I. Lowering cranial pressure and dehydration, diuretic drugs
1. Mannitol (Mannitol)
Pharmacological effects: tissue dehydration. Increase plasma osmolarity, resulting in water in the tissue (including the eye, brain, cerebrospinal fluid, etc.) into the blood vessels, thereby reducing tissue edema, reducing intraocular pressure, intracranial pressure and cerebrospinal fluid volume and its pressure. 1g of mannitol can produce an osmotic concentration of 5, 5mOsm, injection of 100g of mannitol can make 2000ml of intracellular water transfer to the extracellular, urinary sodium excretion 50g.
Uses: Tissue dehydration drug. It is used to treat cerebral edema caused by various reasons, reduce intracranial pressure and prevent brain herniation.
Dosage: 0,25-2g/kg by body weight, prepared as 15%-25% concentration and injected intravenously within 30-60 minutes. When the patient is weak, the dose should be reduced to 0.5g/kg. closely follow up the renal function.
Precautions: 1) Mannitol is easily crystallized in cold, so it should be carefully checked before application, if there is crystallization, it can be placed in hot water or shaken with force to dissolve completely before use. When the concentration of mannitol is higher than 15%, a filtered infusion set should be used. 2) Use with caution in hyperkalemia or hyponatremia.
2.Glycerol and Fructose
Pharmacological effect: Hypertonic preparation, through high osmotic dehydration, can reduce the brain water content, reduce intracranial pressure. The effect of reducing intracranial pressure is slow and long lasting.
Use: Dehydration and lowering of intracranial pressure
Use: Intravenous drip, adults generally 250-500ml once, 1~2 times a day, each time 500ml need to drip 2~3 hours, 250ml need to drip 1~1,5 hours. It can be increased or decreased according to age and symptoms.
Caution: Hemolysis and hemoglobinuria may occur if the drip is too fast. This product contains sodium chloride 0.9%, when using the drug must pay attention to the patient’s salt intake.
Plasma volume expansion drugs
1. Hydroxyethyl Starch
Pharmacological effect: The volume expansion effect and hemodilution effect of hydroxyethyl starch solution depends on the molecular weight size, substitution degree, substitution method and drug concentration of hydroxyethyl starch, as well as the dose and speed of administration. The volume expansion effect is 145%, 100%, and 75% of the infused volume at the 1st, 4th, and 10th hours after rapid infusion of this product, respectively. For at least 3-4 hours, blood volume, hemodynamics and tissue oxygen supply will be improved, as well as blood rheological indices due to hemodilution, reduced erythrocyte aggregation, decreased hematocrit and blood viscosity. Thus, the circulation and microcirculatory system will be improved.
Use: Therapeutic hemodilution
Usage: Infusion rate: 250ml within 0,5-2 hours; 500ml within 4-6 hours; 2×500ml within 8-24 hours. for therapeutic hemodilution, 10 days of treatment is recommended.
Precautions: Patients often develop a refractory pruritus with prolonged medium and high dose infusions of this product. Contraindications: severe congestive heart failure (cardiac insufficiency); renal failure (serum creatinine >2mg/dl or >177μmol/l); severe coagulation disorders (but still considered in life-threatening acute cases); fluid overload (excessive hydration) or severe fluid deficiency (dehydration); cerebral hemorrhage; starch allergy
III. Anti-platelet aggregation drugs
1. Aspirin (Aspirin)
Pharmacological effects: acetylation of platelet cyclooxygenase (i.e. prostaglandin synthase), thereby reducing the generation of thromboxane A2 (TXA2) and producing irreversible inhibition of TXA2-induced platelet aggregation.
Uses: Prevention of cerebral infarction after transient reduction of blood flow to the brain (TIA: transient ischemic attack) and after early symptoms have already appeared (e.g. transient paralysis of facial or arm muscles or transient blindness).
Dosage: It should be taken with warm water after meals, not on an empty stomach. This product is an enteric tablet and must be swallowed whole. 100mg Qd.
Precautions: Common side effects are gastrointestinal reactions such as abdominal pain and slight bleeding from the gastrointestinal tract, occasional nausea, vomiting and diarrhea. Gastric bleeding and gastric ulcers as well as allergic reactions (dyspnea and skin reactions), mainly in asthmatic patients, are extremely rare.
2. Clopidogrel (Clopidogrel)
Pharmacological effects: Inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the secondary ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thus inhibiting platelet aggregation. Clopidogrel must be biotransformed to inhibit platelet aggregation.
Uses: Prevention of atherosclerotic thrombosis in patients with ischemic stroke (from 7 days to <6< span="">months).
Dosage: 75 mg Qd with or without food.
Precautions: Discontinue clopidogrel more than 7 days before surgery. Clopidogrel is not recommended for patients with acute ischemic stroke (within 7 days). Contraindications: Severe liver damage.
IV. Anticoagulation and thrombolytic drugs
1.Low-Molecular-Weight Heparin Calcium
Pharmacological effect: 1ml of low molecular heparin is equivalent to 9500 IU of anticoagulant factor Xa. It has high anticoagulant factor Xa and low anticoagulant factor IIa or antithrombin activity. Does not prolong bleeding time. At prophylactic doses, does not significantly alter APTT.
Uses: Prophylaxis and treatment of thromboembolic disease or thrombosis.
Usage: Prevention of thrombosis 0, 4ml Qd.
Precautions: This drug is generally not indicated in the following conditions: severe renal impairment, hemorrhagic cerebrovascular accident, uncontrolled hypertension. It should not be used together with the following drugs in general: acetylsalicylic acid (analgesic, antipyretic doses), non-steroidal anti-inflammatory analgesics, dextran, ticlopidine. In patients on low-molecular heparin, there is also a risk of severe heparin-induced or immune-related thrombocytopenia and occasionally thrombosis. These conditions usually occur between days 5 and 21 of treatment (most likely on day 10).
2. Warfarin (Warfarin)
Pharmacological action: bicoumarin-like medium-acting anticoagulant. Its mechanism of action is to compete against the action of vitamin K, inhibit the synthesis of coagulation factors in hepatocytes, and also has the effect of reducing the thrombin-induced platelet aggregation reaction.
Uses: It can prevent the formation and development of thrombosis and is used for the treatment of thromboembolic diseases; it can be used prophylactically in patients with previous thromboembolic disease and those at risk of postoperative thrombotic complications.
Dosage: 3-4mg for the first 3 days of oral administration (half dose for the elderly, frail and diabetic patients), and 2,5-5mg for the maintenance dose after 3 days (the dose can be adjusted with reference to the clotting time so that the INR value reaches 2-3).
Precautions: Contraindicated in patients with hepatic or renal impairment, severe hypertension, coagulation disorders with bleeding tendency, active ulcers, trauma, pre-eclampsia, recent surgery. Contraindicated during pregnancy. It should be used with caution in the elderly or during menstruation.
3. Alteplase
Pharmacological effects: A glycoprotein that exhibits a relatively inactive state in the circulatory system when given intravenously. Once combined with fibrin, it is activated and induces the conversion of fibrinogen into fibrinolytic enzymes, leading to fibrin degradation and clot lysis.
Uses: Acute myocardial infarction, acute pulmonary embolism, acute ischemic stroke.
Dosage and Administration: Dissolve (10, 20 or 50 mg) with water for injection to a concentration of 1 mg/ml or 2 mg/ml under aseptic conditions (14). Acute ischemic stroke: The recommended dose is 0, 9 mg/kg body weight (maximum dose is 90 mg), 10% of the total dose is first pushed intravenously and the remaining dose is continued intravenously over the next 60 minutes.
Precautions: Aspirin or intravenous administration of heparin should be avoided for up to 24 hours after treatment with this product. The most common adverse reaction is bleeding, which can result in a decrease in erythrocyte ratio and/or hemoglobin. Contraindicated: severe stroke as assessed by clinical (NIHSS > 25) and/or imaging studies; stroke attack accompanied by seizure; platelet count less than 100 x 109/L; blood glucose less than 50 mg/dl or more than 400 mg/dl.
V. Cerebral vasodilator drugs
1.Nimodipine
Pharmacological effects: It is a second generation dihydropyridine calcium antagonist. It is used to prevent cerebral vasospasm. Recent studies have shown that it has the effect of protecting neurons.
Uses: Prevention and treatment of ischemic neurological injury due to cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Treatment of age-related brain dysfunction, such as: memory loss, disorientation and concentration disorders and mood swings.
Usage: 1. Aneurysmal subarachnoid hemorrhage: Treatment with nimodipine injection for 5-14 days, followed by nimodipine tablets, 60 mg (2 tablets) each time, 6 times daily for 7 days. A small amount of water was used to deliver the complete tablet, independent of the meal. The interval between consecutive doses is not less than 4 hours.
2. Geriatric brain dysfunction: 30mg Tid.
Precautions: In severe hepatic dysfunction, especially cirrhosis, the efficacy and side effects, especially the decrease in blood pressure, will be more pronounced due to the decrease in first pass effect and the decrease in metabolic clearance, leading to the increase in bioavailability of nimodipine. In such cases, appropriate dose reduction according to blood pressure and, if necessary, treatment interruption should also be considered. The combination of nimodipine with rifampicin significantly reduces the efficacy of nimodipine and therefore the combination of nimodipine with rifampicin is prohibited. The combination of oral nimodipine with the antiepileptic drugs phenobarbital, phenytoin or carbamazepine significantly reduces the efficacy of nimodipine and is therefore prohibited.
Anti-epileptic drugs
1.Carbamazepine
Pharmacological effects: Stabilize overexcited nerve cell membranes, inhibit repeated neural discharges, and reduce the transmission of excitatory impulses at synapses.
Uses: Epilepsy; treatment of acute mania, preventive treatment of bipolar disorder; trigeminal neuralgia and primary trigeminal neuralgia due to multiple sclerosis, and primary glossopharyngeal neuralgia; pain due to diabetic neuropathy.
Dosage: Initial dose 100-200mg (half tablet-1 tablet) per dose, Qd~Bid; gradually increase the dose until optimal efficacy [usually 400mg (2 tablets) per dose, Bid~Tid].
Precautions: contraindications: severe hepatic insufficiency; avoid combining carbamazepine (structurally similar to tricyclic antidepressants) with monoamine oxidase inhibitors (MAOIs); discontinue monoamine oxidase inhibitors for at least two weeks prior to taking carbamazepine, or longer if clinical condition permits.
2.Sodium Valproate
Pharmacological effects: Broad-spectrum antiepileptic drug, mainly acting on the central nervous system. May be related to increase the concentration of γ-aminobutyric acid.
Uses: Treatment of generalized and partial epilepsy.
Dosage: The general dose is 20-30mg/kg, however, when seizures cannot be controlled with this dose range, it can be further increased to an adequate dose. If the patient’s daily dosage exceeds 50 mg/kg, the patient should be carefully monitored.
Precautions: May potentiate the effects of nerve blockers, monoamine oxidase inhibitors, antidepressants, and benzodiazepines. class effects. Contraindications: acute and chronic hepatitis.
VII. Antidepressants and anxiety drugs
1.Fluoxetine (Fluoxetine)
Pharmacological effects: inhibit the re-uptake of 5-HT in central neurons.
Uses: depressive episodes; obsessive-compulsive disorder; bulimia nervosa.
Dosage: 20mg/day, can gradually increase the dose to reach the maximum dose of 60mg.
Precautions: Common adverse reactions include insomnia, nausea, agitation, headache, motor anxiety, nervousness, tremor, loss of appetite or hypogonadism occurring with long-term use of the drug.
2, Citalopram (Citalopram)
Pharmacological effects: selective 5-hydroxytryptamine uptake inhibitor.
Use: Depressive psychiatric disorders (endogenous and non-endogenous depression).
Dosage: Starting dose 20mg/day, which can be increased to 40mg/day or maximum dose 60mg/day if clinically indicated. maximum dose 40mg/day for patients over 65 years of age. Generally it takes 4-6 months for manic-depressive psychosis.
Precautions: The most common side effects are: nausea, increased sweating, decreased salivation, headache and shortened sleep duration. They are usually more obvious at the beginning of the 1st or 2nd week of treatment, and generally disappear gradually as the depressive state improves.
3.Paroxetine
Pharmacological effects: Selective 5-hydroxytryptamine uptake inhibitor.
Uses: depression, obsessive-compulsive neurosis, panic disorder
Dosage: Oral, recommended to be taken daily at breakfast, tablets swallowed intact without chewing. The usual dose is 20mg/day. After 2 to 3 weeks of administration, depending on the patient’s response, some patients may need to increase the dose by 10mg per week, with a maximum of 50mg per day according to overseas experience.
Caution: It is generally not advisable to stop the drug suddenly. The dose should be gradually reduced at weekly intervals, with the daily dose of each week reduced by 10mg compared to the daily dose of the previous week, and the dose should be reduced once a week. Due to severe renal impairment (creatinine clearance <30ml/min) or severe hepatic impairment, the blood concentration of this product is higher after taking this product than healthy people. Therefore, the recommended dose is 20 mg/day, and if an increase in dose is needed, it should be limited to the lower limit of the dosing range.
Anti-Parkinsonian drugs
1. Dobutamine (Levodopa and Benserazide Hydrochloride)
Pharmacological effects: Levodopa can cross the blood-brain barrier into the center, as a direct metabolic precursor of dopamine, it makes dopamine replacement therapy feasible. Benserazide inhibits the decarboxylation of levodopa outside the brain.
Uses: Parkinson’s disease, symptomatic Parkinson’s syndrome (post-encephalitis, atherosclerotic or toxic), but not drug-induced Parkinson’s syndrome.
Dosage: The first recommended dose is 1/2 tablet of Medroba per dose, Tid. thereafter the daily dose is increased by 1/2 tablet per week. Until a therapeutic amount appropriate for the patient is reached.
Precautions: This drug is contraindicated in patients with severe endocrine, renal, hepatic and cardiac disease, psychiatric and severe psychoneurological disorders. medroxyprogesterone should not be taken by patients under 25 years of age or by pregnant women.
2.Carbidopa and Levodopa
Pharmacological effects: Levodopa is used to relieve the symptoms of Parkinson’s disease by decarboxylating to form dopamine in the brain. Carbidopa cannot pass the blood-brain barrier and only inhibits the decarboxylation of peripheral levodopa, thus allowing more levodopa to enter the brain and subsequently be converted into dopamine, thus avoiding frequent high doses of levodopa.
Uses: Primary Parkinson’s disease; post-encephalitis Parkinson’s syndrome; symptomatic Parkinson’s syndrome (carbon monoxide or manganese poisoning); patients with Parkinson’s disease or Parkinson’s syndrome taking vitamin preparations containing pyridoxine (vitamin B6); end-of-dose worsening of previous treatment with levodopa/decarboxylase inhibitor combinations or levodopa alone.
Dosage: The recommended starting dose of 50/200 is one tablet two to three times daily. The starting dose of levodopa should not be higher than 600 mg per day or taken no shorter than 6 hours apart.
Precautions: The most common adverse reaction is dyskinesia (an abnormal involuntary movement). Non-selective monoamine oxidase (MAO) inhibitors should not be taken concurrently with this product. Use of these inhibitors must be discontinued at least two weeks prior to initiation of treatment with this product. This product may be used in combination with a selective B-type monoamine oxidase inhibitor (e.g., Slegiline hydrochloride) at the manufacturer’s recommended dose. It is contraindicated in patients with known hypersensitivity to any component of this drug and in patients with angle-closure glaucoma. Because levodopa may activate malignant melanoma, it is contraindicated in patients with suspected skin lesions or a history of melanoma.
The “three elements”
Vitamins, hormones and antibiotics.
Botulinum toxin treatment
1. Mechanism of action: Botulinum toxin type A is an exotoxin produced by Gram-positive Clostridium perfringens in the process of reproduction, which can selectively bind to cholinergic nerve endplates, cleave synaptic-associated protein (SNAP-25) and inhibit muscle contraction. At present, botulinum toxin injection treatment (facial spasm, eyelid spasm, etc.) can be effective quickly, and the side effects are small, such as blurred vision, droopy eyelids and other side effects will recover on their own after a certain period of time, so botulinum toxin injection treatment is gradually becoming the first choice for the treatment of related diseases, and its safety has been recognized by the FDA.
Clinical indications: facial muscle spasm, eyelid spasm, spastic squint, strabismus, chronic daily headache, neuropathic pain comprehensive facial muscle, spastic dysphonia, local muscle dystonia, muscle ankylosis caused by central nerve injury and cosmetic wrinkle removal, etc.
3.Injectable drug and injection method: BOTOX, produced by GlaxoSmithKline, the specification is 100U/stem Injection method: 0.9% saline diluted to 2.5U of botulinum toxin type A per 0.1ml, inject the drug directly into the orbicularis oculi muscle or the corresponding area under the skin with a 1ml skin test syringe and a 4 or 5 needle. The injection site and the dose of the drug are selected according to the size of the affected muscle and the degree of spasm. The dose of the drug is usually not more than 5,0 U at one injection site and the initial treatment dose is not more than 25 U per eye, and the effect usually starts within 3 days after injection and reaches its peak in 1-2 weeks. The efficacy of each treatment is maintained for 3-4 months, after which treatment can be repeated as needed. If the initial treatment dose is considered insufficient for repeat treatment, the injection dose may be increased.