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Section sedative-hypnotics and antipsychotics
Who can promote and maintain a drug similar to physiological sleep is called hypnotics. Only to eliminate irritability, mood drugs to restore calm as sedatives. Sedative hypnotics, including benzodiazepines, barbiturates and other drugs.
Antipsychotic is not to eliminate anxiety and tension inhibit the cerebral cortex of the drug. According to the strength of drugs can be divided into: strong stability, such as phenothiazines and butyrylcholinesterase classes, for the treatment of schizophrenia, also known as antipsychotics; weak antipsychotic drugs such as benzodiazepines, due to strong anti- the role of anxiety, also known as anxiolytics.
Sedative hypnotics, and antipsychotics both antiemetic and more, forgetting and strengthen the role of anesthesia, mainly used in clinical anesthesia before the administration of anesthesia, intravenous anesthesia and local anesthesia adjunct.
First, the benzodiazepine
ã€ã€‘ These drugs in vivo oral absorption of the process completely, easily precipitated by intramuscular injection, absorption slow and irregular, the emergency should be administered intravenously. Plasma protein binding is high, mainly in the liver under the effect of drug biotransformation enzymes, some of the active metabolite of t1 / 2 than the length of its parent drug, so some of the benzodiazepine is not parallel to its duration of action. Enterohepatic circulation because of the existence and continuous use of easy to accumulate. Benzodiazepine and its metabolites are the ultimate combination with glucuronic acid by renal excretion.
Pharmacological action and clinical applicationã€‘
1. The nervous system benzodiazepine drugs in the cerebral cortex, limbic system, brainstem and spinal cord, selective and benzodiazepine receptor binding and excitement of the receptor, resulting in anxiolytic, sedative hypnotic, anticonvulsant and muscle relaxation and other central inhibition.
(1) anxiety: benzodiazepine anxiolytic with a strong role in less than a small dose of sedative to improve the amount of anxiety in patients with tension, anxiety, fear and insomnia symptoms, it is also known as benzodiazepine anxiolytics medicine. Benzodiazepine for anxiety caused by a variety of reasons have a significant effect for the anxiety of choice.
(2) sedative and hypnotic: With the dose increased, benzodiazepines can cause sedative and hypnotic effects. These drugs in clinical anesthesia is widely used.
â‘ Premedication: There eliminate anxiety, have forgotten, reduced metabolism, prevention of local anesthetic toxicity and so on.
â‘¡ parts of Anesthesia adjunct: the patients have sedation, forgetfulness, and prevention of local anesthetic toxicity.
â‘¢ anesthesia induction: mainly used for patients with poor cardiovascular function.
â‘£ components of anesthesia: the role of anesthetics can enhance, r
â‘¤ anticonvulsant, epilepsy: anticonvulsant benzodiazepine effect is very strong, including diazepam (stability), especially with the role, can be used to prevent tetanus, eclampsia, high fever and drug-induced convulsions. Diazepam is the treatment of choice for status epilepticus drugs.
â‘¥ central muscle relaxant: diazepam, a certain degree of central muscle relaxation, but does not affect normal activities, for the treatment of central or local lesions caused by increased muscle tension and muscle spasm.
2. Cardiovascular system benzodiazepine blood pressure can drop. A drop of drug dose and route of administration, but also depends on the state of the body medication. Under normal circumstances, only to fall in blood pressure. Had high blood pressure and decrease in anxiety state were increased. Low blood volume, in general, poor, heart failure patients, the lower blood pressure more significantly, to be used with caution. Effects on myocardial contractility of small, heart rate increased slightly. Before and after the load has fallen due to heart, no significant effect of drug in the cardiac output while reducing myocardial oxygen consumption.
3. Respiration inhibition of the respiratory system than barbiturates light. Typical doses of oral respiration inhibition was not obvious. If the intravenous injection speed, overdose, may occur a transient apnea.
1. Central nervous system response to continuous application of small doses can cause dizziness, fatigue, lethargy and indifference expressions such as, large doses can cause ataxia, so disabled drivers and machine operators.
2. Respiratory and circulatory inhibition of intravenous injection speed too fast prone. Infants under 6 months in patients with myasthenia gravis and disabled.
3. Acute toxic overload can lead to coma and respiratory, circulatory failure, can be used benzodiazepine receptor blocker flumazenil treatment.
4. Dependent long-term use can produce tolerance and dependence, withdrawal reactions may occur suddenly stopping, it is not long-term medication.
5. Teratogenic through the placental barrier, there is teratogenicity, the first 3 months of pregnancy women disabled.
Barbituric acid is urea and malonic acid in the condensate. Barbiturates barbituric acid 5 is the 2 carbon atoms and two hydrogen oxygen carbon replaced by different groups to form derivatives. Substituents affect the role of barbiturates intensity, onset and maintenance time. When the five hydrogen atoms on carbon benzene (phenobarbital) or short chain alkyl (TBARS) instead, the drugs slow onset, long duration; when substituted alkyl has a branch (amobarbital ) or unsaturated bond (the Secretary may barbiturates), the fast onset, short duration; when the two carbon oxygen by sulfur (thiopental) to replace when the fat-soluble drugs increases, faster onset, maintenance shorter.
Pharmacological action and clinical applicationã€‘
1. On the central nervous system of barbiturates on the central nervous system in a dose dependent manner, with the dose increase, in turn causing sedative, hypnotic, anticonvulsant, anesthetic, bulbar palsy and so on.
(1) sedative and hypnotic: Barbiturates may be shortened sleep time, reduce the frequency and extended sleep awakening, but reduced REMS, a long time with the withdrawal can produce prolonged REMS rebound, resulting in more than dreams, insomnia.
(2) anti-convulsant, anti-epilepsy: a certain dose of barbiturates under varying degrees of anticonvulsant effect. Among them, the more prominent the role of phenobarbital, a sedative to generate the amount of anticonvulsant effect on seizures induced by a variety of reasons have good effect, can inhibit the tetanus and seizures due to eclampsia. There antiepileptic effect of phenobarbital.
(3) Anesthesia: barbiturates commonly used in anesthesia and prevention of anesthesia before the administration of local anesthetic toxicity.
2. The role of the respiratory system barbiturates can reduce the sensitivity of the respiratory center to carbon dioxide, the degree of inhibition of respiration and dose related.
3. On the cardiovascular system usually mild hypnotic doses can decrease blood pressure, heart rate slightly slowed down. Higher doses, due to the inhibition of the central cardiovascular and blood pressure, leaving the role of the small arteries decreased significantly.
4. Barbiturates enzyme induction in liver drug metabolizing enzyme inducers, the strongest effect of phenobarbital, can enhance porphyrin production, increased blood disease in acute porphyria, it is banned from acute intermittent purple quality of disease.
1. Consequential effects of hypnotic doses of barbiturates can cause sleepiness after waking, fine motor incoordination, and disorientation, also known as hangover.
2. Respiratory depression can inhibit the respiratory center barbiturates, large doses of barbiturates can lead to acute poisoning, serious cases showed deep coma, a variety of reflex, respiration was significantly suppressed, blood pressure and even shock. Respiratory failure is the main cause of death.
3. Tolerability of repeated application of short-term dependence can produce tolerance to barbiturates.
4. Allergy occasional neutropenia, severe allergic reactions such as exfoliative dermatitis.
ã€Pharmacological effects typical phenothiazines chlorpromazine representatives, and its main role is the role of stability and anti-psychotic, but also has antiemetic effect and influence the role of the autonomic nervous and endocrine. Such drugs are not analgesic itself, but can enhance the role of narcotic analgesics.
Phenothiazine drugs block the main mechanism of action is within the central nervous system dopamine receptors. Block in the brain - the limbic system and the brain - dopamine receptors in cortical pathways, resulting in the role of anti-psychotic and stability; blocking dopamine receptors in tuberoinfundibular Department, impact on the endocrine; block the medullary emetic dopamine chemosensory areas receptor, resulting in antiemetic effect; inhibition of hypothalamic temperature regulation center, so that the temperature change with changes in outside temperature; blocking nigrostriatal dopamine receptors, resulting in extrapyramidal system symptoms. Phenothiazines also block the Î± adrenergic receptor, M cholinergic receptors and H1 receptors, respectively, have blood pressure, anti-cholinergic and anti-histamine effect.
Clinicalã€‘ ã€phenothiazine used to treat schizophrenia or other psychotic manic symptoms, elimination of hallucinations, delusions, and manic and so on. Its strong antiemetic effect is also used to prevent vomiting caused by various reasons (other than motion sickness).
1. The general response, including lethargy, apathy, weakness (central inhibition of symptoms); dry mouth, no sweat, constipation, blurred vision, increased intraocular pressure (M receptor blocker symptoms); stuffy nose. Blood pressure, orthostatic hypotension and reflex tachycardia (Î± receptor blocker symptoms) and so on.
2. Extrapyramidal system response to long-term high doses of medication can cause tremor, paralysis, acute dystonia, akathisia and other extrapyramidal system symptoms. After stopping long-term medication can cause tardive dyskinesia.
3. Nerve relaxant malignant syndrome phenothiazine therapy of patients about 0.5% to 14% can occur in a similar malignant hyperthermia syndrome. First, changes in blood pressure, heart rate and cardiac arrhythmias and other symptoms of autonomic nervous instability; the next 24 ~ 72h, high fever, confusion, general muscle tension increased, and even affect the breathing exercises, often transaminase and creatine phosphokinase increased mortality rate as high as 20% to 30%.
Chlorpromazine (Dong Mianling) The chemical name 2 - chloro -10- (3 - dimethylamino propyl) - Phenothiazine. Clinical use of the hydrochloride salt, acidic and basic drugs should not be mixed. Strong local irritation of the drug can be deep intramuscular injection. Intravenous injection can cause thrombophlebitis, should be diluted with saline or glucose solution was slowly injected.
1. A strong central nervous system of chlorpromazine inhibition of the central nervous system, can significantly affect the control of patients with manic state without feeling. Hypothalamic thermoregulatory center it has a strong inhibitory effect, lowering the body temperature regulation function, body temperature can change with temperature, not only can reduce the body temperature heat can also reduce the normal body temperature. Chlorpromazine also prevents shivering when cold. Chlorpromazine has strong antiemetic effect of small doses of the end of the fourth ventricle inhibited the emetic chemoreceptor. Large doses can directly inhibit the vomiting center.
2. Chlorpromazine block the autonomic nervous system causes blood vessels to dilate adrenergic receptor, blood pressure, high blood pressure or blood pressure medication for the patients, the antihypertensive effect is particularly evident. This can cause blood vessel dilatation orthostatic hypotension, it should not drastically change the position after treatment.
1. Premedication 12.5 ~ 25mg intramuscular injection of chlorpromazine as an anesthetic premedication, can produce sedation, analgesics and anesthetics enhance the effect, and can reduce postoperative nausea and vomiting. Intravenous injection of 10 ~ 20mg can quickly stop the operation occurred in intractable hiccups, vomiting and postoperative vomiting caused by other reasons, there was a significant effect.
2. Hypothermic anesthesia of small doses of chlorpromazine in the cooling block before the use of the autonomic nervous system to prevent shivering and blood vessel spasm, so that peripheral vasodilation, decreased body temperature in favor.
3. Artificial hibernation artificial hibernation can be used for serious infections caused by high fever and convulsions, central high fever, toxic shock, traumatic shock, severe burns, severe brain trauma, severe encephalopathy, intractable pain, thyroid crisis, eclampsia and hypertensive crisis and so on. Chlorpromazine and promethazine, pethidine lytic cocktail composed of 1, and promethazine, procaine mixture composed of hibernation 4.
In addition to these adverse reactions Phenothiazines General Department of response and extrapyramidal symptoms and other adverse reactions, a very small number of patients in the application of the drug 2 to 4 weeks after the jaundice may occur, clinical manifestations similar to the obstructive jaundice, but a rash and fever . Its occurrence has nothing to do with the administration time and dosage in liver damage and jaundice have been more common and more severe patients, it was considered to be an allergy.
Promethazine (non-is the root) In addition to the role of free anti-psychotic, the other central role and chlorpromazine similar. The stronger sedation after treatment can quickly fall asleep. Anti-adrenergic effect is weak, significant anticholinergic effects, can reduce saliva and bronchial secretion. Mild excitatory effects on respiration, minute ventilation and respiratory rate increase, can relax bronchial smooth muscle. This drug is a potent H1 receptor antagonist, a prominent anti-histamine effect, compete with histamine H1 receptors play an anti-allergic effects.
Promethazine for the treatment of allergic diseases. Often as a clinical anesthesia Premedication, better sedation, anti-allergy and anti-vomiting effect, does not inhibit respiration, anesthesia and surgery can reduce nausea and vomiting. Promethazine may enhance the effects of anesthetics to reduce the amount of anesthetic, and pethidine combined form a "different piperazine mixture" (commonly known as the degree of non-mixture), often as a local anesthetic adjuvant.
Second, butyrylcholinesterase benzene
D acid by blocking the limbic system of benzene, hypothalamus and substantia nigra, striatum and other parts of the system's stability and dopamine receptors have a very strong role in antiemetic effect and extrapyramidal system response, but also can produce anti-cholinergic and resistance off Î± adrenergic receptors. Butyrylcholinesterase benzene, only droperidol more commonly used in clinical anesthesia.
The stability and the role of droperidol is equivalent to 200 times of chlorpromazine, haloperidol 3 times for the antiemetic effect of chlorpromazine 700 times. 5 ~ 8min after injection into effect, the best effect lasted for about 3 ~ 6h. The drug can enhance the effects of other central nervous system inhibitors, but does not have forgotten, and no anticonvulsant effect. Can cerebral vasoconstriction, decreased cerebral blood flow, intracranial pressure decreased, but not a corresponding decline in brain oxygen consumption, so the cerebral ischemia patients may have an adverse effect.
Droperidol in the range of 0.1 ~ 0.15mg/kg a negligible effect on the cardiovascular system, and only slightly increased heart rate and blood pressure slightly, and there is the role of anti-adrenaline arrhythmia, which may be extension of myocardial refractory period on . Accompanied by low blood volume, arteriosclerosis, elderly and critically ill patients application, blood pressure decreased significantly.
Droperidol did not inhibit the respiratory center, but can enhance analgesic respiratory depression. Can alleviate the bronchospasm caused by histamine, but also enhance the ventilatory response to hypoxia, which may block the effects of dopamine on the inhibitory effect on carotid body, it can be used for patients with chronic obstructive pulmonary disease Premedication.
Droperidol is the most widely used in clinical anesthesia strong antipsychotic. Premedication mostly as droperidol, pethidine and atropine combination, 1h intramuscular injection before surgery. As an anesthetic adjuvant, droperidol and fentanyl anesthesia can enhance the effect, and the prevention of postoperative nausea and anxiety and other adverse reactions, suitable for elderly and frail, cardiovascular, critical illness and shock the patient's anesthesia.
Section II opioid analgesics and their antagonists
Opioid analgesics include opioid receptor analgesic excited (including the opioid analgesic alkaloids, synthetic opioid) and other drugs with analgesic effect. They are mainly on the central nervous system, to selectively eliminate or alleviate pain, in pain when the conscious, the other senses are not affected, while eliminating the pain caused by emotional reactions. Repeated application of this class of drugs most prone to cause addiction and tolerance, it is also known as analgesic addiction or narcotic analgesics.
Opioid receptor agonists
Opioid receptor agonists is the major role in the Î¼ receptor agonists. The typical representative of the morphine. Since pethidine has been synthesized, but also have synthesized a series of drugs, which clinical anesthesia is the most widely used fentanyl and its derivatives. Narcotic analgesics are mainly referring to these drugs.
ã€ã€‘ Subcutaneous absorption process in vivo is not constant, intramuscular injection is well absorbed, 15 ~ 30min there role, 45 ~ 90min and reached the peak effect of duration 4 ~ 6h. Absorption of the body, only a small amount through the blood - brain barrier into the placenta and breast milk. Mainly in the liver with glucuronide, 10% to methyl morphine metabolism, mainly excreted by the kidneys.
1. Central nervous system
(1) analgesia: characteristics of high selectivity, high efficiency, wide range of effects over time, accompanied by calming the same time. Of dull pain, sharp pain, visceral colic are effective, the strongest inhibition of dull. Emotional reaction to change and improve the body's tolerance to pain, some patients produce euphoria.
(2) inhibition of respiration: respiratory center inhibition, slowing the respiratory rate and tidal volume reduction, mainly to reduce the sensitivity of the respiratory center of the CO2 may be the result of excitement thrown receptor.
(3) The antitussive effect: inhibition of cough center, and its role in the medullary NTS opioid receptors. Because of addictive, is generally not used for cough.
(4), miosis, nausea, vomiting and other effects.
2. Digestive tract caused by diarrhea and constipation. Mainly to improve gastrointestinal smooth muscle, even to the degree of spasticity, motility was inhibited, so that blocked the passage of gastrointestinal contents, it means less reflection, and other factors inhibit the secretion of digestive juice also caused bile duct sphincter contraction, the gallbladder pressure rise high.
3. Cardiovascular system, vascular resistance and capacity expansion of blood vessels, causing orthostatic hypotension, and release of histamine and the role of opioid receptors in the NTS, to the decreased central sympathetic tone.
1. Analgesia on all kinds of pain effective, but addictive, other analgesics for acute invalid sharp pain, biliary colic should be treated with atropine and other antispasmodic drug combination.
2. In addition to oxygen and cardiac asthma, cardiac glycoside used, the intravenous injection of morphine can produce good results.
3. Antidiarrheal opioids are often used in tincture or compound tincture of camphor.
4. Anesthetic premedication and anesthesia can ease the pain and anxiety. Large doses of morphine (1ml/kg) intravenous infusion anesthesia for cardiac surgery was, but not enough to suppress such a depth of anesthesia and hemodynamic stress response more obvious interference, has been of fentanyl and its derivatives replaced.
1. General adverse reactions, dizziness, nausea, vomiting, respiratory depression, constipation, difficulty urinating, drowsiness, bradycardia, orthostatic hypotension.
2. Dependent use 3 to 5 days that produce tolerance, more than 1 week can be addictive.
3. Acute poisoning can cause acute poisoning, overdose, mainly as coma, respiratory depth of depression, the pupil was extremely narrow or needle-like large, blood pressure and even shock. Relief of acute poisoning include artificial respiration, oxygen, etc., intravenous opioid receptor blocker naloxone significantly against the results.
Contraindicationsã€‘ ã€respiratory failure, increased intracranial pressure and brain injury patients, bronchial asthma, pulmonary heart disease decompensation, patients with severe liver dysfunction, breast-feeding women, expectant women, infants disabled.
ã€Pharmacological effects of morphine analgesic strength of 1 / 10 ~ 1 / 8. Equivalent dose of the same generation and morphine analgesia, sedation and respiratory depression, but later appeared to maintain a short time. Moderate increase muscle tension, constipation caused by the role of weak excitatory effect on the bile duct to bile duct sphincter pressure increased, but weaker than morphine. Antitussive effect only slightly. The end of the uterus for pregnancy, non-confrontational uterine oxytocin exciting role, do not change the rhythmic contraction of the uterus, or delay the birth process. No miosis effect (because of their anticholinergic effects.) Less addiction, resulting in slower. A weak local anesthetic effect.
ã€‘ ã€Clinical pain can be a substitute for a variety of morphine. Visceral colic (biliary colic and renal colic) shall be combined with atropine. For labor pain, the need to monitor the goods on the newborn respiratory depression. With chlorpromazine, promethazine mixture composed of artificial hibernation. Also be used for cardiac asthma, before anesthesia and intravenous anesthesia assisted delivery.
Adverse reactions manifested as acute poisoning respiratory depression, drowsiness, then coma, decreased blood pressure; occasionally atropine-like poisoning symptoms can occur: dilated pupils, tachycardia, irritability, delirium and even convulsions, and then transferred to inhibition. The excitement of poisoning and other symptoms occur, naloxone can be to increase, this time only site of diazepam or barbiturates lifted. Contraindications with the morphine.
(C) fentanyl and its derivatives
Fentanyl and its derivatives - sufentanil, alfentanil and remifentanil are the synthesis of phenyl piperidine class of drugs.
ã€Processã€‘ fentanyl body fat-soluble, hence the easy through the blood - brain barrier into the room the brain, can easily be re-distributed from the brain into the body of other organizations, especially muscle and fat tissue. Single injection of a short duration of action, related to its redistribution. If repeated injections may produce cumulative effects, and its action time. 20 ~ 90min after injection blood concentration can be a second lower peak, and drug transfer from plasma on the surrounding room.
Fentanyl major biotransformation in the liver, through the off methyl hydroxylation and acyl hydrolysis, the formation of a variety of non-pharmacological activity of metabolites, with the urine and bile. Less than 8% of the prototype from the urine.
Lipophilic sufentanil fentanyl is about 2 times more through the blood - brain barrier. And plasma protein binding rate than fentanyl, whereas the smaller volume of distribution than fentanyl. Although its short elimination half-life than fentanyl, but due to opioid receptor affinity stronger than fentanyl, it is not only a stronger analgesic effect and duration of action longer. Sufentanil also liver biotransformation, the formation of N-to O-alkyl and demethylation metabolites and excreted with the urine and bile. The prototype from the urine were less than 1%. Its metabolites to the pharmacological activity of a sufentanil sufentanil of about 1 / 10, which is the duration of action of sufentanil long one of the reasons.
Alfentanil compared with fentanyl, lipophilic low volume of distribution of fentanyl is less than 1 / 4, elimination half-life of fentanyl 1 / 3 to 1 / 2. Although alfentanil lipophilic low, but because of pKa 6.8, lower than physiological pH, so the conditions in vivo pH7.4, 85% of alfentanil were non-ionization state (only 9% of the fentanyl ), because through the blood - brain barrier in the proportion of large and rapid onset. Alfentanil in the liver quickly converted into non-pharmacological activity of metabolites, mainly norepinephrine alfentanil.
Remifentanil ester, can be nonspecific tissue and plasma esterase rapid hydrolysis, the main metabolite excreted by the kidneys. Clearance rate is not dependent on liver and kidney function. Regardless of the length of time intravenous infusion, its plasma concentration is always half the time less than 4min; and fentanyl, alfentanil and sufentanil decreased with prolonged infusion time, infusion after 4h were extended to 262.5min, 58.5min and 33.9min.
ã€Clinical pharmacological effects of fentanyl morphine analgesic strength of about 75 to 125 times, the role of time is about 30min. More intense pain of sufentanil, fentanyl is about 5 to 10 times the duration of action is about a 2-fold. Alfentanil compared with fentanyl analgesic strength is small, about the 1 / 4, the duration of action is about a 1 / 3. Potency of remifentanil and fentanyl similar.
Fentanyl and its derivatives could inhibit breathing, mainly for respiratory rate slowed down.
These four drugs on the cardiovascular system are less, does not inhibit myocardial contractility, generally do not affect blood pressure. Nicole fentanyl induced bradycardia and Shufen too, this effect was atropine confrontation. Small dose of fentanyl or sufentanil can be effectively reduced blood pressure response to tracheal intubation, which may be solitary nucleus and the 9th and 10th cranial nerve nuclei are rich in opioid receptors, fentanyl and These receptors can inhibit the binding of the stimulus from the throat.
These four drugs also can cause nausea, vomiting, but did not effect the release of histamine.
ã€‘ ã€Clinical cardiovascular medicine because of the four small, it almost replaced the morphine application in cardiovascular anesthesia. Fentanyl is currently the most commonly used in clinical anesthesia narcotic analgesics, sufentanil and alfentanil of the applications are gradually increased. Remifentanil is a short analgesic effect, with prolonged infusion does not prolong its elimination half-life, etc., is known as the 21st century, opioid drugs.
Fentanyl, sufentanil and alfentanil is mainly used in clinical anesthesia, as part of anesthesia. As the three drugs on the cardiovascular system are small, commonly used in cardiovascular surgery anesthesia. The strongest analgesic effect of sufentanil for anesthesia better results, more stable cardiovascular status. Because the rapid onset of alfentanil, the role of short-term and very little accumulation of short-term operation can be divided into intravenous injection, intravenous infusion of sustainable long surgery, the application more flexible.
Remifentanil because of its unique pharmacokinetic characteristics, is more suitable for intravenous drip. Control infusion rate, can achieve the desired plasma concentration. Used in cardiovascular surgery patients, the clearance rate did not change after cardiopulmonary bypass. The disadvantage is that the end of surgery to stop the rapid infusion of analgesic effect after the disappearance. All current formulations of remifentanil contain glycine, can not be used for spinal injection.
Visible adverse reactions, dizziness, nausea, vomiting, bile duct sphincter spasm, rapid intravenous injection of fentanyl or Shufen too Nicole stiffness caused by chest wall and abdominal muscles to affect breathing, or muscle relaxants can be used opioid receptor antagonist treatment. Because of its pharmacokinetic characteristics of fentanyl or sufentanil injection or repeated injection of large doses, can be 3 ~ 4h after administration delayed respiratory depression, which should be vigilant.
Fentanyl and its derivatives can lead to dependency, but lighter than morphine and pethidine.
Opioid receptor stimulation - blockers
ã€Pentazocine pharmacological effects of morphine analgesic effect as of 1 / 3, respiratory depression for 1 / 2, addiction is very small, non-narcotic analgesics. Cardiovascular effects of different morphine, can cause high blood pressure and heart rate, pulmonary hypertension, increased cardiac load, so is not used for angina patients.
Clinicalã€‘ ã€pentazocine for moderate pain and anesthesia before the administration.
ã€Analgesic effects of pharmacological effects stronger than pethidine, morphine, morphine dose equivalent to 1 / 25. Characterized by slow onset and long duration. Increment after a certain dose the contrary, the pain decreased. Light addiction, does not cause constipation.
ã€ã€‘ Mainly used for clinical application of moderate to severe pain, such as a variety of post-operative pain, cancer pain, burns, limb pain, angina. Also be used for detoxification. In the absence of outstanding advantages, less anesthesia.
Opioid receptor blockers
ã€Pharmacological effects of naloxone and morphine structure similar to opioid receptors completely, competitive blocker, no intrinsic activity, intensity of opioid receptor antagonist were Î¼> Îº> Î´ receptor.
Injection of 0.4 ~ 0.8mg naloxone 1 ~ 2min that can antagonize morphine, pethidine, fentanyl, dihydro Aituo Fei's role in removing toxic symptoms such as respiratory depression, miosis, gastrointestinal spasm, intracranial hypertension, etc., and immediately induce morphine addiction withdrawal reactions.
Clinicalã€‘ ã€narcotic analgesics for acute poisoning, or after surgery due to opioid induced central inhibition of the antagonist, on cerebral infarction, acute alcohol intoxication, sedative hypnotic intoxication has a certain effect. Low-dose opiate addicts for the diagnosis. Analgesic studies is an important tool in medicine.
Second, accept the flexor ketone
Qu satisfied ketone chemical structure very similar pharmacological effects with naloxone, but the oral absorption, bioavailability, the role of strong and durable. In opioid addicts can trigger withdrawal symptoms. Commonly used in the prevention of addiction relapse after withdrawal.
Non-opioid analgesic drugs
ã€Pharmacological effects of tramadol has a weak effect of Î¼ receptor agonist, and can inhibit norepinephrine and 5-HT reuptake. Weaker than morphine in its analgesic effect. No respiratory depression, constipation and other side effects, euphoria, dependency are very low, cardiovascular, liver and kidney function, smooth muscle, skeletal muscle had no obvious effect. Do not suppress morphine withdrawal symptoms, or reminders for the naloxone addiction. Antitussive effect in addition to intensity of about 50% of codeine.
ã€ã€‘ Long-term clinical application can lead to dependency, it is not used for general pain. Used only for surgery, trauma, advanced cancer pain; on respiratory and cardiovascular system smaller, so the elderly and people with respiratory diseases were more applicable. The trial that the drug is kidney stones and gallstones in vitro lithotripsy important adjuvant therapy. Large individual differences in clinical analgesic effects. Tramadol withdrawal symptoms of morphine is invalid, can not serve as a substitute for morphine drugs for detoxification treatment.
Second, topiramate D F
Rapid oral absorption, 20 ~ 30min onset, which lasted for 3 ~ 5h. Oral and rectal bioavailability were 90% and 70%, 70% of liver metabolism in renal excretion after.
The drug with no affinity for opioid receptors, or inhibition of prostaglandin synthesis, the mechanism for the activation of descending pain control system, the function of norepinephrine, but also reduce skeletal muscle tension. Inhibition of respiration or cough without other opioid-like effect, living in a potent analgesic effect and a weak analgesic analgesics between. The pain of various causes have analgesic effects.
For surgery, trauma, burns, and pain caused by toothache, etc., can be used for short-term treatment. This drug may cause temporary skin redness, prurigo, sweating, dry mouth and so on.
Section III anesthetics
General anesthetics is reversible cause varying degrees of feeling and loss of consciousness, which can be implemented surgery drugs. Where produced by inhalation general anesthesia drugs called inhaled anesthetics.
First, the ideal conditions for inhaled anesthetics
1. Physicochemical properties and stability, easy-to-long-term preservation, non-explosive burning, and anesthesia equipment, lime or other drug exposure does not produce toxic substances.
2. No smell, no irritation to the respiratory tract.
3. Blood distribution coefficient, solubility in blood and tissues of the low, easy to adjust depth of anesthesia, controllable.
4. Anesthetic effects, and can be used with low concentration to avoid hypoxia.
5. Induction and wake up quickly, smooth, comfortable, non-consequential effect.
6. A good analgesia, muscle relaxation, stability, amnesia, There were no perception, no or less use of adjuvant drugs.
7. Can inhibit the abnormal stress response, maintaining stable internal environment.
8. In vivo metabolic rate, metabolites had no significant pharmacological effects and toxicity.
9. Safe range, low toxicity, few and mild adverse reactions, especially for circulatory, respiratory little effect on the heart, brain, lung, liver, kidney and other vital organs had no obvious toxic, non carcinogenic, teratogenic, mutation, no serious allergic reaction, do not pollute the air, without prejudice to the health of operating room staff.
10. The necessary equipment is simple, easy to use, rich source of drugs, low prices.
Second, the physical and chemical properties and classification
According to inhaled anesthetics is volatile at room temperature and pressure of liquid or gas, are called volatile anesthetics and gas inhalation shade drunk drugs.
Blood gas partition coefficient is an important property of volatile anesthetics. Partition coefficient refers to the partial pressure equal to dynamic equilibrium is reached when the concentration of anesthetics in the ratio of the two phases. Blood distribution coefficient, that drugs in the blood solubility, induction of slow; Similarly, the low blood gas partition coefficient of anesthetics, such as N2O, is induced more rapid awakening.
Third, the in vivo process
(A) anesthetics during the transfer process
Depth of anesthesia depends on the concentration of anesthetic in brain tissue. Anesthetics into the brain tissue before entering the alveoli, through the alveolar membrane diffusing into the blood, and then with the blood circulating through the blood brain barrier into the brain tissue.
(B) the impact factor by the membrane diffusion rate
Penetration of drug into the brain to be a number of biofilm, partial pressure of inhaled anesthetics are always high from the low side of the spread of the side until the partial pressure is equal on both sides so far. The speed by the membrane diffusion of drugs across the membrane divided by the pressure, drugs in the tissue (including blood) in the solubility, diffusion area and distance, temperature and molecular weight drugs and other effects.
For a given patient and medication, usually only the partial pressure is a variable factor. So, in fact, by the film diffusion rate of drugs across the membrane is determined by the sub-pressure to improve the membrane on both sides of the sub-pressure drugs can accelerate the spread of drugs.
(C) the speed of the alveoli
After inhalation of anesthetic gas in the alveoli and then dispersed into the respiratory tract to blood. The speed of anesthetic into the alveolar two factors: the concentration of inhaled anesthetics and pulmonary ventilation.
1. Inspired concentration of inhaled anesthetics is the concentration of inhaled gas mixture in the concentration, it was positively correlated with alveolar anesthetic concentration, the higher the concentration inhaled into the alveoli, the faster, the faster the alveolar gas concentration, sub-anesthetic blood pressure rose faster, called the concentration effect (concentration effect).
Second gas effect (second gas effect): Inhalation of high concentrations of both (eg N2O) and low concentrations of gases (such as halothane), the low concentration of gas concentration and alveolar concentration in the blood increase the speed, lower than the equivalent alone concentration faster. Due to the higher concentration of high concentrations of gas from the alveoli to the blood faster diffusion, alveolar closing fast, low-density gas in the alveolar concentration increased rapidly, the concentration effect. Meanwhile, the high concentration of gas absorbed by a large number, have a greater negative pressure, so that increased pulmonary ventilation, inhaled the gas mixture also increased, but also bring some mixture of low concentrations of gas, that is, the incremental effect. These two factors have increased the low concentration of gas transfer to the blood. High concentration of gas at this time as the first gas, low concentrations of gas as the second gas, so this effect is called the second gas effect.
2. Pulmonary ventilation of each lung into the suction gave some of anesthetic, if minute ventilation increases, into the anesthetic also increased, increasing the alveolar concentration of anesthetic accelerated in arterial blood partial pressure also will increase rapidly.
(D) into the blood concentrations
Alveoli to the blood transfer, also known as blood intake or lung uptake. Normal alveolar membrane transport of anesthetic gas and out of no barrier obstacles. However, in some pathological conditions will prevent anesthesia gas from the alveoli to the effective transfer of blood, one of which is the uneven distribution of alveolar ventilation to pulmonary emphysema.
Ventilation under normal circumstances, there are three factors that determine the speed of anesthetic into the blood: the solubility of anesthetics in blood, cardiac output and alveolar - venous anesthetic partial pressure. Blood intake of anesthetic gas is equal to the product of more than three factors by dividing the atmospheric pressure, namely:
Intake = Î» Ã— Q Ã— (Pa-Pv) / atm
Chapter XVII insane anti-drug
Mental disorders (psychiatric disorders) is caused by a variety of barriers to mental activity of a class of diseases. Drug treatment of these diseases mental disorders collectively referred to as anti-drug. According to the clinical use fall into three categories: the antipsychotic drugs (antipsychotic drugs), anti-manic depression drug (antimanic and antidepressive drugs) and anxiolytics (antianxiety drugs)
Antipsychotic drugs used to treat schizophrenia and other mental disorders, manic symptoms.
According to the chemical structure can be divided into common phenothiazine antipsychotics (phenothiazines), thia-anthracene class (thioxanthenes), dibutyryl benzene (butyrophenones), and other drugs.
Phenothiazine is composed of sulfur, nitrogen atom linking the two benzene rings (known as phenothiazine nucleus) of a class of compounds. Different groups according to their side chain, into dimethyl amine, piperazine and piperidine (Table 17-1).
These three categories to piperazine antipsychotic strongest, followed by dimethyl amines, piperidines weakest. At present, there are commonly used in clinical chlorpromazine, fluphenazine and trifluoperazine, in order to chlorpromazine most widely used.
Chlorpromazine (chlorpromazine), also known as Dong Mianling (wintermin).
"Intimate process" were easily absorbed orally or by injection, but the absorption rate by the dosage form, the impact of food the stomach, such as concomitant cholinergic receptor blockers, can significantly delay the absorption. 2 ~ 4 hours of oral chlorpromazine plasma concentration peak, intramuscular absorbed quickly, but strong irritant injection should be deep, and its bioavailability than oral high 3 to 4 times, which has a first-pass effect on oral administration. Absorbed, about 90% bound to plasma proteins. Chlorpromazine highly lipophilic, easily through the blood-brain barrier, widely distributed in brain tissue, the following thalamus, basal ganglia, thalamus and hippocampus and other parts of the highest concentrations of plasma concentration of brain concentrations of up to 10 times. Chlorpromazine by liver microsomal enzymes primarily metabolized to a chlorpromazine, phenothiazine chlorine, methoxy or hydroxylated products and glucuronide conjugates. Chlorpromazine and its metabolites mainly via renal excretion. Chlorpromazine metabolism of elderly patients with slow elimination rate. The same dose of oral chlorpromazine different individuals, the plasma drug concentration difference of up to 10 times, therefore, clinical use should be individualized. Chlorpromazine excretion is slow, 2 to 6 weeks after stopping, or even 6 months, may be detectable in the urine, which may be fat-soluble high chlorpromazine, the result of accumulation in adipose tissue.
"Pharmacological effects and clinical application of" mainly chlorpromazine blocking effect on the DA receptors, while also blocking the Î± receptor and M receptors. Therefore, the pharmacological effects of extensive and complex.
DA receptors present in the peripheral nervous system and central nervous system. At least two subtypes of D1 and D2. D1 receptors coupled with the GS protein, which, when excited by the GS protein activates adenylate cyclase, the cAMP increase. Cause peripheral vasodilation, increased cardiac contractility. However, in the central nervous system function remains unclear. D2 receptors in the central nervous system seen in DA neurons in brain pathways. A number of brain DA pathways, mainly the substantia nigra - striatal pathway in the brain - the limbic pathway and brain - cortical pathway. The former is related to extrapyramidal motor function, the latter two pathways and the mental, emotional and behavioral activities. In addition to nodules - funnel pathway, and regulation of hypothalamic secretion of certain hormones. D2 receptor coupled to Gi protein, inhibition of adenylyl cyclase when excited, the other can open potassium channels. Chlorpromazine on brain DA receptors lack of specific selective, and thus the role of diversity.
1. Central nervous system
(1) anti-psychotic effect of normal time after oral administration of 100mg chlorpromazine, appears stable, calm, feeling faint, and react less on the things around, in a quiet environment, easy to induce sleep. Mental illness after treatment, without causing excessive sedation cases, the rapid control of agitation excited. Continue medication, make hallucinations, delusions, mania, and psychomotor excitement gradually disappear, rational recovery, emotional stability, self-care. Hallucinations and paranoid anti-anti-chlorpromazine usually takes the role of continuous medication 6 weeks to 6 months before the full markedly, and no tolerance. However, after continuous treatment, stability, and sedation were gradually weakened, a tolerance.
The major clinical application of chlorpromazine in the treatment of various types of schizophrenia, acute patients with good effect, but no cure, it is essential to maintain the efficacy of long-term use, reduce recurrence. In addition, it can be used for the treatment of mania and other mental illness associated with the excitement, tension and paranoia and other symptoms.
The mechanism of antipsychotic chlorpromazine determined. Early that phenothiazines can improve animal brain metabolite of DA, homovanillic acid (HVA), the production rate. This means that the DA's update adds, so guess this is due to phenothiazines block the DA receptors in the brain, compensatory accelerated the presynaptic DA synthesis and metabolism in the results. Also found that phenothiazines increase the update rate of DA parallel to its intensity. Later found that phenothiazines can inhibit adenylyl cyclase activity in brain. Inhibition of the enzyme with their clinical efficacy and consistent. In addition, radioligand binding analysis also found that phenothiazines with 3H-haloperidol and 3H-DA specific binding site competition in the brain (DA subject), but the strength and competitiveness of phenothiazine parallel anti-psychotic intensity. Now that the clinical symptoms of schizophrenia is due to excessive brain function caused by DA and D2 receptor density in brain has been specifically increased. Phenothiazines is a strong D2 receptor antagonist. So that the phenothiazine antipsychotic effect by blocking the brain - and in the limbic brain - the D2 receptors in cortical pathway occurred.
(2) antiemetic effect has a strong antiemetic effect of chlorpromazine can be against the emetic effects of morphine to the water, a large dose of directly inhibit the vomiting center. Extension of the brain drain of morphine on the bottom of the fourth ventricle area after the emetic very chemosensory areas (chemoreceptor trigger zone, CTZ) of the D2 receptor has a strong emotional effect, showing that the antiemetic effect of chlorpromazine is blocked by CTZ of the D2 caused by the body. However, chlorpromazine and vomiting caused by vestibular stimulation is not valid. Intractable hiccups effective. For the treatment of vomiting caused by various diseases such as cancer, radiation sickness and vomiting caused by certain drugs.
(3) the influence of chlorpromazine inhibition of temperature regulation of hypothalamic temperature regulation center, the failure of temperature regulation, and thus the body temperature changes with environmental temperature down. Hypothermia in cold environments; in high temperature is body temperature. Chlorpromazine not only reduce the fever temperature, but also to decrease slightly the normal body temperature. To physical cooling clinical use of hypothermic anesthesia with chlorpromazine. Combined with some drugs, such as central inhibition, can the patient is in deep sleep, body temperature, metabolism and oxygen consumption decreased volume status, called artificial hibernation therapy. Can be used as severe infection, toxic conditions such as high fever and thyroid storm in the adjuvant therapy.
(4) to strengthen the central role of inhibitors of chlorpromazine can enhance anesthetic, sedative hypnotics, analgesics and the role of ethanol. Chlorpromazine in combination with these drugs should be appropriate reduction, so as not to deepen the central nervous system depression.
(5) the impact of chlorpromazine block of extrapyramidal nigra - striatal D2 receptor pathway, resulting in cholinergic nerve function dominant. Thus a large number of applications in long-term extrapyramidal effects may occur.
2. Autonomic nervous system has obvious chlorpromazine Î± receptor blocking effect, can turn the boost effect of adrenaline, while inhibition of vasomotor center, and have a direct relaxation of vascular smooth muscle, dilation of blood vessels and thus reduce the blood pressure. Antihypertensive effect of repeated drug use, but weakened, it is not suitable for the treatment of hypertension. M chlorpromazine can still block the receptor, but the effect is weak, no therapeutic significance.
3. Nodular endocrine system - the funnel at the DA pathway is the main function of the hypothalamus control the secretion of certain hormones. Chlorpromazine can block the D2 receptor pathway, reducing the release of hypothalamic prolactin inhibitory factor, thereby increasing the secretion of prolactin, causing breast enlargement and lactation. Chlorpromazine disabled patients with breast cancer. In addition to inhibition of gonadotropin-releasing hormone secretion, the follicle stimulating hormone and luteinizing hormone releasing less, causing delayed ovulation; and the inhibition of corticotropin hormone and growth hormone secretion. The latter role can be tested in treatment of gigantism.
"Adverse reaction" chlorpromazine safety range, but long-term large number of applications, more adverse reactions.
1. Common adverse reactions are drowsiness, weakness, blurred vision, nasal congestion, tachycardia, dry mouth, constipation and other central nervous system and autonomic nervous system side effects. Long-term use can cause breast enlargement, amenorrhea, and growth slowed down and so on. Chlorpromazine strong local irritation, the skin should not be injected. Intravenous injection can cause thrombophlebitis, should be diluted with saline or glucose solution was slowly injected. After intravenous or intramuscular injection, there may be postural hypotension, Zhu Huanzhe bed should be 1 to 2 hours before slowly standing.
2. Extrapyramidal effects are long-term application of chlorpromazine in the treatment of schizophrenia when a large number of the most common side effects, the incidence of drug dose, treatment and individual factors. Its performance as follows: â‘ Parkinson's syndrome, appeared increased muscle tone, stiff face (face mask), slow movement, muscle tremors, salivation, etc.; â‘¡ acute dystonia occurring in 1 to 5 days after treatment, due to the tongue, face , neck and back muscle spasms, compulsive patients mouth, Shenshe, stiff neck, breathing and swallowing difficulties in movement disorders; â‘¢ akathisia (akathisia) patients with restless, wandering again. These three symptoms of cholinergic receptor blockers can relieve the Antan. But can also cause symptoms of a rare extrapyramidal reactions, tardive dyskinesia (tardive dyskinesia) or late onset ADHD, manifested as involuntary, rhythmic stereotyped movement, there mouth - tongue - triple cheek disease, such as sucking, licking tongue, chewing. If early detection and timely withdrawal can be restored, but there are still hard to recover after treatment. Application of anti-cholinergic receptor blockers can make the increase. Cause tardive dyskinesia may be due to the long-term blockade and chlorpromazine in postsynaptic DA receptors, so increasing the number of DA receptors, that upward regulation.
3. Allergic reactions common skin rashes, photosensitivity dermatitis. A small number of patients with liver cell micro-duct obstructive jaundice. A small number of patients with acute agranulocytosis should be immediately discontinued and the use of antibiotics to prevent infection.
"Acute poisoning" swallowed a large dose (1 to 2 grams) chlorpromazine, may occur in acute poisoning, drowsiness, blood pressure of shock level, and tachycardia, abnormal ECG (PR interval or QT interval extension, T wave low and flat or inverted), symptomatic treatment should begin immediately.
"Contraindications" can reduce the seizure threshold of chlorpromazine, induced epilepsy, a history of epilepsy disabled. Coma patients (especially the central inhibition after drug application) is disabled. Associated with cardiovascular disease in older patients with caution, prone to cause sudden death in patients with coronary heart disease should be added attention. Severe liver dysfunction disabled.
Other phenothiazine drugs
Perphenazine (perphenazine), fluphenazine (fluphenazine) and Trifluoperazine (trifluoperazine) is a phenothiazine in the piperazine derivatives, their common feature is strong antipsychotic effects, extrapyramidal side effects are very significant , and sedation weak. Among them, fluphenazine and trifluoperazine good effect, the most commonly used, and perphenazine in poorer treatment outcomes. Thioridazine (thioridazine, thioridazine) is a phenothiazine class of piperidine derivatives, effective less than chlorpromazine, but rare extrapyramidal reactions, and strong sedative effect. Characteristics of each drug in Table 17-2.
Table 17-2 antipsychotic effect of phenothiazines compared
(Mg / day)
Sedative side effects
Antihypertensive effect of chlorpromazine
300 ~ 800
(IM) of oral fluphenazine
1 to 20
6 to 20
8 to 32
200 ~ 600
Strong, the second strongest; weak
Second, thia-anthracene class
Thia basic chemical structures of acridine and phenothiazine similar drugs represented Cape thiazolyl tons of chlorine (chlorprothixene), and Mingtaierdeng (tardan). The antipsychotic and anti-hallucinations, delusions, weaker effects than chlorpromazine, but the strong sedative effect, while the anti-adrenergic effect and anticholinergic effects is weak. Also due to the chemical structure and similar to tricyclic antidepressants, there was weaker antidepressant effect. For anxiety or anxiety associated with depression, schizophrenia, anxiety neurosis, menopausal depression. Extrapyramidal side effects reaction, and chlorpromazine similar.
Third, butyrylcholinesterase benzene
The class of drugs haloperidol (haloperidol), its effect and mechanism of phenothiazine similar. Antipsychotic effect and extrapyramidal reactions were strong, calm, weak antihypertensive effect. Because of anti-manic, anti-hallucinations, delusions significant effect, commonly used in the treatment of restless excitement, hallucinations, delusions in schizophrenia and mania. Antiemetic effect was stronger for a variety of diseases and drug-induced vomiting, and persistent hiccups and effective. Extrapyramidal reactions up to 80%, common acute dystonia and akathisia. A large number of long-term use can cause myocardial injury. Generic drug droperidol (droperidol) short duration of the role of clinical often with co-analgesic fentanyl anesthesia for stability.
Fourth, other types of
Five fluoride Lido (penfluridol) for the long-acting antipsychotics. Great after serving 8 to 16 hours, reached the peak plasma concentration, 128 hours after the peak plasma concentration is still 30%. The first 7 days after treatment, the serum can be detected. The long-term causes and stored in adipose tissue, and since one of the slow release into the blood and into the brain organization. Maintain the efficacy of oral once a week. Similar efficacy with haloperidol, but no sedation. Common side effects to extrapyramidal effects. For acute and chronic schizophrenia, especially for chronic patients to maintain and consolidate the results. Similar drugs still pimozide (pimozide), its role in the maintenance of time shorter than five fluorine profitable, orally once daily, efficacy can be maintained for 24 hours.
Sulpiride (sulpiride) on acute and chronic schizophrenia has a good effect on the long-term use of other drugs invalid resistant cases also have some effect. No sedation, little impact on the autonomic nervous system, adverse reactions, extrapyramidal reactions were mild. The antidepressant drugs also can also be used to treat depression.
Clozapine (clozapine) antipsychotic effect was stronger case for other drugs is still valid and effective, but also for chronic schizophrenia. Almost no extrapyramidal system response, which may have a strong and clozapine anticholinergic effects. Can cause neutropenia, should be vigilant.
4. Metabolic endocrine common side effects of prolactin secretion, estrogen and testosterone level changes have been reported commonly in women galactorrhea, amenorrhea, and impaired sexual pleasure. Phenothiazines can produce false positive pregnancy test. More common in men, loss of sexual desire, erectile difficulties and ejaculatory inhibition. Growth hormone levels decreased, but in the use of phenothiazines or dibutyryl maintenance treatment of benzene no growth retardation in children. Abnormal secretion of antidiuretic hormone have also been reported. Chlorpromazine can inhibit insulin secretion, etc., resulting in elevated blood sugar and urine sugar positive.
More common weight gain, increased appetite and activity with the decrease. More complex mechanisms, including histamine receptor antagonist, and mechanisms mediated by the hypothalamus glucose tolerance and insulin release changes. Patients should diet. The role of weight gain than haloperidol phenothiazine less.
5. Mental side effects of many antipsychotic drugs produce sedation, sedative effect that is usually quickly disappear due to tolerance. Often slow because of dizziness and orthostatic hypotension. Piperazine phenothiazines, benzamides and risperidone had mild active and exciting role, can produce anxiety, agitation.
Drugs on cognitive function in schizophrenic patients with the disease itself intertwined with cognitive deficits. Strong sedative effect of phenothiazines tend to inhibit the psychomotor and attention, but generally does not affect the higher cognitive functions. If you include anti-cholinergic drugs and memory may be temporarily affected.
Whether antipsychotic drug can cause depression is not clear. Whether or not medication, patients with schizophrenia can be significant in the emotional fluctuations. Early onset schizophrenia, depression and recovery can occur, suicide is not uncomm
6. Other side effects of antipsychotics and many less common side effects. Antipsychotic effects on the liver is a common alanine aminotransferase (ALT) increased more than a transient, self-healing, usually no symptoms, the light do not stop, the combined treatment of liver protection; weight or jaundice should be immediately discontinued and strengthen Liver treatment. Rare obstructive jaundice liver juice, and sometimes sweat of bile can refuse to harden. Other rare allergic reaction including the eruption, with fever asthma, edema, arthritis, and lymphadenopathy. Severe exfoliative dermatitis drug eruption can occur should be immediately discontinued and active treatment. Previous 1234 Next