Hetastarch side effects. Hetastarch (Hespan): Comprehensive Guide to Side Effects, Uses, and Precautions
What are the primary uses of Hetastarch. How does Hetastarch work in the body. What are the most common side effects of Hetastarch. Who should avoid taking Hetastarch. How is Hetastarch administered and dosed. What precautions should be taken when using Hetastarch. How does Hetastarch interact with other medications.
Understanding Hetastarch: An Essential Plasma Volume Expander
Hetastarch, also known by its brand name Hespan, is a crucial medication used in medical emergencies and surgical settings. This synthetic colloid solution plays a vital role in maintaining blood volume and preventing shock in various clinical scenarios. But what exactly is Hetastarch, and how does it function within the human body?
Hetastarch is derived from natural starch sources and acts as a plasma volume expander. Its primary function is to increase the volume of blood plasma, which can be critically low due to severe bleeding, trauma, or other medical conditions. By boosting plasma volume, Hetastarch helps ensure that red blood cells can effectively circulate and deliver oxygen throughout the body, potentially saving lives in emergency situations.
The Science Behind Hetastarch’s Effectiveness
To understand how Hetastarch works, we need to delve into its composition and mechanism of action. The medication consists of hydroxyethyl starch molecules suspended in a saline solution. When administered intravenously, these large molecules remain in the bloodstream longer than other fluids, effectively drawing and retaining water from surrounding tissues. This process increases the overall blood volume, improving circulation and oxygen delivery to vital organs.
- Increases plasma volume
- Improves circulation
- Enhances oxygen delivery to tissues
- Helps prevent and treat hypovolemic shock
Primary Uses and Indications for Hetastarch
Hetastarch serves a critical purpose in various medical scenarios. Its primary indication is for the treatment and prevention of hypovolemia, a condition characterized by decreased blood plasma volume. But in what specific situations might healthcare providers turn to Hetastarch?
- Severe trauma with significant blood loss
- Major surgical procedures
- Burn injuries
- Septic shock
- Hemorrhagic shock
In these situations, Hetastarch can rapidly restore blood volume, helping to stabilize patients and prevent complications associated with inadequate tissue perfusion. Its ability to expand plasma volume makes it an invaluable tool in emergency medicine and critical care settings.
Comparing Hetastarch to Other Volume Expanders
While Hetastarch is an effective plasma volume expander, it’s not the only option available to clinicians. How does it compare to other solutions such as crystalloids or albumin? Hetastarch offers several advantages, including a longer intravascular half-life and more sustained volume expansion compared to crystalloid solutions. However, it also carries specific risks and contraindications that must be carefully considered when choosing the appropriate volume expander for each patient.
Potential Side Effects and Risks of Hetastarch
As with any medication, Hetastarch can cause side effects, ranging from mild to severe. Understanding these potential adverse reactions is crucial for both healthcare providers and patients. What are the most common side effects associated with Hetastarch administration?
- Itching or skin rash
- Headache
- Muscle pain
- Swollen glands
- Mild flu-like symptoms
While these side effects are generally manageable, there are more serious complications that can occur. These include severe allergic reactions, bleeding disorders, and kidney damage. Healthcare providers must carefully monitor patients receiving Hetastarch for any signs of these more severe side effects.
Recognizing Severe Adverse Reactions
In rare cases, Hetastarch can lead to life-threatening complications. Patients and caregivers should be aware of the following symptoms that may indicate a severe reaction:
- Difficulty breathing or wheezing
- Swelling of the face, lips, tongue, or throat
- Chest pain or rapid heartbeat
- Severe headache or changes in vision
- Unusual bleeding or bruising
- Signs of kidney problems (e.g., decreased urination, swelling, rapid weight gain)
If any of these symptoms occur, immediate medical attention is necessary. Prompt recognition and treatment of severe reactions can prevent potentially life-threatening complications.
Contraindications and Precautions for Hetastarch Use
While Hetastarch can be life-saving in many situations, it’s not appropriate for all patients. There are specific contraindications and precautions that healthcare providers must consider before administering this medication. Who should avoid taking Hetastarch?
- Patients with bleeding or blood clotting disorders
- Individuals with pre-existing kidney disease
- Those with congestive heart failure
- Patients with urination problems not caused by hypovolemia
- Individuals with known allergies to corn or hetastarch
Additionally, caution is advised for patients with liver disease, a history of heart disease, or those who are pregnant or breastfeeding. In emergency situations, it may not always be possible to obtain a complete medical history. Therefore, it’s crucial for patients to inform their healthcare providers about any pre-existing conditions or allergies whenever possible.
Special Considerations for Pregnant and Breastfeeding Women
The use of Hetastarch during pregnancy and breastfeeding requires careful consideration. Currently, Hetastarch is classified as FDA pregnancy category C, meaning that its effects on unborn babies are not fully understood. For breastfeeding mothers, it’s unclear whether Hetastarch passes into breast milk or could potentially harm a nursing infant. In these situations, healthcare providers must weigh the potential benefits against the risks, considering alternative treatments when possible.
Proper Administration and Dosage of Hetastarch
Correct administration of Hetastarch is crucial for its effectiveness and safety. How is Hetastarch typically administered, and what dosages are commonly used? Hetastarch is given intravenously by healthcare professionals in clinical settings. The dosage is carefully calculated based on the patient’s weight, clinical condition, and specific needs.
A typical initial dose for adults might range from 500 to 1000 mL, administered over 1 to 2 hours. However, the exact dosage and rate of administration can vary widely depending on the individual patient’s circumstances. It’s important to note that Hetastarch should not be used for prolonged periods or in excessive amounts due to the risk of adverse effects.
Monitoring During Hetastarch Administration
Close monitoring is essential during and after Hetastarch administration. Healthcare providers will typically assess:
- Vital signs (blood pressure, heart rate, respiratory rate)
- Urine output
- Electrolyte balance
- Coagulation parameters
- Signs of fluid overload or allergic reactions
This careful monitoring helps ensure that the patient receives the optimal benefit from Hetastarch while minimizing the risk of complications.
Interactions Between Hetastarch and Other Medications
Understanding potential drug interactions is crucial when administering Hetastarch. While it’s primarily used in acute care settings, patients may be taking other medications that could interact with Hetastarch. What are some potential interactions to be aware of?
Hetastarch may interact with medications that affect blood clotting, such as anticoagulants or antiplatelet drugs. This interaction could potentially increase the risk of bleeding. Additionally, Hetastarch may affect the accuracy of certain laboratory tests, particularly those related to blood typing and cross-matching.
Managing Potential Drug Interactions
To minimize the risk of adverse interactions, healthcare providers should:
- Obtain a comprehensive medication history when possible
- Adjust dosages of concurrent medications as needed
- Monitor patients closely for signs of bleeding or other complications
- Inform laboratory staff about Hetastarch administration when ordering blood tests
By being aware of potential interactions and taking appropriate precautions, healthcare providers can optimize the safety and efficacy of Hetastarch administration.
Long-term Effects and Follow-up Care After Hetastarch Use
While Hetastarch is primarily used for acute, short-term volume expansion, it’s important to consider potential long-term effects and necessary follow-up care. What should patients and healthcare providers be aware of after Hetastarch administration?
In most cases, the effects of Hetastarch are temporary, with the medication being metabolized and eliminated from the body over time. However, some patients may experience prolonged effects or require additional monitoring, particularly if they have received multiple or high doses of Hetastarch.
Post-administration Monitoring and Care
After receiving Hetastarch, patients may need:
- Regular blood tests to monitor kidney function and electrolyte balance
- Assessment of fluid status and cardiovascular function
- Monitoring for delayed allergic reactions or other adverse effects
- Follow-up appointments to ensure resolution of the original condition necessitating Hetastarch use
Healthcare providers should provide clear instructions to patients about potential symptoms to watch for and when to seek medical attention after discharge. This proactive approach can help identify and address any delayed complications related to Hetastarch administration.
Advancements and Alternatives in Volume Expansion Therapy
As medical science progresses, researchers continue to explore new approaches to volume expansion and shock treatment. What recent advancements have been made in this field, and what alternatives to Hetastarch are currently available or under investigation?
In recent years, there has been increased interest in balanced crystalloid solutions and albumin-based products as alternatives to synthetic colloids like Hetastarch. These alternatives may offer certain advantages in terms of safety profile and specific clinical scenarios. Additionally, research is ongoing into novel volume expanders and hemodynamic support strategies that could potentially offer improved outcomes with fewer side effects.
Emerging Trends in Volume Expansion Therapy
Some promising areas of research and development include:
- Targeted fluid resuscitation protocols
- Goal-directed therapy approaches
- Development of new synthetic colloids with improved safety profiles
- Exploration of blood substitutes and oxygen therapeutics
- Integration of advanced monitoring technologies to guide fluid management
As these advancements continue to evolve, healthcare providers will have an expanding toolkit for managing hypovolemia and shock, potentially leading to improved patient outcomes and reduced complications.
Hetastarch (Hespan) – Side Effects, Interactions, Uses, Dosage, Warnings
Reviewed:
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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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.
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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 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. 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 . 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. 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. 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. 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.
9006 3 Diagnostic approach to anemia |
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
1. European Glaucoma Society. Treatment principles and options. Chapter 3. In: EGS. Terminology and guidelines for glaucoma. 4th ed. Savona; 2014. p. 131–90.
2. Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global Prevalence of Glaucoma and Projections of Glaucoma Burden through 2040: A Systematic Review and Meta-Analysis. Ophthalmology. 2014;121(11):2081–90. https://doi.org/10.1016/j.ophtha.2014. 05.013
3. Hopes M, Broadway D. Preservative-free Treatment in Glaucoma is a Sensible and Realistic Aim for the Future. Eur. Ophthalmic Rev. 2010;4:23–8. http://doi.org/10.17925/EOR.2010. 04.01.23
4. Astakhov SYu, Grabovetsky VR, Nefedova DM, Tkachenko NV. Advantages and disadvantages of antihypertensive drops without preservatives. Ophthalmological records. 2011; IV(2):95–7. Astakhov SY, Grabovetskiy VR, Nefedova DM, Tkachenko NV. [Advantages and disadvantages of hypotensive eye drops without preservatives]. Oftalmological vedomosti. 2011;IV(2):95–7. (in Russian).
5. Pisella PJ, Fillacier K, Elena PP, Debbasch C, Baudouin C.