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

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 pharmacodinamics (Aronson, 2007).

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

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 prescriptions.

Adverse Reactions and Gastrointestinal Tract 515

during hospitalization. In this issue, we try to review the ADRs affecting gastrointestinal

Mainly non steroidal anti-inflammatory drugs and antiplatelet/anticoagulants are implicated in gastrointestinal bleeding. The most frequent lesion is gastric erosions (about 40.2%), combination of gastric ulcer and gastric erosions (16.1%), gastric ulcer (15.0%), duodenal ulcer (13.8%), normal (13.8%) and duodenal erosions (1.1%). In a recent study 26% of patients admitted because of gastrointestinal bleeding had antiplatelet or anticoagulants as the cause of bleeding. The distribution of lesions was quite similar to the study from Devy, being gastric ulcer the most common lesion involved in the bleeding. Inhibition of cyclooxygenase, leading to inhibition of gastric prostaglandin synthesis, and impaired GI defense mechanisms represent additional mechanisms of drug-induced GI bleeding. In the particular setting of Intensive Care Units (ICUs) the most frequent lesion found in patients is the stress-related mucosal bleeding, in which another causes apart from drugs are implicated. In the study from Wikman-Jorgensen (2011) mortality of upper gastrointestinal bleeding was 3,5%, all in

Drugs most frequently causing bleeding were aspirin in 36%, acenocumarol in 27%, clopidogrel in 18%. Combination of aspirin and clopidogrel are responsible of 6% of upper gastrointestinal bleeding. Aspirin is the drug more frequently implicated but it may chance in the future because of the increasing use of doble antiplatelet treatments and new anticoagulants (Rivaroxaban, Apixaban and Dabigatran). It is possible than in the near future we begin to see hemorrhages with dabigatran because of the recent approval in USA for the use of treatment in atrial fibrillation, including patients with low risk of thromboembolism. The risk of bleeding is bigger with Rivaroxaban as shown in the

Also lower gastrointestinal bleeding is increasing because of use of AINES mainly. New techniques for diagnosing lesions in small and large intestine are proving this increase in lower gastrointestinal bleeding. AINES can cause diverticulum perforation, mucosal inflammation, ulceration, causing bleeding in the intestine. Use of aspirin, clopidogrel or anticoagulants and the lower intestinal bleeding is an issue that has to be studied because of its frequency, use and potential harmful in small and large intestine. There´s little

Diarrhoea may be defined by frequency or grams of loose grames per day: 3–5 times per day

It´s estimated that diarrhoea accounts for the 7% of ADRs. There are lot of drugs producing diarrhea as a secondary effect: metformin, some chemotherapies, antibiotics, mainly clavulanic, clindamicin, immunosuppressant… Most of them cause diarrhea only while taking, or only at the beginning of prescription, but some are associated with chronic diarrhoea as metformin. However, the possibility of a drug causing a severe diarrhea is less common except in the case of antibiotics, hipomotility drugs, steroids, proton pump

patients with great comorbidity which limited treatment of bleeding.

prophylaxis studies, but the approval for AF is pending.

information about its presentation and management.

and/or loose stools 200– 300 grams/day (250 mL/day).

inhibitors because of the possibility of Clostridium difficile diarrhea.

tract.

**8.1 GI bleeding** 

**8.2 Diarrhea** 


Abbreviations: ADR, adverse drug reactions; CI, confidence interval; OR, odd ratio.

Table 1. Variables included in the Score (adapted from Onder *et al*)
