmacy and Medicine. Hisgreatest contributions were invention of glass ampoules;the medicine dropper; and apparatus for inhalation ofoxygen.

One of a series: A History of Pharmacy in Pictures, presented by Parke, Davis& Company.George A. Bender, Director © 1957 Robert A. Thom, Artist

STANISLAS LIMOUSIN, PHARMACAL INVENTOR

1Sri Lanka Prescriber, Vol. 20, No. 4, 2012

Prescribing for the elderly

Ours is a fast ageing population. The proportion ofadults over the age of 60 years that was a little over9% in year 2000, rose to over 13% by 2011, and isexpected to rise to over 22% by 2031. Yet geriatricsis not a recognised medical speciality here in eitherState or private health care sectors. In our country,with a population of about 21 million there is not asingle designated specialist geriatrician in clinicalpractice, whereas in the UK with a population ofabout 63 million in 2011 there were 1100 geriatricsspecialists in active practice.

But geriatric specialist clinicians form only a smallpart of an ideal health care system. To make it bothefficient and effective for older adults, developedcountries employ a wide range of other health profes-sionals such as specialist nurses, physiotherapists,occupational and speech therapists, and medical socialworkers in large numbers adequately trained to fulfillthe health care needs of the elderly – but Sri Lankahas very few or none of them. Facilities for mediumor long term institutional care of the elderly are utterlyinadequate; most of the available few are shockinglyfilthy, and frequently frankly negligent or worse. It isin the context of this forlorn background that cliniciansare called upon to protect the life and health of ourelderly mothers, fathers and grand-parents. So let usresolve at least to do what we must to prescribe safely,in accordance with the best available evidence.

Age determined pharmacokinetic and pharma-codynamic changesThe absorption, distribution, metabolism and excretion(ADME processes) of many medicinal drugs aremodified by ageing. In clinical practice the mostimportant change is a decline of renal function withage, which reduces the glomerular filtration rate(GFR), and hence renal excretion of water solubledrugs and their metabolites [1]. These effects areparticularly important for drugs with narrow ratios ofthe desired therapeutic effect to toxic effect such asdigoxin, gentamicin and lithium.

Creatinine clearance is used as a surrogate for GFR.It is calculated from the serum creatinine using theCockroft-Gault formula and reported as eGFR(estimated GFR), normalised to a body surface area(BSA) of 1.73m2. Table 1 gives the staging of renalimpairment in chronic kidney disease (CKD) based

on the NICE guideline 73 (September 2008). Oldpeople tend to have a reduced lean body mass, hencea reduced BSA, which influence both measured bloodcreatinine level and creatinine clearance.

Table 1. Degrees of renal impairment inrelation to calculated eGFR

(NICE guideline: 73)

Degree of impairment eGFR ml/min/1.73 m2

Normal (stage 1) >90*

Mild (stage 2) 60 - 89*

Moderate (stage 3) 30 - 59

Severe (stage 4) 15 - 29

Renal failure (stage 5) < 15

(* with other evidence of renal disease)

Other changes that may significantly affect drugpharmacokinetics in the elderly include reduction ofliver parenchymal cell mass, hepatic blood flow, andgastrointestinal motility and absorptive capacity.Bioavailability of drugs that undergo hepatic first passmetabolism, especially the ones with a high hepaticextraction ratio, may be increased as a consequenceof diminished hepatic functional capacity [2]. Thereduction of total body water (TBW) in old peoplereduces the volume of distribution (VD) for watersoluble drugs and metabolites, hence increases theirblood levels. Others factors that often operate todiminish TBW and VD in the elderly include areduced sensitivity to changes in plasma osmolalityof the cranial osmoreceptor centre and consequentlythe thirst centre, coupled with polyuria as a result ofdiabetes or CKD.

Apart from pharmacokinetic issues, the elderly aremore sensitive to the effects on the central nervoussystem of many drugs, for example benzodiazepines,antidepressants and antipsychotics.

Polypharmacy

Polypharmacy in the elderly patient may be the resultof inappropriate prescribing or rational therapeutic

2 Sri Lanka Prescriber, Vol. 20, No. 4, 2012

intervention for multiple appropriate indications.Irrespective of the cause polypharmacy is linked to anumber of negative outcomes including adverse drugreactions (ADRs), drug interactions, falls, hospitaladmissions, duration of hospital stay and mortality rate[3].

The incidence of negative outcomes of polypharmacymay be minimised by stopping drugs that are notproviding the expected benefit, prescribing only clearlyindicated new drugs, using simple drug regimens,reviewing prescribed medications regularly, and usingonly doses recommended for the elderly.

The Beers criteria for avoiding certain drugs inthe elderly

Since the pharmacokinetics and pharmacodynamicsof drugs change with ageing, an American consensusguideline referred to as the Beers criteria were

Table 2. Some drugs from updated Beers criteria selected from the 2003 list [4],with concerns regarding use in elders

Drug Concerns Rating

Pentazocine Narcotic analgesic, causing confusion hallucinations High

NSAIDS, Aspirin Exacerbation of peptic ulcers, haemorrhage; renal impairment High

Indometacin Highest incidence of CNS effects of all NSAIDs, exacerbation Highof peptic ulcer, haemorrhage

Meprobamate Highly addictive and sedating; falls High

Digoxin Toxicity with decreased GFR and hypokalaemia High

Glibenclamide Prolonged hypoglycaemia High

Amitriptyline Strong anticholinergic action and sedation (Avoid tricyclic Highantidepressants)

Diazepam, Flurazepam Long acting sedation, loss of balance, falls, High

Promethazine, Anticholinergic actions, sedation. Prefer non-anticholiuergic HighChlorphenamine, antihistamines eg cetirizineDiphenhydramine etc

Nitrofurantoin Potential renal impairment. Avoid in CKD. Safer alternatives available High

G.I.T. antispasmodics: Highly anticholinergic, and uncertain effectivenessPropanthelineMebeverine

(*High = High risk of side-effects and/or ADRs)

developed and published in 1991. They have beenlast updated in 2003 [4], and provide a list of drugsregarded by an expert panel as especially likely tocause problems in the elderly. Some drugs includedin the 2003 list are given in table 2.

Adverse drug reactions and side-effects

An adverse drug reaction (ADR) is defined as aharmful or seriously unpleasant reaction to an intendedtherapeutic, prophylactic or diagnostic dose of amedicinal drug that necessitates its withdrawal, dosereduction or prohibition from future use. A side-effectis a minor reaction that occurs with therapeutic doses,is predictable and usually dose related. Both ADRSand side-effects are commoner in the elderly than inyoung adults [3]. Since the elderly often have severalmedical problems requiring multiple medicinal drugs,the incidence of harmful drug-drug interactions is alsohigher in them.

3Sri Lanka Prescriber, Vol. 20, No. 4, 2012

Good prescribing for older adults

Much has been written and spoken about this topicover the last 3 to 4 decades, and several studies fromdeveloped countries have reported slow but steadyimprovement of prescribing practices with continuingeducation of clinicians and nursing staff [5]. We dohave numerous educational programs on varioustopics including good prescribing for practicingclinicians organised by many medical institutions andassociations in Sri Lanka, but I am not aware ofsystematic and reliable studies of their outcomes ortheir outreach. The management of health problemsof the elderly is too important a matter to be left tounplanned, uncoordinated and unsystematicapproaches. Nor should educational programs aboutelderly health care rest predominately in the hands ofthe private sector whose primary objective is themarketing and sale of health care and health careproducts. The Ministry of Health is the appropriateand principal authority for continuing education of allhealth care professionals and other staff.

Consider the UK as an example. Although theproportion of its population over the age of 60 yearsis about 20%, this group receives about 60% of allprescriptions and accounts for over 52% of NHS drugcosts [5]. I do not mean to say or imply therefore

that cost saving rather than benefits to patients is orshould be the prime objective of good prescribing.Earlier on in this essay I have indicated the negativeeffects of polypharmacy on older patients and thehealth services as a whole. Table 3 lists some guidelinesderived from several sources for good prescribing inolder patients.

References

1. Mangoni AA, Jackson SHD. Age-related changes inpharmacokinetics and pharmacodynamics; basicprinciples and practical applications. British Journalof Clinical Pharmacology 2003; 57: 6-14.

2. Milton JC, Hill-Smith I, Jackson SHD. Prescribingfor older people. British Medical Journal 2008; 236:606-9.

3. Frazier SC. Health outcomes and polypharmacy inelderly individuals. Journal of Gerontology Nursing2005; 31: 4-11.

4. Fick DM, Cooper JW, Wade WE, et al Updating theBeers criteria for potentially inappropriate medicationuse in older adults. Archives of Internal Medicine2003; 163: 2716-24.

5. Franklin BD, O’Grady K, Donyal P, et al. The impactof a closed-loop electronic prescribing andadministration system on prescribing errors,administration errors and staff time: a before-and-afterstudy. Quality and Safety in Health Care 2007; 16:279-84.

Professor Colvin Goonaratna, MBBS, FRCP (Lond and Edin), PhD, FCCP. Co-editor, Sri Lanka Prescriber;Chair, Sri Lanka Clinical Trials Registry. Email <si7np5e@gmail.com> I have no competing interests withregard to my designations or this article.

Table 3. Some guidelines for good prescribing in elderly patients

Consider non-pharamacological treatments such as counselling where appropriate (eg senile tremor,loss of taste or smell, memory failure without other signs of dementia, dizziness)

Stop current drugs that are not indicated

Prescribe an additional drug only when clearly indicated

Prescribe the recommended dosages for the elderly

Use simple regimens, using a few appropriate clearly indicated drugs

Use once daily dosing and fixed dose combinations when possible

Discuss the drugs and the regimen with the patient and care givers

Review medication regularly

4 Sri Lanka Prescriber, Vol. 20, No. 4, 2012

IntroductionOne may be born with a hearing disability (congenitaldeafness) or develop a hearing disability after birth(acquired deafness). Hearing community and especiallyhealth professionals consider deafness as a pathologicalcondition. However, congenitally deaf individuals identifythemselves as a separate ethnic group or a communitycalled the ‘Deaf community’ and consider deafness asa different experience rather than a disability. Hencethey use a capital “D” in “Deaf” to imply that they arefrom a different community.

They use sign language to communicate and sharehabits, traditions and beliefs which are common tothem but socially and culturally different from others.In interacting with hearing disabled people, healthprofessionals should understand their thinking andrespect their ideas so as not to embarrass them andhurt their feelings.

Hearing disabled individuals need to take medicinesfor both communicable and non-communicablediseases, acute and chronic. Some become pregnantand may need to take medicine during pregnancy.Some are parents and need to administer medicinesto their children. In short, they need medicine just asmuch as people with good hearing.

Communication barrier makes using medicinesdifficultHearing disabled people face difficulties in usingmedicines due to communication difficulties withdoctors and pharmacists.

1. They have difficulty communicating their healthproblems to doctors.

2. They may not understand the questions askedby doctors during the medical consultation.

3. They may not understand the instructions givenby the doctor or pharmacist on how to takethe medicines.

4. They may find it difficult to clarify any queriesthey have on taking medicines.

5. They may find it difficult to rememberinstructions given by health providers regardingmedicines.

How to communicate instructions on takingmedicines to your hearing disabled patient

These communication barriers hinder safe andeffective medicine use among this community, causedissatisfaction and frustration and poor complianceto treatment. Hence doctors and other health profes-sionals looking after their health needs should havethe knowledge and skills to communicate medicinalinstructions and information effectively to this specialgroup.

During a study done in Sri Lanka it was found thathearing disabled patients frequently felt left out fromthe discussion during medical consultations. Most ofthe time doctors conveyed the necessary informationonly to the interpreter or relative accompanying thepatient, ignoring the patient completely. Healthprofessionals should pay attention to this finding andtry to develop communication skills to rectify thisdeficiency.

How to improve communication with yourhearing disabled patientThe following are some suggestions to improve theinterpersonal communication with the patient.

1. The doctor should be seated so that his face isnot in the dark and the patient can see theexpressions on his face well. Especially if youare going to use a lip reading method with yourpatient this is very important.

2. You should welcome the patient with a friendlygesture such as gently touching his shoulderor shaking his hand.

3. Look at the patient even when you are pro-viding instructions and information on using themedicines to a relative or a sign language inter-preter. Do not communicate with the inter-preter ignoring the patient.

4. You should smile and maintain eye contact withyour patient as much as possible throughoutthe consultation.

Communication methodsThe following are some useful ways to communicatewith hearing disabled patients. Different patients havedifferent preferences and abilities to use these

8 Sri Lanka Prescriber, Vol. 20, No. 4, 2012

Hypertensive disorders of pregnancy

SummaryHypertensive disorders of pregnancy arecommon and represent a spectrum of diseaseranging from chronic and gestational hyper-tension to eclampsia. They are associatedwith increased risk of both adverse maternaland fetal outcomes.

Drug treatment is generally reserved formoderate or severe hypertension. Pre-eclampsia-eclampsia can be life-threateningand requires urgent investigation andintervention. There are limited data about

Key words: antihypertensives, breastfeeding, pre-eclampsia

(Aust Prescr 2012;35:47-50)

ConclusionsCommunication difficulties with doctors and difficultiesin understanding a written language are major limita-tions that hinder medicine use by the deaf and mute.There is a risk of developing negative attitudes anddissatisfaction in them regarding medicine use becauseof these limitations. Health professionals and policymakers should be aware of and sensitive to these limi-tations to promote safe and effective medicine use inthese patients.

Way forwardOfficial sign language interpreters should be madeavailable at healthcare settings frequented by hearingimpaired patients to enable efficient communication.Pictograms and visual sequence maps should be usedby doctors to improve communication with themduring the medical consultation. Medicine labels usingpictorial methods described above should be used at phar-macies to enable these patients to understand andremember the instructions on using medicines better.

Dr. Chamari Weeraratne, MBBS, MD, Senior Lecturer, Department of Pharmacology, Faculty ofMedicine, University of Colombo, Sri Lanka.Email: chamariweera@gmail.comConflicts of interest: None declared

Suggested reading

1. Munoz-Baell IM, Ruiz MT. Empowering the deaf. Letthe deaf be deaf. Journal of Epidemiology andCommunity Health 2000; 54: 40-4.

2. Luke WANV, Weeraratne CL, Maduranga BBS,Madugalle SSB. Limitations to effective use ofmedicine among deaf students and strategies adoptedby themselves to overcome the limitations, 5thSingapore PHOM and 4th Asian Regional HTAConference, 19 and 20 August 2010.

3. Dealing with Hearing-impaired Patients. [Doctor]Patient.co.uk. [http://www.patient.co.uk/doctor/dealing-with-hearing-impaired-patients] (Last accessed16th May, 2013)

4. Chong-hee Lieu C, Sadler GR, Fullerton JT, et al.Communication strategies for nurses interacting withpatients who are deaf. Dermatology Nursing 2007;19: 541-44; 549-55.

5. Desmon P, Weeraratne CL. Communicating medicineinstructions to hearing disabled consumers. Berlin:Lambert Academic Publishing: 2012.

6. Tijus C, Barcenilla J, de Lavalette BC, Meunier J. Thedesign, understanding and usage of pictograms,Studies in Writing 2007; 21: 17-32.

the safety of many hypertensive drugs inpregnancy. ACE inhibitors and angiotensinreceptor blockers should be avoided.

Women who have had any hypertensivedisorder in pregnancy have an increasedcardiovascular risk. They require long-termfollow-up.

9Sri Lanka Prescriber, Vol. 20, No. 4, 2012

placental abruption, fetal growth restriction, prematuredelivery and stillbirth.3

Pre-pregnancy counselling and management ofchronic hypertension is essential. Some commonlyprescribed antihypertensive drugs are contraindicatedor best avoided before conception and during pregnancy(Table 1). These include ACE inhibitors, angiotensinreceptor antagonists, diuretics and most betablockers.3,4

Where indicated, it is advisable to look for secondarycauses of hypertension before conception, as normalphysiological changes in pregnancy can make manyof these screening tests difficult to interpret. If thisis not possible, with the exception of phaeochromo-cytoma, further investigation is often best deferreduntil the postpartum period. In all cases, preconceptionassessment for proteinuria (with urine protein: creatinineratio) is recommended as a baseline measurement.

TreatmentWith the exception of acute, severe hypertension,treatment with antihypertensive drugs duringpregnancy remains controversial. In many cases, thephysiological fall in blood pressure that occurs duringthe first trimester leads to normalisation without theneed for medication. There is no direct evidence thatcontinued treatment of chronic hypertension leads toa reduction in the risk of adverse pregnancy events.3

IntroductionHypertensive disorders affect 10–22% of pregnan-cies and have been classified into four conditions,reflecting potential differences in aetiology andpregnancy outcomes:1,2

• chronic hypertension

• gestational hypertension

• pre-eclampsia–eclampsia

• pre-eclampsia superimposed on chronichypertension.

The incidence of these disorders is not entirely clear,but pre-eclampsia is thought to affect 5–8% ofpregnancies. Chronic hypertension accounts forapproximately 20% of the cases of high blood pressureseen in pregnancy.1,3

Chronic hypertensionChronic hypertension is diagnosed when hypertensionis confirmed before pregnancy or before 20 weeksgestation (blood pressure >140 mmHg systolic and/or >90 mmHg diastolic).3 However, chronic hyper-tension is frequently diagnosed when high bloodpressure fails to resolve post-partum. Women withchronic hypertension require careful monitoring duringpregnancy as they have an increased risk of adverseevents, including superimposed pre-eclampsia,

Table 1. Antihypertensive drugs to avoid in pregnancy and preconception

ACE inhibitors Contraindicated Teratogenic in first trimester.Fetal renal dysfunction, oligohydramnios andskull hypoplasia in second and third trimesters.

Angiotensin receptor blockers Contraindicated Teratogenic in first trimester.Fetal renal dysfunction and oligohydramniosin second and third trimester.

Diuretics Avoid Fetal electrolyte disturbances, reduction inmaternal blood volume.

Beta blockers (except labetalol Avoid Fetal bradycardia, long-term use of atenololand oxprenolol) associated with fetal growth restriction.

Calcium channel antagonist Avoid Maternal hypotension and fetal hypoxia.(except nifedipine)

Antihypertensive Advice Potential adverse events

10 Sri Lanka Prescriber, Vol. 20, No. 4, 2012

Benefits appear to be confined to reducing severehypertension (≥170/110 mmHg), however mostcentres start or continue antihypertensive drugs whenblood pressure exceeds 160 mmHg systolic and/or100 mmHg diastolic on more than one occasion.3

Table 2 outlines the antihypertensive drugs mostcommonly used in pregnancy.3,4

Blood pressure reduction to 140–160 mmHg systolicand 90–100 mmHg diastolic are acceptable treatmentgoals. Stricter blood pressure control may be asso-ciated with fetal growth restriction, presumed to berelated to relative placental hypoperfusion. Impor-tantly, women need to be carefully monitored for anysigns of pre-eclampsia which may include worseninghypertension and new or worsening proteinuria (seeBox). Repeated assessment of fetal wellbeing andgrowth is appropriate, although given that there areno guidelines, the frequency of monitoring is usuallyat the discretion of the woman’s treating obstetrician.

Gestational hypertensionGestational hypertension is defined as:

• new onset of hypertension after 20 weeks gestation

• no other features to suggest pre-eclampsia (seeBox)

• normalisation of blood pressure within three monthspostpartum.

Gestational hypertension is associated with adversepregnancy outcomes. These are more common if itpresents earlier in the pregnancy, if it progresses topre-eclampsia or if hypertension is severe (≥170/110mmHg).3

Although rare, phaeochromocytoma can initiallypresent in pregnancy. It can be fatal. Investigation isneeded if there are any other features to suggest aphaeochromocytoma (for example paroxysmal hyper-tension, episodic headache and sweating), or if theonset of hypertension occurs early in the pregnancyor is severe. Plasma or urinary metanephrines (cate-cholamine metabolites) tend not to be affected bythe physiological changes of pregnancy and are usefulas screening investigations.5

The benefits of treating mild to moderate hypertensionare limited to the prevention of severe hypertensionand appear to have no effect on the potential foradverse pregnancy outcomes. The indications fortreatment with antihypertensive drugs, goals oftherapy and the choice of drug are similar to thetreatment of chronic hypertension in pregnancy (Table2). Up to 25% of women who develop hypertensionin pregnancy will eventually be diagnosed with pre-eclampsia, even if no other manifestations are presentinitially. Regular monitoring of blood pressure, andinvestigation for proteinuria and other features ofpreeclampsia (up to once or twice per week) isreasonable.3

By definition, gestational hypertension should resolvewithin three months postpartum and the patient cangenerally be weaned off antihypertensive drugs withinweeks. If hypertension has not resolved within threemonths, an alternative diagnosis – for example chronic(essential or potentially secondary) hypertension –needs to be considered. There is a risk of recurrencein subsequent pregnancies so increased monitoringwill be required.

Box

Features of pre-eclampsia

Hypertension with onset after 20 weeksgestation

Renal manifestationsSignificant proteinuriaSerum creatinine >90 micromol/L (or renalfailure)Oliguria

Haematological manifestationsDisseminated intravascular coagulationThrombocytopeniaHaemolysis

Hepatic manifestationsRaised serum transaminasesSevere right upper quadrant or epigastric pain

Neurological manifestationsEclamptic seizureHyperreflexia with sustained clonusSevere headachePersistent visual disturbancesStrokePulmonary oedemaFetal growth restrictionPlacental abruption

11Sri Lanka Prescriber, Vol. 20, No. 4, 2012

Pre-eclampsia, eclampsia and superimposedpre-eclampsiaThe aetiology of pre-eclampsia is unclear although acombination of maternal and placental factors arelikely to contribute. Abnormal placental formation,resulting in aberrant angiogenic factor production andsystemic endothelial dysfunction, as well as geneticand immunological factors, are thought to play a role.Risk factors include nulliparity, age less than 18 ormore than 40 years, a past history of pre-eclampsiaand maternal medical comorbidities (hypertension,diabetes mellitus, renal disease, obesity, antiphos-pholipid antibodies or other thrombophilia and con-nective tissue disease).6 Pre-eclampsia is associatedwith fetal growth restriction, preterm delivery,placental abruption and perinatal death.7 Severe pre-eclampsia has the potential for progression toeclampsia, multi-organ failure, severe haemorrhageand rarely maternal mortality.

Pre-eclampsia is a disorder with many manifestations.

New onset hypertension after 20 weeks gestation andproteinuria are the most common presenting features.A urine dipstick for proteinuria can be a usefulscreening test, but is confounded by high false positiveand false negative rates. If there is any uncertainty,assessment of the urine protein:creatinine ratio isadvised. Peripheral oedema is no longer considereda diagnostic feature of pre-eclampsia as it is neithera sensitive nor specific sign. Other clinical mani-festations are outlined in the Box, with their presencesuggesting severe pre-eclampsia.

The presence of severe pre-eclampsia mandatesurgent review. A multidisciplinary team approach(obstetrician, midwife, neonatologist, anaesthetist andphysician) is often required. Delivery is the onlydefinitive management for pre-eclampsia. The timingof delivery is dependent on the gestational age andwell-being of the fetus and the severity of the pre-eclampsia. The pregnancy is rarely allowed to go toterm. Management of pre-eclampsia before 32 weeks

Table 2. Relatively safe antihypertensive drugs in pregnancy

Antihypertensive Class Starting Dose Maximum Dose Important adverse effects

Labetalol Beta blocker 100–200 mg 400 mg three Bradycardia, bronchospasm,twice a day times a day transient scalp tingling

Oxprenolol Beta blocker 40–80 mg 80–160 mg Bradycardia, bronchospasmtwice daily twice daily

Nifedipine Calcium channel 10 mg twice 20–40 mg Severe headache,antagonist a day, 30 mg twice a day, peripheral oedema

daily controlled 120 mg dailyrelease controlled release

Methyldopa Centrally-acting 250 mg 500 mg four Sedation, light-headedness,twice a day times a day dry mouth, nasal congestion,

haemolytic anaemia,depression

Hydralazine Vasodilator 25 mg 50–200 mg Flushing, headache,twice a day total daily dose lupus-like syndrome

Prazosin Alpha blocker 0.5 mg 3 mg total Postural hypotensiontwice a day daily dose

12 Sri Lanka Prescriber, Vol. 20, No. 4, 2012

gestation should occur in specialist centres withsufficient expertise and experience. Severe hyper-tension may require parenteral antihypertensivedrugs (such as hydralazine), which should only begiven in a suitably monitored environment (birth suiteor high dependency unit). Intravenous magnesiumsulfate is given for the prevention of eclampsia insevere cases.8

Although pre-eclampsia progressively worsens whilethe pregnancy continues, outpatient management maybe considered in selected cases. The antihypertensivedrugs used in pre-eclampsia are the same as thoseused to treat chronic and gestational hypertension(Table 2).3 The treatment goals for blood pressurecontrol are also the same (140–160 mmHg systolicand 90–100 mmHg diastolic). Although widelyadvised in the past, there is little evidence to supportbed rest. Given the potential for venous throm-boembolism from immobilisation, bed rest is generallyonly advised with severe, uncontrolled hypertension.9

Postpartum management and secondarypreventionMost of the manifestations of pre-eclampsia resolvewithin the first few days or weeks postpartum. Thefeatures of pre-eclampsia, including hypertension,may worsen before they improve. Rarely the firstmanifestations occur postpartum. Frequent reviewof blood pressure during this period is essential, forexample once to twice weekly. Antihypertensivedoses are reduced or ceased when the bloodpressure falls to less than 140/90 mmHg. Home bloodpressure monitoring with an automated device canbe helpful to avoid hypotension. This is a commonoccurrence, as the features of pre-eclampsia andtherefore antihypertensive requirements can recedeprecipitously. Like gestational hypertension, if theblood pressure does not normalise within three monthsconsider an alternative diagnosis. It is also importantto confirm that proteinuria has resolved.

Pre-eclampsia can recur in subsequent pregnancieswith the most prominent risk factors being previoussevere or early onset pre-eclampsia or chronichypertension. The use of low-dose aspirin has beenshown to be safe and beneficial in decreasing thisrisk in women with a moderate to high risk of pre-eclampsia. Aspirin is therefore generally advised insubsequent pregnancies. It is started at the end of

the first trimester and can be safely continued untilthe third trimester, with most centres ceasing therapyat 37 weeks gestation. Calcium supplements (1.5 g/day) may be of benefit, particularly in women at riskfor low dietary calcium intake. The administration ofvitamin C and E supplements has not been shown tobe beneficial and may be harmful.3

Antihypertensive drugs postpartumThe choice of antihypertensive drugs depends onwhether breastfeeding is attempted. When the womanwishes to breastfeed, consideration must be given topotential transfer of the drug into breast milk. Mostdrugs safely used in pregnancy are excreted in lowamounts into breast milk and are compatible withbreastfeeding. Table 3 shows antihypertensive drugsto use or avoid during lactation.4 Should there be nodesire to breastfeed and adequate contraception isused, the choice of antihypertensive drug is the sameas for any other non-pregnant patient.

Long-term follow-upPre-eclampsia and gestational hypertension appear tobe associated with an increased long-term risk ofcardiovascular disease, including hypertension,ischaemic heart disease, stroke and venous throm-boembolism.10 There may also be a small increasedrisk of chronic renal failure and thyroid dysfunctionafter pre-eclampsia.11,12 Annual assessments of bloodpressure and at least five-yearly assessments for othercardiovascular risk factors are advisable.3 Thyroid andrenal function should also be measured intermittently.

ConclusionPregnancies affected by hypertensive disordersrequire careful monitoring due to the increased risksof adverse pregnancy outcomes. New onset hyper-tension in pregnancy warrants consideration of pre-eclampsia. Antihypertensive drugs for all forms ofhypertensive disorder of pregnancy tend to bereserved for persistent or severe hypertension. Manystandard antihypertensive drugs are contraindicatedin pregnancy and lactation. In women at moderate tohigh risk for recurrent pre-eclampsia, prophylaxis withlow-dose aspirin and calcium supplements insubsequent pregnancies may be of benefit. Long-termfollow-up, particularly in regard to cardiovascular risk,is important in women with a history of hypertensivedisorders in pregnancy.

13Sri Lanka Prescriber, Vol. 20, No. 4, 2012

References

1. ACOG Committee on Obstetric Practice. Clinicalmanagement guidelines for obstetrician-gynecologists. Diagnosis and management ofpreeclampsia and eclampsia. ACOG practice bulletin.2002;33:1-9. http://mail.ny.acog.org/website/SMIPodcast/DiagnosisMgt.pdf [cited 2012 Mar 6]

2. Brown MA, Lindheimer MD, de Swiet M, Van AsscheA, Moutquin JM. The classification and diagnosis ofthe hypertensive disorders of pregnancy: statementfrom the International Society for the Study ofHypertension in Pregnancy (ISSHP). HypertensPregnancy 2001;20:IX-XIV.

3. Lowe SA, Brown MA, Dekker GA, Gatt S, McLintockCK, McMahon LP, et al. Guidelines for themanagement of hypertensive disorders of pregnancy2008. Aust N Z J Obstet Gynaecol 2009;49:242-6.

4. Australian Medicines Handbook. Adelaide: AMH;2010.

5. Sarathi V, Lila AR, Bandgar TR, Menon PS, Shah NS.Pheochromocytoma and pregnancy: a rare butdangerous combination. Endocr Pract 2010;16:300-9.

6. Milne F, Redman C, Walker J, Baker P, Bradley J,Cooper C, et al. The pre-eclampsia communityguideline (PRECOG): how to screen for and detectonset of pre-eclampsia in the community. BMJ2005;330:576-80.

7. Heard AR, Dekker GA, Chan A, Jacobs DJ, VreeburgSA, Priest KR. Hypertension during pregnancy inSouth Australia, part 1: pregnancy outcomes. Aust NZ J Obstet Gynaecol 2004;44:404-9 .

8. Sibai BM. Magnesium sulfate prophylaxis inpreeclampsia: evidence from randomized trials. ClinObstet Gynecol 2005;48:478-88.

9. Meher S, Abalos E, Carroli G. Bed rest with or withouthospitalisation for hypertension during pregnancy.Cochrane Database Syst Rev 2005;19:CD003514.

10. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease andcancer in later life: systematic review and meta-analysis. BMJ 2007;335:974.

11. Vikse BE, Irgens LM, Leivestad T, Skjaerven R,Iversen BM. Preeclampsia and the risk of end-stagerenal disease. N Engl J Med 2008;359:800-9.

12. Levine RJ, Vatten LJ, Horowitz GL, Qian C,Romundstad PR, Yu KF, et al. Pre-eclampsia, solublefms-like tyrosine kinase 1, and the risk of reducedthyroid function: nested case-control and populationbased study. BMJ 2009;339:b4336.

Further reading

Nelson-Piercy C. Handbook of Obstetric Medicine.4th ed. London: Royal College of Obstetricians andGynaecologists; 2010.

Table 3. Antihypertensive drugs during breastfeeding

Class Drugs considered safe Avoid – Potentially harmful, no or limited data

Beta blockers Propranolol, metoprolol, labetalol Avoid atenolol, no data for other beta blockers

Calcium channel Nifedipine More limited data for diltiazem and verapamil –antagonists may be safe; avoid other calcium channel

blockers

ACE inhibitors Captopril, enalapril Other ACE inhibitors

Angiotensin receptor None No datablockers

Thiazide diuretics None Limited data

Other Methyldopa, hydralazine Limited data for prazosin, consider alternatives

This article is reproduced from the Australian Prescriber 2012; 35: 47-50, by prior arrangement, courtesy ofAustralian Prescriber.

Peter Donovan, Consultant endocrinologist, Fellow in clinical pharmacology, Princess Alexandra Hospital, Brisbane.Conflict of interest: none declared.

14 Sri Lanka Prescriber, Vol. 20, No. 4, 2012ISSN 1391-0736

Printed by Ananda Press, Colombo 13.

1. The commonest pathogenic organism causing community acquired bacterial meningitis is(a) Streptococcus pneumoniae(b) Staphylococcus aureus(c) Pseudomonas aeruginosa(d) Listeria monocytogenes(e) Haemophilus influenzae

2. In community acquired bacterial meningitis empirical antibiotic therapy is best started

(a) immediately after clinical diagnosis, before drawing blood for culture and biochemistry

(b) immediately after clinical diagnosis and drawing blood for culture and biochemistry, butbefore lumbar puncture

(c) after completing drawing blood for culture and biochemistry, and completing lumbarpuncture for CSF

(d) only after the urgent CSF report of low blood glucose, or raised neutrophils ± Gramstain positivity is available

(e) After CSF is sent for analysis and after brain imaging

3. Which of the following combination therapeutic regimens for acne is known to cause benignintracranial hypertension (hence absolutely contraindicated)?

(a) oral contraceptive with an oral anti-androgen, plus benzyl peroxide gel for topicalapplication

(b) oral contraceptive with an oral anti-androgen, plus topical tretinoin once daily(c) oral erythromycin 250 mg bd, plus topical tretinoin once daily(d) oral doxycycline 50 – 100 mg daily, plus topical tretinoin once daily(e) oral doxycycline 50 – 100 mg daily (or oral minocycline 50 – 100 mg daily), plus oral

isotretinoin

Answers to self-assessment questions

Question 1. Correct response is a

Question 2. Correct response is b

Question 3. Correct response is e

All the correct responses are simply matters of fact selected from 2 articles in September 2012issue of the SLP, so explanations are unnecessary.

Self-assessment questions(Select the best response in each question)

Professor Colvin Goonaratna, MBBS, FRCP, PhD, Hon DSc Competing interests: none.