Commentary, J Pulm Med Vol: 5 Issue: 4
Review of Pilot Study and Experimental Evidence for Decreased Risk of Complications of Infection associated with Use of Calcium Channel Blockers and Calcineurin Inhibitors
*Corresponding Author: Larry Weinrauch Cardiology Department, Mount Auburn Hospital, Cambridge, USA, Tel: 617-923-0800; E-mail: [email protected]
Received: August 20, 2021; Accepted: September 03, 2021; Published: September 10, 2021
Citation: Elia JAD, Weinrauch LA (2021) Review of Pilot Study and Experimental Evidence for Decreased Risk of Complications of Infection associated with Use of Calcium Channel Blockers and Calcineurin Inhibitors. J Pulm Med 5:4
Keywords: Calcium Channel Blockers, Calcineurin Inhibitors
Despite many negative studies beyond the scope of this brief review, there are areas that involve employment of calcium channel blockers to decrease risk of bacterial infection or parasitic infestation . If calcium channel blockers can avert antibiotic resistance, this would benefit individual patient care and the healthcare budget as newer medications are developed. While many potential mechanisms leading to antibiotic resistance have been researched, the mechanism that has drawn most attention is rapid extrusion of antibiotic from zones of the invading pathogen. The routes of extrusion appear to be channels that can be blocked by calcium channel blockers even if not identified as traditional calcium channels. When these channels are successfully blocked, higher concentrations of antibiotic remain in a position to attack the invading pathogen.
Three retrospective studies of infection in hypertensive populations drew attention to the finding of benefit for study groups treated with calcium channel blockers versus equivalent study groups treated with a different class of anti-hypertensive agent. The groups ranged from general [2,3] to immune suppressed populations  in which pneumonia was the leading, but by no means the only, infectious outcome of concern. At this point we are aware of studies evaluating pneumococcal pneumonia resistant to quinolones  and pulmonary tuberculosis resistant to rifampicin  in which the investigators found benefit with use of calcium channel blockers. Other Gram positive organisms that have been shown to employ the antibiotic extrusion mechanism include Bacillus, Clostridium Listeria, and Staphylococcus while Gram negative organisms that have been shown to use the antibiotic extrusion mechanism include Bacteroides, Brucella, Enterobacter Hemophilus, Neisseria, Pseudomonas, and Vibrio. As newer primary treatments for these serious infections are developed, there may be reduced cost with the assistance of calcium channel blockers, which would require prospective investigation looking at benefit to patient health with the goal of reducing development of antibiotic resistant strains that can be expected when higher antibiotic doses are ordered more frequently.
Beyond in vitro studies of bacteria, several parasite species have been demonstrated to extrude antibiotics, including Plasmodium falciparum , Schistosoma mansoni , Leishmania amazonensis , and Trypanosoma cruzi , and Toxoplasma gondii  in fashions that are common world-wide sources of resistance.
The calcium/calmodulin/calcineurin pathway may be inhibited by both calcineurin inhibitors (cyclosporin, tacrolimus) useful for immunosuppression in solid organ transplantation and by calcium channel blockers. Both calcineurin inhibitors and calcium channel blockers have been demonstrated to inhibit the parasite of malaria Plasmodium falciparum as well as various members of the yeast family of potential pathogens, including Aspergillus fumigatus , Candida albicans , and Cryptococcus neoformans . These studies of yeast are in vitro with no clinical reports to our knowledge.
The most extensive antibiotic resistance problems listed here are tuberculosis for which there is currently a new medication  and malaria for which there is currently a new monoclonal antibody  that may not yet be in wide spread distribution. Some geographical locations where tuberculosis and malaria may be overlapping may also be centers of COVID infection where there is not yet wide spread distribution of vaccine or immune globulin. In that connection a physician might be faced with long term treatment of a bacterium, a parasite, and a virus. Study of the role of calcium channel calcium blockers and calcineurin inhibitors may become a greater necessity if patients require long term treatment.
- D’Elia JA, Weinrauch LA (2018) Calcium channels: Roles in infection and sepsis. Mechanism of calcium channel blocker benefits in immunocompromised patients at risk for infection. Int J Molecul Sci 19:2465-2482.
- Dial S, Nessin S, Kezouh A, Suissa S (2014) Antihypertensive agents acting on the angiotensin system and the risk of sepsis. British J Clin Pharmacol 78: 1151-1158.
- Zeng L, Hunter K, Gaughan J, Podder S (2017) Preadmission use of calcium channel blockers and outcome after hospitalization with pneumonia: A retrospective propensity matched cohort study. American J Therap 24: e30-e38.
- Weinrauch LA, D’Elia JA, Gleason RE, Shaffer D, Monaco AP (1995) Role of calcium channel blockers in diabetic renal transplant patients: Preliminary observations on sepsis protection. Clinical Nephrology; 44: 185-192.
- Pretz M, Mikheylor N, Schumacher U, van der Liden M, Duesberg C, et al. (2013) Antihypertensives suppress the emergence of fluoroquinilone-resistant mutants in pneumococci: An in vitro study. Int J Med Microbiol; 303: 176-181.
- Song L, Cui R, Yang Y, Wu X (2013) Role of calcium channels in cellular anti-tuberculosis effects: Potential of gated-voltage calcium channel blockers in tuberculosis therapy. J Microbio, Immuno Infec 48:471-476.
- Scheibel L, Colambani P, Hess A, Alkawa M, Atkinson T (1987) Calcium and calmodulin antagonists inhibit human malaria parasites (Plasmodium falciparum): Implications for drug design. Proceedings National Academy of Science USA; 84: 7311-7314.
- Gryseels B, Mibayye A, DeVias S, Stelma F, Guisse F, et al. (2001) Are poor responses to praziquantel for treatment of Schistosoma mansoni infections in Senegal due to resistance? An overview of the evidence. Tropical Medicine International Health; 6: 864-876.
- Pollo L, deMoraes M, Cisillotto J, Creczynski-Pasa T, Steindel M, et al. (2017) Synthesis and in vitro evaluation of Ca+2 channel blockers 1,4 dihydropyridine analogues against Trypanosoma cruzi and Leishmania amazonensis. Parasitology International 66: 789-797.
- Kantani S, Fuks J, Olagsson E, Westermark L, Chambers B, et al. (2017) Voltage-dependent calcium channel signaling mediates GABA receptor-induced migrating activation of dendritic cells infected by Toxoplasma gondii. PLoS Pathology; 13: e1006739.
- DiMarco T, Freitas F, Almeida R, Brown N, desReis T, et al. (2012) Functional characterization of an Aspergillus fumagatus calcium transporter (mCA) that is essential for fungal infection. PLoS ONE
- Krauss P, Nichols C, Heightman J (2005) Calcium and calcineurin-independent roles for calmodulin in Cryptococcus neoformans morphogenesis and high-temperature growth. Eukaryote Cell 4:1079-1087.
- Yu Q, Ding X, Bing Z, Xu N, Jia C, et al. (2014) Inhibitory effect of verapamil on Candida albicans hyphae development, adhesion, and gastrointestinal colonization. FEMS Yeast Research 14: 633-641.
- Dorman S, Nahid P, Kurbatova E, Phillips P, Bryant K, et al (2021) for the Tuberculosis Trial Commission. Four-month trial of rifapentine with or without moxifloxicam for tuberculosis. New England J Med 384: 1705-1718.
- Gauchinsky M, Berkowitz N, Irides A, Coates E, Holman L, et al (2021) for the VRC study team. A monoclonal antibody for malaria prevention. New England J Med