第三項はCholinergic receptor[副交感神経受容体]に関連する医薬品のお話。
Cholinergic receptor はmuscarinic[ムスカリン受容体](M1,M2,M3) & nicotinic receptors[ニコチン受容体](NN,NM)の二種類。(作用の強さ : musucarin>nicotin)
<ニコチンNN受容体刺激反応>
- 瞳孔 : 縮瞳(瞳孔括約筋 : 収縮)
- 眼内圧 : 下降(毛様体筋 : 収縮⇒シュレム管 : 開口)
- 心機能 : 抑制
- 気管支 : 収縮
- 胃腸運動 : 促進
- 腸管平滑筋 : 収縮
- 尿 : 出やすい(排尿筋 : 収縮)
- 腺分泌 : 促進
※ 交感神経節：血管(収縮)、汗(分泌増加)
Acetylcholine is natural and most potent[強力な] cholinergic agonist[コリン作動薬].
* quantenary amino alchol
* unstable in the blood (hydrolysis[加水分解] by acetylcholinesterase : acetic acid + choline)
* choline is reused in nerve termination[神経終末]
 |
| Acetylcholine |
- Direct-acting agonists
acetyl group⇒carbamonyl group (more resisitant to acetylecholinesterase)
- Indirect-acting agonists
* reversible (short-acting) agents
* irreversible (long-acting) agents : inhibit or block the activity of cholinesterase enzyme
Therapeutic indications
- Direct-acting agonists
M3: micturition[頻尿] in acute nonobstructive urinary retention[非閉塞性尿閉] (e.g., bethanechol)
M3: miosis[縮瞳] in the treatment of glaucoma[緑内障] (e.g., pilocarpine)
- Inrdirect-acting agonists (cholineesterase inhibitor)
ex) reversible : physostigmine, neostigmine, distigmine, ambenonium
ex) irreversible : echothiophate, sarin, parathion, organophosphate[有機リン酸化合物]
M1: congnitive function[認知能力]↑ in Alzheimer's disease (e.g., tacrine, donepezil, galantamine)
M2: treat paralytic ileus[麻痺性イレウス]、 tarchyarrythmias[不整脈] (e.g., edrophonium)
M3: miosis[縮瞳] in the treatment of glaucoma[緑内障] (e.g., pilocarpine)
NM: treat myathenia gravis[重症筋無力症](caused by nicotinic receptor hypofunction) (e.g., neostigmine, distigmine, ambenonium)
Adverse effects
- topical S.E. : congested conunctivae[結膜]、myopic accommodation[近視調節麻痺]、transient lenticular opacity[一時的なレンズ混濁]
- systemic S.E. : headache, syncope[失神], nausea, vomiting, bradycardia[除脈], hypotension, bronchospasm, abdominal cramps[腹痛], diarrhea, salvation[唾液分泌], sweating, lacrimation[流涙], flushing, tremor[震戦]
Cholinergic Antagonists
competitively inhibit the activity of endogenous acetylcholine
- 1. antimuscarinic agetns : inhibit muscarinic rceptor
- 2. ganglionic-blocking agents : inhibit nicotinic receptor at the ganglia
- 3. neuromuscular-blocking agents : inhibit nicotinic receptor at the neuromuscular
1. Antimuscarinic agents
ex)Atropine (belladonna alkaloid) : its bulky shape prevents acetylcholine
quanternary nitrogen or a tertiary nitrogen
 |
| Atropine |
* M1：control neurleptic-induced extrapyramidal reaction[錐体外路系反応] (e.g., benztropine, trihexyphenidyl)
* M1：induce sedation[鎮静] (e.g., scopolamine)
* M1：motion sickness[乗り物酔い]↓ (e.g., scopolamine)
* M1：treat intoxication[中毒] by acute mushroom poisoning (e.g., atropine)
* M1: treatment of peptic ulcer[消化性潰瘍] (e.g., pirenzepine)
* M1：prophylaxis of miscarriage[流産] & premature labor (e.g., piperidolate)
* M3：mydriasis[散瞳] & cycloplegia[毛様体筋麻痺/弛緩] (e.g., homatropine, tropicamide)
* M3：GI smooth-muscle spasm↓ (e.g., propantheline)
* M3：treat bronchospasm bronchodilation[気管支拡張](e.g., ipratropium)
* M3：glandular[(分泌)腺] & bronchiolar[気管支] secretions↓ before anesthesia[麻酔] (e.g., atropine, glycopyrolate)
* M3：treat urinary frequency[頻尿] (e.g., propiverine, oxybutynine)
2. Ganglionic-blocking agents
* NN：hypertensive crisis (e.g., trimethaphan, mecamylamine, hexamethonium) by sympathetic activity↓
3. Neuromuscular-blocking agents : skeletal muscle relaxation
* Endotracheal intubation[気管支内挿管], adjunct to surgical anesthesia[麻酔]
* Bone placement & manipulation[関節を動かす手法]
* electro convulsive shock therapy[電気痙攣ショック療法] : limit the trauma[外傷] by excessive
skeletal muscle contraction
- competitive nondepolarizing[非脱分極] agents
end-plate potential[終末電位]↓⇒depolarization threshold[閾値] is not reached
ex) tubocurarine (curare[クラーレ] alkaloid) & metocurine : bulky molecules
important structural feature : tertiary-quantenary amine
ex) atracurium, doxacurium, mivacurium (potent synthetic analogues with isoquinolines[イソキノリン]
ex) pancuronium, vecuronium, pipecuronium (steroid derivatives[誘導体])
- noncompetitive depolarizing agents
desensitize the nicotinic receptor
slender aliphatic molecules, (Not bulky molecules like competitive agents)
ex) succinylcholine (& gallamine)
: short duration of action due to hydrolysis by pseudocholinesterase
Adverse effects
- Topical adverse effects
* hyperopic accommodation[遠視調節麻痺] & intraocular[眼内] pressure↑
- Systemic adverse effects
* headache, nervousness, drowsiness, diziness, palpitation[動悸], tachycardia[頻脈]
* dry mouth, mydriasis[散瞳], blurred vision[視力障害], nausea, vomiting, constipation, urinary retention
* respiratory paralysis[麻痺], histamine↑, bronchospasm, hypotention & hypertension,
Today's question
- Cholinergic agents(副交感神経薬)の問題
Q: Adverse reactions to atropine include all of the following except
(A) photophobia
(B) dry mouth
(C) sedation
(D) diarrhea
(E) tachycardia
A: (D) diarrhea
Classic sign and symptoms of muscarinic blockade, as with atropine, include mydriasis, which may cause light sensitivity (photophobia); dry mouth and constipation by decreasing secretory activity and motility in the GI tract; and tachycardia by inhibiting the normal inhibitory cholinergic control of the cardiac system. Diarrhea is one of the common signs of cholinergic agonists (such as salivatio, lacrimation or tearing, urination and diarrhea).
0 件のコメント:
コメントを投稿