Docstoc

Lecture 1 Introduction to Pharmacology - PowerPoint

Document Sample
Lecture 1 Introduction to Pharmacology - PowerPoint Powered By Docstoc
					 Drugs Affecting the
Gastointestinal System


   Pharmacology 49.222
   Dr. Bill Diehl-Jones, RN
      Faculty of Nursing
                    Agenda
• Zen Review
• Drugs used to treat the following disorders
  –   Peptic ulcer
  –   Motility dysfunction
  –   Diarrhea
  –   Constipation
  –   Lactose intolerance
                      GI Drugs
• Drugs for:
  – Peptic ulcers
  – Emesis
  – Motility Disorders
     • Diarrhea
     • constipation
                             Overview of
                             GI Processes

             Food


                        Digestion


Secretion
                       Absorption   Motility


       Blood Vessels
                 Peptic Ulcer Drugs
• The Problems
   – Infection with H. pylori
   – Increased acid secretion
   – Inadequate mucosal defense
• Solutions:
   –   Antimicrobials (amoxicillin)
   –   H2- histamine blockers (Ranitidine)
   –   Prostaglandins (Misoprostol)
   –   Proton pump inhibtors (Omeprazole)
                Anti-Ulcer Agents
              Omeprazole                H+
                                    -
                                                                   -
                                        K+
PARIETAL CELL
  In stomach                                                   Amoxicillin
                                            +
                               Protein Kinase
                          Ca++
                                           +
                                        cAMP
              Ach-R
Pirenzipine     -                       +   AC -
                                                   PG-R
                      Histamine-R
                                    -
               Ranitidine                                 +   Misoprostol
                   Anti-Emesis Drugs
• Why do we vomit?!

• “Vomit” Centers
     • Chemoreceptor trigger zone
         – Takes chemical stimuli
     • Lateral reticular formation
         – Takes vestibular input
         – Controls motor mechanisms
       Flavours of Anti-Emetics
• Phenothiazines (eg: prochlorperazine)
       • Dopamine blocker
•   Benzodiazepines (eg: ?)
•   5-HT blockers (eg: ondansetron)
•   Corticosteroids eg: (dexamethasone)
•   Peppermint oil (yes, peppermint oil)
Anitdiarrheals and Laxatives
  Diarrhea - Three Mechanisms
• Osmotic
  – osmoticant in intestine   H2O

• Secretory
  – excessive mucosal secretion
  – toxins, some tumours
• Motility
  – surgical
           Lactase Deficiency…
           One Cause of Diarrhea
                                    Enzymes
• Deficiency of lactase
  at brush border
• Increased lactose
  provides carbon for
  bacteria
• Presents as bloating,
  crampy pain, osmotic
  diarrhea                Microvillus
           Anti-Diarrheals
• What causes diarrhea?
      So, how do antimotility agents work?
                   First, we need to know about gut motility …



• Two types of movement:
   – Peristaltic
      • moves food forward


   – Segmental
      • Mixing
• Controlled by parasympathetics
     Effect of Parasympathetic Activity
           on Gut Smooth Muscle
• Certain cells generate
  slow wave pacemaker
  potentials               mV


• This is increased by
  ACh                      Force


                                   TIME
Ach controls both motility and secretion …
                             STIMULUS




      STIMULUS                            Vagus


      Short Reflex
                             ACh
                                        Long Reflex
                       ACh
           Secretion
                  Antidiarrheals
• Antimotility Agents
   – Diphenoxylate, loperamide
      • Both are meperidine derivatives
      • Activate presynaptic opioid receptors, inhibit Ach release (see
        next slide)
• Adsorbents
   – Kaolin, pectin
• Agents that modify fluid/electrolyte transport
   – NSAIDS
   – Bismuth subsalicylate (Pepto Bismol)
   Prostaglandins and Bismuth Inhibit
   Secretion of Water and Electrolytes

                     Enterocyte
              Na+                        L
             H2O
                    Na+           Cl-    U
  PG‟s              Cl-
                    K+                   M
             -
             Na+
                    K+            K+
                                         E
Salicylate
                                         N
                     Enterocyte
                Constipation
• Many Causes
  – Neurogenic
     • eg: Hirschsprung‟s
  – Muscle weakness
     • eg: post-surgery
  – Low-residue diets
  Laxatives We Know and Love
• A. Irritants and Stimulants
  – Castor oil, aloe, phenophthalein
     • Castor oil broken down into ricinoleic acid
• B. Bulking Agents                           H20
  – Psyllium, bran, magnesium
• Stool softeners
  – Ducosate, mineral oil, glycerin
                Clinical Gems
• Aspirin and GI bleed
  – Aspirin is an ACID (acetylsalicylic acid, remember?)
  – Over-use, or use by pts. with peptic ulcer
    contraindicated (why?)
  – Enteric-coated aspirin (Entrophen®) or other
    analgesics may be used
  – Why is Ibuprofen also contra-indicated in patients
    with GI bleed??
                 Clinical Gems
• Laxatives and pediatric patients
  – MoM, other oral laxatives to be used as a last resort
  – Rationale: this can cause F/E imbalances
• Alternatives to laxatives:
  – More fibre in diet (examples?)
  – Increase hydration
  – Abdominal massage
                    Clinical Gems
• Antidiarrheals and pediatric patients
  – Usually considered to be contra-indicated
  – They may cause retention of the causative agent
     • Eg: a bacterium or parasite
        – Clostridium difficile
               Clinical Gems
• Over-use of laxatives
  – Long-term use may cause dependence or „lazy
    bowel‟
• What non-pharmacological alternatives can you
  think of?

				
DOCUMENT INFO