Midodrine, known by the trade name Gutron, is used as a drug to treat orthostatic hypotension (low blood pressure). It is a so-called prodrug whose breakdown product (desglymidodrine) is the actual active ingredient.
What is midodrine?
Midodrine is used as a drug to treat orthostatic hypotension (low blood pressure). After use, midodrine is converted to desglymidodrine by cleavage of glycine, which then acts as a direct sympathomimetic. Both midodrine and the degradation product desglymidrine have the same basic structure as the neurotransmitters adrenaline and noradrenaline and thus fulfill the same functions. Midodrine exists chemically as a hydrochloride. It is a white, crystalline and odorless powder with a bitter taste, which is readily soluble in water but poorly soluble in alcohol. When needed, it is administered in tablet form. After oral administration, it is rapidly absorbed by the body and metabolized to the active substance within 120 minutes with glycine cleavage. Excretion is primarily renal (via urine) and is 90 percent complete after 24 hours. Midodrine has a plasma half-life of approximately 15 minutes and desglymidodrine of approximately 5-6 hours.
Pharmacologic effects
The metabolite desglymidodrine is an agonist at alpha-adrenoceptors. These receptors are usually activated by the signaling agents epinephrine and norepinephrine. They are found in large numbers in the nervous system, salivary glands, cardiovascular system, genitourinary tract, and liver. Desglymidodrine, as a direct sympathomimetic, stimulates these receptors, as do the neurotransmitters epinephrine and norepinephrine. Since midodrine and its metabolite desglymidodrine are water-soluble but not lipid-soluble, only the peripheral alpha receptors are excited. This causes the increase in vascular resistance and tonification of capacitance vessels, evoking constriction of blood vessels resulting in an increase in blood pressure. Due to arterial and venous vasoconstriction (vasoconstriction), this affects both systolic and diastolic blood pressure. Furthermore, midodrine also stimulates alpha receptors at the urogenital tract, delaying urinary flow by increasing tone at the bladder outlet. Bronchial muscle constriction also occurs only at doses above 1 mg/kg.
Medicinal use and application
Midodrine is mainly used against low blood pressure resulting from orthostatic dysregulation or from the use of antidepressants and neuroleptics. Specifically, this means its use against blood pressure drop during position change and in neurogenic orthostatic hypotension. It should be noted, however, that all other measures should first be exhausted until it is determined that treatment of the underlying disease has not eliminated the symptoms. Primarily, low blood pressure should be prevented by eating a high-salt diet, avoiding large meals, increasing fluid intake, and taking certain measures, such as standing up slowly or wearing compression stockings. Discontinuation of strong blood pressure lowering drugs can also be the remedy of choice. Only if these measures do not lead to success should one think of treatment with midodrine. In this context, it should also be mentioned that low blood pressure may reduce the quality of life, but as a consequence it rarely leads to serious damage to the organism. The underlying disease can be dangerous, but there it is necessary to treat it causally first anyway. The low blood pressure is raised with midodrine without affecting the underlying disease. In exceptional cases, the drug is also approved for adjunctive therapy in urinary stress incontinence.
Risks and side effects
Midodrine is contraindicated in cardiovascular disease, hyperthyroidism, delayed urination due to prostate enlargement, and also in renal dysfunction and diabetes. Of course, it should also not be used in case of hypersensitivity to the active ingredient. Common side effects when using midodrine may include a tingling sensation, goose bumps, itching, or a cold feeling in the skin. Furthermore, pulse slowing, palpitations, cardiac arrhythmias, hypertension while lying down, and delayed bladder emptying may occur. Less frequently, digestive problems, restlessness, excitability, irritability and headaches occur.If severe palpitations or severe pulse decelerations occur, treatment with midodrine should be discontinued. Alternative treatment should then be considered. Use in combination with various medications such as beta-blockers, tricyclic antidepressants, thyroid hormones, antiallergic agents, anti-inflammatory agents, or even atropine should be avoided, as undesirable side effects may occur.
