Adverse Drug Reactions in patients with Bronchial Asthma - eJManager

Adverse Drug Reactions in Patients with Bronchial Asthma

Adverse Drug Reactions in Patients with Bronchial Asthma Vesna Cukic, Aida Ustamujic, Vladimir Lovre Clinic for Pulmonary Diseases and TB “Podhrastovi”, Clinical Center of University of Sarajevo, Bosnia and Herzegovina Professional paper SUMMARY Adverse reactions to drugs are very common in everyday medical practice. Adverse drug reaction (ADR) is defined as any noxious, unintended and undesired effect to a drug that is administrated in standard doses by the proper route for the purpose of prophylaxis, diagnosis, or treatment . Some drug reactions may occur in everyone whereas others occur only in susceptible patients. These are factors that may impact on clinical practice. Asthmatics have a greater risk of developing ADRs. The majority of asthma patients are atopic. The most common drugs that induce ADRs in asthmatics are: aspirin and non-steroidal anti–inflammatory agents. Avoidance of a drug responsible for adverse reactions is the most important to prevent ADRs . Keywords: adverse drug reaction, bronchial asthma

1. ADVERSE DRUG REACTIONS – DEFINITION AND CLASSIFICATION Adverse drug reaction (ADR) is defined as “Any noxious, unintended and undesired effect to a drug that is administrated in standard doses by the proper route for the purpose of prophylaxis , diagnosis, or treatment” (1,2). Some drug reactions may occur in everyone whereas others occur only in susceptible patients (1, 2). A drug allergy is an immunologically mediated reaction that exhibits specificity and recurrence in re-exposure to the offending drug (2, 3, 4). ADRs are classified into Type A and Type B. Type A are predictable ,dose related , common and explained by the pharmacological properties of the drug; these reactions may occur in anyone : ■■ Drug overdose – Toxic reactions linked to excess dose or impaired excretion or to both ■■ Drug side effect – Undesirable pharmacological effect at recommended doses ■■ Drug interaction – Action of a drug on the effectiveness or toxicity of another drug ■■ Drug reactions related to the properties of the drug such as antibiotics related diarrorhoea (2) ■■ Type B are unpredictable, less common, not doserelated and not explained by the pharmacological properties of the drug and occur only in susceptible subjects: ■■ Drug intolerance – A low threshold to the normal pharmacological action of a drug ■■ Drug idiosyncrasy – A genetically determined, qualitatively abnormal reaction to drug related to a metaProfessional papers

bolic or enzyme deficiency ■■ Drug allergy – An immunologically mediated reaction , characterised by specificity, transferability by antibodies or lymphocytes ,and recurrence on reexposure ■■ Pseudoallergic reaction – A reaction with the same clinical manifestations as an allergic reaction ( e.g. as a result of histamine release) but lacking immunological specificity (2) 1.1. Risk factors for ADRs

Adverse drug reactions occur mainly in young and middle aged adults and are twice in common in women. Genetic factors may be important. The HLA type may predispose to reaction to aspirin (HLA-DQw2). The role of atopy in predisposing to drug reactions is controversial. Intravenous administration of drug gives the most serious reactions (2) Asthma and pregnancy may exacerbate adverse reactions to drugs (3, 4). 1.2. Mechanisms of drug allergy

Allergic reactions to drugs are classified according to Coomb’s types I-IV. (2) 1.3. Risk factors for drug allergy

Patient related: age, sex, genetics, atopy, AIDS. Drug related: macromolecular size: bivalency, haptens, route, dose, duration of treatment. Aggravating factor: β-blockers, asthma, pregnancy (2). Numerous mechanisms have been implicated in adverse reactions to drugs. However, these mechanisms are not fully understood, which may explain the difficulty in differentiating drug allergy from other forms of drug reactions and to assessing the incidence ADRs, evaluating risk factors, and defining management strategies (2, 4).

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Adverse Drug Reactions in Patients with Bronchial Asthma

2. ADVERSE DRUG REACTIONS– INCIDENCE Adverse reactions to drugs are very common in everyday medical practice. Studies have shown that hospitalized adult patients in the United States receive on average 10 drugs during hospitalization .Outpatient adults take on average about two drugs on a regular basis ( i.e., at least once a week). ADRs have been estimated to occur in up to 30% of hospital inpatients and in a similar number of outpatients (3). Results from in-hospital studies indicate that some type of adverse reaction occurs about once in every 20 drug treatments. Most of these drug reactions are clinically minor and reversible, but about 10% of adverse reactions are regarded as life threatening. Virtually all organ systems have been involved with adverse drug effects. Deaths in hospitalized patients that are attributable to drugs are rare and tend to occur in patients who are quite ill from their primary illness and receive potent drugs such as antitumour agents. However, some drug-induced illnesses appear to be preventable. Out-patient drug toxicity is the cause of about 3% of all hospitalizations. When considered with the enormous use of drugs in the outpatient population, however, this number of admissions secondary to drug toxicity seems to represent a small coincidence (3). Allergic and other immunological reactions account for only a small proportion of all drug reactions – 6 to 10%–and 1 in 10 000 drug reactions are fatal (2). Drug allergies are adverse reactions resulting from immunologic responses to drugs or their metabolites. These reactions result in predictable patterns of organ-specific or systemic hypersensitivity that usually recur on subsequent exposure to the same drug. Although diagnostic testing for drug allergy is available for only a few drugs, protocols have been developed to assist in management of allergic reactions to many drugs and biologic agents. Other protocols assist in the management of patients who develop drug reactions while undergoing multiple drug therapy or those with a history of adverse drug reactions who again require treatment for the same condition (4). A French study of 2067 adults aged 20- 67 years attending a health centre for a check up reported that 14,7% gave reliable histories of systemic adverse reactions to one or more drugs. In Swiss study of 5568 hospital inpatients, 17% had adverse reactions to drugs. Fatal drug reactions occur in 0,1 % medical inpatients and 0,01% of surgical inpatients. The main drugs implicated are antibiotics and non-steroid anti-inflammatory drugs. Adverse reaction to drugs during anaesthesia (muscle relaxant, general anaesthetics and opiates) although less common (1 in 6000 patients receiving anaesthesia) are life threatening with mortality of about 6 % (2).

3. ADVERSE DRUG REACTIONS IN ASTHMATICS The question is whether asthmatics have a greater risk of developing ADRs, and if they are more severe. These are factors that may impact on clinical practice. The majority of asthma patients are atopic. Atopy is a risk factor for developing allergic reactions to latex and for adverse drug reactions

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to radiographic contrast medium. It is not a risk factor for penicillin allergy or allergic reactions occurring during anaesthesia. It is a risk factor for some complementary medicines (CAMs) e.g. Royal jelly, and Echinacea .CAM should be used with caution in asthma (1,2). β- blockers are relatively contra-indicated in asthma –including topical βblockers such as timolol used in glaucoma (1,2). Aspirin is contra-indicated in Samter`s triad and where asthma is aggravated by aspirin. Aspirin sensitivity is present in 4-6 % of asthmatics on history, but if aspirin challenges are conducted, 20 to 30% of asthma patients are shown to be aspirin sensitive. Paradoxically, aspirin has been reported to improve asthma symptoms in some patients. Whether aspirin should have a blanket prohibition in asthma is debatable. Non-steroidal anti–inflammatory agents fall into the same group as aspirin. The alternative, paracetamol (acetaminophen) has recently be reported to increase the risk of development of asthma when given to young children. Anaphylaxis has been reported to paracetamol. Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) programme investigated the association between paracetamol consumption and asthma. Authors have shown that use of paracetamol in the first year of life and in later childhood, is associated with the risk of asthma, rhinoconjuctivitis and eczema at age 6 to 7 years .They suggest that exposure to paracetamol might be a risk factor for the development of asthma in childhood. Attributable risks are between 22% and 38 (5). The risk of adverse reactions to allergen immunotherapy is greater in asthmatics. The possibility of adverse reactions to seemingly unlikely therapies must always be entertained, for example corticosteroids, or exipients of medications.

4. MANAGEMENT

As a general rule avoidance of a drug responsible for adverse reactions is the most important to prevent ADRs.

5. CONCLUSION

Adverse reactions to drugs are very common in everyday medical practice. It is shown that some drugs cause ADRs in asthmatics and that asthmatics have a greater risk of developing ADRs. As a general rule avoidance of a drug responsible for adverse reactions is the most important to prevent ADRs.

REFERENCES 1.

Walls SR. Drug compliance and hypersensitivity in asthma. Asthma 2009; 10 (suppl.1): 31-32

2.

Vervolet D, Durham S. Adverse reactions to drugs. BMJ, 1998; 16: 1511-4.

3.

Jick H. Adverse drug reactions: the magnitude of the problem. J.Allergy Clin Immunol, 1984; 74: 555-7.

4.

De Shazo RD, Kemp SF. Allergic reactions to drugs and biologic agents. JAMA, 1997; 278: 1895-1906.

5.

Beasley R, Clayton T, Crane J. et al. Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjuctivitis and eczema in children aged 6-7 year: analysis from Phase Three of the ISAAC programme .Lancet, 2008; 372: 1039-48 Corresponding author: Vesna Cukic, MD, Mr sci. Bjelave 99 ,Sarajevo, telefon 061 480 228.E-mail vesnacukic @ hotmail.com

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