I. Anti-vomiting drugs
(a) The principles of treatment of vomiting
1, treatment for the cause, such as lifting intestinal obstruction, stop taking certain drugs.
2, block the vomiting reflex with drugs, although the basic cause can not be removed quickly or can not be removed, for example, acute pancreatitis often due to severe abdominal pain reflexively caused by vomiting, pain relief can effectively stop vomiting. During chemotherapy, drugs can be used to block or reduce the vomiting response.
3, according to the gastrointestinal motility of the choice of drugs. For example, when complete mechanical pyloric obstruction vomiting, the gastric sinus is already in a high dynamic state, it can no longer be used to enhance the gastric sinus dynamics of the gastric reanimation. Postoperative gastric incomplete paralysis causes vomiting, giving atropine will aggravate the retention of the stomach.
4.In case of severe vomiting, oral administration of the drug is not recommended to avoid failure to achieve therapeutic effect due to vomiting.
5.Supportive treatment should be strengthened to correct the water and electricity imbalance.
(II) Therapeutic medication
1.Anticholinergic drugs
(1) Scopolamine butylbromide (Buscopan): It is a peripheral anticholinergic drug with a weak central effect. It has a stronger antispasmodic effect on smooth muscle than atropine and can selectively relieve smooth muscle spasm of gastrointestinal tract, biliary tract and urinary tract and relieve vomiting due to spasmodic abdominal pain. Its side effects are lighter than those of atropine and 654-2. However, it is contraindicated in patients with glaucoma and prostatic hypertrophy.
(2) Others: e.g. 654-2, atropine, etc.
2.Anti-dopamine receptor blockers
(1) Metoclopramide (Metoclopramide): It produces potent central antiemetic effects through dopamine receptors in the medulla oblongata. Peripheral antiemetic is its action on dopamine receptors in the smooth muscle of the gastrointestinal tract, producing choline-like neurological effects, increasing lower esophageal sphincter pressure, accelerating gastric emptying, lowering the pressure threshold for peristalsis, increasing the frequency of longitudinal smooth muscle contraction, and synergizing the dynamic activity of the gastric body, pylorus, and duodenum to produce consistent off-mouth movements. The effect starts 10 min after intramuscular injection of 10 mg of gastric receptor and lasts for 2 h. This drug can be used for
(i) vomiting caused by non-obstructive gastric retention, such as postoperative incomplete paralysis of the stomach, sinus rhythm disorder syndrome, idiopathic gastric depression;
②Vomiting caused by certain drugs, including chemotherapy drugs, digitalis, certain anesthetics, tetracycline, para-aminosalicylic acid, etc;
(iii) vomiting in uremia, diabetic ketosis;
(iv) motion sickness;
⑤ Brain tumors or trauma and other disorders.
Since gastroflucan can pass the blood-brain barrier, patients often have side effects such as drowsiness and weakness. A few people have extrapyramidal signs, such as nystagmus, lower limb muscle twitching, double upward vision, dysphonia, and ataxia. This is all due to the relative hyperactivity of cholinergic receptors after blocking the central dopamine receptors. Oral anandamide has anticholinergic effects. These side effects of gastrofacial limit its long-term use.
(2) Domperidone (Domperidone) is also known as morpholine (Mortilium). It is a strong dopamine receptor antagonist. It can not pass the blood-brain barrier, only peripheral blocking effect, side effects are lighter than gastric receptors. It has a half-reduction period of 8h and becomes an inactive metabolite in the liver, which is excreted with bile. It is mainly used for vomiting caused by various non-obstructive gastric retention. It can be taken orally, 10-20mg each time, 3 times a day; also available in its suppository, 60mg/time, incorporated into the anus, 3 times a day.
3, H1 receptor blocker Its antiemetic is through the medulla chemoreceptor trigger zone (CTZ) and the central anticholinergic effect. They are mainly used in motion sickness, early pregnancy vomiting and vomiting caused by chemotherapy. In addition to Benadryl and Promethazine, Buclizine and Diphenidol have stronger antiemetic effects.
4.Phenothiazines The common ones are chlorpromazine. Chlorpromazine (Chlorpromazine) is a complex thick ring compound, because its dominant structural part overlaps with the dopamine phase, so it can affinity with dopamine receptors, and block dopamine receptors. Small doses of chlorpromazine inhibit dopamine receptors in the CTZ of the delayed brain, while large doses directly inhibit the vomiting center. It can be used for all types of central vomiting. After intramuscular injection of 25-50 mg, peak blood concentration is rapidly reached, with a bucket reduction period of about 30 h. It is mainly metabolized in the liver and excreted from the kidney. Since chlorpromazine has α-adrenergic receptor blocking effect, it can cause vasodilation and postural hypotension, which should be noted. Generally, 25-50mg is used for intramuscular injection.
Second, anti-diarrheal drugs
(A) diarrhea treatment principles Severe diarrhea can rapidly lead to dehydration, loss of large amounts of electrolytes and loss of alkaline acidosis. Diarrhea drug treatment principles in addition to the etiology and diarrhea mechanism, can be selected according to the presence of increased peristalsis or abnormal. If there is accelerated gastrointestinal motility, anticholinergic or other drugs that slow down gastrointestinal motility can be used. However, these drugs are not used for all diarrhea. When intestinal motility is abnormally reduced, small intestine bacteria can overgrow, affecting the role of digestive enzymes, and bacterial decomposition and binding of bile salts can cause diarrhea, for which the application of drugs to increase gastrointestinal motility and anti-inflammatory treatment can be expected to be effective. Diarrhea in patients with ulcerative colitis limited to the rectum and sigmoid colon is mainly due to inflammatory irritation and irritation, while the whole gastrointestinal passage time is not shortened, and anti-inflammatory treatment should be given.
(II) Therapeutic drugs
1.Pethidine derivatives
(1) Phenylephrine (Diphenoxylate, Lomotil): a derivative of pethidine (dulcolax). No analgesic effect, can reduce intestinal peristalsis, and has an astringent effect. It can be used for various kinds of diarrhea caused by increased gastrointestinal motility, such as some so-called “functional diarrhea”, and also such as ulcerative colitis of the whole colon type or when the scope of involvement is extensive, colon passage is often increased. After absorption, the drug is rapidly metabolized in the liver, and its metabolites are excreted in the bile, and a small amount is excreted in the urine. The side effects are minimal in regular doses, but can produce euphoria in large doses, and long-term use can lead to addiction and dependence. Liver and renal impairment, especially in severe liver disease, this drug can induce hepatic coma. In severe ulcerative colitis, toxic colon dilatation can be induced due to inhibition of intestinal peristalsis.
(2) Phenylbutazide (Loperamide, or Imodium): Its chemical structure is similar to that of phenylephrine. It can inhibit smooth muscle contraction and intestinal peristalsis. Its strength of action is greater than morphine and atropine. It is easily absorbed after oral administration and reaches its peak in 4-6 h. The half-reduction period is 9-13 h. It is distributed in liver and kidney and excreted from urine and feces. The indications for application are the same as those for phenylephrine. Its effects also include ① blocking calcium channels and inhibiting intestinal motility; ② inhibiting secretion; ③ inhibiting calmodulin and increasing Na+ and Cl- absorption. It has stronger effect than phenylephrine and stops diarrhea quickly after administration. 2-3 times a day, 2mg each time. can be reduced or stopped as appropriate after the condition improves.
2.Adrenergic drugs Clonidine: It is an α2-adrenergic drug, which stimulates the specific postganglionic α2-adrenergic receptors on intestinal cells, promotes the absorption of Na+ and Cl-, inhibits the secretion of HCO-3 and Cl-, and is a powerful antidiarrheal agent. However, its central hypotensive and sedative effects limit its application. The exception is that in diabetic patients with severe vegetative neuropathy, there is no hypotension but only antidiarrheal effect. after oral administration of colistin, it is well absorbed, with an onset of action in 30 min, a peak in 2-4 h, and a half-reduction period of 8.5 h. It is partially metabolized in the liver, but 60% is excreted from urine in its original form.
3, growth inhibitor (Somatostatin, STT) is a 14 amino acid peptide, exists in the whole gastrointestinal mucosa, pancreas and central nervous system, STT inhibits intestinal motility, and strongly inhibits pancreatic and gastrointestinal secretion. Its antidiarrheal effect is not the result of direct action on the mucosa, but the inhibition of pro-secretory hormone release from tumor cells. In pancreatic cholera, plasma vasoactive intestinal peptide (VIP) levels decreased to normal after IV STT, and net secretion from the jejunum shifted to absorption. IV STT also inhibited diarrhea in carcinoid and thyroid carcinomas. However, it is not effective in non-hormonal diarrhea. STT also reduces diarrhea in patients with short bowel syndrome as a result of STT decreasing the levels of glucagon, gastrin suppressing peptide, and pancreatic polypeptide.
STT has a very short half-reduction period and requires continuous intravenous dosing. SMS201-995, a long-acting formulation of 10 amino acids, is a comparable drug to STT and is more than 75 times more potent than natural STT. It not only inhibits the secretion of pro-secretin in certain tumors, but also controls diarrhea caused by ileal resection, colonic pseudo-intestinal obstruction, acquired immunodeficiency, and cryptococcal infection. This suggests that SMS201-995 also has a direct inhibitory effect on mucosal secretion.
4, non-hormonal anti-inflammatory drugs Anti-inflammatory pain (Indomethacine): Prostaglandine (Prostaglandine E, PGE) promotes the secretion of intestinal epithelium, which can cause severe diarrhea after oral administration or instillation into the intestinal lumen. Oral administration of anti-inflammatory pain inhibits secretory diarrhea in pancreatic cholera, thyroid cancer, and rectal villous adenocarcinoma, all of which achieve an antidiarrheal effect due to the reduction of PGE2 levels by anti-inflammatory pain. However, in ulcerative colitis and Crohn’s disease, anti-inflammatory pain has no antidiarrheal effect.
Recent studies have shown that 5-aminosalicylic acid (5-ASA) and Sulfasalazine inhibit tissue PGE synthase and reduce PGE levels to achieve antidiarrhea. The antidiarrheal effect of prostaglandin synthase inhibitors may have a promising development.
5, calcium and calmodulin antagonists Intracellular free calcium plays an important role in regulating the active transport of ions and water in the intestine. Increased intracellular free calcium decreases Na+ and Cl- absorption, but stimulates Cl- secretion. The final hurdle in controlling fluid and electrolyte transfer is not intracellular free calcium, but intracellular calcium-binding proteins called calmodulin. It is most likely the messenger that regulates mucosal Na+ and Cl- permeability. Both calcium channel blockers and calmodulin antagonists have antidiarrheal effects.
(1) Nifedipine, Verapamil, and Dilthiazem: Because calcium channel blockers inhibit calcium inward flow and decrease smooth muscle contractility, they can reduce postprandial colonic frontal potential activity in patients with irritable bowel syndrome, and may be used in patients with the diarrheal form of irritable bowel syndrome. Calcium channel blockers also inhibit the secretion of water and electrolytes, resulting in a change from net secretion to net absorption. Therefore it is effective for diarrhea due to increased secretion.
(2) Phenylbutazone: see previous.
6, astringent adsorbent Such as silicon-carbon silver, tannin, bismuth subcarbonate, etc., can be used optionally for inflammatory diarrhea. All are given orally at 0.6g 3 times a day.
7, opiates inhibit intestinal nerves, stimulate secretion, stimulate adrenaline action, promote absorption, inhibit secretion, movement. Such as enkephalin, tincture of opium.
Third, laxative
(A) the principle of treatment of constipation
1, for the cause of treatment, avoid the abuse of laxatives.
2, the complete mechanical intestinal obstruction caused by constipation, mainly in the release of obstruction, fasting, gastrointestinal decompression, prohibit oral laxatives. For chronic incomplete intestinal obstruction, use lubricating laxatives to soften the stool and make it thinner, which is conducive to laxation. If it is pseudo-intestinal obstruction or weakened intestinal peristalsis, it should stimulate intestinal peristalsis and promote emptying.
3, for habitual constipation, the focus is to establish a normal defecation reflex, to develop regular defecation habits, to reduce the threshold of the desire to defecate, do not abuse laxatives.
4.For those who are prone to fecal impaction and defecation difficulties, laxatives should be given to soften the stool. If fecal impaction has been formed, it should be given open celery, soap and water enema to soften the feces, if necessary, with gloves to pick out the hard fecal block in the rectum.
5, elderly patients with constipation abuse too much laxative, some are prone to cause fecal incontinence. At this time, should not be excessive with antidiarrheal agents, so as not to cause constipation again. Should stop the drug or choose a laxative, can receive good results.
(B) the treatment of drugs
1, contact laxatives
(1) phenolphthalein: after meeting the alkaline intestinal fluid, the formation of soluble salts, stimulate the colonic mucosa, promote colon peristalsis; and block the absorption of intestinal fluid, increase the diffusion of water and electrolytes into the intestinal cavity, play a slow diarrhea. Take 0.1~0.2g before bedtime, and cause defecation after 8~10h. About 15% of phenolphthalein is absorbed and most of it proceeds to enterohepatic circulation, and its effect can last for 3 to 4 days.
(2) Anthraquinone glycosides: such as rhubarb, senna, aloe vera, etc. After taking rhubarb (Rheumofficimale), senna (Sennalenf) or aloe vera orally, they are absorbed from the small intestine, turned into rhodopsin in the body, and then secreted from the large intestine. Rhubarb stimulates the large intestine and increases propulsive peristalsis, causing slow diarrhea without abdominal pain. Take 3g of rhubarb or 5g of senna, drink it as tea, and it can cause defecation after 6~8h.
(3) Castor oil (Castor oil): After taking orally, it is hydrolyzed by lipase in the upper part of the small intestine into stimulating ricinoleic acid, which promotes peristalsis of the intestine, especially the small intestine. It can be taken orally in 20-30ml and cause bowel movement in 2-6h. It is a powerful laxative and can cause temporary constipation after inducing diarrhea.
2, volumetric laxatives
(1) magnesium sulfate (Magnesium sulfate): for salt laxatives. Magnesium sulfate is not absorbed, maintain a certain osmotic pressure in the intestine, so that the intestine retains a large amount of water, increase the volume, mechanical stimulation of intestinal peristalsis, causing diarrhea. Caused by the time of defecation and concentration, after taking 5% 400ml 2 to 4h that diarrhea, and 20% 100ml need a longer time, so should drink more water.
(2) Mannitol (Mannitol) is a polyol sugar. After oral administration, it is not absorbed in the gastrointestinal tract. 5.07% aqueous solution is isotonic solution, oral administration of hypertonic mannitol solution increases intestinal osmotic pressure, thus increasing the volume, stimulating intestinal peristalsis and causing watery diarrhea. After taking 100-250ml of 20% mannitol for 1 to 2h, then drink 300-500ml of water respectively, which can increase watery diarrhea. Used for intestinal cleansing, acute poisoning, or to prevent hepatic coma in patients with hepatic sclerosis complicated by gastrointestinal bleeding, etc.
(3) Lactulose (Laotulose): It is a synthetic disaccharide, which is not hydrolyzed by disaccharidase in the intestine and is decomposed into lactic acid and acetic acid by intestinal bacteria after entering the colon, increasing the osmotic pressure and achieving osmotic laxative effect, see medicine for hepatic coma.
(4) open plug: containing magnesium sulfate, sorbitol, etc.. After injection into the rectum, stimulate the rectal mucosa, causing rectal defecation reflex.
3, lubricating laxatives
(1) liquid paraffin (Liquid paraffin): not absorbed in the intestine, softening the stool, making it thin, lubricating the intestinal wall so that the stool can be easily discharged. Take 15-30ml orally at bedtime, or 10ml 3/d, can discharge thin stool.
(2) peanut oil (Arachis oil): 100-200ml of peanut oil taken orally before going to bed, the next day can be discharged dilute soft stool. Used for incomplete intestinal obstruction, especially when it is necessary to make intestinal barium examination, oral peanut oil to ensure daily defecation, and then perform intestinal barium examination, continue to use peanut oil after the examination, so that the barium is all discharged.
Fourth, abdominal pain medication
(A) the principles of treatment of abdominal pain
1. If the cause of abdominal pain is not known, analgesics, especially narcotic analgesics, should be used with caution to avoid masking the disease and delaying the diagnosis.
2, treatment for the cause and abdominal pain mechanism. The abdominal pain of acute gastroenteritis should be anti-inflammatory, and when there is intestinal spasm, it should be antispasmodic and analgesic. Acute intestinal obstruction and perforation should be treated with fasting, gastrointestinal decompression, timely surgery and active anti-inflammation. In case of liver abscess or acute congestive hepatomegaly, the tension of liver peritoneum should be reduced, and in the former case, pus should be drained by puncture, and in the latter case, cardiotonic diuretics should be used.
3. Correct water-electrolyte and metabolic disorders. Patients with acute abdominal pain are often accompanied by vomiting, diarrhea, high fever, etc. Loss of water and salt should be supplemented; some need emergency surgery, water-electrolyte balance should be corrected before surgery and supportive therapy should be given.
4, for non-surgical abdominal pain and accompanied by obvious psychiatric factors, in addition to treatment of the original disease, if necessary, combined with suggestive therapy, avoid analgesics to avoid addiction.
(B) Therapeutic drugs
1.Anticholinergic drugs are mainly used for spasmodic abdominal pain of hollow organs, such as intestinal spasm, biliary colic, etc.
(1)Scopolamine butylbromide: Please see antiemetic drugs.
(2)Others: such as 654-2, atropine, serving stopping, etc.
2, antacids and acid suppressants In ulcer disease, erosive gastritis, high acid secretion can cause epigastric pain when stimulating the ulcer and erosive surface, and sometimes the pain is severe. Antacids can immediately neutralize stomach acid, while acid suppressants inhibit acid secretion, thereby reducing pain. Commonly used antacids include aluminum hydroxide gel, Gastrodex, Gastrodex, and Gastrodex. The latter three antacids are composed of several antacid drugs to enhance the effect and reduce side effects. There are several types of acid suppressants as follows.
(1) H2 receptor antagonists: commonly used are mecamylguanidine (Cimetidine), furanylamide (Ranitidine, Ranitidine). After oral administration of mecamidine, it is rapidly absorbed in the proximal small intestine, reaching peak blood concentration in 60-90 min, with a half-reduction period of 2 h. After oral administration of 300 mg of mecamidine, the acid-suppressive effect can be maintained for more than 4 h. The acid inhibiting effect of furanilamide is 5-6 times stronger than that of mecamylguanidine. Meclizine can cause neurological reactions due to the effect of the drug on H2 receptors in neural tissue through the blood-brain barrier. A small number of patients can cause an increase in serum transaminases. The side effects of furanilamide are less than those of metformin.
(2) Gastrin receptor antagonist: Proglumide (Proglumide) has a structure similar to the end of the gastrin structure and can compete for gastrin receptors on the wall cells, thus inhibiting gastric acid secretion, and also has a protective effect on the mucosa.
(3) Cholinergic receptor antagonists: anticholinergic drugs act on cholinergic receptors on the wall cells to inhibit gastric acid secretion; they also reduce gastric acid secretion through the inhibition of the vagus nerve; in addition, they can also release smooth muscle spasm to achieve pain relief.
3, nitrites and calcium channel blockers nitroglycerin (Nitroglycerol) and nitric acid isosorbide (Isosorbide dinitrate). These drugs directly relax smooth muscle. Relieve the spasm of biliary sphincter. They work 2-3 min after oral administration, nitroglycerin is maintained for 30 min, and cardiac pain can be more than 6 h. They are used for biliary colic. Because nitrites can reduce the pressure of the lower esophageal sphincter, after oral administration can reduce the symptoms of choking on food and chest pain in patients with cardia incontinence.
Calcium channel blockers block calcium inward flow and relax smooth muscle, which can also be used for pain caused by smooth muscle spasm. In recent years, it has been used for the treatment of cardia incontinentia. After 10 min of oral cardiac pain, the pressure of the lower esophageal sphincter decreases, and the maximum effect is reached in 1 to 2 h (please see antidiarrheal drugs).
Nitrite and calcium channel blockers can dilate blood vessels, after taking may cause headache, vertigo.
4, magnesium sulfate (Magnesium sulfate) for salt laxatives (see before). Oral administration of 33% magnesium sulfate 50ml, can stimulate the duodenal mucosa, reflexively relax the lower end of the common bile duct Oddi sphincter, so that the gallbladder contraction, bile emptying. For small stones caused by biliary colic, combined with other treatment is likely to achieve stone removal and pain relief.
5.Analgesics
(1) Morphine (Morphine): It is an opioid receptor agonist and has a powerful analgesic effect. Its analgesic mechanism is to bind with the relevant opioid receptors in the central nervous system, simulating the effect of endogenous antinociceptive substances enkephalin and activating the antinociceptive system in vivo. Morphine excites smooth muscle and increases bile duct, ureter and bronchial smooth muscle tone. Therefore, when used alone for biliary colic and renal colic, it increases the spasm of bile ducts and ureters instead, so it should be used in combination with antispasmodic drugs. It is also used for post-operative abdominal surgery and abdominal trauma. Morphine is metabolized in the liver and excreted through the kidney, which may cause dizziness, vomiting and constipation. Forbidden to use in obstructive pulmonary disease, serious liver disease, so as not to aggravate respiratory failure and liver failure.
(2) Pethidine (Pethidine, Dolantin): Its mechanism of action is basically the same as morphine. The analgesic effect is weaker than morphine (about 1/8 to 1/10). It is mainly used for severe visceral colic, and also needs to be used in combination with anticholinergic drugs. After injecting 50-100mg of dulcolax, the analgesic effect is produced in 10min, maintained for 2-4h, and the half-reduction period is 3h. dulcolax is also metabolized in the liver.
6.Acetylsalicylic acid (Aspirin) Ascaris lumbricoides likes alkali and is acidic, and retreats when it meets acid. It is used for the treatment of biliary colic in biliary tract ascariasis. 2 to 3 days after taking it, the biliary colic stops and the roundworm is expelled. Note that it should be used with caution in patients with ulcer disease.
V. Hepatic coma
(A) principles of treatment of hepatic coma See Chapter 36.
(B) Treatment drugs
1.Lowering blood ammonia drugs This class of drugs combines with ammonia to make amines, thus reducing the toxic effects of ammonia on the brain.
(1) Glutamic acid (Glutamic acid 1) and its sodium, potassium and calcium salts: its lowering of blood ammonia is due to the combination with ammonia into glutamine. Depending on the condition, sodium glutamate or potassium glutamate can be given in a 3:1 or 2:1 mixture. In case of low blood potassium, potassium salt is used; in case of calcium deficiency, calcium glutamate can be given. Add 5-10g of vitamin C to the drip to prevent the liquid from being alkaline, which is detrimental to lowering blood ammonia. Note that glutamate should not be given too fast in the IV. For cirrhosis with extensive portal-body collateral circulation formation, those who have obvious triggers for elevated blood ammonia may have a better effect of lowering blood ammonia and improving symptoms. When using the drug, pay attention to testing blood pH and electrolytes and kidney function.
(2) Arginine (Arginine): One of the routes of ammonia is the formation of urea. In the ornithine cycle of urea formation, arginine and ammonia produce urea and ornithine. Arginine can be used for patients in hepatic coma with alkalosis, where large amounts of sodium ions should not be input. However, because the activity of arginase is often reduced in hepatic coma, it affects the effect of lowering blood ammonia. At the same time, arginine is a hydrochloric acid preparation, which is prone to hyperchloremic acidemia and should be used with caution in renal insufficiency.
2, reduce intestinal ammonia production drugs
(1) Lactulose: Since there is no disaccharidase in the small intestine to hydrolyze lactose, it is decomposed into lactic acid and acetic acid by bacteria after entering the colon, making the intestinal pH acidic and thus NH3 easily becomes NH+4; at the same time, the absorption of NH3 in the colon is also affected by the intestinal pH, and when the pH is lower than 5, the colonic mucosa no longer absorbs NH3, but also excretes NH3 into the intestine. In addition, the generation of lactic acid and acetic acid increases the osmotic pressure in the intestinal lumen, leading to osmotic diarrhea, which is especially suitable for constipated people. Oral lactoside 45g/d in 3 oral doses. It can significantly improve the symptoms of patients in hepatic coma. If the dose is not sufficient, it is difficult to be effective. It can also be used as enema. It has been reported that 15% lactulose 1000ml, after 1h rectal enema, can reduce the blood ammonia concentration and make the liver coma significantly better.
(2) lactose: disaccharide, most people lack lactase, so it is not digested and absorbed, and is fermented by bacteria in the colon to produce lactic acid, formic acid, etc., similar to the mechanism of action of lactulose, can also be enema. Usage: 20% lactose, 100ml each time, 3 times a day, taken orally.
(3) Vinegar: vinegar diluted enema, pH 4~5, can reduce the production and absorption of intestinal ammonia and lower blood ammonia.
(4) Antibiotics: Urea in the blood circulation diffuses into the intestine and is broken down into ammonia by intestinal bacteria. In addition, bacteria also decompose proteins to produce ammonia, especially in the case of gastrointestinal bleeding, making the blood ammonia significantly higher. Therefore, inhibiting intestinal bacteria can reduce ammonia production. The commonly used antibiotic is Neomycin, which in combination with lactulose can enhance the inhibition of ammonia production and also increase the tolerance to food protein. However, it should not be taken for a long time to avoid absorption causing toxic reactions in the kidneys and VIII to the brain nerves. Aminobenzyl penicillin, kanamycin (less absorption when taken orally), balomycin or methotrexate can also be used.
(5) Lactase raw (Epifermin, Biofermin): contains lactic acid bacillus, which can decompose sugars and generate lactic acid to increase the acidity in the intestine, inhibit the reproduction of intestinal pathogenic bacteria, interfere with the growth of E. coli and reduce the production of ammonia. When using, pay attention to the expiration date, have enough live Lactobacillus, take 3~4g each time, 3~4 times a day, should not be combined with antibiotics, antibacterial drugs, adsorbents.
3.Pseudoneurotransmitter antagonists
(1) branched-chain amino acid 3H (branched-chain amino acid 3H, BCAA, 3H): The branched-chain amino acid family includes leucine, isoleucine, and valine. It inhibits and reduces the entry of aromatic amino acids (AAA) into the brain, inhibits and reduces the production of pseudo-neurotransmitters, improves brain cell function, and enables patients to wake up. At the same time, BCAA can reduce protein decomposition in muscle and liver as a source of muscle energy, and also replenish essential amino acids that are lacking in the patient’s organism and promote protein anabolism. The concentration of branched-chain amino acid 3H is 3 times of foreign FO80. Intravenous drip of 4.26% BCAA 250ml each time, twice a day, can make most patients with cirrhotic hepatic encephalopathy awake. However, it is less effective in severe liver disease, and the BCAA/AAA ratio decreases again after stopping the drug.
(2) 14 amino acids 800: It is formulated with 14 amino acids (including leucine, isoleucine and valine) in appropriate proportions. It can increase the BCAA/AAA ratio, inhibit and reduce the production of pseudo-neurotransmitters. It can increase plasma protein content and reduce plasma non-protein nitrogen and urea nitrogen content, which is beneficial to the proliferation of hepatocytes and recovery of liver function. It is suitable for those with cirrhotic hepatic coma, hepatic coma with hepatitis and hypoproteinemia with hepatic insufficiency. 250ml of 14 amino acids 800 with equal amount of 10% glucose per drip, twice daily. Reduce by half after sobriety, available for 10-15 days.
(3) Levodopa (Levodopa, L-dopa): a predecessor of norepinephrine and dopamine, can cross the blood-brain barrier and can revive patients in hepatic coma. In normal time, protein is hydrolyzed into amino acids in the intestine and then cleared by the action of decarboxylase to produce amines such as phenylethylamine and coolamine, which are decomposed in the liver. However, in hepatic failure, these amines cannot be broken down in the liver and enter the central nervous system by the body circulation. After side chain β-position dihydroxylation, phenylethanolamine or norethindrone is formed, which is a pseudo-neurotransmitter and its structure is similar to that of norepinephrine and dopamine. Levodopa can be converted into a large amount of dopamine and norepinephrine in the central nervous system to counteract the pseudotransmitter and wake up the patient. The peak blood concentration is reached after 1 h of oral administration, and the half-reduction period is 1 to 3 h. Since dopamine is formed in the liver after absorption, and the formation of dopamine is reduced in severe liver disease, levodopa enters the central nervous system and exerts the above effects. It can cause nausea and vomiting due to excitation of the chemoreceptor-promoted zone (CTI) of the delayed brain. It can also have postural hypotension, etc.
4.Bromocriptine is a dopamine agonist, which specifically excites dopamine receptors. Its mechanism of action is similar to levodopa. It is effective for intractable chronic hepatic encephalopathy and is not used for the treatment of acute hepatic encephalopathy.
VI. Gastrointestinal bleeding
(A) the principles of treatment of gastrointestinal bleeding
(B) Therapeutic drugs
1, posterior pituitary containing Vasopressin (Vasopressin) and Oxytocin (Oxytocin). Both are peptides composed of 9 amino acids containing disulfide bonds. Vasopressin constricts visceral capillaries and small arteries, reduces portal blood flow, and lowers portal pressure. At the same time, pressin also constricts esophageal smooth muscle and increases lower esophageal sphincter pressure. Therefore, pressin can reduce the blood flow of the lateral branches of the gastroesophagus during esophageal variceal bleeding, achieving the purpose of reducing bleeding and stopping bleeding. The effect of posterior pituitary hormone starts after 3-5 min of intravenous injection and is maintained for 20-30 min. most of the pressin is destroyed in liver and kidney, so it should be maintained. In case of emergency bleeding, 10u plus 5% glucose 20-40ml can be used for sedation, and then maintained by 0.1~0.3u/min sedation. Arterial perfusion of posterior pituitary hormone is also used for arterial bleeding in addition to esophageal variceal bleeding. However, it is technically difficult, complications can occur, and it is not preferred. Since pressin constricts coronary arteries and causes myocardial ischemia, it should be used with special caution in the elderly, especially in patients with coronary heart disease.
2.Vasodilators Nitroglycerin and cardiac pain directly dilate blood vessels, and cardiac pain is a calcium channel blocker, which makes blood vessels dilate. Due to the expansion of portal vein branches and intrahepatic vessels, the portal pressure decreases; at the same time, due to the decrease in arterial pressure, reflexively causing the visceral arteries to contract, further reducing the portal blood flow and lowering the portal pressure. In the case of hemorrhage from ruptured esophageal varices, after replenishment of blood volume, if combined with posterior pituitary hormone, it can counteract the effect of posterior pituitary hormone in raising blood pressure and constricting coronary arteries, and also achieve the purpose of lowering portal pressure and stopping hemorrhage. Generally do not use these drugs alone, so as not to vasodilate and blood pressure drop.
3, growth inhibition (Somatosatin, STT) can selectively dilate visceral blood vessels, and thus reduce portal pressure, its efficacy is similar to that of posterior pituitary hormone, but the effect on coronary arteries is very small, the half-reduction period is 1-4 min. 50μg for the first time, and then 250-450μg/kg of IV maintenance. Growth inhibitor can also be used for other causes of gastrointestinal bleeding.
4.Metoclopramide and Domperidine are dopamine receptor blockers, which are used as adjuvant therapy for esophageal variceal bleeding due to increasing the lower esophageal sphincter pressure and enhancing the blockage of esophageal-gastric junction blood flow. It is administered intramuscularly at 10 mg every 6-8 h. Domperidone is available as a suppository, 60mg/dose, incorporated into the anus.
5. H2 receptor antagonists These drugs can be used for upper gastrointestinal bleeding caused by ulcer disease, stress ulcer, reflux esophagitis, etc. When H2 receptors are blocked, gastric acid secretion is inhibited, thus reducing mucosal erosion and ulcerative lesions and bringing bleeding under control. In acute upper gastrointestinal bleeding, the drug is often administered intravenously. Metformin is commonly used 400mg every 8h. In severe cases, 400mg per dose every 6h can be administered up to 100mg/h by drip. The dosage is reduced after the disease is alleviated and can be changed to oral administration. Furanilamide has strong acid inhibition and long duration of action, 50mg every time, every 8h, intravenous slow injection. The oral dose is 150mg every 12h. Losec has a stronger inhibitory effect. 1 to 2 times a day, 20mg each time, orally, and intravenous preparations.
6.Vasoconstrictor Used for gastrointestinal bleeding caused by mucosal erosion and ulcer. Norepinephrine excites alpha receptors and constricts small arteries and small veins. It is rarely absorbed after oral administration and is rapidly destroyed by alkaline intestinal fluid in the intestine. It can be taken orally or instilled through the gastric tube for local hemostasis in case of upper gastrointestinal bleeding. However, if there is a large amount of blood in the stomach, it is advisable to aspirate the net before administering the drug and to bring the drug into contact with the bleeding lesion. In recent years, direct injection or spraying of epinephrine at a concentration of 1:10,000 on the bleeding lesion under endoscopy can stop the bleeding immediately.
7, Monsell’s solution (Monsell’s solusion) for alkaline iron sulfate, molecular formula Fe4(OH)2(SO4)5. is a powerful astringent, forming a brown-black film on the bleeding wound, so that blood coagulation, to achieve hemostasis; and make the stomach wall contraction, enhance hemostasis. It can be used for stress ulcers, hemorrhagic gastritis, ulcer disease, bleeding after gastrectomy and bleeding from esophageal varices. Meng’s liquid is not absorbed in the gastrointestinal tract, but there are symptoms of gastrointestinal irritation, astringent taste and strong acidity. It can be fed in through the nose or added with 4% sodium bicarbonate to eliminate discomfort.
8.Sclerotherapy Endoscopic sclerotherapy of esophageal veins has become an important treatment. The sclerosing agent is injected around the varicose vein and within the vein to make the tissue around the vein coagulate and necrosis, fibrous proliferation, vein compression, wall thickening, lumen embolization, blocking the side branch blood flow of the stomach-esophagus and preventing rebleeding. Commonly used are ethoxysklerol (Aethoxysklerol), sodium cod liver oil acid (Sodmorrhuate), etc.