DRUGS ACTING ON DIGESTIVE SYSTEM

 Orexigenic Agents

                Prevention (or) treatment of inappetence is an important facet of therapeutics. Several agents are commonly used to promote appetite, although no definitive evidence is available to prove their worth.

1.         Vitamins of the B–complex group.

2.         Corticasteroids: Anabolic steroids: have been advocated as appetite stimulants. Action of above drugs is mainly to make the animal feel better rather than any specific action on the control of feed in take.

3.         Bitters such as gentian and Nuxvomica are used to promote digestion and feed intake.

4.         Zinc: Inappetence is a prominent and early feature of zinc deficiency. This element is necessary for normal taste acuity. Response to zinc supplementation is often excellent.

5.         Chemicals exert a positive influence on the short-term control system    like satiety center/hunger center are also increases appetite.

a)          Elfazepam – it is a Benzodiazepine compound that increases feed intake in cattle and sheep.

b)         Diazepam or chlordiazepoxide: Cats react favorably. It acts by suppression of satiety center.

c)          Cyprohepatadine: H₁ and 5HT₁ receptor blocker promote appetite in humans.

6.         Other provisions like highly palatable feed at frequent intervals restore appetite of sick or recovering animals. Warming the food for carnivorous enhance their intake.

Anorexigenic Agents (Appetite suppressants)

Not often used in veterinary medicine to treat obesity because in most instances it is a simple matter to reduce or modify the feed intake of an animal. Anorectic drugs act mainly on the satiety center in the hypothalamus to produce inappetence but tolerance develops rapidly. These also have various metabolic effects involving fats and carbohydrate metabolism, which are secondary to weight loss.

E.g.: Amphetamine, chlorphentermine.

Drugs affecting Mouth, Pharynx

Salivary stimulants: Sialagogues increase the volume and fluidity of saliva. They may be used in cases of iatrogenic hypoptyalism or to correct xerostomia resulting from other causes such as radiotherapy of the buccal cavity and pharynx. These are commonly used as constituents of tonic preparations.

1.         Bitters: Reflex sialagogues, vegetable origin that stimulate taste buds and promote the cephalic phase of digestion.

                E.g.         Simple bitters – Gention, quassia, and columba.

                                Alkaloidal bitters – Nuxvomica (strychnine and brucine),

                                                        Cinchona (quinine).

2.         Nauseauts and emetics: Have reflex sialic effect.

3.         Cholinergic sialagogues: Parasympathomimetic effect on salivary gland these stimulate production of serous saliva.

E.g. Cholinesters,

     Cholinomimetic alkaloids – Arecoline, neostigmine.

     Cholinesterase inhibitors.

4.         Direct acting sialagues: directly acts on the salivary gland and increases the sectetion of saliva.

      E.g. Anethole trithione,

           Mercurialism condition

           Iodinism condition.

Antisialagogues: Salivary inhibitors, decrease flow and fluidity of saliva, this is usually accompanied by reduction in respiratory and digestive secretions. Used for preanesthetic medication to reduce excessive salivation.

E.g. Cholinolytics: Atropine and related belladonna alkaloids,        

     Synthetic antimuscarinic drugs like glycopyrrolate.

Alimentary demulcents

High molecular mass and often water-soluble compounds, which lubricate, coat and protect upper alimentary mucous membranes. In addition, they are used to mask unpleasant tastes, stabilize emulsions and act as suspending agents. E.g.:

1.         Syrup, honey, starch and glycerol.

2.         Natural plant hydrocolloids – Gum tragacanth, guargum, agar, alginic acid, glycerrhiza, methyl cellulose.

3.         Low molecular mass compound – Propylene glycol, polyethylene glycol.

4.         Mineral oils – Liquid paraffin.

5.         Proteins - Egg albumin and gelatin.

Stomachics

                Agents promote the functional activity of the stomach by increasing secretions and motility.

1. Muscarinic agents: Acts by stimulating gastric cholinergic receptors. E.g. Pilocarpine, Arecoline, physostigmine

2. Dopamine antagonist – Metaclopramide Hcl

                 Increases tone in lower oesophageal spincter, increase the force and frequency of gastric antral contractions, relaxes pyloric sphincter, promotes peristalsis in the duodenum and jejunum, resulting in accelerated gastric emptying and upper intestinal transit. Metoclopramide also exerts local and central antiemitic actions.

Dose – dogs and cats: 0.1 – 0.3 mg/kg b.wt at 8 hours interval orally/parentarally.

3. Alkalain stomachics: Carbonate and Bicarbonate salts.

                Carbonate and bicarbonate salts will generate carbon dioxide in the acidic environment of the simple stomach. Released co₂ stimulates gastric secretion and vasodilatation in gastric mucosa.

4. Bitters: Also act as stomachics. Reflexly stimulate salivary and gastric secretion.

5. Gastric Acid secretogogues: These agents are used specifically to stimulate gastric secretions in cases of suspected hypochlorhydria (or) achlorhydria.

a)              Betazole hydrochloride: Has less effect on blood pressure and smooth muscle than Histamine. Used for clinical testing of gastric secretion.

b)            Pentagastrin: Synthetic polypeptide with actions of natural gastrins. Acts as physiologic secretagague, diagnostic agent for evaluation of gastric acid secretary function, dose 6 micro grams per kg body weight, S/c.

Antistomachics or gastric sedatives

Gastric sedatives are the agents that decrease gastric secretions and movements.

1.         Antimuscarinic drugs: Parasympatholytics.

2.         Adrenergic agents (sympathomimetics).

3.         GI spasmodics: Phenanthrene alkaloids of opium, morphine, and codeine, delay gastric emptying.

4.         H₂–Receptor Antagonists: Cemetidine, Ranitidine reduce gastric secretion of both Hcl and pepsin.

Therapeutic uses: Uremic gastritis, gastic duodenal ulcers, stress–related erosive gastritis and hyper secretary conditions such as gastrinoma, (or) systemic mastocytosis. Also used in gastrooesophageal reflex disorders, and  Oesophagitis.

Carminatives:

Carminatives are the agents that promote expulsion of gas from the stomach (eructation). They have mildly irritant action on mucous membranes and tend to relax the gastro intestinal musculature.

E.g.:  Capsicum, Ginger, Peppermint, Eucalyptus, and Anise.

            Volatile compounds – Chloroform, ether, alcohols.

Agents control meteorism

Semithicone: (dimethyl polysiloxane) is a surfactant used as antiflatulent to control meteorism. Defoaming action relieves flatulence by dispersing and preventing formation of mucous surrounded gas pockets in the gastro intestinal tract.

Agents that protect the GI tissues from Hcl and Pepsin

                Gastric acid secretion occurs in four phases. The first three phases refered as cephalic, gastric and intestinal and are stimulated by food and mediated by gastrin. Secretion is persistent during these phases and gastric PH progressively decreases as nutrients traverse the GI tract. Gastrin secretion is inhibited as gastric PH declines to 3.5 and is completely inhibited at a PH 1.5 to begin again only when PH is approximately 3.0-3.5. The fourth phase of gastric acid secretion is basal and occurs in the absence of external stimuli. 

These are broadly classified in

1.         Gastric antisecretary drugs.

2.         Antacids.

3.         Cytoprotective agents.

1. Gastric antisecretary drugs: used to prevent or modulate gastric acid secretion.

a)         Anticholinergics: less effective, but potentiate inhibitory effect of H₂ receptor antagonists. Pirenzepine, an M₁ antagonist inhibits food-induced secretion by 50-60% with fewer antimuscarinic side effects.

b)        H₂ receptor antagonists: Ranitidine, Cemitidine, Famotidine, Nizatidine.

c)         Proton pump inhibitors: Omeprazole.

d)        Prostaglandins: gastric acid secretion can also be modulated by prostaglandins of E series. PGE action is by binding to receptors present on basolateral membrane and decreases intracellular concentration of CAMP, which inturn decreases protein kinase activity and hydrogen ion concentration. Misoprostol is methyl ester analog of PGE₁. It is pharmacologically active following oral administration with effects lasting longer than those of endogenous PGs. Its action tends to be restricted to the local environment with systemically absorbed drug rapidly metabolizes by the liver.   

2. Antacids

These are basic agents used to counteract or chemically neutralize gastric hyperacidity and luminal P^H is increased to an acceptable level.

Since pepsin activity for peptic digestion is optimal at P^H 2-3, effective antacids should raise the P^H of gastric fluids to at least 3 or 4 with out causing systemic alkalosis. The action of gastric antacids is usually transient and lasts only 1-2 hours. Neutralization of acid in the stomach antrum removes negative-feed back control of gastrin release, which in turn leads to elevated gastrin levels and enhance Hcl secretion with increase tone of the lower esophageal sphincter. These drugs must be administered frequently or with a meal to avoid this rebound effect.

Mainly used in gastric hyperacidity, peptic ulcers, gastritis, reflex oesophagitis, and chronic renal failure. A major use of antacids in veterinary medicine is in treatment and prevention of ruminal acidosis from grain overload.

Systemic antacids

Sodium bicarbonate: water-soluble. Gastric P^H rises to alkaline levels, but duration of action is short and rapid liberation of carbon dioxide may lead to gastric distention. Acid rebound effects often occur. Systemic alkalosis occurs due to absorption.

Non systemic Antacids

Aluminum Hydroxide: It is good adsorbent as well as antacid. Inactivates pepsin, binds bile salts and also induces the local synthesis of mucosal protenctants. Side effects, cause constipation decreases phosphates absorption. Dose: Cattle 30g, Dog 100–200mg.

Magnesium Hydroxide: Good antacid. This tends to cause laxation effect, used in combination with other Al, Ca salts. Prompt neutralization effect with prolonged action. 20% of salt administered is absorbed in to the systemic circulation, which is rapidly excreted by kidney. However renal dysfunction and repeated administration can result in dangerous degree of retention.

Dose: Calves/Foals – 30–60 ml

               Dog – 1–20 ml.

Calcium carbonate: Effects are rapid and prolonged in duration, however slowly develops metabolic alkalosis, hyper calcimia, calciurea with metastatic calcification and urolithiasis. Disadvantage is it causes constipation.

3. Cytoprotective agents

Sucralfate: orally administered disaccharide (sucrose) aluminium hydroxide produce, which binds to and protects the ulcerated site from acid, bile and pepsin activity. In the acid environment of stomach the sucrose is freed from the AlOH and cross polymeriges and binds to exposed (damaged) anions of GI epithelial cell membranes. Sucralfate also binds to and inactivates bile acids and pepsin. In addition to binding and protection of cells, the polymerized sucrose prevents exudation of protein and electrolytes into gastric lumen. Although the amount of aluminium hydroxide will not effectively neutralize gastric acidity, it appears to be the stimulus for potentiated formation of local mediators, which protect the gastric mucosa, such as PGs and possibly sulphydril ions. Sucralfate binds epidermal growth factor, thus causing it to accumulate in ulcerate lesions. Also induces local blood flow either by inducing local nitric oxide or PG production or by direct stimulation of local angiogenesis.

                Safest drug for treatment of gastroduodenal ulcers. Sucralfate binds and inhibits Cimetidine absorption.

Emetics

Emetics are the agents that produce vomition, used in the treatment of poisonic cases to remove unabsorbed toxicants. Basing on their site of action they are classified into three types 1) peripherally acting, 2) centrally acting, 3) both central and peripherally acting emetics.

Peripherally acting reflex Emetics

                These will induce vomition by irritating the epithelium of the pharynx, Oesophagus, stomach, or duodenum.

1.         Warm water: can be used in case of non-corrosive substances, dilutes the poison and induces emesis.

2.         Warm saturated (strong) Nacl solution: Dogs causes emesis.

3.         1% cupper sulfate solution: 50 ml administered orally produces vomition with in 10 minits. May not cause toxicity due to poor absorption.

4.         Pinch of table salt placed in pharyngeal region may also induce emesis in dogs.

5.         H₂0₂ 3% solution by mouth induces emesis in dog/cat.

6.         Ipecac contains alkaloid emetine, which acts both locally and peripherally. Tr. Ipecacunhae.

7.         Sodium carbonate:

Centrally Acting emetics

These cause emesis through the stimulation of dopaminergic receptors in chemoreceptor trigger zone (CTZ). These are mainly used as preanesthetic medication, and have additional advantage of causing central depression subsequent to evacuation of the digestive tract.

E.g. Apomorphine Hcl: Stimulation of CTZ.

                      Dose: – Dog – 0.04 mg /kg b.wt  i/v

                                    0.07 mg/ kg b.wt  i/m

     Xylazine – produce emesis in cats 1mg/kg b.wt i/m.

Both central and peripheral actions

Ipecac (emetine) act by irritating the upper gastro intestinal epithelium and stimulating the CTZ. E.g.: Tr. Ipecacunnhae.

Antiemetics

Agents, which prevent nausea or vomition. Basing on their site of action they are classified into 1) peripheral acting, 2) central acting antiemetics.

I. Peripheral acting (local acting) antiemetics: protect the gastro intestinal epithelium from further irritation.

1.        Demulcents and protectants: kaoline, pectine, bismuth salts.

2.        Topical anesthetics: Benzocaine in oral preparations.

3.        Anticholinergic drugs: These will block the muscarinic receptors in GIT.  Do not cross BBB, so no central action.

4.        Antidopaminergic drugs: Metaclopramide, domperidone. These have both central and peripheral action.

Dose – Domperidone dog    0.1–0.5 mg/kg. I/m.

                          0.5–1 mg / kg. oral.

II. Centrally Acting Antiemetics: these drugs act on central nervous system and suppress the vomition.

1. Antihistamines: Drowsiness and xerostomia are the side effects.

E.g. Cyclizine Hcl                25 – 100 mg/kg orally

     Meclizine Hcl  2 -10 mg/kg   orally

     Diphenhydramine          2 – 5 mg/kg orally

2. Antimuscarinic Agents: E.g. Natural alkaloid - scopolamine

                               Synthetic - Dicyclomine Hcl,   Isopropamide

Duration of action of synthetic drugs is short that is 6 hrs. Xerostomia and drowsiness are common side effects.

3. Antidopaminirgic agents: blocks the CTZ and inhibits the vomition.

    E.g.: Haloperidol, Droperidol.

4. Phenothiazine derivatives: tranquilizers.

    E.g.: Chloropramazine, Triflupramazine.

 Intestinal Astringents

Agents precipitate proteins, alter surface characteristics, and tend to form a protective layer on the mucosal surface.

1.            Metallic Astringents: Sulfates and hydrochlorides of zinc, copper, aluminum and iron. These are caustic and toxic.

2.            Vegetable Astringents: Tannic acid precipitates the mucous membrane protein and forms insoluble salts with heavy metals alkaloids, glycosides and decrease their toxicity.

Dose:-   Cattle    : 10-20g

                    Horse      : 4-8g

               Sheep&goat : 2-3 g

3.            Catechu along with ginger, chalk and creta as astringent powder in cattle.

4.            Aluminum hydroxide gel: for dogs orally 2 -4 ml.

Drugs affecting the intestinal tract

Gastric prokinetics

                Agents, which enhance the transit of intraluminal contents. Clinically use of these drug is limited because of systemic effects.

Metaclopramide: lipid soluble derivative of PABA. In addition to its central antidopaminergic (antemetic effects), peripherally acts both as an antidopaminergic and as a direct and indirect stimulator of cholinergic receptors. Clinically effects limited to upper GIT.

Domperidone: dopaminergic antagonist. Similar to above but it does not cross blood brain barrier as readily as metaclopramide. It acts peripherally to coordinate antroduodenal contractions, accelerates small intestinal transit but colonic activity is not affected.

Cisapride: has broad spectrum of action of prokinetic agents, does dependent increase in action of all sites (stomach to large colon). Prokinetic action is due to indirect stimulation of cholinergic nerves because secretion is not enhanced, stimulation probably occurs at the level of myenteric plexus and well absorbed from oral administration.

Purgatives

Agents promote defecation. Depending on the intensity of effect they are classified into

Laxatives: Promote elimination of a soft–formed stool.

Purgatives: Tend to produce more fluid evacuation

Cathartics: produce the watery stools with straining and gripping.

The difference between above type of effects may be just a matter of dose. In general purgatives can be classified into five types

I. Emollient laxatives:

These are also called as Lubricant laxatives, Mechanical laxatives or fecal softeners. They are unchanged in the GIT, not absorbed and simply soften and lubricate the fecal mass, which in turn facilitates expulsion. These are not reliable in ruminant.

Mineral oil (liquid paraffin): Dose: Cattle/horse - 0.5–2 liters.

                                     Calves/foals – 60–120 ml.

                                     Dogs         - 2-60 ml.

It is bland and generally safe to use. But chronic use may impair absorption of fat–soluble vitamins, other nutrients and coadministered therapeutic agents. This may decreased irritability of the intestinal mucosa and ensures chronic constipation. Anal leakage of mineral oil may be a nuisance in a house pet animals and will interfere with healing of wounds in the anorectal area.

II. Simple Bulk laxatives

These are hydrophilic in nature and are not digested with in the GIT. They adsorb water and swell and an emollient gel forms. The increased volume or bulk leads to distention, with resultant reflex contraction producing peristaltic activity. The feces remain soft and hydrated.

Agar, Acacia with drinking water for small animals.

Methylcellulose: dosage: Dogs –  0.5–5g,

                         Cats - 0.5–1g.

Wheat bran and rice bran in drinking water and fruits for large animals.

                Besides the bulk action of these laxatives, it should be noted that the celluloses and hemicelluloses present are fermented in the hindgut by bacteria to produce volatile fatty acids and other products that in turn exert an osmotic effect and thus enhance laxative action.

III. Osmotic purgatives (saline purgatives):

Consists of salts (or) compounds that are either not absorbed at all (or) only slowly and incompletely absorbed from the gastro intestinal tract. They retain or attract water into the intestinal lumen mainly by osmotic forces, although enhanced mucosal secretion of fluid may contribute to their effect. These are contraindicated in dehydrated condition and free access to water should be there. Purgation occurs with 3-12 hrs in monogastric animals and with in 18 hrs in ruminants.

Magnesium sulfate (Epsom salt): Horse/cattle - 250–500 g

                                Goat/calf    - 25 -50 g.

                       Sheep, goat and Swine – 25–125 g.

Magnesium oxide (milk of magnesia) and other magnesium salts are used.

           Goat/calf – 2-10 g.

                 Dog – 0.5–2 gm.

Sodium sulfate (Glauber’s salt), Mannitol and sorbitol also induce osmotic purgation.

Synthetic disaccharide, lactulose: Not digested, in large intestine fermented by saccharolytic microflora and produce acetic, lactic and other acids and exert an osmotic effect. These also absorbs water, softens fecal mass, and colonic peristalsis ensues.

IV. Irritant/stimulant purgatives

Stimulate the mucosal lining of the GIT there by initiate local myenteric reflexes that would enhance intestinal transit, also provoke fluid accumulation by activating secretary mechanisms.

A) Vegetable oils: Bland vegetable oils

 Mechanism of action of vegetable oils is on hydrolysis by pancreatic lipase in the small intestine fatty acids are released and they form into irritant soaps by combining with sodium and potassium salts. This soaps differ in potency depending on oil used.

Castor oil: ricinoleic acid → ricinoleates more irritant.

Linseed oil: less irritant linoleates.

Olive oil: mild oliveates.

Castor oil has strong action, evacuation of the whole intestinal tract occurs leading to complete emptying. Used in non-ruminants, purgation occurs with in 4–8 hr in small animals and 12-18 hr in large animals.

B) Diphenylmethane derivatives: Acts on large intestine.

E.g.: phenolphthalein should use only in primates and swine

      Bisacodyl: inhibits glucose absorption and                  Na⁺,k⁺adenotriphosphatase activity as well as altering                  motor activity of the visceral smooth muscle.

C) Anthraquinone derivatives (Emodin purgatives): Exert an indirect secondary purgative action. These are plant origin. All the anthraquinone derivatives are structurally related to substance 1,8Dihydroxy anthraquinone or Danthron. Orally administered glycosides and these are not absorbed and are hydrolyzed by bacterial enzymes in the large intestine to release the active aglycon known as emodins, which act by stimulating myenteric plexuses.

Prolonged use of these agents, myenteric plexuses actually degenerate with a resultant loss in intestinal motility. Effect occurs in 6-14 hr in small animals, 12-36 hrs in large animals.

D) Natural sources

Senna – leaflets of Cassia acutifolia for cattle/horse – 125 g,.

            Cassia augustifolia dog:– 2-8 gms orally

Cascara sagrada – Bark of Rhamnus purshiana

Dog:  liquid extract:- 2-4 ml

      Dry extract:– 0.1-0.5 g orally.

Aloes: It is the residue obtained by evaporating the liquid from the cut leaves of aloe plants. Aloe vera, Aloe chinensis.

              Horse:– 15–30g

             Cattle:– 40–60gm

               Dog:- 0.5–2 gm.

Danthrone: synthetic agent. Horse/cattle:– 15–45 g

                                                Dog:– 200–400 mg

Sheep:– 2–5 g

E) Other irritant purgatives: Cathartics/drastic purgatives, Highly irritant and may cause severe colic and super purgation, not used clinically.

E.g.: Croton oil, Barium chloride, Jalap, Podophyllum, Colocynth.

V. Neuromuscular purgatives

                Cholinergic agents with muscarinic actions will initiate hyper motility of GIT and promote defecation. Peristaltic activity increased with in 10-30 minutes of parenteral administration, 2–4 hrs of oral administration. Colic is side effect.

E.g.: Neostigmine, Physostigmine, Bethenecol and Carbochol

Agents Reducing Intestinal motility

Antispasmodics / Spasmolytics: Belladonna alkaloids - Atropine, Hyoscine

Opeates – tincture of opium (laudanum), Camphorated tincture of opium (paregoric), oxymorphine, codeine, meperidine.

G1 Protectants and adsorbents

Compounds that are not absorbed from GIT and either line the mucosal surface (or) adsorb toxic compounds are often incorporated into antidiarrheal mixtures. Protectants produce coating of gastro intestinal epithelium that prevents irritation or erosion by harmful substances.

Adsorbents: Physically bind chemical compounds which precludes their absorption, and they are then eliminated in the feces. Many drugs possess both properties.

E.g.: Magnesium Trisilicate

      Hydrated magnesium aluminum trisilicate

      Kaolin (natural hydrated aluminum silicate)

      Aluminum OH and Po₄

      Bismuth salts, Calcium carbonate, Pectin, activated charcoal.

Digestive Adjuvants

Digestive adjuvants are used therapeutically to control specific gastro intestinal diseases by promoting digestive processes. These consist of normal digestive enzymes or related substances that are used for replacement therapy in deficiency states.

A) Hcl: Various hydrochloride salts, which release Hcl in gastric fluid. Used for treatment of achlorhydria and hypochlorhydria. Effectiveness is questioned.

E.g.: Glutamic acid hydrochloride Dog: – 100-600 mg/12hrs.

      Betaine Hcl, Piperidolate Hcl.

B) Digestive enzymes:

1.         Pepsin: Administered along with Hcl to treat gastricachylia dose for calves/foals is 4 gm, dog is 0.1–1 gm orally.

2.         Pancreatic extracts that stimulate pancreatic exocrine secretions are used in cases of chronic pancreatitis and pancreatic hypoplasia, where glandular function is diminished or destroyed. This should be administered as enteric-coated preparation to prevent gastric destruction.

    E.g.: Pancreatine obtaine from hog pancreas. Dog:– 0.5–6 gm.

3.         Bile acids and salts: Promote absorption of long–chain fatty acids and fat–soluble vitamins.

E.g.: Dihydrochloric acid 100 mg/kg body weight.

      Chenodiol, Sodium tauroglycocholate.

      Florantyrone – crude extract of Ox and hog bile.

4.         Diastases and amylolytic enzymes: Obtained from malt and Aspergillus oryzae used for replacement of pancreatic α-amylase and to control flatulence caused by gas production from soluble carbohydrates by bacterial flora.

Drugs affecting liver

Cholagogues: Substances that cause contraction of the gall bladder and increases flow of bile into small intestine.

E.g.: Ceruletide: Has properties of gastrin and CCK – pancreozymin in                     mammals.

       Vagus stimulation will also contracts Gall bladder.

Choleritics: Increases secretion of bile by the hepatocytes.

a) Hydrocholeretic: Stimulates the liver to increase output of bile of low specific gravity.

E.g.: Hormone secretine, vagus Nerve stimulation.

Above two increases water and bicarbonate content of bile.

b) Bile salt dependent flows: A number of natural bile salts and several partially synthetic derivatives are used therapeutically as choleritics.

E.g.: - Dehydrocholic acid: most potent one.

        Glycocholate, taurocholate – increases lesser extent.

        Chenodiol, ox bile extracts Florantyrone, tocamphyl.

Bile salts have dual action–directly promoting fat absorption and stimulating biliary secretion after they have been absorbed. Over dosage causes diarrhea.

Liver protectants & Hepato tropic agents

                These are the agents having special affinity for the liver or for exerting a specific effect in the liver.

Lipotropic agents

                                Hasten removal of fat or decreases its deposition in the liver.

Choline: indispensable metabolite of body. It may promote conversion of liver fat into choline containing phospholipids, which are more rapidly transferred from liver into blood. It is thought that the lipotropic agents methionine, betaine and lecithin are effective because they contain choline or promote choline synthesis. Large quantities of choline seen to be needed for prevention of a fatty liver when the liver is already damaged. Choline is extremely valuble in the multitherapeutic approach to prevention and cure of fatty liver (Diabetes, Malnutrition, Cirrhosis).

L-Methionine: readily donates its terminal methyl group for methylation of various compounds. It is principle methyl donor of the body & supplies its labile methyl group to ehtanolamine to form choline. In addition to this methyl group methionine(cysteine) contains a sulfhydryl group, which appears to protect the liver against the noxious action of certain poisons. Orally administered methionine can however aggravate hepatic coma. Bacterial flora may convert methionine to mercaptan derivatives such as methanethiol and ethanethiol, which are themselves capable of inducing coma.

S-adenosyl-L-methionine (SAMe): is naturally occurring endogenous methyl donor, improves bile secretion that is impaired by a variety of toxins and pregnancy. Drug induced hepatotoxicity and chronic liver disease were also reduced.

Lecithin: contains choline as part of the molecule, which is liberated upon hydrolysis. Dogs used as lipotropic agent.

Vitamin-B₁₂: hydroxycobalamin stored in liver, mainly in mitochondria, but there is also a microsomal fraction. This microsomal vitamin may be of importance in hepatic protein metabolism. Essential for incorporation of methionine and alanine into protein. General liver protein synthesis is depressed. B12 has lipotropic effect involves in metabolism of labile methyl groups and in formation of choline, necessary for overall utilization of fat. When intake is low, the demand for this vitamin in heamopoisis exceeds.

                Use of lipotropic agents (choline, methionine, cysteine, betaine, lecithin, hydroxycobalamine) to increase mobilization of hepatic lipids is of proven value only in cases in which deficiencies of these substances exist. Deficiencies may be present in hepatic disease as a result of anorexia or insufficient dietary protein. Nutritious diet with adequate amounts of protein donot requires supplementation with lipotropic agents.

Selenium & Vitamin E: selenium is known to be essential for tissue respiration and to protect against dietary hepatic necrosis, extremely active, required in minute quantities. Se is an essential component of glutathione peroxidase, which catalyzes oxidation of reduced glutathione.

                2 glutathione-SH + H₂O₂          glutathione-S-S-glutathione + H₂O

                This glutathione peroxidase catalyzes removal of H2O2 and fatty acid hydroperoxides and so exerts a protective effect on all cells, but especially on muscle, liver and erythrocytes. The essential substances required for removal of peroxides are reduced glutathione and glutathion peroxidase. Vitamin E maintains glutathione in the reduced form by preventing formation of hydroperoxides; it is an antioxidant and so reduces the amount of glutathione peroxidase required.

                Selenium and vitamin E enhance each other’s action and together protect cells, especially hepatocytes, against harmful building of peroxides.

Glucose and Fructose:  liver efficiency is impaired when hepatocytes are laden with fat administration of hypertonic solution of glucose and fructose produces favorable responses in a variety of hepatic abnormalities. High glycogen content protects liver cells from damage and inhibition of gluconeogenesis.

Vitamins: liver disease, the fat-soluble vitamin K should be supplemented, since hepatic stores may be quite rapidly depleted. The water-soluble vitamins of the B-complex are frequently employed in therapeutic regimens for hepatic insufficiency. Rationale behind their clinical use is based on ensuring an adequate supply of metabolic co-factors.