Diuretics. Drugs affecting myometrium.

Diuretics may be represented by the following groups.I. Diuretics have a direct effect on the function of the epithelium of renal tubules

Substances containing sulfa groupa) the ThiazidesDihlotiazid Tsiklometiazidb) The compounds of different ("netiazidnoy") structure Furosemide Klopamid Oksodolin2. Dichlorophenoxyacetic acid derivatives of ethacrynic acid3. Xanthine Eufillin4. Pteridine derivatives Triamterene5. Amiloride derivatives pirazinoilguanidinaII. Aldosterone antagonists SpironolactoneIII. Osmotically active diuretics mannitol Urea

Dihlotiazid proves ¬ Vaeth also some influence on the proximal tubules. In a small degree ¬ nor inhibits carbonic anhydrase, which is manifested in a decrease in reabsor ¬ btsii hydrogen. Increases the secretion of potassium ions. Violates ionov'magniya excretion. All this leads to increased urinary excretion of sodium, chlorine, potassium and magnesium and HCO3 It will be appreciated that prolonged use dihlotiazid delays renal excretion of calcium ions. This can have a beneficial effect in the presence of kidney stones contain calcium.In addition, dihlotiazid in small doses reduces the excretion (secretion) mo ¬ chevoy acid and can cause hyperuricemia, gout in the presence of her Techation in this case is compounded. In large doses dihlotiazid promotes exported cultural Deniyu uric acid.

The drug remains active with acidosis and alkalosis. Is well absorbed from the gastrointestinal tract. The action develops in 30-60 minutes and reaches a maximum for the 2nd hour. The total duration of effect ¬ ta 8-12 hours The drug is partially bound to plasma proteins (60%). Excreted by the kidneys. Getting used to it practically does not occur. In addition to the diuretic action, we are dihlotiazida antihypertensive properties.Dihlotiazid applied as a diuretic antihypertensive agent as, glaucoma, as well as diabetes insipidus, wherein it is ¬ reducing diuresis (unclear mechanism of action), as well as hypercalciuria. The main side effects - hypokalemia and hypomagnesemia. Their prevention and treatment ¬ tic is the appointment of potassium chloride tablets "Asparkam" panangina, magnesium chloride. It is also possible gipohloremichesky ¬ cue metabolic alkalosis. Sometimes there is nausea, vomiting, diarrhea, weakness, hyperglycemic ¬ mia, various allergic reactions.

Has similar properties tsiklometiazid (cyclopenthiazide, salimid). On chemical structure it is similar to dihlotiazidom, but about 50 times more active than him.Prolonged diuretic different "netiazidnye" drugs clopamide (brinaldiks) and especially oksodolim (chlorthalidone, gigroton). Klopamid characterized by high activity. Its duration of action up to 1 day or more (in average 8-18 hours). Oksodolina effect develops within 2-4 hours and lasts up to 3 days. Increased diuresis under the influence of these substances is mainly due to inhibition of the reabsorption of sodium and chloride in the distal tubules and partly - in the proximal. Both drugs reduce blood pressure. From the gastro-intestinal tract are absorbed well. Excreted by the kidneys and intestines. Indications for use and side effects similar to those of the tech dihlotiazida.

By "netiazidnym" compounds containing sulfa grouping ¬ ku, applies indapamide (arifon). From the digestive tract of the drug is absorbed well. tl / 2 ~ 18 hours Assign 1 time per day. Apply advantage ¬ tively to lower blood pressure. Of the possible side effects ¬ HN hypokalemia, allergic reactions.A group of "loop" diuretics are furosemide and ethacrynic acid. Highly efficient, fast, and the drug is short-¬ Xia furosemide (Lasix). Basically, it inhibits the active reabsorption of sodium and chlorine in the large segment of the ascending loop of the nephron. Furosemide also reduces the reabsorption of sodium in the proximal tubule, but it is of secondary importance. Increases the excretion of potassium and magnesium. Furthermore, furosemide increases renal blood flow.

The combination of these influences ¬ tions leads to a significant increase in urine output. The activity of carbonic anhydrase is not affected. Delays in the body of uric acid. May cause hy ¬ perglikemiyu. Increases the excretion of calcium ions, which can be used with an overdose of ergocalciferol or hyperparathyroidism. The effectiveness of furosemide is not affected by fluctuations in acid-base status. When intra ¬ intravenously administered drug effect develops in 3-4 minutes and lasts for 1 - 2 hours Entering into diuresis observed after 20-30 min and with ¬ preserved up to 3-4 hours, about 95% of the drug binds to plasma proteins. 60-70% excreted by the kidneys and the rest - the intestines. Furosemide has a mind ¬ rennoy hypotensive activity.

It is used as a diuretic to lower blood pressure ¬ tion in hypertension (including in combination with other hypotensive ¬ sive drugs), pulmonary edema, swelling of the brain, for the forced diuretic ¬ for acute poisoning by chemicals hypercalcemia. In the appointment of furosemide may develop hypokalemia, hypomagnesemia, metabolic alkalosis gipokaliemicheskogo, dyspeptic disorders. Some patients have hearing loss, headache, dizziness, allergic reactions.Slightly inferior furosemide diuretic activity by ethacrynic acid (Uregei). Localization of action ethacrynic acid is similar to the one ¬ kovoy for furosemide. There is a depression of active NaCl reabsorption in the thick ¬ Dental segment of the ascending loop of the nephron. Also, ethacrynic acid inhibits the reabsorption of sodium ions in the proximal tubules. It exists as a way to ¬ excretion of magnesium ions.

In a small degree increases exported cultural ¬ denie potassium ions. No effect on carbonic anhydrase. May cause hypokalemic metabolic alkalosis. When violations of the acid-base balance of the activity of ethacrynic acid is maintained.With intravenous administration of its effect after 15 minutes and lasts for 3-4 hours Entering into the drug takes effect within 60-90 minutes; continue ¬ tive of up to 8 hours Associated with plasma proteins. In the form of conjugates excreted by the kidneys (2/3) and to a lesser degree (1/3) - intestines. It has a mild hypotensive activity.Indications for use are the same as those of furosemide. Possible side effects: hypokalemia, hypomagnesemia, alkalosis, weakness, dizziness, diarrhea, loss of hearing (sometimes pronounced).Synthesized derivative of ethacrynic acid - indakrinon, ¬ turn out a diuretic and uricosuric action.

The so-called "potassium and magniysberegayuschim" diuretics of this group ¬ Py are triamterene and amiloride. Triamterene (pterofen) - a derivative of pteridine. Refers to diuretics, trapped in the body of potassium and magnesium ions. Diuretic triamterene efficiency is low. Urine output is increased due to inhibition of sodium reabsorption. At the same time shows the chloride ions. The main localization of action - collecting tubes and distal tubules in which the drug blocks sodium channels. In the non ¬ greatly increases the elimination of uric acid.Triamterene absorbed from the intestine quickly. About 50% of its bound to plasma proteins. The maximum effect occurs in about 2 hours Pro ¬ duration of action 6-8 hours Provided by the kidneys, mainly in the form of metabolites ¬ litas. Triamterene usually employed in combination with diuretics causing hypokalemia (eg dihlotiazidom). ¬ side effects you: dyspepsia, headache, dizziness, possible hyperkalemia, azotemia, cramps in the muscles of the lower extremities.

By "potassium and magniysberegayuschim" diuretic amiloride relates. On chemical structure is pirazinoilguanidinom. Localization ¬ quences of his action is similar to that triamterene. By diuretic efficiency ustu ¬ dihlotiazidom Paet. Has a hypotensive effect.Appointed inside. About 50% of absorbed drug. The plasma protein is not snizyvaetsya. The action develops within 2h and continues until 24h. Biotransformation ¬ formation is not exposed to amiloride. Excreted by the kidneys. Usually used with other diuretics that cause hypokalemia. Ana ¬ logical triamterena somewhat increases the excretion of uric acid and reduce ¬ decreases the excretion of calcium ions. Of the side effects are possible hyperkalemia, nausea, vomiting, head ¬ tion pain.Relatively ineffective as a diuretic xanthine derivatives for example ¬ eufillin. Om violates the reabsorption of sodium and chloride in the proximal and distal tubules. Slightly increased excretion of potassium. ¬ acid-base status but does not change. The drug affects the cardiovascular system; Unlike caffeine had more pronounced sosudorasshi ¬ fying action. It increases renal blood flow and increases the glomerular filtration ¬ radio.

Aldosterone antagonistsPowered by two kinds of mineralocorticoid aldosterone antagonists. One corner ¬ Neta its synthesis, others counteract the effect of aldosterone on renal function ¬ governmental tubules. The second group of substances acts more selectively and representation ¬ is of interest for practical medicine. One such drug, called spironolactone (Aldactone, veroshpiron) is used as a diuretic.It is known that aldosterone excretion of sodium ions decreases (increases their reabsorption) and increases the secretion of potassium ions. This occurs in the collecting tubes and distal renal tubules. Spironolactone dei ¬ corresponds to the same parts of the nephron, but in the opposite direction: it blocks ¬ ruet intracellular receptors, which interact with aldosterone, and increases urinary excretion of sodium, chlorine, and appropriate amounts of water. The secretion of potassium ions it lowers and their concentration in blood increases

In this respect, spironolactone acts like triamterene, but there ¬ tively different from most other diuretics that causes ¬ vayut in varying degrees, expressed hypokalemia. The mechanism of "potassium-sparing" ("kaliyzaderzhivayuschego") effect in the spironolactone and triamterene different. Spironolactone has also "magniysberegayuschee" effect. Keys ¬ leaf itself, the ground state does not violate the spironolactone. Effective with the se ¬ acidosis and alkalosis. The accumulation of uric acid in the body usually does not. In the body produces the active metabolite of spironolactone, canrenone named, through which mainly operates and spironolactone.Spironolactone - relatively inactive diuretic. Most effective when it ¬ venous edema associated with increased production of aldosterone. Its action develops slowly over 2-5 days, t spironolactone is 10 minutes, and canrenone - 16 hours Spironolactone is often prescribed in combination with other diuretics, especially those that cause hypokalemia. The drug also has antihypertensive properties. Take it inside.

Of the side effects sometimes observed dizziness, drowsiness, skin rash may occur hyperkalemia, gynecomastia.Osmotic activity of diureticsOperation of such diuretics (which include mannitol and urea) is such that when the lumen of the tubules, they are creating ¬ high osmotic pressure (mannitol absorption is inversely a small extent, and urea - 50%). This significantly reduces ¬ is the reabsorption of water and, to some extent - of sodium ions. They operate mainly in the proximal tubule, although the effect is maintained in some degree ¬ penalties throughout the tubules (in the descending loop of the nephron, a collector ¬ governmental tubes). On the acid-base status is not affected. Excretion of ka ¬ lence may slightly increase.In practical medicine mainly used mannitol.Mannitol (mannitol) unlike urea (carbamide) does not penetrate cell membranes and tissue barriers (e.g., blood-brain ba ¬ Riera) does not increase the content of residual nitrogen in the blood, which may be mo ¬ that when using urea (especially impaired function kidneys).

Mannitol is used as a diuretic and dehydrating agent (cerebral edema), acute poisoning by chemicals. Urea was applied ¬ out mainly as a dehydrating agent (sometimes to reduce the intra ¬ riglaznogo pressure in glaucoma).Urea is injected intravenously and sometimes inside, mannitol - only intravenously (in the digestive tract it is not absorbed).Side effects of mannitol: headache, nausea, vomiting, dizziness, pain in the chest.Drugs are contraindicated in violation of renal excretory function. Urea is also not recommended to assign with severe hepatic and ser ¬ dechno-vascular insufficiency.

DRUGS AFFECTING idiometritisContractile activity and tone of the myometrium regulated neyrogumoralnytmi mechanisms. In the myometrium are m-cholinergic receptors, as well as the a-and p-adrenergic receptors. M-cholinergic stimulation and a-adrenoceptor ¬ shows you the stimulating effect, and p3-adrenoceptor - depressing. In addition, a significant stimulatory effect on the contractile activity of mi ¬ ometriya have a female sex hormone estrogen, the hormone back to ¬ a pituitary oxytocin and prostaglandins. However, there are endogenous substances that suppress its contractile activity (progesterone and prostacyclin).Means, which influence on the myometrium are divided into the following groups:1) Means, which influence mainly on the contractile activity of the myometrium Reinforcing the contractile activity:Nutrients-oxytocin, pituitrin, prostaglandin F2 alpha (dinoprost), prostaglandin E2 (dinoprostone).

Herbal drugs-pahikarpin hydriodide.Synthetic means-izoverin.                Debilitating contractile activity:Substances that stimulate beta 2-adrenergic receptors, salbutamol, fenoterolMeans of anesthesia - sodium hydroxybutyrateMiscellaneous equipment - magnesium sulphate2) Decreasing the tone of the uterine cervix, atropine sulfate, dinoprost, dinoproston 3) Means, which increase primarily tone of the myometriumHerbal drugs-ergometrine maleate, ergotamine tartrate, an extract of ergot thick ergotal.Synthetic agents - kotarnina chloride

Of the funds that increase the contractile activity of the myometrium of special interest natural metabolites.Oxytocin - the hormone of the posterior lobe of the pituitary gland, produced synthetically, increases the contractile activity of the myometrium. The pregnant uterus is more sensitive to it. The effect of oxytocin is most pronounced during birth and persists for several days after birth. In large doses, oxytocin causes the increase in the tone of the myometrium.It is used primarily to induce and stimulate labor, sometimes in the postpartum uterine atony and bleeding. Injected intravenously with glucose.There is a synthetic analogue of oxytocin - dezaminooksitotsina. It has greater activity than oxytocin. Buccal tablets, or it is used under the tongue. It is well absorbed by the oral mucosa. It is used to accelerate the uterine involution and to stimulate lactation.

Oxytocin is also contained in pituitrina. The latter is an aqueous extract of the posterior lobe of the pituitary gland of beef cattle. In addition to oxytocin, pita ¬ rin contains vasopressin (antidiuretic hormone). Because of vasopressin it increases the blood pressure. However, the drug has a posterior pituitary gifototsin (pituitrin M) which primarily contains ¬ zhitsya oxytocin. Both drugs dispensed in units of (ED). In akusherskoginekologichsskoy practice they are used for the same indications as the ca-sitotsin. Administered subcutaneously and intramuscularly.Much attention is attracted by prostaglandins. This active biogenic compounds found in many tissues and organs. They belong to the pro ¬ polinenasyscheppyh derivatives of fatty acids containing a cyclopentane molecule structure. In the body, the prostaglandins are synthesized from arachidonic acid. Today we know a great chisloprostaglandinov. Usually designated by their letter indices (E, F, etc.). Many of prostaglandipon have a pronounced stimulatory effect on uterine myometrium at all stages of pregnancy, and some prostaglandins - and in respect of non-pregnant uterus.

As preparations for artificial abortion and rodouskoreniya ¬ are using drugs and F2alfa prostaglandin E2.Dinoprostu has a strong stimulation ¬ liruyuschim influence on the myometrium. It causes rhythmic contraction and elevated tone ¬ pregnant and non-pregnant uterus along with the expansion necks ¬ ki uterus. However, the spectrum of activity is not limited to dinoprostu myometrium. Dinoprostu clearly increases the tone of the bronchial muscles. The latter effect is especially pronounced in patients with bronchial asthma. This drug increases cardiac output, heart rate quickens. At the doses used in obstetric practice, dinprost systemic arterial pressure prac ¬ cally no effect, and in large doses, it increases somewhat. It narrows le ¬ pulmonary vessels, increases the motility of the gastrointestinal tract.Under the influence of dinoprostu increases the permeability of blood vessels. For the action of this substance is typical degeneration of the corpus luteum (luteolysis).A more pronounced and prolonged effect on the myometrium has metildinoprost (15-methyl-prostaglandin F2u).

Dinoprostone (prostaglandin E2, enzaprost E) also causes a marked increase in the rhythmic contractions of the myometrium of the pregnant uterus and build ¬ tion of its tone. Relaxes the cervix. Lowers blood pressure (total peripheral resistance drops). Causes a compensatory tachycardia. Extend (unlike dinoprost) pulmonary vessels and bronchi. Increases the permeability of capillaries.Vascular 'effects of prostaglandins associated with their modulatory effect ¬ tion on adrenergic innervation. Prostaglandins that increase adrenergic effect, narrowing the blood vessels to weaken - expanding it. In the former case, the accumulation of cAMP in the second - a decrease in its content.Intestinal motility dinoproston increases (due to the stimulation of the longitudinal muscles), inhibits the secretion of gastric glands. Has lyuteoliticheskoe action.