Safety of Intranasal Steroids in Long-Term Use

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¬“ µ’√Õ¬¥åæàπ®¡Ÿ° (intranasal steroids) ‡ªìπ¬“∑’ËÕÕ°ƒ∑∏‘Ï‡©æ“–∑’Ë∑’Ë‡¬◊ËÕ∫ÿ®¡Ÿ°‰¥â¥’ ·≈–¡’º≈µàÕ∑—Ë«√à“ß°“¬ (systemic effect) µË” ‰¥â‡√‘Ë¡¡’°“√π”¬“ µ’√Õ¬¥åæàπ®¡Ÿ°¡“„™â√—°…“‚√§ ®¡Ÿ°Õ—°‡ ∫¿Ÿ¡‘·æâ (allergic rhinitis) µ—Èß·µàªï æ.». 2517 πÕ°®“°®–„™â¬“ µ’√Õ¬¥åæàπ®¡Ÿ° √°…“‚√§¥— ß°≈— “«·≈à «â ¬“ µ√Õ¬¥’ æå π®¡à °¬Ÿ ß¡— ∑’ „™’Ë „π‚√§Õâ πÊ◊Ë Õ°’ ‡™πà ‚√§®¡°ÕŸ °‡ ∫™π— ¥‰¡‘ ·æà â (nonallergic rhinitis), ‰´π Õ— °‡ ∫‡©— ¬∫æ≈’ π— (acute rhinosinusitis), ‰´π Õ— °‡ ∫‡√— Õ√◊È ß— (chronic rhinosinusitis), √‘¥ ’¥«ß®¡Ÿ° (nasal polyp), ‡¬◊ËÕ∫ÿ®¡Ÿ°Õ—°‡ ∫®“°°“√„™â¬“À¥À≈Õ¥‡≈◊Õ¥ ‡©æ“–∑’Ëπ“π‡°‘π‰ª (rhinitis medicamentosa) „πªí®®ÿ∫—π¡’¬“ µ’√Õ¬¥åæàπ®¡Ÿ°∑’Ë®”Àπà“¬„π ª√–‡∑»‰∑¬ 6 ™π‘¥ §◊Õ - Beclomethasone dipropionate - Budesonide - Fluticasone propionate - Triamcinolone acetonide - Mometasone furoate - Fluticasone furoate ‡πÕß®“°¡◊Ë °“√„™’ ¬“ µâ √Õ¬¥’ æå π®¡à °„π‚√§µŸ “ßÊà ‡æ¡¡“°¢‘Ë π÷È ´ß¡÷Ë °®–‡ª— π‚√§∑ì ‡√’Ë Õ√◊È ß— ·≈– µâÕß„™â√–¬–‡«≈“π“π„π°“√√—°…“ ®÷ß¡’§”∂“¡µ“¡¡“«à“ °“√„™â¬“ µ’√Õ¬¥åæàπ®¡Ÿ°‡ªìπ√–¬–‡«≈“ π“π„π‚√§¥—ß°≈à“« ª≈Õ¥¿—¬À√◊Õ‰¡à ‚¥¬‡©æ“–„πºŸâªÉ«¬‡¥Á°. °“√∑’Ë¬“ µ’√Õ¬¥åæàπ®¡Ÿ°®–∑”„Àâ‡°‘¥º≈¢â“ß‡§’¬ß∑’Ë‰¡àæ÷ßª√– ß§å‚¥¬‡©æ“–º≈µàÕ∑—Ë« √à“ß°“¬ (systemic adverse effect) ‰¥âπ—Èπ ¬“ µ’√Õ¬¥åæàπ®¡Ÿ°®–µâÕß¡’°“√¥Ÿ¥´÷¡‡¢â“ Ÿà°√–· ‚≈À‘µ„πª√‘¡“≥∑’Ë Ÿß¡“°æÕ ‡¡◊ËÕæàπ¬“ µ’√Õ¬¥åæàπ®¡Ÿ°‡¢â“‰ª„π‚æ√ß®¡Ÿ° ¬“ µ’√Õ¬¥å æàπ®¡Ÿ° à«πÀπ÷Ëß®–¡’°“√¥Ÿ¥´÷¡ºà“π‡¬◊ËÕ∫ÿ®¡Ÿ° ·≈–‡¢â“ Ÿà°√–· ‚≈À‘µ‰¥â‚¥¬µ√ß (·ºπ¿Ÿ¡‘∑’Ë 1) Õ’° à«πÀπ÷Ëß´÷Ëß‡ªìπ à«π„À≠à (¡“°°«à“√âÕ¬≈– 50 ¢Õß¬“ µ’√Õ¬¥åæàπ®¡Ÿ°) ®–∂Ÿ°ºŸâªÉ«¬°≈◊π≈ß ‰ª„π∑“ß‡¥‘πÕ“À“√ ·≈–¡’°“√¥Ÿ¥´÷¡ºà“π‰ª¬—ßµ—∫ ‡æ◊ËÕºà“π°√–∫«π°“√ first pass inactivation À≈—ß®“°π—Èπ à«π active ¢Õß¬“®÷ß®–∂Ÿ°¥Ÿ¥´÷¡‡¢â“ Ÿà°√–· ‡≈◊Õ¥ ¥—ßπ—Èπ ª√‘¡“≥¢Õß¬“ µ’√Õ¬¥å

ª“√¬– Õ“»π–‡ π æ.∫., √Õß»“ µ√“®“√¬ å “¢“‚√§®¡°·≈–‚√§¿Ÿ ¡Ÿ ·æ‘ â ¿“§«™“‚ µ‘ π“ °‘ ≈“√ß´‘ «å ∑¬“‘ §≥–·æ∑¬»“ µ√»å √‘ √“™æ¬“∫“≈‘ ¡À“«∑¬“≈‘ ¬¡À— ¥≈‘

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æàπ®¡Ÿ°∑’Ë∂Ÿ°¥Ÿ¥´÷¡‡¢â“ Ÿà°√–· ‡≈◊Õ¥ (systemic bio- us ·≈â«‰ª®—∫ glucocorticoid response element availability) ·≈–∑”„À‡°â ¥º≈¢‘ “ß‡§â ¬ß∑’ ‰¡’Ë æà ßª√– ß§÷ å ´ßÕ¬÷Ë ∫πŸà chromatin ¢Õß steroid-responsive gene1 ®÷ß‡ªìπº≈√«¡√–À«à“ß¬“ µ’√Õ¬¥åæàπ®¡Ÿ°∑’Ë∂Ÿ°¥Ÿ¥´÷¡ °“√®—∫¢Õß steroid-receptor complex °—∫ DNA ºà“π‡¬◊ËÕ∫ÿ®¡Ÿ°‚¥¬µ√ß ·≈–¬“ µ’√Õ¬¥åæàπ®¡Ÿ°∑’Ë∂Ÿ° ¥—ß°≈à“« ∑”„Àâ‡°‘¥À√◊Õ¬—∫¬—Èß‰¡à„Àâ‡°‘¥ gene tran- ¥Ÿ¥´÷¡ºà“π∑“ß‡¥‘πÕ“À“√ À≈—ß®“°ºà“π°√–∫«π°“√ scription mRNA transcripts ∑’Ë‰¥â®–∂Ÿ°π”ÕÕ°‰ª first pass inactivation „πµ—∫·≈â«. „π cytoplasm ¢Õß‡´≈≈å ·≈–∂Ÿ°π”‰ª √â“ß‚ª√µ’π ‚¥¬ ribosome2,3 ‚ª√µπ¥’ ß°≈— “«®–∑”Àπà “∑â ¬’Ë ∫¬— ß°“√—È °≈‰°°“√∑”ß“π¢Õß¬“ µ’√Õ¬¥åæàπ®¡Ÿ° √â“ß pro-inflammatory cytokines ‡™àπ interleu- ¬“ µ’√Õ¬¥åÕÕ°ƒ∑∏‘Ï‚¥¬§«∫§ÿ¡°“√ —ß‡§√“–Àå kin (IL)-1, IL-2, interferon (IFN)-α, tumor ‚ª√µ’π ‡¡◊ËÕæàπ¬“ µ’√Õ¬¥å‡¢â“‰ª„π‚æ√ß®¡Ÿ° ¬“ necrosis factor (TNF), colony-stimulating µ√Õ¬¥’ ®–ºå “πà cell membrane ‡¢“‰ª„πâ cytoplasm factors (CSFs) ™π¥µ‘ “ßÊà ·≈–¬∫¬— ß°“√ √—È “ßâ proin- ¢Õß‡´≈≈ å ·≈«‰ª®â ∫°— ∫— glucocorticoid receptor ‡ªπì flammatory enzymes (‡™àπ collagenase, elastase) steroid-receptor complex ·≈â«‡§≈◊ËÕπ‡¢â“ Ÿà nucle- ·≈– ¬—∫¬—Èß lymphocyte proliferation.

8 §≈‘π‘° ªï∑’Ë 29 ©∫—∫∑’Ë 1 ¡°√“§¡ 2556 º≈¢â“ß‡§’¬ß¢Õß¬“ µ’√Õ¬¥åæàπ®¡Ÿ° º≈¢Õß°“√µ—¥‡¬◊ËÕ∫ÿ®¡Ÿ°‰ªµ√«®°àÕπ‡√‘Ë¡°“√√—°…“ 1. º≈¢â“ß‡§’¬ß∑’Ë‰¡àæ÷ßª√– ß§å‡©æ“–∑’Ë Minshall ·≈–§≥–14æ∫«à“°“√„™â mometasone (local adverse effects) furoate „πºŸâªÉ«¬‚√§®¡Ÿ°Õ—°‡ ∫¿Ÿ¡‘·æâ‡ªìπ√–¬–‡«≈“ °“√„™â¬“ µ’√Õ¬¥åæàπ®¡Ÿ° Õ“®‡°‘¥º≈¢â“ß‡§’¬ß 1 ª ï‰¡æ∫«à “¡à ‡¬’ Õ∫◊Ë ®¡ÿ°‡ÀŸ ¬«Ω’Ë ÕÉ À√Õ°“√‡ª≈◊ ¬π·ª≈ß’Ë ‡©æ“–∑’Ë‰¥â ‡™àπ ‡¬◊ËÕ∫ÿ®¡Ÿ°·Àâß, ¡’ –‡°Á¥, ‡≈◊Õ¥ ¢Õß epithelial thickness ·≈–¡’ focal metaplasia °”‡¥“‰À≈ (epistaxis), Õ“°“√· ∫À√◊Õ√–§“¬‡§◊Õß ¥¢’ π.÷È ¢Õß‡¬◊ËÕ∫ÿ®¡Ÿ° º≈¢â“ß‡§’¬ß¥—ß°≈à“«‡°‘¥‰¥â√âÕ¬≈– 5 - °“√»÷°…“Õ’° 2 °“√»÷°…“· ¥ß„Àâ‡ÀÁπ«à“°“√ 104,5 ´÷Ëßº≈¢â“ß‡§’¬ß‡©æ“–∑’Ë¥—ß°≈à“«¡—°À“¬‰¥â‡Õß „™â triamcinolone acetonide ‡ªìπ√–¬–‡«≈“π“π πÕ°®“°π—Èπ ¬—ß¡’√“¬ß“π°“√‡°‘¥ºπ—ß°—Èπ™àÕß®¡Ÿ° „πºŸâªÉ«¬‚√§®¡Ÿ°Õ—°‡ ∫¿Ÿ¡‘·æâ™π‘¥‡ªìπµ≈Õ¥ªï ‰¡à ∑–≈ÿ (nasal septal perforation) À≈—ß®“°°“√„™â¬“ ∑”„Àâ¡’°“√‡ª≈’Ë¬π·ª≈ß¢Õß§«“¡Àπ“¢Õß‡¬◊ËÕ∫ÿ®¡Ÿ° µ’√Õ¬¥åæàπ®¡Ÿ°√ÿàπ·√°Ê6 ´÷Ëßº≈¢â“ß‡§’¬ß‡©æ“–∑’Ëπ’È ´÷Ëß‡ªìπ¥—™π’∑’Ë∫àß™’È∂÷ß‡¬◊ËÕ∫ÿ®¡Ÿ°‡À’Ë¬«ΩÉÕ ‡¡◊ËÕ‡ª√’¬∫ “¡“√∂À≈’°‡≈’Ë¬ß‰¥â ∂â“„™â¬“ µ’√Õ¬¥åæàπ®¡Ÿ°Õ¬à“ß ‡∑’¬∫°—∫ºŸâªÉ«¬‚√§®¡Ÿ°Õ—°‡ ∫¿Ÿ¡‘·æâ™π‘¥‡ªìπµ≈Õ¥ªï ∂Ÿ°«‘∏’7 §◊Õ·π–π”„Àâæàπ¬“‰ª —¡º— °—∫‡¬◊ËÕ∫ÿ®¡Ÿ°∑’Ë ∑’Ë‰¥â√—∫°“√√—°…“¥â«¬ cetirizine8,15 Baroody ·≈– Õ¬Ÿà¥â“π¢â“ß¢Õß‚æ√ß®¡Ÿ°„Àâ¡“°∑’Ë ÿ¥‡∑à“∑’Ë®–¡“° §≥–16æ∫«à“°“√„™â fluticasone propionate „π ‰¥â ‚¥¬‰¡à„Àâæàπ¬“‡¢â“‰ª∑’Ëºπ—ß°—Èπ™àÕß®¡Ÿ°´÷ËßÕ¬Ÿà ºŸâªÉ«¬‚√§®¡Ÿ°Õ—°‡ ∫¿Ÿ¡‘·æâ™π‘¥‡ªìπµ≈Õ¥ªï‡ªìπ µ√ß°≈“ß. √–¬–‡«≈“ 1 ªï ‰¡à∑”„Àâ‡°‘¥°“√‡ª≈’Ë¬π·ª≈ß¢Õß πÕ°®“°¡’º≈¢â“ß‡§’¬ß¥—ß°≈à“«·≈â« ‘Ëß∑’Ëπà“ ‡¬◊ËÕ∫ÿ®¡Ÿ° ‡¡◊ËÕ‡ª√’¬∫‡∑’¬∫°—∫ºŸâªÉ«¬‚√§®¡Ÿ°Õ—°‡ ∫ °—ß«≈§◊Õ ¬“ µ’√Õ¬¥åæàπ®¡Ÿ°¡’º≈µàÕ°“√∑”ß“π¢Õß ¿¡Ÿ ·æ‘ ™πâ ¥‡ª‘ πµ≈Õ¥ªì ∑ï ‰¥’Ë √â ∫°“√√— °…“¥— «¬â terfena- ¢π°«—¥„π®¡Ÿ° (nasal mucociliary clearance) dine. À√◊Õ∑”„Àâ‡¬◊ËÕ∫ÿ®¡Ÿ°‡À’Ë¬«ΩÉÕ (nasal mucosal atro- ¥—ßπ—Èπ ®“°À≈—°∞“π∑’Ë°≈à“«¡“∑—ÈßÀ¡¥ · ¥ß„Àâ phy) ‡À¡◊Õπ°“√„™â¬“ µ’√Õ¬¥å∑“º‘«Àπ—ß‡ªìπ√–¬– ‡ÀÁπ«à“°“√„™â¬“ µ’√Õ¬¥åæàπ®¡Ÿ°‡ªìπ√–¬–‡«≈“π“π ‡«≈“π“π ·≈â«‡°‘¥ skin atrophy À√◊Õ‰¡à Klossek ¡’§«“¡ª≈Õ¥¿—¬µàÕ‡¬◊ËÕ∫ÿ®¡Ÿ°∑—Èß¥â“π‚§√ß √â“ß ·≈– ·≈–§≥–8 æ∫«“°“√„™à â triamcinolone acetonide „π °“√∑”ß“π πÕ°®“°π—Èπ¬“ µ’√Õ¬¥åæàπ®¡Ÿ°∫“ß™π‘¥ ºŸâªÉ«¬‚√§®¡Ÿ°Õ—°‡ ∫¿Ÿ¡‘·æâ™π‘¥‡ªìπµ≈Õ¥ªï (peren- ¡’ “√ benzalkonium chloride ‡ªìπ preservative nial allergic rhinitis) ‡ªìπ√–¬–‡«≈“ 6 ‡¥◊Õπ °Á “¡“√∂„™â‰¥âÕ¬à“ßª≈Õ¥¿—¬„π√–¬–¬“«‚¥¬‰¡à∑” ‰¡à‰¥â∑”„Àâ mucociliary function „π®¡Ÿ°‡ ’¬‰ª Õ—πµ√“¬µàÕ‡¬◊ËÕ∫ÿ®¡Ÿ°‡™àπ°—π17. Naclerio ·≈–§≥–9 æ∫«à“°“√„™â budesonide À√◊Õ mometasone furoate „πºªŸâ «¬‚√§®¡É °ÕŸ °‡ ∫¿— ¡Ÿ ·æ‘ â 2. º≈¢â“ß‡§’¬ß∑’Ë‰¡àæ÷ßª√– ß§åµàÕ∑—Ë« ™π‘¥‡ªìπµ≈Õ¥ªï ‡ªìπ√–¬–‡«≈“ 2 —ª¥“Àå ‰¡à‰¥â∑” √à“ß°“¬ (systemic adverse effects) „Àâ mucociliary function „π®¡Ÿ°‡ ’¬‰ª‡™àπ°—π. 2.1 º≈¢Õß¬“ µ’√Õ¬¥åæàπ®¡Ÿ°µàÕ °“√»÷°…“ 3 °“√»÷°…“· ¥ß„Àâ‡ÀÁπ«à“ °“√ Hypothalamic-Pituitary-Adrenal (HPA) „™â beclomethasone dipropionate ‡ªìπ√–¬– axis ‡«≈“π“π∂÷ß 6 ªï‰¡à∑”„Àâ‡°‘¥‡¬◊ËÕ∫ÿ®¡Ÿ°‡À’Ë¬«ΩÉÕ10-12 ¡’ß“π«‘®—¬¡“°¡“¬∑’Ë«—¥º≈°√–∑∫¢Õß¬“ Pipkorn ·≈–§≥–13æ∫«à“°“√„™â budesonide „π µ’√Õ¬¥åæàπ®¡Ÿ°µàÕ°“√∑”ß“π¢Õß HPA axis °“√ ºŸâªÉ«¬‚√§®¡Ÿ°Õ—°‡ ∫¿Ÿ¡‘·æâ µ—Èß·µà√–¬–‡«≈“ 1-5 ªï »÷°…“ à«π„À≠à‰¡àæ∫°“√‡ª≈’Ë¬π·ª≈ß¢Õß HPA ‰¡à∑”„Àâ‡°‘¥‡¬◊ËÕ∫ÿ®¡Ÿ°‡À’Ë¬«ΩÉÕ ‡¡◊ËÕ‡ª√’¬∫‡∑’¬∫°—∫ axis18-33 Õ¬“ß‰√°à µ“¡Á ¡∫“ß√“¬ß“π∑’ æ∫«’Ë “¬“ µà √Õ¬¥’ å

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™π‘¥¢Õß¬“ µ’√Õ¬¥åæàπ®¡Ÿ° Õ“¬ÿ∑’Ë‰¥â√—∫°“√√—∫√Õß‚¥¬ Õß§å°“√Õ“À“√·≈–¬“¢Õßª√–‡∑» (ªï) À√∞Õ‡¡√— °“‘ ‰∑¬ Fluticasone furoate ≥ 2 ≥ 2 Triamcinolone acetonide ≥ 2 ≥ 2 Mometasone furoate ≥ 2 ≥ 3 Fluticasone propionate ≥ 4 ≥ 4 Budesonide ≥ 6 ≥ 6 Beclomethasone dipropionate ≥ 6 ≥ 6

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