ABSTRACT
This descriptive cross sectional survey was conducted on healthcare professionals working at different healthcare facilities in Nnewi North L.G.A of Anambra state to determine their awareness, attitude and practice to ADR reporting. The research was carried out after an approval from Nnamdi Azikiwe University teaching Hospital ethical committee. Written consent was obtained from the heads of different health facilities and informed consent was obtained from individual respondents during the administration of the questionnaires. Simple random sampling technique was used to select the health facilities studied and numbers of different professional groups sampled was proportionately determined. Consecutive recruitment method was used until the required sample was attained.
A total of 372 respondents [including 241 (64.8%) nurses/related health care workers, 109 (29.3%) doctors and 22 (5.9%) pharmacists] were studied. Two hundred and twenty one (59.4%) respondents were not aware of the existence of ADR reporting scheme in Nigeria. 241 (64.8%) of them lack the knowledge of reporting guideline. Though 85.8% of the respondents believe ADR reporting to be their professional responsibility, 310 (83.3%) suspected an ADR without reporting it, Uncertainty of reactions caused by drug, ignorance on how to report, fear, unavailability of reporting forms/guideline and lack of electronic means of reporting were mentioned as obstacles to ADR reporting.
There was indeed poor awareness (40.6%), poor attitude, and poor practice (0.9%) of
ADR reporting among health professionals working in Nnewi North Local Government
Area of Anambra state.
CHAPTER ONE
INTRODUCTION
1.1. HISTORICAL BACKGROUND
Adverse drug reaction (ADR) has been defined in so many ways. WHO defines ADR as any response to a drug which is noxious and unintended, and which occurs at doses normally used in man for prophylaxis, diagnosis, therapy of disease, or for the modification of physiological function1. A definition by Karch and Lasagna2 puts ADR as any response to a drug that is noxious and unintended, and that occurs at doses used in humans for prophylaxis, diagnosis, or therapy, excluding failure to accomplish the intended purpose. The American society of health system Pharmacists (ASHP) 3 defines a significant ADR as any unexpected, unintended, undesired, or excessive response to a drug that;
• Requires discontinuing the drug (therapeutic or diagnostic),
• Requires changing the drug therapy,
• Requires modifying the dose (except for minor dosage adjustments),
• Necessitates admission to a hospital,
• Prolongs stay in a health care facility,
• Necessitates supportive treatment,
• Significantly complicates diagnosis,
• Negatively affects prognosis, or
• Results in temporary or permanent harm, disability, or death.
Consistent with this definition, an allergic reaction (an immunologic hypersensitivity, occurring as the result of unusual sensitivity to a drug) and an idiosyncratic reaction (an abnormal susceptibility to a drug that is peculiar to the individual) are also considered
ADRs. Other definitions of ADRs exist, including that of the United state Agency for Food and Drug Administration (FDA) 4.
For reporting purposes, FDA categorizes a serious ADR as one in which the patient’s outcome is death, life-threatening (real risk of dying), hospitalization (initial or prolonged), disability (significant, persistent, or permanent), congenital anomaly, or required intervention to prevent permanent impairment or damage. It should be noted that side effect {an effect with predictable frequency; an effect whose occurrence are related to the size of the dose; or an expected, well-known reaction resulting in little or no change in patient management (e.g., drowsiness or dry mouth due to administration of certain antihistamines or nausea associated with the use of antineoplastics)}, drug withdrawal, drug-abuse syndromes, accidental poisoning, and drug-overdose complications should not be defined as ADRs.4
TYPES OF ADVERSE DRUG RACTION
ADRs may be categorized in five groups. The two most common are dose related effects (type A: augmented) and effects related to abnormal interaction between patient and drug (type B: bizarre). 5
Type A: Adverse drug reactions:
Type A: (augmented) reactions are normal pharmacologic effects of the drug exaggerated to the point of being undesirable or intolerable for patients. Type A ADRs are the most common, accounting for 75-80% of those reported. 4 Reactions of this type are also called ‘predictable’, because they are predictable from the pharmacology of the drug, whether caused by an excessive effect of the main pharmacological action (such as hypotension with antihypertensive drugs), or by an undesired secondary pharmacological action (such as the dose-dependent adrenal suppression caused by inhaled corticosteroids, which is of particular concern in children) 4.
Type A reactions are dose-related, occurring at a dose that is too high for the individual, and tend to have a relatively high morbidity. However, because type A reactions are usually slow in onset, the associated mortality rate is lower than in type B reactions. A type A drug reaction is more likely to occur with drugs that have a narrow therapeutic index (such as theophylline), and tend to occur more often in elderly people and neonates.
In general, drugs causing type B and serious type A reactions need to be stopped, whereas drugs causing less severe type A reactions may be continued at a reduced dose.4 For type A reactions, other management options might include substitution of a similar but more selective drug, or giving additional drugs to antagonize the unwanted effects of the primary agent 3, 6. Examples – Warfarin or heparin, which causes bruising; or diphenhydramine, which causes drowsiness. Another form of type A reaction involves a drug’s recognized pharmacologic property other than the primary desired one. For example, b-adrenergic blocking agents exert their effect on receptors other than those targeted in the heart and vasculature, leading to the potential of bronchospasm due to b-blockade of certain receptors in the pulmonary tree
Type B Adverse drug reactions:
Type B (bizarre) reactions are often more severe adverse effects unrelated to the known pharmacologic action of the drug and include most immunologic reactions. Unless patients are tested for antibody markers, these reactions are unpredictable and may or may not be dose-dependent. Type B reactions account for about 20-25% of those reported3. Because these reactions are not predictable from the pharmacology of the drug {such as Amoxicillin Clavulanic acid causing cholestatic jaundice, anaphylactic reaction to penicillin (rash)}. They are also known as unpredictable idiosyncratic reactions. Individual susceptibility to this type of reaction varies greatly.
Type B reactions are usually rapid in onset and there is a higher risk of mortality than in type A reactions7. Patients need to be able to recognize the warning signs of such a reaction if it is known to have occurred before with their medication.
Type B reactions are often allergic, sometimes involving anaphylaxis, which typically occurs on second or third exposure to the drug7. Patients with a history of anaphylaxis and atopic individuals with a history of asthma are more likely to experience anaphylaxis. Other type B reactions include those attributable to unpredictable genetic factors that can affect drug metabolism2. Type B reactions usually require the causative drug to be stopped, because the reaction can occur at any dose, and the reaction is
Other types of ADRs include Type C, D and E.5 While Type C ADR is associated with long-term use and dose accumulation (e.g., phenacetin and interstitial nephritis or antimalarials and ocular toxicity, NSAID induced renal failure), Type D is a delayed effects (dose independent) and occurs some time after use of drug {such as Carcinogenicity (e.g immunosuppressants) and Teratogenicity (e.g., fetal hydantoin syndrome and limb defects with thalidomide in first trimester and)}.7 On the other hand, type E is a withdrawal syndrome associated with end of use of the drug. It is related to discontinuation that is too abrupt, for example, addisonian crisis after steroid withdrawal 7, 8. ADR can also be classified based on
• Onset of event: { Acute (within 60 minutes), Sub-acute (1 to 24 hours), Latent
( > 2 days )} and
• Severity of reaction: {Mild ( bothersome but requires no change in therapy),
Moderate (requires change in therapy, additional treatment, hospitalization),
Severe (disabling or life-threatening)}
RISK GROUPS FOR ADVERSE DRUG REACTION
All drugs have the potential to cause ADRs, although most produce no ill effects in most patients. ADRs are more likely to occur if doses above the usual recommended level are given, but there are several other predisposing factors/groups2,9,10 including Older patients due to altered drug handling; for example: reduced drug metabolism and elimination by the liver and kidneys, poor drug distribution, and increased sensitivity to the effects of medications; the young (neonates, particularly premature babies) due to poor development of metabolizing and elimination enzymes, increased sensitivity and underdevelopment of physiological systems, such as renal function and the blood-brain barrier and the fact that many medicines have not been developed in pediatric doses and are used off-label, so that dosage in children is often inaccurate9. Women because they are more susceptible to the toxic effects of drugs, including commonly used agents such as digoxin, heparin and captopril. Also, few data are available on the safety of medicines used in pregnant and lactating women. Women may be inadvertently exposed to unsafe products and there is a particular lack of information, education and guidance in resource-limited settings9; Patients with impaired hepatic or renal function; Patients taking several drugs: Polypharmacy increases the risk of ADRs and the likelihood of ADRs increases sharply with the number of drugs administered mainly due to drug interactions. Mistakes may also occur if drug regimens are complicated and involve several drugs. The number of drugs prescribed should always be kept to a minimum to reduce the risk of drug interactions, and very clear instructions on how to take them should be given, particularly to older patients; Atopic individuals: Patients with a history of anaphylaxis and atopic individuals with a history of asthma are more likely to experience anaphylactic reactions (type B adverse effects); Individuals with specific genetic variations in drug-metabolising enzymes: Genetic variability in drug-metabolising enzymes is an important contributing factor to the incidence of ADRs (particularly type B reactions), in some individuals 10. Certain ethnic groups have been identified as being more susceptible to ADRs with particular drugs because of genetic polymorphism. For example, glucose-6-dehydrogenase (G6PD) deficiency, which predisposes to some drug-induced haemolytic anaemias, is more common in people who are African, in Kurdish and Iraqi Jews, and in some Mediterranean people and Filipinos; Individuals with co-existing disease: Certain disease states can precipitate ADRs to certain drugs if the disorder alters the pharmacokinetics of a drug (absorption, distribution, metabolism, elimination), or if it increases the individual’s sensitivity to the action of a drug (for example, patients with obstructive airway disease are more sensitive to the bronchoconstriction caused by beta-blockers); Variations in drug formulations that result in the delivery of higher than expected quantities of the active drug can cause ADRs; and Error at any stage in the supply of a medication; for example, confusion can arise over milligrams and micrograms and between similar drug names or a drug might be administered at the wrong dose, or to the wrong site.
FREQUENCY AND OCCURRENCE OF ADRs
ADRs are common. A study by general practitioners estimated that the presenting symptom of 1.7% of their consultations over a six month period was a manifestation of an ADR 11. Furthermore, 2-6% of hospital admissions are for ADRs. 12,13 Although a shorter timeframe is more common, ADRs can occur months or years after a drug was started and may not be obvious unless a thorough drug history is taken. These long-term ADRs can be predictable: type A reactions (such as osteoporosis with corticosteroids, or bladder cancer in patients taking cyclophosphamide), or idiosyncratic, type B reactions (such as, pulmonary fibrosis with amiodarone). The frequency of adverse reactions are generally described in the manufacturer’s product literature as follows14.
• common → occurring in 1:100 to 1:10 of the patients.
• very common → more than 1:10
• uncommon → 1:1,000 to 1:100
• rare → 1:10,000 to 1 :1,000
• Very rare → less than 1:10,000.
AVOIDING ADRs
Though ADR is common, a study on ADRs in nursing homes suggest that more than
half of the events are preventable 15-18 and that 70% are associated with monitoring errors15. Also, serious ADRs are more likely to be preventable than those of a less serious nature15. Understanding the causes of ADRs is essential to efforts to decrease their frequency and severity.
WHO’S ROLE TO REPORT ADRs
While pharmacists head the establishment of ADRs programs in health institutions and facilitate activities surrounding reporting of ADRs, the core reporting of ADRs is a collective activity of all health professionals.11,20,21 According to The Guide for Detecting and reporting of Adverse Drug reactions19, all healthcare
professionals/workers including doctors, dentists, pharmacists, nurses, traditional medicine practitioners and other health professionals are requested to report all suspected adverse reactions to drugs including orthodox medicines, X-ray contrast media, medical devices, cosmetics, traditional and herbal medicines. This guide also stressed that it is vital to report even when it is uncertain that the medicine in question is the actual cause of the reaction.
MANAGEMENT OF A SUSPECTED ADR
The symptoms of an ADR can be similar to those of diseases with other causes, and there are few specific clinical or laboratory methods to differentiate them7. When trying to determine whether an unwanted effect is an ADR, it may be helpful to find out whether the reaction has been reported before for the drug in question.
ADRs must be treated according to their cause and severity. In general, drugs causing type B and serious type A reactions need to be stopped, whereas drugs causing less severe type A reactions may be continued at a reduced dose. Specific management according to Oliver Jones7 is as follows:
For type A reactions, the management is simply reduction in the dose or withdrawal of the medication. Other management options might include substitution of a similar but more selective drug, or giving additional drugs to antagonize the unwanted effects of the primary agent.
By contrast, type E reactions require reintroduction of the drug and more gradual withdrawal. Type C or D reaction may be irreversible or only partially reversible on drug withdrawal.
Type B reactions are both uncommon, unpredictable, and have high morbidity and mortality. The first step is always the immediate withdrawal of the drug. If the reaction is mild, no further intervention may be necessary. Urticarial rashes, and to a lesser extent non-urticarial rashes, may be treated with antihistamines such as chlorpheniramine and an adrenocortical steroid. In more severe cases, these drugs may be given intravenously or intramuscularly. If angioedema develops with threatened laryngeal oedema, consideration should be given to adrenaline.
Anaphylaxis is a medical emergency. High skilled help should be summoned, including an anaesthetist. The patient should be positioned flat, with feet raised and airway secured. Oxygen should be administered and 0.5-1.0mg of adrenaline given intramuscularly as first line treatment (equivalent to 0.5-1.0ml of 1:1000 adrenaline). This is repeated every ten minutes according to cardiovascular parameters and clinical improvement. Chlorpheniramine (10-20mg) should also be administered by slow intravenous injection, and hydrocortisone (100-300mg), though the onset of action of the latter may not be for several hours. Further deterioration may necessitate intravenous fluids, nebulised inhalers, and intubation or tracheostomy. Other ADRs may involve any body system and manifest in several different ways. The correct management of these patients should be considered on an individual basis. Often this is delayed by failure to consider an ADR as the underlying cause of a patient’s
deterioration.
Other management options include the use of “tracer” drugs that are used to treat common ADRs (e.g., orders for immediate doses of antihistamines, epinephrine, and corticosteroids), or stat orders for laboratory assessment of therapeutic drug levels and Provision of supportive or palliative care e.g., hydration, glucocorticoids, warm / cold
compresses, analgesics or antipruritics, rechallenge or desensitization.7, 15
Reports of birth defects related to thalidomide use in pregnant women prompted FDA to develop an adverse event surveillance program in 196122 and with the amended Food, Drug, and Cosmetic Act of 1962, drug manufacturers were required to report any adverse events associated with their products.
The World Health Organization (WHO), in 1968, created the International Drug
Monitoring Program for the purpose of collecting information about Adverse Drug Reactions (ADR) that were not observed during clinical drug trials.23 This program has been exceptional in identifying the early signs of ADRs .24 ADR monitoring and reporting programs encourage ADR surveillance, facilitate ADR documentation, promote the reporting of ADRs, provide a mechanism for monitoring the safety of drug use in high-risk patient populations, and stimulate the education of health professionals regarding potential ADRs25.
1.1. STATEMENT OF THE PROBLEM:
Globally, physicians are faced everyday with problems of adverse drug reactions (ADRs) 12, 26 , 27 and about 95% of such cases go unreported Worldwide 28,29. Even though they are under-reported worldwide, they are much more under-reported in Nigeria30. Studies have also shown that adverse drug reaction (ADR) is the 4th to 6th
cause of death in the United States26, 27. Studies conducted in developed countries have consistently shown that approximately 5% of hospitalized patients are admitted into hospital as a result of an adverse drug reaction while 6-10% of inpatients experience a serious ADR during hospitalization12. The percentage of hospital admissions due to ADRs in some countries is approximately 10% 31-34 and treatment of ADRs imposes a high (15-20 %) financial burden on health care 35, 36. According to Med Watch 2, the Food and Drug Administration’s (FDA’s) Office of Drug Risk Assessment has stated that these numbers are vastly underestimated, as its research has shown that only 1% of ADRs are reported. The purpose of ADR reporting is to reduce the risk associate with prescribing and administration and ultimately improve patients care, safety and treatment outcome.
The National Agency for Food, Drug Administration and Control (NAFDAC) therefore introduced pharmacovigilance in 2004 to encourage ADR monitoring and reporting in Nigeria. Unfortunately, there is very limited information about adverse drug reactions in developing countries32, including Nigeria due to poor reporting of ADRs. The information which we receive on adverse drug effect from other countries may not be applicable to Nigeria due to various differences that may influence patient’s response 19 including;
• Disease and prescribing practices;
• Treatment seeking behavior e.g. self medication;
• Genetics, Diet, Traditions of people e.g. high carbohydrate, fat, kola nut consumption rate etc;
• Drug manufacturing process used which influence pharmaceutical, quality and composition;
• Drug distribution and use including indications, dose, storage and availability;
• The use of traditional and complementary drugs ( e.g. herbal remedies) which may pose specific toxicological problems when used alone or in combination with other drugs; and
• Racial differences.
This study was designed to determine the awareness, attitude and practice of ADR reporting among health care professionals working in Nnewi North L. G. A., Anambra state with a view to encourage health professionals to see ADR monitoring and reporting as a professional obligation. With improvement on ADR reporting in this area,
ADR induced morbidity, mortality and death will be drastically reduced.
1.2. OBJECTIVE OF THE STUDY
1.2.1. GENERAL OBJECTIVE
To determine the awareness, attitude and practice of ADR reporting among health care professionals working in Nnewi North L. G. A, Anambra state.
1.2.2. SPECIFIC OBJECTIVES
• To find out the level of awareness of health professionals in Nnewi North L.G.A to the national Adverse drug reaction reporting scheme/guideline.
• To access the attitudes of health professionals in different settings of health care in Nnewi North L.G.A [Health posts, Primary Health centres (PHC), Private hospitals and tertiary health institution] towards the reporting of ADR.
• To compare the ADR reporting practices of different categories of health care professionals.
• To determine factors influencing the reporting of ADR by health professionals.
• To determine the proportion of health practitioners that has ever had training on ADR reporting.