There are more drugs for the treatment of Alzheimer’s disease, which can be divided into neurotransmitter drugs, cerebrovascular dilators, and brain metabolizing drugs according to their pharmacological effects, and the effects of each type are crossed with each other. For example, in cerebrovascular dementia (VD), cerebrovascular dilators, drugs that improve cerebral circulation and increase blood oxygen content should be preferred, while brain metabolism activators and blood viscosity reducing drugs should be used together. For patients with Alzheimer’s disease (AD) with brain cell atrophy, cholinergic drugs should be preferred, along with cerebrovascular dilators and neuropeptides.
At present, the commonly used puzzling drugs are as follows.
1, cholinesterase inhibitors: Since the 1970s, research results on neurotransmitters related to the disease, especially on neurotransmitter concentrations, receptor numbers and neurotransmitter synthesis enzymes in AD brain, have shown that Alzheimer’s disease of various causes has specific neurotransmitter defects in the cholinergic neuron system. Impaired function of the cholinergic system can cause memory and learning impairment, and if the concentration of cholinergic mediators, especially acetylcholine, in the brain tissue is increased, the learning and memory ability of the elderly can be significantly improved. Therefore, alterations in the cholinergic system are closely related to the degree of cognitive impairment in this disease, which is known as the cholinergic hypothesis. Cholinesterase inhibitors are used clinically to inhibit the intensity of acetylcholinesterase hydrolysis of acetylcholine, thus increasing the concentration of acetylcholine in the brain to treat AD, and thus cholinesterase inhibitors are the drugs of choice for AD treatment.
Currently, the following drugs are commonly used.
(1) Donepezil, the trade name of Anisin, can be taken once a day at a dose of 5 mg/day, increasing to 10 mg/day after 4 weeks. It is effective for about 50% of mild and moderate AD, and can alleviate the deterioration of cognitive function and reduce behavioral disorders in dementia patients, especially for behavioral disorders such as irritability, hostility, delusions, disorganized behavior and disinhibition. 50% of patients have “activating” effects after taking the drug, showing emotional activity, increased language, increased agility, etc., but to a lesser extent. The effect is mild. The adverse effects are small, no hepatotoxic effects, and no ALT (SGPT) monitoring is required. Common adverse reactions include gastrointestinal reactions (nausea, vomiting, poor appetite, etc.), cardiovascular reactions (bradycardia, syncope), headache, dizziness, insomnia, etc. Most of the adverse reactions are dose-related. Because of the cholinomimetic effect of this drug, it should be used with caution in people with severe bronchial asthma, cardiac conduction hysteresis, and bradycardia. In China, 65 patients with mild to moderate Alzheimer’s disease were treated with this drug for 12 weeks, and the results showed that 12.31% of the patients showed significant improvement in symptoms, 52.31% showed improvement in symptoms, 27.69% showed no change in symptoms, and 7.69% showed deterioration in symptoms, with an effective rate of 64.62%.
(2) Saposhnikin A (Shuangyiping), the trade name of Shuangyiping and Haberin. This drug is the first reversible cholinesterase inhibitor drug developed and studied in China, which is an alkaloid extracted from the genus Saxifraga, family Saxifraga. The starting dose is 0.05 mg orally two to three times a day; it can be increased to 0.2 mg two to three times a day. Adverse effects include dry mouth, drowsiness, bradycardia, gastrointestinal reactions, blurred vision, etc. Domestic clinical double-blind controlled trials have confirmed that the drug can improve human pointing memory, associative learning, graphic recall, meaningless graphic recognition and portrait recall, and can improve dementia and memory impairment caused by organic brain lesions. It is effective in 70.42% of early and mid-stage Alzheimer’s disease.
(3) Risperdalin (Rivastigmine, RSM), the trade name is Arsenal, the starting dose is 1.5 mg twice a day; after two weeks, if it is well tolerated, the dose can be gradually increased to 3 mg twice a day; if it continues to be well tolerated for two weeks, the dose can be increased to 4.5 mg or even 6 mg twice a day. The maximum recommended daily dose is 6 mg twice a day. If adverse reactions occur during dosing, the dose may be reduced to the previous dose level tolerated by the patient. The most common adverse reactions are gastrointestinal symptoms such as nausea, vomiting, diarrhea, as well as dizziness, headache and bradycardia, which are more common in women. In case of severe nausea and vomiting, antiemetic drugs may be considered. For patients with severe overdose, atropine can be used for treatment.
2.Glutamate receptor antagonist: Memantine is the first NMDA receptor antagonist used for the treatment of moderate and severe AD. Memantine can inhibit the excessive release of glutamate, the main excitatory neurotransmitter, and reduce neuronal cell poisoning, damage and death caused by excessive release of glutamate and excessive calcium ions. This improves the symptoms and functional problems of patients with dementia, and is well tolerated and safe to use.
3, cerebral vasodilators: these drugs have the effect of relaxing the smooth muscle of small arterial walls, promoting vasodilation and increasing blood flow to the brain, improving the blood and oxygen supply to the brain cortical cells. Such as flunarizine (Cipro, Sibelium), 5 to 10 mg, taken orally every night. The most commonly used drugs are calcium antagonists, which also have the effect of eliminating calcium overload in nerve cells and preventing cell death, and are currently recognized as the drugs of choice in the treatment of cerebrovascular disease. For example, nimodipine, the dose is 120-180 mg/day. Adverse effects are mild, with occasional gastrointestinal discomfort, dry mouth, transient dizziness and skin redness and oxygenation. Use with caution if you have cerebral edema and increased intracranial pressure. Use with discretion in pregnant or lactating women, and avoid using with other calcium antagonists or beta-blockers if possible.
4, brain metabolism activation drugs: the role of these drugs is more complex, mainly to expand cerebral blood vessels, increase the use of oxygen, glucose, amino acids and phospholipids in brain cortical cells, promote the recovery of brain cells, improve brain cell function, so as to achieve the purpose of improving memory. At present, there are many such drugs, commonly used are dihydroergotoxine (Xidezhen), nicergoline (brain pass), oral biracetam (brain rehab), aniracetam (Sanlexi), pyrithione (brain rehab), etc.
5. Chinese medicine: the causes of this disease are quite complex, involving various organs and systems of the human body, requiring multi-linked treatment. No matter single or double herbs, they contain multiple ingredients, which can be used as multi-system, multi-link and multi-method comprehensive treatment for this disease, and the adverse effects are small. When there is a lack of effective methods for treating this disease, the potential of Chinese medicine for dementia should be explored. Chinese medicine believes that the pathogenesis of senile dementia is related to the aging of the internal organs, the gradual depletion of the heart and blood, and the deficiency of the Shen essence, resulting in the loss of nourishment of the heart and kidneys and the emptiness of the medulla oblongata, and generally adopts the treatment of nourishing the liver and kidneys, activating blood circulation, resolving phlegm and clearing the ligaments. At present, there are dozens of Chinese herbal medicines for the treatment of this disease, but the ones commonly used in clinical practice are Tongxinluo, Brain Failure Tablets, Huijing Decoction, Heart and Brain Blood Health, etc.
6.Other.
(1) Cytophosphorylcholine (cytidylcholine) nucleoside derivative, a coenzyme. It increases the partial pressure of cerebral blood oxygen by increasing cerebral blood flow, and promotes the brain to wake up. It is used for motor disorders, disorders of consciousness and cerebral hypoxia associated with traumatic brain injury and brain surgery. The daily dose is 500 mg in 5% glucose solution intravenously for 1 to 2 weeks as a course of treatment. Occasionally, there are adverse effects such as transient drop in blood pressure, nausea, dizziness, lethargy and insomnia. It should not be applied during the period of intracerebral hemorrhage. It should not be injected repeatedly at the same site and should be injected slowly.
(2) Ginkgo biloba extract (EGB761) has more trade names, such as Bailout, Brainen, Stelon, etc. It is Ginkgo biloba extract. The dose is 2 to 3 tablets, 2 to 3 times a day.
Its pharmacological effects are.
① Increasing tolerance to cerebral hypoxia.
② Inhibiting the development of trauma and toxin-induced cerebral edema.
③ Reducing retinal edema and damage.
④ inhibition of the reduction of senile cholinergic and adrenergic receptors and increase of choline reabsorption in the hippocampus.
⑤ Improving cerebral circulation, thereby improving the brain’s memory and learning capacity.
⑥ Inhibition of platelet-activating factor, thus exerting neuroprotective effects. Currently, it is mainly used clinically for cognitive impairment caused by organic brain diseases (e.g. Alzheimer’s disease). Adverse reactions are rare and may occasionally include mild gastric discomfort, headache, and skin allergic reactions.