Pharmacology powerpoint git drugs


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Pharmacology powerpoint git drugs

  1. 1. Pharmacology of the GITPharmacology of the GIT systemsystem
  2. 2. LECTURE OutlineLECTURE Outline • REVIEW the Anatomy of the GIT • REVIEW the physiology of the GIT • Review common GI drugs in the following categories: – 1. Drugs affecting GI secretions – 2. Laxatives – 3. Anti-diarrheals – 4. Emetics and anti-emetics
  3. 3. Drugs affecting GI secretionsDrugs affecting GI secretions There are five types of drugs that affect gastric acid secretions and are useful for the treatment of peptic ulcer. 1. Histamine (H2) receptor antagonist/blockers 2. Antacids 3. Proton pump inhibitors 4. Mucosal protectants 5. Prostaglandin analogs
  4. 4. Drugs affecting GI secretionsDrugs affecting GI secretions Histamine (H2) receptor blockers • These drugs BLOCK the release of hydrochloric acid in the stomach in response to gastrin • Preventing histamine fromPreventing histamine from binding to its receptor inbinding to its receptor in parietal cells.parietal cells.
  5. 5. Drugs affecting GI secretionsDrugs affecting GI secretions Antacids • These drugs interact with the gastric acids at the chemical level to neutralize them
  6. 6. Drugs affecting GI secretionsDrugs affecting GI secretions Proton pump inhibitors • These drugs suppress the secretion of hydrochloric acid into the lumen of the stomach • Stimulation of proteinStimulation of protein kinases that phosphorylatekinases that phosphorylate H*/K* ATPase.H*/K* ATPase.
  7. 7. Drugs affecting GI secretionsDrugs affecting GI secretions Mucosal protectants • These are agents that coat any injured area in the stomach to prevent further injury from acid
  8. 8. Drugs affecting GI secretionsDrugs affecting GI secretions Prostaglandin analogs • These are agents that inhibit the secretion of gastrin and increase the secretion of mucus lining of the stomach, providing a buffer. • Activate inhibitory proteinsActivate inhibitory proteins that block histaminethat block histamine activation of adenylateactivation of adenylate cyclasecyclase
  9. 9. The H2 Blockers- “tidines”The H2 Blockers- “tidines” Prototype: Cimetidine • 1. Ranitidine • 2. Famotidine • 3. Nizatidine
  10. 10. The H2 Blockers- “tidines”The H2 Blockers- “tidines” Pharmacodynamics: Drug Action • The H2 blockers are antagonists at the receptors in the parietal cells of the stomach. • The blockage results to inhibition of the hormone gastrin. • There will be decreased production of gastric acid from the parietal cells. • Also, the chief cells will secrete less pepsinogen.
  11. 11. The H2 Blockers- “tidines”The H2 Blockers- “tidines” Therapeutic use of the H2 blockers • Short-term treatment of active duodenal ulcer or benign gastric ulcer • Treatment of hypersecretory conditions like the Zollinger-Ellison syndrome • Prevention of stress-induced ulcers and acute GI bleeding • Treatment of erosive GERD (reflux disease) • Relief of Symptoms of heart burn and acid indigestion
  12. 12. The H2 Blockers- “tidines”The H2 Blockers- “tidines” Precautions and Contraindications • Any known allergy is a clear contraindication to the use of the agents. Conditions such as pregnancy, lactation, renal dysfunction and hepatic dysfunction should warrant cautious use. • Nizatidine can be used in hepatic dysfunction.
  13. 13. The H2 Blockers- “tidines”The H2 Blockers- “tidines” Pharmocodynamics- Side effects and adverse effects • GIT= diarrhea or constipation • CNS= Dizziness, headache, drowsiness, confusion and hallucinations • Cardio= arrhythmias, HYPOTENSION (related to H2 receptor blockage in the heart) • Cimetidine= Gynecomastia and impotence in males
  14. 14. The H2 Blockers- “tidines”The H2 Blockers- “tidines” Drug-drug Interactions • Cimetidine, Famotidine, Ranitidine are metabolized in the liver- they can cause slowing of excretion of other drugs leading to their increased concentration. These drugs can be anticoagulants, phenytoin, alcohol, antidepressants.
  15. 15. The AntacidsThe Antacids • These are drugs or inorganic chemicals that have been used for years to neutralize acid in the stomach. The following are the common antacids that can be bought OTC: • Aluminum salts (hydroxide) • Calcium salts (carbonate) • Magnesium salts (milk of magnesia) • Sodium bicarbonate • Magaldrate (aluminum and magnesium combination)
  16. 16. 2 types2 types •Systemic • NaHCO3, Na citrate • alkalosis
  17. 17. • Non – systemic • ALOH3 – adsorbs pepsin and removes it from solution at Ph > 3 • Relaxes stomach,delays GET • Stimulates secretion of mucus enhancing mucosal barrier to acid
  18. 18. • MgOH - diarrhea • CaCO3 – rebound acidosis
  19. 19. The AntacidsThe Antacids Pharmacodynamics: drug action • These agents act to neutralize the acidic pH in the stomach. • They do not affect the rate of gastric acid secretion.
  20. 20. The AntacidsThe Antacids Pharmacodynamics: drug action • The administration of antacid may cause an acid rebound. • Neutralizing the stomach content to an alkaline level stimulates gastrin production to cause an increase in acid production and return the stomach to its normal acidic state.
  21. 21. The AntacidsThe Antacids Therapeutic Indications • Symptomatic relief of upset stomach associated with hyperacidity • Hyperacidic conditions like peptic ulcer, gastritis, esophagitis and hiatal hernia
  22. 22. The AntacidsThe Antacids Precautions of Antacid Use • Known allergy is a clear contraindication. Caution should be instituted if used in electrolyte imbalances, GI obstruction and renal dysfunction.
  23. 23. Antacids are combined toAntacids are combined to • I.I. Antagonize the side effect ofAntagonize the side effect of the other componentthe other component II.II. Obtain a product with aObtain a product with a rapid onset and sustained actionrapid onset and sustained action III.III. Lower the dose of eachLower the dose of each componentcomponent
  24. 24. • Slow onset,long duration – ALOH • Fast onset,short duration – MgOH,Na bicarb • Fast onset, LONG duration – CaCO3
  25. 25. The AntacidsThe Antacids Pharmacokinetics • These agents are taken orally and act locally in the stomach
  26. 26. The AntacidsThe Antacids Pharmacodynamics: Effects of drugs 1. GIT= rebound acidity; alkalosis may occur. • Calcium salts may lead to hypercalcemia and milk-alkali syndrome. • Magnesium salts can cause DIARRHEA • Aluminum salts may cause CONSTIPATION and hypophosphatemia by binding with phosphates in the GIT. 2. Fluid retention due to the high sodium content of the antacids.
  27. 27. The PPIThe PPI These are the newer agents for ulcer treatment • The “prazoles” Prototype: Omeprazole • Lanisoprazole • Esomeprazole • Pantoprazole
  28. 28. The PPIThe PPI Pharmacodynamics: drug action • They act at specific secretory surface receptors to prevent the final step of acid production and thus decrease the level of acid in the stomach. • The “pump” in the parietal cell is the H-K ATPase enzyme system on the secretory surface of the gastric parietal cells
  29. 29. 3 therapy3 therapy • Omeprazole +chlarithromycin+amoxicillin /metronidazole
  30. 30. The PPIThe PPI Clinical use of the PPIs • Short-term treatment of active duodenal ulcers, GERD, erosive esophagitis and benign gastric ulcer. • Long-term- maintenance therapy for healing of erosive disorders. Precautions with the use of the PPIs • Known allergy is a clear contraindication. Caution if patient is pregnant
  31. 31. The PPIThe PPI Pharmacodynamics: Adverse effects • CNS- dizziness, headache, asthenia (loss of strength), vertigo, insomnia, apathy • GIT- diarrhea, abdominal pain, nausea, vomiting, dry mouth and tongue atrophy • Respi- cough, stuffy nose, hoarseness and epistaxis.
  32. 32. The Mucosal ProtectantThe Mucosal Protectant Sucralfate • This is given to protect the eroded ulcer sites in the GIT from further damage by acid and digestive enzymes
  33. 33. SucralfateSucralfate Pharmacodynamics: Action of drug • It forms an ulcer-adherent complex at duodenal ulcer sites, protecting the sites against acid, pepsin and bile. • This action prevents further breakdown of proteins in the area and promotes healing.
  34. 34. SucralfateSucralfate Clinical use of sucralfate • Short and long term management of duodenal ulcer. • NSAIDs induced gastritis • Prevention of stress ulcer • Treatment of oral and esophageal ulcers due to radiation, chemotherapy or sclerotherapy.
  35. 35. SucralfateSucralfate Precautions on the use of Sucralfate • This agent should NOT be given to any person with known allergy to the drug, and to those patients with renal failure/dialysis because of build-up of aluminum may occur if used with aluminum containing products.
  36. 36. The Mucosal ProtectantThe Mucosal Protectant Pharmacodynamics: Side-effects & adverse reactions • Primarily GIT= CONSTIPATION, occasionally diarrhea, nausea, indigestion, gastric discomfort, and dry mouth may also occur • CNS= dizziness, drowsiness, vertigo • Others= rash and back pain
  37. 37. The Mucosal ProtectantThe Mucosal Protectant Drug-drug interactions • If used with aluminum salts= high risk of accumulation of aluminum and toxicity. • If used with phenytoin, fluoroquinolones and penicillamines- decreased levels of these drugs when taken with sucralfate
  38. 38. Prostaglandin analogueProstaglandin analogue Misoprostol • This agent is a synthetic prostaglandin E1 analog that is employed to protect the lining of the mucosa of the stomach
  39. 39. Prostaglandin analogueProstaglandin analogue Misoprostol: Pharmacodynamics • Being a prostaglandin analog, it inhibits gastric acid secretion to some degree • It INCREASES mucus production in the stomach lining.
  40. 40. Prostaglandin analogueProstaglandin analogue Misoprostol: Clinical use • NSAIDs-induced gastric ulcers • Duodenal ulcers unresponsive to H2 antagonists.
  41. 41. Prostaglandin analogueProstaglandin analogue Precautions of Misoprostol Use • This drug is CONTRAINDICATED during pregnancy because it is an abortifacient. • Women should be advised to have a negative pregnancy test within 2 weeks of beginning therapy and should begin the drug on the second or third day of the next menstrual cycle. • They should be instructed in the use of contraceptives during therapy.
  42. 42. Therapeutic Indications of theTherapeutic Indications of the LaxativesLaxatives • SHORT term relief of Constipation • Prevention of straining in conditions like CHF, post-MI, post partum, post-op • Preparation for diagnostic examination • Removal of poison or toxins • Adjunct in anti-helminthic therapy
  43. 43. Contraindications in Laxative useContraindications in Laxative use • ACUTE abdominal disorders – Appendicitis – Diverticulitis – Ulcerative colitis
  44. 44. Pharmacokinetics:Pharmacokinetics: Common Side-effects of the LaxativesCommon Side-effects of the Laxatives • Diarrhea • Abdominal cramping • Nausea • Fluid and electrolyte imbalance • Sympathetic reactions- sweating, palpitations, flushing and fainting • CATHARTIC dependence
  45. 45. LaxativesLaxatives • Generally used to INCREASE the passage of the colonic contents • The general classifications is as follows: 1. dietary fibers/Bulk formers 2. Mechanical /stimulant 3. Lubricants/emolient 4. Osmotic and saline laxatives
  46. 46. Bulk-forming LaxativesBulk-forming Laxatives • - fiber (fruits, vegetables, cereals), bran, methyl cellulose, psyllium • - increases stool bulk causing peristalsis • Increase bacteria
  47. 47. Osmotic LaxativesOsmotic Laxatives • saccharides: lactulose, sorbitol
  48. 48. Stool Softeners/EmollientStool Softeners/Emollient LaxativesLaxatives • - docusate • - surfactant which facilitates mixing of water and oily materials • - used to prevent constipation • (post-MI, rectal surgery etc)
  49. 49. Stimulant LaxativesStimulant Laxatives • - stimulates mucosal nerves in the colon • diphenylmethane derivatives:bisacodyl, phenolphthalein • anthraquinone derivatives: cascara sagrada, sennosides, casanthrol • castor oil- active: ricinoleic acid • S/E: dependence on laxatives; daily use is discouraged
  50. 50. Lubricant laxativesLubricant laxatives • Ex. Mineral oil • Interferes with H2O and fat absorption
  51. 51. The Anti-diarrhealsThe Anti-diarrheals • These are agents used to calm the irritation of the GIT for the symptomatic relief of diarrhea • General Classifications
  52. 52. Clinical Indications of drug useClinical Indications of drug use • Relief of symptoms of acute and chronic diarrhea • Reduction of fecal volume discharges from ileostomies • Prevention and treatment of traveler's diarrhea
  53. 53. Contraindications of anti-diarrhealContraindications of anti-diarrheal UseUse • Poisoning • Drug allergy • GI obstruction • Acute abdominal conditions
  54. 54. Pharmacokinetics: Side effectsPharmacokinetics: Side effects • Constipation • Nausea, vomiting • Abdominal distention and discomfort • TOXIC MEGACOLON
  55. 55. Oral Rehydration Salts/ Oral Glucose-Oral Rehydration Salts/ Oral Glucose- Electrolyte Solution (Oresol)Electrolyte Solution (Oresol) • prevents dehydration • - contains sodium, chloride, potassium, glucose and citrate (245 mOsm/L)
  56. 56. AdsorbentsAdsorbents • kaolin-pectin mixture, polycarbophil, attapulgite • Traditional remedies
  57. 57. Antimotility agents/Opiods • - opiods: diphenoxylate (+ atropine), loperamide, paregoric, opium tincture, difenoxin (metabolite of diphenoxylate) • Inc GIT contraction but non propulsive and they close the sphincter
  58. 58. Antisecretory/ Astringents • a. bismuth subsalicylate- treatment and prevention of traveler’s diarrhea • Local anti- inflammatory effect of salicylate • Antibacterial effect of bismuth
  59. 59. The Anti-diarrhealsThe Anti-diarrheals Type Prototype Action Local reflex inhibitor Bismuth subsalicylate Locally coats the lining of the GIT to soothe irritation that may stimulate the reflex Local anti- motility Loperamide Directly inhibits the intestinal muscle activity to SLOW peristalsis Central acting agent Opium derivatives (paregoric) Stops GIT spasm by CNS action
  60. 60. Emetics and Anti-emeticsEmetics and Anti-emetics Emetic Agent • Ipecac Anti-emetics • 1. Phenothiazines • 2. Non-phenothiazines • 3. Anticholinergics/Antihistamines • 4. Serotonin receptor Blockers • 5. Miscellaneous
  61. 61. EMETICEMETIC • Prototype: Ipecac Syrup
  62. 62. EMETICEMETIC Pharmacodynamics • Ipecac syrup irritates the GI mucosa locally, resulting to stimulation of the vomiting center • It acts within 20 minutes
  63. 63. EMETICEMETIC Clinical Use of ipecac • To induce vomiting as a treatment for drug overdose and certain poisonings
  64. 64. EMETICEMETIC Contraindications of Ipecac use • Ingestion of CORROSIVE chemicals • Ingestion of petroleum products • Unconscious and convulsing patient
  65. 65. EMETICEMETIC Pharmacokinetics: side effects of Ipecac • Nausea • Diarrhea • GI upset • Mild CNS depression • CARDIOTOXICITY if large amounts are absorbed in the body
  66. 66. ANTI-EMETICSANTI-EMETICS • These are agents used to manage nausea and vomiting • They act either locally or centrally
  67. 67. ANTIEMETICSANTIEMETICS Anti-emetic types Common examples Phenothiazines Prochlorperazine, promethazine Non-phenothiazines Metoclopramide Anticholinergics and Antihistaminics Meclizine, buclizine Serotonin Receptor blockers “setron”- dolasetron Miscellaneous Dronabinol, hydroxyzine
  68. 68. ANTIEMETICSANTIEMETICS Types Pharmacodynamics Phenothiazines Centrally block the vomiting center in the medulla Non-phenothiazine Reduces the responsiveness of the nerve cell in the medulla Anticholinergics Block the transmission of the impulses to the medulla Serotonin receptor blockers Centrally and locally inhibits the serotonin receptors Miscellaneous Act in the CNS , either in the medulla or in the cortex
  69. 69. ANTIEMETICSANTIEMETICS Types Clinical Use Phenothiazines N/V associated with anesthesia, intractable hiccups Non-phenothiazine N/V associated with chemical stimulation Anticholinergics N/V associated with motion sickness Serotonin-receptor Blockers N/V associated with chemotherapy Miscellaneous N/V associated with chemotherapy
  70. 70. ANTIEMETICSANTIEMETICS Contraindications • 1. Severe CNS depression • 2. Severe liver dysfunction
  71. 71. ANTIEMETICSANTIEMETICS Pharmacokinetics: Side-effects 1. PHOTHOSENSITIVITY 2. Drowsiness, dizziness, weakness and tremors and DEHYDRATON 3. Phenothiazines= autonomic effects like dry mouth, nasal congestion and urinary retention
  72. 72. An example of a weakly basic prodrug thatAn example of a weakly basic prodrug that when protonated,form covalent disulfidewhen protonated,form covalent disulfide linkages with H+/K+ ATPase and inactivateslinkages with H+/K+ ATPase and inactivates • A. maalox • B. nexium • C. tagamet • D. buscopan
  73. 73. Anti – ulcerant drugs exert their effortAnti – ulcerant drugs exert their effort through which of the ff mechanismsthrough which of the ff mechanisms • I. stimulation of protein kinases that phosphorylates H/K ATPase • II. Prevent the histamine from binding to its receptor in parietal cells • III. Activate inhibitory proteins that block histamine activation of adenylate cyclase • A. I only C. I and II • B. II only D. II and III only • E. I , II, III
  74. 74. Which of the H2 receptor blocker has almostWhich of the H2 receptor blocker has almost complete oral bioavailabiltycomplete oral bioavailabilty • A. nizatidine • B. famotidine • C. ranitidine • D. cimetidine
  75. 75. Evaluate the ff regarding emeticsEvaluate the ff regarding emetics • I. they induce vomiting • II. They cause vomiting reflex by irritating the upper GI tract • A. I only • B. II only • C. both • D. none
  76. 76. Evaluate the ff statements regardingEvaluate the ff statements regarding laxativeslaxatives • I. they accelerate fecal passage in the colon • II. They increase fecal consistency • A. I only • B. II only • C. both • D. none
  77. 77. Different antacids are combined in oneDifferent antacids are combined in one preparation topreparation to • I. antagonize the side effect of one component • II. Obtain a product with rapid onset and sustained action • III. Lower the dose of each component A. I only C. I and II • B. II only D. II and III only • E. I , II, III
  78. 78. Antacids prevent the formation of thisAntacids prevent the formation of this proteolytic enzyme that is thought toproteolytic enzyme that is thought to mediate tissue injury in gastric ulcerationmediate tissue injury in gastric ulceration • A. pepsin • B. pepsinogen • C. chymotrypsin • D. chymotrypsinogen
  79. 79. Gastric acid by parietal cells is/are regulatedGastric acid by parietal cells is/are regulated byby • I. neurocrine cells • II. Paracrine cells III. Endocrine cells A. I only C. I and II • B. II only D. II and III only • E. I , II, III
  80. 80. This acts as the most common mediator andThis acts as the most common mediator and the most potent stimulus of gastric acidthe most potent stimulus of gastric acid secretionsecretion • A. acetylcholine • B. Histamine • C. gastrin • D. none
  81. 81. Prostaglandin analogs increases gastricProstaglandin analogs increases gastric mucosal resistance to injury bymucosal resistance to injury by • I. increasing mucus secretion • II. Increasing bicarbonate secretion • III. Increasing gastric emptying time A. I only C. I and II • B. II only D. II and III only • E. I , II, III