Clement Kabakama¹*, Aneena Suresh², Abdul Rafey Usmani³ and Zahra D Khan⁴

¹Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Tanzania
²Department of Pharmacy Practice, JSS High Academy of Higher Education and Research, India
³Department of Pediatric, University of Dodoma Teaching Hospital, Tanzania
⁴Department of Cardiology, TMJ Multi Speciality Hospital, Tanzania

*Corresponding Author: Clement Kabakama, Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Tanzania.

Received: May 22, 2021; Published: June 07, 2021

Abstract

  Alprazolam induced pedal edema is a rare entity. Alprazolam acts at several sites within the central nervous system, including the limbic system and reticular formation effects which may be mediated through GABA (A) sub unit receptor system where by leading to increase in neuronal membrane permeability to chloride ions enhances the inhibitory effects of GABA. We report a case of a 70 year-old-female patient with complaint of difficulty in breathing, tiredness and palpitations. She was later diagnosed with congestive heart failure. On the third day patient had complaint of difficult in sleeping and was prescribed alprazolam.

  The following day, during the ward round, odema was reported and alprazolam was stopped and reported as an ADR through spontaneous reporting form of an adverse drug reaction. During Hospitalization the Prognosis of the patient to withdrawal of the causative agent was done and the Patient her swollen left leg, managed with loop diuretic. Hence forth we report a rarely incidence of alprazolam inducing pedal edema.

Keywords: Incidence; Alprazolam; Pedal edema; Adverse Drug Reaction

Introduction

  Alprazolam induced pedal edema is a rare entity. Alprazolam acts at several sites within the central nervous system, including the limbic system and reticular formation effects which may be mediated through GABA (A) sub unit receptor system where by leading to increase in neuronal membrane permeability to chloride ions enhances the inhibitory effects of GABA.

Case Report

A 70-year-old female Patient was admitted to Female Medical ward at Government Hospital with complaints of difficult in breathing, tiredness and chest pain.

However, her medication history were not identified.

  The patient was diagnosed with congestive heart failure. On the first day patient was prescribed with tablet digoxin 0.25 mg, injection cefotaxime, injection gentamycin. On the second day patient was added up with injection deriphyllin for her complaint of breathlessness. On the third day patient had complaint of difficult in sleeping and was prescribed with alprazolam, initially the patient pedal edema was not present on the time of the admission the following day during the ward rounds, patient had aggravating severe pedal edema and because she was class II stage diagnosed heart failure, her left leg presenting with pedal edema as shown in figure 1 and the main cause was ruled out and suspected drug for her pedal edema was detected.

Figure 1: Presentation of Left foot with pedal edema.

  Alprazolam was stopped and reported as an ADR through spontaneous reporting form of an adverse drug reaction. During hospitalization the prognosis of patient to withdrawal of the causative agent was done and patient her swollen left leg was managed with combination of loop diuretic as well with the potassium sparing diuretic.

Discussion

  Drug induced edema is presently clinical manifestation caused by variously medication prescribed in patients [1]. Majority of medication prescribed are NSAIDs medications, antihypertensive drugs, anticancer drugs and so on. Alprazolam is a benzodiazepine which is used for the management of anxiety including panic disorder, Alprazolam act by the binding to GABA sub unit A receptor which associate with binding into receptors at several sites within Central Nervous System including the limbic system and reticular formation effects may be mediated through GABA receptor system increasing in neuronal membrane permeability to chloride ions enhances the inhibitory effects of GABA the shift in chloride ions causes hyperpolarization and stabilization of the neuronal membrane [2].

  Inspite of that some of the drug causing pedal edema have been reported with recently few literatures. However, researchers noted that this adverse event appeared to be dose dependent but also idiosyncratic as no predisposing features were identified in patients who did develop edema following drug induced edema. Furthermore, researchers concluded that development of edema resulted in extensive medical evaluation in some patients and was only minimal responsive to diuretic therapy [3]. Alprazolam acts at several sites within the CNS, including the limbic system and reticular formation effects which may be mediated through GABA (A) sub unit receptor system increase in neuronal membrane permeability to chloride ions enhances the inhibitory effects of GABA.

  Despite of that there are few studies of the case report which has elaborated of the drug induced pedal edema for example on the use of dihydropyridine calcium blockers to cause pedal edema it is well to be known [4]. In our case study left leg pedal edema has been observed as an adverse drug reaction to a noticeable point of Alprazolam administration which is used for management of insomnia and inspite of that it is well documented with Food and Drug Administration to cause peripheral edema [5]. However mechanism of Alprazolam induced pedal edema it is not well understood, Although Leg edema might occur in systemic circulation and to local types as well. Systemic edema could be caused by congestive cardiac failure, renal failure, hypoalbuminemia or proteinuria [6].

  There are many factors could cause above mentioned adverse drug reaction, into our patient we suggest that an incidence of edema due to alprazolam administration into her prescription which led to aggravating her pedal edema, despite the use of diuretics which were prescribed later on after reporting the incidence. The probability assessment scale of adverse drug reaction was done according to Naranjo Scale Probability for assessment of Adverse drug Reaction (ADR) was found to be possible with the average score of +4 [7].

Table 1: Scoring for Naranjo algorithm: >9 = definite ADR; 5–8 = probable ADR; 1–4 = possible ADR; 0 = doubtful ADR.

Conclusion

  We report a rarely case of alprazolam induced pedal edema, alprazolam induced pedal edema is rarely entity to be observed. However, withdrawal of suspicious drug is the mainstay for prevention of drug induced pedal edema especially towards diagnosed patient with class two congestive heart failure. The main stay treatment of patient presented with pedal edema due to the drug induced is discontinuation of responsible drug. However, patient may be treated with combination therapy of diuretics as to improve the overall patient prognosis of drug induced pedal edema.

References

1. Kaizu K and Abe M. “Drug induced edema”. Japanese Journal of Clinical Medicine 1 (2005): 102-106.
2. Charles G., et al. “Benzodiazepine Pharmacology and Central Nervous System-Mediated Effects”. Ochsner Journal 2 (2013): 214-223.
3. Reza Bidaki., et al. “Gabapentin induces edema, hyperesthesia and scaling in a depressed patient; a diagnostic challenge”. Advanced Biomedical Research 1 (2016): 2277-9175.
4. Sirker A., et al. “Dihydropyridine calcium channel blockers and peripheral side effects”. Journal of Human Hypertension 10 (2001): 745-746.
5. Kaplan GB., et al. “Single dose pharmacokinetics and pharmacodynamics of alprazolam in elderly and young subjects”. Journal of Clinical Pharmacology 1 (1998): 14-21.
6. Peter Gorman., et al. “Swollen lower limb general assessment and deep vein thrombosis”. Western Journal of Medicine 2 (2001): 132-136.
7. Naranjo CA., et al. “A method for estimating the probability of adverse drug reactions”. Clinical Pharmacology and Therapeutics 30 (1981): 239-245.

Citation

Citation: Clement Kabakama., et al. “A Case Report on Alprazolam Induced Pedal Edema”. Acta Scientific Gastrointestinal Disorders 4.7 (2021): 03-06.

Copyright

Copyright: © 2021 Clement Kabakama., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.