What are the primary uses of diazoxide and chlorothiazide. How are these medications administered to patients. What are the potential side effects of diazoxide and chlorothiazide. Who should avoid taking these medicines. How do diazoxide and chlorothiazide interact with other medications.

Understanding Diazoxide and Chlorothiazide: Their Roles in Medical Treatment

Diazoxide and chlorothiazide are two medications often prescribed together to manage specific medical conditions. Diazoxide is primarily used to treat persistently low blood sugar levels (hypoglycemia) caused by excessive insulin production (hyperinsulinism). It functions by blocking the release of insulin in the body. On the other hand, chlorothiazide is a diuretic that increases urine production by the kidneys. It is commonly prescribed alongside diazoxide to counteract fluid retention, a side effect of diazoxide treatment.

Primary Functions of Diazoxide and Chlorothiazide

• Diazoxide: Treats hypoglycemia by inhibiting insulin release
• Chlorothiazide: Manages fluid retention and reduces edema

These medications are often used in combination to provide comprehensive treatment for patients with specific medical needs. The synergistic effect of these drugs helps maintain proper blood sugar levels while managing potential side effects.

Administration and Dosage Forms of Diazoxide and Chlorothiazide

How are diazoxide and chlorothiazide administered to patients? Both medications are typically given orally, with specific dosing schedules tailored to individual patient needs.

• Diazoxide: Administered two to three times daily
• Chlorothiazide: Usually given twice daily

These medications are available in various forms to accommodate different patient preferences and needs:

1. Suspension (liquid medicine): Commonly used for younger patients or those who have difficulty swallowing pills
2. Tablets: Available for older children and adults who prefer solid dosage forms
3. Capsules: Another option for those who can swallow solid medications

It’s important to note that diazoxide and chlorothiazide suspensions may not be readily available at community pharmacies. They often need to be imported from abroad by licensed pharmaceutical import companies, which can lead to longer wait times for obtaining these medicines.

Potential Side Effects and Precautions for Diazoxide and Chlorothiazide

As with any medication, diazoxide and chlorothiazide can cause side effects. It’s crucial for patients and caregivers to be aware of these potential effects and to monitor for any adverse reactions.

Common Side Effects of Diazoxide

• Loss of appetite, nausea, and vomiting
• Raised levels of uric acid in the blood
• Retention of salts and fluid, leading to puffiness (edema)
• High blood sugar levels
• Low blood pressure
• Irregular or fast heart rate
• Increased hair growth

Common Side Effects of Chlorothiazide

• Weakness and low blood pressure
• Mild upset stomach
• Changes in blood count

It’s important to note that individual reactions to these medications can vary. Not every patient will experience all or any of these side effects. However, if any side effects become severe or persist for an extended period, it’s crucial to consult with a healthcare provider.

Contraindications: Who Should Avoid Diazoxide and Chlorothiazide?

Certain individuals should exercise caution or avoid using diazoxide and chlorothiazide altogether. Who should not take these medicines? Patients with the following conditions or circumstances should discuss the use of these medications with their healthcare provider:

• Hypersensitivity to diazoxide, chlorothiazide, or any of their ingredients
• Pregnancy, potential pregnancy, or breastfeeding
• Existing heart or lung problems, such as:
  • Pulmonary hypertension
  • Meconium aspiration
  • Respiratory distress
  • Transient tachypnea
  • Pneumonia
  • Sepsis
  • Congenital diaphragmatic hernia
  • Congenital heart disease

It’s crucial for patients to provide a comprehensive medical history to their healthcare providers before starting treatment with diazoxide and chlorothiazide. This ensures that the medications are safe and appropriate for their specific health conditions.

Drug Interactions: Understanding the Interplay with Other Medications

Diazoxide and chlorothiazide can interact with various other medications, potentially altering their effectiveness or increasing the risk of side effects. How do these drugs interact with other common medications?

Medications Known to Interact with Diazoxide

• Anti-hypertension medicines, including:
  • ACE inhibitors
  • Angiotensin II receptor agonists
  • Beta blockers
  • Calcium channel blockers
  • Some diuretics
• Alcohol
• Anti-depressants
• Anti-epileptics, including phenytoin
• Anti-psychotics

Medications Known to Interact with Chlorothiazide

• Anti-diabetic medicines
• Anti-hypertension medicines (as mentioned above)
• Cholestyramine and colestipol resins
• Corticosteroids
• Lithium
• Non-steroidal anti-inflammatory drugs (NSAIDs)

Due to these potential interactions, it’s essential for patients to inform their healthcare providers about all medications, including over-the-counter drugs, herbal supplements, and vitamins, that they are taking. This allows for proper monitoring and adjustment of treatment plans as necessary.

Proper Storage and Handling of Diazoxide and Chlorothiazide

To ensure the effectiveness and safety of diazoxide and chlorothiazide, proper storage and handling are crucial. How should these medications be stored?

• Keep medicines in a safe place out of reach of children
• Store suspensions, tablets, or capsules at room temperature
• Protect from bright light, direct sunlight, and heat
• Avoid storing in bathrooms or other humid environments

Proper storage not only maintains the medication’s efficacy but also prevents accidental ingestion by children or pets. Always check the expiration date before administering the medication and dispose of any expired or unused medication properly.

Monitoring and Follow-up: Ensuring Safe and Effective Treatment

Regular monitoring is essential when using diazoxide and chlorothiazide to ensure their effectiveness and minimize potential side effects. What should patients expect in terms of follow-up care?

• Regular blood tests to monitor blood sugar levels, electrolyte balance, and uric acid levels
• Blood pressure checks to ensure proper management of hypertension
• Periodic assessment of fluid retention and edema
• Evaluation of any potential side effects or drug interactions

Healthcare providers may adjust dosages or recommend additional treatments based on these regular check-ups. Patients should attend all scheduled appointments and promptly report any unusual symptoms or concerns to their healthcare team.

Special Considerations for Pediatric Patients

Diazoxide and chlorothiazide are often prescribed to pediatric patients, particularly those with congenital hyperinsulinism. What special considerations should be taken into account when administering these medications to children?

• Dosage calculations based on the child’s weight and specific medical condition
• Careful monitoring of growth and development, as these medications can affect fluid balance and metabolism
• Vigilance for respiratory side effects, especially in newborns and infants
• Regular assessment of hair growth, as diazoxide can cause hypertrichosis
• Consideration of long-term effects on bone density and mineral metabolism

Parents and caregivers should be educated about the importance of consistent medication administration and the need for regular follow-up appointments. They should also be trained to recognize potential side effects and know when to seek immediate medical attention.

Recognizing Emergency Situations

While diazoxide and chlorothiazide are generally safe when used as prescribed, certain symptoms may indicate a serious reaction requiring immediate medical attention. What signs should prompt an emergency response?

• Difficulty breathing or rapid breathing
• Flaring nostrils or unusual chest movements
• Feeding difficulties in infants
• Blue tinge to lips or skin
• Severe swelling or rapid weight gain
• Signs of allergic reaction, such as rash, itching, or swelling of the face, tongue, or throat

In case of any of these symptoms, patients or caregivers should seek immediate medical attention or go to the nearest emergency department.

Alternative Treatments and Future Developments

While diazoxide and chlorothiazide are effective for many patients, ongoing research continues to explore alternative treatments and potential improvements in managing conditions like hyperinsulinism. What other options might be available now or in the future?

• Targeted genetic therapies for specific forms of congenital hyperinsulinism
• Novel insulin inhibitors with fewer side effects
• Advanced surgical techniques for partial pancreatectomy in severe cases
• Continuous glucose monitoring systems for better blood sugar management
• Combination therapies that may reduce the need for high doses of individual medications

Patients and caregivers should stay informed about new developments in the field and discuss potential alternative treatments with their healthcare providers. As medical knowledge advances, treatment options may expand, offering improved outcomes and quality of life for those affected by conditions requiring diazoxide and chlorothiazide therapy.

Patient Education and Support Resources

Effective management of conditions treated with diazoxide and chlorothiazide often requires comprehensive patient education and support. What resources are available to help patients and caregivers navigate treatment?

• Educational materials provided by healthcare institutions, such as Great Ormond Street Hospital
• Support groups for patients with hyperinsulinism and related conditions
• Online forums and communities for sharing experiences and advice
• Nutritional counseling to manage dietary aspects of treatment
• Pharmacist consultations for medication management and side effect information

Patients and caregivers should take advantage of these resources to enhance their understanding of the treatment process and to connect with others facing similar challenges. Building a strong support network can significantly improve the overall treatment experience and outcomes.

The Role of Multidisciplinary Care

Managing conditions that require diazoxide and chlorothiazide often involves a team of healthcare professionals. How does a multidisciplinary approach benefit patients?

• Endocrinologists for hormone-related aspects of treatment
• Pediatricians for overall child health and development
• Pharmacists for medication management and education
• Dietitians for nutritional guidance
• Genetic counselors for hereditary aspects of certain conditions
• Psychologists or social workers for emotional and social support

This collaborative approach ensures that all aspects of the patient’s health and well-being are addressed, leading to more comprehensive and effective care. Patients and caregivers should feel empowered to communicate with all members of their healthcare team and actively participate in treatment decisions.

Diazoxide and chlorothiazide suspensions | Great Ormond Street Hospital

Diazoxide is used to treat persistently low blood sugar levels (hypoglycaemia) caused by the body producing too much insulin (hyperinsulinism). Chlorothiazide is a diuretic, that is, a medicine that increases the amount of urine produced by the kidneys. This page from Great Ormond Street Hospital (GOSH) describes diazoxide and chlorothiazide, which are usually prescribed together. It explains how they are given and some of their side effects. Each person reacts differently to medicines so your child will not necessarily suffer every side effect mentioned.Diazoxide works by blocking the release of insulin by the body. Chlorothiazide is used in conditions where the body retains too much fluid, causing puffiness (oedema) especially around the eyes or affecting the hands or feet. Chlorothiazide is commonly prescribed alongside diazoxide, as a side effect of this medicine is fluid retention.

How are they given?

Diazoxide is given by mouth two or three times a day. Chlorothiazide is usually given twice a day.

Both are available as a suspension (liquid medicine). For guidance on how to give your child liquid medicines, please read our information sheet or watch our video podcast available on our websiteor the GOSH YouTube™ channel.

Diazoxide and chlorothiazide suspensions are not readily available from your community pharmacy. Neither medicine is available in the UK and so has to be imported from abroad by a licensed pharmaceutical import company. Supplies of these medicines may take longer than usual to obtain, usually several days.

Currently, the Pharmacy department at GOSH obtains diazoxide suspension under the brand name of Proglycem®. The packaging gives the strength of the medicine as 50mg of active ingredient in 1ml of suspension, which is equivalent to 250mg in 5ml. It also contains preservatives, colouring, flavourings and sweetener.

There have been incidents when the wrong strength of other types of medicine have been prescribed so please check the label before giving it your child. If you are given the wrong strength of diazoxide, please inform the team immediately and do not give to your child.

Chlorothiazide suspension is supplied at GOSH in the strength of 250mg of active ingredient in 5ml of suspension. It also contains preservatives, colouring, flavourings and sweetener.

Older children may prefer to take diazoxide and chlorothiazide in tablet or capsule form. Talk to your doctor about this.

Who should not take these medicines?

People with the following conditions should discuss taking these medicines with their doctor.

• Hypersensitivy to diazoxide, chlorothiazide or any of their ingredients
• Pregnant, could be pregnant, trying to become pregnant or breastfeeding
• Existing heart or lung problems, such as pulmonary hypertension, meconium aspiration, respiratory distress, transient tachypnoea, pneumonia, sepsis, congenital diaphragmatic hernia or congenital heart disease.

What are the side effects?

Note: If your child shows any signs of breathing difficulties, such as flaring nostrils, unusual chest movements, rapid breathing, feeding difficulties or a blue tinge to their lips or skin, please see your doctor or take your child to your nearest Accident and Emergency (A&E) department.

If any of the side effects described below are severe or carry on for a long time, please tell your doctor.

Diazoxide

• Loss of appetite, nausea and vomiting
• Raised levels of uric acid in the blood, retention of salts and fluid, puffiness (oedema)
• High blood sugar levels
• Low blood pressure
• Irregular or fast heart rate
• Increased hair growth

Chlorothiazide

• Weakness and low blood pressure
• Mild upset stomach
• Changes in blood count

Interactions with other medicines

Some medicines can react with diazoxide and/or chlorothiazide, altering how well they work. Always check with your doctor or pharmacist before giving your child any other medicines, including herbal or complementary medicines. The following are known to react with diazoxide and/or chlorothiazide so your child will require regular careful monitoring.

Diazoxide

• Anti-hypertension medicines, including ACE inhibitors, angiotensin II receptor agonists, beta blockers, calcium channel blockers and some diuretics
• Alcohol
• Anti-depressants
• Anti-epileptics including phenytoin
• Anti-psychotics

Chlorothiazide

• Anti-diabetic medicines
• Anti-hypertension medicines as above
• Cholestyramine and colestipol resins
• Corticosteroids
• Lithium
• Non-steroidal anti-inflammatory drugs (NSAIDs)

Important

• Keep medicines in a safe place where children cannot reach them
• Keep the suspension, tablets or capsules at room temperature, away from bright light or direct sunlight and away from heat. Do not store in a fridge.
• If you forget to give your child a dose and it is within a few hours of when the dose was due, give it as soon as you remember. Otherwise, do not give this dose but take the next dose when it is due. Do not give a double dose.
• If your child vomits straight after taking the dose, inform your local doctor or nurse, as your child may need to take another one
• If your doctor decides that your child should stop taking these medicines or they pass the expiry date, return any remaining suspension to your pharmacist. Do not flush it down the toilet or throw it away.

Compiled by:

The Pharmacy and Endocrinology departments in collaboration with the Child and Family Information Group Please read this information in conjunction with any patient information leaflet provided by the manufacturer.

Last review date:

July 2020

Ref:

2020F0376

Diazoxide | VCA Animal Hospitals

What is diazoxide?

Diazoxide (brand names: Proglycem®, Eudemine®, Glicemin®, Hypertonalum®, Proglicem®, Sefulken®, Tensuril®) is a medication used to treat low blood sugar in pets with an insulinoma (a tumor of insulin producing cells in the pancreas).

Its use in cats, dogs, ferrets, and other small mammals to treat low blood sugar due to an insulinoma is ‘off label’ or ‘extra label’. Many drugs are commonly prescribed for off label use in veterinary medicine. In these instances, follow your veterinarian’s directions and cautions very carefully as their directions may be significantly different from those on the label.

How is diazoxide given?

Diazoxide is given by mouth in the form of a liquid suspension or compounded capsule. Give with food. Shake liquids well before dosing. Measure liquid forms carefully.

This medication should take effect within 1 to 2 hours; however, effects may not be visibly obvious and therefore laboratory tests may need to be done to evaluate how well this medication is working.

What if I miss giving my pet the medication?

If you miss a dose, give it when you remember, but if it is close to the time for the next dose, skip the dose you missed and give it at the next scheduled time, and return to the regular dosing schedule. Never give your pet two doses at once or give extra doses.

Are there any potential side effects?

The most common side effects include drooling, lack of appetite, vomiting, and diarrhea. Serious side effects include a fast heartbeat, fever, bleeding, bruising, drinking and urinating more, prolonged lack of appetite, muscle weakness, severe vomiting, muscle twitches, seizures, or collapse. In ferrets, side effects include lack of appetite, vomiting, diarrhea, tiredness, and bone marrow abnormalities.

This short-acting medication should stop working within 24 hours, although effects can be longer in pets with liver or kidney disease.

Are there any risk factors for this medication?

Diazoxide should not be used in pets that are allergic to it or thiazide diuretics. Do not use in pets with low blood sugar due to anything other than a tumor. Diazoxide should be used cautiously in pets with heart or kidney disease and very cautiously in pregnant or nursing pets as safety has not been established.

Are there any drug interactions I should be aware of?

The following medications should be used with caution when given with diazoxide: alpha-adrenergic agents, glucocorticoids, hypotensive agents, phenothiazines, phenytoin, or thiazide diuretics.

Be sure to tell your veterinarian about any medications (including vitamins, supplements, or herbal therapies) that your pet is taking.

Is

there any monitoring that needs to be done with this medication?

Blood sugar levels, blood cell counts, and physical examinations should be performed at regular intervals. Your veterinarian may monitor your pet to be sure that the medication is working. Monitor your pet at home for serious side effects.

How do I store diazoxide?

Store the capsules and liquid suspensions between 2°C and 30°C (36°F and 86°F) and protect from light and freezing. Do not use liquid suspensions that have darkened in color, as this may indicate that the medication is no longer effective.

What should I do in case of emergency?

If you suspect an overdose or an adverse reaction to the medication, call your veterinary office immediately. If they are not available, follow their directions in contacting an emergency facility.

Diazoxide – instructions for use

Diazoxide

Instruction:

• Pharmacological action
• Pharmacokinetics
• Readings
• Contraindications
• With care
• Pregnancy and breastfeeding
• Dosage and Administration
• Side effects
• Overdose
• Interaction
• Special instructions
• Transport Management
• Classification

Pharmacological action

Diazoxide is a peripheral arteriolar vasodilator of myotropic action, has a rapid hypotensive (lowering blood pressure) effect due to peripheral vasodilation (expansion of the lumen of the vessels). Expands predominantly resistive vessels, activates potassium channels, causes the release of K ⁺ and hyperpolarization of the membrane of vascular smooth muscle cells, disrupts the function of voltage-dependent Ca2+ channels and reduces the entry of Ca ²⁺ into cells. When administered intravenously, it causes a rapid decrease in systolic and diastolic blood pressure, which is not accompanied by the phenomena of orthostatic hypotension. Leads to retention of Na ⁺ and water. It has a strong relaxing effect on the gastrointestinal tract and uterus. Reduces glomerular filtration and inhibits the excretion of uric acid in the tubules of the kidneys.

Pharmacokinetics

When administered intravenously, the maximum plasma concentration (C _max ) is reached after 2-5 hours.

Plasma protein binding is 90%.

Metabolized in the liver (up to 60%), excreted by the kidneys. The half-life is 2-28 hours.

Indications

Hypertensive crises, especially those associated with acute encephalopathy, acute glomerulonephritis and eclampsia.

Contraindications

• Hypersensitivity to diazoxide;
• acute cerebrovascular accident;
• acute stage of myocardial infarction;
• functional hypoglycemia;
• period of childbirth;
• lactation.

Precautions

• Ischemic heart disease;
• angina;
• heart failure;
• diabetes mellitus;
• pregnancy.

Pregnancy and breastfeeding

Use in pregnancy

FDA fetal category C.

Adequate and strictly controlled studies on the safety of the use of diazoxide during pregnancy have not been conducted. The potential risk to humans is unknown.

In experimental studies on animals, a decrease in the growth and survival of fetuses, an increase in the duration of labor was revealed.

The use of diazoxide during pregnancy is not recommended, except in cases of emergency, on the advice of a physician and if the potential benefit to the mother outweighs the possible risk to the fetus.

Childbirth

Due to the pronounced relaxing effect, the introduction of diazoxide in the first stage of labor can lead to the termination of independent labor.

Use during breastfeeding

Special studies on the safety of the use of diazoxide during breastfeeding have not been conducted.

It is not known if diazoxide passes into breast milk.

If necessary, breast-feeding should be avoided.

Dosage and Administration

Intravenous bolus, undiluted, 1–3 mg/kg. The maximum single dose is 150 mg. If there is no effect, re-introduction at the same dose after 5-15 minutes.

Side effects

Headache, dizziness, redness of the skin, edema, hyperglycemia, severe arterial hypotension (up to collapse), the appearance of signs of ischemia of the heart or brain, confusion, allergic reactions.

Overdose

Symptoms

Hyperglycemia, which may be combined with ketoacidosis, as well as glucosuria.

Treatment

Insulin administration and fluid and electrolyte rebalancing. Due to the long half-life of the drug (approximately 30 hours), overdose symptoms require long-term observation (up to 7 days) until the blood glucose concentration returns to normal. Successful reduction of blood diazoxide concentrations has been reported with peritoneal dialysis in one patient and hemodialysis in another.

Interactions

• Diuretics (diuretics) – the hyperglycemic and hyperuricemic effects of diazoxide may be enhanced by the simultaneous administration of thiazides or other commonly used diuretics;
• Anticoagulants (drugs that prevent blood clots) coumarin derivatives – the use of diazoxide in patients taking coumarin and its derivatives may lead to increased anticoagulant action and require a reduction in the dose of anticoagulant;
• Diphenylhydantoin (epilepsy medicine) – administration of diazoxide to patients taking diphenylhydantoin may cause loss of control of seizures;
• Chlorpromazine (antipsychotic drug) – the hyperglycemic effect of diazoxide may be enhanced by concomitant use of chlorpromazine;
• Insulin (blood glucose lowering drug) blocks the hyperglycemic action of diazoxide. In addition, diazoxide, by inhibiting glucagon-induced insulin release, may cause a false-negative glucagon test;
• alpha-blockers (expand blood vessels and reduce their tone, most often used in the treatment of arterial hypertension and prostate adenoma) – reduce the severity of the hyperglycemic action of diazoxide;
• Antihypertensive drugs (drugs that lower blood pressure) – Diazoxide may increase the effect of antihypertensive drugs.

Special instructions

Diabetes mellitus requires correction of hypoglycemic therapy.

Influence on the ability to drive vehicles and control mechanisms

It is recommended to refrain from driving and engaging in activities that require increased concentration and speed of psychomotor reactions.

Classification

• ATX

  C02DA01, V03AH01

• Pharmacological group

  Vasodilators

• ICD code 10

  I10 Essential (primary) hypertension

• FDA pregnancy category

  C
  (risk not excluded)

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Find out more about the active substance Diazoxide:

• INN
• Reviews
• Questions
• Latin name
• Chemical formula

Information about the active substance Diazoxide is intended for medical and pharmaceutical professionals, for reference purposes only. The instructions are not intended to replace professional medical advice, diagnosis or treatment. The information contained here may change over time. The most accurate information on the use of drugs containing the active substance Diazoxide is contained in the manufacturer’s instructions attached to the package.

composition, indications, dosage, side effects, analogues, contraindications, MedOboz, latest health news, Health Reviewer

Mainly dilates resistive vessels, stimulates potassium channels, causes K + release and hyperpolarization of the membrane of vascular smooth muscle cells, disrupts the function of voltage-dependent Ca2 + channels and reduces the intake of Ca2+ into cells. When administered intravenously, it quickly reduces systolic and diastolic blood pressure, which is not accompanied by symptoms of orthostatic hypotension. Leads to Na+ water retention. It has a strong relaxing effect on the uterus and organs of the gastrointestinal tract. Reduces the glomerular filtration rate and inhibits the excretion of uric acid in the tubules of the kidneys.

Composition and formulation

Diazoxide is produced as a solution for parenteral administration in ampoules of 20 ml, one package contains one ampoule. The active substance is diazoxide.

Indications

Used in the treatment of hypertensive crises associated with acute encephalopathy, acute glomerulonephritis and eclampsia.

Contraindications

Not prescribed for patients with acute cerebrovascular accident, in the acute period of myocardial infarction and hypersensitivity to diazoxide.

It is recommended to be especially careful when prescribing the drug to patients who suffer from coronary heart disease, heart failure, angina pectoris and diabetes mellitus.

Use in pregnancy and lactation

Diazoxide should only be used in pregnant women for vital signs. In addition, the introduction of the drug is highly undesirable in the first stage of labor, as it can provoke a complete cessation of independent labor in a woman.

If it is impossible to treat a lactating woman without the use of diazoxide, then lactation should be abandoned for the duration of treatment.

Method of administration and doses

Diazoxide is used only in extreme cases, since when it is administered, there is a high probability of developing an uncontrolled decrease in blood pressure.

The drug is intended for intravenous bolus administration in undiluted form at a dosage of 1 to 3 mg per kg of body weight. The highest single dose is 150 mg. If after the first administration of the drug it was not possible to achieve the necessary pharmacological effect, then after 5 or 15 minutes the administration of the drug is repeated at the same dosage.

With repeated administration, it should be remembered that in this case, diazoxide can cause a pronounced retention of sodium and water.