What Are the Different Cholinesterase Inhibitors?

Cholinesterase inhibitors are a class of drugs that can bind to cholinesterase (ChE) and inhibit the activity of ChE (also called anticholinesterase drugs). Their role is to accumulate Ach released by cholinergic nerve endings It exhibits enhanced M-like and N-like effects and excites choline receptors, so this class of drugs is also called pseudocholine drugs.

Cholinesterase inhibitors are a class of drugs that can bind to cholinesterase (ChE) and inhibit the activity of ChE (also called anticholinesterase drugs). Their role is to accumulate Ach released by cholinergic nerve endings It exhibits enhanced M-like and N-like effects and excites choline receptors, so this class of drugs is also called pseudocholine drugs.

Chinese name

Cholinesterase inhibitor

Effect

Play a role in exciting choline receptors

Also known as

Choline-like drugs

Function

Binding to cholinesterase and inhibiting ChE activity

Cholinesterase inhibitor profile

Cholinesterase inhibitors are a class of drugs that can bind to cholinesterase (ChE) and inhibit the activity of ChE (also known as anti-cholinesterase drugs). Their role is to accumulate Ach released by cholinergic nerve endings. It exhibits enhanced M-like and N-like effects and excites choline receptors, so this class of drugs is also called pseudocholine drugs. Can be divided into: reversible or transient cholinesterase inhibitors, such as neostigmine, chlorstigmine, etc .; these drugs have clinical therapeutic effects. Irreversible (or irreversible) cholinesterase inhibitors, such as organic phosphates, including agricultural pesticides and war gas.

() Cholinesterase inhibitor acetylcholinesterase (cholinesterase)

Cholinesterase is an enzyme that rapidly hydrolyzes acetylcholine in the body. There are two types of this enzyme: AChE is a real cholinesterase, which is present in cholinergic neurons, cholinergic synapses and red blood cells, and is an essential enzyme for hydrolyzing endogenous acetylcholine. Pseudocholinesterase mainly exists in plasma, liver and glial cells, and has no major role in terminating the effect of endogenous acetylcholine. Therefore, the pseudocholine effect produced by the inhibition of this enzyme is not significant.

Cholinesterase has two active centers on its surface, namely, a negatively charged anion site and an esterolysis site.

() Cholinesterase inhibitors 2. Cholinesterase inhibitors (anti-cholinesterase drugs)

Neostigmine

Neostigmine is a synthetic dimethyl carbamate with quaternary ammonium groups.
[Pharmacological action] Neostigmine can reversibly inhibit cholinesterase activity, protect acetylcholine from hydrolysis and produce M-like and N-like effects in the accumulation of cholinergic nerve endings. Relative selectivity: It has the strongest excitatory effect on skeletal muscles. In addition to inhibiting choline caseinase, it can also directly stimulate N2 receptors on the terminal plate and promote the release of acetylcholine from motor nerve endings. has a strong role in exciting gastrointestinal smooth muscle. It has weak excitatory effect on eyes, glands and bronchial smooth muscle.

[] Cholinesterase inhibitor [Pharmacokinetics]

This product is a quaternary ammonium compound, which has low fat solubility, so it is less irregular and absorbed orally, and the oral dose is more than 10 times the subcutaneous dose. t1 / 2 is about 3 hours. The drug does not easily penetrate the blood-brain barrier and has no obvious central effect. It is difficult to enter the anterior chamber through the cornea when the eye drops, so the effect on the eye is also weak. A part of neostigmine entering the body is hydrolyzed by cholinesterase in the plasma. The hydrolysate and the original part are excreted from the urine.
[Clinical application]
1. Myasthenia gravis is a chronic disease of motor neuromuscular junction transmission dysfunction. Its clinical characteristics are progressive muscle weakness after continuous contraction of skeletal muscles for a short period of time, manifested as eye sags, difficulty chewing and swallowing, and severe breathing difficulties. Etc. Myasthenia gravis. The disease is now considered to be an autoimmune disease. N2 choline receptor antibodies are present in the patient's serum, and the disintegration of the receptor is induced, resulting in a decrease in the number of N2 receptors on the end plate. The rapid injection of neostigmine subcutaneously or intramuscularly Improve symptoms, can be maintained for 2 to 4 hours. Oral administration can be used in general cases, and the dosage should be mastered. Overdose can cause long-term depolarization and cause "cholinergic crisis", which can increase myasthenia gravis.
2. Asthma and urinary retention of neostigmine can stimulate gastrointestinal smooth muscles and bladder detrusor muscles to promote postoperative gas drainage and urination.
3 Paroxysmal supraventricular tachycardia slows atrioventricular conduction and decreases ventricular rate through neostigmine-like choline M-like effects.
4 Excessive poisoning of muscle relaxants can be used to rescue non-depolarizing muscle relaxants such as tubercoxine in excess.
5. Other bromazeptine eye drops treat glaucoma.
[Adverse reactions]
1. General reaction Over-use over a long period of time can produce nausea, vomiting, abdominal pain, sweating, increased saliva, muscle tremors and muscle weakness. In severe cases, patients are abnormally weak and fatigued, muscles are paralyzed in the upper limbs, neck, shoulders, tongue, etc. , Gait instability, convulsions or clonics, and even coma, of which M-like effects can be countered by atropine.
2. The "cholinergic crisis" poisoning dose caused a long-term depolarization of the neuromuscular junction and blocked choline receptors, resulting in a mixed response of choline-like and muscarinic toxicity. Respirator for respiratory failure.
[medicine interactions]
1. Aminoamidine antibiotics, capreomycin, lincomycin, polymyxin, intravenous injection of lidocaine, intramuscular injection of quinine can all act on the neuromuscular junction and weaken skeletal muscle tension.
2. Because this class of drugs inhibits the activity of cholinesterase, the esters and local anesthetics are slowly hydrolyzed in the body and toxic reactions occur, and amide-type local anesthetics can be used.
3 Can antagonize the muscle relaxation effects of general anesthetics such as ether, isoflurane, etc.
4 Atropine acts on M choline receptors to mask adverse reactions when this class of drugs is overdose.
5. The combination of different varieties of this class of drugs should be avoided, and other esterase inhibitors, such as desmagnesium bromide, ecoiodate, etc. should be avoided.
6. Antihypertensive drugs guanethidine and mecamyl can reduce the effects of this class of drugs, and patients with myasthenia gravis are prone to swallowing and dyspnea.
7. Should not be used with succinylcholine, can reduce the decomposition of succincholine.
Pyridazine is a synthetic drug with a chemical structure similar to neostigmine. Its pharmacological effect is slightly weaker than that of neostigmine. Exciting gastrointestinal smooth muscle and anti-dart poisoning effect is about 1/4 of neostigmine, but the maintenance time is long, up to about 5 hours. It is mainly used in the treatment of myasthenia gravis, and is also suitable for postoperative abdominal distension, urinary retention and antagonistic non-depolarizing muscle relaxants. There are few side effects and rarely cholinergic crisis. The contraindication is the same as that of neostigmine.
Ambelium chloride Ambelium chloride (inhibinine) is a quaternary ammonium compound that selectively inhibits acetylcholinesterase. Its anticholinyl esterase effect and skeletal muscle stimulation are both new Mingqiang, lasting effect, can be administered orally. It is mainly used to treat myasthenia gravis. Adverse reactions and precautions are the same as neostigmine. Mystine (Eselin) is an alkaloid extracted from the seeds of poisonous lentils produced in Africa. It can also be artificially synthesized and is a reversible cholinesterase inhibitor. After absorption, pseudocholine effects occur in the periphery. Differences from Neostigmine are: It is a tertiary amine compound and easily penetrates the blood-brain barrier, so its effect on the central nervous system is low-dose excitement; large-dose inhibition; it can cause respiratory paralysis when poisoned. The absorption effect is less selective and the side effects are more obvious. Therefore, clinical treatment of glaucoma can reduce the pupil. It lowers intraocular pressure and causes adjustment spasm. Its effect is stronger and longer-lasting than that of pilocarpine, but it is caused by headache and local irritation due to ciliary muscle contraction, so it is mostly used for the rescue of acute glaucoma. First use this product for eye drops for treatment, then use pilocarpine (pilucapin) for maintenance.
Galantamine Galantamine is a biologically active substance extracted from the plant Amaryllidaceae and is a transiently reversible cholinesterase inhibitor. The in vitro anticholinesterase titer is about 1/10 of that of venomine, which can be used for the treatment of myasthenia gravis, but the effect is poor; it can also be used for the treatment of poliomyelitis (poliomyelitis) sequelae. Disabled in patients with epilepsy, bronchial, asthma, bradycardia and angina.
Preparation and usage: Bromazepam bromide tablets: 15mg / tablet, orally, 15mg / time, 3 times / day or depending on the condition. Extreme: 30mg / time, 100mg / day.
Neostigmine methyl sulfate: injection: 0.25 mg / ml, 0.5 mg / m1. 0.25 to 0.5 mg / time, subcutaneous or intramuscular injection. Extreme amount: 1mg / time. Sealed and protected from light.
Pyridine bromide sustained-release tablets: 180 mg / tablet, orally, for severe myasthenia gravis, 3 times / day. 360mg / day. Injection: 5mg / ml, 10mg / 2ml, injected subcutaneously or intramuscularly. 1 2mg / time for adults, 0.05 0.15mg / time for children, 4 6h once for myasthenia gravis, 2mg / time for adults, every 2 3h;
Syrup: 1.2% (g / ml), 60 to 120 mg / time for adults, 3 to 4 times / day.
Enzyme tablet: oral, 5-25mg / time, 3 times / day.
Salicylic acid lentiline eye drops: 0.25 to 0.5% solution, once every 4 to 6 hours, or as many times as needed, the solution is not available after it turns red. Eye ointment: 0.25%, apply before bedtime or as needed. Injection: 1mg / ml, 2mg / ml.
Bromide eye drops: 0.25% solution, once every 12 to 48 hours or as directed by your doctor.
Galantamine hydrobromide tablets: 10 mg / tablet. oral. 102mg / time. 3 times / day; injection: 1mg / ml, 2.5mg / ml, 5mg / ml, subcutaneous or intramuscular injection, 2.5 ~ 10mg / time, once / day. Children from 0.05 to 0.1 mg / kg / time.
Summary of Nursing Medicines Cholinesterase inhibitors such as neostigmine and other treatments are evaluated before administration for myasthenia gravis and sequelae of poliomyelitis to restore skeletal muscle tension. It is used to slow heart rate for rapid tachycardia. It is used for gastrointestinal peristaltic exhaust after gastrointestinal and bladder surgery, to eliminate intestinal flatulence and promote urination; it can also be used for the rescue of tube poison poisoning. Used in glaucoma to reduce internal pressure. Basic information For patients with urinary retention, the amount of fluid in and out should be recorded. Patients with myasthenia gravis should evaluate their muscle tone, muscle fatigue, swallowing ability, etc. to determine the degree of neuromuscular junction dysfunction,
(3) Identification of cholinesterase inhibitors in high-risk patients is prohibited in patients with mechanical obstruction of the intestine or urethra. Use with caution in patients with ulcers, slowed heart rate, asthma or hyperthyroidism.
2. The route of administration: neostigmine: oral or intramuscular, intravenous.
The use of new stigmine diagnosis of myasthenia gravis, generally 1.5mg in adults, intramuscular injection, muscle tension improved within a few minutes and last for 1 hour, at the same time with the signs and electromyography to adjust the dose. For the treatment of myasthenia gravis, the adult is 0.0l 0.04mg / kg, intramuscularly or subcutaneously, if the intravenous injection is used, the dose is halved. Urinary retention of detrusor muscle weakness after treatment, 0.25 mg / time for adults, once every 4 to 6 hours for 2 to 3 days. Intestinal flatulence after treatment, 0.5 mg / time for adults, intramuscular injection, and repeated administration at regular intervals, prepare atropine 0.6 ~ 1.2 mg at any time, intramuscular or intravenous injection to prevent bradycardia. It is used as an antagonist of non-depolarizing muscle relaxant. For adults, it is 0.5-2.0 mg for the first time, intravenous injection, the maximum amount is 5 mg, and the additional maintenance amount is less than 0.5 mg / time. Oral: 5mg / time, 3 times / day. Extreme amount 30mg / time, 100mg / day. Galantamine hydrobromide: used for myasthenia gravis, 2.5-10mg / time for adults, intramuscular or subcutaneous injection; 0.05 ~ 0.1mg / kg / time for children. Salicylic acid lentiline: used for awakening, 0.5 to 2.0 mg for adults, intravenous or intramuscular injection. Antagonistic scopolamine 3.0-4.0mg, after 15 minutes of intravenous injection are not satisfied with the effect, can be injected 1.5-2.0mg. For ophthalmology, eye drops 2 to 3 times a day, eye ointment 1 to 3 times a day. Do not use in children.
(3) Promote the patient to cooperate with the treatment to tell the patient that myasthenia gravis cannot be cured, and medication is required for life. Encourage patients to adhere to treatment as directed by their doctor. In addition, because such patients are at risk for fatal complications, such as cholinergic crisis, myasthenic crisis, patients are encouraged to carry with them a clear statement that they have the disease and are treated with a certain drug Marking so that in case of an accident, it helps emergency doctors understand their condition and make proper diagnosis and treatment.
3 Continuously evaluate the efficacy and safety Evaluate the therapeutic effect Monitor and record the number of administrations, the number of times of muscle fatigue after administration, determine the state of muscle tension recovery, observe the patient's hand grip, whether eye sags, swallowing ability, and No paralysis. Based on these observations, the dose should be adjusted in time to achieve the therapeutic effect without producing a cholinergic crisis. Monitor the myasthenic crisis (extreme muscle weakness, respiratory muscle paralysis) due to insufficient dose of cholinesterase inhibitors, and immediately perform tracheotomy and emergency treatment with artificial respirator.
Reduce adverse effects Excessive M-like acetylcholine accumulation at the M-type choline receptor can cause a large amount of drooling, visual adjustment spasm, bronchoconstriction and slow heart rate. Tell the patient that once these symptoms occur, they should be reported to the doctor and can be treated with atropine To counteract excessive M-like reactions.
Cholinergic crisis is caused by excessive use of cholinesterase inhibitors. Manifested as skeletal muscle paralysis and the above M
This kind of excessive excitement was treated with artificial respiration and atropine. Note that a strict distinction must be made between cholinergic and myasthenic crisis.