Antipsychotic Agent抗思覺失調症藥

• 和長照相關，照顧壓力可能會引起悲劇(2017年05月19日 10:24東森新聞高雄砍頭案／兄怨照顧妹好累　其實「喘息服務」可幫喘口氣)。
• 抗精神病藥(antipsychotic drugs、Neuroleptic drugs)或稱精神安定劑(major tranquilizers)。
• 因為主要用來治療思覺失調症(舊名精神分裂症)(schizophrenia)，所以也稱作抗思覺失調症藥(舊名抗精神分裂症藥)(antischizophrenic drugs)，但是他也可以治療其他psychotic states，像是manic states、譫妄(delirium)

治療學

• Patients who have had two or more schizophrenic episodes should receive maintenance therapy for at least five years, Low dose of antipsychotic drugs are not as effective as higher-dose maintenance therapy in preventing relapse.

分類 (機轉)

• 依有無錐體外症候群分成typical neuroleptics和atypical neuroleptics.
• typical neuroleptics: 作用在mesolimbic pathway的D2 receptor競爭性拮抗劑，因此有阻斷nigrostriatal pathway所造成的錐體外症候群，通常用來治療思覺失調症(舊名精神分裂症)的positive symptoms
• atypical neurleptics:的機轉不是D2 receptor競爭性拮抗劑，因此不像typical neuleptics有阻斷nigrostriatal pathway所造成的錐體外症候群，通常用來治療思覺失調症(舊名精神分裂症)的negative symptoms
  • 2014研究:atypical neurleptics治療精神病的機轉可能和對Toxoplasmosis弓漿蟲感染的抑制效果有關。弓漿蟲與思覺失調症有關 bioforum.tw/modules/tadnews/index.php?nsn=2811

• 大部分的抗精神病藥都會同時阻斷M、α、D₁、D₂、H₁接受體，但主要作用是阻斷D₂接受體，而有精神安定作用。除了D₂之外的其他接受體作用就成了不可獲免的副作用。
• 但是typical neuroleptics主要的副作用是錐體外症候群；而atypical neuroleptics則無此負作用。

• 其中typical neuroleptics又分成low pottency和high pottency。

• high pottency one常常做成長效型:Fluphenazine decanoate and haloperidol decanoate are slow-release (up to three weeks)formulations that are administered by intramuscular injection.

• As a result, The actions of the neuroleptic drugs are antagonized by agents that raise the dopamine concentration -for example, levodopa and amphetamines.

• The newer atypical agents appear to exert part of their unique action through inhibition of serotonin receptors (5-HT)-5-HT2A autoreceptors.

• The atypical neuroleptic aripiprazole is a partial agonist at D2 and 5-HT1A receptors as well as a blocker of 5-HT2A receptors.

分類（化學結構）

• Phenothiazines
  • Propylamine side-chain
  • Piperidine side-chain
  • Piperazine side-chain
• Phenothiazines-likes
  • Thioxanthenes
  • Dibenzothiazepines
  • Dibenzoxazepines
  • Dibenzodiazepines
  • Thienobenzodiazepines
• Fluorobutyrophenones
• β-Aminoketones
• Benzamides
• Antimanic agents

個論

Phenothiazines

Propylamine side-chain

• Promazine
• prototype:Chlorpromazine
• Triflupromazine

Piperidine side-chain

• Thioridazine
• Mesoridazine
• Piperacetazine

Piperazine side-chain

• Prochlorperazine
• Trifluoperazine
• Thiethylperazine
• Perphenazine
• Fluphenazine
• Acetophenazine
• Carphenazine

Phenothiazines-likes

Thioxanthenes

• Chlorprothixene
• Thiothixene

Dibenzothiazepines

• Quetiapine
• Metiapine
• Clothiapine

Dibenzoxazepines

• Loxapine

Dibenzodiazepines

• clozapine

Thienobenzodiazepines

• Olanzapine

Fluorobutyrophenones

• Haloperidol
• Droperidol
• Risperidone
• Penfluridol
• Pimozide

β-Aminoketones

• Molindone
• Ondansetron

Benzamides

• Sulpiride:精神安定、消化性潰瘍、孕婦用藥分級:D 級
• Sultopride
• Remoxipride

Antimanic agents

• 機轉和精神病不同，但是很多書編在同一章，見主條目Antimanics
• Lithium Salts
• 部分抗癲癇藥 Ex. carbamazepine和valproate

分類

TIPICAL

弱效

• Chlorpromazine: Phenothiazines:Propylamine side-chain
• Thioridazine: Phenothiazines:Piperidine side-chain
• Prochlorperazine: Phenothiazines:Piperazine side-chain

強效

• Fluphenazine: Phenothiazines:Piperazine side-chain
• Thiothixene :Phenothiazines-likes:Thioxanthenes
• Haloperidol :Fluorobutyrophenones
• Pimozide:Fluorobutyrophenones

ATYPICAL

• clozapine:Phenothiazines-likes:Dibenzodiazepines
• Quetiapine:Phenothiazines-likes:Dibenzothiazepines
• Olanzapine:Phenothiazines-likes:Thienobenzodiazepines
• Risperidone:Fluorobutyrophenones

抗精神病藥的其他功能

腸胃道作用

• Be useful in the treatment of drug-induced nausea.尤其是prochlorperazine
• antiemetic effects:With the exception of thioridazine most of the neuroleptic drugs have antiemetic effects that are mediated by blocking D2-dopaminergic receptors of the chemoreceptor trigger zone of the medulla.

治療慢性神經痛

• Neuroleptics are used in combination with narcotic analgesics for treatment of chronic pain with severe anxiety.

其他

• Chlorpromazine is used to treat intractable hiccups.
• Promethazine not good antipsychotic drug; however, this agent is used in treating pruritus because of its antihistaminic properties.
• Pimozide primarily indicated for treatment of the motor and phonic tics of Tourette disorder.

副作用

• In the pituitary, neuroleptics block D2 receptors, leading to an increase in prolactin release.
• Blockade of α -adrenergic receptors causes lowered blood pressure, orthostatic hypotension and light-headedness
• Antimuscarinic effects:The neuroleptics often produce dry mouth, urinary retention, constipation, and loss of accommodation.
• Sedation occurs in those drugs that are potent antagonists of the H1 histamine receptor, including chlorpromazine and clozapine.
• Drowsiness occurs due to CNS depression, usually during the first two weeks of treatment.
• Confusion is sometimes encountered.
• The neuroleptics depress the hypothalamus, causing amenorrhea, galactorrhea, infertility, and impotence.
• The neuroleptics also alter temperature-regulating mechanisms and can produce pikilothermia (body temperature varies with the environment).

毒性

• Neuroleptic malignant syndrome:This potentially fatal reaction to neuroleptic drugs is characterized by muscle rigidity, fever, stupor, unstable blood pressure, and myoglobinemia. Treatment necessitates discontinuation of the neuroleptic and Administration of dantrolene or bromocriptine may be helpful.

藥物連用的結果

• The neuroleptic drugs produce some tolerance(耐受性) but little physical dependence.

Cautions and contraindications

• Acute agitation accompanying withdrawal from alcohol or other drugs may be aggravated by the neuroleptics. Stabilization with a simple sedative, such as a benzodiazepine, is the preferred treatment.
• Chlorpromazine and clozapine are contraindicated in patients with seizure disorders, because these drugs can lower seizure threshold. The neuroleptics can also aggravate epilepsy.

相關條目

• 精神安定劑
• 安神藥
• 強安神藥
• 弱安神藥
• 止吐劑