The intersection of lung and the intersection of artery and to treat _'s treatment target of high pressure

The intersection of lung and the intersection of artery and to treat _'s treatment target of high pressure
To the treatment medicine to the above-mentioned many kinds of targets had illness coming on in the mechanism and not already developed or developed some pertinence with links of high pressure of lung artery in recent years, unite application with the original traditional therapeutic medicine, has enriched the artery high-pressure medicine treatment means of lung greatly.
1. The base-line treats the target to click
( l) Change the life style
The high-pressure patient of lung artery often has nervous and mental depression at various degrees, the doctor should pay attention to this one and treat the target to click, launch patient's education actively, tell a patient lie in bed for a long time, encourage the appropriate activity. Prevent the overweight physical exertion from or take a trip to plateau ' It is higher than 1500m that above sea level) ,Need to supplement the oxygen, limit sodium diet (<2400mg day) by air ,Improve organism immunity, try hard to prevent influenza and pneumonia and streptococcus pneumonia, avoid taking appetite inhibitor, shrink nasal sinus medicine. Pay attention to some medicines and treat the interaction of the high-pressure medicine of lung artery, lower candy or encircle fungus to be plain Porson smooth while being excellent, the intersection of nitrate and the west and that. Avoid gestation, giving a birth and strong manual labor, estrogen contraceptive may increase the risk of thromboembolism of intravenous thrombus. Lung the intersection of artery and high-pressure the intersection of patient and the intersection of alternative and surgery should weigh risk interests than. ( 2) Tradition treatment
According to patient heart function situation appropriate application diuretic, lighten the right heart depletedly. Employ and observe electrolyte and renal function change in the course closely. Patient of a dose of syndrome of Eisenman employs diuretic to need even more to be prudent.
The hypoxia is one of the main factors causing the lung blood vessel to shrink. The oxygen intake of the low flow can improve oxygen deficiency and reduce the artery pressure of lung continuously, disease patient of chronic hypoxemia (Pa02<60mmHg) It should be long Cheng oxygen is treated, make the arterial oxygen saturation more than 90%.
Digoxin can improve lung artery high-pressure right room of patient function complete, and can the right heart ranks about 10% of blood volume at increasing the quiet interest, then relieve the situation that the left ventricle is pinched, can apply to cardiac dilatation, patient low in cardiac output. Especially erupt the vibrant patient of atrium simultaneously.
Person who send the intersection of lung and the intersection of artery and high-pressure patient offer forest, law of China, can lengthen the time of surviving after the treatment specially, it is main it is for patient for lung in reason blood vessel bed can normal position thrombosis,last lung pathological changes vascular. So propose the high-pressure patient of lung artery takes China to send the forest and make INR keep among 1.5-2.0 conventionally. The intersection of lung and the intersection of artery and high pressure that relevant factor lead to the fact employ anticoagulant opinion yet inconsistent, although the desmosis or high-pressure patient of door pulse can increase the gastrointestinal tract and bleed, but generally propose for the anticoagulatory treatment under having taboo situation. Should pay attention to the interaction with some medicines.
2.The calcium passway blocks pharmaceuticals
About 10% of the specially sending high-pressure patients' acute lung blood vessels of lung artery are expanded and tested for being for a long time positive, therefore block pharmaceuticals to the calcium passway sensitively. Block life quality and notably insensitive patient of the survival rate of the long-term sensitive patient of pharmaceutical to the calcium passway, survival rate is nearly 100% its 10, but sensitive survival rate will obviously drop in a short time. So need to emphasize, the acute lung blood vessel expands and tests the negative patient to employ the calcium passway to resist pharmaceuticals and basically have no benefit short of moneyly, may also result in worsening, so the taboo uses the calcium passway to resist pharmaceuticals short of moneyly in lacking the experimental foundation of vascular medicine. Using medicine must observe security and validity that the calcium passway blocks pharmaceutical in the course closely, adjust the dosage according to the condition. Which use medicine based on the principle heart rate quick patient consider the intersection of sulphur and tall and erect the intersection of type and medicine, basic slow heart rate ' < 60bpm) Patient consideration two hydrogen pyridines medicine.
Bad reaction:
Keep in touch with pour into and lack proper care and aggravate, increase and shunt in the lung, the partial pressure of oxygen of arterial blood drops;
The contradiction lung arterial pressure rises;
Kindling is in heart failure or lung edema;
Die suddenly.
So, high-pressure patients of lung artery of serious disease should observe to use the calcium passway in hospital while blocking pharmaceuticals, usually begin with low dose, and need to observe the administration and react closely, especially when it is early to use medicine and increase the dosage.
3. The new target is to the medicine
( 1) The inner cover plain receptor resists pharmaceuticals short of moneyly
The inner cover is plain - a (Endothelin-1, ET-1) It is effective endogenous vasoconstrictor and smooth muscle cell that urge to split plainly, can make the intersection of lung and blood vessel shrink with the hyperplasia of transition causing the artery high pressure of lung. The function of ET-1 is lain between and lead by ETA and ETB receptor.
Porson is smooth (Bosentan) It is a non- alternative inner cover plain receptor that resists pharmaceuticals short of moneyly, can inhibit ET-1 and ET-A from being accorded with by the body and ET-B receptor competitively, thus block the function of ET-1. Porson is smooth can obviously improve 6min walking distance and blood flow dynamics, and lengthen the time of surviving. Specially suitable for the hierarchical II_IV grade of WHO function the sending artery high pressure of lung, congenital heart disease and relevance lung artery high pressure and treatment of the high-pressure patient of lung artery of the desmosis relevance.
Because Porson has bad reaction that potential liver damages frankly, propose monitoring liver function per month at least during the treatment period. If transaminase increases and is no more than 3 times of high limit of normal value, can continue the administration to observe; 3- Between 5 times, can be reduced by half the dosage and continued using or delaying using medicine, monitor liver function every 2 weeks, use again after transaminase returns to normal; Between 5-8 times, delay using medicine, monitor liver function every 2 weeks and can consider using medicine again after transaminase returns to normal, up to 8 more than o'clock, need to be out of use, does not consider using medicine again again.
At present it is at Europe and U.S.A. is already alternative ETA receptor listing last pharmaceutical short of moneyly,west he give birth to smooth and grow smooth Ann shellfish, preliminary clinical research reveals that safe and effective to the high-pressure patient of lung artery, there is long-term curative effect to further studying.
( 2) Plain and structural analog of forefront ring
The high pressure therapeutic medicine of lung artery listed initially is FLOLAN, the endogenous forefront ring is plain (epoprostenol) ,Up to now remain patient's first-selected therapeutic method of IV grade of the heart function, but our country is not listed at present. In addition, this medicine costs an arm and a leg, it is complicated to use, there are more bad reactions.
It is plain (llalprost) to suck forefront of Lip river of Iraq Similar to endogenous plain structure of forefront ring, the chemical property is steady, half-life is relatively short. It is verified that multiple clinical trials including AIR are studied, the artery high pressure of severe lung in the plain treatment that can be safe and effective of forefront of Lip river of Iraq, employ but improvement 6min walking distance in short term, the dynamics parameter of the blood flow and time of surviving. Sanctioned being used for treating the high-pressure patient of lung artery of the hierarchical III-IV grade of WHO function by U.S.A. FDA in 2004. This medicine was listed on our country in March of 2006. Because arteriolar with ending in the alveolus detailed bronchus and alveolus dissect the relation to adjoin, forefront of Lip river of Iraq is deposited on the surface of alveolus at first after usually sucking, make close to small lung artery, arteriole smooth muscle and capillary of the alveolus the sphincter is expanded preferablies, and the influence of passing the effect of avoiding one plays a therapeutic role in medicine to the greatest extent.
The plain dosage that sucks of forefront of Lip river of Iraq each time should vary with each individual, the acute lung blood vessel of concrete need expands the test to appraise. Employ this medicine for a long time, can reduce artery pressure of lung and lung blood vessel resistance, improve the able to bearing amount of sports, quality of making the life better. Patients of children complying with difference, seldom use this kind of medicine. Suck the common bad reaction of Iraq's Lip river with plain forefront and cough, have a headache, congested, specific can cause and generate heat. Sanction, have the intersection of song and the intersection of forefront and the intersection of ring and plain, the intersection of shellfish and the intersection of forefront and getting plain ring by listing the intersection of forefront and the intersection of ring and plain kinds of medicine already abroad in addition. Especially the forefront ring of the song is plain, long-term curative effect is relatively approved by foreign doctor.
( 3) Phosphoric acid diesterase inhibitor
The skin is damaged in the high-pressure patient's lung artery of lung artery, NO formates and drops, it is an ideal target to therapeutic method to supplement NO, but the dosage is very difficult to control to operate, it is especially unable to realize temporarily at home.
NO can activate sour ring enzyme (cGMP) of glucoside of soluble bird directly ,And cGMP can activate cGMP kinase, makes the potassium ionophore open, inhibits the indraft of calcium ion, make the calcium density in cells reduce, relax the blood vessel smooth muscle of lung. So NO relaxation blood vessel effect depends on increasing and keeping the content of cGMP in the smooth muscle cells of blood vessel. And cGMP degrades and mainly relies on phosphoric acid diesterase 5( PDE5) ,PDE-5 inhibitor can prevent cGMP from degrading in this link, increases the density in the cells of cGMP, produce it and expand function of blood vessel. PDE-5 high expression to employ inhibitor, PDE5 of alternative, treat the intersection of lung and the intersection of artery and molecule foundation of high pressure in the intersection of lung and the intersection of blood vessel and smooth muscle at the same time.
PDE5 inhibitor already listed at present does not have ground that in the west (Sildenafi1) Medicines such as non- that,etc. with cutting down, among them ground that has not already increased indication of the artery high pressure of lung abroad in the west, one brute force, highly selectively the intersection of PDE-5 and inhibitor, can improve the intersection of lung and the intersection of artery and high-pressure the intersection of movement and able to bearing amount, function grading and blood flow dynamics of patient. The west bad reaction that have headache, blush, indigestion and nosebleed.
New the intersection of PDE-5 and inhibitor cut down those demonstrate better curative effect in the domestic clinical trial non-. Cut down that it inhibits function of PDE5 to be the west 20 that; And the price is not cheaper than that in the west, but less to its research in the world, it may benefit the high-pressure patient of lung artery to only study and point out it on a small scale; Carrying on relevant clinical research at home, the preliminary result reveals safe and effectively. The long-term result awaits to further study.
( 4) Jointly treat
Have illness coming on in the mechanism under high pressure according to the lung artery already expounded, jointly employ to with treating the medicine that the target is lighted, will become artery high pressure of lung more effective treatment choice. Some medicines such as PDE inhibitors can improve and lengthen the function of other medicines such as forefront with plain ring. Unite the therapeutic purpose to lie in fully giving play to the role of various medicines, reduce the emergence of the bad reaction to the greatest extent. A present one use medicine scheme often from the intersection of forefront and the intersection of plain, the west and that, Lip river of Iraq, jointly and Porson choose two or three union while being arbitrary in being smooth, most experts recommend PDE-5 inhibitor and Porson's smooth union at present, used for patient's treating for a long time. Patient to that the acute right heart is depleted and seriously in heart failure, can consider uniting forefront of Lip river of Iraq plainly with PDE-5 inhibitor in a short time, but notice, this scheme is not fit for long-term application.
4. Other new targets are to therapeutic method
( l) Gene therapy
McMurtry,etc. discovers, 6 specially sending high-pressure patient's lung artery survivin genes of lung artery are excessively expressed, suck the intersection of survivin and mutant that adenovirus carry, carry on gene therapy to the intersection of tattle and the intersection of lung and the intersection of artery and loud mouse of high pressure that alkali induce, can reduce the blood vessel resistance of lung, the right room is loose and the membrane is plump in the lung artery. Internal and external experiments of body show, inhibit surivivin inducible lung artery smooth muscle cells from withering and dying, reduce hyperplasia, inhibit lung artery survivin inappropriate to express, become target to treat the intersection of lung and the intersection of artery and new tactics of high pressure in the high-pressure patient.
( 2) Active intestines peptide (Vasoactive intestinalpeptide, VIP) of blood vessel
VIP is neural peptide playing a neurotransmission role at first, think now it is that an effective body lung circulates the blood vessel and expands pharmaceuticals. Petkov,etc. discovers, VIP is scarce in specially sending blood plasma and lung of high-pressure patient of lung artery are organized, and the substitution of hormone treat but substantive the intersection of blood flow and the intersection of dynamics and parameter and prognostic parameter, patient of improvement, have bad reaction. In 8 patients studying, VIP can reduce lung artery and press, improve cardiac output and mix intravenous blood and oxygen saturation lever equally. So VIP might it becomes targets to be specially the intersection of lung and the intersection of artery and a new kind of medicines of high pressure of taking place etc. to treat.
( 3) PDE-lc inhibitor
Main phosphoric acid diesterase isoenzyme is PDE-5 in the lung is organized. And PDE-1 mainly expresses in brain and blood vessel smooth muscle cell. Schermuly,etc. discovers, PDE-lc expressions in the oxygen deficiency type big mouse's lung artery of high pressure of lung artery raised, increase with the blood vessel resistance of lung and is concerned with, PDE-lc inhibitor can inhibit the artery blood vessel smooth muscle cell hyperplasia of lung, thus has offered the new target for treating the lung artery under high pressure to click.
( 4) Anticancer drug
Can be proliferated one kind of pathological changes of clump formed by endothelial cells in 20%-80% of the vascular disease patients of lung, discover one kind of pathological changes of clump in specially 77% in the sending artery high pressure of lung is cloned only, turn the characteristic " Small tumour " ,IPAH the intersection of endothelial cell and form clone hyperplasia, announce new biological forming might with morbidity of IPAH in the patient
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