インデラルは精神安定剤として使えるか？

メディカル朝日『ささらいの循環器病学』より　2014年7月号

・人前でしゃべるとき緊張する→心臓がバクバクする ・交感神経とカテコラミンが関与している ・となると交感神経をブロックするβ遮断薬が有効ではないか ・亢進している交感神経をβ遮断薬で抑えるのは割合簡単 ・低下している副交感神経を上げるのは意外と困難 ・具体的にどうしているか 　・インデラル10mgをしゃべる1時間前に１T服用 　・プレッシャーが強いときは２T服用 　・ただし心不全、気管支喘息、徐脈性不整脈のある人は注意 ・術前の患者にインデラル20mg〜40mg投与すると落ち着くという観察研究もある（Khadke VV et al:J Indian Med Assoc 110:457-460,2012※１) 　・この報告では40mgでは徐脈、低血圧の副作用が多いので20mgを推奨 ・本当に怖いときにインデラル効くかということを『バンジージャンプ』で検討（Truijen J et al :Clin Sci 〈Lond〉 120:161-167. 2011） 　･横になっても立てになっても心拍数は低下しており、有効

Oral propranolol--efficacy and comparison of two doses for peri-operative anxiolysis. Khadke VV et al:J Indian Med Assoc 110:457-460,2012 Abstract Patients undergoing surgery are having high levels of anxiety and stress. Though not life threatening it adds an unnecessary financial burden to the hospital. We assessed the anxiolytic effects of oral propranolol 20 mg and 40 mg when given as premedication. This is a double blind, randomised, prospective clinical study involving 60 healthy patients (ASA I and II) undergoing minor elective surgery. Subjects in control group without any anxiolytic premedication (group I, n = 20) were compared with those receiving oral propranolol 20 mg (group II, n = 20) or 40 mg (group III, n = 20) with sips of water 2-hour prior to surgery. Anxiety level was assessed using 4-point anxiolysis score (1--tearful, 2--anxious but easily reassured, 3--calm, 4--asleep) in the holding area, after entering operating room, immediate postoperative and 2 hours after surgery. Fluctuation in pulse rate and BP was recorded. Statistical data was analysed using one-way ANOVA with posthoc test.Value of p < 0.05 was taken as significant. Twenty subjects in each group were required as calculated from reference study with difference of up to 30%, type I error of 0.5 and power of 80%. Anxiolysis score in operating room (group I--1.40 +/- 0.48, group II--1.95 +/- 0.58, group III--1.90 +/- 0.53) and immediate postoperative period (group I--1.25 +/- 0.43, group II--1.90 +0.53, group III--2.10 +/- 0.29) were significantly improved (p < 0.05) in groups II and III compared with control group. Variations in systolic BP and pulse rate were less in test groups (p < 0.05). No statistically significant difference was found after Intergroup comparison of test groups. Bradycardia (25%) and hypotension (10%) were more with 40 mg propranolol. Both 20 mg and 40 mg doses of propranolol are effective for pre-operative anxiolysis but 20 mg dose gives significant reduction in anxiety with minimal side-effects. Thus 20 mg propranolol premedication for reducing peri-operative anxiety and for cardiovascular stability is recommended.

Truijen J, Davis SC, Stok WJ et al (2011) Baroreflex sensitivity is higher during acute psychological stress in healthy subjects under beta-adrenergic blockade: Clin Sci 120: 161?167 Abstract Acute psychological stress challenges the cardiovascular system with an increase in BP (blood pressure), HR (heart rate) and reduced BRS (baroreflex sensitivity). β-adrenergic blockade enhances BRS during rest, but its effect on BRS during acute psychological stress is unknown. This study tested the hypothesis that BRS is higher during acute psychological stress in healthy subjects under β-adrenergic blockade. Twenty healthy novice male bungee jumpers were randomized and studied with (PROP, n=10) or without (CTRL, n=10) propranolol. BP and HR responses and BRS [cross-correlation time-domain (BRSTD) and cross-spectral frequency-domain (BRSFD) analysis] were evaluated from 30 min prior up to 2 h after the jump. HR, cardiac output and pulse pressure were lower in the PROP group throughout the study. Prior to the bungee jump, BRS was higher in the PROP group compared with the CTRL group [BRSTD: 28 (24?42) compared with 17 (16?28) ms・mmHg?1, P<0.05; BRSFD: 27 (20?34) compared with 14 (9?19) ms・mmHg?1, P<0.05; values are medians (interquartile range)]. BP declined after the jump in both groups, and post-jump BRS did not differ between the groups. In conclusion, during acute psychological stress, BRS is higher in healthy subjects treated with non-selective β-adrenergic blockade with significantly lower HR but comparable BP.

・インデラルの開発 　・英国のジェームズ・ブラック（1988年ノーベル生理学医学賞受賞）が開発 　・1948年アドレナリン受容体にαとβの2種類があることを報告 　・β遮断薬の開発に着手し、インデラルを開発 ・その後、メインテート（ビソプロロール）、セロケン（メトプロロール）などいろんなβ遮断薬が開発された ・アーチスト（カルベジロール）はβ遮断薬だが構造が上記とは異なる ・インデラルは半減期が短いこと、α、β両方を遮断する（選択性が低い）のであまり使われなくなった 　・2013年に偏頭痛の適応をとっている 　・血管の緊張をコントロールする自律神経に作用し、知覚刺激に対する脳血管の反応を改善する 　　※Min JH et al:J Neurol Sci 305<1-2>:136-138,2011

The effect of propranolol on cerebrovascular reactivity to visual stimulation in migraine Journal of the Neurological Sciences Volume 305, Issue 1 , Pages 136-138, 15 June 2011 Abstract Background Propranolol is effective for migraine prophylaxis. However, its exact mechanism is not known. We postulated that the protective effect is due to the lowering of cerebrovascular reactivity (CVR). To verify this, we applied photic stimuli to migraineurs and analyzed the results. Methods We checked the mean flow velocity (MFV) of the posterior cerebral artery by transcranial Doppler in 22 migraineurs during a headache-free period and in 14 normal controls. During the photic stimulation, MFV was remeasured and the CVR was estimated in both groups. Migraineurs received prophylactic propranolol for 2months, and they were then reevaluated for the above-mentioned parameters and assessed for a headache index (HI).

私見）私はテノーミンで効果がありました。

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