ANALYSIS ON 85 CASE REPORTS OF ADVERSE DRUG REACTIONS

This study investigated the occurrence and characteristics of adverse drug reactions (ADR) in our hospital and provide references for clinical rational drug use. We collected the 85 case reports of adverse drug reactions in our hospital in 2010 and made retrospective statistical analysis on them. The varieties of anti-infective drugs used are the most used. It also had the highest proportion of adverse drug reactions; the common symptom of adverse drug reactions is skin and accessory damage. Adverse drug reactions are affected by many factors, and relevant departments should strengthen ADR monitoring, to reduce or avoid the occurrence of adverse drug reactions.


Introduction
Adverse drug reactions (ADR) refer to the harmful reactions unrelated with drug use purposes caused by approved drugs under normal usage and dosage, including side effects, allergic reactions, toxic reactions, drug dependence, mutation, distortion, canceration, etc.With the continuous and deepened implementation of ADR monitoring system in our country, ADR incidence continues to increase.In order to improve body physiology, improve the quality of clinical treatment and reduce medical disputes, ADR monitoring and reporting have become the legal obligations for medical institutions (Jin et al., 2004).With the continuous strengthening of drug use management, ADR monitoring becomes increasingly important to guaranteeing public drug use safety, and strengthening.ADR monitoring function has become an important content of the current epidemiological studies on drugs (Zhao et al., 2009).This paper assorts and analyzes the 85 ADR cases in our hospital reported in 2010 and summarizes the occurrence and characteristics of adverse reactions, providing scientific references for clinical safe, rational effective drug use.

Data resource
A total of 85 effective reports of ADR were reported by all the Departments in our hospital in 2010.These were collected physicians and pharmacists who filled in the "Adverse drug reactions report form", and the overall ADR summary was made after the preliminary analysis and evaluation by clinical pharmacists.

Methods
A retrospective analysis was made on the clinical data of the 85 cases of ADR, to summarize ADR patients' gender and age distribution, routes of drug administration and clinical manifestations.Incidence of ADR caused by monotherapy and combination therapy, and ADR treatment outcomes were also analysed.

Drug varieties causing ADR and incidence
We make the classification statistics on the drugs involved by ADR according to the drug classification method of Chinese Pharmacopoeia Commission (Chinese Pharmacopoeia Commission., 2001).The 85 cases of ADR involve a total of 50 drugs in 12 categories, in which, 65 cases of ADR were caused by antibiotics, accounting for the largest proportion (65/85, 76.47%), including 1 case of severe allergic shock, and the others were mostly rash and other allergic-like reactions.In the cases of ADR, the varieties ranked in decreasing order: amoxicillin sulbactam sodium, ceftriaxone and levofloxacin injection.

Prognosis
All the symptoms of ADR relieve or disappear after drug withdrawal or changing/replacing for other treatment, and there was no case report of death.

Discussions Relationship between ages and gender of patients and ADR
It can be seen from Table 1 that in the 85 cases of ADR in our hospital, the incidence in female is slightly higher than that in male, and they can occur at any age group.The proportion in children below 10 years old and elderly above 60 years old is significantly higher than other age groups, which may be related with the physiological characteristics of the elderly and children (Xie et al., 2004).For the elderly, because of visceral dysfunction, plasma and drug binding capability decreases, and different renal clearance rates result in different ADR incidence and severity.For children, underdevelopment of systems and organs and incomplete development of nervous system could be ascribed to the cause of ADR.In the 85 cases of ADR reports, 31 cases were above 60 years old, accounting for 36.47% of the total.The reasons are that the elderly have many Jin and Min Afr J Tradit Complement Altern Med.(2013) 10(3):508-515 http://dx.doi.org/10.4314/ajtcam.v10i3.18511 chronic diseases, the frequency and quantity of drug use are higher than the youth and adults, and also the physiological functions and activities of the systems and drug metabolism capacity in the elderly begin to weaken (Jian et al., 2003) (2) in the elderly, liver and kidney volume gradually decrease, blood flow relatively decreases, liver and kidney blood flow is only about half of a strong man, its metabolic capacity is very low, the first-pass effect is gradually weakened, the bioavailability relatively increases, drug metabolism slows down, and drug half-life is relatively prolonged; (3) the elderly usually have many chronic diseases, concomitant medication is common, and drug interaction and other reasons cause poor medication compliance; (4) because of weakened body functions in the elderly, the ability to digest and absorb drug orally administrated is low, the volume distribution for target organs of fat-soluble drugs increases, albumin in plasma reduces, protein binding of the drugs with high protein binding rate drops sharply, and free drug concentration body increases, resulting in more prone to poisoning and adverse reactions than the youth.Therefore, hospital doctors should choose drugs cautiously according to the special physiological and pathological characteristics of the elderly, adhere to the principles of

Relationship between family allergic history and past ADR history and ADR
It can be seen from Table 2 that unknown family history and past history account for 54.12% and 60.00% respectively, indicating that a large proportion of patients did not pay sufficient attention to the family and past ADR history.In daily clinical work in hospital, paying attention to past allergic history or ADR history will improve drug use safety factor, and emphasize on preventive and protective measures to reduce the risk of drug use.

Relationship between drug administration routes and ADR
It can be seen form Table 3 that in the 85 cases of ADR, 73 cases were caused by intravenous administration, indicating that ADR caused by intravenous administration route is much higher than other routes, because the drug administration route of intravenous infusion is taken as the main treatment method in inpatients.At intravenous infusion, drugs directly enter human circulation, with fast action and no first-pass effect, the pharmacological effects and adverse reactions are stronger than oral administration, and many factors induce ADR, including pH value, osmotic pressure, temperature, particulates, creotoxin, etc (Ling et al., 2005).The requirements of intravenous administration are much higher than other preparations, so improper preparation operation, low preparation quality, inappropriate drug combination, long-term preparation liquid placing, high impurity content and fast (low) infusion will cause ADR.Therefore, at clinical drug administration, doctors should strictly ask patient's medication history, try to minimize intravenous administration, and adopt oral administration or intramuscular injection instead of intravenous administration if possible (Wang et al., 2009;Zhao et al., 2009).In case of special demand for intravenous administration, drug administration speed should be controlled, especially for certain stimulant drugs.

Relationship between drug combination and ADR
Drug combination always causes drug interactions, and more drugs are combined, the higher the incidence of ADR is.
Drug combination is an important cause of ADR, and the combination of antimicrobial drugs with other drugs can induce or aggravate adverse drug reactions (Wu et al., 2010).Therefore, it is suggested to minimize the drug varieties needed for clinical treatment.

Relationship between drugs and ADR
It can be seen from Table 4 that the 85 cases of ADR involve a total of 50 drugs in 12 categories, in which, the most involved is antimicrobial drugs, whether the varieties of ADR caused or the number the cases rank the first, consistent with the similar domestic report result (Yang et al., 2001).This may be related with gradually increased frequency and dosage of clinical use of antimicrobial drugs, increased bacterial resistance, non-indicative drug use, drug combination, overdose, long drug use time, etc. Irrational use of antibiotics not only increases the economic burden of patients, and also increases the incidence of ADR, as well as causes bacterial resistance, increases associated complications and prolongs the course of disease.Therefore, doctors need focus on the rational use of antibiotics and the scope of application, and the antibiotics causing ADR are mostly cephalosporins and fluoroquinolones.Cephalosporins have broad antimicrobial spectrum, obvious bactericidal effects, stable action on β-lactamase, relatively low toxic reactions and good clinical efficacy and are very Jin and Min Afr J Tradit Complement Altern Med.(2013) 10(3):508-515 http://dx.doi.org/10.4314/ajtcam.v10i3.18514 commonly used in clinical conditions, so the ADR cases are more reported.This should remind us that doctors should pay full attention to ADR caused by cephalosporins.The clinical manifestations are mainly allergic-like reactions and involve many organs and systems, so clinicians should use antibiotics in strict accordance with the "Guiding principles for clinical use of antibiotics", and it is suggested to make skin test when cephalosporins use is indicated, to reduce the incidence of adverse reactions (Jin et al., 2004).

Relationship between clinical manifestations and ADR
It can be seen from Table 5 that the clinical manifestations of ADR are mostly skin and accessory damage and secondly digestive system and nervous system damages, however, it is easy to find and diagnose these two reactions in clinical conditions.The incidence of allergic skin reaction is high, but the majority of disease conditions are mild, and the symptoms will disappear immediately after drug withdrawal or giving antihistamines.In addition, some commonly used drugs in clinical use, such as traditional Chinese medicine compound, anti-infective drugs, etc, are antigens, easy to cause allergic reactions after entering into body, so as to cause dermatitis, rash and other symptoms (Zhang et al., 2010).

Conclusion
It is impossible for completely prevent ADR, but it is possible to reduce the incidence of ADR.In clinical drug use, the following can be adopted to reduce the incidence of ADR: Adverse drug reaction is very harmful, and it increases medical costs and brings big economic losses, and in severe cases, causes deformity, cancer and mutation and even endangers the life of patients, therefore, medical care staff must pay high attention to them.Hospital administration departments should pay full attention to the service functions of clinical pharmacist, and pharmacists should cooperate with physicians to make rational drug use regimens and actively carry out the following responsibilities in clinical monitoring of ADR: (1) to help doctors find ADR events in time and accurately fill in the relevant reports; (2) to collect and assort ADR information in the whole hospital in certain period, timely feedback to clinicians, and increase the warning capability for the drugs causing ADR; (3) to monitor drug use in special populations, such as patients with liver and kidney dysfunction, infants and children, elderly patients and breastfeeding women; (4) to release timely ADR information to clinical professional journals and improve preventive consciousness to clinical drug-induced diseases.

( 1 )
Pay attention to patient's constitution and past medical history; to be cautious to use drugs in the elderly and children and strictly master the indications and dosage.(2) Pay attention to drug administration methods and compatibility: to minimize the proportion of intravenous administration and combination of many drugs.(3) Strengthen the rational use of anti-infective drugs: to reduce or avoid long drug use, many combined drugs and long course of treatment.(4) Strengthen ADR event reporting and feedback, provide and perfect drug safety data, and avoid or reduce potential ADR.

Table 2 :
Relationship between family and past ADR history and ADR Distribution of drug administration routes causing ADRThe 85 cases of ADR involve a total of 3 drug administration routes, including 73 cases of intravenous infusion (73/85, Jin

and Min Afr J Tradit Complement Altern Med. (2013) 10(3):508-515 http
The relationship between different drug administration routes and ADR is shown in Table3.

Table 3 :
Distribution of drug administration routes causing ADR

Table 4 :
. Four reasons make elderly patients prone to ADR (Xie et al., 2004): (1) With age increases, the organs in the elderly degrade year Drug varieties causing ADR and incidence