**1. Introduction**

510 New Advances in the Basic and Clinical Gastroenterology

[79] Riggio O, Ridola L, Pasquale C, Nardelli S, Pentassuglio I, Moscucci F, et al. Evidence of

Clin Gastroenterol Hepatol. 2011 Feb;9(2):181-3.

persistent cognitive impairment after resolution of overt hepatic encephalopathy.

Adverse drug reactions are common and there is an increasing interest in recognizing them. There are several studies that try to identify epidemiology, true incidence in hospitalized and not hospitalized patients and the main concerns about their causes and possible solutions. Gastrointestinal tract, mainly haemorrhages and peptic disease are the most common site of adverse drug reactions; that´s the reason why we should recognize this problem and how to manage. Also we try to review the most common drugs affecting gastrointestinal tract. Less common and, usually less severe, liver disease and pancreatitis can be produced by adverse drug reactions. In this chapter we review theses aspects of adverse drug events, particularly, those related to drugs affecting gastrointestinal tract.

#### **2. Definition of adverse drug reactions**

An adverse drug event is an unwanted and unintended medical event related to the use of medications. An adverse drug event is considered an adverse drug reaction (ADR) when there is a causal link between the event and use of the drug. An adverse drug reaction is considered serious when the patients outcome is one of the following: death, lifethreatening, hospitalization (initial or prolonged), disability –significant, persistent or permanent change, impairment, damage or disruption in the patient's body function/structure or physical activities or quality of life, congenital anomaly or require intervention to prevent permanent impairment or damage [Supplementary information in Appendix 1].

Causality assessment is necessary to determine the likehood that a drug caused a suspected ADR. There are a number of different methods used to judge causation, the first attempts were proposed by Karch and Lasagna (1977), Lecenthal et al. (1979) and Naranjo et a.l (1981). Most of these approaches to assigning causality are based on the following clinical features: temporal relationship between drug exposure and the onset of adverse drug event, characteristic symptoms and laboratory abnormalities and/or histology, and challengedechallenge-rechallenge (improvement after stopping the suspected drug and reappearance after starting the agent in question).

Adverse Reactions and Gastrointestinal Tract 513

These statistics do not include the number of ADRs that occur in ambulatory settings. The exact number of ADRs is not certain and is limited by methodological considerations. However, whatever the true number is, ADRs represent a significant public health problem. In a Sweden study there were reviewed the death reports in one year in relation with adverse drugs reactions. They found 3.1% of deaths associated with fatal adverse drug events, mostly haemorraghes. 89% of patients died at hospital meanwhile only 35% of

So most of studies trying to establish epidemiology and cost of adverse drug reactions demonstrate that these events are harmful and we have to make great efforts to diminish the

In western countries, drug-related illnesses account 5% to 10% of inhospital costs, and being associated with a substantial increase in morbidity and mortality. In addition to their impact on human health, ADRs also have significant impact on healthcare costs. These costs are essentially hospital costs, in particular arising from an increase in length of stay caused by an ADR. Although has been estimated that the occurrence of an ADR during hospitalization or leading to hospitalization is responsible in U.S.A. (data from 1997) for a cost of approximately 2800 Euros in an additional length of stay of 2.2 days, several studies have also pointed out that the structure of ADR cost is heterogeneous, a factor which must be taken into account when developing preventive strategies. Although data of costs were not calculated, Sanchez Muñoz-Torrero et al (2010) study found an increase in hospital staying in almost 9 days (18±17 days vs 9.6±5.8, p<0.001), which accounts for more direct and indirect costs of the hospitalization. Also another Spanish (Carrasco Garrido et al, 2010) study found an increase in

Older patients are particularly vulnerable to drug-related illness because they are usually on multiple drug regimens, which expose them to the risk of drug interactions (Mallet et al, 2007), and because age is associated with changes in pharmacokinetics and

Onder et al. (2010) developed and validated a risk stratification model (The GerontoNet ADR Risk Score) to identify patients 65 years or older who are at risk for an ADR during hospitalization. They used data from the Italian Group of Pharmacoepidemiology in the Elderly to develop an ADR risk score. The ADR risk score was then validated in a sample of older adults who were admitted to 4 university hospitals in Europe. The number of drugs and history of an ADR were the strongest predictors of ADRs, followed by heart failure,

Recently Sánchez Muñoz-Torrero et al found that renal function and drug–drug interactions were statistically significant associated with the appearance of ADR. Also duration of hospitalization was associated but it wasn't possible to establish that if duration of hospitalization was the cause or the consequence of ADR. Recently Hamilton et al (2011) reviewed the adverse drug reactions in older people with potentially inappropriate

19% of hospital costs associated with the appearance of adverse drug events.

liver disease, presence of 4 or more conditions, and renal failure (Table 1).

**6. Potential causes implicated in adverse drug reactions** 

patients dead at hospital with no relation with drug events.

incidence and morbidity.

**5. Cost of adverse drug reactions** 

pharmacodinamics (Aronson, 2007).

prescriptions.

ADRs can be considered "on-target" effects, if they are result of exaggerated pharmacology that may be managed by dose reduction or other therapeutic modifications, i.e. hypoglycemia associated with antidiabetic agents. "Off-target" toxicities are frequently more problematic because they may not be predicted from pharmacology and toxicology studies, and they may occur only after prolonged exposure, i.e. hypersensibility reactions associated to antiepileptics. Unexpected ADRs that first appear after marketing authorization of the medication continue trouble clinicians, regulators, and drug sponsors. The most notably cause is the use by large number of patients, providing sufficient statistical power to detect rare events. Other factors include use in special populations, drug inte ractions, renal and hepatic insufficiency, long duration of use and drug withdrawal.
