Proton Pump Inhibitors and Anti-emetic Cocktail - A remedy for all

A blend of Proton Pump Inhibitor and anti emetics is something that a bulk of patients get, sometimes without a reason. I think it is time to step back and always question ourselves prior to ordering these medications. More importantly, we need to get rid of the thought that pushes us to prescribe thinking that "if there is no benefit, they are probably not going to hurt". Let us look at some possible downsides of these drugs. 

Proton Pump Inhibitors

They are used for a myriad of concerns such as headache, vomiting, nausea, abdominal pain (regardless of presumed etiology), eradicate H. Pylori, ZE Syndrome, gastroenteritis, GERD and so on.. While a single dose may not have much side effects but in the long run, there are potential downsides that might accompany these medications. In addition, these are freely available as over the counter preparations and therefore, have the possibility of being misused. 

Possible Adverse Effects with long term use (other than GI Distress and Headache)

1. Hypocalcemia, Osteoporosis and Fractures Probably because dietary calcium absorption is dependent upon an acidic environment in the gut.

2. Hypomagnesemia (May present as arrhythmias)

3. Anemia (B12 and Iron deficiency)

PPIs may also affect vitamin B12 levels because the body can’t absorb the vitamin without stomach acid to uncouple the vitamin from protein in food. 

It is unlikely that patients with normal iron stores will develop iron deficiency anemia from PPI use alone. However, patients with low baseline iron stores may be more susceptible to further iron depletion with concurrent PPI therapy.

4. Increased risk of infections (Pneumonia and Clostridium Difficle)

PPIs blunt the gastric acid secretion that act as a defense mechanism against enteric bacteria. Increased gastric pH during PPI use allows for colonization of opportunistic microbes) 

5. Alters the composition of gut flora 

6. Interact with Clopdrogel (click here to read more on this interaction)

PPI therapy in combination with clopidogrel (Plavix) use may increase the risk of cardiac events.

Ondansetron (AKA Emeset, Zofer, Zofran)

It is a 5HT3 receptor antagonist that is frequently used for Postoperative and Chemo  Induced Nausea Vomiting , also prescribed for N&V in general and gastroenteritis. It is metabolised by liver.

Concerning Adverse Effects

1. QT prolongation
2. Headache, Dizziness, Fever 
3. Rash, Bronchospasm
4. Diarrhoea/Constipation
5. Serotonin Syndrome (with concomitant use of serotonergic meds)

References:

1  Hutchinson C, Geissler CA, Powell JJ, Bomford A. Proton pump inhibitors suppress absorption of dietary non-haem iron in hereditary haemochromatosis. Gut. 2007;56(9):1291–1295.

2  Ito T, Jensen RT (2010). "Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B₁₂, iron, and magnesium". Current Gastroenterology Reports 12(6): 448–57. 

3  Focks JJ, Brouwer MA, van Oijen MG, Lanas A, Bhatt DL, Verheugt FW (2013). "Concomitant use of clopidogrel and proton pump inhibitors: impact on platelet function and clinical outcome- a systematic review". Heart 99(8): 520–7. 

4   Cardoso RN, Benjo AM, DiNicolantonio JJ, Garcia DC, Macedo FY, El-Hayek G, et al. (2015). "Incidence of cardiovascular events and gastrointestinal bleeding in patients receiving clopidogrel with and without proton pump inhibitors: an updated meta-analysis". Open Heart 2 (1): e000248. 

5   Lambert AA, Lam JO, Paik JJ, Ugarte-Gil C, Drummond MB, Crowell TA (2015). "Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and meta-analysis". PLoS ONE 10 (6): e0128004. 

6  Corleto VD et al. Proton pump inhibitor therapy and potential long-term harm. Current Opinion in Endocrinology, Diabetes and Obesity. 2014 February;21(1):3-8. doi:10.1097/MED.0000000000000031 PMID 24310148

7   US Food and Drug Administration. (2012). FDA Drug Safety Communication: New information regarding QT prolongation with ondansetron (Zofran). Retrieved from http://www.fda.gov/Drugs/DrugSafety/ucm310190.htm

8  Gollapudy, Suneeta, Vikram Kumar, and M. Saeed Dhamee. "A case of serotonin syndrome precipitated by fentanyl and ondansetron in a patient receiving paroxetine, duloxetine, and bupropion." Journal of clinical anesthesia 24.3 (2012): 251-252.