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GI drugs - Coggle Diagram

- - - - sends signal to vomiting center
  - - - grass
      - scavenging
      - motion sickness
      - parvoviral gastroenteritis
      - some toxicants
    - - grass
      - hair balls
      - motion sickness
      - thyroid, liver, or kidney disease
- - - - Symptomatic patients
        
        impaired behavioral/neural status, impaired gag reflex, already vomiting, or showing toxicosis since toxin was already absorbed
      - Pre-existing conditions
        
        risk for aspiration pneumonia, recent abdominal sx/sutures, unstable/debilitated patients, species can't vomit
      - nature of ingested material
        
        you cannot induce vomiting with caustic/burning, low viscosity (aspiration risk) or FBO in lower esophageal tract
    - - for Decontamination in early stages of poisoning only (i.e. before gastric emptying)
        
        Limited to Small Animal use only
  - - - Locally acting
        
        Administered orally
        
        iritate or distend the gut
        
        stimulate gastric afferents to the brain vomiting center
        
        the drugs
        
        Dogs
        
        Hydrogen Peroxide
        
        oral
        
        0.03% formulation given with small amount of food
        
        mucosal irritant
        
        Cats
        
        none
        
        SYRUP OF IPECAC?
        
        Not used anymore due to
        
        slow action (15-30minute onset)
        
        alkaloid emetine
        
        gastric irritant
      - Centrally acting
        
        the drugs
        
        Cats
        
        Hydromorphone
        
        opioid receptor agonist (CNS)
        
        less sedative and bradycardic effects but...
        
        1 more item...
        
        IM or IV
        
        Xylazine and Dexmedetomidine (not used together but they have similar rates of success and MOA)
        
        Alpha2-adrenergic agonist (CNS)
        
        IM or IV
        
        blocked by A2 antagonists such as ATIPAMEZOLE
        
        side effects
        
        A2 agonists:
        
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        Dogs
        
        Tranexamic acid
        
        neurokinin pathways (DIRECTLY ACTS ON CNS)
        
        IV bolus
        
        drug interactions
        
        Inhibited by neurokinin antagonists MAROPITANT (CERENIA)
        
        Side effects
        
        RARE BUT...
        
        1 more item...
        
        Apomorphine
        
        dopamine D2 agonist (CNS)
        
        DRUG INTERACTIONS
        
        2 more items...
        
        Eye drop
        
        induces vomiting w/in 2-10 minutes
        
        Side effects
        
        sedation
        
        powerful emetic
        
        Act on the CNS usually stimulating Alpha2 or Dopamine receptors
- - - - DO NOT USE TO COVER UP PRIMARY DISEASE
      - Reducing gastric irritation or distention
        or
        interrupt peripheral sensory input to vomiting center
        
        helps manage
        
        electrolyte imbalances (metabolic alkalosis)
        
        malnutrition
        
        dehydration
      - Indications
        
        motion sickness from vestibular input
        
        uremia, liver dz, endotoxemia, and other systemic dz states
        
        that have blood-borne chemicals producing emesis
        
        GASTROINTESTINAL IRRITATION, DISTENION AND REDUCE MOTILITY
        
        FROM TOXINS OR GI INJURY/DZ
    - - non-monogastrics
  - - - Peripheral sites of action (gastric)
        
        Coating agents
        
        kaolin-pectin, dismuth subsalicate
        
        frequent oral dosing necessary
        
        Gastric Prokinetic agents
        
        Metoclopramide, Cisapride
        
        serotonin receptors stimulate upper gi motlity and prevent relaxation of the stomach and LES (needed for vomiting)
        
        H2 Histamine antagonists
        
        famotidine, pepcid
        
        reduces gastic acid output
      - Centrally acting
        
        Chemoreceptor trigger zone (CTZ)
        
        Neurokinin receptors,5-HT3, DA2, AR 2,
        
        Dopamine receptor antagonist drugs
        
        Chlorpromazine/Acepromazine (-azine drugs); Metoclopramide (low dose)
        
        effective in inhibiting vomiting evoked by drugs and toxicants or associated with metabolic diseases
        
        SIDE EFFECTS: SEDATION AND HYPOTENSION IN SMALL ANIMALS
        
        Serotonin (5-HT3) antagonist drugs
        
        Dolazetron;ondansetron, Metoclopramide (high dose)
        
        Extra label use, for SEVERE FREQUENT VOMITING in DOGS AND CATS
        
        Cancer chemotherapy
        
        paroviral infections
        
        pancreatitis
        
        indicated when other antiemetics have failed
        
        less effective for
        
        2 more items...
        
        not used in puppies: causes bone marrow depression
        
        Metoclopramide
        
        HIGH DOSE
        
        BLOCKS SEROTONIN RECEPTORS IN VAGAL AFFERENTS AND CTZ
        
        LOW DOSE
        
        CROSS BBB AND BLOCKS DOPAMINE RECEPTORS
        
        MORE EFFECTIVE IN DOGS THAN CATS
        
        Use for puppies first!
        
        1 more item...
        
        Neurokinin antagonist
        
        Maropitant (Crenia)
        
        look below
        
        Emetic center (medulla)
        
        Neurokinin receptors (NK1), mACH, H1
        
        Neurokinin antagonist drug
        
        Maropitant (Crenia)
        
        prototypic drug
        
        approved for dogs >16 weeks, effective in cats
        
        Oral and SC; SID
        
        blocks neurokinin (substance P) receptors in CTZ and vomiting center
        
        hepatic clearance
        
        Do not use in dogs with liver dysfunction
        
        Neurokinin receptors are the most effective
    - - mACh receptor drugs
        
        Scopolamine
        
        Crosses BBB and affects emetic center on peripheral vagal nerves
        
        IM OR SC to cats/dogs; for 6 hrs of action
        
        might have side effects
      - H1 - histamine receptor drugs
        
        Histamine in general affects vomiting in two areas (but we are focusing on H1 receptors for motion sickness)
        
        CNS H1
        
        increases Ca+ in vestibular system and vomiting center = motion sickness
        
        Antagonists block receptors to these pathways
        
        diphenhydramine, dimenhydrinate, meclizine (bonine)
        
        3 more items...
        
        Peripheral H2 receptors
        
        increase cAMP in parietal cells = increased gastric acid production
- - - - stimulate or inhibit other types of molecular "targets" to increase contractility (motility)
        
        Lidocain
        
        multiple mechanisms?
        
        Misoprostil
        
        prostaglandin E receptors in colon
        
        Motilides
        
        agonists action of smooth muscle motilin recptors
        
        Novel drugs
        
        increase Myocyte [cGMP]; increase Cl- channel activity
      - Decrease myorelaxation produced by inhibitory mediators
        
        Metoclopramide (DA antagonist)
        
        Peripheral opioid antagonists
      - Increase Cholinergic tone (Motility) in smooth muscle increasing contractions
        
        Serotonin agonists (like benzamides)
        
        Motilides
        
        stimulate neural motilin receptors linked to ACh release
        
        Cholinomimetic drugs (last resort)
    - - GI obstructions
      - post-surgical anastomoses
    - - Esophagus
        
        Achalasia, Gastro-esophageal reflux (dilated lower esophageal sphincter)
      - Stomach
        
        delyaed gastric mixing and emptying (gastroparesis)
      - intestinal tract
        
        Chronic constipation, post operative ileus (POI)
      - REDUCE VOMITING
        
        by stimulating gastric motility and preventing relaxtation of stomach and LES
        
        METOCLOPRAMIDE stimulates ACTH release and blocks DA receptors in the GI tract
    - - Inhibited by Dopamine and opioids; increased with ACh receptors (increased contractions) and Serotonin receptors; Benzamides
      - Benzamides
        
        increase oral (promixmal) muscle contraction [cisapride] and relax aboral (distal) muscles [metoclopramide
  - - - Macrolides antibiotics "Motilides"
        
        agonist at motilin receptors on cholinergic nerves and GI smooth muscle
        
        Erythromycin
        
        AT LOSE DOSES it has prokinetic effects
        
        Motility of STOMACH AND UPPER SMALL INTESTINE
        NO EFFECT ON COLON
        
        prokinetic actions unrelated to antimicrobial activity
        
        clarithomycin and azithromycin also have prokinetic effects
        
        Safe in most species
        
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        Indications
        
        Small intestine
        
        Esophagus and stomach/rumen
      - H2 Histamine antagonists?
        
        indications
        
        Esophagus and stomach/rumen
      - Benzamides
        
        Indications
        
        Esophagus and stomach/rumen
        
        Colon
        
        Small intestine
    - - blocks Na channels in enteric nerves to "reset" intestinal motility
        
        IV to horses with
        
        ileus or Upper small intestinal inflammation
    - - Serotonin receptor agonists
        
        Prucalopride
        
        initates peristalsis in COLON
        
        not approved in the US
      - cGMP-elevating and Cl- channel activing drugs
        
        linaclotide and Lubiprostone
        
        speed up intestinal transit
- - - - theraputic goal: raise pH to >/= 3 to promote healing
  - - - Maalox and Mylanta
      - Rapid onset!
      - Short duration: 20-30 minutes
      - Often renal clearance
    - - Proton Pump inhibitors
      - H2- HIstamine Antagonists