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Drugs acting on the motility of gastro intestinal tract, Urinary system & reproductive system

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  1. 1. An Assignment On Drugs acting on the motility of GIT, Urinary system, & Reproductive system.Submitted to- Dr.H.B.Patel (assistant prof,of veterinary pharmacology & toxicology) Submitted by- Pavar Jayesh. P -Sem- 6th College of veterinary science & Animal husbandry. Sardar krushinagar Dantiwada Agricultural University. Sardar krushinagar-385506.
  2. 2. • The Drugs Acting on the motility of Gastro intestinal tract(GIT) are: - STOMACHICCS -ANTISTOMACHICS -ANTIDIARRHOEL DRUG -Rumenotonics -PROKINETICS -PURGATIVES (LAXATIVES)
  3. 3. Drugs which promote functional activity of stomach increasingsecretion & motility Use:- – Anorexia – Hyposhlorohydria – Ruminal atony – Achlorohydria E.g.1.Muscarinic agents: (Ach, Carbachol Bethanechol Pilocarpine Neostigmine Physostigmine ) 2.Histamine agonist(H2) Histamine,Betazole
  4. 4. 3.Dopamine antagonist: E.g. Metoclopramide (perinorm) MOA-Blocks inhibitory D2 receptor. Use- -To promote gastric emptying in pre-operative condition - Oesophageal spasm - Oesophageal obstruction4.Alkalin salts: -sodium bicarbonate - carbonate salt MOA-liberate CO2 which increases secretion & vasodilation in gastric mucosa.
  5. 5. 4.Bitters: -gentian -ginger -turpentine oilMOA-by irritation stimulation5.Cisapride, mosapride, neostigmine: -MOA-↑ GI motility, inhibit ACh degradation
  6. 6. ANTISTOMACHICS Also called as Gastric sedatives. Drugs which supress functional activity of stomach by decreasing secretion & gastric motility. Uses: - Hyperacidity -Diarrhoea -Ulcer E.g. 1. Antimuscarinic agents (e.g. atropine) 2. Adrenergic drugs (e.g. adrenaline) 3. Antispsmotic (e.g. morphine, codeine, pethidine) Morphine, nicotine→ Decreases motility →antidiarrhoeal agent 5.H2 blockers (e.g Renitidine, cimetidine) 6.Cholecystokinin. 7. Gastric inhibitory peptides.
  7. 7. ANTIDIARRHOEL DRUG Act against acute diarrhoea. Classification: a) GI/mucosal adsorbent or protectant: b) GI motility inhibitors/spasmolytic/antispasmotic c) Antiinfective agents/antimicrobial agents d) NSAIDs GI motility inhibitors/spasmolytic/antispasmotic: -Reduces motility of GIT. - Spasm is associated with diarrhoea - Spasm is increased/prolonged contraction of muscles.
  8. 8. • E.g. 1.Opium derivatives: (Morphine, Pethidine) MOA-Decrese bowel motility and relieve rectal spasm. 2.Atropine 3. Loperamide & diphenoxylate Contraindicated in cat & children below 2 years of age as it produces toxicity Dose: 0.08 mg/kg BW 4.Dicyclomine: -Act on ANS - β- Agonist in cattle, buffalo, horse, sheep, goat, cat, dog.
  9. 9. Rumenotonics Drugs which increases ruminal motility E.g. - Antimony potassium tartrate - Cobalt sulphate/cobalt chloride - Ferrous sulphate -Copper sulphate -Manganese sulphate - Zink sulphate Choline - chloride/thiamine monohydrate - Nicotinic acid - Dried yeast -Sodium acid phosphate reases ruminal motility.
  10. 10. PROKINETICS• Drugs which enhance the passage of intraluminal contents of the gastrointestinal tract.• Enhances Gastro intestinal motility.• Use: -Gastritis -IMpaction -Reflex oesophagitis.• Classification: - Dopamine antagonist. -5-HT Agonists. - Cholinomimetic agents.
  11. 11.  Dopamine antagonist: -E.g. Metoclopramide, Domperidone.  increase oesophageal peristalsis.  increase tone of cardiac sphincter (contraction)  decrease tone of pyloric sphincter (relaxation)  enhance gastric emptying but have no effect upon small intestine or colon motility. Dose Dog & cat: 0.2-0.5 mg/kg, P/O or S/C, TID 5-HT Agonists: (By increase release of Ach) E.g. Cisapride, Mosapride (5-HT2 & 5-HT4 Agonists)  ↑ the small and large intestine motility but have no effect upon oesophageal motility.
  12. 12.  Cholinomimetic agents: (by inhibition of AchE enzyme) E.g. Neostigmine, pyridostigmine. - Neostigmine can enhance gastric, small intestine, and colon emptying.
  13. 13. Purgatives• These are drugs, which cause evacuation of the bowel Purgatives also known Laxatives . MOA-They ↓ the viscosity of contents of Large intestine.• Ideal purgative should be: Effective. Devoid of systemic effect. Not be habit forming. Not cause after constipation.
  14. 14. • Use:-  To prevent straining while defecation in case of advance pregnancy Before gastrointestinal surgery.  Bowel preparation.  Chronic constipation.  Chronic immobility. Contraindication:  Should not given in advanced pregnancy. (causes abortion)  Should not given in obstruction in GIT. (causes rupture of intestine)  Should not given in lactating animals.(if given causes young one diarrhoea )
  15. 15. Classification of purgativesClassification:A. Bulk forming purgativesB. Osmotic/saline purgativesC. Irritant/stimulatory purgatives a) Anthraquinone derivatives/emodine purgatives b) Diphenylmethane (DPM) purgatives c) Lubricating/emollient purgativesD. Neuromuscular purgativesE. Drastic purgativesF. Faecal softeners/stool surfactant agents
  16. 16. A. Bulk forming purgatives: Bulk-forming laxatives are indigestible, hydrophilic colloids that absorb water, forming a bulky, emollient gel that distends the colon and promotes peristalsis. E.g. Methylcellulose Carboxy methylcellulose Psyllium/Isabgul Agar Acacia Polycarbophil (Synthetic fibers)B. Osmotic/saline purgatives:Magnesium sulfate, milk of magnesia (oxide & hydroxide) &magnesium citrate are commonly used as purgatives -Act within 1-2 hours. -Given early on empty stomach. -Poorly absorbed from GIT. -Absorb water & increase the bulk. -Mg sulfate (50% a single dose retention enema) is used to reduce ICP in neurosurgery.
  17. 17.  A/E: These agents may cause dehydration and magnesium poisoning in patients with renal impairment.Dose: -Cattle: 250-400 gm - foetal/calf: 25-50 gm -Horse: 50-100 gm -Dog: 5 gm - Cat: 2-5 gm - Sheep, goat, swine: 25-100 gm
  18. 18. C.Irritant/stimulatory purgatives: Act locally on the large bowel and stimulate evacuation of its contents.a) Anthraquinone derivatives/emodine purgatives: Glycosides derivatives of 1,8-dihydroxy anthraquinone.E.g. Natural emodines -Aloe (leaf powder of Aloe vera & Aloe chinensis) - Senna (leaflet of Casia acutifoia) -Cuscara - Sagarda -Rhubarb Synthetic emodines -Danthrone Dose of danthrone: Cattle: 20-40 gm, Horse: 15-45 gm ,Sheep: 2-5 gm
  19. 19. b) Diphenylmethane (DPM) purgatives: E.g. phenophtheline Bisacodyl bisacodyl is also used in human in the treatment of oedema.c) Lubricating/emollient purgatives: E.g. Vegetable oils (castor oil, linseed oil)MOA: Castor oil & linseed→ oil Digestion in small intestine→ Linolenic acid (fatty acid)→ Formation of irritant soap with bile (saponification)→ Irritation to intestine→Purgation. Uses: Used in large animals - In prolapse/advance pregnancy - In post-operative GIT surgery - In dog & cat, in anal leakage
  20. 20. D. Neuromuscular purgatives:E.g Carbachol -Horse & cattle: 2.5 mg/kg, S/C -Sheep: 0.25-0.50 mg/kg, S/C Physostigmine - Cattle: 30-45 ml/kg, S/C Neostigmine - Cattle: 0.-001-0.02 ml/kg, S/CE. Drastic purgatives:• Not used clinically Used for malafied intension E.g Croton oil Jatropha oil (in children) Barium chloride
  21. 21. F. Faecal softeners/stool surfactant agents: These agents soften faecal material, permitting water and lipids to penetrate. They may be administered orally or rectally.E.g. - docusate (oral or enema) - glycerin suppository - Mineral oil (liquid paraffin) (chronic use causes the deficiency of fat soluble Vitamins A, D, E, K) -Docusate→ increases fluid secretion & soften the intestinal ingesta -Mineral oil (liquid paraffin) → decreases water absorption from the feces Dose: Dog: 2 mg/kg Cat: 10-15 mg/kg
  22. 22. Drugs acting on the motility of reproductive system-Ecbolics-Oxytocics-Tocolytics 1.Ecbolics Drugs that stimulate the non-pregnant uterus motility These are used for the purpose of cleaning effect in the atonic uterus. E.g. oxytocics, prostaglandins, ergot alkaloids
  23. 23. Oxytocics• Drugs that induce rapid birth by stimulating the contraction of uterine muscles at term.• Classification: Oxytocics are of 3 types: 1) Natural oxytocics 2) Ergot alkaloids 3) Prostaglandins1) NATURAL OXYTOCICS: E.g. oxytocin Oxytocin is synthesized in supraotic & paraventricular nucleus in the posterior pituitary.
  24. 24.  Pharmacokinetics of oxytocin: Absorption ,Metabolism and Excretion• Not effective orally• Administered intravenously• Also as nasal spray• Not bound to plasma proteins• Catabolized by liver & kidneys• Half life = 5 minutes Onset of action: -I/V →1-2 minutes -I/M →5-10 minutes iv Duration of action: =I/V→ 3-5 minutes - I/M→ 60 minutes
  25. 25. • CLINICAL USES OF OXYTOCIN: - Uterine inertia -Speeding up expulsion of foetus unless foetal presentation & position is normal. -To facilitate the uterine involusion. -In case of retained placenta. -To facilitate letting down of milk
  26. 26.  Doses of oxytocin:i. When administered I/M -Cow & mare 10-40 IU -Ewe, doe & sow 2.5-10 IU -Bitch 01-10 IU -Queen 0.5-5.0 IUii. When administered I/V -Cow & mare 2.5-10 IU - Ewe & doe 0.5-2.5 IU -Bitch 0.5 IU
  27. 27. 2) ERGOT ALKALOIDS:• These are obtained from fungus Claviceps purpurea.• E.g. ergometrine, ergotamine• USES: -Uterine atony -Uterine inertia -Metrorrhagia: after abortion uterine discharge of blood & exudate -Post-partum haemorrhage control -After labour in association with caesarian section -Sub involution of uterus: means retain normal size & shape
  28. 28. ERGOT ALKALOIDS: ParmacokineticsAbsorption ,fate and excretion• Absorbed orally from GIT(tablets)• Usually given I.M• Extensively metabolized in liver.• 90% of metabolites are excreted in bile
  29. 29.  Ergot is itself not used because it produces spasmodic contraction. Methylergometrine is available as many trade names such as Methergin, oxymetrin, utergin, satergin etc. Dose of methylergometrine: -Cow & mare 10-20 mg -Sow 0.5-1.0 mg -Bitch 0.2-1.0 mg
  30. 30. PROSTAGLANDINS:E.g. PGE2 (Dinopristone) & PGF2α (Dinoprost)• Therapeutic uses 1. Induction of abortion (pathological) 2. Induction of labor (fetal death in utero) 3. Postpartum hemorrhage• Side Effects a)Nausea , vomiting b)Abdominal pain c)Diarrhea d)Bronchospasm (PGF2α) e)Flushing (PGE2)
  31. 31. • Contraindications: a)Mechanical obstruction of delivery b)Fetal distress c)Predisposition to uterine rupture
  32. 32. Tocolytics Drugs which suppress the premature labour by relaxation of uterine muscles are called as tocolytics. These are also called as anti-contraction or labour depressant or uterine relaxant or uterine sedatives or uterine spasmolytics.E.g.• i. MgSO4 It is muscle relaxant so inhibit the uterine contraction by inhibiting the myosin light chain• ii. Ethyl alcohol Inhibit the uterine motility
  33. 33. • iii. Ca+2 channel blockers E.g. nifedipine Produce the relaxation of myometrium It delays the parturion for 4-27 days• iv. β2–adrenoreceptor agonist E.g. retodrin, terbutaline• Uses of retodrin: -In premature labour/threaten abortion- to delay it -To reduce the foetal stress during transport of mother to hospital during preparation for operative delivery of foetus
  34. 34. Drugs acting on the motility Urinary system• Loop diuretics• α2 – agonistLoop diuretics:• Loop diuretics selectively inhibit NaCl reabsorption in the Thick Ascending Loop of Henle (TALH).• Increase renal prostaglandins, resulting in the dilation of blood vessels and reduced peripheral vascular resistance• E.g. Furosemide, Bumetanide, Torsemide, Pirelamide, Ethacrynic acid, Mazolamine
  35. 35. • PHARMACOLOGICAL EFFECTS OF FUROSEMIDE: -Decreases ECF -Decreases B.P -Produce dehydration -Produce Hypokalemic metabolic alkalosis -Produce hypocalcemia -Produce hypomagnesemia• MOA: They block the Na/K/2Cl transporter in TAHL. K & Cl symport is inhibited by by binding with chloride ion carrier. So no Na, K, Cl reabsorption hense there is loss of Na, K, Cl along with H2O. Also reduces Aldosterone secretion.
  36. 36. • PHARMACOKINETICS: -Oral bioavailability is excellent. -Extensive protein binding.• INDICATIONS: -Pulmonary oedema -Mammary oedema: occur during the large stage of pregnancy due constriction of mammary vein by foetus. -Brisket oedema -Hyperkalemia -Acute renal failure -Anion overdose: treating toxic ingestions of bromide, fluoride, and iodide.
  37. 37. • CONTRAINDICATION: - Hepatic cirrhosis -Borderline Renal failure - Heart failureMisuse: Furosemide is used in dopping in horses during horse shows because it reduces ECF so clear cut demarcation of muscles is there
  38. 38.  α2 Agonist: E.g.- Clonidine -Xylazine -Guanafacine -Guanabenz -Detomidine -Remifidine