Eye drops for glaucoma

Pharmacodynamics and pharmacokinetics

Pharmacodynamics

Aceclidine is a stimulator of M-cholinergic receptors . It is a tertiary amine , therefore it penetrates the BBB . The mechanism of action is associated with the stimulation of M-cholinergic receptors in neurons of various organs of the heart, intestinal and bronchi muscles, eyes, and sweat glands. Causes miosis and flattening of the iris, which improves the outflow of intraocular fluid and reduces intraocular pressure . Causes a spasm of accommodation ( myopia ). Increases salivary secretion, sweating, lacrimation and bronchial mucus. In high doses, it slows down the heart rate, inhibiting the conduction of impulses and causes bronchospasm , stimulating contraction of the bronchial muscles.

Strengthens intestinal motility, increases the tone of the gallbladder and bladder, while reducing the tone of the sphincters. It is used for glaucoma , atony of the bladder and intestines, promoting their emptying.

Pharmacokinetics

Features high absorption. Easily absorbed through various routes of administration - subcutaneous and when instilled into the eye.

Aceclagin®

The simultaneous use of Aceclagin® and other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, should be avoided.

Adverse events can be minimized by using the lowest effective dose and reducing the duration of treatment needed to control symptoms.

Effect on the gastrointestinal tract

Bleeding, ulcers or perforation of the gastrointestinal tract with a fatal outcome were observed when taking any NSAIDs during any period of treatment, both in the presence of corresponding symptoms and a history of serious gastrointestinal diseases (peptic ulcer of the stomach and duodenum, Crohn's disease, ulcerative colitis, etc.), and and without them. The risk of bleeding, ulceration, and gastrointestinal perforation increases with increasing doses of NSAIDs in patients with a history of peptic ulcers, especially those accompanied by bleeding or perforation, and in elderly patients. These patients should take the minimum effective dose of the drug. Combination therapy with protective drugs (eg, misoprostol or proton pump inhibitors) should be considered. Such treatment is necessary for patients who take small doses of aspirin or other drugs that negatively affect the gastrointestinal tract.

Patients with gastrointestinal diseases, including the elderly, should report any unusual symptoms associated with the gastrointestinal tract (especially bleeding), including when initially taking the drug. Particular caution should be exercised in patients concomitantly taking drugs that may increase the risk of bleeding or ulceration, such as: systemic corticosteroids, anticoagulants (such as warfarin), selective serotonin reuptake inhibitors or antiplatelet agents (such as acetylsalicylic acid).

If gastrointestinal bleeding or ulcers occur in patients taking Aceclagin®, treatment should be discontinued.

Cases of drug-induced pancreatitis are rare. However, cases of pancreatitis have been reported in association with NSAID use.

Effects on the cardiovascular and central nervous system

Patients with arterial hypertension and/or mild or moderate congestive heart failure require appropriate monitoring, since fluid retention and edema are associated with the use of NSAIDs. Aceclofenac is structurally close to diclofenac and has similar metabolism. With regard to diclofenac, there is evidence indicating an increased risk of thromboembolic complications (for example, myocardial infarction or stroke, particularly with long-term treatment with high doses). There is also an increased risk of developing acute coronary syndrome associated with aceclofenac. Patients with chronic heart failure (class I according to the New York Heart Association classification) and patients with risk factors for developing complications from the cardiovascular system (for example, arterial hypertension, diabetes mellitus, smoking) should begin treatment with aceclofenac only after an informed decision by the physician. Cardiovascular risks may depend on the dose and duration of treatment, so the drug should be prescribed at the lowest effective dose and for the shortest possible period of time.

Effect on the liver and kidneys

Taking NSAIDs can cause a dose-dependent decrease in prostaglandin formation and acute renal failure. The importance of prostaglandins in maintaining renal blood flow should be taken into account when taking Aceclagin® in patients with impaired cardiac, renal or hepatic function, in patients receiving diuretics or in patients after surgery, as well as in elderly patients. Caution should be exercised when using Aceclagin® in patients with mild or moderate hepatic and renal dysfunction, as well as in patients with other conditions predisposing to fluid retention in the body. In such patients, the use of NSAIDs can lead to impaired renal function and fluid retention. In patients taking diuretics and those at increased risk of hypovolemia, caution should also be exercised when taking Aceclagin®. It is necessary to use the minimum effective dose and regular medical monitoring of kidney function. Adverse renal events usually resolve after discontinuation of aceclofenac. Aceklagin® should be discontinued if changes in liver function tests persist or worsen, clinical signs or symptoms of liver disease develop, or other manifestations occur (eosinophilia, skin rash). Hepatitis can develop without prodromal symptoms.

The use of NSAIDs in patients with hepatic porphyria may precipitate an attack.

Hypersensitivity and skin reactions

Like other NSAIDs, aceclofenac can cause allergic reactions, including anaphylactic/anaphylactoid reactions, even when aceclofenac is taken for the first time. Severe skin reactions (some of which can be fatal), including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been very rare after taking NSAIDs. The highest risk of these reactions occurring in patients is observed at the beginning of taking aceclofenac, and the development of these adverse reactions is observed during the first month of taking aceclofenac. If skin rash, damage to the oral mucosa or other signs of hypersensitivity occur, you should stop taking Aceclagin®.

In some cases, chickenpox can cause skin and soft tissue infections.

At present, the role of NSAIDs in worsening the course of these infections cannot be ruled out. Therefore, you should avoid taking Aceclagin® for chickenpox.

Hematological disorders

Aceclofenac may cause reversible inhibition of platelet aggregation.

Respiratory system disorders

Caution should be exercised when taking Aceclagin® in patients with bronchial asthma (including a history of asthma), since taking NSAIDs can trigger the development of sudden bronchospasm in such patients.

Elderly patients

Caution should be exercised when taking Aceclagin® in elderly patients, as they are more likely to experience side effects (especially bleeding and perforation of the gastrointestinal tract) when taking NSAIDs. Complications can be fatal. Older patients are also more likely to suffer from kidney, liver or cardiovascular diseases.

Long-term use

All patients receiving long-term treatment with NSAIDs should be closely monitored (eg, complete blood count, liver function tests, and renal function tests).

Due to the antiprostaglandin properties of NSAIDs, caution should be advised in women taking mifepristone, as concomitant use with NSAIDs could theoretically reduce the effectiveness of the drug. Clinical significance unknown.

Aceclidine, instructions for use (Method and dosage)

It is administered subcutaneously. The highest single dose is 4 mg.

For atony of the intestines, bladder, stomach, uterus - 1-2 ml of solution. If necessary (in case of insufficient effect), repeat injections are performed twice after 20 minutes.

Preparation for x-ray examination. To diagnose achalasia , administer 1 ml 15 minutes before taking a barium suspension . To diagnose gastric motility disorders after an X-ray examination, 1 ml of solution is used, the patient drinks an additional portion of barium suspension and a repeat examination is done 15 minutes later.

In ophthalmology, drops of different percentages of the active substance are prescribed, prepared according to a prescription in a pharmacy from powder. Instillation is carried out 3 to 6 times a day. After a single instillation, the hypotensive effect is observed for up to 6 hours.

When instilling, it is necessary to press the area of ​​the lacrimal sac for several minutes so that the solution does not flow into the nasal cavity through the lacrimal canal.

Linezolid (Linezolidum)

In an open-label study of critically ill patients with intravascular catheter-associated infections, there was an excess of mortality in patients receiving linezolid compared with patients receiving vancomycin/dicloxacillin/oxacillin [78/363 (21.5%) vs 58/363 (16.0%). %)].

The main factor influencing mortality was the gram-positive pathogen at the initial stage. The mortality rate was similar among patients whose infections were caused only by gram-positive organisms, but was significantly higher in the linezolid group when other organisms were also detected or were not initially detected. The greatest imbalance was noted during treatment and within 7 days after the end of antibiotic therapy. During the study, more patients in the linezolid group acquired gram-negative organisms and subsequently died from gram-negative or polymicrobial infections. Therefore, for complicated skin and soft tissue infections, linezolid should be used in patients with known or possible co-infection with Gram-negative organisms only if no alternative treatment options are available. In these cases, additional use of drugs acting on gram-negative microflora is simultaneously indicated.

In some patients taking linezolid. Reversible myelosuppression (with anemia, thrombocytopenia, leukopenia and pancytopenia) may develop, depending on the duration of therapy. Older patients are also at increased risk of developing this condition. Thrombocytopenia occurred more often in patients with severe renal failure, regardless of the patient's use of hemodialysis. In this regard, during treatment it is necessary to monitor blood counts in patients with an increased risk of bleeding, a history of myelosuppression, as well as with simultaneous use of drugs that reduce hemoglobin or platelet count and/or their functional properties, with severe renal failure, as well as in patients receiving linezolid for more than 2 weeks. Linezolid is used in such patients only when close monitoring of hemoglobin, white blood cell and platelet counts is possible. If significant myelosuppression develops during linezolid therapy, treatment should be discontinued unless continued therapy is considered absolutely necessary. In this case, intensive monitoring of blood counts and appropriate treatment are necessary. In addition, it is recommended that blood tests (including hemoglobin, platelet count, and white blood cell count (with leukocyte count calculation)) be performed weekly in patients receiving linezolid, regardless of baseline blood test values. A higher incidence of severe anemia was observed in patients receiving linezolid for more than the maximum recommended duration of 28 days. These patients required blood transfusions. Cases of sideroblastic anemia have been reported in the post-marketing period. In most cases, the duration of linezolid therapy exceeded 28 days. In most patients, manifestations were completely or partially reversible after discontinuation of linezolid treatment with or without specific anemia treatment. In patients taking antibacterial drugs, including linezolid, the risk of developing pseudomembranous colitis of varying severity should be considered.

About cases of diarrhea associated with Clostridium difficile,

has been reported in association with the use of virtually all antibacterial drugs, including linezolid.
The severity of diarrhea can range from mild to severe. Treatment with antibacterial drugs disrupts the normal intestinal flora, leading to overgrowth of Clostridium difficile.
Clostridium difficile produces toxins A and B, which lead to Clostridium difficile-associated diarrhea
.
Excessive amounts of toxins produced by
Clostridium difficile
may cause increased mortality in patients, as such infections may be resistant to antimicrobial therapy and may require colonectomy. Do not use medications that inhibit intestinal motility.

Clostridium difficile- associated diarrhea

should be considered in all patients with diarrhea following antibiotic use.
Close medical observation for 2 months is necessary for patients who experience diarrhea associated with Clostridium difficile
after administration of antibacterial drugs. If symptoms of deterioration in visual function appear, such as changes in visual acuity, changes in color perception, blurred vision, visual field defects, it is recommended to immediately consult an ophthalmologist for consultation. Visual function should be monitored in all patients taking linezolid long-term (more than 28 days) and in all patients with new-onset symptoms of visual impairment, regardless of the duration of therapy. In the event of development of peripheral neuropathy and optic neuropathy, the risk/benefit ratio of continuing linezolid therapy in these patients should be assessed. The risk of developing neuropathy is higher if linezolid is used in patients who are currently using or who have recently taken antimycobacterial drugs to treat tuberculosis.

Lactic acidosis has been reported in association with linezolid use. Patients who experience repeated nausea or vomiting, abdominal pain, unexplained acidosis, or a decrease in bicarbonate anion concentrations while taking linezolid require careful monitoring by a physician. Linezolid inhibits mitochondrial protein synthesis. Side effects such as lactic acidosis, anemia, and neuropathy (peripheral or optic) may result from this inhibition; these effects are more common when the drug is used for more than 28 days.

Convulsions have been reported in patients taking linezolid, with most cases having a history of convulsions or risk factors for their development. Patients should obtain a detailed history regarding previous episodes of seizures.

If it is necessary to use the drug in combination with selective serotonin reuptake inhibitors, patients should be constantly monitored to identify signs and symptoms of serotonin syndrome, such as impaired cognitive function, hyperpyrexia, hyperreflexia and impaired motor coordination. If these symptoms appear, one or both medications should be discontinued. When you stop taking a serotonergic drug, withdrawal symptoms may occur.

Cases of reversible superficial discoloration of tooth enamel have been reported with the use of linezolid. These discolorations were removed by professional teeth cleaning.

Cases of symptomatic hypoglycemia have been reported in patients with diabetes mellitus receiving linezolid concomitantly with insulin or hypoglycemic agents. Although a cause-and-effect relationship between the use of linezolid and the development of hypoglycemia has not been established, patients with diabetes mellitus should be warned about the possibility of developing hypoglycemia. If hypoglycemia occurs, dose adjustment of insulin/hypoglycemic drugs or discontinuation of linezolid is necessary. Patients should be advised not to consume large quantities of foods containing tyramine (such as red wine, old cheese, some alcoholic beverages, smoked meats).

There have been no clinical studies examining the effect of linezolid on the normal microflora of the human body. The use of antibacterial drugs can sometimes lead to increased growth of microorganisms that are resistant to it. Clinical studies have shown that approximately 3% of patients receiving recommended doses of linezolid developed antibiotic-associated candidiasis. If superinfection occurs while taking linezolid, appropriate medical measures should be taken. Clinical researches

The safety and effectiveness of linezolid for more than 28 days have not been established. Controlled clinical trials did not include patients with diabetic foot syndrome, pressure ulcers or ischemic disorders, severe burns or gangrenous lesions. Thus, experience with linezolid in the treatment of these conditions is limited.

Types of drops that reduce intraocular pressure

Drops for the treatment of glaucoma are produced in large quantities. Each of them contains certain drugs, which can be divided into several groups:

1. Based on the active component, beta blockers, prostaglandins, cholinomimetics, etc. are distinguished.
2. According to the mechanism for eliminating intraocular hypertension, there are drugs that reduce the synthesis of aqueous humor, drugs that improve its outflow, and combined drugs.

Prostaglandin analogues

Prostaglandins are the safest and most effective agents for the treatment of glaucoma. 2 hours after instillation of this group of medications, the pressure inside the eye begins to decrease, and the maximum effect is observed after 12 hours.

This group of drugs includes Travatan, Tafluprost, Xalatan. All of them appeared relatively recently, but due to their high efficiency and duration of action (up to 24 hours), these drugs have become very popular in the treatment of patients with glaucoma.

Prostaglandins help restore the outflow of aqueous humor through additional pathways. However, these drugs also have some side effects. These include:

• Temporary redness of the eyes as a result of an increase in the diameter of the superficial arteries;
• Changes in the color of the iris due to pigment accumulation;
• Stimulates the growth of eyelash hairs; they also darken and become thicker (this effect is sometimes beneficial and can be used for cosmetic purposes).

Beta blockers

The mechanism of action of beta blockers is to reduce the synthesis of aqueous humor. They begin to act half an hour after instillation, and the effect reaches its maximum after about 2 hours. The frequency of use is higher than that of prostaglandins (usually 2 times a day), which is less convenient for the patient. Often, beta blockers for the treatment of glaucoma are combined with prostaglandins to increase the effectiveness of therapy.

There are a large number of eye drops belonging to this group (Timolol, Okumol, Arutimol, Okumed, Okupress, etc.). The active substance used in the drops is usually the same, so they are all interchangeable.

Beta blockers can have negative effects on body systems, such as causing bradycardia or bronchospasm. Therefore, this group of drugs is not used in patients with concomitant pulmonary emphysema, heart or vascular diseases, or bronchial asthma.

Highly selective beta blockers, which have significantly fewer side effects, include Betoptik.

Carbonic anhydrase inhibitors

Carbonic anhydrase inhibitors include Azopt and Trusopt. The mechanism of their action is associated with inhibition of intraocular moisture production. These medications are quite effective and, at the same time, safe, since there are practically no side effects when using them. The only thing is that patients with certain diseases of the excretory system need to be careful. Typically, carbonic anhydrase inhibitors are prescribed for double use; they are often combined with other groups of drugs (beta blockers, prostaglandins).

Diacarb tablets have a similar effect to Azopt, so it can also be prescribed to patients with glaucoma, especially during an acute attack of intraocular hypertension.

Cholinomimetics

The drugs Pilocarpine and Carbocholine are used to normalize the outflow of aqueous humor through the drainage system. They lead to narrowing of the pupillary opening and contraction of other muscle fibers, as a result of which the angle of the anterior chamber is freed from obstructions. Most often, cholinomimetics are prescribed to patients with angle-closure (narrow-angle) glaucoma to increase the size of the angle. The frequency of use is 1-2 times a day. These drugs are combined with drugs from other pharmacological groups (beta blockers, prostaglandins, carbonic anhydrase inhibitors).

Due to the pronounced narrowing of the pupillary opening, when using these medications, the field of vision may narrow and pain may appear in the temporal, frontal and superciliary areas.

Combination drugs

For the convenience of patients, several eye drops have been developed, consisting of active substances from different groups. This allows you to reduce the number of vials with medications, and sometimes the frequency of instillation.

Most often, ophthalmologists prescribe the following combination drops:

• Xalacom, which includes Timolol and Xalatan;
• Cosopt, consisting of Timolol Trusopt;
• Fotil, which contains Pilocarpine and Timolol.

Analogs

Synonyms for Aceclidine are drugs with the same active substance - Glaudin, Glaucostat and Glaunorm. Medicines with a similar mechanism of action include:

• Damelium;
• Dimetpramide;
• Domet;
• Ganaton;
• Domperidone;
• Domstal;
• Itomed;
• Melomide Hydrochloride;
• Metoclopramide;
• Motilak;
• Motilium;
• Motinorm;
• Motonium;
• Passengers;
• Cerucal;
• Perinorm;
• Tseruglan;
• Motizhekt;
• Itopra.

Indications for use

The drug is prescribed to patients in the absence of tone of internal organs, for example:

• Atony of the muscles of the gastrointestinal tract;
• Bladder atony, directly related to neurogenic disorders;
• Subinvolution (reduced contraction) and decreased uterine tone after childbirth.

For women, Aceclidine is prescribed to stop bleeding in the postpartum period.

In ophthalmological practice, the drug is used to reduce intraocular pressure and pupil constriction.

The instructions for Aceclidine say that it can also be used as a diagnostic tool for radiography of the duodenum, stomach and esophagus.