2018年06月17日

スタチンと不飽和脂肪酸

スタチンと不飽和脂肪酸を一緒に摂取していたら体にいいのか悪いのか いいような感じもするが スタチンの種類によってもできたアラキドン酸とEPA・DHAの比率が異なるようである。結局 血中のアラキドン酸が少なくなりEPA・DHAが多くなってゆく比率結果が体にはいいようだが。

The Role of n-3 Long Chain Polyunsaturated Fatty Acids in Cardiovascular Disease Prevention, and Interactions with Statins

Abstract: Decreases in global cardiovascular disease (CVD) mortality and morbidity in recent decades can be partly attributed to cholesterol reduction through statin use. n-3 long chain polyunsaturated fatty acids are recommended by some authorities for primary and secondary CVD prevention, and for triglyceride reduction. The residual risk of CVD that remains after statin therapy may potentially be reduced by n-3 long chain polyunsaturated fatty acids. However, the effects of concomitant use of statins and n-3 long chain polyunsaturated fatty acids are not well understood. Pleiotropic effects of statins and n-3 long chain polyunsaturated fatty acids overlap. For example, cytochrome P450 enzymes that metabolize statins may affect n-3 long chain polyunsaturated fatty acid metabolism and vice versa. Clinical and mechanistic study results show both synergistic and antagonistic effects of statins and n-3 long chain polyunsaturated fatty acids when used in combination.

This has led some researchers to conclude that “weak” statins (simvastatin, pravastatin) increase the ARA/EPA ratio, while “strong” statins (atorvastatin, rosuvastatin or pitavastatin) increase the ARA/DHA ratio.

とあったが、組み合わせるときは弱いスタチンがいいのかな・・。
posted by dokusan at 07:03| 青森 ☁| リウマチ | このブログの読者になる | 更新情報をチェックする

2018年05月28日

子癇前症とアスピリン

Aspirin May Help Some Pregnant Women Avoid Preeclampsia

女性で妊娠で高血圧になってゐる場合は メチルドーパやラベタロールを使うことが知られているが、アスピリンもいいようだ。

血圧が高いと診断されるのは妊娠20週後の最高血圧が140mmHgまたは最低血圧が90mmHgを4時間以上おきの2度の測定で上回る場合であるとある。

https://ja.wikipedia.org/wiki/%E5%AD%90%E7%99%87%E5%89%8D%E7%97%87

Hauspurg's research showed taking a low-dose aspirin reduced the risk of developing preeclampsia by 39 percent in women with stage 1 hypertension compared to those taking a placebo.

posted by dokusan at 05:09| 青森 ☁| リウマチ | このブログの読者になる | 更新情報をチェックする

2018年05月26日

抗うつ剤をのんでいると太るのかな

最近の向精神薬には糖尿病の原因となる血糖値を挙げるという話を聞くことがあるが、抗うつ薬にもそんな作用もあるものなのか。


>
Results In the year of study entry, 17 803 (13.0%) men and 35 307 (22.4%) women with a mean age of 51.5 years (SD 16.6 years) were prescribed antidepressants. During 1 836 452 person years of follow-up, the incidence of new episodes of ≥5 weight gain in participants not prescribed antidepressants was 8.1 per 100 person years and in participants prescribed antidepressants was 11.2 per 100 person years (adjusted rate ratio 1.21, 95% confidence interval 1.19 to 1.22, P<0.001). The risk of weight gain remained increased during at least six years of follow-up. In the second year of treatment the number of participants treated with antidepressants for one year for one additional episode of ≥5% weight gain was 27 (95% confidence interval 25 to 29). In people who were initially of normal weight, the adjusted rate ratio for transition to overweight or obesity was 1.29 (1.25 to 1.34); in people who were initially overweight, the adjusted rate ratio for transition to obesity was 1.29 (1.25 to 1.33). Associations may not be causal, and residual confounding might contribute to overestimation of associations.


Conclusion Widespread utilisation of antidepressants may be contributing to long term increased risk of weight gain at population level. The potential for weight gain should be considered when antidepressant treatment is indicated.

小生はどんな抗うつ剤が体重増加に寄与しているか、論文の一欄表を見てみた、

Mirtazapine appeared to be associated with the greatest adjusted rate ratio of weight gain (1.50, 95% confidence interval 1.45 to 1.56). Figure 4 shows the relative frequencies of prescribing compared with the adjusted rate ratio for individual antidepressants−in order of frequency of use: amitriptyline (25.9%):トリプタノール, citalopram (19.8%):レクサプロ, fluoxetine (16.0%), sertraline (9.0%):ジェイゾロフト, venlafaxine (6.4%), paroxetine (5.5%), mirtazapine (4.5%), dosulepin (3.9%), escitalopram (3.7%), trazodone (1.9%):レスリン, duloxetine (2.1%):サインバルタ, and nortriptyline (1.1%):ノリトレン錠.

よく薬局で見受けられるparoxetine :パロキセチンは(5.5%)くらいか・。この仲間うちでは中間くらいか
変えるならレスリンくらいがいいのかな、症状にもよるけれど・・。

2018年05月15日

ビスホスホネート製剤の休薬と継続

小生薬剤師でビスホスホネート製剤を調剤しているが、この薬って 長期に飲んでゐても大丈夫なものなのかなと思うが本当のところは
どうなんであろう。以前 5年以上も飲んでゐると かえって骨がもろくなるとか聞いたこともあるが。今日の論文では休薬期間をもうけると
かえってリスクを上げる危険性があるとか。

OSTEOPOROTIC FRACTURES DURING BISPHOSPHONATE DRUG HOLIDAY

Results: Sixty-two (15.4%) patients developed a fracture during follow-up. The yearly incidence of fractures ranged from 3.7 to 9.9%, peaking at 9.9% and 9.8% during years 4 and 5, respectively. The mean age of the fracture group was higher than the nonfracture group, though not significantly different (69.24 ± 12.26 years vs. 66.42 ± 10.18 years; P = .09). Compared to the nonfracture group, the fracture group had lower femoral neck BMD (0.75 ± 0.12 g/cm2 vs. 0.79 ± 0.10 g/cm2; P = .03) and T-scores (−2.13 ± 0.99 vs. −1.78 ± 0.79; P = .01) at baseline.

Conclusion: Patients who begin BP drug holidays at high risk of fracture based on BMD, age, or other clinical risk factors warrant close follow-up, especially as its duration lengthens. Fracture risk analysis needs to be regularly assessed during the drug holiday and treatment resumed accordingly.
しかし、これだけだとよくわからない。

他の情報は:
http://makinoly.com/%E3%83%93%E3%82%B9%E3%83%9B%E3%82%B9%E3%83%9B%E3%83%8D%E3%83%BC%E3%83%88%E3%81%AE%E4%BC%91%E8%96%AC%E3%81%AF%E5%BF%85%E8%A6%81%EF%BC%9F/

抜粋
・3〜5年で休薬の検討が望ましいが、顎骨壊死や非定型骨折のリスクよりも、休薬による大腿骨骨折や椎体骨折のリスクが大きいため、積極的な休薬は必要ない
・骨密度を計測して、十分な骨密度があれば休薬をするが、骨密度が十分でなければ継続してほしい
・顎骨壊死は口腔ケアをしっかり行うことで、回避可能な副作用である


いいものさし あるようだ。
https://www.sheffield.ac.uk/FRAX/tool.aspx?country=3
posted by dokusan at 04:59| 青森 ☁| リウマチ | このブログの読者になる | 更新情報をチェックする

2018年05月07日

CYP2C19 or CYP3A5 Genotyping Does Not Predict Clinical Response to Clopidogrel

一般的にはプロピドグレルはCYP2C19 とかCYP3A5で代謝されているというが、そしてまた相互作用に注意すべきとされているが、実際臨床ではあまり気にせず 処方されているケースはままある。 それらを裏付けるような論文である。

https://www.ncbi.nlm.nih.gov/pubmed/29723426



Along with aspirin, clopidogrel has been a widely used antiplatelet therapeutic regimen. Although generally well tolerated, its efficacy varies among individuals, with the main hypothesis that its bioavailability relies on its bioconversion to the active compound, which, in turn, depends on the genetic background and/or interactions with other drugs. To determine which factors influenced response in our patients, 368 patients receiving combined antiaggregation therapy with aspirin and clopidogrel were followed for 1 year to record 30 novel cardiovascular acute events. This clinical relapse was considered a surrogate end point to measure therapeutic response under the influence of the CYP2C19*2, *3, and *17 and CYP3A5*3 alleles, as well as the effects of concomitant medication and the presence of known cardiovascular risk factors and comorbidity. We show that either single CYP2C19 or CYP3A5 genotyping or combined were not useful to predict clinical efficacy in this cohort. Rather than genetic testing, we have found that clinical observations such as suffering type 2 diabetes mellitus requiring insulin, having several vessels affected, and concurrent medication with calcium channel blockers, regardless of CYP3A5 genotype or drug class were, in that order, the strongest independent predictors of disease relapse.

CYP2C19 やCYP3A5 の遺伝子変異のあることとは関係なく:役に立たなく、むしろインシュリンを必要とする糖尿病患者でCaチャンネルブロッカーを使用している場合に影響が出てゐるとか・。 論文の中身は見てはいないが、詳細は知りたいところではある。

CYP3A5はあまり知られてはいないが、ヘルペッサー:ジルチアゼム、ドルミカムなどの代謝酵素のようだ。
https://www.jstage.jst.go.jp/article/jssxmeeting/17/0/17_0_63/_pdf



ラベル:薬物相互作用
posted by dokusan at 05:51| 青森 ☁| PPI | このブログの読者になる | 更新情報をチェックする

2018年05月01日

抗コリン剤の中でも長期服用で認知症になる傾向のものがある。

抗コリン作用といえばいろいろな意味で副作用がある場合がある。緑内障とかであるが、抗うつ剤、泌尿器科なんかでの頻尿などのお薬、またはパーキンソン治療剤なんかにもそれらの作用はあるのだが、20年近く それらを服用したりしていると、認知症にもなる傾向が出てくるという。

Anticholinergic drugs and risk of dementia: case-control study


Results 14 453 (35%) cases and 86 403 (30%) controls were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. The adjusted odds ratio for any anticholinergic drug with an ACB score of 3 was 1.11 (95% confidence interval 1.08 to 1.14). Dementia was associated with an increasing average ACB score. When considered by drug class, gastrointestinal drugs with an ACB score of 3 were not distinctively linked to dementia. The risk of dementia increased with greater exposure for antidepressant, urological, and antiparkinson drugs with an ACB score of 3. This result was also observed for exposure 15-20 years before a diagnosis.


Conclusions A robust association between some classes of anticholinergic drugs and future dementia incidence was observed. This could be caused by a class specific effect, or by drugs being used for very early symptoms of dementia. Future research should examine anticholinergic drug classes as opposed to anticholinergic effects intrinsically or summing scales for anticholinergic exposure

それにしてもパーキンソン病は認知症とも関係していて、治療薬に抗コリン剤もその一つとはなっているとは皮肉だね。でも今では使用される頻度は少ないようだ。アキネトン、トリモール、アーテンなんかがそうなのかな。

http://www.aupairs4ireland.com/base/post-3.html

http://utanohosp.jp/html/patient/know/neurology_08.html

消化管に作用する抗コリン剤はこの場合は関係しないという。
posted by dokusan at 04:34| 青森 ☁| リウマチ | このブログの読者になる | 更新情報をチェックする

2018年04月19日

糖尿病予備軍に高血圧が加わると心臓に影響してくる。

Impacts of Prediabetes Mellitus Alone or Plus Hypertension on the Coronary Severity and Cardiovascular Outcomes

糖尿病予備軍に高血圧が加わると心臓に影響してくる。とのこと、小生も高血圧の薬を服用中ではあるが、いまだ糖尿病という名前はいただいてはいないが、決して血糖値が正常とは言えない。つまり予備軍である。

Abstract

Whether prediabetes mellitus (Pre-DM) alone or combined with hypertension is an independent risk factor for cardiovascular disease has not been fully clarified. This study aimed to further confirm whether the relation of Pre- DM to cardiovascular disease differs between individuals with or without hypertension. A total of 7121 consecutive patients with angina-like chest pain who received coronary angiography were evaluated and 4193 patients with angiography-proven stable, new-onset coronary artery disease were enrolled into the study. They were divided into 3 groups according to diabetes mellitus status and further stratified by hypertension. The severity of coronary artery disease was assessed by number of diseased vessels and Gensini score. All subjects were regularly followed up for the occurrence of the composite end points. Comparisons of coronary artery disease severity and outcomes were performed among these groups. During an average of 11 338 patient-years of follow-up, 434 (10.35%) cardiovascular events occurred. No significant difference was observed in coronary severity and composite end point events between Pre-DM and normal glucose regulation groups (both P>0.05). However, when hypertension was also incorporated as a stratifying factor, cardiovascular disease risk, assessed by coronary severity and clinical prognosis, was significantly elevated in Pre-DM plus hypertension and diabetes mellitus plus hypertension groups, compared with the reference group with normal glucose regulation and normal blood pressure (all P<0.05). The present study indicated that among patients with stable, new-onset coronary artery disease, the increased cardiovascular risk with Pre-DM is largely driven by the coexistence of hypertension rather than Pre-DM per se

小生の対策として 糖尿病予備軍から抜け出すために歩くこと、無糖のチョコレート、クルミ、無糖のコーヒーなどを飲むようにしているが、どれほど効果があるか、今のところはわからない。
posted by dokusan at 05:13| 青森 ☁| リウマチ | このブログの読者になる | 更新情報をチェックする

2018年04月17日

オレキシン受容体拮抗薬のせん妄予防効果

睡眠薬といえばベンゾジアゼピンのことばかり頭に浮かぶが、最近では別の作用機序のお薬も出てゐるようで
自分でも本当は試してみたいとおも思っている。

スボレキサント、ラメルテオンなどであるが、スボレキサントにはせん妄を抑える効果もあるとか。

Preventive Effects of Suvorexant on Delirium

Results: We found that delirium developed significantly less often among patients taking suvorexant than among those taking placebo (0% [n/N = 0/36] vs 17% [6/36], respectively, P = .025). Comparison by log-rank test also showed that delirium developed significantly less often among patients taking suvorexant than among those taking placebo (χ2 = 6.46, P = .011). Analysis of variance revealed a tendency for main effect of treatment (F = 3.79, P = .053) on the sleep-wake cycle disturbance score (item 1) of the Japanese version of the Delirium Rating Scale-Revised-98 (DRS-R-98-J). There were no significant differences in adverse events.

https://prtimes.jp/main/html/rd/p/000000034.000021495.html

Conclusions: Suvorexant administered nightly to elderly patients admitted for acute care may provide protection against delirium. Larger studies are needed to show the potential of suvorexant to improve the circadian core domain of delirium.
posted by dokusan at 06:21| 青森 ☀| 面白い薬の作用 | このブログの読者になる | 更新情報をチェックする

2018年04月15日

ノアックには相互作用はないものばかりと思っていたが・・。

Potential drug–drug interactions with direct oral anticoagulants in elderly hospitalized patients

ノアックには相互作用はないものばかりと思っていたが・・。ダビガドランではアミオダロン、ベラパミル、
イグザレルトなんかではNSAIDsなんかにも気を配らんといけないのかな。当然抗ウイルス剤、抗真菌剤、酵素誘導作用のある薬剤はもちろんではあるが・・。


Methods:
This was a retrospective observational study. Inclusion criteria were: aged over 65 years; taking apixaban, rivaroxaban or dabigatran; and admitted to the Repatriation General Hospital between April 2014 and July 2015. A list of clinically relevant ‘perpetrator’ drugs was compiled from product information, the Australian Medicines Handbook, the Australian National Prescribing Service resources, and local health network guidelines. The prevalence and nature of potential DDIs with DOACs was determined by comparing inpatient drug charts with the list of perpetrator drugs.

Results:
There were 122 patients in the study with a mean age of 82 years. Most patients had nonvalvular atrial fibrillation and were taking DOACs to prevent thrombotic stroke (83%). Overall, 45 patients (37%) had a total of 54 potential DDIs. Thirty-five patients had potential pharmacodynamic DDIs with antidepressants, nonsteroidal anti-inflammatory drugs and antiplatelets (35/122, 29%). Nineteen patients had potential pharmacokinetic DDIs (19/122, 16%). Of these, 68% (13/19) were taking drugs that increase DOAC plasma concentrations (amiodarone, erythromycin, diltiazem or verapamil) and 32% (6/19) were taking drugs that decrease DOAC plasma concentrations (carbamazepine, primidone or phenytoin). There were no cases of patients taking contraindicated interacting drugs.

Discussion:
Potential DDIs with DOACs in elderly hospital inpatients are relatively common, particularly interactions that may increase the risk of bleeding. The risk–benefit ratio of DOACs in elderly patients on polypharmacy should always be carefully considered.
posted by dokusan at 04:57| 青森 🌁| 相互作用 | このブログの読者になる | 更新情報をチェックする

2018年04月08日

禁酒のお薬

最近 禁酒を補助するお薬ができたとか。
できれば自分も 飲んでみたいな。特にアルチューでもないが、飲まなけれな 健康にはいいのであろう。
作用機序は従来とは違うとか・・。

アルコール依存では、中枢神経系の主要な興奮性神経であるグルタミン酸作動性神経の活動が亢進し、興奮性神経伝達と抑制性神経伝達の間に不均衡が生じると考えられています。レグテクトの作用機序は明確ではありませんが、アルコール依存で亢進したグルタミン酸作動性神経活動を抑制することで神経伝達の均衡を回復し、飲酒欲求を抑制すると推察されています。 一方、抗酒薬(ジスルフィラム、シアナミド)は、アセトアルデヒドデヒドロゲナーゼ(ALDH)を阻害することにより、飲酒時の血中アセトアルデヒド濃度上昇による不快感を連想させることによって断酒を期待する薬剤です。そのため、抗酒薬は飲酒欲求そのものを標的としておらず、本剤と抗酒薬は異なる作用機序の薬剤ですとあったが・。
http://www.nippon-shinyaku.co.jp/sp/regtect/instruct_point.php

アルコール20gがビール1本とか
http://www.arukenkyo.or.jp/health/base/

目的: 肥満ラットに, 高コレステロール食とアルコールを摂取し, リンゴポリフェノール(Apple polyphenol:AP)の添加が脂肪蓄積量や脂質異常症に及ぼす影響を明らかにすることを目的とした. 方法:5週齢肥満モデル雄ラットを購入し, 4週間飼育した.実験飼料は, 高コレステロール食と10 %アルコール摂取で, リンゴポリフェノール無添加をControl群とし, リンゴポリフェノール添加群をAP群とした.臓器重量, 血清脂質濃度などの測定を行った.結果: 体重増加量, 総飼料摂取量に差は見られなかった.後腹壁脂肪重量は, Control群よりAP群で低下傾向を示した.血清中の総コレステロール, トリグリセリド濃度および血清ALTは, Control群よりAP群で有意に低値を示した. 結論:アルコール摂取肥満ラットにおいて, リンゴポリフェノールは, 血清脂質濃度を低下することが明らかとなった.リンゴポリフェノール摂取が, 脂質代謝異常や脂肪肝の予防に役立つことが期待される.

小生は林檎を毎日 一個食っているがどうなんであろうと論文を探してみた。でてきました。

Effects of Dietary Apple Polyphenol on Alcohol-induced Dyslipidemia in Obese Zucker Rats

Objectives: We studied the effects of the apple polyphenol (AP) with added alcohol on the weight of accumulated fat and dyslipidemia in obese (fa/fa) Zucker rats. Methods: The Zucker fatty rats of 5weeks male were fed for 4 weeks with the experimental diets used high cholesterol diet with 10% alcohol. The fatty rats were divided Control group and AP group. The control group without apple polyphenol, AP group was that there apple polyphenol. It was measured the posterior abdominal wall fat and testicle peripheral fat weight, the concentrations of serum and liver lipids.Results: The posterior abdominal wall fat weight indicated a tendency to decrease in the AP group compared to the Control group. The concentrations of serum total cholesterol and triglyceride decreased in the AP group compared to the Control group. There was no different between each group with respect to the concentration of cholesterol and triglyceride in the liver. The alanine aminotransferase decreased in the AP group compared to the Control group.Conclusion: These results suggested that the alcohol diets containing the apple polyphenol appear to effectively decrease the concentration of serum lipids and the alanine aminotransferase. The apple polyphenol were expected to prevent dyslipidemia and fatty liver.

まあ、リンゴを食っていたなら 缶ビール 一個くらいなら許せるかな・・。
posted by dokusan at 04:26| 青森 ☔| 面白い薬の作用 | このブログの読者になる | 更新情報をチェックする