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属于胆碱能增强药
【体内过程】
口服个体差异大，食物可明显影响其吸收。饭后服，t1/2约2～4h。
【药理作用】
临床使用始于1993年。脂溶性高，易透过血脑屏障，对AChE有抑制作用，是常用药物。
【机制】
① 抑制脑内AChE，增加脑内ACh含量。
② 促进脑内AChE的释放。
③ 增加大脑皮质和海马的N-R密度。
④促进脑组织对葡萄糖的利用，改善学习、记忆能力的降低。
【临床应用】
治疗阿尔茨海默痴呆(与磷脂酰胆碱合用) ，可延缓病程6～12个月，提高患者的认知能力和自理能力。
【不良反应】
最常见的不良反应为肝毒性及消化道反应。多奈哌齐肝脏毒性较低，患者耐受较好
他克林Tacrine (盐酸他克林)（tacrine，Cognex®）、
【药理作用】能可逆性抑制中枢AChE活性。
【体内过程】本品口服后，可迅速经胃肠道吸收，血浆浓度可在2小时达高峰，口服后肝脏首关消除明显，但其生物利用度和血浆峰值的个体差异较大，胃内容物存在可使本品的吸收减少soX～40％左右。本品可被微粒体细胞色素P450酶系统(主要为CYPlA2)所代谢，主要代谢产物为维那克(velnacrine)，亦具有AChE抑制作用。他克林血浆蛋白结合率为55％，易进入中枢，并可较长时间滞留在中枢。其消除相半衰期约为3小时。他克林原形经尿排泄很少。
根据21位患者的3项研究提示，口服盐酸他克林 25mg或50mg后，其血浆达峰时间为0.5～3小时，而口服的生物利用度从不到5％直到36％。口服25mg后，药物的平均消除相半衰期为l.37～1.59小时；而口服 50mg后，药物的平均消除相半衰期为2.14～3.2小时。药物主要经肝代谢消除，在1位病人中发现，原形药物在尿中的浓度低于用量的3％。
【副作用及注意事项】肝脏毒性为本品最常见和最重要副作用，约有30％接受低剂量该药治疗病人可出现转氨酶升高，尤其在治疗开始后头3个月内。故在开始给药后的18周内，应每周测定血清转氨酶，如正常，以后可每隔3月测定1次。每增加一次剂量，应重新每周测定 1次，至少持续6周。如肝功能异常，则应减量或停药。一般认为，如转氨酶升高3～5倍，则本品每日剂量应递减40mg。如升高幅度更大，则应停用本药。如病人出现黄疸，应立即停药。一旦病人肝功能恢复正常，可重新服用本品，但曾有黄疸出现的病人除外。停用本品后，约 90％病人肝功能可恢复正常。其它副作用为AChE抑制后所引起反应。突然停用他克林或大幅度减少用量病人可引起行为障碍及识别能力下降。
由于本品在体内主要经肝细胞色素P450酶(CYPlA2) 系统代谢，故抑制或诱导此酶活性的药物均可升高或降低他克林的血药浓度。
【用途】主要用于阿尔茨海默病的治疗，可使病人的认知能力改善，亦可改善定向能力，但以前者更为显著。
多中心研究证明，该药对轻、中度病人较好。
一般认为本品开始剂量为lomg／次，4次／日，至少6周，在此期间，不宜增加用量，因为用药过程中会出现潜在迟缓性血清转氨酶升高。因此必须定期检测病人血清转氨酶，如此酶未明显升高，剂量可调整为20mg／次，4次／日，再服6周，即每隔6周，可每日增加40mg，直至获得满意疗效，但最大剂量不超过160mg／d，疗程为2～12个月，有效率约为l5％～30％。由于本品并不能改变神经变性过程，故对非阿尔茨海默病和晚期病人所伴随的行为障碍疗效较差。本品应空腹给药，以增加其胃肠道吸收，但如病人的胃肠道副作用明显，则可采用药物与食物同服的方式。本品也用于延长琥珀酰胆碱的作用和拮抗竞争性肌松药的作用。此外，本品还可用作呼吸兴奋剂，并作为吗啡治疗时的辅助用药，以减轻阿片类生物碱引起的呼吸抑制作用。
【制剂】：盐酸他克林胶囊：70mg；盐酸他克林片： 20mg，30mg，40mg。
Brand names: Cognex®
Tacrine Hydrochloride Oral capsule
What is this medicine?
TACRINE (TAK reen) is used to treat mild tomoderatedementiacausedbyAlzheimer's disease.
This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.
What should I tell my health care provider before I take this medicine?
They need to know if you have any of these conditions:
•difficulty passing urine
•heart disease, slow heartbeat
•jaundice
•liver disease
•lung or breathing disease, like asthma
•seizures
•stomach or intestinal disease, ulcers or stomach bleeding
•an unusual or allergic reaction to tacrine, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding
How should I use this medicine?
Take this medicine by mouth with a glass of water. Follow the directions on the prescription label. It is best to take this medicine on an empty stomach, at least 1 hour before or 2 hours after meals. If this medicine upsets your stomach, you can take it with food. Take your doses at regular intervals. Do not take your medicine more often than directed. Continue to take your medicine even if you feel better. Do not stop taking except on the advice of your doctor or health care professional.
Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.
Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.
What may interact with this medicine?
•atropine
•benztropine
•cimetidine
•dicyclomine
•donepezil
•fluvoxamine
•galantamine
•glycopyrrolate
•ipratropium
•medicines for motion sickness like dimenhydrinate, meclizine, scopolamine
•medicines that relax your muscles for surgery
•NSAIDs, medicines for pain and inflammation, like ibuprofen or naproxen
•oxybutynin
•propantheline
•rivastigmine
•theophylline
•tolterodine
•trihexyphenidyl
This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.
What should I watch for while using this medicine?
Visit your doctor or health care professional for regular checks on your progress. Your doctor will need to regularly check your blood to monitor the effect of this medicine on your liver. Check with your doctor or health care professional if there is no improvement in your symptoms or if they get worse.
Avoid alcohol while you are taking this medicine. Alcohol may increase the risk of getting liver damage. Also try to avoid smoking. Smoking tobacco may lessen the effect of this medicine. Ask your doctor or health care professional for ways to help you stop smoking or drinking.
You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how this medicine affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells.
What side effects may I notice from receiving this medicine?
Side effects that you should report to your doctor or health care professional as soon as possible:
•allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
•changes in vision
•dark yellow or brown urine
•diarrhea, if it is severe or does not stop
•dizziness, fainting spells, or falls
•increase in frequency of passing urine, or incontinence
•muscle pains
•nervousness, agitation, or increased confusion
•pain in the stomach or abdomen
•slow heartbeat, or palpitations
•sweating
•uncontrollable movements
•vomiting
•yellowing of eyes or skin
Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
•diarrhea
•dry mouth
•indigestion
•loss of appetite
•nausea
This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Where should I keep my medicine?
Keep out of reach of children.
Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Protect from moisture. Throw away any unused medicine after the expiration date.
Last updated: 7/1/2002 | 
