カルシウム拮抗薬 = カルシウムチャネル遮断薬、カルシウムチャネル拮抗薬、カルシウムチャネル阻害薬、Ca antagonist、calcium antagonist、calcium blocker

WordNet

direct the flow of; "channel information towards a broad audience" (同)canalize, canalise
a television station and its programs; "a satellite TV channel"; "surfing through the channels"; "they offer more than one hundred channels" (同)television channel, TV channel
a passage for water (or other fluids) to flow through; "the fields were crossed with irrigation channels"; "gutters carried off the rainwater into a series of channels under the street"
(often plural) a means of communication or access; "it must go through official channels"; "lines of communication were set up between the two firms" (同)communication channel, line
a path over which electrical signals can pass; "a channel is typically what you rent from a telephone company" (同)transmission channel
a deep and relatively narrow body of water (as in a river or a harbor or a strait linking two larger bodies) that allows the best passage for vessels; "the ship went aground in the channel"
a class of drugs that inhibit (block) some biological process (同)blocking_agent
a football player whose responsibility is to block players attempting to stop an offensive play
a white metallic element that burns with a brilliant light; the fifth most abundant element in the earths crust; an important component of most plants and animals (同)Ca, atomic number 20
official routes of communication; "you have to go through channels"

PrepTutorEJDIC

〈C〉『水路』(川・湾・運河の船の通行ができる深い部分) / 〈U〉河床・川底 / 〈C〉『海峡』 / 〈C〉みぞ(groove),(道路の)水渠(すいきょ) / 《複数形で》(運搬・伝達の)正式の経路(手続き);(一般に)経路 / 〈C〉(テレビ・ラジオの)チャンネル / …‘に'水路を開く / …‘に'みぞを堀る / …'を'伝える,流す
『カルシウム』(金属元素;化学記号は『Ca』)

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/03/18 10:59:00」(JST)

wiki en

A calcium channel blocker (CCB) is a chemical that disrupts the movement of calcium (Ca²⁺) through calcium channels.^[1]

CCB drugs devised to target neurons are used as antiepileptics^{[citation needed]}. However, the most widespread clinical usage of calcium channel blockers is to decrease blood pressure in patients with hypertension. CCBs are particularly efficacious in treating elderly patients.^[2] Calcium channel blockers are also frequently used to alter heart rate, to prevent cerebral vasospasm, and to reduce chest pain caused by angina pectoris. Despite their effectiveness, CCB's often have a high mortality rate over extended periods of use, and have been known to have multiple side effects.^[3] Potential major risks however were mainly found to be associated with short-acting CCB's.^[4]

Mechanism of action

Calcium channel blockers work by blocking voltage-gated calcium channels (VGCCs) in cardiac muscle and blood vessels. This decreases intracellular calcium leading to a reduction in muscle contraction. In the heart, a decrease in calcium available for each beat results in a decrease in cardiac contractility. In blood vessels, a decrease in calcium results in less contraction of the vascular smooth muscle and therefore an increase in arterial diameter (CCBs do not work on venous smooth muscle), a phenomenon called vasodilation. Vasodilation decreases total peripheral resistance, while a decrease in cardiac contractility decreases cardiac output. Since blood pressure is determined by cardiac output and peripheral resistance, blood pressure drops. Calcium channel blockers are especially effective against large vessel stiffness, one of the common causes of elevated systolic blood pressure in elderly patients.^[2]

With a relatively low blood pressure, the afterload on the heart decreases; this decreases how hard the heart must work to eject blood into the aorta, and so the amount of oxygen required by the heart decreases accordingly. This can help ameliorate symptoms of ischaemic heart disease such as angina pectoris.

Unlike beta blockers, calcium channel blockers do not decrease the responsiveness of the heart to input from the sympathetic nervous system. Since moment-to-moment blood pressure regulation is carried out by the sympathetic nervous system (via the baroreceptor reflex), calcium channel blockers allow blood pressure to be maintained more effectively than do beta blockers.

However, because calcium channel blockers result in a decrease in blood pressure, the baroreceptor reflex often initiates a reflexive increase in sympathetic activity leading to increased heart rate and contractility. A beta blocker may be combined with a dihydropyridine calcium channel blocker to minimize these effects.

Ionic calcium is antagonized by magnesium ions in the nervous system. Because of this, bioavailable supplements of magnesium, possibly including magnesium chloride, magnesium lactate, and magnesium aspartate, may increase or enhance the effects of calcium channel blockade.^[5]

Cardiac action

The calcium channel blockers known as non-dihydropyridines decrease the force of contraction of the myocardium (muscle of the heart). This is known as the negative inotropic effect of calcium channel blockers. It is because of these negative inotropic effects that the nondihydropyridine calcium channel blockers, such as verapamil or diltiazem, may be avoided (or used with caution) in individuals with cardiomyopathy.^[6]

Many calcium channel blockers also slow down the conduction of electrical activity within the heart, by blocking the calcium channel during the plateau phase of the action potential of the heart (see: cardiac action potential). This results in a negative chronotropic effect, or a lowering of heart rate. This can increase the potential for heart block. The negative chronotropic effects of calcium channel blockers make them a commonly used class of agents in individuals with atrial fibrillation or flutter in whom control of the heart rate is generally a goal. Negative chronotropy can be beneficial when treating a variety of disease processes because lower heart rates represent lower cardiac oxygen requirements. Elevated heart rate can result in significantly higher "cardiac work," which can result in symptoms of angina.

Only the non-dihydropyridine CCBs are considered to have negative inotropic and chronotropic effects. The dihydropyridine CCBs increase contractility and heart rate, therefore decreasing vascular resistance.

Classes

Dihydropyridine

Dihydropyridine calcium channel blockers are often used to reduce systemic vascular resistance and arterial pressure, but are not used to treat angina (with the exception of amlodipine, nicardipine, and nifedipine, which carry an indication to treat chronic stable angina as well as vasospastic angina) because the vasodilation and hypotension can lead to reflex tachycardia. Dihydropiridine calcium channel blockers can worsen proteinuria in patients with nephropathy.^[7] This CCB class is easily identified by the suffix "-dipine".

Amlodipine (Norvasc)
Aranidipine (Sapresta)
Azelnidipine (Calblock)
Barnidipine (HypoCa)
Benidipine (Coniel)
Cilnidipine (Atelec, Cinalong, Siscard)
Clevidipine (Cleviprex)
Isradipine (DynaCirc, Prescal)
Efonidipine (Landel)
Felodipine (Plendil)
Lacidipine (Motens, Lacipil)
Lercanidipine (Zanidip)
Manidipine (Calslot, Madipine)
Nicardipine (Cardene, Carden SR)
Nifedipine (Procardia, Adalat)
Nilvadipine (Nivadil)
Nimodipine (Nimotop)
Nisoldipine (Baymycard, Sular, Syscor)
Nitrendipine (Cardif, Nitrepin, Baylotensin)
Pranidipine (Acalas)

Side effects of these drugs may include but are not limited to:

Dizziness, headache, redness in the face
Fluid buildup in the legs
Rapid heart rate.
Slow heart rate.
Constipation
Gingival overgrowth
Ankle edema

Non-dihydropyridine

Phenylalkylamine

Skeletal formula of verapamil

Phenylalkylamine calcium channel blockers are relatively selective for myocardium, reduce myocardial oxygen demand and reverse coronary vasospasm, and are often used to treat angina. They have minimal vasodilatory effects compared with dihydropyridines and therefore cause less reflex tachycardia, making it appealing for treatment of angina, where tachycardia can be the most significant contributor to the heart's need for oxygen. Therefore, as vasodilation is minimal with the phenylalkylamines, the major mechanism of action is causing negative inotropy. Phenylalkylamines are thought to access calcium channels from the intracellular side, although the evidence is somewhat mixed.^[8]

Verapamil (Calan, Isoptin)

Benzothiazepine

Structural formula of diltiazem

Benzothiazepine calcium channel blockers are an intermediate class between phenylalkylamine and dihydropyridines in their selectivity for vascular calcium channels. By having both cardiac depressant and vasodilator actions, benzothiazepines are able to reduce arterial pressure without producing the same degree of reflex cardiac stimulation caused by dihydropyridines.

Diltiazem (Cardizem)

Nonselective

While most of the agents listed above are relatively selective, there are additional agents that are considered nonselective. These include mibefradil, bepridil, fluspirilene,^[9] and fendiline.^[10]

Toxicity

Mild CCB toxicity is treated with supportive care. Non-dihydropyridine CCB 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. IV 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 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.

Hyperinsulinemia-euglycemia (HIE) therapy has emerged as a viable form of treatment. Although the mechanism is unclear, it has been hypothesized that increased insulin mobilizes glucose from peripheral tissues to serve as an alternative fuel source for the heart (the heart mainly relies on oxidation of fatty acids). Theoretical treatment with lipid emulsion therapy has been considered in severe cases, but is not yet standard of care.

Caution should be taken when using verapamil with a Beta blocker due to the risk of severe bradycardia. If unsuccessful, ventricular pacing should be used.^[11]

References

^ "calcium channel blocker" at Dorland's Medical Dictionary
^ ^a ^b Nelson M (2010). "Drug treatment of elevated blood pressure" (pdf). Australian Prescriber 33 (4): 108–112. http://www.australianprescriber.com/upload/pdf/articles/1120.pdf.
^ "Calcium Channel Blockers". MedicineNet. p. 2. http://www.medicinenet.com/calcium_channel_blockers/page2.htm#side%20effects.
^ Norman M Kaplan, MD; Burton D Rose, MD (Apr 3, 2000). "Major side effects and safety of calcium channel blockers". Chinese Medical & Biological Information. http://cmbi.bjmu.edu.cn/uptodate/hypertension/drg%20therpy/Major%20side%20effects%20and%20safety%20of%20calcium%20channel%20blockers.htm.
^ Iseri LT, French JH (1984). "Magnesium: Nature’s Physiologic Calcium Blocker". American Heart Journal 108 (1): 188–193. doi:10.1016/0002-8703(84)90572-6. PMID 6375330.
^ Lehne R (2010). Pharmacology for Nursing Care (7th ed.). St. Louis, Missouri: Saunders Elsevier. p. 505. ISBN 978-1-4160-6249-3.
^ Remuzzi G, Scheppati A, Ruggenenti P (2002). "Clinical Practice. Nephropathy in Patients with Type 2 Diabetes". New England Journal of Medicine 346 (15): 1145–1151. PMID 11948275. http://www.nejm.org/doi/full/10.1056/NEJMcp011773.
^ Hockerman GH, Peterson BZ, Johnson BD, Catterall WA (1997). "Molecular Determinants of Drug Binding and Action on L-Type Calcium Channels". Annual Review of Pharmacology and Toxicology 37: 361–396. doi:10.1146/annurev.pharmtox.37.1.361. PMID 9131258.
^ Bezprozvanny I, Tsien RW (1995). "Voltage-Dependent Blockade of Diverse Types of Voltage-Gated Ca²⁺ Channels Expressed in Xenopus Oocytes by the Ca²⁺ Channel Antagonist Mibefradil (Ro 40-5967)". Molecular Pharmacology 48 (3): 540–549. PMID 7565636. http://molpharm.aspetjournals.org/content/48/3/540.abstract.
^ Scultéty S, Tamáskovits E (1991). "Effect of Ca²⁺ Antagonists on Isolated Rabbit Detrusor Muscle". Acta Physiologica Hungarica 77 (3–4): 269–278. PMID 1755331.
^ Buckley N, Dawson A, Whyte I (2007). "Calcium Channel Blockers". Medicine 35 (11): 599–602. doi:10.1016/j.mpmed.2007.08.025.

External links

Calcium+Channel+Blockers at the US National Library of Medicine Medical Subject Headings (MeSH)
Official Adalat (Nifedipine) site, Bayer
Video - Calcium Channel Blockers

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. カルシウム拮抗剤の主な副作用および安全性 major side effects and safety of calcium channel blockers
2. 本態性高血圧における治療選択：推奨 choice of therapy in essential hypertension recommendations
3. 安定狭心症のマネージメントにおけるカルシウム拮抗剤 calcium channel blockers in the management of stable angina pectoris
4. 収縮機能障害による心不全におけるカルシウム拮抗剤 calcium channel blockers in heart failure due to systolic dysfunction
5. 不整脈治療におけるカルシウムチャネル遮断剤拮抗剤 calcium channel blockers in the treatment of cardiac arrhythmias

English Journal

Functional role of the KCa3.1 potassium channel in synovial fibroblasts from rheumatoid arthritis patients.

Friebel K1, Schönherr R, Kinne RW, Kunisch E.
Journal of cellular physiology.J Cell Physiol.2015 Jul;230(7):1677-88. doi: 10.1002/jcp.24924.
Rheumatoid arthritis synovial fibroblasts (RA-SFs) show an aggressive phenotype and support joint inflammation and tissue destruction. New druggable targets in RA-SFs would therefore be of high therapeutic interest. The present study shows that the intermediate-conductance, calcium-activated potassi
PMID 25545021

A novel tacrine-dihydropyridine hybrid (-)SCR1693 induces tau dephosphorylation and inhibits Aβ generation in cells.

Wang XL1, Xiong Y2, Yang Y3, Tuo QZ3, Wang XC3, Chen R4, Tian Q3, Zhang ZP4, Yan X3, Yang ZY3, Wang JZ5, Liu R6.
European journal of pharmacology.Eur J Pharmacol.2015 May 5;754:134-9. doi: 10.1016/j.ejphar.2015.02.022. Epub 2015 Feb 28.
AChE inhibitors are the first choice for the treatment of Alzheimer׳s disease (AD), but they could only delay the progression of cognitive and behavioral dysfunction, and fail to reverse neuronal damage. Calcium channel blockers have been identified to have protective effect on neurons. Thus, thera
PMID 25732864

CACNA1D De Novo Mutations in Autism Spectrum Disorders Activate Cav1.3 L-Type Calcium Channels.

Pinggera A1, Lieb A1, Benedetti B1, Lampert M1, Monteleone S2, Liedl KR2, Tuluc P1, Striessnig J3.
Biological psychiatry.Biol Psychiatry.2015 May 1;77(9):816-22. doi: 10.1016/j.biopsych.2014.11.020. Epub 2014 Dec 8.
BACKGROUND: Cav1.3 voltage-gated L-type calcium channels (LTCCs) are part of postsynaptic neuronal signaling networks. They play a key role in brain function, including fear memory and emotional and drug-taking behaviors. A whole-exome sequencing study identified a de novo mutation, p.A749G, in Cav1
PMID 25620733

Japanese Journal

Improvements in Augmentation Index and Urinary Albumin Excretion With Benidipine in Hypertensive Patients With Chronic Kidney Disease

International Heart Journal 57(1), 53-60, 2016
NAID 130005121002

The Who, What, Why, When, How and Where of Vasospastic Angina

Circulation Journal 80(2), 289-298, 2016
NAID 130005120904

Heavy metal chelator TPEN attenuates fura-2 fluorescence changes induced by cadmium, mercury and methylmercury

Journal of Veterinary Medical Science advpub(0), 2016
NAID 130005119387

Related Pictures

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★リンクテーブル★

リンク元	「カルシウム」「カルシウム拮抗薬」
関連記事	「channel」「blocker」「calcium」「calcium channel」

「カルシウム」

　　[★]

英: calcium
関: カルシウムイオン、リン; calcium channel blockers, calcium channels

基準値

血清総Ca 8.6-10.1 mg/dl(臨床検査法提要第32版)
8.6-10.2 mg/dL (QB)　　　だいたい　　9.4 ± 0.8
血清Caイオン 1.15-1.30 mmmol/l(臨床検査法提要第32版), 4.6-5.1 mg/dl

血液ガス

血液ガスでは (mEq/l)で出されるが 4倍すれば (mg/dl)に変換できる　　原子量が約40ゆえ

溶解度積

http://taniwa.hp.infoseek.co.jp/gyunyu/no9.html

リン酸カルシウム	366x10^-6	（30℃）
リン酸カルシウム	0.35x10^-6	（38℃）
炭酸カルシウム	0.0087x10^-6	（25℃）
酒石酸カルシウム	0.0077x10^-6	（25℃）
シュウ酸カルシウム	0.00257x10^-6	（25℃）
オレイン酸カルシウム	0.000291x10^-6	（25℃）
パルチミン酸カルシウム	0.000000161x10^-6	（23℃）

カルシウムの吸収(SP.744)

＋健康成人の1日あたりの食物Ca摂取0.6g
＋消化管分泌物と脱落上皮細胞のCa 0.6g
－吸収されるCa　　　　　　　　　 0.7g
－そのまま排泄　　　　　　　　　　0.5g
正味吸収されるCa 0.1g

カルシウムの吸収部位

十二指腸

カルシウム代謝の調節機構

副甲状腺ホルモン、1,25水酸化ビタミンD₃、コルチゾール、カルシトニン、酸塩基平衡異常

副甲状腺ホルモン

血中Ca上昇＋血中P低下を行う。

1. 破骨細胞に作用してCa,Pが血中へ。
2. 腎の遠位尿細管に作用してCa再吸収の亢進、近位尿細管でのP再吸収の抑制。
3. 近位尿細管に作用して酵素を活性化し、1,25水酸化ビタミンD3の産生亢進。

1,25(OH)2D3

血中Ca上昇＋血中P上昇

1. 空腸からのCaとPの吸収。
2. 骨形成促進。
3. 遠位尿細管でのＣａとPの再吸収促進。
4. 副甲状腺ホルモンの合成を抑制

尿細管における部位別カルシウム輸送

糸球体で濾過されるのはイオン化Caと陰イオン複合型Ca(蛋白結合型Caは濾過されない)
濾過されたカルシウムのうち95%が再吸収される。

近位尿細管：60-70%
ヘンレループ：20-25%
遠位尿細管、集合管：10-15%

近位尿細管

Na⁺依存的に再吸収。受動輸送80%、能動輸送20%

基底側のCa²⁺ ATPase, 3Na⁺-Ca²⁺逆輸送系

ヘンレループ

太いヘンレループ上行脚で
受動輸送：管腔内電位が正であるため

基底側の^Ca2+ ATPase

遠位尿細管～集合管

糸球体濾過量の10-15%が再吸収されている　→　量としては少ないが能動的に吸収が行われる部位。
能動輸送：管腔内電位が負であるため。
PTH、カルシトニンに調節されている

チアジド系利尿薬により細胞内Na↓となるとCa再吸収↑となる！！！！　←　ループ利尿薬と違う点。よって高カルシウム血症が起こることがある。

接合尿細管

管腔側：Ca2+チャネル/非選択的カチオンチャネル
基底側：Na+-K+ ATPase, 3Na+-Ca2+交換系

尿細管におけるカルシウムの輸送の調節 SP.796

循環血漿量

Ca2+の尿中排泄量はNa+の尿中排泄量と比例。循環血漿量が増加するとCa2+排泄も増加

血漿電解質濃度

Ca2+の尿中排泄量は血漿Ca2+濃度と比例する。

酸塩基平衡

Ca2+の尿中排泄量は代謝性アシドーシスで増加。遠位尿細管でのCa2+再吸収が抑制されるため。

血清カルシウム濃度

血液中でCa2+は調節を受けて一定に保たれるが、蛋白と結合しているCaはアルブミンの量によって増減する。

血清アルブミン濃度 4 g/dl、血清Ca濃度 9mg/dl。補正Ca濃度 9mg/dl　→　正常

血清アルブミン濃度 2 g/dl、血清Ca濃度 7mg/dl。　→　大変！！低カルシウム血症！！　→　ホント？　ってことになる。アルブミンの量が減ってAlb-Caが減っただけで生理的に重要なCa2+は保たれているのではないか。　→　こんな時に補正Ca濃度を用いるのである

　　　　　　　　　　　　　　　　　　　　　　　→補正Ca濃度 9mg/dl →　正常

つまり、低アルブミン血症ではCa2+は保たれているにもかかわらず、血清Caは低値となりそのままでは評価できないために補正を行う。

補正Ca濃度(mg/dl)＝Ca実測値(mg/dl)＋(4－血清アルブミン濃度(g/dl))　・・・Payneの式

アルブミンのpIは7より小さく、アシデミアでは負に帯電しているアルブミンが減少、アルカレミアでは負に帯電しているアルブミンが増加する。すなわち、pHが下がるとアルブミンとくっつなくなったCaが増加するので、血液pH0.1の低下につきfreeイオン化Ca(Ca2+)は0.12mg/dl増加する？？？？？？？？？？？