Abstract Objectives To identify factors that predict repeat admission to hospital for adverse drug reactions (ADRs) in older

adults. Design Population based retrospective cohort study. Setting All public and private hospitals. Adverse drug reactions (ADRs) are a frequently overlooked complication of drug therapy. The categories of drugs most commonly implicated include anticoagulants, antimicrobials, cardiac agents, CNS agents, diagnostic agents, no steroidal anti-inflammatory agents, and hormones. In addition to knowing what drug classes most commonly produce ADRs, the clinician should also recognize what drugs are most frequently associated with specific ADRs. Anaphylaxis is one of the most serious, and potentially lifethreatening, ADRs. Treatment of an anaphylactic reaction involves correcting the physiologic effects of released chemical mediators and also inhibiting the release of additional mediators. The mainstay of therapy is aqueous epinephrine. Severe reactions may require administration of aminophylline, inotropic agents, antihistamines, corticosteroids, and intravenous fluids. The best treatment for any ADR is prevention. Pharmacists can actively participate in the monitoring of risk factors, especially the number of drugs in a regimen, potential drug interactions, and drug allergies, which may predispose patients to ADR development. Pharmacists can also assist in the detection of ADRs by monitoring alerting orders. Other potential activities for pharmacists include providing timely and accurate information about ADRs ; educating patients, physicians, and other health care professionals; and influencing prescribing patterns to minimize the trend towards polypharmacy

Definitions For the purposes of this review, definitions of adverse drug reaction are those given below: Adverse Drug Reaction: an event that is noxious and unintended and occurs at doses in humans for prophylaxis, diagnosis, therapy or modification of physiologic functions. This definition excludes intentional or deliberate overdose and drug abuse.

ADR rate: proportion (percentage) of patients or admissions who had an ADR definitely or probably related to a drug. ADRad: Patients admitted to hospital due to an adverse drug reaction ADRin: Patients experiencing an ADR while in a hospital. Type A reactions are caused by known toxicity of the drug and related to dose and pharmacological effect, like bleeding caused by the anti-coagulant wayfaring. This group of reactions is potentially preventable. Type B reactions are idiosyncratic or allergic in nature. Reactions that usually occur from the initial use of a drug in a patient are not predictable and therefore not preventable. Background Adverse drug reactions cause considerable morbidity and mortality worldwide and in many cases are avoidable. Adverse drug reactions were responsible for around 6.5% of all acute hospital admissions. Adverse drug reactions are one of the leading causes of death in the population. Hence, adverse drug reactions have a major impact on public health, reducing patients' quality of life and imposing a considerable financial burden on the health care systems at a time when many health care systems are under considerable financial strain. Drug reactions can be typically described in two groups. Type A reactions "intrinsic" (which are often dose-dependent) are relatively common. Type B reactions are usually more serious: idiosyncratic reactions that are not necessarily dose-dependent. We expect the majority of ADR admissions to be Type A reactions. Notification to pharmacovigilance agencies is designed to capture new ADRs not known at the marketing stage, i.e. usually but not exclusively, Type B reactions. Adverse drug reactions are commonest amongst the elderly. This is not surprising as the elderly generally have the highest prevalence of long-term diseases. Poly-pharmacotherapy, combined with a poorer physiological reserve, puts the elderly particularly at risk of adverse drug reactions. Polypharmacotherapy amongst elderly patients is likely to increase. This rewards tighter meeting of 'treatment targets' for specific long-term diseases, such as high blood pressure or high cholesterol, which commonly results in prescribing of higher doses of medication or poly-pharmacotherapy with higher number of different medications than in the past.

Patient injuries resulting from drug therapy are among the most common types of adverse events that occur in hospitals. Although the incidence of ADEs and their effect on costs have been investigated in only a few hospitals in the United States, the implications are clear from published results that ADEs constitute a widespread problem that causes injuries to patients and disproportionately increases expenses. More evidence-based prescribing for long-term diseases will benefit patients, but may also increase the number of adverse drug reactions in the population merely because of the potential for increased drug reactions. The number of older people in the population of developed countries is also increasing rapidly. Despite the importance of adverse drug reactions, methods for monitoring them are limited. Some adverse drug reactions are identified during clinical trials during drug development and testing, however, rare reactions may fail to be detected. Once a drug is marketed, detection of adverse drug reactions generally depends on notifications to regulatory authorities. However, even for serious and well-recognized ADRs notification of adverse drug reactions from such spontaneous reporting schemes is low, often less than 10% and even lower where the association between the drug and the adverse event is unknown. Hence, many adverse drug reactions do not become apparent until a drug has been in widespread use for several years. Consequently, current systems for the detection of ADRs have serious limitations. For example, the associations between COX-2 inhibitors and increased risk for myocardial infarction and stroke were only highlighted and reviewed after these drugs had been used for several years by hundreds of thousands of patients, although initial concerns were identified from trial data. Other information on adverse drug reactions comes from ad-hoc studies. Medication Errors Are a Frequent Cause of Adverse Drug Events: Medication errors occur at any point in the medication administration processduring ordering, transcription (the process of manually transferring the physician order onto medication sheets), dispensing, and administering medications. However the majority of errors occur during the ordering and administration stages. Other specific errors have also been associated with ADEs include:

Missed dose.

Wrong technique. Illegible order. Duplicate therapy. Drug-drug interaction. Equipment failure. Inadequate monitoring. Preparation error.

METHODS: This was a case-control study in which unscheduled admissions of patients who had been admitted to the hospital during the two previous months were assessed during a 21-month period. The patient was considered a case when the main diagnosis of readmission complied with the World Health Organizations definition of an ADR. For each case, two controls were selected from those patients that had been admitted for ADR without readmission. Information on drugs and other risk factors was obtained from cases by interview and from controls by clinical record review.

Number of drugs: The number of drugs per patient per day was determined by counting the different drugs which the patient claimed to have used during the 2 weeks before admission. For the combined preparations, the different pharmacologically active ingredients were counted separately, based on the assumption that the different substances could be candidates for causing different ADRs. Signals: These signals, routinely recorded in a medical record, are clinical identifiers that indicate an ADE might have occurred:

Rash. Change in respiratory rate, heart rate, hearing, or mental state. Seizure. Anaphylaxis. Diarrhea. Fever.

Diagnoses: For each patient we counted the number of diagnoses requiring medication and the number of new diagnoses on admission. The diagnoses relating to ADRs were not included in the total number of diagnoses. The diagnoses were then categorized into:

Chronic obstructive pulmonary exacerbation of symptoms. Cardiovascular any cardiac vascular disease and stroke.

disease disease,

with

or

without

an

hypertension,

peripheral

Diabetes mellitus non-insulin and insulin dependent diabetes mellitus. Terminal renal insufficiency subjects on peritoneal or haemodialysis, or after renal transplantation.

Interaction between age and number of medicines: A number of studies examined ADR rates according to the number of medicines taken, and age, or the number of medicines taken in older people. Reasons why the older people are more liable to adverse drug reactions include: The elderly receive more drugs. Illnesses in the elderly tend to be treated with drugs with a poor therapeutic ratio. Drug interactions occur due to polypharmacy. Poor compliance. Altered pharmacokinetics and pharmacodynamics. Elderly may have more type A reactions and fewer type B Medication errors and ADEs are often the result of unique combinations of interactions among health care providers, patients, and medications. Costs of ADEs are very high and patients can suffer irreversible injuries that can result in permanent disability or death. Although ADEs cannot be predicted, they often can be prevented using computerized systems that:

Monitor patients. Provide physician order entry. Integrate patient, pharmacy, and lab data. Track the incidence of ADEs.

MORE Drug-induced lupus erythematosus: Drug-induced lupus erythematosus is an autoimmune disorder that is brought on by a reaction to medication. Causes Drug-induced lupus erythematosus is similar to systemic lupus erythematosus (SLE). It is caused by a hypersensitivity reaction to a medication. The drug may react with cell materials, causing the body to form antibodies that attack the body's own healthy cells. Several medications are known to cause drug-induced lupus. They include: Chlorpromazine Hydralazine Isoniazid Methyldopa Penicillamine Procainamide Quinidine Sulfasalazine Symptoms tend to occur after taking the drug for at least 3 to 6 months. Persons with drug-induced lupus erythematosus may have symptoms that affect the joints (arthritis), heart, and lungs. Other symptoms associated with SLE, such as lupus nephritis and nervous system (neurological) disease, are rare. Drug-induced lupus affects men and women equally. Symptoms Blurred vision Fever General ill feeling (malaise) Joint pain Joint swelling Loss of appetite Pleuritic chest pain Skin rash o Gets worse with sunlight o "Butterfly" rash across bridge of nose and cheeks Weight loss Exams and Tests

The health care provider will listen to your chest with a stethoscope. The doctor may hear a sound called a heart friction rub or pleural friction rub. There may be signs of pericarditis. A skin exam shows a rash. Tests that may be done include: Antihistone antibody Antinuclear antibody (ANA) panel Lupus erythematosus cell test (rarely used) A chest x-ray may show signs of pleuritis or pericarditis. An ECG may show that the heart is affected. Treatment Usually, symptoms go away within several days to weeks after stopping the medication that caused the condition. Treatment may include: Nonsteroidal anti-inflammatory drugs (NSAIDs) to treat arthritis and pleurisy Corticosteroid creams to treat skin rashes Antimalarial drugs (hydroxychloroquine) to treat skin and arthritis symptoms Very rarely, high doses of corticosteroids (prednisone, methylprednisolone) and immune system suppressants (azathioprine or cyclophosphamide) are used to treat persons with severe drug-induced lupus that affects the heart, kidney, and neurological system. Protective clothing, sunglasses, and sunscreen are recommended. Outlook (Prognosis) Drug-induced lupus erythematosus is usually not as severe as SLE. Usually, the symptoms go away within a few days to weeks after stopping the medication. You should avoid the medication in the future, or symptoms usually return. Routine eye exams are recommended to detect eye complications early. Possible Complications Infection Thrombocytopenia purpura -- bleeding near the skin surface, resulting from a low number of platelets in the blood Hemolytic anemia Myocarditis Pericarditis When to Contact a Medical Professional Call for an appointment with your health care provider if: Your symptoms do not improve after you stop taking the medication that caused the condition

You develop new symptoms

Prevention Be aware of the risk when taking medications that are known to cause this reaction. If symptoms begin to appear, contact your doctor. RESULTS: The study included 100 patients, of which 50 were male and 50 were female with average age of 42.95 years. The hospital stay at the internal medicine ward for the sample was 10.07 , with an average of medications administered of 7.77. The first five causes of hospitalization correspond to cardiovascular disease (HTA, 25%; acute coronary disease, 12%; and heart failure, 10%), chronic renal insufficiency (16%), and AIDS (12%). The groups of medications prescribed most were cardiovascular drugs and analgesics. In the study, 99 adverse events were identified related to medications in 45 patients, corresponding to probable ADRs (n=29), possible ADRs (n=21), and doubtful ADRs (n=49), after applying the Naranjo algorithm. None of the adverse events was classified as definite. Additionally, doubtful ADRs were not considered adverse effects to medications. In five patients, two ADR events were present simultaneously. The cardiovascular medications are associated with the greatest number of adverse effects. Of these, enalapril caused the greatest ADRs, consisting of dry cough (n=9), coetaneous rash (n=1), and pharmacological interactions with other cardiovascular medications (n=2), followed by amlodipine (n=8), furosemide (n=6), clindamycin (n=4), lovastatin (n=3), and ceftriaxone (n=3). All ADRs associated with enalapril were catalogued as slight. Other cardiovascular medications related to ADRs were amlodipine and furosemide that mainly caused palpitations and orthostatic hypotension (n=12). Additionally, the antilipemic lovastatin was associated to myalgia in three patients. The second group of medications most frequently linked to ADRs was antibiotics, primarily clindamycin and ceftriaxone, both associated with diarrhea and coetaneous rash.

DISCUSSION: In the current study, a descriptive analysis was performed of the adverse reactions to medications at an internal medicine service. In gathering the data, we were aware that the medical history could have incomplete

information; hence, the medications prescribed to each patient (presentation, dose, and route of administration) were confirmed by the format of medication administration used by nursing personnel and by the physicians responsible for the ward. In spite of the limitation in collecting data through the medical history, previous studies of pharmacological surveillance have described a high correlation between medications administered to patients and those registered in the medical history. Active pharmacological surveillance in hospital settings presents multiple advantages with respect to programs of voluntary notification of adverse effects. The strategy for detecting adverse effects applied in this study permits obtaining complete information of the patients illness and the drugs administered. Additionally, this methodology permits checking the veracity of the data related to the administration of the medication (dose, commercial presentation, route of administration, date of prescription) indispensible in determining if there is or isnt causality of an adverse effect. This system of pharmacological surveillance is low cost and can be easily applied in hospitalization services in our country to increase the prevention and early detection of adverse effects in hospitalized patients

Conclusion:

In summary, there are significant differences between younger and older patients, often not realized by doctors or patients. Increasing awareness of these differences will result in the prescription of far fewer drugs to older adults, and those that are prescribed will be given at lower doses in most instances. By detecting and preventing ADEs, a hospital can reduce expenses while providing better quality care to its patients.

REFERENCES 1. World Health Organization. Safety of medicines: a guide to detecting and reporting adverse drug reaction. Geneva: WHO; 2002. 2. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998; 279: 1200-5. 3. Hazell L, Shakir SA. Under-reporting of adverse drug reactions: a systematic review. Drug Saf. 2006; 29: 385-96. 4. Kvasz M, Allen IE, Gordon MJ, Ro EY, Estok R, Olkin I, et al. Adverse drug reactions in hospitalized patients: A critique of a meta-analysis. MedGenMed. 2000; 2: E3. 5. Tribino G, Maldonado C, Segura O, Daz J. Direct costs and clinical aspects of adverse drug reactions in patients admitted to a level 3 hospital internal medicine ward. Biomedica. 2006; 26: 31-41.