Microsoft PowerPoint - OSA藥師 [相容模式]

Size: px

Start display at page:

Download "Microsoft PowerPoint - OSA藥師 [相容模式]"

斯东
9 years ago
Views:

睡眠呼吸障礙症及牙科止鼾器的治療 101 年藥師持續教育課程口醫部黃振勳醫師 5/05 ( 六 ) 08:30~10:10 第三講堂睡眠呼吸障礙症及牙科止鼾器的治療課程題目睡眠呼吸障礙症及牙科止鼾器的治療教學目標瞭解睡眠呼吸障礙的致病機轉, 牙科止鼾器的治療時機及作用綱要說明 1. 認識睡眠呼吸障礙的病因 2. 睡眠呼吸障礙的治療 3.

1 睡眠呼吸障礙症及牙科止鼾器的治療 101 年藥師持續教育課程口醫部黃振勳醫師 5/05 ( 六 ) 08:30~10:10 第三講堂睡眠呼吸障礙症及牙科止鼾器的治療課程題目睡眠呼吸障礙症及牙科止鼾器的治療教學目標瞭解睡眠呼吸障礙的致病機轉, 牙科止鼾器的治療時機及作用綱要說明 1. 認識睡眠呼吸障礙的病因 2. 睡眠呼吸障礙的治療 3. 睡眠呼吸障礙的藥物治療新近發展認識睡眠呼吸障礙的病因睡眠呼吸障礙是一種疾病會影響日常生活作息及工作速率與安全會發生許多共患病 (COMORBIDITY), 例如高血壓心血管疾病腦血管疾病糖尿病等影響伴侶的睡眠品質, 也會讓個人困擾健康青年人的睡眠圖表睡眠分為兩種狀態 : 快速動眼睡眠 (REM) 和非快速動眼睡眠 (NREM), 通過腦部調控, 這兩種狀態每晚固定地交替出現一般熟睡後首先開始約 80 分鐘的非快速動眼睡眠, 跟隨轉為快速動眼睡眠約 10 分鐘, 如此在整個過程中重複 4 至 6 次非快速動眼睡眠時, 腦部及軀體的生理功能都降下 ; 快速動眼睡眠時, 腦部及軀體功能則呈短暫性活躍人類睡眠的結構口咽 ( 上呼吸道 ) 的構造比較青年人與老年人的睡眠, 老年人睡眠時間較短, 深層睡眠期 (3, 4) 較少, 容易被吵醒 (Harrison) 口咽位於口腔後面, 承上連接鼻咽腔, 向下連結下咽腔前方為軟顎懸壅垂及舌部, 後方為咽喉壁兩側咽喉壁有扁桃腺, 上方有時有腺樣體張口發啊的聲音時, 於軟顎及舌部之間即可看到一部分口咽腔 1

2 睡眠呼吸障礙罹患睡眠呼吸障礙者的呼吸道較正常人狹窄, 白天清醒時, 咽喉部肌肉收縮, 使呼吸道保持暢通開放但是夜間睡眠時, 因為神經的興奮性下降, 造成肌肉鬆弛 : 舌頭軟顎後垂, 咽喉收縮肌鬆弛, 因此呼吸道變狹窄鼾聲發作的原因鼾聲發作的原因主要是睡眠時, 口腔軟組織 ( 舌頭軟顎或懸壅垂 ) 肌肉放鬆, 垂向後方喉嚨, 造成呼吸通道狹窄 ; 當呼吸氣流通過時, 在此造成氣體迴流而發出聲響睡眠呼吸障礙 (OSA) 睡眠時, 因為上呼吸道的肌肉張力放鬆 ; 造成舌部軟顎及口咽肌肉鬆弛, 上呼吸道狹窄當病患深睡時, 上呼吸道的肌肉放鬆, 造成呼吸道狹窄或阻塞血氧濃度會降低, 而刺激呼吸中樞 ; 病患由深睡變為淺睡或覺醒這時病患會發出鼾聲或倒抽一口氣, 而恢復正常呼吸換氣但是隨著病患熟睡, 上述情形週而復始, 反覆發生 ; 病患沒有良好的睡眠睡眠呼吸障礙的症狀睡眠呼吸障礙症打鼾, 睡眠時常發生嗆到或倒吸一口氣早上起床沒有精神或頭痛白天嗜睡疲倦記憶或認知退化焦慮或躁動易怒 2

3 睡眠時的呼吸狀態睡眠呼吸障礙睡眠時正常的呼吸打鼾阻塞性睡眠呼吸中止中華民國胸腔醫學會在民國八十年就曾針對國人睡眠時的打鼾情形, 在頭份大溪地區進行盛行率調查 ; 發現我國四十歲以上的人口在睡眠中呈現打鼾的盛行率是 43.48%, 其中男性 51.69% 女性 35.52% 其中輕度中度重度鼾聲的盛行率分別為 26.83% 13.21% 與 3.44% 蕭光明 1995 打鼾者的比率打鼾者的健康風險在台灣, 有 86% 的男性及 65% 的女性自述會打鼾, 其中有 44% 的男性及 14% 的女性是每天都會打鼾體重越重者 [ 即身體質量指數 (BMI) 越高者 ] 以及年紀越大者, 打鼾的機率也愈高打鼾者中有 10% 至 15% 的病患合併有阻塞型睡眠呼吸中止症陳濘宏等 % 的每天打鼾者有高血壓, 為正常人的三倍,11 % 的打鼾者合併有心臟病, 是正常人的四倍打鼾者有心肌梗塞氣喘慢性肺病, 以及過敏性鼻炎等病變的機率都比沒有打鼾者高陳濘宏等 2007 睡眠呼吸障礙根據 Young 等學者的研究發現美國一般中年男性約 24% 中年女性約 9% 有睡眠呼吸障礙 ; 倘若這些病患併有習慣性打鼾情形, 則他們罹患中重度阻塞性睡眠呼吸終止的比例大為增加而臨床統計發現大部分的睡眠呼吸障礙患者並未被診斷出來, 或接受妥善的醫療照護 Young 等學者 ( ) 嗜睡度量表 (The Epworth Sleepiness Scale) 說明 : 請依據您最近的生活情形, 評估下列情況中打瞌睡的可能性, 0 = 從未 : 不會打瞌睡, 1 = 很少 : 稍微打瞌睡 ( 大都能維持清醒 ), 2 = 一半以上 : 中度打瞌睡 ( 可能維持清醒 ), 3 = 幾乎都會 : 高度打瞌睡 ( 很少能維持清醒 ), 然後選出最適合的數字 (0-3) 請問您在下列情況打瞌睡的可能性 1. 靜坐閱讀書報時? 2. 觀看電視節目時? 3. 靜坐於未有活動的公共場合時? 4. 靜坐於連續開了一個小時的車子時 ( 乘客 )? 5. 下午躺下來休息時 ( 環境許可 )? 6. 靜坐與別人交談時? 7. 午餐後安靜坐著時 ( 未曾喝酒 )? 8. 乘坐車子停頓幾分鐘時? 3

4 愛普渥斯嗜睡度量表 (The Epworth Sleepiness Scale) 分析結果 0~7 分您的嗜睡情況正常 8~9 分您的嗜睡情況稍多 10~15 分您的嗜睡情況明顯, 很可能患有睡眠呼吸中止症, 請視情況諮詢醫生意見及安排睡眠檢查 16~24 分您的嗜睡情況嚴重, 應立即諮詢醫生意見以及安排睡眠檢查睡眠呼吸障礙的檢查口腔鼻咽腔呼吸道的臨床檢查牙科 X 光檢查及側顱 X 光分析電腦斷層或核磁共振影像分析檢查身高體重及 BMI 頭圍頸圍及腰圍睡眠研究分析診斷睡眠呼吸障礙最重要的檢查是睡眠分析睡眠呼吸障礙的檢查牙科 X 光分析睡眠呼吸障礙的口腔表現 Mallampati score & Tonsil grade 4

是睡眠呼吸障礙的最重要的檢查大於 3 項回答是者, 是阻塞型睡眠呼吸終止高危險群 Chung et al.

5 正常和睡眠呼吸障礙的呼吸道睡眠呼吸障礙危險因子 BMI: >25 kg/m2 頸圍 Neck Size Men: > 17inches Women: > 16 inches 家族史年齡 > 40 男性高血壓飲酒 l: 解剖構造 : 巨舌腺狀腫扁桃腺腫下巴後縮肥胖促進因子 Tallent, 2008 STOP-Bang 評分系統 Polysomnography 是睡眠呼吸障礙的最重要的檢查大於 3 項回答是者, 是阻塞型睡眠呼吸終止高危險群 Chung et al 認識睡眠呼吸障礙的診斷 Severity AHI: events/hour Mild 5-15 Moderate Severe >30 (AASM) 打鼾及睡眠呼吸終止的治療正壓呼吸輔助器下頜前伸矯正器止鼾手術養成良好睡眠習慣減重側睡選擇合適的枕頭睡前宵夜勿吃太飽或油膩 5

6 睡眠呼吸障礙的治療 CPAP 的作用機轉正壓持續呼吸器 (CPAP) 正壓持續呼吸器是傳統非侵襲性及有效的治療方式 ( 睡眠呼吸障礙的治療最優先選擇是 CPAP) Device, mask, humidifier. 正壓持續呼吸器 (CPAP) 呼吸器將空氣經由面罩送入口咽腔, 調整壓力維持上呼吸道的暢通空氣的壓力則需要依個人條件調整 Oral Surgery Surgery is site-specific, meaning it requires the identification of specific anatomic area contributing to airway obstruction. 1.Maxillomandibular advancement 2.Anterior inferior mandibular osteotomy Uvulopalatopharyngoplasty Fijita et al. (1981) suggested that the anatomical indications for UPPP were a long uvula, redundant pharyngeal wall tissue and/or excess tonsillar tissue. 6

7 Maxillo-Mandibular Advancement Genioplasty or geniotubercular advancement may augment the pharyngeal space further when combined maxillary/mandibular advancement 牙科止鼾裝置的作用原理利用牙科裝置套在牙齒上將下顎向前牽引以增加口腔空間並將舌部及口底組織牽引向前以增加口咽腔的空間讓呼吸的空氣流動順暢 ditions/sleep-apnea-device.jpg 牙科止鼾裝置下頜前伸矯正器的種類可調整可開口牙科下顎前移裝置適用於輕及中度睡眠呼吸障礙調整上下顎關係可調節式不可調節式配戴時開口活動可以開口不可以開口是否是否是是牙科睡眠止鼾裝置治療同意書止鼾器的佩戴病患因睡眠呼吸障礙接受牙科睡眠止鼾裝置的治療此一裝置是在睡眠時, 佩戴依附於牙齒上 ( 上顎或下顎牙齒或兩者 ) 目的在於幫助病患在睡眠時的呼吸順暢, 在初期佩戴時, 有異物感或壓痛, 需門診調整處理晚上佩戴時, 有些病患會覺得影響睡眠晚上佩戴時, 可能會有口腔呼吸及口乾症狀早上起來, 可能會有短暫的咬合改變或上下牙齒咬不起來, 一般在用完早餐後會改善一般使用約一年需視個人使用及保養情形, 以及是否有磨牙情況睡眠時有誤吞的可能性長期配戴的影響, 可能有顳顎關節障礙或牙齒咬合改變 ( 牙齒移位 ) 所以必須定期回診檢查, 定期潔牙保健如有上述情形發生, 則須接受進一步的治療 7

8 配帶前後的側顱 X 光分析佩戴止鼾器前後比較 -- 口咽區範圍變寬可能的副作用唾液淤積顳顎關節障礙或疼痛早晨醒來牙齒或牙齦不舒服牙齒咬合關係改變不適合使用的狀況中樞型睡眠中止症 Central sleep apnea 不適用於重度睡眠呼吸中止有顳顎關節障礙的病患鼻腔阻塞扁桃腺增生或腫下頜前伸矯正器的保養 CPAP Efficacy vs. Oral Appliance Effectiveness 請保持清潔定期使用清潔劑清洗未佩帶使用請至於清水中保持濕潤以免變形裝在矯正器盒中以免遺失或撞斷變形定期檢查是否有裂痕或掛鉤鬆動定期回門診檢查保養 8

比較 CPAP 與 OA 療效 Oral appliances for obstructive sleep apnoea (Review) OA versus control appliances (six studies): OA 在白天嗜睡及 AHI 的改善較對照組好 OA versus CPAP (ten studies): CPAP 能有效改善 AHI 及血氧濃度效果較 OA 好,

9 比較 CPAP 與 OA 療效 Oral appliances for obstructive sleep apnoea (Review) OA versus control appliances (six studies): OA 在白天嗜睡及 AHI 的改善較對照組好 OA versus CPAP (ten studies): CPAP 能有效改善 AHI 及血氧濃度效果較 OA 好, 兩者在症狀改善沒有顯著差異, 但是病患較喜歡 OA OA versus corrective upper airway surgery (one study): 手術後一年內白天嗜睡的症狀改善教 OA 明顯, 但是長期來看 OA 效果較好 Lim et al Lim et al 治療睡眠呼吸障礙症的藥物改善睡眠呼吸障礙症的藥物睡眠呼吸障礙症的輔助藥物改善睡眠呼吸終止症的藥物 Selective serotonin reuptake inhibitors Estrogen and Progesterone Cardiac/ Cardiovascular medication Theophylline increases ventilatory drive Theophylline 可能經由抑制 adenosine, 來增加 ventilatory drive 在一個雙盲交叉實驗 12 位 OSA 病患接受 800mg theophylline 4 週只有輕微降低 AHI (40 vs 49/hr of sleep), 但降低睡眠品質 Mulloy et al Antihypertensives Most of the studies used different antihypertensive agents, which variably affect OSA. As an example, propranolol may worsen OSA, while metoprolol may have beneficial effects. In light of the potential risks and uncertain effect, antihypertensive agents are not recommended as a primary therapy for OSA. Atwood et al

OSA 與 REM 呼吸中止 (apnea) 可以發生在非快速動眼期 (NREM) 或快速動眼期 (REM) 睡眠, 通常非快速動眼期較常發生呼吸中止, 而發生在快速動眼期則較嚴重三環類抗抑鬱藥 Protriptyline 是 tricyclic antidepressant, 抑制 REM sleep 有 anticholinergic 副作用 Protriptyline

10 OSA 與 REM 呼吸中止 (apnea) 可以發生在非快速動眼期 (NREM) 或快速動眼期 (REM) 睡眠, 通常非快速動眼期較常發生呼吸中止, 而發生在快速動眼期則較嚴重三環類抗抑鬱藥 Protriptyline 是 tricyclic antidepressant, 抑制 REM sleep 有 anticholinergic 副作用 Protriptyline 在小型的雙盲交叉實驗, 可以減少 REM 時間及白天嗜睡症狀, 其中部分可以降低 AHI Brownellet al Selective serotonin reuptake inhibitors Serotonin 是一個主要的神經傳導物質 (neurotransmitter), 可以調控上呼吸道肌肉的張力 (upper airway tone) Hypoglossal nerve 支配 genioglossus 肌肉會被 serotonin 去極化在睡眠時 ( 尤其 REM 睡眠期 )serotonergic output to hypoglossal nucleus 會減少, 顯示在神經核增加 serotonin 的濃度, 有助於增加上呼吸道肌肉的張力, 進而改善睡眠呼吸障礙 Sunderram et al. (2000) 研究正常受試者睡眠時 genioglossus 的肌電圖 (electromyography) 發現使用 paroxetine (SSRI) 可以顯著增加 genioglossus 的張力 SSRI 對於 genioglossus 的作用 (OSA) Berry et al. (1999) 提供 8 位嚴重睡眠呼吸抑制病患睡前 40mg paroxetine, 結果顯示 genioglossus activity 增加 (the peak inspiratory EMGgg (29.8+/-2.4 (SE) versus 24.4+/-2.7 % max, p<0.05) 但是對於 AHI 並無顯著改善 (paroxetine: 75.2+/-5.5 versus placebo: 73.7+/-6.9 events/hour) Berry et al SSRI 對 OSA 及 AHI 的作用 Kraiczi et al. (1999) 進行 paroxetine 的病例對照交叉試驗 (case-controlled crossover trial), 20mg paroxetine 或 placebo 各 6 週, 中間 wash out 4 週 AHI 在 NREM sleep,paroxetine 對 placebo sleep (30 vs 36 events/per hour; -35%, p = 0.003), 有顯著改善 (not during REM sleep ) 但在 OSA 症狀並沒有明顯改善 Kraiczi et al Hormone Replacement Therapy Post-menopause women 的 AHI 較 pre-menopause women 高 50 歲以上使用 HRT 的婦女, 罹患睡眠呼吸障礙 (AHI>15) 是非使用者的一半 Avidan

AHI of 5 or More versus AHI of Less Than 5 Odds Ratio (95% CI) AHI of 15 or More versus AHI of Less Than 5 Unadjusted model Premenopause Reference category Perimenopause 1.66 (1.05, 2.60) 1.18 (0.

07 (0.52, 2.20) Peri/postmenopause 1.80 (0.79, 4.12) 3.13 (1.06, 9.20) Postmenopause 2.60 (1.41, 4.81) 3.49 (1.38, 8.78) Age, 5 yr 1.17 (0.98, 1.38) 1.10 (0.82, 1.48) BMI, kg/m 2 1.14 (1.11, 1.17) 1.

11 AHI of 5 or More versus AHI of Less Than 5 Odds Ratio (95% CI) AHI of 15 or More versus AHI of Less Than 5 Unadjusted model Premenopause Reference category Perimenopause 1.66 (1.05, 2.60) 1.18 (0.83, 1.69) Peri/Postmenopause 2.82 (1.41, 5.65) 1.82 (1.04, 3.21) Postmenopause 3.22 (2.23, 4.66) 2.59 (1.64, 4.09) Adjusted model * Premenopause Reference category Perimenopause 1.23 (0.68, 2.22) 1.07 (0.52, 2.20) Peri/postmenopause 1.80 (0.79, 4.12) 3.13 (1.06, 9.20) Postmenopause 2.60 (1.41, 4.81) 3.49 (1.38, 8.78) Age, 5 yr 1.17 (0.98, 1.38) 1.10 (0.82, 1.48) BMI, kg/m (1.11, 1.17) 1.20 (1.15, 1.25) 停經婦女與睡眠呼吸障礙 Prevalence of SDB indicated by an AHI of 5 or greater for premenopausal women and perimenopausal plus postmenopausal women by body mass index (BMI). Values represent a 5-unit moving average. Young et al 疼經婦女睡眠呼吸障礙的荷爾蒙治療睡眠呼吸障礙的荷爾蒙治療 While the data are preliminary and based on a small number of subjects, estrogen appeared to have a substantial beneficial effect on measures of SDB in postmenopausal women. Overall, no additional benefit was seen with the addition of progesterone. In fact, progesterone attenuated the beneficial effects of estrogen in 4 out of the 6 participants. Manber et al Hormone replacement therapy in post-menopausal women may cause adverse health outcomes including breast cancer, venous thromboembolism, and symptomatic coronary heart disease. In light of the risks of hormonal therapy and the absence of consistent clinical benefit, the routine use of progestational agents in patients with OSA is not warranted Thyroxine OSA 與 hypothyroidism 有許多相同症狀 Hypothyroidism 的病患中罹患 OSA 有 25%, 而 OSA 病患中並有 hypothyroidism 者僅有 3% Thyroxine therapy 對於 hypothyroidism 病患併有 OSA 有初步療效甲狀腺機能低下與睡眠呼吸障礙 Bahammam et al

12 Categories of pharmacological treatment options that have been used for OSA Drug Mechanism of action Outcome Protriptyline Fluoxetine Paroxetine Tricyclic antidepressant Selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitor Increased XII output, reduced rapid eye movement sleep, reduced AHI Reduced rapid eye movement sleep, Reduced AHI Increased peak genioglossus activity NREM sleep. No change in tonic activity or OSA index Saboisky et al Categories of pharmacological treatment options that have been used for OSA Drug Mechanism of action Outcome Thyroxine Thyroid substitution treatment Reduced OSA severity Acetazolamide Decreases blood ph Increased incidents of apnoeas Increased ventilation Medroxyprogesterone Increased ventilation (mixed responses, used in hypercapnic patients) Theophylline Inhibits adenosine Reduced central apnoeas Not useful in OSA Saboisky et al Modafinil 可改善 CPAP 療效輔助藥物 (Modafinil) Weaver et al In this secondary analysis of data from patients with OSA and excessive sleepiness despite CPAP use, modafinil was associated with improvements in patients' functional outcomes and their ability to engage in a broad array of everyday activities Mean change from baseline in Functional Outcomes of Sleep Questionnaire (FOSQ) Total and individual domain scores for the combined populations with obstructive sleep apnea in the studies. p < 0.05 versus placebo. Values are shown as SEM. Modanifil 是 wakepromoting agent, 有助於改善 OSA 治療後殘餘的白天嗜睡問題但是不能取代傳統的 OSA 治療方式 :CPAP dental appliance 等 Black & Hirshkowitz 2005 使用 CPAP 的配合度 Long-term use of CPAP therapy for sleep apnea/hypopnea syndrome. Proportion of patients continuing CPAP over time. The proportion adhering to CPAP continues to fall over the first 4 years of therapy. McArdle et al Modafini Modafinil is a wakefulness-promoting agent that has been approved by the FDA as an adjunct for the management of residual sleepiness in patients with OSA who are receiving effective therapy for the underlying upper airway obstruction. The AASM recommends modafinil for the treatment of residual sleepiness in patients who receive effective PAP treatment with OSA and who lack any other identifiable causes for their sleepiness. 12

13 Drugs for OSA? Various drugs have been investigated as treatment for OSA. Acetazolamide, theophylline, nicotine, opioid antagonists and medroxyprogesterone have been used to increase respiratory drive. Clonidine has been tested with the aim of reducing rapid eye movement sleep when OSA is often most severe. Various antidepressants have been used to suppress rapid eye movement sleep and to preferentially activate the upper airway dilators Smith et al Drugs for OSA? The drug trials have often been of poor design and none has included more than a few patients. Most of the drugs have been found to be ineffective and those that have worked for some patients (acetazolamide and protriptyline) have produced intolerable adverse effects. Smith et al 惡化睡眠呼吸終止症的藥物有 OSA 病史的病患, 使用 anesthetics, analgesics, anticonvulsants, antihistamines, and antipsychotics 需特別注意, 這些藥物可能惡化 OSA 的症狀止痛藥品 Opioids 抑制呼吸藉由直接作用於 brainstem 的呼吸中樞, 並降低對於 CO2 及缺氧 (hypoxia) 的呼吸反應鎮靜劑 Barbiturates 治療 anxiety disorders, mood disorders, and isomnia. 也是術前常用的鎮靜劑 Barbiturates 有睡眠呼吸抑制及隔日 hangover, 白天嗜睡 Barbiturates 對於 OSA 病患的呼吸抑制效應難以估計, 不建議使用於 severe OSA 病患 13

14 Practice Parameters for the Medical Therapy of Obstructive Sleep Apnea Standards of Practice Committee of the American Academy of Sleep Medicine Selective serotonergic uptake inhibitors (SSRIs) are not recommended for treatment of OSA. Protriptyline is not recommended as a primary treatment for OSA. Methylxanthine derivatives (aminophylline and theophylline) are not recommended for treatment of OSA. Estrogen therapy (estrogen preparations with or without progesterone) is not indicated for the treatment of OSA. Modafinil is recommended for the treatment of residual excessive daytime sleepiness in OSA patients who have sleepiness despite effective PAP treatment and who are lacking any other identifiable cause for their sleepiness. 您的選擇? Pharmacotherapy for sleep bruxism Insufficient evidence-based data to draw definite concerning the effects of various drugs on bruxism. Dopaminogic, serotonergic, and adrenergic systems suppressor trials. Clonidine (adrenergic receptor antagonist) to reduce sleep bruxism motor activity by decreasing cardiac sympathetic tone in minutes before the onset of SB, thus preventing the the subuence ofautonomic sleep arousal that leads to motor activation in the genesis of SB. Lavigne

University of Science and Technology of China A dissertation for master s degree Transdermal Delivery of Gut Hormone PYY3-36 for the treatment of Obes

中国科学技术大学硕士学位论文肠激素 PYY3-36 透皮给药治疗肥胖症的研究作者姓名 : 学科专业 : 导师姓名 : 完成时间 : 陈敏细胞生物学温龙平教授二一年八月三十一日 University of Science and Technology of China A dissertation