CHAPTER 1

1.0 Introduction

In Yemen as well as in many other developing countries the quality of health services which constitute social indicators of justice and equity is far from being satisfactory. Inappropriate, ineffective, and inefficient use of drugs commonly occurs at different health facilities (Abdo-Rabbo, 1993; Abdo-Rabbo, 1997). Irrational prescribing is a habit, which is difficult to cure. This may lead to ineffective treatment, health risks, patient non-compliance, drug wastage, wasteful of resources and needless expenditure. According to the Yemeni constitution, “patients have the right to health care and treatment” i.e. appropriate care, consent to treatment and acceptable safety. Therefore, health workers should concentrate on making patients better and patients should concentrate on geting better.

Health care in general and particularly the drug situation in any country is influenced by the availability, affordability, and accessibility of drugs as well as the prescribing practices. There are many individuals or factors influence the irrational prescribing such as patients, prescribers, workplace environment, the supply system, including industry influences, government’s regulations, drug information and misinformation (Geest S. V. et al, 1991; Hogerzeil H. V., 1995).Improving rational use of drugs (RUD) is a very complex task worldwide because changing behavior is very difficult. The 1985 Nairobi conference on the rational use of drugs marked the start of a global effort to promote rational prescribing (WHO,1987). In 1989, an overview of the subject concluded that very few interventions to promote rational drug use had been properly tested in developing countries (Laing et al., 2001).

The selection of drugs to satisfy the health needs of the population is an important component of a national drug policy. The selected drugs are called “essential drugs” which are the most needed for the health care of the majority of the population in a given locality, and in a proper dosage forms. The national list of essential drugs (NEDL) is based on prevailing health conditions, drug efficacy, safety, and quality, cost- effectiveness and allocated financial resources.

WHO’s mission in essential drugs and medicines policy is to help save lives and improve health by closing the huge gap between the potential that essential drugs have to offer and the reality that for millions of people particularly the poor and disadvantaged medicines are unavailable, unaffordable, unsafe or improperly used. The organization works to fulfill its mission in essential drugs and medicines policy by providing global guidance on essential drugs and medicines, and working with countries to implement national drug policies to ensure equity of access to essential drugs, drug quality and safety, and rational use of drugs. Development and implementation of national drug policies are carried out within the overall national health policy context, with care taken to ensure that their goals are consistent with broader health objectives. All these activities ultimately contribute to all four WHO strategic directions to:

• reduce the excess mortality of poor and marginalized populations
• reduce the leading risk factors to human health
• develop sustainable health systems,and
• develop an enabling policy and institutional environment for securing health gains.

The greatest impact of WHO medicines activities is, and will continue to be, on reducing excess mortality and morbidity from diseases of poverty, and on developing sustainable health systems.

“The people of our world do not need to bear the present burden of illness. Most of the severe illness that affects the health and well-being of the poorer people of our world could be prevented. But first, those at risk need to be able to access health care — including essential medicines, vaccines and technologies. Millions cannot — they cannot get the help they need, when they need it. As a result they suffer unnecessarily, become poorer and may die young. A country’s health service cannot respond to people’s needs unless it enables people to access essential drugs of assured quality. Indeed, this access represents a very important measure of the quality of the health service. It is one of the key indicators of equity and social justice.”

(Dr Gro Harlem Brundtland, Director-General, World Health Organization
Opening remarks, Parliamentary Commission on Investigation of Medicines, Brasilia, 4 April 2000).

1.1 Background

1.1.1 Brief history of antibiotics

According to the original definition by Waksman, antibiotics substances which are produced by microorganisms and which exhibit either an inhibitory or destructive effect on other microorganisms. In a wider, though not universally accepted definition; antibiotics are substances of biological origin, which without possessing enzyme character, in low concentrations inhibit cell growth processes (Reiner, 1982).

Up to now, more than 4,000 antibiotics have been isolated from microbial sources and reported in the literature, and more than 30000 semi-synthetic antibiotics have been prepared. Of these, only about 100 are used clinically as the therapeutic utility not only depends on a high antibiotic activity but also on other important properties such as good tolerance, favorable pharmacokinetics etc. These antibiotics are today among the most efficient weapons in the armoury of the physician in his fight against infectious diseases. They are therefore used a large extent and constitute the largest class of medicaments with respect to turnover value. Today, antibiotics are also used in veterinary medicine and as additives to animal feed. In the past they were used addition, as plant protection agents and as food preservatives.

In this review we have confined ourselves to a brief description clinicallyuseful antibiotics. These belong to various classes of chemical compounds, differ in origin, mechanism of action and spectrum activity, and are thus important and representative examples of known antibiotics.

1.1.2 Problem Statement

This study examines drug use in Yemen and factors leading to inappropriate use of medicines particularly antibiotics and the prescribing pattern. It defines rational drug use and describes policy developments, which aim to encourage appropriate use.

In Yemen, as well as in many developing countries, the quality of health services is far from being achieved. Therefore, doctors should concentrate on making patients better and patients should concentrate on getting better. The rational use of drugs requires that patients received medications in appropriate to their clinical needs, in doses that meets their own requirements for an adequate period of time and at the lowest cost to them and their community (Bapna et al, 1994). This means deciding on the correct treatment for an individual patient based on good scientific reasons. It involves making an accurate diagnosis, selecting the most appropriate drug from these available, prescribing this drug in adequate doses for a sufficient length of time according to standard treatment. Furthermore, it involves monitoring the effect of the drug both on the patient and on the illness.

There is plentiful evidence of the inappropriate use of drugs, not through self-medication or unauthorized prescribing, but inadequate medical prescribing and dispensing.

Normally, patients in Yemen enter health facilities with a set of symmetrical complaints, and with expectations about the care they typically receive; they typically leave with a package of drugs or with a prescription to obtain them in a private market. In previous study in Yemen (misuse of antibiotics in Yemen, a pilot study in Aden) (Abdo-Rabbo, 1997) showed that imported quantity and total consumption of antibiotics is increasing. There is a lack of information about the problems created from antibiotics among the community and about the proper efficacy, safety, and rational use of antibiotics among health authority and workers. No supervision or strict rules are applied in the use of antibiotics. They are easily obtained without prescription and available in some shops. The percentage of prescriptions containing antibiotics was more than a quarter of the total prescriptions contained antibiotics, also antibiotics constituted about 25% of all prescribed drugs.

1.1.2.1 Inappropriate Drug Use

Increasing use of medicines may lead to an increase in the problems associated with medication use. The use of medicines, as well as improving health, can lead to undesirable medical, social, economic and environmental consequences. Aspects of drug use, which lead to such undesirable consequences, have been called inappropriate drug use (DHHCS, 1992; WHO, 1988). Inappropriate drug use may include under-use, over-use, over-supply, non-compliance, adverse drug reactions and accidental and therapeutic poisoning (DHHCS, 1992). It also includes medicating where there is no need for drug use, the use of newer, more expensive drugs when lower cost, equally effective drugs are available (WHO, 1988) and drug use for problems which are essentially social or personal (Frauenfelder and Bungey, 1985).

1.1.2.2 Quality Use of Medicines

In an attempt to encourage the appropriate use of medicinal drugs and to reduce the level of inappropriate use in Yemen, a policy was developed on the quality use of medicines. The stated aim of the policy is: “to optimise medicinal drug use (both prescription and OTC) to improve healthoutcomes for all Yemenis”. The policy endorses the definition of quality drug use as stated by the World Health Organisation, “Drugs are often required for prevention, control and treatment of illness”. When a drug is required, the rational use of drugs demands that the appropriate drug be prescribed, that it be available at the right time at a price people can afford, that it be dispensed correctly, and that it be taken in the right dose at the right intervals and for the right length of time. The appropriate drug must be effective, and of acceptable quality and safety. The formulation and implementation by governments of a national drug policy are fundamental to ensure rational drug use (WHO, 1987; DHHCS, 1992). The rational use of drugs can be impeded by the inappropriate selection of management options, the inappropriate selection of a drug when a drug is required, the inappropriate dosage and duration of drug therapy and the inadequate review of drug therapy once it has been initiated.

1.1.2.3 The Requirement of Drug Information for Quality Use of Medicines

“A medicine has been described as an active substance plus information.” (WHO, 1994). Education, together with, objective and appropriate drug information have been two of the factors consistently identified as necessary for rational drug use (Naismith, 1988; Soumerai, 1988; Carson et al, 1991; Dowden, 1991; Henry and Bochner, 1991; Tomson and Diwan, 1991). The WHO guidelines for developing national drug policies also identify the importance of information provision for facilitating drug use: “Information on and promotion of drugs may greatly influence their supply and use. Monitoring and control of both activities are essential parts of any national drug policy” (WHO, 1988). Objective and appropriate drug information is a necessary factor for quality drug use. It is the basis for appropriate prescribing decisions by medical practitioners. Medical practitioners require objective product, specific drug information and comparative prescribing information. Objective drug information is available to medical practitioners through continuing education programs co-ordinated by professional bodies, medical and scientific journal articles, drug information services and drug formularies and guidelines.

1.1.2.4 Problem with antibiotic use

The concerns regarding inappropriate antibiotic use can be divided into four areas: efficacy, toxicity, cost, and resistance. Inappropriate use of antibiotic can be due to: –

1. Antibiotic use where no infection is present, e.g. continuation of peri-operative prophylaxis for more than 24 hours after clean surgery.
2. Infection, which is not amenable to antibiotic therapy, e.g. antibiotics prescribed for viral upper respiratory infection.
3. The wrong drug for the causative organism, e.g. the use of broad anti-Gram negative agents for community acquired pneumonia.
4. The wrong dose or duration of therapy.

Such inappropriate use has a measurable effect on therapeutic efficacy. For example, one study showed that mortality in gram-negative septicemia is doubled when inappropriate empiric agents were used (Kreger et al., 1980). Since most initial antibiotic therapy is empiric, any attempt at improving use must tackle prescribing habits, with particular emphasis on guidelines for therapy based on clinical criteria.

Inappropriate antibiotic use exposes patients to the risk of drug toxicity, while giving little or no therapeutic advantage, antibiotics are often considered relatively safe drugs and yet direct and indirect side effects of their use are frequent and may be life-threatening, allergic reactions, particularly to beta-lactam agents are well recognized and have been described in reaction to antibiotic residues in food (Barragry, 1994).

Life threatening side effects may be occur from the use of antibiotics for apparently simple infections, it is estimated, for example, that eight people per year in UK die from side effects of co-trimoxazole usage in the community (Robert and Edmond, 1998). Indirect side effects are often overlooked: especially as may occur sometime after the antibiotic has been given. These include drug interactions (such as interference of antibiotic with anti-coagulant therapy and erythromycin with antihistamine) (BNF, 1998), side effects associated with the administration of antibiotics (such as intravenous cannula infection) and super-infection (such as candidiasis and pseudomembranous colitis). Each of these may have a greater morbidity, and indeed mortality, than the initial infection for which the antibiotic was prescribed (Kunin et al., 1993).

The medical benefit of antibiotics does not come cheap. In the hospital setting, up to fifty percent of population receive one antibiotic during their hospital stay, with surgical prophylaxis accounting for thirty percent of this (Robert and Edmond, 1998).

The first penicillin resistant isolate of Staphylococcus aureus was described only two years after the introduction of penicillin. Within a decade, 90% of isolates were penicillin resistant. This pattern of antibiotic discovery and introduction, followedby exuberant use and rapid emergence of resistance has subsequently been repeated witheach new class of antibiotics introduced. Bacteria can so rapidly develop resistance due to two major evolutionary advantages. Firstly, bacteria have been in existence for some 3.8 billion years and resistance mechanisms have evolved over this time as a protective mechanism against naturally occurring compounds produced by other microorganisms. In addition, they have an extremely rapid generation time and can freely exchange genetic material encoding resistance, not only between other species but also between genera. The vast quantities of antibiotics used in both human and veterinary medicine, as a result present in the environment, have lead to emergence of infection due to virtually untreatable bacteria. Multiply drug resistant tuberculosis is already widespread in parts of Southern Europe and has recently caused outbreaks in hospitals in London (Hiramatsu et al., 1997).

Anti-infective are vital drugs, but they are over prescribed and overused in treatment of minor disorder such as simple diarrhea, coughs, and colds. When antibiotics are too often used in sub-optimal dosages, bacteria become resistant to them. The result is treatment failure where patient continue to suffer from serious infections despite taking the medication (Mohamed, 1999).

Drugs prescribed are in no way beneficial to the patient’ s management if there are some negative interactions among the various agent prescribed, over prescribed, under prescribed or prescribed in the wrong dosage schedule.

• How does one ensure that good drug are not badly used, misused, or even abused?
• How can drugs be used rationally as intended?
• What is rational use of drugs? What does rational mean?

1.1.3 Rational Use of Drug

“Rational use of drugs requires that patients receive medications appropriate to their clinical needs, in doses that meet their own individual requirements for an adequate period of time, and the lowest cost to them and their community” (Bapna et al., 1994).

These requirements will be fulfilled if the process of prescribing is appropriately followed. This will include steps in defining patient’s problems (or diagnosis); in defining effective and safe treatments (drugs and non-drugs); in selecting appropriate drugs, dosage, and duration; in writing a prescription; in giving patients adequate information; and in planning to evaluate treatment responses. The definition implies that rational use of drugs; especially rational prescribing should meet certain criteria as follows (Ross et al., 1992):

• Appropriate indication. The decision to prescribe drug(s) is entirely based on medical rationale and that drug therapy is an effective and safe treatment.
• Appropriate drug.The selection of drugs is based on efficacy, safety, suitability, and considerations.
• Appropriate patient. No contraindications exist and the likelihood of adverse reactions is minimal, and the drug is acceptable to the patient.
• Appropriate information. Patients should be provided with relevant, accurate, important, and clear information regarding his or her condition and the medication(s) that are prescribed.

Appropriate monitoring. The anticipated and unexpected effects of medications should be: appropriately monitored (Vance and Millington, 1986).

Unfortunately, in the real world, prescribing patterns do not always conform to these criteria and can be classified as inappropriate or irrational prescribing. Irrational prescribing may be regarded as “pathological” prescribing, where the above- mentioned criteria are not fulfilled. Common patterns of irrational prescribing, may, therefore be manifested in the following forms:

1. The use of drugs when no drug therapy is indicated, e.g., antibiotics for viral upper respiratory infections,
2. The use of the wrong drug for a specific condition requiring drug therapy, e.g., tetracycline in childhood diarrhea requiring ORS,
3. The use of drugs with doubtful/unproven efficacy, e.g., the use of antimotility agents in acute diarrhea,
4. The use of drugs of uncertain safety status, e.g., use of dipyrone,
5. Failure to provide available, safe, and effective drugs, e.g., failure to vaccinate against measles or tetanus, failure to prescribe ORS for acute diarrhea,
6. The use of correct drugs with incorrect administration, dosages, and duration, e.g., the use of IV metronidazole when suppositories or oral formulations would be appropriate.
7. The use of unnecessarily expensive drugs, e.g., the use of a third generation, broad spectrum antimicrobial when a first-line, narrow spectrum, agent is indicated.

Some examples of commonly encountered inappropriate prescribing practices in many health care settings include: (Avorn et al., 1982).

1. Overuse of antibiotics and antidiarrheals for non-specific childhood diarrhea,
2. Multiple drug prescriptions, prescribe unnecessary drugs to counteract or augment,
3. Drugs already prescribed, and
4. Excessive use of antibiotics in treating minor respiratory tract infection.

The drug use system is complex and varies from country to country. Drugs may be imported or manufactured locally. The drugs may be used in hospitals or health centers, by private practitioners and often in a pharmacy or drug shop where OTC preparations are sold. In some countries, all drugs are available over the counter.

Another problem among the public includes a very wide range of people with differing knowledge, beliefs and attitudes about medicines.

1.1.3.1 Factors Underlying Irrational Use of Drugs

There are many different factors that affect the irrational use of drugs. In addition, different cultures view drugs in different ways, and this can affect the way drugs are used. The major forces can be categorized as those deriving from patients, prescribers, the workplace, the supply system including industry influences, regulation, druginformation and misinformation, and combinations of these factors (Table 1.1) (Ross et al., 1992).

Table 1.1: Factors affecting irrational use of drug

Impact of Inappropriate Use of Drugs

The impact of this irrational use of drugs can be seen in many ways: (Avorn et al., 1982).

1. Reduction in the quality of drug therapy leading to increased morbidity and mortality,
2. Waste of resources leading to reduced availability of other vital drugs and increased costs,
3. Increased risk of unwanted effects such as adverse drug reactions and the emergence of drug resistance, e.g., malaria or multiple drugs resistant tuberculosis,
4. Psychosocial impacts, such as when patients come to believe that there is “a pill for every ill”. This may cause an apparent increased demand for drugs.

1.1.3.2 The Rational Prescription (i.e. the right to prescribe)

The rights to prescription writing must be ensuring the patient’s five rights: the right drug, the right dose, by the right route, to the right patient, at the right time. Illegible handwriting and misinterpretation of prescriptions and medication orders are widely recognized causes of prescription error. The medicines should be prescribed only when they are necessary, should be written legibly in ink or, other wise, should be led, and should be signed in ink by the prescriber, The patients full name and address, diagnosis should be written clearly, the name of drugs and formulations should be written clearly and not abbreviated, using approved titles only. Dose and dose frequency should be stated; in the cases of formulations to be taken as required, a minimum dose should be specified (British National Formulary, 1998).

1.2 Overview on Essential Drug Concept (EDC)

Essential drugs relate to an international concept proposed by the World Health Organization (WHO) in 1977. WHO in that year published the first model list of essential drug and WHO has put in enormous resources into the campaign to promote the concept of essential drugs (EDL). Essential drugs were defined as a limited number of drugs that should be available at any time to the majority of population in appropriate dosage forms and at affordable prices. In other words, it meets the criteria generally abbreviated as SANE [that mean safety , availability, need efficacy] (John, 1997). The essential drug concept is important in ensuring that the vast majority of the population is accessible to drugs of high quality, safety and efficacy relevant to their health care needs, and at reasonable cost (New Straits Times, 1997a).

In support of this concept, the WHOissued a model drug list that provided examples of essential drugs. The list is drawn up by a group of experts based on clinical scientific merits, and provides an economical basis of drug use. This list is regularly, revised and, since 1997, eight editions have been published. This ensures that the need for essential drugs is always kept up-to-date with additions and deletions. Despite such rigorous revision, the number of drugs in the list remains at about 300, although the initial list comprised less. Most of the drugs are no longer protected by patents and can therefore be produced in quantity at a lower cost without comprising standards (WHO, 1995). This is indeed important for countries like Yemen not only because health care are rapidly escalating, but also because the country is still very dependent on imports of strategic commodities like drugs. The EDC will enable Yemen to focus on becoming self-reliant where generic equivalents of essential drugs can be manufactured and popularized to meet the health needs of the majority of the people.

The limited number of drugs regarded as essential on the list offers a useful guide for practitioners as well as consumers. It underscores the general principle thata majority of diseases can be treated by similar drugs regardless of national boundaries and geographical locations (New Straits Times, 2000) Moreover, certain self-limiting diseases may not need “drug treatment” as such. For example, in the case of diarrhea, certain so-called potent anti-diarrhoeal drugs (including antibiotics) are not generally recommended. The more preferred treatment is oral rehydration salt that could easily be obtained or prepared at a fraction of the cost while giving the most optimum outcome. The goal of the Yemen Drug Policy was to:

1. Prepare a list of essential drugs to meet the health of needs of the people.
2. Assure that the essential drugs made available to the public are of good quality
3. Improve prescribing and dispensing practices
4. Promote rational use of drug by the public
5. Lower cost of the drugs to the government and public
6. Reduce foreign exchange expenditure

1.3 Yemen Essential Drug List and Drug Policy in Yemen

The Concept of Essential Drugs (EDC) developed by World Health Organization (WHO) in 1977 has provided a rational basis, not only for drug procurement at national level but also for establishing drug requirements at various levels within the health care system.

The WHO’s Action Program on Essential Drugs (DAP) aimed to improve health care. It was established in order to provide operational support in the development of National Drug Policies (NDP), to improve the availability of essential drugs to the whole population and to work towards the rational use of drugs and consequently the patient care. The program seeks to ensure that all people, whenever they may be, are able to obtain the drugs they need at the lowest possible price; that these drugs are safe and effective; and that they are prescribed and used rationally.

The first WHO Model List of Essential Drugs was published in 1977 (WHO, 1977). Since that time essential drugs become an important part of health policies in developing countries; but the Essential Drugs Program has been criticized because it emphasis in improving supply of drugs rather than their rational prescribing. The recent revised WHO Model List of Essential Drugs was published the 13th edition in April 2003 (WHO, 2003). Yemen was one of the first countries in the region adapted the EDC in 1984 and implemented this concept in the public sector (Hogerzeil et al., 1989). The first Yemen (National) Essential Drugs List (YEDL) was officially issued in 1987 based on the WHO List of Essential Drugs and other resources. The second edition of the Yemen Drugs list and the Yemen Standard Treatment Guidelines were published in 1996 (MoPH&P/NEDL, (1996); MoPH&P/NSTG, (1996).Recently the latest edition was published in 2001 with the Standard Treatment Guidelines (STG) in the same booklet (MoPH&P/YSTG and YEDL, 2001). The new edition of the Treatment Guidelines and the Essential Drugs List has been created through a long process of consultation of medical and pharmaceutical professionals in Yemen and abroad. Review workshops were held in Sana’a and Aden and more than 200 representatives of the health workers from different governorates including the major medical specialists participated.

Essential drugs are selected to fulfil the real needs of the majority of the population in diagnostic, prophylactic, therapeutic and rehabilitative services using criteria of risk-benefit ratio, cost-effectiveness, quality, practical administration as well as patient compliance and acceptance (Budon-Jakobowiez, 1994).

The YEDL was initially used for the rural health units and health centers as well as some public hospitals, but not applied for all levels of health care and the private sector. However, despite the recognition of the essential drug concept by the government of Yemen represented by the Ministry of Public Health and Population (MoPH&P), drugs remain in short supply to many of the population and irrationally used. Procurement cost is sometimes needlessly high. Knowledge of appropriate drug use and the adverse health consequences remain unacceptably low. In addition, diminished funding in the public sector resulted in shortage of pharmaceuticals.

The 20th century has witnessed an explosion of pharmaceutical discovery, which has widened the therapeutic potential of medical practice. The vast increase in the number of pharmaceutical products marketed in the last decades has not made drug available to all people and neither has resulted in the expected health improvement. While some of the newly invented drugs are significant advance in therapy, the majorities of drugs marketed as “new” are minor variations of existing drug preparations and do not always represent a significant treatment improvement. In addition, the vast number “brand names” products for the same drug increases the total number of products of this particular drug resulting in an unjustified large range of drug preparations marketed throughout the world.

The regular supply of drugs to treat the most common diseases was a major problem for governments in low-income countries. The WHO recommends that activities to strengthen the pharmaceutical sector be organized under the umbrella of the national drug policy (WHO, 1988). In 1995, over 50 of these countries has formulated National Drug Policies (NDP). The NDP is a guide for action, containing the goals set by the government for the pharmaceutical sector and the main strategies and approaches for attaining them. It provides a framework to co-ordinate activities of patients involved in pharmaceutical sector, the public sector, the private sector, non-governmental organizations (NGOs), donors and other interested parties. A NDP will therefore, indicate the various courses of action to be in relation to medicines within a country.

The Yemen National Drug Policy was developed since 1993 with the objectives of ensuring availability of essential drugs through equitable distribution, ensuring drugs efficacy and safety, as well as promoting the rational use of drugs. Unfortunately, it has n