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Hetastarch side effects: Hetastarch (Hespan) – Side Effects, Interactions, Uses, Dosage, Warnings

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Hetastarch (Hespan) – Side Effects, Interactions, Uses, Dosage, Warnings

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Hetastarch (hydroxyethyl starch) is made from natural sources of starch. Hetastarch increases the volume of blood plasma that can be lost from bleeding or severe injury. Plasma is needed to circulate red blood cells that deliver oxygen throughout the body.

Hetastarch is used to treat or prevent hypovolemia (decreased blood plasma volume, also called “shock”) that may occur as a result of serious injury, surgery, severe blood loss, burns, or other trauma.

Hetastarch may also be used for purposes not listed in this medication guide.

uses

What is Hetastarch (Hespan) used for?

  • Hypovolemia

warnings

What is the most important information I should know about Hetastarch (Hespan)?

You should not receive this medication if you are allergic to hetastarch, or if you have:

  • a bleeding or blood clotting disorder;
  • kidney disease;
  • congestive heart failure; or
  • urination problems not caused by hypovolemia (decreased blood plasma volume).

If possible before you receive hetastarch, tell your doctor if you have:

  • liver disease;
  • a history of heart disease; or
  • if you are allergic to corn.

FDA pregnancy category C. It is not known whether hetastarch will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether hetastarch passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

In an emergency situation it may not be possible to tell your caregivers about your health conditions, or if you are pregnant or breast-feeding. Make sure any doctor caring for your pregnancy or your baby knows you have received this medicine.

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Side Effects

What are the side effects of Hetastarch (Hespan)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers right away if you have:

  • wheezing or gasping for breath, rapid breathing, sweating, and anxiety;
  • a light-headed feeling, like you might pass out;
  • weak pulse, slow breathing;
  • chest pain, fever, chills, cough; or
  • easy bruising, unusual bleeding, or any bleeding that will not stop.

Rare but serious side effects may include:

  • severe headache, vision or speech problems, mental changes;
  • drooping eyelids, loss of feeling in your face, tremors, trouble swallowing; or
  • severe skin reaction — fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Hetastarch can harm your kidneys. Call your doctor at once if you have any of these symptoms of kidney damage: swelling, rapid weight gain, unusual tiredness, nausea, vomiting, feeling short of breath, red or pink urine, painful or difficult urination, or little or no urinating.

Common side effects may include:

  • mild itching or skin rash;
  • mild headache;
  • muscle pain; or
  • swollen glands, mild flu symptoms.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Pregnancy & Breastfeeding

Can I take Hetastarch (Hespan) if I’m pregnant or breastfeeding?

FDA pregnancy category C. It is not known whether hetastarch will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether hetastarch passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Interactions

What drugs and food should I avoid while taking Hetastarch (Hespan)?

Follow your doctor’s instructions about any restrictions on food, beverages, or activity.

Dosage Guidelines & Tips

How to take Hetastarch (Hespan)?

Use Hetastarch (Hespan) exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended.

What should I do if I missed a dose of Hetastarch (Hespan)?

Because you will receive hetastarch in a clinical setting, you are not likely to miss a dose.

Overdose Signs

What happens if I overdose on Hetastarch (Hespan)?

Since hetastarch is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

If you think you or someone else may have overdosed on: Hetastarch (Hespan),  call your doctor or the Poison Control center

(800) 222-1222

If someone collapses or isn’t breathing after taking Hetastarch (Hespan), call 911

911

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Medical Disclaimer

Drugs A-Z provides drug information from Everyday Health and our partners, as well as ratings from our members, all in one place. Cerner Multum™ provides the data within some of the Overview, Uses, Warnings, Side Effects, Pregnancy, Interactions, Dosage, Overdose, and Images sections. The information within all other sections is proprietary to Everyday Health. 

Hetastarch Uses, Side Effects & Warnings

Generic name: hetastarch [ HET-a-starch ]
Brand names: Hespan, Hextend
Dosage form: intravenous solution (60 mg/mL-LR; 60 mg/mL-NaCl 0.9%)
Drug class: Plasma expanders

Medically reviewed by Drugs.com on Jul 19, 2022. Written by Cerner Multum.

What is hetastarch?

Hetastarch (hydroxyethyl starch) is made from natural sources of starch. Hetastarch increases the volume of blood plasma that can be lost from bleeding or severe injury. Plasma is needed to circulate red blood cells that deliver oxygen throughout the body.

Hetastarch is used to treat or prevent hypovolemia (decreased blood plasma volume, also called “shock”) that may occur as a result of serious injury, surgery, severe blood loss, burns, or other trauma.

Hetastarch may also be used for purposes not listed in this medication guide.

Warnings

You should not receive this medication if you have a bleeding or blood clotting disorder, congestive heart failure, kidney disease, or urination problems not caused by hypovolemia (decreased blood plasma volume).

Hetastarch can harm your kidneys. Call your doctor at once if you have any of these symptoms of kidney damage: swelling, rapid weight gain, unusual tiredness, nausea, vomiting, feeling short of breath, red or pink urine, painful or difficult urination, or little or no urinating.

Before taking this medicine

You should not receive this medication if you are allergic to hetastarch, or if you have:

  • a bleeding or blood clotting disorder;

  • kidney disease;

  • congestive heart failure; or

  • urination problems not caused by hypovolemia (decreased blood plasma volume).

If possible before you receive hetastarch, tell your doctor if you have:

FDA pregnancy category C. It is not known whether hetastarch will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether hetastarch passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

In an emergency situation it may not be possible to tell your caregivers about your health conditions, or if you are pregnant or breast-feeding. Make sure any doctor caring for your pregnancy or your baby knows you have received hetastarch.

How is hetastarch given?

Hetastarch is injected into a vein through an IV. A healthcare provider will give you this injection.

Your breathing, blood pressure, oxygen levels, kidney function, and other vital signs will be watched closely while you are receiving hetastarch. Your blood will also need to be tested daily during treatment.

What happens if I miss a dose?

Because you will receive hetastarch in a clinical setting, you are not likely to miss a dose.

What happens if I overdose?

Since hetastarch is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

What should I avoid after receiving hetastarch?

Follow your doctor’s instructions about any restrictions on food, beverages, or activity.

Hetastarch side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers right away if you have:

  • wheezing or gasping for breath, rapid breathing, sweating, and anxiety;

  • a light-headed feeling, like you might pass out;

  • weak pulse, slow breathing;

  • chest pain, fever, chills, cough; or

  • easy bruising, unusual bleeding, or any bleeding that will not stop.

Rare but serious side effects may include:

  • severe headache, vision or speech problems, mental changes;

  • drooping eyelids, loss of feeling in your face, tremors, trouble swallowing; or

  • severe skin reaction — fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Hetastarch can harm your kidneys. Call your doctor at once if you have any of these symptoms of kidney damage: swelling, rapid weight gain, unusual tiredness, nausea, vomiting, feeling short of breath, red or pink urine, painful or difficult urination, or little or no urinating.

Common side effects of hetastarch may include:

  • mild itching or skin rash;

  • mild headache;

  • muscle pain; or

  • swollen glands, mild flu symptoms.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Hetastarch dosing information

Usual Adult Dose for Hypovolemia:

Dosage for Acute Use in Plasma Volume Expansion: 500 to 1000 mL IV
Maintenance dose: Total dosage and rate of infusion depends on the amount of blood or plasma lost and the resultant hemoconcentration.
Maximum dose: Doses more than 1500 mL per day (approximately 20 mL per kg of body weight) are usually not required although higher doses have been used in postoperative and trauma patients with severe blood loss.

Dosage in Leukapheresis: 250 to 700 mL to which citrate anticoagulant has been added and administered to the input line of the centrifugation apparatus at a ratio of 1:8 to 1:13 to venous whole blood.

Comments:
-Hetastarch and citrate should be thoroughly mixed to assure effective anticoagulation.
-Hetastarch admixtures of 500 to 560 mL with citrate concentrations up to 2.5% are compatible for 24 hours at room temperature.

Uses:
-For treatment of hypovolemia when plasma volume expansion is desired
-This drug in leukapheresis improves the harvesting and increasing the yield of granulocytes by centrifugal means

What other drugs will affect hetastarch?

Other drugs may interact with hetastarch, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

More about hetastarch

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  • During pregnancy
  • Drug class: plasma expanders
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Patient resources

  • Advanced Reading
  • Hetastarch/sodium chloride (Advanced Reading)
Other brands

Hextend, Hespan

Professional resources

  • Prescribing Information

Related treatment guides

  • Blood Disorders
  • Hypovolemia

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer

Copyright 1996-2023 Cerner Multum, Inc. Version: 2.02.

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12/14/2014

Horses often suffer from circulatory collapse secondary to acute or chronic blood loss, significant hypoalbuminemia, and septic shock. The treatment of these critically ill patients is limited to restoring blood pressure and delivering oxygen to vital organs such as the brain, kidneys, and liver. Commonly used treatments include the administration of crystalloids and colloids. Infusion of large volumes of crystalloids leads to a decrease in oncotic pressure due to their diluting effect, while intravascular hydrostatic pressure temporarily increases. On the contrary, infusion of colloids leads to an increase in plasma oncotic pressure due to the delivery of large osmotically active molecules that are retained in the vascular bed. Therefore, fluid replacement with colloids may lead to greater improvements in cardiovascular status than with crystalloids. Natural colloids include whole blood, blood components and plasma. Synthetic colloids are hetastarch, dextran, gelatin and polymerized hemoglobin.

NATURAL COLLOID TREATMENT

Whole blood transfusion

cast red blood cells and compatibility testing (cross-testing for compatibility). Whole blood transfusion is indicated for horses with hematocrit at or below 12% secondary to acute blood loss or hemolysis. Whole blood transfusion is also indicated in patients with a hematocrit less than or equal to 8% due to chronic blood loss or hemolysis. Of course, these figures are not absolute, and the clinical condition of the patient as a whole must be taken into account along with the determination of the presence of blood loss or hemolysis.
In addition to assessing the severity and cause of anemia, the short lifespan of transfused RBCs must be taken into account. Allogeneic equine erythrocytes are cleared from the bloodstream by a system of mononuclear phagocytes 4 days after transfusion as a result of the formation of serum antibodies against foreign erythrocyte antigens on days 3-10 in about half of the horses after a single transfusion. Therefore, any necessary subsequent transfusions should be administered with caution if they occur more than 3 days after the first transfusion.
Horses show great polymorphism of blood groups. At least 30 different erythrocyte antigens (alloantigens) that make up numerous blood groups (A, C, D, K, P, Q and U) for about 400,000 equine blood phenotypes. Therefore, it is almost impossible to achieve perfect donor-recipient compatibility. However, suitable matching can be achieved by initial typing of the donor’s blood and agglutination cross-testing. Initial knowledge of the donor’s blood group helps to avoid donors who have the Aa and Qa alloantigens. These alloantigens are considered the most immunogenic, and transfusion of blood containing these antigens can lead to severe hemolysis. In horses of the Quarter Horse and Belgian breeds, the frequency of occurrence of Aa and Qa alloantigens is low. The saline agglutination test can be divided into major and minor cross reactions. A large cross-reaction combines washed donor erythrocytes and recipient serum, which are tested for agglutination. Conversely, a small cross-reaction combines the donor’s serum and the recipient’s erythrocytes, which are also tested for agglutination. Unfortunately, such testing does not provide information on hemolysing antibodies (hemolysin), which, if present, cause severe hemolysis of transfused RBCs. Testing for hemolysins requires the addition of exogenous complement from rabbit serum to the reaction mixture. Such testing is carried out only in a few laboratories, since rabbit serum requires special handling and storage conditions. Compatibility testing should precede transfusion, however, this is not always possible. In the absence of information on the donor’s blood group, cross-reactivity, or testing for hemolysins, the ideal blood donor is an adult gelding who has tested negative for infectious anemia virus and has never received blood or plasma transfusions. In addition, the first transfusion of whole blood to a cross-tested or never previously administered patient with blood and blood components is generally well tolerated. In case of bleeding into the body cavity, autotransfusion of blood can be considered if it can be aseptically collected.
Although whole blood transfusion can greatly improve a patient’s current condition, it has its own challenges. As noted earlier, the short lifespan of transfused RBCs and the formation of alloantibodies limit the long-term benefit of whole blood transfusion. In addition, blood transfusion suppresses the bone marrow response to anemia by reducing the production of erythropoietin by the kidneys. Healthy bone marrow begins to replace lost cells after 5 days. Therefore, whole blood transfusion provides only a temporary improvement in oxygen delivery to vital tissues. Thus, even after whole blood transfusion, identifying and correcting the cause of anemia remains critical.

Whole blood collection

Donor whole blood is collected in special sterile plastic bags or sterile glass containers that contain citric acid-dextrose (acid-citrate-dextrose, ACD) or citrate-phosphate-dextrose (Baxter; Deerfield, 111 . ). The desired ratio of ACD to whole blood is approximately 1:10. Depending on individual preference, a sterile glass container may be more suitable for efficient collection of whole blood due to the negative pressure it holds while under vacuum. However, when they fill up, they become heavy; in the event of a fall, all content may be lost. Regardless of the container, blood is collected aseptically through an intravenous catheter or large bore needle attached to an extension system. The determination of the total volume of blood to be collected and transfused depends on the size of the donor and the expected blood loss of the recipient. A medium-sized horse (450 kg) with a hematocrit of 35-40% can produce approximately 20% (8-10 liters for an adult horse) of its blood volume every 30 days. In general, 20-30% of the recipient’s total blood volume (I – 11 L for a 450 kg horse) is sufficient to restore oxygen supply to vital tissues before the bone marrow is able to respond. Alternatively, if whole blood transfusion is warranted and the estimate of blood loss is inaccurate, 15 mL/kg whole blood (6-8 L for a 450 kg horse) may be administered. Whole blood is best used immediately after collection, but may be stable at 4°C for 2-3 weeks if ACD is added.

Blood Administration

Whole blood is filtered prior to use and then infused into the recipient via an aseptic catheter in the jugular vein. Initially (5-10 minutes), the infusion rate should be slow (0.1 ml/kg) to watch for any signs of adverse reactions. They include tachypnea, shortness of breath, restlessness, tachycardia, piloerection (ruffled hair), muscle fasciculations (fibrillar contractions), or sudden collapse. Further, the transfusion rate can be increased to 20 ml/kg/h, but no more. If severe adverse reactions occur, the transfusion should be stopped and epinephrine (0.01-0.02 ml/kg, 1:1000) administered simultaneously with isotonic solutions. If only mild reactions occur, the rate of transfusion can be reduced and corticosteroids or NSAIDs administered.

Treatment with blood components

The use of concentrated specific components of equine plasma rather than whole blood may be more appropriate for the treatment of granulocyte, platelet or erythrocyte deficiencies. This is especially true in patients with cell groups deficient due to cell destruction rather than blood loss. These horses are not deficient in blood volume, but rather deficient in specific constituents. Therefore, transfusion of whole blood to such patients may result in fluid overload, while the administration of individual missing components may be more appropriate. Centrifugal apheresis is a method for concentrating granulocytes, platelets and red blood cells from whole blood. In addition to these cell types, other blood components such as immunoglobulins and clotting factors can be concentrated and applied. Concentrated lyophilized immunoglobulin (Lyphomune, Diagnon Corporation, Rockville, Md.) is commercially available for the treatment of deficient passive transmission in foals, selective immunoglobulin deficiency, and immune-mediated disorders. Cryoprecipitate (a mixture of factor VIII:C, fibrinogen, and fibronectin) is used to treat hemophilia in dogs and humans, but is difficult to obtain or too expensive to use in horses. The collection of whole blood and the use of blood components should follow the same guidelines as above. In addition, aseptic handling of blood components during centrifugal apheresis is critical to avoid bacterial contamination prior to use.

Alternatives to blood component therapy

In addition to transfusion for the treatment of granulocyte deficiency (neutropenia), some alternative products are used. These products include hematopoietic growth factors such as canine and bovine recombinant granulocyte colony stimulating factors. In one study, healthy foals treated with bovine granulocyte colony stimulating factor showed an increase in neutrophils without side effects. The second study showed an increase in bone marrow cellularity and increased myeloid activity after administration of recombinant canine granulocyte colony-stimulating factor to foals. The effectiveness of these products is supported by these studies, however, more work is needed to develop a therapeutic approach for horses of all ages. The use of human recombinant erythropoietin in horses can lead to severe, sometimes fatal anemia.

Plasma transfusion

Horses suffering from falling intravascular oncotic pressure due to protein deficiency or neonatal foals suffering from passive transmission deficiency are candidates for plasma administration. Foals require 1-2 L (20-40 ml/kg) of plasma to sufficiently raise IgG levels, and adult hypoproteinemic horses (450 kg) require 6-8 L of plasma to raise oncotic pressure. In general, administration of 7 L of equine plasma, which contains 7 g/dL of protein, will result in a 1 g/dL increase in total protein.
Plasma retains some advantages over synthetic colloids as a source of functional proteins (coagulation factors), immunoglobulins and complement. However, the disadvantages of plasma include poor ability to increase oncotic pressure and high cost of the product. Plasma can be purchased from commercial suppliers (Lake Immunogenics, Ontario, N.Y.; Veterinary Dynamics, Inc. , Chino, Calif; Immvac, Inc., Columbia, Mo.; Veterinary Immunogenics, LTD, Cumbria, England) or obtained from whole blood that was centrifuged or settled at room temperature for 1-2 hours, followed by removal of erythrocytes settled under gravity. Whole blood collection and plasma administration should be performed as described previously. In addition, aseptic handling of blood components during plasma separation is critical to avoid bacterial contamination prior to administration. Because of the high risk of plasma contamination from large quantities of whole blood, it may be ideal to store liter jars of commercially available equine plasma for future use at 0 0C for up to 1 year. In addition to normal plasma, hyperimmune plasma is commercially available from horses that have been immunized against specific agents responsible for diseases such as rhodococcal pneumonia, salmonellosis, and botulism (Lake Immunogenics, Veterinary Dynamics, Inc., Immvac, Inc., Veterinary Immunogenics , LTD). The efficacy of these products remains unknown, however, there is evidence that the incidence or severity of rhodococcal pneumonia may be reduced in foals who receive hyperimmune plasma.

SYNTHETIC COLLOID INJECTION

Synthetic colloids (getastarch, dextran, gelatin, and polymerized hemoglobin) can be used as an alternative to natural colloid administration for the treatment of hypovolemic and hypooncotic conditions in horses. Hetastarch is a synthetic colloid composed predominantly of amylopectin. It is available as a 6% saline solution and is commonly used in horses in circulatory shock and for the treatment of low oncotic pressure secondary to hypoalbuminemia. The recommended dose is 5-15 ml/kg intravenously over 2-3 days. Interestingly, drug infusion does not result in an increase in total refractive serum dry matter, but rather in a decrease caused by dilution of intravascular proteins. The Hetastarch treatment has some advantages over the administration of other colloids. Large molecules of the drug are less prone to extravasation through intercellular junctions, thus providing a positive colloidal effect for a long time. Moreover, large molecules can act as plugs to prevent further leakage of albumin into the interstitial space. Hetastarch has been associated with the development of coagulopathy in some animal species, but this is rather a rare complication.
Other synthetic products that are just beginning to find their way into veterinary medicine are hemoglobin-based oxygen carriers such as oxyglobin (Oxyglobin, 30 ml/kg bw, IV; Biopure, Cambridge, Mass.). Oxyglobin contains polymerized hemoglobin molecules that circulate in the plasma and transport oxygen to the tissues after infusion. These drugs are designed to overcome the problems associated with allogeneic blood transfusion and to treat severe anemia. Preliminary studies in experimental models of acute bleeding in dogs and rats show a positive effect on the cardiovascular system. Also, preliminary data obtained in foals revealed the benefit of Oxyglobin due to its immediate effect on oxygen tension. Unfortunately, the drug has a lifespan of approximately 24 hours and a whole blood transfusion is likely to be required the next day. These drugs are of limited use in horses due to their high cost.

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Ways to minimize the side effects of antiglaucoma drugs

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Author: Super User
Published: 14 March 2019
Look back: 2238

UDC 617.7–007.681:546.131:615.038
https://doi.org/10.30702/Ophthalmology.2019/09.105461

Demin Yu.A.1, Dr. med. Sci., Prof., Head of the Department of Ophthalmology

Shebanov R. V.2, Physician of the Diagnostic Department

1 Kharkov Medical Academy of Postgraduate Education, Kharkov, Ukraine

2 Ophthalmika International Medical Center, Kharkiv, Ukraine

Summary . Medical therapy is the first choice in the treatment of glaucoma. Side effects associated with topical use of drugs can adversely affect the patient’s desire to follow the prescribed treatment (compliance), doctor-patient interaction, and the patient’s quality of life. Benzalkonium chloride (BAC) is the most commonly used preservative currently used in eye drops for the treatment of glaucoma. It is a highly effective antimicrobial preservative, but it also has a toxic effect on cells in various structures of the eye. An alternative to the use of antiglaucoma drops with BAC are other, less toxic preservatives or preservative-free forms of preparations. At the beginning of 2019The first non-preservative antiglaucoma drug from the group of prostaglandin analogues (prostamide) is available in Ukraine – Bimikan® IVF in a multi-dose vial. The bottle of Bimikan® ECO is equipped with a special dropper patented as the Novelia® system manufactured by Nemera (France).

Keywords : glaucoma, BAC, preservative-free forms, Bimikan® IVF, Novelia® system.

Glaucoma is a group of chronic progressive neuropathies that share common morphological changes in the optic nerve head and in the retinal epithelium, characterized by progressive ganglion cell death and loss of visual fields. Glaucoma is the leading cause of blindness worldwide [1]. The global prevalence of glaucoma among the population aged 40–80 years is 3.54%. In 2013, the number of people aged 40–80 years with glaucoma reached 64.3 million. According to the mathematical model, the number of patients with glaucoma will increase to 76 million by 2020 and to 111.8 million by 2040 [2].

Glaucoma therapy is based on the reduction of intraocular pressure (IOP), which is the most important risk factor in the etiology of glaucomatous optic neuropathy. Currently, ophthalmologists can offer their patients several treatment options: drug therapy, laser or surgical intervention, the purpose of which is to reduce IOP and prevent or delay visual function loss. It is generally accepted that drug therapy is the method of first choice in the treatment of glaucoma [3]. According to modern ideas about the conservative treatment of glaucoma, when choosing an antihypertensive drug, a number of factors should be taken into account: its effectiveness, the frequency of instillations, cost, impact on general and local hemodynamics, the presence of local and systemic side effects [4]. However, adverse events associated with topical use of drugs can adversely affect the patient’s desire to follow the prescribed treatment (compliance), doctor-patient interaction, and patient quality of life (Figure 1) [3].

In recent years, special attention has been paid to the toxicity of the drug in relation to the surface structures of the eyeball. Most authors associate it with the preservatives that make up the eye drops. Preservatives under the terms of the pharmacopoeia ensure the stability of ophthalmic solutions and prevent their microbial contamination both during storage and during use of the drug. The severity of the toxic effect depends on the type of preservative, its concentration, the frequency of instillations and the duration of therapy. That is why among patients with glaucoma who are forced to receive antihypertensive drugs for many years, the effect of the preservative on the tear film and epithelial cells of the conjunctiva and cornea becomes especially noticeable [3].

Benzalkonium chloride is the most commonly used preservative currently used in eye drops for the treatment of glaucoma. Its concentration range is from 0.004 to 0.02%. From a chemical point of view, BAC is a quaternary ammonium compound that acts as a cationic detergent. The drug is a highly effective antimicrobial preservative, but it also has a toxic effect on the cells of various eye structures [4].

In vitro studies have shown that even low concentrations of BAC lead to toxic changes and apoptosis of trabecular meshwork cells. Therefore, theoretically, long-term topical therapy with antiglaucoma drugs that use BAC as a preservative may cause a decrease in trabecular function and a potential worsening of glaucoma. In addition, BAC is involved in the etiology of cataracts. The Ocular Hypertension Treatment Study (OHTS), a large, long-term, prospective, randomized controlled trial, concluded that the incidence of cataracts was higher in eyes treated with preservative-containing topical antiglaucoma drugs. There are certain areas of the eye surface that can be affected by preservatives, causing undesirable side effects: precorneal tear film, cornea, conjunctiva, and tissues of the adnexa of the eye [4].

Figure 1. Unwanted ophthalmic effects of topical drug therapy

Preservatives such as BAC act as detergents [5] by creating a low surface tension by destroying the superficial lipid layer of the precorneal tear film, which leads to a reduction in tear film rupture time, subsequent evaporation of the middle aqueous layer and precipitation of the mucin layer components. In addition, the toxic effect on the conjunctiva reduces the number and suppresses the function of conjunctival goblet cells, leading to impaired mucin production and subsequent deterioration of corneal epithelium hydration. Therefore, long-term use of eye drops containing BAC as a preservative may cause the development of secondary dry eye syndrome.

The effect of BAC on the cornea has been studied in numerous in vivo studies. It has been proven that even low concentrations of BAC (0.01%) caused the destruction of the epithelial barrier of the cornea [6] and led to a delay in the healing of the cornea, and BAC at a concentration of 0.02% completely suppressed the healing process after keratectomy in the eyes of rabbits [7].

In addition, long-term use of drugs with BAC leads to a decrease in the number of conjunctival goblet cells, disruption of intercellular contacts of corneal epithelial cells with the development of their excessive desquamation, as well as epithelial metaplasia [8]. At the cellular level, BAC induces oxidative stress, causes lysis of cell membranes and protein denaturation, triggering the apoptosis mechanism, activates and maintains the immune-inflammatory response, causing the so-called pro-inflammatory readiness of the conjunctiva and contributing to the development of subconjunctival fibrosis [9]. An alternative to the use of antiglaucoma drops with BAC are other, less toxic preservatives or preservative-free forms of preparations. The European Medicines Agency (EMEA) recommends that preservative-containing antiglaucoma drops be avoided in patients with intolerance.

In today’s practice, physicians and their patients have the choice of topical antiglaucoma drugs that do not contain BAC or other preservatives in monodose dropper bottles, as well as drugs with alternative preservatives – polyquad. However, they are expensive and in some cases inconvenient to use. So far, multi-dose vials that provide long-term sterility have only been available in Ukraine for a range of artificial tears and anti-allergic products: ABAK® patented filtration system, Continuous Single Dose System (COMOD®), Airless Antibacterial Distribution System (AADSTM), and VISMED® Multisystem .

Figure 2. Operation of the Novelia® delivery device manufactured by Nemera (France)

At the beginning of 2019, an antiglaucoma drug from the group of prostaglandin analogues (prostamide) – Bimikan® ECO, manufactured by Polpharma (Poland) is available in Ukraine. This is the first and only non-preservative antiglaucoma drug in a multi-dose vial currently available for use by patients in Ukraine. The Bimikan® ECO bottle is equipped with a special dropper, patented as the Novelia® system manufactured by Nemera (France), which provides a three-month sterility due to the dropper with a system of silicone valves acting as a filtering ventilation system, which allows air to enter during use, but prevents penetration microorganisms. In addition, due to the silver coating on the inside, the sterility of the solution inside the vial is maintained (Figure 2).

CONCLUSIONS
Reducing the incidence of local side effects is one of the ways to increase patient adherence to therapy. A patient who complains of side effects is usually not adherent to therapy, so it is necessary to monitor the condition of the eyelid margins, cornea and conjunctiva during each visit. Particular attention should be paid to glaucoma patients with pre-existing ocular surface lesions or dry eye syndrome [1]. The use of antiglaucoma drugs with alternative preservatives and preservative-free forms of drugs are priority for use as a medical treatment for glaucoma.

Djomin Yu. A.1, Dr. med. Sci., Prof., Head of the Department of Ophthalmology

Shebanov R. V.2, Doctor of Diagnostic Department

1Kharkiv Medical Academy of Postgraduate Education, Kharkiv, Ukraine

2 International Medical Center “Oftalmika”, Kharkiv, Ukraine

WAYS TO MINIMIZE THE SIDE EFFECTS OF ANTIGLAUCOMA DRUGS

Summary . Drug therapy is the first choice method in treating glaucoma. Side effects associated with medical drug stagnation can cause an unacceptable impact on the patient’s condition, to achieve recognized compliance (compliance), in the relationship between the doctor and the patient and the quality of life of the patient a. Benzalkonium chloride (BAC) is a preservative that is most often found in ophthalmic drops for the treatment of glaucoma. It is a highly effective antimicrobial preservative, however, it also copes with toxic action on cells of various structures of the eye. An alternative to using antiglaucoma drops with BAC is other, less toxic preservatives or preservative-free formulations. On the cob 2019The first preservative-free antiglaucoma drug from the group of prostaglandin analogues (prostamide) – Bimikan® EKO in a multi-dose vial, has become available in Ukraine. A bottle of Bimican® ECO is provided with a special dropper, patented as the Novelia® system of brewing by Nemera (France).

Key words : glaucoma, BAC, non-preservative forms, Bimican® ECO, Novelia® system.

Demin Yu. A.1, Doctor of Medical Sciences, Prof., Head of the Department of Ophthalmology

Shebanov R.V.2, Physician

1Kharkiv Medical Academy of Postgraduate Education, Kharkiv, Ukraine

2International Medical Center “Ophtalmica”, Kharkiv, Ukraine

THE WAYS OF MINIMIZATION THE SIDE EFFECTS OF ANTIGLAUCOMA DRUGS

Summary . Drug therapy is the method of first choice in glaucoma. Adverse events, that are associated with local usage of drugs, can have an effect on the patient’s adherence to prescribed treatment, the interaction between the doctor and the patient, and the quality of life. BAC (benzalkonium chloride) is the most commonly used preservative currently used in eye drops for the treatment of glaucoma. BAC is a highly effective antimicrobial preservative, but it also has a toxic effect on the cells of various structural eyes. In vitro studies, even low concentrations of BAH lead to toxic changes and apoptosis of the trabecular apparatus cells. Theoretically, long-term topical therapy with antiglaucoma drugs, in which BAC is used as a preservative, can cause of decreasing of trabecular function and worsening of glaucoma. In addition, prolonged use of drugs with BAC leads to a decrease in the number of cells of the conjunctiva, disruption of the intercellular contacts of epithelial cells of the cornea with the development of their excessive desquamation, as well as epithelial metaplasia. At the cellular level, BAC induces oxidative stress, causes cell membrane lysis and protein denaturation, triggering the mechanism of apoptosis, activates and maintains the immune-inflammatory response, causing the so-called pro-inflammatory readiness of the conjunctiva and promoting the development of subconjunctival fibrosis. An alternative to antiglaucoma drops with BAC is using other, less toxic preservatives or non-preservative forms of drugs. At the beginning of 2019, the first non-preservative anti-glaucoma preparation from the group of prostaglandin analogues (prostamide), Bimikan ECO in a multi-dose vial, is available in Ukraine. The bottle of Bimikan® ECO is supplied with a special dropper, patented, as the system Novelia® produced by Nemera (France).

Keywords : glaucoma, BAC, non-preservative forms, Bimikan® ECO, Novelia® system.

LIST OF REFERENCES USED
REFERENCES
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