Adrenergic antagonist腎上腺素接受器拮抗劑/腎上腺素受體拮抗劑

吳宗穎藥師整理，有錯請多指教~

Nonselective α-antagonist: alkylating agent: β-haloalkylamine der. (irreversible)→aziridinium(ethylene iminium)
Phenoxybenzamine Phenoxy-benzyl			pheochromocytoma
Nonselective α-antagonist: imidazoline (reversible): pheochromocytoma
Tolazoline 似α1 agonist, tolene				Author    JaGa
Phentolamine Phenol-toluene
Selective α1-antagonist: ergot(麥角)
Ergotamine →dihydroergotamine
Selective α1-antagonist: quinoxalines(quinazolines) ~zosin
Prazosin(minipress) Furan Antihypertensive drug
Terazosin(Hytrin) Tetrahydrofuran Antihypertensive drug, drug for BPH, too. Longer-acting
Doxazosin Benzodioxane Antihypertensive drug, drug for BPH, too. Longer-acting
Trimazosin B(RxC)沒
Alfuzosin(Xatral) α1A, open ring piperazine- propylenediamine first-line agent for BPH without antihypertensive activity
Selective α1-antagonist: nonquinazolines benzensulfonamides
Tamsulosin first-line agent for BPH without antihypertensive activity long-acting
Selective α1-antagonist: indole
Indoramin BRxC沒
Selective α2-antagonist
Yohimbine(育亨賓) Antagonize clonidine
Nonselective β-antagonist, first generation β-blocker 有p N-isopropyl Penbutol不算，其pen為cyclopentyl 沒p N-tert-butyl
Nonselective β-antagonist, first generation β-blocker. (R)-arylethanolamines. 皆N-isopropyl.
Dichloroisoproteranol(DIC) 有ISA
Pronethalol Nephthacene Cause tumor
Sotalol Urinary Elim Class III antiarrythmia
Nonselective β-antagonist, first generation β-blocker. (S)-aryloxypropanolamines. Ex. Phenyloxypropanolamine            N-isopropyl
propranolol(2C19 Substrate):由pronethalol加上oxymethylene得到most lipophilic among all beta-blockers. 所以CNS-side effect, treat anxiety( can’t be used in depression ) Prophylasis of migrain Hepatic Elim
Pindolol(有ISA) Indole Urinary Elim
Nonselective β-antagonist, first generation β-blocker. (S)-aryloxypropanolamines. Ex. Phenyloxypropanolamine            N-tert-butyl
Nadolol(hydrophilic) urinary Elim Long duration
S-(-)- timolol(2D6 Substrate)少一個C Hepatic Elim Glaucoma D
S-(-)-penbutolol(有ISA) hepatic Elim Cyclopentyl
S-(-)-Bunolol (levobunolol)
Carteolol(有ISA) urinary Elim
Nonselective β-antagonist, first generation β-blocker. 4-substituted aryloxypropanolamines. 青光眼    N-isopropyl
Metipranolol 非beta1-selective的 4-substituted aryloxypropanolamines.
Selective beta1-antagonist: second generation beta-blockers. 皆 4-substituted aryloxypropanolamines. 皆 N-isopropyl
Acebutolol(有ISA) Hepatic Elim
Esmolol   Ester Methyl ester of carboxylic metabolite of metoprolol, 所以susceptable by serum esterase,所以short t1/2, creat inactive metabolite and readily to be excreted. 所以is used to control supraventricular tachycardia during surgery when a short-acting beta1-antagonist is desired.
Atenolol Amide(hydrophilic, hepatic Elim,同local anesthetics)
metoprolol(2D6 Substrate)Hepatic Elim, inverse agonist, methoxy
Betaxolol Hepatic elim Inverse agonist
Bisoprolol Urinary Elim Treat CHF
Practolol童(Rxlogy)
Mixed α/β-adrenergic antagonist,所以this kind of β-adrenergic antagonists ( nonselective β-antagonist ) have side effect of orthostatic hypertension as α1 antagonist Third generation β-blockers are drug that also possess vasodiltion activity through blockade of α1 receptor Step1 agent to treat hypertension,treat essential and renal hypertension
Phenylethanolamine
Labetalol(Normodyne, Trandate) α-methyl substituent attached to the N-arylalkyl gr. Appears to be responsible for the adrenergic blocking activity. Possess 2 chiral centers and, is administered as a mixture of 4 enantiomers (1R,2R): R(OH), R(CH3)=dilevalol: β-blocker with minimal α1-blocking activity R(OH),S(CH3): α1 antagonist Urinary Elim dilevalol
Aryloxyethanolamines
Carvedilol(Coreg) S(-)-enantiomer: α- and β-blockers R(+)-enantiomer: α1-blocker
Third generation beta-blocker為nonselective,所以同first generation beta-blocker, can’t be used in asthma 白老師 我 Beta1-blocker(台語):阿天(atenolol)、阿些(acebutolol)被他(betaxolol)逼死(bisoprolol),罵個(metoprolol)要死(esmolol)不會累(practolol) Diminish portal veinpressure: propranolol, nadolol Glaucoma drug(台語):沒(metipranolol)淚(leveobunolol)鐵(timolol)腳(carteolol)伯(betaxolol),所以得青光眼 Ischemic heart disease:timolol, propranolol, metoprolol Partial agonist(台語):阿些(acebutolol)給(carteolol)騙(penbutolol)餅(pindolol),吃下去產生部分作用 CHF(白):bi(bisoprolol)-car(carvedilol)-met(metoprolol) Membrane-stablizing activity(local anesthetic activity)(台語):阿些(acebutolol)破(propranolol)病(pindolol)讓他(labetalol)遇到(metoprolol)病情就穩定下來 高血壓 一般人 很多 孕婦 gestational妊ㄖㄣˋ娠ㄔㄣˊ hypertension 用methyldopa 250 mg 2~3 times daily，alternative: clonidine，methyldopa+hydralazine可用在慢性高血壓 哺乳婦 CCB:nefedipine，一般不用。哺乳婦可用 ACEI不能用在懷孕；captopril和enalapril可用於哺乳婦 臨床上用左旋者:累喔(levobunolol)~提(timolol)筆(penbutolol) Hyperthyroidism:propranolol Highest lipophilicity Propranolol Highest hydrophilicity Nadolol 心跳過快atenolol Longest t1/2 nadolol Shortest t1/2 Esmolol E(renal) E(hepatic)
NE biosynthesis inhibitor
(S)-metyrosine (α-methyl-L-tyrosine) Pheochromocytoma( compatitive).  It inhibits the enzyme tyrosine hydroxylase
(S)-carbidopa Treat Parkinson’s disease It   inhibits aromatic-L-amino-acid decarboxylase (DOPA Decarboxylase or DDC).
阻止NE儲存: nonselective(PNS & CNS)-(-)→VMAT
Reserpine
syrosingopine
抑制交感神經釋放 selective(only PNS)-(-)→VAMPs
Guanethidine P.S.  Guanethidine-like Antihypertensive: debrisoquin(2D6 Substrate)
Guanadrel
Brtylium

β blocker

→bradycardia/四肢冰冷。沒有姿態性低血壓

α blocker

→有姿態性低血壓/反射性心跳加速tachycardia