Mildronate

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Mildronate, also known as Meldonium is a cytoprotective antiischemic drug. The main indications for use of Mildronate are heart ischemia and its consequences. Besides that, this drug has found wide usage in the treatment of cerebrovascular disorders and in sport.

Mildronate was developed in the 1970s by Latvian Institute of Organic Synthesis. Initially, it was synthesized from the rocket fuel and supposed to be used in agriculture as stress-protector and growth-promoting agent for cattle. After discovering the cardioprotective properties of Meldonium, it began to be used in clinical practice, sport and in the military medicine. In 2015, 17% of professional Russian athletes and 2% of athletes from other countries had Mildronate in their system.

Usage in medicine and indications for use

Mildronate belongs to the partial fatty acid oxidation inhibitors class. It adjusts metabolism and energy supply of the body tissues under heavy loads and in ischemic conditions. The field of clinical application and indications include:

  • Cardiology – angina, myocardial infarction, chronic cardiac insufficiency, and cardiomyopathy. It also can be used as prophylaxis of heart diseases which is most important for athletes.
  • Neurology – stroke, cerebrovascular insufficiency and other cerebrovascular disorders.
  • Ophthalmology – Intraocular hemorrhage, retinal vein thrombosis and retinopathy of various origins (diabetic or hypertensive retinopathy).
  • Decreased work performance, mental and physical overloads.
  • Alcohol abstinence syndrome.

Pharmacological effects and mechanism of action

Mildronate decrease carnitine levels by inhibiting its biosynthesis and renal reabsorption. Carnitine is involved in the transportation of fatty acids across the mitochondrial membrane, and in the fatty acids oxidation. Fatty acids are the primary energy source of the myocardium. The other sources are glucose and ketone bodies.

Because of the decreased fatty acid oxidation in mitochondria, the cells switch to the glycolytic source of ATP production. This allows the heart muscle to use oxygen more efficiently. Glucose provides 6.33 mole of ATP per one mole of oxygen, while palmitate (fatty acid) produces 5.61 mole of ATP out of the same amount of oxygen. It is a significant advantage in diseases associated with compromised oxygen delivery, like heart failure.

Besides that, Meldonium increase 2,3-bisphosphoglycerate levels thus enhancing the ability of red blood cells to release the oxygen.

Possible side effects are:

  • Allergic reactions (redness, rash, itching, swelling).
  • Digestive problems.
  • Increased heart rate.
  • Hypertension or hypotension (increased/decreased blood pressure).
  • Agitation.

Recommended dosage varies depending on the indication.

Heavy physical and mental loads – 500mg daily for 10-14 days. The course can be repeated after 2-3 weeks if needed. It is recommended to take Mildronate in the first half of the day.

In the complex treatment of myocardial infarction – 5-10ml a day intravenously. In ischemic heart disease and chronic cardiac insufficiency 5-10ml a day intravenously, or 5ml intramuscular 1-2 times a day, with a transition to oral administration after 10-14 days. The total length of the course is 4-6 weeks.

In the complex treatment in the acute phase of cerebrovascular disorders – 5ml daily administered intravenously, with a transition to oral administration after 10 days. The total length of the course is 4-6 weeks.

In ophthalmology (hemophthalmia, retinopathy) 0.5ml daily peribulbar injections for 10 days.