What are antipsychotics?

I. Introduction of Antipsychotics Antipsychotics are drugs for the treatment of psychotic symptoms, mainly used for schizophrenia and related psychotic disorders (Table 3-4).

Table 3-4 Classification of Antipsychotics

1. Pharmacokinetics Tables 3-5 and 3-6 list the pharmacokinetic parameters of some antipsychotics. CYP enzyme degrades substances in the body through oxidation, which is easy to remove. Haloperidol, perphenazine, risperidone and thiopyridazine are mainly metabolized by CYP2D6, and clozapine is mainly metabolized by CYP 1A2, but CYP3A3/4 is also involved in its metabolism.

Table 3-5 Pharmacokinetic Parameters of Some Antipsychotics (I)

Table 3-6 Pharmacokinetic Parameters of Some Antipsychotics (II)

2. Functions and Uses Antipsychotics have a wide range of functions on central transmitters, but their specificity is obviously different. For example, chlorpromazine can block DA, ACh, ne, 5-HT and histamine receptors. Sulpiride mainly blocks D2 receptor. (1)DA system ①DA neurons are mainly located in the midbrain, and there are four pathways in the center: substantia nigra-striatum pathway, which mainly regulates the function of extrapyramidal system and manages motor regulation, and is related to the occurrence of extrapyramidal side effects (EPS) of antipsychotics. Stimulation not only affects the movement of animals, but also causes behavioral changes such as curiosity, exploration and foraging. The midbrain-cortex system is related to higher mental activities. The midbrain-limbic system is related to emotional and instinctive activities, and the antipsychotic effect of drugs is related to the blocking of this pathway by DA receptors. Knot-funnel pathway, which mainly regulates pituitary endocrine function, is related to side effects such as lactation caused by antipsychotics. ② Dopamine receptor subtypes: Five subtypes of dopamine receptor (D 1 ~ D5) were found by cloning technology, which were divided into two families. D 1 family (D 1, D5), coupled with adenylate cyclase (AC). D2 receptor is not coupled with AC. All antipsychotics have antagonistic effects on D2 receptor, and the efficacy of antipsychotics is related to the blocking strength of D2 receptor. Through the combined application of positron emission scanning (PET) and radioactive ligand method, we can directly study the receptor density and the affinity between drugs and receptors in the living brain. D2 receptors have high affinity for agonists and blockers. D3 has high affinity for agonists and low affinity for blockers. D4 has low affinity for agonists and high affinity for blockers. D 1 receptor is mainly located in cortex, D2 receptor is located in striatum, and D3 and D4 are mainly distributed in limbic system (Table 3-7).

Table 3-7 Effects of several antipsychotics on various types of DA

* * AC—- adenylate cyclase activity; Antipsychotics.

It has been found that the D2 density of caudate nucleus of schizophrenic patients who have not taken drugs is 65438 02 times higher than that of normal people. The increase of D2 density is not entirely the result of the use of antipsychotics, which may be related to the pathological mechanism. At present, it is believed that the positive symptoms of schizophrenia are related to the increase of D2 receptor density or abnormal function, because traditional antipsychotic drugs that antagonize D2 receptor are effective for positive symptoms; The ratio of antipsychotic drugs binding to D2 receptor has obvious clinical significance. When the binding rate of antagonist to D2 is less than 70%, it has antipsychotic effect, and when the binding rate is more than 80%, it will cause extrapyramidal adverse reactions. The binding rate of traditional antipsychotics to D2 is more than 80%, so the binding rate of EPS and clozapine to D2 is less than 70%, which has antipsychotic effect, but EPS is less. Because clozapine and sulpiride do not conform to the DA hypothesis of schizophrenia, the blocking effect of clozapine on D2 receptor is only half that of chlorpromazine, but it has a strong blocking effect on 5-HT2, α 1 and histamine 1 (H 1) receptors. Some people speculate that its antipsychotic effect may be related to these receptors, especially 5-HT2 receptor, so it is classified as a non-classical antipsychotic drug. Sulpiride can selectively block D2 receptor, but rarely causes EPS, so it is also classified as a nonclassical antipsychotic. Schizophrenia patients with negative symptoms have poor efficacy on traditional antipsychotics and are often accompanied by cognitive impairment, which may be related to the decline of DA function in the prefrontal lobe. Therefore, some people tend to think that the biochemical abnormality of schizophrenia is mainly DA dysfunction in cortical area. Clozapine can improve the negative symptoms of patients by increasing the release of DA from prefrontal cortex, which is related to clozapine's strong blocking of 5-HT receptor in prefrontal cortex. The density of D4 in the brain was originally low, but the density of D4 in the brain of schizophrenic patients increased six times. Overactivation of D4 receptor may play an important role in the pathogenesis of schizophrenia. Clozapine has a high affinity for D4 receptor, and some people think that the antagonistic effect of clozapine on D4 receptor may be related to its therapeutic mechanism. (2)5-HT receptor: 5-HT nerve pathway. The cell bodies of 5-HT neurons are mainly concentrated in the raphe nucleus of the brain stem, projecting forward to the forebrain and laterally to the vast area of neocortex. 5-HT is the most abundant neurotransmitter in the central nervous system, which plays a role in many aspects of brain function, especially in controlling the level of awakening and the sleep-wake cycle, and is also closely related to emotional depression and suicidal behavior. It can be divided into 5-HT 1a, 5-HT 1b, 5-HT 1c, 5-HT 1d, 5-HT 1e, 5- ht1f. Except for 5-HT2 receptor, other subtypes of 5-HT are G protein-coupled receptors, and 5-HT2 receptor is closely related to schizophrenia. For example, the hallucinogen lysergic acid diacetyl amide (LSD) and cactus venom are indole substances, which have an exciting effect on 5-HT2 and can cause psychotic symptoms. Destruction of occlusal suture nucleus can improve the rigidity caused by antipsychotics, and the more thorough the destruction, the better the improvement. Bethany( 1993) and others found that 5-HT 1a receptor agonists can antagonize or reverse the stiffness of dentures by blocking the release of 5-HT neurons. Korsgaard( 1985) confirmed by primate experiments that 5-HT2 receptor blockers can reduce EPS. Kapus et al. (199 1) pointed out that antagonizing 5-HT2 receptor with 5-HT receptor blocker can relieve the inhibition of 5-HT on DA system, thus enhancing DA function. Weinberger et al. (1995) reported that 5-HT2 receptor blockers can not only reduce EPS, but also improve negative symptoms when combined with antipsychotics. It has been suggested that blocking 5-HT and DA systems at the same time can produce antipsychotic effect and reduce the side effects of EPS. It is found that 5-HT2 antagonist Litanserin can improve the negative and emotional symptoms of schizophrenia, and it can be combined with haloperidol to form risperidone, which can be used to treat schizophrenia, so as to play this beneficial role. However, it should be pointed out that this beneficial effect only exists in a certain dose range, and when the dose increases to a certain extent beyond the DA blocking threshold, this complementary effect will disappear. On this basis, the nonclassical antipsychotics developed are olanzapine, seroquel, gabrinone and zotepine. The common feature of these drugs is that they are effective for positive symptoms, partially effective for negative symptoms, and there are few EPS. There are complex interactions among neurotransmitter systems such as DA, NE and 5-HT in the central nervous system. It is not comprehensive to explain the pathological mechanism of schizophrenia and the mechanism of antipsychotic drugs only by changing the function of one of the neurotransmitters. Neuroanatomy and physiological data support the last highway theory of anatomy and physiological function, and the advanced nerve function-mental activity on this basis should also conform to the last highway theory, that is, normal mental activity is based on the dynamic balance (steady state) formed by the complex interaction of various central functional systems. When mental disorder is caused by various reasons, it often involves multiple system abnormalities and destroys the normal dynamic balance. Clinical symptoms are the external manifestations of the dead end after the dynamic balance of central function is unbalanced. The receptor theory of antipsychotic drugs only explains part of the problem, so other possible mechanisms can not be ignored. For example, in recent years, we advocate the appropriate application of clozapine combined with sulpiride, clozapine combined with risperidone, and even olanzapine combined with risperidone in the treatment of schizophrenia. The main theoretical basis is to consider the multifunctional system effect of drugs on the central system and make the unbalanced central functional system reach a new balance again. Of course, this needs to be verified by further clinical and basic experiments. (3)nee energy system: The blocking effect of antipsychotics on α 1 receptor is stronger than that of α2 receptor. The blocking effect of antipsychotic drugs on α receptor can cause excessive sedation and hypotension (especially postural hypotension), reflex tachycardia, dizziness and other side effects. The order is chlorpromazine > clozapine > chlorothiazide > perphenazine > trifluorothiazide and fluperphenazine. Antipsychotics have a weak effect on β receptor. (4) Cholinergic system: Central cholinergic receptors are mostly muscarinic (M) receptors, which are mainly related to memory and motor function. In the periphery, it is related to gastrointestinal peristalsis, urination and other functions. The blocking effect of antipsychotics on cholinergic receptors is clozapine > piperidines of phenothiazine > fatty amines > piperazines, and haloperidol is similar to piperazines. Can cause blurred vision, glaucoma, dry mouth, tachycardia, constipation, urinary retention, memory disorders and other side effects. (5) Histamine energy system: There are two kinds of histamine receptors, 1 (H 1) receptor is related to allergic reaction and appetite, and type 2 (H2) receptor is related to gastric acid secretion. Most antipsychotics have a strong blocking effect on the central H 1 receptor. It can cause sedation and drowsiness, and may also be related to weight gain and blood pressure reduction. (6) Clinical adaptation symptoms (target symptoms): When using antipsychotic drugs in clinic, it is necessary to make a clear diagnosis and identify the adaptation symptoms. For example, chlorpromazine, haloperidol or clozapine can be used for those with obvious symptoms of excitatory hallucinations and delusions; Understand the past medication history, such as the efficacy, side effects and allergic history of previous antipsychotics, pay more attention to the latest systematic treatment for patients with repeated treatment, and also consider the medication history of those with similar family history; Comprehensive physical examination, pay attention to gender, age, individual differences and coexisting physical diseases, and complete necessary laboratory examinations such as blood picture, liver function and chest X-ray; Pay attention to the difference of medication between patients with acute positive symptoms and patients with long-term negative symptoms; Doctors' knowledge and experience of specific drugs (Table 3-8).

Table 3-8 Indications of Some Antipsychotics

3. The adverse reaction (1) is sedative, which is common at the initial stage of treatment. Chlorpromazine and clozapine are more obvious. (2) Drug-induced mental disorders, including excitement, disturbance of consciousness, depression and tension syndrome. (3) Seizure: Chlorpromazine and clozapine can increase θ wave, slightly increase δ wave and decrease β wave. Chlorpromazine and clozapine can produce epileptic waves, which can cause seizures in clinic. Patients with a history of convulsions should use them with caution. (4) Orthostatic hypotension: Antipsychotic drugs can produce orthostatic hypotension due to the extension of pharmacological action, so susceptible patients (old age, weak body, poor diet, rapid rise, large dose, drug injection, history of orthostatic hypotension, etc. It should be suggested that, especially in hot weather, when you get up or stand up by changing your posture, you should move slowly and sit for a while before standing up. (5)EPS: Parkinson's disease, akathisia's disease, acute dystonia, harelip syndrome and TD, the first three are more common in China. ① Parkinson's disease is caused by neuroleptics blocking DA receptor, resulting in low DA function in substantia nigra, relatively high acetylcholine (ACh) function and imbalance of DA-ACh (Table 3-9). Reserpine can reduce DA in synapses and cause Parkinson's disease by emptying DA stored in synapses of central nervous system. Therefore, levodopa can treat Parkinson's disease caused by reserpine, but it cannot treat Parkinson's disease caused by other antipsychotics. ② Mental anxiety and physical anxiety caused by akathisia drugs. It can be treated with propranolol and diazepam. ③ Acute dystonia is a persistent spasm of individual muscle groups. Ocular muscle spasm produces oculomotor nerve crisis, laryngeal muscle spasm has difficulty in speech and swallowing, limb or trunk muscle spasm can be seen as torsion spasm, and there are autonomic nervous excitement phenomena such as increased heart rate and sweating. Scopolamine 0.3 ~ 0.6 mg should be injected intramuscularly as soon as possible.

Table 3-9 Relationship between DA and Parkinson's Disease

(6) Influence on autonomic nervous system: Antipsychotics can block multiple receptors, so the influence on autonomic nervous system is very complicated. For example, chlorpromazine blocks DA receptors in basal ganglia and produces EPS, which often requires anticholinergic drugs. The anticholinergic effect of chlorpromazine itself causes blurred vision and dilated pupils by affecting ciliary muscles, which makes bladder detrusor relax and intestinal peristalsis decrease, leading to urinary retention and even paralytic intestinal obstruction. (7) Granulopenia: Antipsychotic drugs can cause granulocytopenia, and the clinical manifestations are fever, headache, sore throat and fatigue. Laboratory examination showed that leukopenia was severe. Clozapine is more common. In addition, antipsychotics can also cause ECG changes. Liver function is impaired, even jaundice. It is reported that psychotropic drugs can also cause malignant symptoms. (8) Contraindications of antipsychotic drugs: serious cardiovascular diseases such as heart failure and severe hypertension; Severe liver disease; Kidney diseases such as acute nephritis and renal insufficiency; Severe central depression or coma; Severe hematological diseases or hematopoietic dysfunction; Antipsychotic allergy; Acute infection, the elderly, pregnant women, children with caution. Phenothiazine should not be combined with adrenaline to avoid severe hypotension caused by adrenaline reversal. 4. Subjective and objective data of evaluation of nursing procedures for antipsychotic drug treatment: (1) Thinking: hallucination, delusion, logic and consistency of thinking, intelligence, etc. Reaction to the environment. (2) Emotion: anxiety, depression, apathy and excitement. (3) Behavior: gait, movement, sound, appetite, sleep. (4) Laboratory tests: such as three routine tests, heart, liver, kidney, thyroid function, blood electrolytes, etc. (5) Identification of high-risk patients: These drugs are prohibited for patients with the following diseases: ① Parkinson's disease, severe hematological diseases or myelosuppression; Severe central depression, coma or convulsion tendency. ② Serious cardiovascular, liver and kidney diseases, such as heart failure, severe hypertension, acute nephritis and renal insufficiency. ③ Patients with glaucoma, hypotension, prostatic hypertrophy, urinary retention and intestinal paralysis are prohibited from taking chlorpromazine, thiolidazine, chlorpromazine and other ineffective antipsychotic drugs. ④ Antipsychotic allergy. Use with caution for the elderly, children and pregnant women. ⑤ Phenothiazine drugs should not be combined with adrenaline, so as not to cause the reversal of adrenaline action and cause severe hypotension. The nursing goal is to control the symptoms of schizophrenia and related mental diseases, prevent their recurrence, maximize the recovery of patients' self-care ability and promote their early return to society. Nursing measures (1) Most mental patients can't actively cooperate with the treatment because of mental symptoms and lack of insight, and can't correctly reflect the curative effect and adverse reactions. Therefore, when dispensing medicine, we must strictly implement the operating rules, so as to make three checks and eight pairs: three checks, check when taking medicine, check when releasing medicine (pumping medicine) and check when returning medicine; Eight pairs, bed number, name, drug name, dosage, concentration, usage, time and patient appearance. (2) When dispensing medicine, prepare warm water for the patient and watch the patient take the medicine. Under the premise of not hurting their self-esteem, carefully check their hands, mouth and cups to prevent patients from hiding drugs, affecting treatment or accumulating sudden suicide. (3) When dispensing medicine, the medicine cart should not be placed casually to prevent some patients from grabbing medicine or knocking over the medicine cart. (4) Before various treatments are given to patients, the purpose and precautions should be explained as appropriate, such as oral and written gestures, and the patients and their families should be informed of the importance of taking drugs as planned, the medication scheme, the use of drugs, possible adverse reactions and their mitigation methods, so as to gain their cooperation and trust. (5) For uncooperative patients, more than two people are required to cooperate to avoid accidents. Check whether the materials are complete after treatment, and do not leave cotton swabs, ampoules, etc. Cause danger in the ward. (6) Reduce the frequency of administration as much as possible, and use long-acting preparations when necessary or take them once a day before going to bed. (7) Continuously evaluate patients' response to drugs or treatments. If there are adverse reactions (such as drug dermatitis, drug anxiety, postural hypotension, etc.). ), to timely handover, and reported to the doctor. (8) Health education: ① Carry out medication knowledge education, teach patients about adverse reactions, and master the basic knowledge of prevention and treatment of adverse reactions. Susceptible patients, such as the elderly, weak, poor appetite, large dosage, rapid increment, injecting drugs, and a history of postural hypotension, should be advised to change their posture (such as lying or squatting to stand or walk), move slowly, and sit for a while before standing. ② Through the guidance and careful nursing of patients, the therapeutic relationship of mutual trust was established. Strive for patients' active cooperation, so as to take medicine better after discharge. (3) Encourage patients to take drugs as planned, teach patients' families to keep and distribute drugs for patients, observe patients' medication, and prepare for discharge maintenance treatment. Re-evaluation should pay attention to the evaluation and re-evaluation of curative effect and safety, and compare the improvement of patients' mental disorders before and after medication to evaluate the curative effect. Although antipsychotic drugs have extensive safety, long-term use will produce serious adverse reactions. 2. Pharmacokinetics of chlorpromazine, a dimethyl alkyl-phenothiazine antipsychotic drug, is easy to be absorbed orally, but less absorbed when taken with food and alkaline drugs. The time to peak (tmax) of single oral administration was 2 ~ 4h hours. T 1/2 is about 17h, and it reaches the steady state level in 5 ~ 10 days. At this time, T 1/2 is about 30h. The effective plasma concentration is 500 ~ 700 ng/ml. Intramuscular injection can avoid the first-pass effect of liver metabolism, and its bioavailability is about 3 times higher than that of oral administration. The binding rate of plasma protein is about 96%. High lipophilicity, easy to pass through the blood-brain barrier (BBB) and placental barrier, and stored in tissues, especially brain, liver and other organs. The ratio of cerebral blood concentration is 5∶ 1. In the liver, it is mainly oxidized by CYP or combined with glucuronic acid, and its metabolites are 160, such as 7- hydroxychloropromazine. 70% ~ 80% is excreted by kidney (the original drug is about 10%), 5% ~ 30% is excreted by feces, and a small amount is excreted by milk, which affects infants. Function and application: D2/D 1 receptor blocker with high affinity for 5-HT6 and 5-HT7 receptors. (1) Excitement, hallucination, thinking disorder, hostility and weird behavior. Paranoia and adolescence have better therapeutic effects on schizophrenia, followed by neuroticism. It can also be used for mania, psychogenic mental disorder, and as an auxiliary drug for treating anxiety disorder. It can also be used in a small amount for brain organic or somatic mental disorders. (2) Sedation and hypnosis, lowering body temperature and strengthening the role of central depressants are used for artificial hibernation, intensive anesthesia, preoperative and trigeminal neuralgia. (3) Treating intractable hiccups by inhibiting emetic chemoreceptor area of medulla oblongata. Intravenous drip can treat biliary ascariasis. (4) It can be combined with analgesics to treat the severe pain of advanced cancer. (5) It can also be used for heart failure. Dosage and usage: oral: 25 ~ 50m g bid or tid at the initial onset of schizophrenia, 50 ~ 100mg each time as appropriate, up to 600 ~ 750mg/d, maintenance dose of 200 ~ 300mg/d ... intramuscular injection: 25 ~ 50mg excitement, 0.3mg heroin, bid or tid. Can also be intravenous drip 100 ~ 200mg diluted with 500ml of 5% glucose, 60 drops per minute, qd. Heart failure: intramuscular injection of a small dose of 5 ~ 10 mg, qd or bid, or intravenous drip, 0.5mg/min. Adverse reactions (1) Central nervous system: excessive sedation, and the therapeutic dose made about half of the patients feel weak and sleepy; Slow down brain waves; Spastic effect; EPS drug-induced mental disorder (2) Endocrine: it can increase prolactin, lactation, sexual dysfunction, feminization of male breasts, menstrual changes of women, etc. (3) Autonomic nervous system: The effect on autonomic nervous system is very complicated due to blocking various receptors. (4) Cardiovascular system: It has complex functions, including central and peripheral autonomic nervous system, and has a direct effect on the cardiovascular system. It can cause orthostatic hypotension and ECG changes. (5) Others: such as abnormal liver function, jaundice, drug dermatitis, etc., long-term medication can lead to pigmentation of skin, organs and retina. A few patients may have neutropenia. (6) Contradictory reactions: The adverse reactions caused by the central and peripheral autonomic nervous system functions of antipsychotics and their direct effects on organs, except the main manifestations, occasionally have opposite adverse reactions. For example, chlorpromazine can reduce blood pressure, body temperature, sedation and hypnosis and reduce constipation caused by intestinal peristalsis, which is the main adverse reaction. But occasionally you can see high blood pressure, high body temperature, insomnia and diarrhea. (7) Combination of Antan or lithium salt can reduce the plasma concentration of chlorpromazine. Use alkaline drugs such as aluminum hydroxide and weishuping to affect absorption. (8) Can cause allergic reactions, such as drug dermatitis, rash, contact dermatitis, exfoliative dermatitis, asthma, purpura, etc. The pharmacokinetics of promethazine is easy to be absorbed orally. 1.5 ~ 30 min takes effect, Tmax 1h lasts for 4 ~ 6 h, and T 1/2 is about 12.2h, which is mainly metabolized by the liver and excreted by the kidney. Function and use: H 1 receptor blocker, with sedative, cooling and antiemetic effects. It can strengthen the central inhibition of hypnotics, analgesics and anesthetics. Can be used for various allergies, such as urticaria, allergic rhinitis, bronchial asthma, etc. It is used to prevent allergic reactions such as burns, radiation injury and blood transfusion, and to assist anesthesia and artificial hibernation. Treat motion sickness, vomiting during pregnancy and nausea and vomiting caused by other reasons. The effect of antipsychotics is extremely weak. Parenteral administration can be used to treat dyskinesia caused by antipsychotics. Dosage and usage: oral or intramuscular injection: sedation is 25 ~ 50mg each time. Antiemetic or antihistamine 12.5 ~ 25mg. Because of its irritating effect, subcutaneous injection is not suitable. Adverse reactions may include postural hypotension, drowsiness, lethargy, dry mouth and occasional gastrointestinal irritation and dermatitis. Caution should be given to those who have allergic reaction to drugs, and to those with epilepsy and hepatic and renal insufficiency. Avoid driving vehicles, operating machines or working high above the ground during medication. It is not suitable for mixed injection with aminophylline, nor for compatibility with alkaline and alkaloid drugs. 3. methylpiperazine sidechain)—— The pharmacokinetics of phenothiazine antipsychotic drug trifluoperazine is1/2+03.3 0.9h, and the main active metabolites are sulfur oxides, N- demethylation and 7- hydroxy metabolites. D2 and D 1 receptor blockers have strong functions and uses, and the potency of antipsychotic drugs is 10 ~ 20 times higher than chlorpromazine. It has the advantages of quick onset, long duration, sedative and hypnotic effects and weak antihistamine effects. Used for simple, nervous and paranoid schizophrenia. It plays a significant role in eliminating hallucinations and delusions, relieving stupor and encouraging chronic abstinence patients to be active. It can also be used for anxiety, compulsion and phobia. It has poor curative effect on communication disorder, mania and emotional euphoria. Dosage and usage: oral administration: at first, 5 ~ 10 mg/d, divided into bid~tid, and gradually increased to 20 ~ 40 mg/d, with a maximum of 60 mg/d, and the maintenance dose was 10 ~ 20 mg/d, and the adverse reaction EPS was obvious. Four. Perphenazine, a piperazine-ethanol glycoside chain-phenothiazine antipsychotic drug, was taken orally for about 9 hours, and was distributed all over the body after absorption, with the highest content in brain, lung, liver, spleen and kidney. Substances excreted through bile can be reabsorbed in the intestine. Metabolites are excreted from urine and feces. Function and use: the high-priced DA receptor blocker is 6 ~ 10 times higher than chlorpromazine. Sedative effect is weak. Can be used for various mental diseases, such as paranoia, reactive mental disorder, simple type and chronic schizophrenia. Has little side effect on other organs, and can be used for patients with mental disorder and somatic diseases. Neurosis can be treated with a small amount of drugs. It can also be used to control severe nausea and vomiting. Dosage and usage: Oral: 8 ~ 12 mg/d at the initial stage of psychiatric treatment, and gradually increased to 20 ~ 60 mg/d, divided into 2 ~ 3 times. Maintenance dose 10 ~ 20 mg/d neurosis or antiemetic: 2 ~ 4 mg, bid~tid. Intramuscular injection: 5 ~ 10 mg each time, which can be used repeatedly after 6 hours. Long-acting perphenazine heptanoate and kwai decanoate were administered at intervals of 1 ~ 3 weeks and 2 ~ 4 weeks respectively. Adverse reactions may include EPS. Sleepiness and autonomic nervous system adverse reactions are slight, and have little effect on liver function and hemogram. A few patients have symptoms such as dry mouth, constipation, frequent urination and tachycardia. Some patients can see endocrine disorders such as breast enlargement and menstrual disorder. Those with a history of phenothiazine allergy are prohibited. This medicine can strengthen the sedative or analgesic effect, and should be reduced when used together. The pharmacokinetics of fluphenazine fluphenazine oral T 1/2 is about 13h. The active metabolites are sulfoxide, N- hydroxyl and 7-8- hydroxyl derivatives. After injection of fluphenazine decanoate, it was slowly released in tissues, with a T 1/2 of 3.7 days, taking effect after 42-72 hours, and the most obvious effect after 48-96 hours, lasting for 2-4 weeks. Function and application: It is a D 1/D2 receptor blocker with high affinity for 5-HT6/5-HT7 receptor. As a highly effective antipsychotic drug, its oral potency is 25 times higher than that of chlorpromazine, and its effect is rapid and lasting. Hypotensive hypnotic effect is weak, and antiemetic effect is strong. Used for chronic schizophrenia, it can improve contact and cheer up mood. Fluphenazine decanoate is a long-acting ester compound of fluperphenazine, and its action time is 9 ~ 20 times longer than that of fluperphenazine. It is suitable for maintenance treatment and chronic schizophrenia, and can be used as the first choice for patients who refuse to take medicine or Tibetan medicine. Dosage and usage: oral: 2 ~ 10 mg/d at first, divided into 2 ~ 3 times, and gradually increased to 10 ~ 20 mg/d, with the maximum of 60mg/d, and the maintenance dose 1 0 ~ 20mg/d. intramuscular injection: fluphenazine decanoate each time. It can be gradually increased to 25 ~ 50mg every 2 weeks. The dosage of the elderly is halved. EPS has many adverse reactions. Adverse reactions of autonomic nervous system can be seen as dry mouth, sweating and blurred vision. No obvious damage to blood, liver and kidney. Occasionally hypotension and granulocytopenia. It should be used with caution by the elderly and infirm who suffer from organic diseases of heart, liver and brain. 5. Pharmacokinetics of phenothiazine antipsychotic drug pyridine Sullidazine is easily absorbed by oral administration, with TMAX of 2.5 ~ 4.5h and T 1/2 of 16h. There are many active metabolites, such as thiazine (T 1/2 about 16h) and sulfonamides. Functions and Uses: Piperidine side-chain phenothiazine is a representative drug, which is used for schizophrenia and mania with excitement, anxiety and tension. It is also effective for severe neurosis, catatonic depression and epileptic mental disorder. It is also used for ADHD and behavioral disorders in children. Old people have a good tolerance for it, so it is widely used. Dosage and usage: oral: at first, 25 ~ 50mg, bid～tid, which can be gradually increased to the maximum of 600 ~ 800 mg/d. Children take it three times a day 1mg/kg. Maintenance dose 100 ~ 300mg/d, EPS was less, but anticholinergic side effects, orthostatic hypotension and ECG abnormalities were more common than other drugs. The ECG changes are mainly abnormal T wave and prolonged Q-T ... It is forbidden for patients with organic heart disease and should be used with caution for premature beats. Pigmented retinopathy can occur after long-term large-scale administration. Combined with lithium carbonate, it can produce convulsion and encephalopathy syndrome; Combined with imipramine and phenytoin sodium, it may cause serious reactions such as intestinal paralysis, atropine poisoning-like disorder and even cardiac arrest. The pharmacokinetics of pitatazine is easily absorbed by oral administration, lasting for 24 hours once, and the T 1/2 is about 1 1 hour. Piperazine palmitate was used every 4 weeks 1 time, and Tmax was reused for about 14 days. Slow excretion, intestinal and liver circulation can be excreted through bile, 50% in 20 days, most of them are excreted from feces, and 2% ~ 7% are excreted from urine. Functions and uses DA receptor blockers have weaker hypotensive and cooling effects than chlorpromazine. Can be used for hallucinations, delusions, uncoordinated psychomotor excitement, impulsiveness and other symptoms, and can activate chronic behavior withdrawal. Mainly used for maintenance treatment of paranoid and unclassified acute schizophrenia and chronic schizophrenia. Dosage and usage: 5 ~ 15 mg/d, qd, gradually increased to 60mg/d or higher. Intramuscular injection: Piperazine palmitate starts at 25 ~ 50mg each time, and the therapeutic dose is 50 ~ 100 mg each time, and it is injected/kloc-0 every four weeks. The main adverse reaction was EPS, but less than chlorpromazine. Occasionally severe insomnia, jaundice and neutropenia can be seen. Use with caution in patients with heart, liver and kidney diseases and the elderly and infirm. Patients with agranulocytosis and angle-closure glaucoma are prohibited. 6. Thione antipsychotics The mechanism of action of Thione antipsychotics is related to blocking D2 receptor. Compared with phenothiazine, the sedative effect is weak, but it has certain anti-anxiety and anti-depression effects. Mental disorder with anxiety and depression is the first choice. Some varieties have activating and uplifting effects, and are suitable for indifference and withdrawal of chronic schizophrenia. Thianthracene can enhance the effect of central depressants, and you can't drink alcohol during taking the medicine. Guanethidine, adrenergic drugs and levodopa should not be used together because they will reduce their effects. ? Tylden chlorprothixene is easily absorbed by oral administration, with Tmax 1 ~ 3h and T 1/2 of 8 ~ 12h. The effect of intramuscular injection remained above 65438±0.2h, and the effective blood concentration was about 40ng/ml. It is mainly metabolized by the liver and mostly excreted by the kidney. Functions and uses: D 1/D2 receptor blocker can also block 5-HT2 receptor, and has high affinity for 5-HT6/5-HT7 receptor. Anticholinergic and adrenergic effects are weaker than chlorpromazine. It has weak anti-anxiety and anti-depression effects, and can be used for schizophrenia and menopausal mental disorder with agitation, depression and anxiety symptoms. It is also used to improve anxiety, tension, depression and sleep disorders. It has poor curative effect on numbness, apathy and other symptoms. Anti-hallucination delusion is not as good as phenothiazine drugs. Dosage and usage: oral administration: 50 ~ 100 mg/d at first, divided into 2 ~ 3 times, and gradually increased to 300 ~ 400 mg/d, which can be increased to 600mg/d, with a maximum of 800 mg/d. Maintenance dose100 ~ 200 mg/d. Intramuscular injection: Large doses can cause seizures. Occasionally, liver damage, granulocytopenia and rash occur. Patients with serious heart and liver diseases, bone marrow suppression, glaucoma, prostatic hypertrophy, urinary retention and epilepsy should use it with caution. Children under 6 years old are prohibited. This product may have cross-allergic reaction with phenothiazine drugs; Combined with antacids will affect absorption; Combined with TCA, the sedative and anticholinergic effects are enhanced. The pharmacokinetics of clopentatiophene is easy to be absorbed by oral administration, with Tmax4h and T 1/2 about 20h, and the bioavailability is 44%. The effective blood concentration is about 65438±00n g/ml. It takes about 19 days for intramuscular injection of thiazide long-acting injection T12. It is distributed all over the body, with higher concentration in liver, lung and kidney and lower concentration in brain. In liver metabolism, the main metabolites are inactive sulfur oxides, N- demethylated compounds and glucuronic acid compounds, which are excreted from feces and urine. Function and use of D 1/D2 receptor blockers. Long-term use is not easy to produce drug resistance and allergic to DA receptor. It has a good therapeutic effect on mental symptoms such as hallucination and delusion, thinking disorder, behavior disorder, and agitation, and can be used for acute schizophrenia with hallucination and delusion and thinking disorder, manic agitation state, chronic schizophrenia, mental retardation with psychomotor excitement state, children with severe aggressive behavior disorder, and senile arteriosclerosis dementia. Chlorothiolate decanoate is used for maintenance treatment or chronic schizophrenia. Dosage and usage: oral administration: at the initial stage of schizophrenia 10 ~ 50mg/d, divided into 2 ~ 3 times, and increased to 20 ~ 75mg/d, with a maximum of150mg/d. intramuscular injection: 5 ~ 20mg each time, bid or tid, with a maintenance amount of 20 ~ 40mg/d. Adverse reactions can be seen as drowsiness, dry mouth, blurred vision, constipation and EPS. TD is occasionally used for a long time. In addition, dizziness, urinary retention, postural hypotension and transient liver injury will occur. Use with caution in patients with heart, liver and kidney diseases and pregnant women. The pharmacokinetics of flupentixol trifluoride is easy to be absorbed orally, Tmax4h, and the bioavailability is 40%. The T 1/2 of (Z)- isomer is about 35h. T 1/2 is injected for about 3-8 days, and the effect lasts for 2-3 weeks. T 1/2 of trifluoroxanthate palmitate was injected for about 7 days. Intestinal and hepatic circulation is obvious. After liver metabolism, the metabolite is a combination of N- dehydroxy compound and glucuronic acid, which has no pharmacological activity. It is mainly excreted by feces and a small amount by urine. Function and use: D 1/D2/5-HT2 receptor blocker can strongly inhibit the increase of AC activity caused by DA. No sedative effect. The efficacy of antipsychotic drugs is 4-8 times that of bootle Deng Qiang, and it has an uplifting effect. Used for schizophrenia, it has good curative effect on symptoms such as apathy, decreased will and disobedience. It is also used for post-schizophrenia depression. Thiofluoride decanoate is a long-acting preparation, which is used for maintenance treatment or chronic schizophrenia. Dosage and usage: oral administration: 1 ~ 4 mg/d, divided into 2 ~ 3 times, therapeutic dose 10 ~ 60 mg/d, maintenance dose 5 ~ 20 mg/d. intramuscular injection: trifluoride.