Hetastarch side effects. Hetastarch (Hespan): Uses, Side Effects, Dosage, and Warnings
What is Hetastarch used for. How does Hetastarch work in the body. What are the potential side effects of Hetastarch. How is Hetastarch administered. What precautions should be taken when using Hetastarch. Who should not use Hetastarch. How does Hetastarch interact with other medications.
Understanding Hetastarch: A Crucial Plasma Expander
Hetastarch, also known by its brand name Hespan, is a medication derived from natural starch sources. Its primary function is to increase blood plasma volume, making it an essential treatment for hypovolemia – a condition characterized by decreased blood plasma volume, often referred to as “shock”. This synthetic colloid solution plays a vital role in emergency medicine and critical care settings.
But what exactly makes Hetastarch so important in medical emergencies? The answer lies in its ability to rapidly expand plasma volume, which is crucial for maintaining circulation and oxygen delivery throughout the body. When a patient experiences severe blood loss, trauma, or other conditions that lead to hypovolemia, Hetastarch can help restore blood volume and improve tissue perfusion.
How Does Hetastarch Work?
Hetastarch functions as a plasma volume expander by drawing fluid into the bloodstream through osmotic pressure. This mechanism helps to:
- Increase circulating blood volume
- Improve blood flow to vital organs
- Enhance oxygen delivery to tissues
- Stabilize blood pressure in shock conditions
By effectively increasing the volume of circulating plasma, Hetastarch ensures that red blood cells can continue to deliver oxygen throughout the body, even in situations of severe blood loss or trauma.
Medical Applications and Uses of Hetastarch
Hetastarch finds its primary use in treating or preventing hypovolemia, but its applications extend beyond this core function. Healthcare providers may administer Hetastarch in various clinical scenarios, including:
- Severe injuries resulting in significant blood loss
- Major surgical procedures
- Burn injuries causing fluid shifts
- Trauma cases with potential shock
- Sepsis and septic shock
In these situations, the rapid plasma expansion provided by Hetastarch can be life-saving. But how exactly do medical professionals determine when to use this medication?
When is Hetastarch Typically Administered?
Hetastarch is usually reserved for acute situations where rapid plasma volume expansion is necessary. Clinicians assess various factors before administering Hetastarch, including:
- The patient’s hemodynamic status
- The extent of blood or fluid loss
- The presence of shock or impending shock
- The patient’s overall health condition and any contraindications
It’s important to note that while Hetastarch is a powerful tool in emergency medicine, its use is carefully controlled due to potential side effects and risks associated with overuse.
Side Effects and Potential Risks of Hetastarch
Like all medications, Hetastarch carries the potential for side effects. While many patients tolerate the drug well, especially when used appropriately in emergency situations, it’s crucial to be aware of possible adverse reactions.
Common Side Effects
Some of the more frequently reported side effects of Hetastarch include:
- Mild itching or skin rash
- Headache
- Muscle pain
- Swollen glands
- Mild flu-like symptoms
These effects are generally mild and often resolve on their own. However, more severe side effects can occur, particularly with prolonged or excessive use of Hetastarch.
Serious Side Effects and Complications
While less common, serious side effects of Hetastarch can include:
- Allergic reactions (hives, difficulty breathing, swelling of face, lips, tongue, or throat)
- Bleeding disorders or increased bleeding tendency
- Kidney damage or failure
- Cardiovascular issues
- Severe skin reactions
These serious side effects require immediate medical attention. But how can patients and healthcare providers balance the benefits of Hetastarch against these potential risks?
Precautions and Contraindications for Hetastarch Use
Given the potential for serious side effects, certain precautions must be taken when administering Hetastarch. Additionally, the medication is contraindicated in some patient populations.
Who Should Not Receive Hetastarch?
Hetastarch should not be administered to patients with:
- Known allergies to hetastarch or corn-based products
- Bleeding or blood clotting disorders
- Severe kidney disease
- Congestive heart failure
- Urination problems not caused by hypovolemia
Additionally, caution is advised when considering Hetastarch for patients with liver disease or a history of heart problems. But what about special populations, such as pregnant women or nursing mothers?
Hetastarch in Pregnancy and Breastfeeding
Hetastarch falls under FDA pregnancy category C, meaning its effects on unborn babies are not fully known. Similarly, it’s unclear whether Hetastarch passes into breast milk or could harm a nursing infant. In emergency situations, the potential benefits of using Hetastarch may outweigh the risks, but this decision should be made carefully by healthcare providers.
Administering Hetastarch: Dosage and Guidelines
The administration of Hetastarch requires careful consideration of the patient’s condition, the severity of hypovolemia, and potential risks. But how is the correct dosage determined?
Dosage Considerations
Hetastarch dosage is typically based on the patient’s weight and the clinical situation. Some general guidelines include:
- Initial dose: Usually 500 to 1000 mL for adults
- Maximum daily dose: Generally not to exceed 1500 mL/day for adults
- Pediatric dosing: Determined based on weight and clinical need
It’s crucial to note that these are general guidelines, and actual dosing may vary based on individual patient needs and response to treatment.
Administration Method
Hetastarch is administered intravenously, typically as an infusion. The rate of infusion can vary depending on the urgency of the situation and the patient’s response. In emergency situations, rapid infusion may be necessary, while in less urgent cases, a slower infusion rate might be preferred to minimize side effects.
Monitoring and Follow-up Care After Hetastarch Administration
Given the potential for side effects and complications, close monitoring is essential during and after Hetastarch administration. But what specific parameters should healthcare providers watch?
Key Monitoring Parameters
Healthcare providers typically monitor:
- Vital signs (blood pressure, heart rate, respiratory rate)
- Urine output
- Electrolyte levels
- Kidney function
- Coagulation parameters
- Signs of allergic reactions or fluid overload
Regular assessments help ensure the patient is responding appropriately to treatment and allow for early detection of any adverse effects.
Follow-up Care
After receiving Hetastarch, patients may require ongoing monitoring and follow-up care. This might include:
- Regular blood tests to assess kidney function and electrolyte balance
- Monitoring for signs of bleeding or clotting disorders
- Assessing fluid status and cardiovascular function
- Addressing any persistent symptoms or side effects
The duration and intensity of follow-up care will depend on the individual patient’s condition and response to treatment.
Hetastarch in the Context of Modern Emergency Medicine
While Hetastarch has been a valuable tool in emergency medicine for many years, its use has come under scrutiny in recent times. But what factors have led to this reevaluation?
Evolving Perspectives on Hetastarch Use
Recent studies and clinical experiences have led to a more cautious approach to Hetastarch use. Some key points in this evolving perspective include:
- Increased awareness of potential kidney damage with high doses or prolonged use
- Recognition of the risk of coagulopathy (blood clotting disorders) in some patients
- Development of alternative fluid resuscitation strategies
- Updated clinical guidelines recommending more judicious use of synthetic colloids like Hetastarch
These factors have led many healthcare systems to reassess their protocols for fluid resuscitation in emergency situations.
Alternatives to Hetastarch
As medical knowledge advances, alternative treatments for hypovolemia have gained prominence. Some alternatives to Hetastarch include:
- Crystalloid solutions (like normal saline or Ringer’s lactate)
- Other colloid solutions (such as albumin)
- Blood products (in cases of severe blood loss)
- Balanced electrolyte solutions
The choice between these options depends on the specific clinical situation, patient characteristics, and institutional protocols.
Future Directions in Plasma Volume Expansion and Emergency Medicine
As our understanding of fluid resuscitation and shock management continues to evolve, what does the future hold for treatments like Hetastarch? Several exciting developments are on the horizon:
Emerging Research and Technologies
Ongoing research is focusing on:
- Development of novel synthetic plasma expanders with improved safety profiles
- Advanced monitoring techniques to guide fluid therapy more precisely
- Personalized approaches to fluid resuscitation based on individual patient characteristics
- Integration of artificial intelligence in fluid management decisions
These advancements promise to enhance our ability to manage hypovolemia and shock while minimizing risks to patients.
Shifting Paradigms in Emergency Fluid Management
The field of emergency medicine is witnessing a shift towards more nuanced approaches to fluid resuscitation. This includes:
- Greater emphasis on balanced fluid strategies
- Increased use of goal-directed therapy
- Recognition of the importance of the glycocalyx (the protective layer lining blood vessels) in fluid management
- Growing interest in small-volume resuscitation techniques
These evolving paradigms may reshape how we approach plasma volume expansion in the future, potentially reducing reliance on traditional colloid solutions like Hetastarch.
As we continue to refine our understanding of fluid resuscitation and shock management, the role of medications like Hetastarch will undoubtedly evolve. While it remains a valuable tool in certain emergency situations, its use is likely to become more targeted and judicious. Healthcare providers must stay informed about the latest research and guidelines to ensure optimal patient care in critical situations.
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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Further information
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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
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