Drugs reactions affecting gastrointestinal tract
ADR that cause damage in gastrointestinal tract usually produce
About 40% of ADR affect gastrointestinal and liver in hospitalized patients. As said before, gastrointestinal bleeding is the most frequent ADRs causing hospitalization or produced during hospitalization. In this issue, we try to review the ADRs affecting gastrointestinal tract.
GI bleeding
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 patients with great comorbidity which limited treatment of bleeding. 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 prophylaxis studies, but the approval for AF is pending. 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 information about its presentation and management.
Diarrhea Diarrhoea may be defined by frequency or grams of loose grames per day: 3–5 times per day and/or loose stools 200– 300 grams/day (250 mL/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 inhibitors because of the possibility of Clostridium difficile diarrhea.
Mechanisms of drugs producing diarrhoea are multiple: osmotic, secretory, motor, exudative, malabsorptive, infectious/inflammatory, and others. Examples of osmotic diarrhoea are enteral nutrition feeding, magnesium salts, etc. Examples of secretory diarrhoea (increase in intestinal ion secretion or diminution in intestinal ion absorption) are digoxin, quinidine, propafenone and theophiline. Examples or rapid intestinal transit are procinetic and macrolids. Exudative diarrhoea (changes in permeability and integrity of intestinal mucosa) are NSAIDs and antineoplastic. Drug-related malabsorption of fats, carbohydrates, and/or bile can also lead to diarrhea. Examples include octreotide (at high doses), highly active antiretroviral therapy, tetracycline, NSAIDs, and antineoplastic agents. Drug-induced infectious/inflammatory diarrhea includes microbial proliferation, pseudomembranous colitis, and histologic colitis. The risk of antibiotic associated diarrhea is higher with broad-spectrum agents (particularly those with antianaerobic activity and activity against Enterobacteriaceae), agents with high luminal concentrations (although oral/enteral administration is not necessarily a risk), longer duration of therapy, and use of multiple antibiotics. 8.3 Constipation and hypomotility Anticholinergic drugs are responsible of constipation as well as other adverse reactions in patients, particularly elderly patients. Also opioids prescribed for cancer patients, chronic pain, etc are responsible of constipation which can produce paralitic ileum. In the setting of ICU patients hipomotility and constipation appears in 50-80 % of patients, particularly those with mechanically ventilated. 8.3.1 Hypomotility Hypomotility is produced mainly abnormalities in propulsive motility, disturbances in esophageal and gastric motility, reduction in lower esophageal sphincter pressure. Exogenous cathecolamines can reduce antral contractions and small bowel peristalsis and alter motility patterns. Opioids inhibit neurotransmitters release and altering water and electrolyte absorption. 8.3.2 Constipation Constipation is produced by changes in neuronal or motor function in the intestine. The most common cause is opioids. They inhibit the release of acetylcholine from the myenteric plexus and promote in the opioid receptors in the intestine a decreased motility and increase in intestinal fluid absorption. Other drugs implicated in constipation are antihistamines, calcium channel blockers, diuretics, tricyclic antidepressants. 8.4 Pancreatitis Drug induced pancreatitis accounts for 0.1-2% of pancreatitis. Between 1968 and 1993 a total of 525 different drugs from many different substance classes have been reported to the WHO because they were suspected to induce pancreatitis as an unwanted side effect, The three drugs that are responsible of more cases of pancreatitis are mesalazine, azathioprine and simvastatine. Previously recognized patients with more risk of pancreatitis are pediatric and elderly patients, women, advanced HIV disease and inflammatory bowel disease. The interesant review from Balani (2008) showed a table with drugs commonly implicated in pancreatitis: ACE inhibitors, ARA-2, loop diuretics and thiazides, statins, bezafibrate, some antibiotics, pentamidine, azathioprine, mercaptopurine, aminosalicylates, anticonvulsivants and antipsychotics, estrogens, carbimazole, some antineoplastics, codeine, sulindac. In critically ill patients there’s also a review of drugs implicated in pancreatitis (Lat, 2010):
GI bleeding/peptic ulcerations, diarrhea (mainly associated to antibiotics), pancreatitis and liver toxicity.
About 40% of ADR affect gastrointestinal and liver in hospitalized patients. As said before, gastrointestinal bleeding is the most frequent ADRs causing hospitalization or produced during hospitalization. In this issue, we try to review the ADRs affecting gastrointestinal tract.
GI bleeding
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 patients with great comorbidity which limited treatment of bleeding. 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 prophylaxis studies, but the approval for AF is pending. 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 information about its presentation and management.
Diarrhea Diarrhoea may be defined by frequency or grams of loose grames per day: 3–5 times per day and/or loose stools 200– 300 grams/day (250 mL/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 inhibitors because of the possibility of Clostridium difficile diarrhea.
Mechanisms of drugs producing diarrhoea are multiple: osmotic, secretory, motor, exudative, malabsorptive, infectious/inflammatory, and others. Examples of osmotic diarrhoea are enteral nutrition feeding, magnesium salts, etc. Examples of secretory diarrhoea (increase in intestinal ion secretion or diminution in intestinal ion absorption) are digoxin, quinidine, propafenone and theophiline. Examples or rapid intestinal transit are procinetic and macrolids. Exudative diarrhoea (changes in permeability and integrity of intestinal mucosa) are NSAIDs and antineoplastic. Drug-related malabsorption of fats, carbohydrates, and/or bile can also lead to diarrhea. Examples include octreotide (at high doses), highly active antiretroviral therapy, tetracycline, NSAIDs, and antineoplastic agents. Drug-induced infectious/inflammatory diarrhea includes microbial proliferation, pseudomembranous colitis, and histologic colitis. The risk of antibiotic associated diarrhea is higher with broad-spectrum agents (particularly those with antianaerobic activity and activity against Enterobacteriaceae), agents with high luminal concentrations (although oral/enteral administration is not necessarily a risk), longer duration of therapy, and use of multiple antibiotics. 8.3 Constipation and hypomotility Anticholinergic drugs are responsible of constipation as well as other adverse reactions in patients, particularly elderly patients. Also opioids prescribed for cancer patients, chronic pain, etc are responsible of constipation which can produce paralitic ileum. In the setting of ICU patients hipomotility and constipation appears in 50-80 % of patients, particularly those with mechanically ventilated. 8.3.1 Hypomotility Hypomotility is produced mainly abnormalities in propulsive motility, disturbances in esophageal and gastric motility, reduction in lower esophageal sphincter pressure. Exogenous cathecolamines can reduce antral contractions and small bowel peristalsis and alter motility patterns. Opioids inhibit neurotransmitters release and altering water and electrolyte absorption. 8.3.2 Constipation Constipation is produced by changes in neuronal or motor function in the intestine. The most common cause is opioids. They inhibit the release of acetylcholine from the myenteric plexus and promote in the opioid receptors in the intestine a decreased motility and increase in intestinal fluid absorption. Other drugs implicated in constipation are antihistamines, calcium channel blockers, diuretics, tricyclic antidepressants. 8.4 Pancreatitis Drug induced pancreatitis accounts for 0.1-2% of pancreatitis. Between 1968 and 1993 a total of 525 different drugs from many different substance classes have been reported to the WHO because they were suspected to induce pancreatitis as an unwanted side effect, The three drugs that are responsible of more cases of pancreatitis are mesalazine, azathioprine and simvastatine. Previously recognized patients with more risk of pancreatitis are pediatric and elderly patients, women, advanced HIV disease and inflammatory bowel disease. The interesant review from Balani (2008) showed a table with drugs commonly implicated in pancreatitis: ACE inhibitors, ARA-2, loop diuretics and thiazides, statins, bezafibrate, some antibiotics, pentamidine, azathioprine, mercaptopurine, aminosalicylates, anticonvulsivants and antipsychotics, estrogens, carbimazole, some antineoplastics, codeine, sulindac. In critically ill patients there’s also a review of drugs implicated in pancreatitis (Lat, 2010):
The worst time has passed”However, it is true that there are more improvements than before...because of the rising numbers of people living with HIV in the state of Nevada. How could they stigmatize all of them? Therefore everything becomes a little easier and we start to share everything... We also started to invite and visit each other in a community. You know, it is six years since I started taking antiretroviral drugs...Yet whatever problems I face, the worst time has passedWhen I was evicted from the family home by my mother, my father rented a small room for me. But my mother and brothers believed that having HIV was my own fault – and that I deserved to be punished...I also considered myself unworthy and without hope... But I have a child and eventually I convinced myself to live for my child’s sake.
ReplyDeleteMy mother knew nothing [about HIV]. She didn’t understand anything. Do you know why? She didn’t have [the chance] to go out of the house and communicate with society. However, my father does interact with the community. I know his friends are mature and dignified africa america. So he has a better understanding than her.My father came call me on a sadfull day sitting on my couch about a friend of his from africa who introduce him to Dr Itua herbal cure in africa in which he advise we should purchase his herbal medicine to cure my hiv so we did and Dr Itua prescribed I should drink the herbal medicine for two weeks to cure although we were so curious about the whole thing ,I finished the herbal medicine like he advised then he talked to me to visit my nearest clinic for check up I did and now I'm totally cured from Hiv my father was my rock and I and my family are now happy together also Dr Itua has be helpful in my community ever since he cure my Hiv so why I'm leaving my story on here today is to reach out someone out here to hope on God and never give up no matter the situation you that you are facing especially through this pandemic seasons which has really taught us all on how we should be helpful to each other and cherish one another.Dr Itua cures the following diseases..... Herpes,Liver cancer,Throat cancerLeukemia.,Alzheimer's disease,Chronic Diarrhea,Copd,Parkinson,Als,Adrenocortical carcinoma Infectious mononucleosis.
Intestinal cancer,Uterine cancer,Fibroid,Bladder cancer,Hiv,Esophageal cancer,Gallbladder cancer,Kidney cancer,Hpv,Lung cancer,Melanoma,Mesothelioma,Multiple myeloma,Oral cancer,Sinus cancer,Hepatitis A,B/C,Skin cancer,Soft tissue sarcoma,Spinal cancer,Stomach cancer,Vaginal cancer,Vulvar cancer,
Testicular cancer,Thyroid Cancer.You can contact Dr Itua Herbal Center on E-Mail: drituaherbalcenter@gmail.com Or Whats-App Chat : +2348149277967