Calcium channel blocker: Difference between revisions

'''Calcium channel blockers''' ('''CCB'''), '''calcium channel antagonists''' or '''calcium antagonists'''<ref name=Lange2011>{{cite book|last=Olson|first=Kent|title=Poisoning & drug overdose|date=2011|publisher=McGraw-Hill Medical |isbn=978-0-07-166833-0|edition=6th |chapter=40. Calcium Channel Antagonists}}</ref> are a group of [[medication]]s that disrupt the movement of [[calcium]] ({{chem|Ca|2+}}) through [[calcium channel]]s.<ref>{{DorlandsDict|nine/20112461|calcium channel blocker}}</ref> Calcium channel blockers are used as [[antihypertensive drug]]s, i.e., as medications to decrease [[blood pressure]] in patients with [[hypertension]]. CCBs are particularly effective against large vessel stiffness, one of the common causes of elevated [[Systole|systolic]] blood pressure in [[elderly care|elderly patients]].<ref name=nps01>{{cite journal | author = Nelson M | title = Drug treatment of elevated blood pressure | journal = Australian Prescriber | year = 2010 | volume = 33 | issue = 4 | pages = 108–12 | doi = 10.18773/austprescr.2010.055 | doi-access = free }}</ref> Calcium channel blockers are also frequently used to alter [[heart rate]] (especially from atrial fibrillation), to prevent peripheral and [[cerebral vasospasm]], and to reduce [[chest pain]] caused by [[angina pectoris]].

CCBs have been shown to be slightly more effective than [[beta blockers]] at lowering [[cardiovascular]] [[Mortality rate|mortality]] associated with stroke, but they are associated with more [[side effects]].<ref>{{cite journal |vauthors=Chen N, Zhou M, Yang M, Guo J, Zhu C, Yang J, Wang Y, Yang X, He L | year = 2010 | title = Calcium channel blockers versus other classes of drugs for hypertension | journal = Cochrane Database of Systematic Reviews | volume = 8 | issue = 8| page = CD003654 | doi = 10.1002/14651858.CD003654.pub4 | pmid=20687074}}</ref><ref>{{cite web|url=http://www.medicinenet.com/calcium_channel_blockers/page2.htm#side%20effects|title=Calcium Channel 0799653155Blockers|page=2|website=MedicineNet|access-date=2013-01-19|archive-date=2012-04-21|archive-url=https://web.archive.org/web/20120421102911/http://www.medicinenet.com/calcium_channel_blockers/page2.htm#side%20effects}}</ref> Potential major risks however were mainly found to be associated with short-acting CCBs.<ref>{{cite web|url=http://cmbi.bjmu.edu.cn/uptodate/hypertension/drg%20therpy/Major%20side%20effects%20and%20safety%20of%20calcium%20channel%20blockers.htm|title=Major side effects and safety of calcium channel blockers|author1=Norman M Kaplan, MD|author2=Burton D Rose, MD|date=Apr 3, 2000|website=Chinese Medical & Biological Information|access-date=July 23, 2012|archive-url=https://web.archive.org/web/20111230013813/http://cmbi.bjmu.edu.cn/uptodate/hypertension/drg%20therpy/Major%20side%20effects%20and%20safety%20of%20calcium%20channel%20blockers.htm|archive-date=December 30, 2011}}</ref>

* [[Diltiazem]] (Cardizem) (also used experimentally to prevent migraine){{cncitation needed|date=March 2022}}

[[Gabapentinoid]]s, such as [[gabapentin]] and [[pregabalin]], are selective blockers of [[CACNA2D1|α2δ subunit]]-containing [[voltage-gated calcium channel]]s. They are used primarily to treat [[epilepsy]] and [[neuropathic pain]].<ref>{{cite journal |last1=Zamponi |first1=GW |last2=Striessnig |first2=J |last3=Koschak |first3=A |last4=Dolphin |first4=AC |title=The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential. |journal=Pharmacological reviewsReviews |date=October 2015 |volume=67 |issue=4 |pages=821-70821–70 |doi=10.1124/pr.114.009654 |pmid=26362469|pmc=4630564 }}</ref>

[[Ziconotide]], a [[peptide]] compound derived from the omega-[[conotoxin]], is a selective [[N-type calcium channel]] blocker that has potent [[analgesic]] properties that are equivalent to approximate 1,000 times that of [[morphine]]. It must be delivered via the intrathecal (directly into the cerebrospinal fluid) route via an intrathecal infusion pump.<ref name="McDowell 2016">{{cite journal |last1=McDowell GC |first1=2ndGC |last2=Pope |first2=JE |title=Intrathecal Ziconotide: Dosing and Administration Strategies in Patients With Refractory Chronic Pain. |journal=Neuromodulation : journal of the International Neuromodulation Society |date=July 2016 |volume=19 |issue=5 |pages=522-32522–32 |doi=10.1111/ner.12392 |pmid=26856969|pmc=5067570 }}</ref>

* [[Peripheral edema]], which can occur in as much as 70% of people receiving calcium channel blocker, is caused by calcium channel blockers' [[Arteriolar vasodilator|preferential arteriolar or precapillary dilation without commensurate dilation in the venous or postcapillary circulation]].<ref name="Sica 2003 pp. 291–295">{{cite journal | last=Sica | first=Domenic A. | title=Calcium Channel Blocker‐RelatedBlocker-Related Peripheral Edema: Can It Be Resolved? | journal=The Journal of Clinical Hypertension | publisher=Wiley | volume=5 | issue=4 | year=2003 | issn=1524-6175 | doi=10.1111/j.1524-6175.2003.02402.x | pages=291–295| pmid=12939574 | pmc=8099365 | doi-access=free }}</ref><ref name="CV Pharmacology">{{cite web | title=Calcium-Channel Blockers (CCBs) | website=CV Pharmacology | url=https://www.cvpharmacology.com/vasodilator/CCB | access-date=2020-02-07}}</ref><ref name="Domenic A. Sica, MD">{{cite web |author=Domenic A. Sica | title=Calcium Channel Blocker-Related Peripheral Edema | website=Medscape | url=http://www.medscape.com/viewarticle/460070 | access-date=2019-10-26}}</ref><ref name="Matthew R. Weir, MD">{{cite web | author=Matthew R. Weir | title=Incidence of Pedal Edema Formation With Dihydropyridine Calcium | website=Medscape | url=http://www.medscape.com/viewarticle/463535 | access-date=2019-10-26}}</ref><ref name="Mohanakumar Telinius Kelly Hjortdal p. ">{{cite journal | last1=Mohanakumar | first1=Sheyanth | last2=Telinius | first2=Niklas | last3=Kelly | first3=Benjamin | last4=Hjortdal | first4=Vibeke | title=Reduced Lymphatic Function Predisposes to Calcium Channel Blocker Edema: A Randomized Placebo-Controlled Clinical Trial | journal=Lymphatic Research and Biology | publisher=Mary Ann Liebert Inc | date=2019-08-20 | volume=18 | issue=2 | pages=156–165 | issn=1539-6851 | doi=10.1089/lrb.2019.0028 | pmid=31429625 | s2cid=201094829 }}</ref> Since lymphatic drainage relies on contraction of the [[smooth muscle]] inside the [[lymphatic vessel]]<ref name="Clinical features and diagnosis of peripheral lymphedema">{{cite web |author=Babak Mehrara |editor=John F Eidt |editor2=Joseph L Mills Sr |editor3=Harold J Burstein |editor4=Kathryn A Collins | title=Clinical features and diagnosis of peripheral lymphedema | website=UpToDate | url=https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-peripheral-lymphedema | access-date=2019-10-27}}</ref> supported by voltage-gated calcium channels, inhibition of voltage-gated calcium channel poses a threat towards lymphatic removal of interstitial fluid essential for normal lymphatic system functioning.<ref name="Mohanakumar Telinius Kelly Hjortdal p. "/> (See also: [[Lymphedema]].)

Mild CCB [[toxicity]] is treated with supportive care. Nondihydropyridine CCBs may produce profound toxicity, and early [[decontamination]], especially for slow-release agents, is essential. For severe [[overdoses]], treatment usually includes close monitoring of vital signs and the addition of vasopressive agents and intravenous fluids for blood pressure support. Intravenous [[calcium gluconate]] (or [[calcium chloride]] if a central line is available) and atropine are first-line therapies. If the time of the overdose is known and presentation is within two hours of [[ingestion]], [[activated carbon|activated charcoal]], [[gastric lavage]], and [[polyethylene glycol]] may be used to decontaminate the gut. Efforts for gut decontamination may be extended to within 8 hours of ingestion with extended-release preparations.{{cncitation needed|date=July 2022}}

Research on the desert grass spider, ''[[Agelenopsis aperta]],'' has shown that agatoxins IVA and IVB found in their venom selectively block calcium channels. These agatoxins are found in other spider species as well. Desert grass spider bites to insects result in rapid paralysis, but bites to humans are not considered medically significant.<ref>{{Cite journal|last=Adams|first=Michael E.|date=April 2004|title=Agatoxins: ion channel specific toxins from the american funnel web spider, Agelenopsis aperta|journal=Toxicon|volume=43|issue=5|pages=509–525|doi=10.1016/j.toxicon.2004.02.004|pmid=15066410|bibcode=2004Txcn...43..509A |issn=0041-0101}}</ref>

In the body's tissues, the concentration of calcium ions ({{chem|Ca|2+}}) outside cells is normally about 10,000-fold higher than the concentration inside cells. Embedded in the [[cell membrane|membrane]] of some cells are [[calcium channel]]s. When these cells receive a certain signal, the channels open, letting calcium rush into the cell. The resulting increase in intracellular calcium has different effects in different types of cells. Calcium channel blockers prevent or reduce the opening of these channels and thereby reduce these effects.{{cncitation needed|date=July 2022}}