PHARM

Several effective arms to this policy have been implemented. The Australian Pharmaceutical Health and Rational Use of Medicines (PHARM) Committee has placed QUM high in priority on the national health agenda. QUM is considered to mean: (1) selecting management options wisely; (2) choosing suitable medicines if considered necessary; and (3) using medicines safely and effectively. Information sources supported include the journal Australian Prescriber, the Therapeutics Resource and Educational Network for Doctors (TREND), Therapeutic Guidelines and the Australian Medicines Handbook, as well as Consumer Medicine Information (CMI) handouts, which are usually included inside packs of medicines or are available from pharmacists. Barriers to QUM were identified, such as waste or hoarding of medicines, inappropriate demand and poor compliance. Many campaigns on using medicines wisely have been supported at national, state and local levels.

NPS

The Australian National Prescribing Service (NPS) was set up (1998) with representation from doctors and pharmacists to improve health outcomes for all Australians, enhance continuity of QUM programs and coordinate activities influencing prescribing. The NPS has the mission to improve health outcomes for all Australians through QUM. Through its educational activities targeted to doctors, pharmacists, nurses, other health practitioners, consumers and the pharmaceutical industry, the NPS has achieved some significant savings in drug costs. Its computer-based prescribing curriculum is being adopted and implemented by many medical schools, and is seen as providing excellent training of medical students in clinical pharmacology and prescribing of drugs, previously a serious deficit in many programs which led to inadequate prescribing skills in new medical graduates.

New Zealand Medicines Strategy

In New Zealand, the Preferred Medicines List provides guidelines aimed at achieving QUM in the health system in that country (see also CIB 2-2 later). The Pharmacology and Therapeutics Advisory Committee (PTAC) and the Best Practice Advocacy Centre have responsibility for implementing the WHO Medicines Strategy, and are working on developing a New Zealand National Formulary. Primary Health Organisations (PHOs) are funded by District Health Boards to provide essential primary health care services to those people who are enrolled with the PHO (see CIB 2-2). PHARMAC (the Pharmaceutical Management Agency) has responsibility for purchasing medicines and managing supplier contracts under a capped national medicines budget; this has effectively kept down the costs of subsidising drugs compared to the escalating costs in many other developed countries.

New technologies

Until the early 20th century, most drugs were from natural sources such as plants (morphine, cocaine), minerals (iodine, iron) and animals (vaccines, tissue extracts). As chemical industries developed, synthetic and semisynthetic drugs such as antibacterial sulfonamides, thiazide diuretics, volatile general anaesthetics, corticosteroids and oral contraceptives, safe antihypertensives and effective antipsychotic agents became available. Genetic engineering has produced human insulin and other hormones and proteins. Many older, less effective and less safe drugs (such as bromide hypnotics and mercurial diuretics) have become obsolete.

New uses for old drugs

Drugs are sometimes found to have additional uses to those for which they were initially developed. Minoxidil, an antihypertensive agent, was found to cause increased growth of hair and found a new use as a hair restorer. Methylphenidate, originally an appetite suppressant and stimulant, found new application in treating attention deficit hyperactivity disorder.

Better understanding of mechanisms

The discovery of the mechanism of action of aspirin (inhibiting synthesis of prostaglandins) led to further evaluation of its actions. Results of clinical trials showed that subjects receiving aspirin suffered fewer adverse cardiovascular events, demonstrating the antithrombotic actions of aspirin, hence its now widespread prophylactic use against heart attacks and strokes.

Better understanding of aetiology of disease

The evolution of better drugs to treat peptic ulcers followed studies over many decades of the causes of peptic ulcers. First, sedatives were prescribed to reduce stress, then antacids to neutralise gastric acid, then antimuscarinics, histamine H₂-receptor antagonists and proton-pump inhibitors to reduce production of acid, and recently antibacterials to reduce infection with Helicobacter pylori were added to the gastroenterologist’s armamentarium. Similarly, rapid advances in understanding of the biochemical pathways involved in control of cell division have led to many new anti-cancer drugs (Chapters 41 and 42).

Old ‘remedies’ proven useless

For centuries syphilis was treated with arsenic- or mercurycontaining compounds, perhaps because no effective treatment was available. These very toxic medicines were used for hundreds of years despite a total lack of efficacy. Only when safe oral antibacterials became available (and the concept of clinical trials developed) did arsenicals and mercurials drop out of pharmacopoeias.

Drug combinations shown to be unjustified

Complex combinations of drugs (galenicals) date back to the time of the ancient Greek physician Galen (CIB 1-3; Figure 1-1). Even into the mid-20th century, doctors often wrote prescriptions for complex mixtures ‘for nerves’ or as ‘tonics’—see an example in Figure 2-3A. Frequently, combinations of antimicrobials or of antihypertensives were formulated together. It is now recognised that it is usually better to prescribe drugs individually, as doses can then be adjusted individually and the drug with the longer half-life does not accumulate and cause toxicity, or the drug with the shorter half-life drop below the therapeutic level.

Changes in popularity of drugs

There is a recognised cycle in popularity of many new drugs (as for many new gadgets): as a drug is developed and marketed—often aggressively to both prescribers and consumers—it rapidly surges in popularity. Adverse reactions inevitably become apparent and its expense is noted, so its use wanes. Then, as rational evidence of the benefits and risks are evaluated, the drug regains a medium but more stable position in the drug usage charts (Figure 2-1).

Figure 2-1 The ‘action potential of popularity’ of a new drug

after Figure 1 in Clinical Pharmacology 5th edn, DR Laurence and PN Bennett, Churchill Livingstone, Edinburgh, 1980.

Changes in availability of drugs

There may be a major change in the use of a drug as it is moved between drug schedules (see Chapter 4) and becomes either more or less readily available or expensive. When the histamine H₂-receptor antagonists were introduced, they rapidly became very popular and hospital drug budgets blew out. Restrictions were placed on the frequency of their prescribing to rationalise their use and costs. Similarly, when new COX-2 inhibitors (celecoxib, rofecoxib) and statins (simvastatin etc) were introduced in Australia, they were very expensive. Public (and drug company) pressure led to their being subsidised and listed on the PBS, when their use skyrocketed, at great expense to governments (i.e. taxpayers). However, when patent protection for new drug molecules expires, other companies can legally manufacture and market the drug, so competition (hopefully) reduces the price.

Withdrawal of useful drugs

Drug companies may decide to discontinue production and marketing of a useful drug for various reasons: an old drug may become redundant or unprofitable, an old manufacturing process become obsolete, rare unexpected adverse reactions may become apparent, a disease may become much less prevalent or company mergers may bring competitor products into the same ‘house’. However, there can be important implications for patients who may have been stabilised on a particular drug for many years and are intolerant or unresponsive to other drugs. Change to a new drug may cause withdrawal reactions, recurrence of illness or new ADRs or interactions. A coordinated approach between drug companies, government and health professional organisations is required to minimise these problems.

The ‘popularity action potential’ for rofecoxib

A good example of the caution necessary in rapidly prescribing new drugs is the case of the COX-2 inhibitor rofecoxib (Vioxx). This anti-inflammatory agent was introduced in Australia in 1999 after trials in over 5000 patients who had received it for less than 6 months; there was a reported low overall incidence of thromboembolic events. Rofecoxib rapidly became very popular (as was celecoxib) for treatment of painful and inflammatory conditions in patients who might be at risk of gastrointestinal side effects from the older NSAIDs. Meanwhile, analyses of cardiovascular events occurring during larger-scale longer trials and post-marketing use showed that people taking 25 mg rofecoxib daily over a long term had about double the risk of heart attacks and strokes compared to placebo (more details are given in CIB 47-2, and reviews by Jones [2005] and Krumholz et al [2007]). The drug was withdrawn in Australia in 2004; since that time, related COX-2 inhibitors have been closely monitored for similar effects. (Hundreds of patients in Australia have joined legal class actions against the manufacturer of rofecoxib, claiming that the manufacturer knew about the increased risk of cardiovascular events long before the drug was withdrawn. It is reported that, in the year before its withdrawal, the manufacturer Merck reaped revenue of at least US$2.5 billion from sales of Vioxx.)

Cost-effectiveness of new drugs

To be listed by the Australian Pharmaceutical Benefits Scheme (PBS) as a subsidised drug, a drug must be proved to be not only safe and effective but also cost-effective, which requires an economic evaluation of the additional cost of any extra benefit over the current standard therapy. Listing as a ‘restricted benefit’ or as ‘authority required to prescribe’ helps limit the PBS use of a drug to those in whom it will be most effective.

For example, a cost-effectiveness analysis of the platelet aggregation inhibitor clopidogrel compared to aspirin in secondary prevention of coronary heart disease showed that clopidogrel alone or in routine combination with aspirin would add a cost of $130,000 (US$, 2002) per quality-adjusted year of life gained³ (see Gaspoz et al [2002]). The Australian approved indications for authority to prescribe clopidogrel list only a few very specific situations in which the drug can be subsidised by the PBS, for example to prevent recurrence of stroke or heart attack in patients who are unable to take aspirin safely. The National Prescribing Service guidelines conclude that ‘clopidogrel has similar efficacy to aspirin plus dipyridamole … low-dose aspirin is a more affordable option for people who do not meet the PBS authority restrictions for clopidogrel’ (NPS News 62, 2009).

The ‘doctor’s bag’ of drugs

Traditionally, doctors visiting patients in the community carried a black bag holding various drugs that the doctor could supply or administer as needed, particularly in emergencies. These ‘doctor’s bag’ supplies may also be important for emergencies or other serious medical conditions that occur in the surgery or office. The PBS still allows doctors to carry such drugs, most of them in parenteral (injectable) form and subsidised by the PBS; choice depends on practice location, conditions likely to be encountered and shelf-life of the formulation. Examples are adrenaline (for cardiac arrest and severe allergic reactions), atropine (for cardiac arrhythmias or poisoning with insecticides), benzylpenicillin (for bacterial infections especially meningococcal), haloperidol (for psychiatric emergencies), frusemide (a potent diuretic drug used in hypertension and acute pulmonary oedema), hydrocortisone (an anti-inflammatory and immunosuppressant agent), lignocaine (anti-arrhythmic and local anaesthetic), glucagon (for hypoglycaemia), morphine (to treat severe pain and pulmonary oedema) and naloxone (an opioid antagonist used to treat overdose with opioids such as heroin). Other non-injectable drugs include soluble aspirin tablets (first-line treatment for anyone suspected of having had a myocardial infarction), diazepam (sedative, antianxiety and anticonvulsant), glyceryl trinitrate spray or patch (for angina or myocardial infarction), salbutamol aerosol (for asthma), methoxyflurane inhalation (for painful procedures on conscious trauma patients) and possibly antiemetics (to prevent vomiting), antibiotics and analgesics. It is suggested that doctors also carry supplies of normal saline and water for injection, as well as a sharps container, disposable gloves and dressing packs. Logbooks of supplies need to be kept, and a system for checking expiry dates implemented (see Baird [2007]).

Nurse practitioners

In several countries, laws have been changed recently to allow nurses with special expertise and training (including in pharmacology and principles of prescribing) to apply for endorsement as nurse practitioners. The scope of the role is still being established and models are being trialled and evaluated in consultation with doctors and pharmacists.

The Australian Nursing and Midwifery Council (ANMC) has developed a set of National Competency Standards for the Nurse Practitioner (see http://www.anmc.org.au/professional_standards), in which a nurse practitioner is defined as follows:

It is envisaged that the scheme might include permission for approved nurse practitioners, in their defined area of expertise, to:

In part, this movement is in response to the problems in country areas where there are insufficient doctors. There is at present no single published formulary of drugs that nurse practitioners may prescribe, but the process of diagnosis, drug choice, prescribing, counselling and monitoring therapy would be within the guidelines of the QUM program. Examples of areas in which nurse practitioners may specialise are rural health, diabetes management, drug and alcohol management, geriatric medicine, palliative care and sexual health. It is recognised that, for optimal implementation of the changes, nurse practitioners will also need to be able to access MBS and PBS subsidies for their prescribing, as well as indemnity insurance (see McMillan and Bellchambers [2007]).

In New Zealand, registered Nurse Practitioners™ are classed as designated prescribers under the 1999 Medicine Act Amendments and can prescribe medicines from the schedule of the Medicines (Designated Prescriber: Nurse Practitioners) Regulations (2005) or Schedule 1A of the Misuse of Drugs Regulations (1977) (http://www.legislation.govt.nz/). Prescription of medicines must be within the Nurse Practitioner’s designated area of clinical practice. Under the auspices of the Health Professionals Competence Assurance Act (2003), the New Zealand Nursing Council has responsibility for approval of the scope of practice and registration of Nurse Practitioners. Competency requirements for New Zealand Nurse Practitioners and scopes of practice can be found on the New Zealand Nursing Council website: http://www.nursingcouncil.org.nz/download/68/guidelines-np-sept09.pdf.

Compounding by pharmacists

Traditionally, most of a pharmacist’s work involved compounding of medicines, i.e. the preparation and supply of a single unit of a product, such as an oral mixture, intended for immediate use by a specific consumer. Nowadays virtually all drugs are bought in by a pharmacist from a mass-manufacturing drug company supplier, and the pharmacist selects, dispenses into a suitable container, labels and provides the medicine, with appropriate counselling. However, compounding is still taught as part of the pharmacy school curriculum, and pharmacies are required to maintain basic compounding equipment for this purpose, although they no longer must be able to prepare and sterilise specialised formulations such as eye-drops or parenteral injections. Some compounding is still done, mainly in hospital pharmacies, as many preparations are not available in paediatric formulations or in sugar-free mixtures, or patients may be able to swallow oral solutions but not tablets. Extemporaneously prepared medicines are not subject to control by the Therapeutic Goods Administration (TGA), and so there are risks attached to their preparation and use. The Pharmaceutical Society of Australia has developed professional standards for compounding practice (see Feldschuh [2008]).

Clinical pharmacy

In hospitals, pharmacists also carry out many specialist roles, such as filling and maintaining ward stocks of drugs (imprest cabinets and drug trolleys); preparing sterile parenteral solutions, parenteral nutrition solutions and oncology drugs; and participating in ward rounds, medication history reviews, drug usage evaluations, therapeutic drug monitoring, advice on drug therapy and provision of drug information as specialists in drug therapy. Pharmacists in retail practice often take on responsibilities for medication management services, i.e. overview of the drug therapy of people in nursing homes and domiciliary medication reviews for patients in their own homes.

Compliance

Obviously the primary determinant of drug response is whether or not the person takes the drug.⁵Compliance means following all aspects of a treatment plan. In the context of drug therapy, it implies administering the drug according to the five rights (see Nurses’ roles, above). All the other advice given related to therapy must also be followed, including lifestyle aspects such as diet modification, weight reduction, cessation of smoking and moderation in alcohol intake. This can be demanding and, when many drugs are prescribed, may become a formidable challenge. Poor compliance may involve taking either too little or too much of the drug, or taking it at the wrong time or with other medicines, whether prescribed or OTC.

There are many causes of poor compliance, such as:

The consequences of poor compliance are more serious than just wasted drugs and time. Drug levels in the body may fall below the therapeutic range, leading to inadequate responses and lack of effect, or may rise to potentially toxic levels and cause adverse drug reactions. The doctor cannot properly monitor and adjust therapy if lack of response is due to poor compliance and may waste effort in revising the diagnosis, increasing doses, adding more drugs or sending the patient for more tests. In particular situations, poor compliance with therapy may result in pregnancy (oral contraceptives), convulsions (antiepileptic drugs), strokes or heart attacks (anticoagulant or antithrombotic drugs).

Studies have shown that good compliance is the exception rather than the rule and, despite Hippocrates’ warning, that doctors are not good at predicting which patients are likely to be good or poor compliers. Ways of assessing compliance include careful counts of tablets or other dose forms remaining after a specified period (but patients can get cunning in flushing away the tablets they should have taken) and assays (measurements) of drug levels in blood samples—see later section, ‘Therapeutic Drug Monitoring’.

It must be recognised that people have a right to autonomy in their own medical care and may justifiably refuse to take drugs for good reasons. However, it is important that the prescribers be made aware if drugs are not being taken as directed, so that allowances can be made and doses altered or different drugs substituted as appropriate.

Drug interactions

After a person has been stabilised on repeated doses of a drug, the responses to the drug may be affected by interactions with any other drug taken, including non-prescribed OTC drugs and CAM therapies, as well as other ingested compounds such as food and drinks. As a person takes, or a patient is prescribed, more and more drugs, the possibility of drug interactions rises exponentially. The topic of drug interactions is discussed in Chapter 9 and in individual Drug Monographs where clinically relevant. There are exhaustive lists of common drug interactions in reference texts such as the Australian Medicines Handbook (Appendix), MIMS Annual (Index to Drug Interactions Table) and Avery’s Drug Treatment (Appendix B: Guide to Clinically More Important Drug Interactions).

Drug interactions may involve either the pharmacokinetics of the drugs involved (e.g. monoamine oxidase inhibitors inhibiting the metabolism of many other drugs) or pharmacodynamic aspects (e.g. antihistamines and alcohol having additive CNS-depressant effects, or β-blockers used for hypertension and β₂-agonists used for asthma having opposing effects on receptors).

Polypharmacy

Polypharmacy is defined as ‘the concurrent use of multiple medications’, usually five or more drugs including prescribed, OTC and CAM. In the clinical context, it has the connotation of implying prescription and use of too many or unnecessary drugs, or use at frequencies greater than therapeutically essential. Polypharmacy is thus a situation in which multiple drug interactions can occur and is potentially harmful to the patient.

An Australian National Health Survey (1995, reviewed in NPS Newsletter 13, 2000) found that 10.7 million Australians—almost 60% of the population—were taking prescribed or OTC medications (excluding CAM therapies) at any one time. If CAM had been included, the proportion would have been much higher. Of those using at least one medication, 14.5% were taking four or more drugs and 4.6% were taking six or more. In persons over 75 years, the proportions were about 40% and 17%, respectively. This very high reliance on drugs (Australia has been called ‘the overmedicated society’) means that many people are at high risk of adverse drug reactions and drug interactions, and older people particularly are at risk of falls (see Hilmer [2008]).

Polypharmacy is not the sole responsibility of prescribing doctors; various health professionals can initiate the steps recommended for managing and avoiding polypharmacy:

A case involving polypharmacy, and a successful resolution of the problems, is described in Clinical Interest Box 2-3.

Placebo effect

The Latin word placebo literally means ‘I will please’. In the pharmacological context, it refers to a harmless or inactive preparation prescribed to satisfy a patient who does not require an active drug. In a clinical trial, it is formulated to look identical to the active drug under trial, to maintain ‘double blinding’, so that neither subject nor clinician knows which treatment group the subject is in.

Patients and subjects in trials frequently appear to respond to placebos, with therapeutic or adverse effects. This ‘placebo response’ may be a significant but temporary alteration in the person’s condition, due to the person’s expectations or other unexplained psychological effect. Factors possibly inducing the response include the relationship between the patient and the health professional, the wish to be seen to respond, response to the increased care and attention and aspects such as the colour and taste of the dose form or pain on injection (no gain without pain).

What is the problem?

The question is: ‘What is going wrong here?’ A full health history may take at least 30 minutes to complete and should list all the patient’s current problems, including medications, past drug history, allergies, ADRs and interactions, relevant family history, use of social drugs such as alcohol and tobacco and CAM therapies, and all treatment modalities being used. For effective treatment the starting point is the problems specified in terms of pathophysiology or altered anatomy or psychology, not necessarily a proven diagnosis.

Is there a drug-based solution?

There may not be a drug-based solution to the problem—not all medical problems are currently treatable with pharmacotherapy. It is important to attempt to identify what changes need to be brought about in the person’s functioning and whether drug treatment can cure the condition or improve symptoms. Practitioners should keep an open mind here and consider all modalities—surgery, nursing care, physiotherapy, podiatry, lifestyle changes (e.g. diet, exercise, stress levels), psychotherapy, CAM methods and combinations of therapies, as well as drug treatment.

If so, which drug?

Assuming that there are safe, effective drugs available to treat the problem, there are many decisions to be made:

What does the drug do and how does it act?

What is known about the drug’s pharmacodynamics? What actions does it have and what is the mechanism—does it affect receptors, enzymes, ion channels, transport processes? How will this affect the person’s problems? What do we not know that could be important? What are the common ADRs and potential drug interactions? Checking a drug monograph for the drug is helpful here.

How long will the patient be treated?

This requires knowing the usual course of the condition and prognosis. Will the patient get better after a few days of treatment (e.g. after an acute infection), might there be ongoing relapses and remissions (as with multiple sclerosis) or will the condition progress relentlessly (as do diabetes and dementia)? Are there long-term effects of the drug?

How will you monitor therapy?

The patient’s progress must be monitored to evaluate effects of the therapy. It is possible to monitor several parameters (see later section on therapeutic drug monitoring):

How much drug should be given?

What dose is being prescribed, for what effect, and is it appropriate? Doses need to be individualised so do not feel you have to rely on memory—look it up! Pharmacokinetic principles will determine the frequency of dosing and possibly the appropriate route. The drug’s therapeutic index will determine how critical the exact dose is. The route may determine the formulation or there may be choices: if oral, will it be tablets, capsules, a mixture, a sustained-release form?

What is special about this patient?

If the patient is not the standard 70-kg fully functioning adult, what is the patient’s age and weight? Is the person particularly susceptible to adverse effects? Might a woman patient be pregnant or breastfeeding? How effective are the liver and kidney functions likely to be? (These affect pharmacokinetic parameters such as protein binding and drug elimination, and are discussed in Chapters 6–8). Are there other concurrent medical conditions? Is the drug contraindicated in any of these situations? Are there relevant socio-cultural aspects relating to values, beliefs, cultural differences or restricted income that might affect compliance or responses to therapy? Is the person taking any other medications, whether prescribed, OTC or CAM? If so, what drug interactions are possible or clinically significant?

Can you write (or dispense, or administer) the prescription?

Are the ‘five rights’ (patient, drug, dose, route, time) right? Does the prescription seem appropriate? Does it conform with PBS and institutional requirements and QUM guidelines? Are the instructions to the patient adequate and correct? (See later under ‘Prescriptions’.)

Are there any warnings for the patient or staff?

Patients have the right to get as much medical information as they want. In particular, they need to know about their condition, why a drug is being prescribed and for how long, whether it is to treat the disease or to relieve symptoms and how and when to take the medicine. Patients need to be warned about possible significant adverse reactions, how to recognise them and what to do if they occur, drug and food (and alcohol) interactions and what to do if they miss a dose. Printed consumer product information should be included in the drug package with all relevant details. Patients’ carers, both family and nursing staff, may also need warnings about some adverse reactions to help them in their roles.

Prescriptions

A prescription must be clear, concise and correct. It has elements that can be correlated with the five nursing rights of medication administration: the patient’s name, address and age (right patient); date written; generic or proprietary drug name (right drug); drug dose, strength and dosage form (right dose); route of administration (right route); dosage instructions or frequency of administration (right time); and bears the signature, name, address and contact number of the prescriber. The number of times the prescription can be repeated should also be specified.

All the elements should be clearly written to avoid any chance of error; for example, if there is any chance that ‘μg’ might be read as ‘mg’, then the word ‘microgram’ should be written in full or abbreviated to mcg. Formerly, it was required that prescriptions be written indelibly in the prescriber’s own handwriting, but now they can be computer-generated and printed. All efforts must be made to prevent forgery of details or of entire prescriptions. Only accepted abbreviations should be used (see below). If any confusion or doubt exists, the prescriber is contacted for clarification.

It is suggested that, for good prescribing practice, prescribers should have a finite list of ‘personal preferred drugs’ (their P-list), with which they are very familiar, and feel confident in their ability to evaluate new information and prescribe wisely.

Telephone orders and standing orders

Drugs are also sometimes prescribed by doctors as ‘telephone orders’ or standing orders if the doctor cannot be present at the time. A doctor may telephone a drug prescription through to a pharmacist, who is legally entitled to dispense the prescription, and to a nurse entitled to administer it on the oral instructions. The doctor must then, as soon as is practicable, write out the drug order on a prescription pad, sign it and post or deliver it to the pharmacy or use the hospital drug chart. A faxed prescription copy can confirm an oral order but is not legally acceptable, as the signature has to be original, i.e. in the doctor’s handwriting; the pharmacist must see the original prescription before releasing the drug to the client.

‘Standing orders’ are sometimes left by doctors as ongoing prescriptions in a hospital, nursing home or residential care setting. These have no legal validity unless properly written, dated and signed as for any normal prescription. Repeating prescriptions without clinical review of the patient brings the risks of unnecessary and/or unsafe drug use.

Hospital drug charts

Prescriptions in hospitals are usually written on a drug chart or medication therapy chart (Figure 2-3C). These can become quite complicated and may run to many pages in a patient’s medical record, as patients in hospital are frequently prescribed 10–15 drugs during one stay. In a typical chart, the users are instructed:

Specialised medication charts are also available to record phone orders, comments on administration discrepancies and errors, IV orders (covering fluids administered, drip rates and additives), diabetes management and fluid balance. There are also forms designed for recording other aspects of health care, such as for physiotherapy and podiatry progress notes, nursing admission data, neurological observations, patient’s consent to treatment, delivery and neonatal records and residential care information.

Instructions and abbreviations in prescriptions

A clearly written drug order specifies the conditions for drug administration; for example, a routine order means that the drug is administered until discontinued by the prescriber; a prn (pro re nata = when necessary) order is administered only when needed by the patient, while a stat (statim = immediately) order is for immediate administration of one dose of medication.

Many abbreviations and symbols are used in drug ordering (see Table 2-1 for a list of commonly used forms). Use of abbreviations can lead to potentially serious errors in administration; only those shown asterisked (Table 2-1) are recommended by the Australian Medicines Handbook. Drug names should never be abbreviated; if there is any possibility of confusion, all words should be written in full: ‘If in doubt, write it out!’

Table 2-1 Common abbreviations and symbols in prescriptions^*

Abbreviation	Unabbreviated	Form meaning
*ac	Ante cibum	Before meals
ad lib	Ad libitum	Freely
am	Ante meridiem	Morning
*aq	Aqua	Water, aqueous
*bd, bid	Bis die, bis in die	Twice each day
c	Cum	With
*cap	Capsule	Capsule
cc, cm3	Cubic centimetre	Cubic centimetre (=1 mL)
D5W	Dextrose 5% water	5% Dextrose in water (5 g/100 mL)
DW	Distilled water	Water purified by condensation from steam
EC	Enteric-coated	Tablet or capsule formulation whose coating prevents dissolution until reaching the small intestine
elix	Elixir	Elixir
*g, gm	Gram	1000 milligrams
gtt	Gutta	Drop
h, hr	Hora	Hour
hs	Hora somni	At bedtime
IA	Intra-arterial	Into an artery or arteriole
ID	Intradermal	Into the skin
*IM	Intramuscular	Into muscle
*inj	Injection	Injection
IT	Intrathecal	Into the subarachnoid space
IU	International Unit	Unit of pharmacological activity for a particular drug, as defined by an international convention
*IV	Intravenous	Into a vein
IVPB	IV piggyback	Secondary IV line
kg	Kilogram	1000 grams
KVO	Keep vein open	Very slow infusion rate
L	Litre	Litre (1000 cm3)
M	Mitte	Send, supply
*mane	Morning	In the morning
μg, mcg	Microgram	One millionth of a gram
*mg	Milligram	One thousandth of a gram
mEq	Milliequivalent	One thousandth of the gram equivalent weight of a solute in an electrolyte solution mist Mistura Mixture
*mL	Millilitre	One thousandth of a litre, 1 cm3
NG	Nasogastric	Into the stomach via the nose
*nocte	At night	At night
NS	Normal saline	0.9% Sodium chloride solution
oc	Oculorum	Eye
os	Os	Mouth
OTC	Over-the-counter	Non-prescription drug
otic	Otikos	The ear
*pc	Post cibum	After meals
pm	Post meridiem	After noon
PO	Per os	By mouth, orally
PR	Per rectum	Into the rectum
*prn	Pro re nata	According to necessity (lit. for the thing [i.e. need] having arisen)
PV	Per vagina	Into the vagina
q	Quaque	Every
*qd, qid	Quater in die	Four times a day
qh	Quaque hora	Every hour
q4h, qqh	Quaque quarta hora	Every 4 hours
qs	Quantum satis	Suffficient quantity
	Receipt, recipe	Take (or dispense, provide)
s	Sine	Without
SC	Subcutaneous	Into subcutaneous tissue
Sig.	Signature	Label, instructions
SL	Sub linguam	Under the tongue
SOS	Si opus sit	If necessary
ss	Semis	A half
*stat	Statim	At once
*tab	Tablet	Tablet
tbsp	Tablespoon	Tablespoon (15 mL)
*tid or TDS	Ter in die	Three times a day
TO	Telephone order	Order received over the telephone
top	Topically	Applied to the skin
tsp	Teaspoon	Teaspoon (4 or 5 mL)
U	Unit	A dose measure for insulin, heparin
ung	Unguentum	Ointment
VO	Verbal order	Order received verbally
×	Times	As in two times a week

* Only the abbreviations marked with an asterisk are approved by the Australian Medicines Handbook.

Electronic prescribing

General practitioners (GPs) in Australia have been encouraged to adopt the use of computers in their practices. A study in 2000 showed that about 65% of GPs used electronic prescribing packages. While there are some disadvantages (initial cost, information overload, invasion of patient’s privacy, intrusiveness of advertising), the advantages are many:

There are risks that drug company advertisements included in prescribing packages will influence the prescriber’s choice of drugs.

Underprescribing

The most common type of sub-optimal prescribing is underprescribing, where drugs are not prescribed despite guidelines recommending them, or doses are subtherapeutic. Elderly people in particular are often not treated optimally; for example, ACE inhibitors and statins are used less effectively than recommended.

Inappropriate prescribing

Overprescribing (e.g. various NSAIDs for different conditions in one patient) and irrational prescribing (such as antibiotics for viral infections, or cough suppressants in productive cough) also contribute to unsuccessful prescribing. Prescribing errors occur frequently, particularly when busy prescribers in hospitals or general practice fail to consider all the ‘questions to answer’ before prescribing.

Tablets

The oral route of administration is by far the most common: about three-quarters of all drugs prescribed are administered orally and, of these, about 60% are in tablet form. Tablets are compressed mixtures of active drug with various other chemicals, called excipients, which assist in the formulation. For example, pharmacologically inert chemicals may be present as diluents (fillers), binders, adhesives, disintegrants, lubricants, flavours, colours, sweeteners or absorbents. Thus the active drug may make up only a very small fraction of the total tablet weight. The weight quoted for the tablet (e.g. aspirin tablets commonly 300 mg) refers to the average amount of active drug in the tablet; the whole tablet will actually weigh considerably more.

Tablets may appear as simple white discs or may be multilayered or coated with a film⁷ to mask an unpleasant taste. Some tablets are prepared for sublingual administration (dissolved under the tongue) or as effervescent tablets that fizz and dissolve in water so that they are easier to take.

Tablets may also be available for use by a pharmacist or scientist in preparing solutions of particular strengths.

The rate of release of active drug from a tablet—and thus the drug concentration in the circulation and at the active site—can be manipulated by pharmaceutical processing. Finely ground powders are more quickly dissolved than are coarse powders or granules. It is possible to combine an active drug with a resin or other substance from which it is slowly released, to delay absorption (sustained-release [SR], or controlled-release [CR] preparations). In addition, it is possible to prepare a tablet with a coating that offers relative resistance to the digestive action of stomach contents (enteric coating, EC). Enteric coatings on drugs are used:

Other oral dose forms

Other formulations for oral administration include capsules, solutions, elixirs, powders, syrups and lozenges; further pharmaceutical detail about these dose forms is beyond the scope of this text.

Parenteral administration

Parenteral administration of drugs is the administration of drugs by injection and is the most rapid form of systemic therapy. The intravenous (IV) route, in which the drug is injected directly into the circulation, avoids any delay during absorption. Other parenteral routes include intradermal (into the skin), intramuscular, intra-arterial and subcutaneous (into the fatty tissue under the skin); specialist techniques for local anaesthetics include the epidural (= extradural) and intrathecal routes—see Figure 14-10.

Equipment and solutions

Because any injection is an invasive procedure with the potential for infection being introduced, drugs formulated as solutions for parenteral administration must be sterile, filtered, particle-free and preferably isotonic with body solutions (i.e. with normal saline, 0.9% sodium chloride solution) and buffered to body pH. Solutions that are acidic or alkaline, hypertonic or contain irritant drugs can damage tissues into which they are injected. If solid particles are injected, they can cause granulomas, ischaemia or phlebitis.

Usually, parenteral solutions consist of the drug dissolved in an aqueous solution, but in some cases a drug that is very insoluble in water and which must be administered parenterally, such as the general anaesthetic propofol (Drug Monograph 14–3), can be formulated in an oily emulsion suitable for injecting.

Solutions for injection are usually presented in glass ampoules or bottles or plastic bags. The equipment for delivery of a drug by an IV infusion is complicated (Figure 2-4) and may include sterile tubing, an in-line filter and drip chamber, clamps to adjust the flow rate and a cannula for insertion into the vein. Most institutions will have guidelines as to the use of such IV sets, with lists of appropriate infusion solutions and possible admixtures (agents added to IV fluids). Compatibilities of drugs with parenteral drug solutions are dependent on many chemical and physical factors. The general rule is that, unless an admixture is specifically allowed, it should not be made, unless a hospital pharmacist or drug information centre has approved the addition. (As always, if in doubt, don’t!)

Figure 2-4 Diagram of a typical intravenous infusion set-up, showing a secondary ‘piggyback’ bottle with a reservoir of drug in IV fluid; the main solution is now most commonly contained in a plastic pack.

For example, it is recommended that morphine sulfate (a powerful pain-reliever) can be injected during infusion with dextrose, saline, dextrose/saline or Hartmann’s solution, and mixed in a syringe with metoclopramide (an antiemetic) or bupivacaine (a long-acting local anaesthetic), but must not be mixed in a syringe or pack with aminophylline, flucloxacillin, phenytoin or several other listed drugs (see Murney [2008]).

Procedures for monitoring by plasma concentration

The drug concentration measured will be compared to the therapeutic range (published values of the concentration of the drug in plasma at steady state during effective therapy [Css]). This is reached after about five half-lives during regular dosing; the plasma drug concentration will fluctuate between peaks and troughs—see Figure 8-6. Therapeutic ranges are valid for about 80% of the population and are a good guide to expected plasma concentration of the drug. Trough levels (the lowest level likely to be in blood, measured by taking a blood sample immediately before the next dose) are usually assayed. In some situations, e.g. to avoid toxic levels, peak levels are measured at the time of maximum plasma concentration.

Drug concentration is measured by highly accurate and specific techniques such as immunoassay, highperformance liquid chromatography (HPLC), gas chromatography or flame photometry.

Typical procedure

The usual procedure for TDM is:

If the therapy appears well controlled, further measurements may be taken 6–8 weeks later and again at 6–12-monthly intervals.

Drug screens

Drug screens are a particular example of TDM by drug blood levels, in which samples taken from patients are screened for the presence of a range of drugs, usually for medicolegal reasons. They may be carried out to detect drugs of abuse, drugs possibly taken in overdoses or, in the forensic context, to detect poisons. Almost any body fluid can be screened, as well as solid tissues such as hair, bone or nails. False-positive results may arise from interference from other drugs that have been appropriately taken, and false-negatives because of levels below the detection limit, owing to inappropriate sampling time or insufficiently sensitive methods. Some toxic substances that are rapidly metabolised, including insulin, succinylcholine and potassium, may be undetectable by any method after a delay (see CIB 2-4).