I. Classification of anti-glaucoma drugs
1.IOP-lowering drugs
2.Proposed parasympathomimetic drugs
3.Sympathomimetic drugs (epinephrine-like drugs)
4.Anti-adrenergic drugs (adrenergic receptor blockers)
5.Carbonate glucosidase inhibitors
6, hypertonic agents
Second, the proposed parasympathomimetic drugs
Divided into two groups, a group of cholinergic simulants (such as maurobamate), a group of anticholinesterase drugs, and divided into reversible (such as toxic lentil, neostigmine) and irreversible cholinesterase inhibitors (such as iodophosphine). All act on M-choline receptors and cause contraction of the pupillary sphincter and ciliary muscle.
They are divided into two groups, one for cholinergic mimetics (e.g., maurobamate) and one for anticholinesterase agents, which are subdivided into reversible (e.g., toxaprine, neostigmine) and irreversible cholinesterase inhibitors (e.g., iopromide). All act on M-choline receptors and cause contraction of the pupillary sphincter and ciliary muscle.
(i) Pilocarpine
1. Mechanism of action
(1) For closed-angle glaucoma, the main effect is to reduce the accumulation of iris root, open the atrial angle and increase the outflow of atrial fluid;
(2) For open-angle glaucoma, it is believed that the contraction of the ciliary muscle, which pulls open the scleral prominence, changes the trabecular structure and the morphology of Schlemn’s canal; the trabecular meshwork enlarges and increases the atrial aqueous drainage; at the same time, the contraction of the ciliary muscle reduces the blood supply to the anterior ciliary artery that travels between them.
2.Clinical application
Physical properties: commonly used its nitrate, easily soluble in water and lipid, because of biphasic solubility, so the corneal penetration is good, the utilization of the drug is high. Concentration of 0.5% to 4%, commonly used concentrations of 1% and 2%, topical application of 10-15 minutes after the onset of effect, 60 minutes intraocular pressure decreased significantly, can last for 4-8 hours, generally 2-6 times a day point drug. Dosage form: Maohuoyunxianine slow-release film, Maohuoyunxianine gel.
Application in different stages of acute closed glaucoma, chronic closed-angle glaucoma and open-angle glaucoma. Use of tragacanthine induces ciliary ring block glaucoma: In closed-angle glaucoma with anatomical features such as small cornea, short eye axis and shallow anterior chamber, the use of this drug can induce ciliary ring block glaucoma.
3.Side effects
Local side effects: Regulatory myopia is the most common side effect. Others such as long-term use produce tonic pupil narrowing, post-pupillary adhesion; iris and ciliary body congestion; cataract; retinal detachment, etc. In addition, it can cause conjunctival congestion, superficial keratitis, etc.
Systemic side effects: less frequent. There may be manifestations of parasympathetic excitation, such as headache, supraorbital nerve pain, nausea, vomiting, sweating, shortness of breath, bradycardia, and emotional restlessness.
Sympathomimetic drugs (epinephrine-like drugs)
Adrenaline-like drugs
Acting on α-receptors (such as norepinephrine, neofulvin, etc.)
Acts on a- and beta-receptors (e.g., epinephrine, diphenhydramine, etc.)
Acts on β-receptors (e.g., isoprenaline, etc.)
Adrenaline
1, mechanism of action: its antihypertensive mechanism needs to be further elucidated. There are the following theories.
(1) It is generally believed that epinephrine can act directly or indirectly on the ciliary body epithelial cells to inhibit their secretion of atrial fluid;
(2) It is possible that the rate of atrial fluid elimination is improved by prostaglandins or other metabolites of the adenylate cyclase pathway;
(3) Removal of viscous protein material from the trabecular meshwork, resulting in increased permeability of the trabeculae.
2.Physical properties: This drug has very poor stability and is easily oxidized when exposed to light, heat or air, therefore, it has been replaced by dipivoxil. The preparation is 1% or 2% eye drops, which can significantly lower the pressure within 1 hour after dosing, and still maintain a good hypotensive effect up to 12 hours, 1~2 times a day.
3, clinical application: mainly used for open-angle glaucoma and closed-angle glaucoma after surgery.
4, side effects: conjunctival congestion, blepharoconjunctivitis, foreign body sensation, burning sensation, eye pain, headache, temporary blurred vision, etc.; systemic may appear, tachycardia, increased blood pressure, irregular heart rate, pallor, etc.
Fourth, anti-adrenergic drugs (adrenergic receptor blockers)
There are two types of drugs: α-blockers and β-blockers. The latter is mainly talked about.
β-blockers are a kind of drugs developed in the early 1960s for the treatment of cardiovascular diseases, mainly used for the treatment of angina pectoris, arrhythmia, hypertension, etc. The introduction of ophthalmic dotted-eye preparations after 1967 has made a breakthrough in the pharmacological treatment of ophthalmic glaucoma.
(I) β-blockers
1. Common features of β-blockers.
(1) Local spotting of the eye can cause a significant decrease in intraocular pressure;
(2) The effect is long-lasting, lasting 12 to 24 hours, and the eye can be ordered once or twice a day;
(3) It does not cause spasm of ciliary muscle or change in pupil size;
(4) Mechanism of lowering pressure: It is mainly through the inhibition of atrial aqueous production to lower IOP. The mechanism of inhibition of atrial aqueous production is not clear.
(5) Side effects: The function of β-receptor effectors is inhibited. The main effects are on the cardiovascular system and respiratory system. The cardiovascular system manifests as: bradycardia, slowed pulse, decreased blood pressure, atrioventricular block, etc.; respiratory system: bronchospasm, asthma attacks, etc. Local side effects of the eye include: local irritation symptoms, congestion, punctate keratitis, etc.
(6) Indications are open-angle glaucoma and high intraocular pressure, but can also be used after closed-angle glaucoma surgery, or in combination with other types of secondary glaucoma.
(7) Drug resistance: The phenomenon of “drift” or “escape” of timolamide has been reported for a long time, and whether other β-blockers have this phenomenon needs further study.
(8) Combination of drugs: The combination of β-blockers with vincristine and trigonelline can further reduce IOP.
V. Carbonic acid glycosidase inhibitors
Acetazolamide (acetazolamide)
1.Mechanism of action.
(1) Acetazolamide acts directly on the carbonic acid glycosidase in the ciliary body epithelium to inhibit its activity, which reduces the secretion of atrial fluid and thus lowers the IOP;
(2) When carbonic acid glycosidase is inhibited, the osmotic pressure of atrial fluid is reduced and less water enters the eye from the blood, resulting in a decrease in intraocular pressure;
(3) At the renal tubules, the exchange of Na and H ions is reduced, and the reabsorption of Na and HCO3 ions is decreased, causing diuretic effects. Acetazolamide can reduce atrial water production by 50% to 60%.
2.Clinical application.
Generally used for glaucoma acute attack, the first oral dose of 500mg, 2-4 hours to produce the maximum IOP lowering response, at least 6 hours, to be stable IOP, reduce the amount to 125-250mg, 2-3 times a day, and then gradually reduce the amount. Acetazolamide sodium salt can also be injected intravenously, once the amount of 500mg, 30 minutes ~ 4 hours to show the maximum hypotensive response.
3, side effects: mainly manifested as systemic side effects.
(1) Electrolyte balance disorder: due to the reduction of K ion, Na ion and HCO3 ion reabsorption, easily produce metabolic acidosis and hypokalemia, manifested as, general weakness, limb paralysis, nausea and vomiting, abdominal distension, etc. Therefore, patients with poor renal function should be cautious.
(2) Urinary stones: Due to metabolic acidosis, the citrate excretion in the urine is reduced, resulting in easy precipitation of calcium ions and the formation of calcium phosphate crystals and urinary stones.
(3) Neurological symptoms: common are abnormal sensation, such as numbness at the ends of the hands and feet, face and corners of the mouth, ankylosis; loss of appetite, a few symptoms such as tinnitus and vertigo.
(4) Atopic reactions: including bone marrow suppression, exfoliative dermatitis, allergic nephritis, etc. If long-term application, attention should be paid to prevent the above side effects, such as attention to potassium supplementation, low-calcium diet, sulfonamide allergy is not used or used with caution (because acetazolamide is a derivative of sulfonamide); attention should be paid to supplement NaHCO3.
Sixth, hypertonic agents
The mechanism of action of hypertonic agents: after the application of hypertonic agents, hypertonic diuretic effect is produced, so that the osmotic pressure of plasma increases, and the intraocular tissues are in a hypotonic state, so that water is discharged from the eye into the blood vessels, and the intraocular pressure decreases.
(i) Glycerine
The dosage is 1~2g/Kg body weight, the concentration of preparation is 50%, 120ml/bottle, the hypotension starts 10 minutes after oral administration, the effect is most obvious in 30 minutes, and can be maintained for 4~6 hours, with fast absorption, fast action and great safety. It is generally preferred as the clinical hypertonic drug.
Note: Glycerol is converted into glucose in the liver and is involved in glucose metabolism, and is contraindicated in diabetic patients.
(ii) mannitol
1, clinical application: 1 ~ 2g/Kg body weight, generally with 20% solution 250 ~ 500ml (50 ~ 100g), rapid intravenous drip (3 ~ 10ml/min), generally within 30 ~ 60 minutes after the static point. The IOP drops significantly in 20-30 minutes and reaches the lowest level in 1-2 hours, and the effect can last for 3-4 hours.
2. Precautions.
(1) Use with caution in cardiac and renal insufficiency; especially when long-term use is required, electrolyte disorders and hypokalemia are likely to occur, so pay attention to timely replenishment of potassium ions to prevent cardiac, cerebral and vascular accidents.
(2) Use with caution in diabetes mellitus (although it does not participate in glucose metabolism, it will itself be osmotic diuretic);
(3) If the injection speed is too fast, it can produce injection site pain, transient headache, blurred vision, vertigo, and brain herniation in severe cases; therefore, it is better to let the patient lie flat for infusion.
(4) It is easy to form crystals when the temperature is low, so it should be used after the crystals are melted by heating.