Drugs Acting on Gastrointestinal Tract | Animals | Pharmacology

After reading this article you will learn about the various drugs acting on gastrointestinal tract.

Sialagogues:

Sialagogues or sialics are the salivary stimulants which increase the volume and fluidity of saliva.

Uses:

(i) Iatrogenic (drug-induced) hypoptyalism.

(ii) Xerostomia (dryness of the mouth due to lack of normal secretion) resulting from other causes such as radiotherapy of the buccal cavity and pharynx.

(iii) As constituents of tonic preparations.

Examples of Sialagoues:

(a) Reflex sialogoue:

(i) Bitters-

1. Simple bitters- (a) Gentian (b) Quassia (c) Calumba

2. Alkaloidal bitters- (a) Nux vomica (strychnine and brucine) (b) Cinchona (quinine)

(ii) Nauseants and emetics.

(iii) Turpentine oil

(b) Cholinergic Sialagogue:

(i) Choline esters

(ii) Cholinomimetic alkaloids

(iii) Cholinesterase inhibitors

(iv) α-adrenergic drugs (produce viscous saliva)

(v) Nicotine

(c) Direct acting sialagogue:

(i) Anethole Trithione

(ii) Mercurials (toxicity)

(iii) Iodine

(iv) Alcohol (small doses)

Anti-sialagogues:

These are salivary inhibitors which decrease flow and fluidity of saliva. This effect is usually accompanied by reduction in respiratory and digestive secretions.

Uses:

1. The principle use of this group of drug is for ‘preanesthetic medication’ to reduce excessive salivation that may occur during inhalation anesthesia or morphine narcosis.

Examples:

(i) Cholinolytic agents:

(a) Atropine

(b) Hyoscyamine

(c) Glycopyrrolate (synthetic anti-muscarinic drug).

(ii) Neuroleptics

(iii) Anticonvulsants

(iv) Antihistaminics

Stomachics:

These are the drugs which promote the functional activity of stomach by increas­ing secretions and motility.

Uses:

(i) Hypochlorhydria and Achlorhydria.

(ii) Anorexia

Examples:

(i) Muscarinic agents:

(a) Ach

(b) Carbachol

(ii) Dopamine antagonist:

(a) Metoclopramide hydrochloride (Reglan)

(iii) Alkaline stomachics:

(a) Carbonate salts

(b) Bicarbonate salts

(iv) Bitters:

(a) Gentian

(b) Nux vomica

(v) Histamine agonists:

(a) Histamine

(b) Betazole hcl (Histalog) [H₂ agonist]

(vi) Synthetic Pentapeptide-

(a) Pentagastrin.

Mechanism of Action:

(i) Muscarinic agents- by stimulating gastric cholinergic receptors.

(ii) Metochlopramide- (a) ↑ tone in the lower oesophageal sphincter.

(b) ↑ force and frequency of gastric antral contractions (gastro kinetic effect).

(c) Relaxes the pyloric sphincter

(d) Promotes peristalsis in the duodenum and jejunum.

Results in accelerated gastric emptying and upper intestinal transit.

(e) It also exerts local and central antiemetic actions.

Dose:

Dog and Cat- 0.1-0.3 mg/kg/8hr. orally or i.m. or -0.02 mg/kg/hr, i.v.

(iii) Alkaline stomachics – CO₂ is generated in simple stomach → stimulates gastric secretion and vasodilation in the gastric mucosa.

(iv) Betazole has less marked effects on B.P. and smooth muscle than histamine. An H₁-antihistaminic drug is used 30 min prior to histamine therapy. Both of them act on H₂ receptors to secrete HCl.

(v) Pentagastrin → contains the C-terminal tetra peptide responsible for the actions of natural ‘gastrins’. It acts as a physiologic gastric acid secretagogue.

Human dose: 6 mg/kg/ s.c. inj.

Anti-stomachics or Gastric Sedatives:

Examples:

(i) Anti-muscarinic drugs.

(ii) Adrenergic agents

(iii) GI spasmodics:

(a) Phenanthrene alkaloids of opium.

(i) Morphine

(ii) Codeine

(iv) H₂-receptor antagonists- ranitidine, cimetidine.

(v) Secretin

(vi) Cholecystokinin (CCK)

(vii) Gastric inhibitory peptide (GIP)

(v), (vi) and (vii) inhibit gastric employing by slowing gastric motility and increasing pyloric tone.

Rumenotorics:

These are the drugs which increase ruminal tonicity.

Examples of stomachics and rumenotorics:

1. Antimony potassium tartrate

2. Cobalt sulphate and chloride

3. Dried ferrous sulphate

4. Copper sulphate

5. Choline bi-tartrate and chloride

6. Thiamine monohydrate

7. Manganese sulphate

8. Nicotinic acid

9. Dried yeast

10. Sod. hyd. phos./Sod. acid phosphate

11. Zinc sulphate

12. Brassica

Carminatives or Antiflatulants:

These are the drugs which, when administered orally, cause the expulsion of gases from the stomach (Also called as ‘eructation’)

Mechanism of Action:

They have a mild irritant action on mucous membranes and tend to relax the GI musculature, particularly the cardiac sphincter of stomach, for a period of up to 30 min which probably plays a large part in releasing gases from the stomach.

Examples:

They are mainly volatile compounds:

(i) Compounds which contain volatile oils:

(a) powdered aniseed/anise.

(b) Ginger.

(ii) Pure volatile oils:

(a) Turpentine oil

(b) Peppermint oil

(iii) Substances obtained from volatile oils by cooling:

(a) Stearoptenes camphor.

(b) Stearoptenes menthol

(iv) Volatile anaesthetics:

(a) Ether

(b) Chloroform

(v) Other volatile compounds:

(a) Alcohol

(vi) Miscellaneous:

(a) Simethicone/activated dimethicone/dimethyl polysiloxane: a surfactant; the defoaming action of it relieves flatulance by dispersing and preventing formation of mucous- surrounded gas pockets in GIT.

Antizymotics:

These are (he drugs which prevent or decrease bacterial or enzyme fermentation. Their use is aimed at the prevention of further gas production in tympany and bloat in ruminants, or flatulent or tympanitic colic in horses.

Tympany or Bloat:

It is the presence of free gas in the rumen.

Drugs used in Tympany and Bloat:

1. Volatile oils (especially turpentine)

2. Formalin

3. Phenol

4. Phenolic compounds (Salol, cresol and lysol)

5. Chloroform

6. Chloral hydrate.

7. Ethyl alcohol/ethanol.

8. Ruminal fluid/rumen content from normal ruminating animal or slaughtered animal. Administer it immediately to non-ruminating (diseased) animals.

Treatment of Tympany/Bloat:

(i) Remove the gas by stomach tube or trocar and cannula (or wide-bored needle) inserting through the left flank

(ii) Give ruminal fluid as above in no. 8, of above paragraph.

(iii) Give anti-zymotic agents: (by stomach tube or inject into rumen by 8 cm wide-bore needle).

(a) Turpentine oil + Linseed oil

Cattle – 15-30 ml + 250-500 ml respectively

Sheep – 4-8 ml + 60 -300 ml respectively

(b) Formalin + water

Cattle – 4 ml + 300 ml respectively, t.i.d.

Sheep – 0.6 -1 ml + 100 ml.

(c) Tympolax liquid (Formain 3%, Turpentine oil 12%, arachis 35%) Cattle and Horse-100-140 ml.

B. Drugs used in Frothy Bloat:

Gas locked in the bubbles of a froathy mass.

1. Turpentine oil

2. Paraffin (Kerosene)

3. Organic silicones

(a) Methyl silicone

4. Fixed oil-detergent mixture

5. Polyethylene glycol surfactants.

6. Other emulsifying agents.

7. Penicillin – 50-200 mg.

Dose: (by stomach tube or intra ruminal inj.)

1. Turpentine Oil:

Cattle – 15-60 ml

Horse – 15-90 ml

Sheep – up to 12 ml

Pigs – up to 4 ml

For Horse Colic:

Chloral hydrate – 15gm

Turpentine oil – 30 ml

linseed – up to 300 ml.

2. Polymerized Methyl Silicone:

2-5% in fluid hydrocarbons (e.g. purified kerosene)

Dose-50-100 ml (i.e dosage vary from 50 ml of higher conc. to 100 ml of lower conc.)

Antispasmodic Drugs:

An agent that relieves spasms of GIT.

Examples of Antispasmodics:

1. Atropine

2. Homatropine 

3. Hyoscine

4. Hyoscyamus

5. Pethidine

6. Ginger (tonicity initially increased which is followed by decrease)

7. Dicyclomine (anticholinergic)

8. Propantheline (Anticholinergic are most useful).

Alimentary Demulcents:

These are a group of compounds that are generally of high molecular mass and often water soluble. They lubricate, coat and protect upper alimentary mucous mem­branes. In addition, they are used to mask unpleasant tastes, stabilize emulsions, and act as suspending agents.

Examples of Demulscents:

1. Syrups

2. Honey

3. Starch

4. Glycerol

5. Natural plant hydrocolloids

(a) Gum tragacanth,

(b) Guar gum,

(c) Agar,

(d) Alginic acid,

(e) Glycyrrhiza

(f) Methylcellulose

6. Propylene glycol,

7. Polyethylene glycol (low molecular mass)

8. Liquid paraffin (mineral oil)

9. Proteins

(a) Egg albumin

(b) Gelatin

Cholagogue:

Substances that cause contraction of the gall bladder are called cholagogues.

Examples:

1. Ceruletide

(a decapetide isolated from the skin of the Australian frog).

2. Endogenous compounds

(a) Gastrin

(b) CCK-pancreozymin (CCK- Cholecystokinin)

3. Vagus stimulation.

Choleretics:

Substances that increase secretion of bile by the hepatocytes are known as Choleretics.

Hydroeholeretic:

A drug that stimulates the liver to increase out of bile of low specific gravity is called a hydroeholeretie.

Examples:

1. HCl (potent hydrocholeretic agent)

2. Natural bile salts

(a) Glycocholate

(b) Taurocholate

3. Chenodiol,

4. Ox bile extract,

5. Florantyrone

6. Tocamphyl

7. Oxybutyric acid derivatives.

(a) Clanobutin

(b) Genebile

Bile salts used therapeutically have a dual action in directly promoting fat absorp­tion and stimulating biliary secretion after they have been absorbed. Over-dosage with these compounds will tend to cause diarrhoea.

Antacids:

These are the basic substances which neutralize gastric acid and raise the pH of gastric contents.

Indications:

(i) Gastric hyperacidity

(ii) Peptic ulcer,

(iii) Gastritis,

(iv) Reflux oesophagitis,

(v) Chronic renal failure (uremia)

(vi) Abomasal ulceration in cattle.

(vii) Ruminal acidosis from grain overload.

Mechanism of Action:

(a) They neutralize HCl present in gastric fluid.

(b) They inactivate pepsin raising the gastric pH to at least 3 to 4 without causing systemic alkalosis (since pepsin activity for peptic digestion is opti­mal at pH 2-3)

Action of gastric antacids is usually transient and lasts up to only 1-2 hrs.

Drawback:

(i) Neutralization of acid in the stomach antrum removes negative feedback control of “gastrin” release, which in turn will lead to elevated gastrin levels and enhanced HCl secretion (acid rebound effect)

(ii) Side Effects: NaHCG₃ – alkalosis, acid rebound; Al (OH)₃ – Constipation; Mg (OH)₂ – loose stools or diarrhoea, CaCO₃ – constipation, alkalosis, acid rebound etc.

(A) Systemic Antacids:

Examples of systemic antacids:

(i) Sodium bicarbonate (NaHCO₃)

(ii) Sodium citrate

(iii) Sodium acetate

Disadvantages of Systemic Antacids:

(a) They can cause metabolic alkalosis which can be compensated by secreting alkaline urine. But in renal failure, dangerous alkalosis may result.

Sodium Bicarbonate:

This is still widely used by the lay people, as it produces prompt relief from heartburn and dyspepsia. Because of its high water solubility, it is immediately effective in neutralizing the HCl in the stomach:

NaHCO₃ + HCl → NaCl + H₂CO₃

H₂CO₃ → H₂O + CO₂

Disadvantage:

(i) Duration of action is short.

(ii) Rapid liberation of CO₂ may lead to gastric distention, perforation of ulcer, belching.

(iii) Acid rebound.

(iv) Metabolic alkalosis, and disturbance of acid base balance.

(B) Non-systemic Antacids:

Examples:

(i) Aluminium Salts:

(a) Al(OH)₃

(b) Al-Mg-cilicate

(c) AIPO₄

(ii) Magnesium salts:

(a) Mg(OH)₂

(b) MgO

(c) (Mg-trisilicate)

(d) MgCO₃

(iii) Calcium salts:

(a) CaCO₃.

Non-systemic antacids may also be classified according to their capacity to in­crease gastric pH:

(i) Buffer Antacids:

(a) Aluminium hydroxide gel [Al (OH)₃]

(b) Aluminium phosphate gel [AIPO₄]

(c) Magnesium trisiticate

They limit the rise of gastric pH below neutrality,

(ii) Non-buffer Antacids: (alkali antacids)

(a) Calcium carbonate (or creta) [CaCO₃]

(b) Tribasic calcium phosphate.

(c) Magnesium oxide [MgO]

(d) Magnesium carbonate [MgCO₃]

(e) Magnesium hydroxide [Mg(OH)₂]

They potentially permit an elevation in pH above neutrality:

(iii) Miscellaneous Antacids:

(a) Sodium carboxymethyl cellulose.

The non systemic antacids are used either alone or in combination with each other or with various protectants, adsorbents astringents, They neutralize gastric HCl, but not tend to cause systemic alkalosis because they are insoluble basic com­pound and hence poorly absorbed. So, they do not disturb acid base balance. In case of peptic ulcer, these drugs are preferred.

However, continuous or large dose may increase their absorption which may lead to alkalosis.

Aluminium Hydroxide:

It is a frequently used salt.

Dose:

Cattle – 30gm.

Dogs – 100-200mg.

Cats – 50-100mg.

It is a good adsorbent as well as an antacid. To prevent constipation, aluminium salts are often mixed with magnesium salts, e.g. Gelucil® which contains aluminium hydroxide gel 250 mg and Magnesium trisilicate 500 mg per tab.

Al(OH)₃ decreases phosphate absorption by forming insoluble aluminium phos­phate in the intestine. Aluminium hydroxide gel is a mixture of aluminium hydroxide, hydrated aluminium oxide, and small amount of basic aluminium carbonate.

The normal pH of dog stomach is 3.5 to 4.5. AlCl₃ formed in the stomach reacts with the alkaline intestinal juices and Al(OH)₃ is re-precipitated. The drug causes a reduction of gastric acidity only to about pH 4 and thus does not cause complete suppression of peptic digestion.

The drug is a good adsorbent and adsorbs toxins, gases and bacteria.

Magnesium Hydroxide:

Mg(OH)₂ or its suspension in water is the most com­monly used form of magnesium.

Dose:

Calves and Foals → 30-60 ml,

Dogs – 1-20 ml.

Cats – 1-5 ml.

Mg(OH)₂ is a good antacid, having a prompt neutralizing effect with a prolonged action, but tends to increase the pH to rather high levels (about 7) which may hamper the normal digestion process. Magnesium salts tend to be laxative and are often found in combination which aluminium and calcium salts. The cathartic effect results from soluble but unabsorbed magnesium salts that remain in the intestine, thus retaining water.

Disadvantages:

(i) Normally about 20% magnesium is absorbed which is rapidly excreted through kidney. However, renal dysfunction or repeated dose can result in dangerous degree of retention.

Calcium Carbonate:

Dose:

Cattle → 60-360 gm.

Horse → 30-60 gm.

Sheep and Swine → 8 – 15 gm.

Dogs → 0.5-4 gm.

It is another commonly used antacid. Its effects are rapid in onset and prolonged in duration.

Side Effects:

(i) Slowly developing metabolic alkalosis,

(ii) gastric acid rebound,

(iii) hypercalcemia

(iv) Calciurea

(v) metastatic calcification and urolithiasis,

(vi) hypophosphatemia, and

(vii) Constipation.

Drugs for Peptic Ulcer:

Peptic ulcer occurs in that part of the GIT which is exposed to gastric acid and pesin, i.e., the stomach and duodenum. It results due to an imbalance between the ‘aggressive’ (acid and pepsin) and the ‘defensive’ (gastric mucus and the innate resist­ance of the mucosal cells) factors. In gastric ulcer, generally, acid secretion is normal or low. In duodenal ulcer, acid secretion is high in half and normal in the rest.

Classification:

The main aim in treatment of peptic ulcer is reduction of the aggressive factor, acid secretion.

Approaches for the treatment of peptic ulcer are:

1. Neutralization of gastric acid: Antacids.

(a) Systemic: Sod. bicarbonate

(b) Non-systemic: Calcium carbonate

Aluminium hydroxide gel

Manesium carbonate/hydroxide/trisilicate.

Magaldrate.

2. Reduction of gastric acid secretion:

(a) Anticholinergics: Atropine, propantheline, oxyphenonium, pirenzepine, Trimipramine, Doxepin.

(b) H₂ antihistaminics: Cimetidine, Ranitidine, Famotidine, Nizatidine, Oxmetidine

(c) Proton pump inhibitor (H⁺ – K⁺ ATPase): Omeprazole (a substituted benzimidazole)

(d) Prostaglandin: PGE₂ and analogs.

3. Ulcer healing drugs: Carbenoxolone sod., Deglycyrrhizinized liquorice, Gefarnate.

4. Ulcer protectives: Sucralfate Tripotassium dicitratohismuthate

5. Miscellaneous: Metoclopramide

Carbenoxolone Sodium:

It is a steroid-like synthetic triterpenoid obtained from glycyrrhetinic acid (found in liquorice root).

Mechanism of Section:

Carbenoxolone has no effect on the volume or pH of gastric juice:

(i) It may reduce peptic activity (by interfering which activation of pepsinogen).

(ii) Its most important action is to increase mucus (gastric mucoproteins) produc­tion and secretion, specially the viscid mucus that remains adherent to the gastric mucosa. It prolongs the lifespan of gastric epithelial cells. Mitosis in the regeneration zone around the ulcer has been found to be increased.

(iii) An additional effect of it is to enhance pyloric tone; prevents bile reflux that promotes back diffusion of H⁺ in the gastric mucosa which is probably important in breaking the mucosal barrier.

It is contraindicated in hypertension, renal and hepatic disease.

Sucralfate:

It is recently introduced drug of its own kind. It is a complex formed from sucrose octasulphate and polyaluminium hydroxide (so it is a basic aluminium salt of sulfated sucrose).

Sucralfate is inherently viscous in acidic medium. It polymerizes at pH < 4 by cross linking of molecules, assuming a sticky gel like consistency. It preferentially adheres to ulcer base, specially duodenal ulcer; and remains there for over 6 hrs.

It precipitates surface proteins at ulcer base and acts as an acid resistant physical barrier preventing acid, pepsin and bile from coming in contact with the ulcer base. Dietary proteins get deposited on this coat, forming another layer.

Interaction of sucralfate polyanions with substrate proteins inhibit peptic activity so that pepsin is not able to bind to surface proteins of eroded mucosa and digest it. It has no acid neutralizing action.

Antacids should not be taken with it because its polymerization is dependent on acid pH.

It interferes with the absorption of tetracyclines, cimetidine, phenytoin, and digoxin.

Dose: Ulcekon®

Dogs – 1 gm/25 kg/8 hrs.

Metoclopramide:

A gastric hurring agent; has been found to help healing in gastric ulcer, probably by preventing the reflux of bile into stomach which acts to break the gastric mucosal barrier.

However, its efficacy is lower than other drugs. It is practically ineffective in “duodenal ulcer”.

Cimetidine and Ranitidine:

H₂ antihistaminics.

Therapeutic Uses:

(i) Gastric and duodenal ulcers,

(ii) Uremic gastritis,

(iii) Stress-related erosive gastritis,

(iv) Hyper secretory conditions (gastrinoma or systemic mastocystosis).

(v) Upper GIT bleeding

Doses:

Cimetidine:

Dogs: 5- 10 mg/kg/ 6-8 hrs., orally

or – 10 mg/kg/6 hrs. slow i.v. inj over 30-40 min.

Ranitidine:

0.5 mg/kg/12 hr.

Antidiarrhoeals:

Classification:

A. Specific (antimicrobials):

(a) Antimicrobials are regularly used in:

(i) Cholera:

(a) Tetracycline

(b) Cotrimoxazole

(c) Chloramphenicol

(ii) Yersinia enterocolitica-(common in colder places, not in tropics.)

(a) Cotrimoxazole

(iii) Clostridium difficile-(Pseudomembranous enterocolitis)

(a) Vancomycin

(b) Metronidazole

(iv) Diverticulitis (diarrhoea associated with bacterial growth in blind loops)

(a) Tetracycline

(b) Metronidazole

(v) Amoebiasis and Giardiasis:

(a) Metronidazole

(b) Diloxanide furoate

(c) Furazolidone

(b) In severe diseases associated with diarrhoea: (not in milder one)

(i) Travellers diarrhoea:

mostly due to ETEC, campylobactor or virus, (only in severe cases).

(a) Cotrimoxazole

(b) Doxycycline

(c) Erythromycin

(ii) Enteropathogenic E. Coli. (EPEC): (less common)

(a) Cotrimoxazole

(b) Colistin

(c) Nalidixic acid.

(iii) Shigella enteritis:

only when associated with blood or mucus in blood.

(a) Cotrimoxazole (b) Ampicillin (resistance may develop) (c) Nalidixic acid.

(c) Not effective in diarrhoea due to non infective causes:

Examples:

(i) Irritable bowel syndrome

(ii) Coeliac disease

(iii) Pancreatic enzyme deficiency

(iv) Tropical sprue (except when there is secondary infection)

(v) Thyrotoxicosis

(vi) Salmonella food poisoning (antibiotics are harmful. The disease is generally self-limiting)

B. Nonspecific Anti-Diarrhoeal Agents:

(a) Absorbents:

(i) Isapgol (i) Irritable bowel

(ii) Psyllium (ii) Ileostomy/colostomy diarrhoea

(iii) Methyl cellulose

(b) Adsorbents:

(i) Kaolin (ii) Pectin Nonspecific diarrhoea (iii) Chalk (iv) Charcoal (Little actual benefit) (v) Cholestyramine – Bile salt diarrhoea.

(c) Anti-secretory:

(i) Aspirin – Radiation sickness, food intolerance.

(ii) Bismuth Subsalicylate – Traveller’s diarrhoea

(iii) Chlorpromazine – Severe cholera

(iv) Sulfasalazine – Ulcerative colitis, regional ileitis.

(v) Sod. cromoglycate – Food allergies.

(vi) Atropine – Nervous diarrhoea, drug- induced diarrhoea

(d) Anti-motility: (opioids)

(i) Codeine (i) Non-infective or mild travellers diarrhoea,

(ii) Diphenoxylate (ii) After anal surgery, -atropine

(iii) Loperamide (iii) Colostomy, (also anti-secretory)

Doses:

1. Kaolin (natural aluminium silicate):

Horse and cattle – 50-250 gm.

Calf and foal – 15-60 gm.

Dog – up to 8 gm.

2. Bismath Salts: (Carbonate, salicylate and sub-nitrate)

H & C → 15-30 gm.

Calf & foal – 2-4 gm.

Dog – 0.3-2 gm.

Cat – 0.1-0.3 gm.

Rehydration Therapy in Diarrhoea:

1. Intravenous rehydration:

NaCl → 85 mM → 5gm

KCl → 13 mM → 1gm

or Sod. acetate,

or Sod. lactate, or NaHCO₃ → 48 mM → 4gm

water → 5% glucose solution – 1 litre.

2. Oral rehydration:

Emetics:

True emesis is not possible in the horses, ruminants and rats. When it occurs in adults the animal seldom lives long after the event. Any regurgitation in the horses occurs via the nose.

Vomiting (emesis) occurs due to stimulation of the emetic (vomiting) centre situ­ated in the medulla oblongata.

True emesis is a reflex in which the pylorus and the pyloric area of the stomach contract, the fundus relaxed and the cardia opens; abdominal contraction allied with throacic and diaphragmatic relaxation then drives the stomach contents into the oesopha­gus; the oesophagus and thorax then contract, forcing some of the material back into the stomach and the rest into the mouth.

Emesis may be caused reflexly by irritation of the stomach mucosa, or centrally by the stimulation of the vomiting centre situated in the medulla just below the third ventricle.

Several afferent pathways may be responsible for initiating emesis. These are represented diagrammatically in Figure 19.1 and 19.2.

Clinical uses of Emetics:

(i) This is usually desirable prior to induction of general anaesthesia if there is any possibility of food being in the stomach.

(ii) This is also employed as a rapid means of eliminating orally ingested noncorrosive poisons.

Classification of Emetics:

(A) Peripherally acting or reflex emetics

(B) Centrally acting emetics.

A. Peripherally acting emetics:

A number of substances can be used to induce emesis by irritating the epithelium of the pharynx, oesophagus, stomach, or duodenum.

1. Warm water (given, in poisoning with noncorrosive substance, by stomach tube)

2. Warm, saturated NaCl solution.

or → NaCI Crystals → 1/2 t.s.f. (on to the back of the tongue)

or → NaCI Crystals → 1-2 t.s.f. in 1/2 cup tepid (lukewarm) water

3. Sod. Carbonate (Washing soda → one sizeable crystal pushed over the back of tongue).

4. Copper sulphate (CuSO₄) Sol. → 50 ml of 1% sol. (emesis occurs within about 10 min).

5. Zinc sulphate (ZnSCy sol → 50ml of 1% sol.

(less reliable than CuS0₄)

6. Mustard → 1/2-1 t.s.f. in 1/2 cup of tepid water.

(Freshly ground mustard seed (not prepared mustard or mustard powder should be used)

7. Hydrogen peroxide (H₂O₂) → 3%

[Purgatives or gastric lavage are needed if vomiting does not follow the admin­istration of copper or zinc salts, which are all toxic following absorption.]

8. Syrup ipecac (contains “emetine”)

(by irritating gastric mucosa). 15-20 ml in adult man, 10-15 ml in children, 5 ml in infants.

[Emetine has the both peripheral and central effects.]

9. Veratrine → an alkaloid obtained from Veratrum sp. (plant) acts as locally/ peripherally acting emetic.

B. Centrally Acting Emetics:

Drugs in this group stimulate CTZ centre in the medulla oblongata, which in term stimulates the vomiting centre.

1. Apomorphine Hydrochloride:

It is a synthetic derivative of morphine, pro­duced by reaction with hydrochloric acid (Morphine + HC1 <$E symbol A> apomorphine). Its emetic activity is enhanced but the secondary depressant effects are minimised.

It stimulates dopaminergic receptors in the CTZ and vomiting occurs within 2-10 min.

Dosage:

Dogs → 0.04 mg/kg, i.v. inj.

0.07 mg/kg, i.m. inj.

0.02 mg/kg, into conjunctival sac.

3.0 mg (1.5-7.5 mg), s.c. inj. (preferable route)

6.0 mg, orally, (less reliable).

Excessive or repeated doses should be avoided because of its depressant action upon the CNS and respiratory centre.

2. Xylazine Hydrochloride:

This is sedative analgesic agent also used as a preanesthetic drug. Vomiting occurs in cats more consistently than in dogs. Dogs and Cats → 1 mg/kg, i.m. inj

3. Ipecac (syrup or powder):

Not used now-a-days due to its toxic effects.

Anti-emetics:

Anti-emetics control vomiting by either a central action or a local protectant effect. Centrally acting anti-emetics may either block dopaminergic receptors in the CTZ or depress the emetic centre in the medulla. Locally acting anti-emetics protects the GI epithelium from further irritation.

Clinical Uses:

(i) Centrally acting anti-emetics are used as a prophylactic measure for motion sickness in pets being transported.

(ii) They are also employed to control vomiting induced by drugs, uremia, radiation therapy, gastritis, gastroenteritis, and other disease conditions affecting various visceral organs.

Peripherally Acting Antiemetic:

1. Demulscent (dextrose, glycerin) and protectants (kaolin, pectin, bismuth salts) They may be of limited benefit

2. Antispasmodics (gastric sedatives):

(i) Topical anaesthetics

(a) Benzithine – Dogs and Cats – 0.3 gm., t.i.d.

(b) Amethocaine – Dogs and Cats – 0.3 gm., t.i.d.

(c) Chlorbutol – Dogs and Cats – 0.3 gm., t.i.d.

3. Antacids:

(i) Fast-acting antacids (soluble in water)

(a) Sod. bicarbonate

(ii) Slow-acting antacids (less soluble)

(a) Calcium carbonate.

(b) Magnesium carbonate.

(c) Calcium hydroxide and oxides.

(d) Magnesium hydroxide and oxides.

(e) Aluminium silicates.

(f) Magnesium silicates

(g) Aluminum hydroxide gel.

(h) Bismuth glycinate.

(i) Aluminium glycinate.

4. Anti-muscarinic agents: (anticholinergic drugs).

(They can not cross the BBB)

(a) Metoclopramide:

It is both a central and peripherally acting antiemetic. It possesses anti-dopaminergic activity and thereby depresses the CTZ centre but also promotes the release of and increases the sensitsisty of visceral smooth muscle to acetylcholine.

Metoclopramide is contraindicated in:

(i) Gl obstruction or perforation

(ii) Epilepsy and in

(iii) Patients receiving neuroleptics,

(iv) Atropine and the opioid analgesics antagonise the action of metoclopromide.

(b) Domperidone:

Dogs: 0.1-0.5 mg/kg, i.m. inj.

or 0.5- 1.0 mg/kg, orally.

It is also a dopamine antagonist and can not cross the BBB.

(c) Peripherally acting anti-muscarinic drugs:

(i) glycopyrrolate

(ii) propantheline

(iii) methscopolamine (not to be used in cats)

(iv) isopropamide

They inhibit afferent vagal impulses, relief GI smooth muscle spasms and inhibit gastroenteric secretions.

The delay in gastric emptying may itself cause vomiting, and anticholinergics should not be used for longer than 3 days in the vomiting patient.

Centrally Acting Anti-emetics:

1. Antihistaminics (Certain Antihisaminics): orally

(a) Cyclizine hcl → in motion sickness in dose 25-100 mg (total oral dose)

(b) Meclizine hcl → Dogs → 2-10 mg/kg up to 10 kg b.wt. or 2-6 mg/kg over 10 kg b.wt.

(c) Buclizine hcl → Dogs → 2.5 mg/kg, orally.

(d) Diphenhydramine hydrochloride → Dogs → 2-5 mg/kg, orally

(e) Dimenhydrinate hydrochloride.

Their antiemetic effect is independent of their antihistaminic or sedative potencies, but seems to have direct effect on neural pathways arising in the vestibular apparatus.

side effects → drowsiness and xerostomia

2. Anti-muscarinic Drugs: (used for controlling motion sickness in dogs)

(a) Belladonna alkaloids

(i) Hyoscine (scopolamine)

(b) Synthetic compounds.

(i) Dicyclomine hydrochloride → Dog → 5-10 mg (total oral dose)

(ii) Isopropamide iodide Dog → 0.2-1.2 mg/kg

Side effects → drowsiness and xerostomia.

3. Broad-Spectrum Antiemetics:

They control vomiting induced by most causes other than labyrinthine stimulation. They block the CTZ at low doses (be­cause of their anti-dopaminergic activity) and the emetic centre at higher doses (perhaps because of a weak anticholinergic action).

(i) Phenothiazine derivatives (neuroleptics):

(a) Chlorpromazine

(b) Triflupromazine

(c) Trifluoperazine

(d) Prochlorperazine

(e) Perphenazine

(f) Mepazine

(ii) Butyrophenone derivatives (major tranquilizers):

(a) Haloperidol

(b) Droperidol.

Potent anti-dopaminergic agents.

(iii) Diphenylbutyl piperidines:

(a) Pimozide → dog: 0.025-0.1 mg/Kg, orally.

It has long duration of action up to several days.

(iv) Trimethobenzamide hydrochloride:

It is a weak antihistaminic but a powerful antiemetic agent that suppresses the CTZ without affecting the emetic centre. It is effective in management of vomiting caused by radiation sickness, drugs, infections, anaesthesia and uremia.

(v) Diphenidol:

It is a complete antiemetic suppressing vomiting from labyrinthine stimula­tion as well as that from impulses from the CTZ.

Side effects-drowsiness, depression, disorientation, xerostomia and transient hypotension.

(vi) Sedatives:

(a) Barbiturates

(b) Benzodiazepines

They control psychogenic and behavioral vomiting.

Laxative (Aperients) and Purgatives (Cathartics):

Laxatives and purgatives both are used for defecation. Laxatives promote soft formed stool whereas purgatives tend to produce a more fluid evacuation. Laxative causes similar action but the effect is milder and rarely causes more than a slight intensification of intestinal activity. Small doses of purgatives may act as laxative and a laxative in high dose may cause purgation. Exception is liquid paraffin which even in higher dose can not pro­duce purgation.

Super Purgation:

An over dose of purgatives causes extreme and continued intestinal activity known as super purgation. There is a frequent arid painful evacuation of fluid and blood stained faeces may come out. This can cause shock, dehydration and death of animals. Therefore, purgatives be used intelligently and only when necessary.

Classification:

1. Lubricant laxatives (Emollient laxative, mechanical laxatives or faecal soften­ers) e.g., Liquid paraffin.

2. Bulk Purgatives:

(a) Simple bulk purgatives

e.g., Agar-agar, Pysllium, Sodium carboxymethyl cellulose, wheat bran and isapgol husk.

(b) Saline bulk purgatives

e.g., Sodium chloride, Magnesium oxide, Magnesium Sulfate and Magnesium Carbonate.

3. Irritant purgatives:

(a) Direct irritant purgatives

e.g., Mercury compounds, Phenolphthalein and Vegetable oils.

(b) Indirect irritant purgatives e.g., Anthracene compounds —

Aloes, Senna, Cascara, rhubarb, Synthetic anthraquinones.

(c) Drastic irritant purgatives

e.g., Jalap, podophyllum, corotonril, barium chloride and colocynth.

4. Neuromuscular purgatives:

e.g., parasympathomimetic drugs — Pilocarpine, Arecholine, Physostigmine and carbaminoyl chloride.

Lubricant laxatives:

Their effect is totally mechanical and are not absorbed from gastrointestinal tract. Their oily and lubricant character is useful for laxative effect. They coat the mucosa and cause smooth passage of faecal material. Untowards action:

(i) chronic constipation or may even be aggra­vated by oil.

(ii) Hinders absorption of food.

e.g., Liquid paraffin:

Dose:

Dog – 4 to 30 ml depending on size of dogs.

Bulk Purgatives:

Simple Bulk Purgatives:

They increase the volume of intestinal contents. The increase causes distension of the intestines, that produces reflex counter contraction of musculature and increases peristalsis. Bulk purgatives are indicated after swallowing of sharp needles in small animals.

e.g., Methyl cellulose

Dose:

Dog – 0.5 to 5g orally

Cats – 0.5 to 1g orally.

Saline Purgatives (Osmotic Cathartics):

Salts or compounds that are not absorbed at all or only slowly and incompletely absorbed from the gastrointestinal tract. They retain or attract water into the intestinal lumen mainly by osmotic forces. Enhanced mucosal secretion of fluid may contribute to their effect.

The important points to be remembered are:

(i) Saline purgatives are contraindicated in dehydrated animals.

(ii) Action in 3-12 hours in monogastric animals.

(iii) Action in ruminants is within 18 hours.

(iv) It is less reliable in horse.

e.g., Magnesium Salt (Epsom’s Salts), Sodium sulfate (Glauber’s Salt), Dose of Magnesium Sulfate:

Purgative:

Cow – 0.24 to 0.48 kg

Sheep – 60 to 120 g

Laxative:

Cow – 60 to 120 g

Horse – 30 to 60 g

Sheep – 7.5 to 15 g

Pig – 15 to 30 g

Direct Irritant Purgatives:

e.g., vegetable oils: cause sponification with alkaline bile salts of small intestine. This process produces monobasic, dibasic and tribasic soaps. Glycerol is the by-product of this saponification, it lubricates and breaks the faecal masses. It also exerts strong osmotic pressure to retain fluid within the intestinal lumen.

The following vegetable oils produce different kinds of irritant salts.

Olive oil → Oleic acid

Castor oil → Ricinoleates

(Choice of purgative in Dog)

Lin seed oil → Linoleates and Linolenates

Dose:

Linseed oil:

Horse – 0.5 to 1 litre

Foal, calf, pig – 30 to 180 ml

Dog – 4 to 30 ml

Action:

Within 4 to 8 hour in smaller species. There is complete clearance of intestine.

Important:

(i) Not indicated in chronic constipation because it may aggravate after temporary relief.

(ii) Linseed contains cyanogenic glycoside which produces prussic acid-when acted by enzymes. The enzymes are activated by steeping the seed in luke warm water and sufficient acid is produced to kill adult.

Castor Oil:

Mechanism of Action:

Castor oil is obtained from bean of Ricinus communis. It contains extremely toxic protein-ricin. Oil of castor contains triglyceride of ricinoleic acid which accounts for the drastic purgation action.

In the small intestine, pancreatic lipases hydrolyse the oil to glycerol and ricinoleate which like other surfactants reduces the absorption of water and electrolytes and stimulates intestinal motility. Due to the action of castor oil starting relatively high up in small intestine the pur­gation is rapid and drastic.

Side Effects:

(i) Abdominal colic.

(ii) Dehydration and electrolytic imbalance.

(iii) Uterine contraction in pregnancy.

(iv) Chronic use leads to intestinal mucosal damage.

Anthraquinone (Emodin Purgatives):

They are naturally occurring anthraquinone glycosides (plant origin) e.g., senna, Cascara sagrada and aloe.

Drastic purgatives:

They cause colic and super purgation. They are dangerous and not used therapeutically, e.g., Jalap, podophyllum, colocynth, coroton oil and barium chloride.

Neuromuscular Purgatives:

e.g., cholinergic agents with muscarinic action. They cause-

(i) Hyper-motility of GI tract.

(ii) Promote defecation

(iii) Urination

(iv) Peristaltic activity is increased.

e.g., Carbachol, Bethanechol, Physostigmine, Neostigmine etc.

Enema:

Introduction of solution into rectum is the simple method to correct constipation, e.g., soft anionic soap, mineral oil, olive oil. Enema preparations containing phosphate should not be used in cats because it can cause fatal hyperphosphatemia, hypocalcemia and hypernatremia.