pg 93 122 Gastrointestinal Drugs Dr Dipa Brahmbhatt VMD MpH MS dbrahmbhyahoocom OBJECTIVES Basic physiology that controls the GI tract Mechanism of emesis and antiemetics ID: 581378
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Chapter 4 - 2 pg 93 - 122Gastrointestinal Drugs
Dr. Dipa Brahmbhatt VMD MpH, MSdbrahmbh@yahoo.comSlide2
OBJECTIVESBasic physiology that controls the GI tractMechanism of emesis and antiemeticsGI motility and drugs that affect these
Mechanism of GI ulcers and anti-ulcer drugsDrugs modification in the ruminant GI tractSlide3
AntiemeticsVomiting has many causes including:Viral and bacterial infections, dietary indiscretion, food intolerance, surgery, pain, GI disease, kidney/liver failure, metabolic conditions (
hypoadrenocorticism), CNS disorders or other drugsThe vomiting center of the brain have many inputs that tell it to activate including:Equilibrium changes in the ear, responses due to pain or fear, intracranial pressure changes, vagus nerve stimulation in the GI tract, and activity in the chemoreceptor trigger zoneSlide4
Antiemetics AntiemeticsDrugs that control vomiting that help alleviate discomfort and help control electrolyte balance
Most are given parenterally, as the patient may vomit the medication before it can be absorbed through the GI tractExamples:Phenothiazine derivatives: Acepromazine, Chlorpromazine, Prochlorperazine (Compazine)Antihistamines: Dimenhydrinate (Dramamine), Diphenhydramine (Benadryl)Anticholinergics
Procainamide
derivatives
Serotonin receptor antagonistsSlide5
AntiemeticsPhenothiazine derivatives (vasodilation, hypotension)
Alpha adnergic receptor antagonist (hence vasodilates)Vomiting by motion sicknessBlock dopamine receptors in CRTZ and emetic centerAntihistamine effects helps with motion sickness in dogsDoes not stop PNS (GI, peritoneal, pharyngeal or other *visceral) effectively unless in high dosesSide effects include
hypotension and
sedation
Don’t use with
seizure animals (exacerbates condition),
vomiting
animals
or with
abnormal GI motility
Hydration has to be goodExamples:AcepromazineChlorpromazine: acute gastroenteritisProchlorperazinePerphenazineSlide6
AntiemeticsAntihistaminesBlock H1 receptors in the CRTZ from vestibular system
Large # H1 receptor – CRTZ - dogControls vomiting when the vomiting is due to motion sickness, vaccine reactions, or inner ear problemsNot effective for PNS or * Vagus n. gastroenteritisA side effect is sedationDon’t use 4 days before allergy testingExamples:Trimethobenzamide (Tigan
)
Dimenhydrinate
(Dramamine)
Diphenhydramine
(Benadryl)Slide7
AntiemeticsAnticholinergics (Sympathomimetic/
parasympatholytic nervous system drugs)Block PNS (vagus n.) - acetylcholine peripherally, which decreases intestinal motility and secretionsMay decrease gastric emptying – gastric atony (which may increase the tendency to vomit)Side effects include dry mouth, constipation, urinary retention, and tachycardiaExamples:Aminopentamide (
Centrine
)
Atropine
Isopropamide
Hyoscine
(scopolamine:
Donnatal
human product)
Useful for irritable bowel syndrome, high **** PNSSlide8
AntiemeticsProcainamide
derivatives or ProkineticsWork centrally by blocking the CRTZ (dopamine (more in dogs hence better for them) and serotonin receptors) Peripherally (prokinetic) by speeding gastric emptying, strengthening cardiac sphincter tone, and increasing the force of gastric contractionsShould not be used in animals with GI obstructions, GI perforation, or GI hemorrhage
SE: sedation (don’t use with
phenothazine
tranquilizers)
An example used in veterinary medicine is
metoclopramide (
reglan
)
Chemotherapeutic agents
Bile (duodenum) and mucus vomitus in otherwise healthy
DogProkinetics: Cisapride (
Propulsid
)
Serotonin antagonist effects
Cats –
megacolon
Off market: human
arrhythmias
but available for vets in compounding pharmacies
Frenzied catSlide9
AntiemeticsSerotonin receptor antagonistsWork selectively on 5-HT
3 receptors, which are located peripherally and centrally - CRTZWork on the theory that some chemicals cause vomiting because they increase serotonin release from small intestinal cellsExamples:Ondansetron (Zofran): 0.5 – 0.1 mg/kgChemotherapy, parvovirus$$DolasetronSlide10
Quinuclidine
class: Maropitant (Cerenia®)Slide11
AntiemeticsNeurokinin receptor antagonistsWork on NK1 receptors located in the center of the brainWork by inhibiting substance P, the key neurotransmitter involved in vomiting
Maropitant citrate (Cerenia®)Used to prevent acute vomiting and motion sicknessSide effects include:Pain at the injection site, hypersalivation, and diarrheaExtra label in catsSlide12
Diarrhea Diarrhea: abnormal frequency and liquidity of fecal material due to GI tract unable to absorb
fluidExudative diarrhea: protein/ fluid/ serum or blood loss in lumenDehydration and electrolyte imbalanceDecrease uptake of nutrientsMuscle weaknessAcid-base disturbances CausesInfectious: bacterial endotoxins,parvovirus, transmissible Gastroenteritis - swineForeign body
Toxins: toxins
Inflammatory
Neoplasm
Metabolic:
EPI – young shepherds
LaxativesSlide13
Small
IntestineLarge IntestineAmountIncreased (volume)
Decreased
Frequency (times/day
2-4
4-10
Tenesmus
No
Yes
Weight
loss
+/-
No
Blood
Melena
Frank
Mucous
No
YesSlide14
AntidiarrhealsAntidiarrheals are drugs that decrease
peristalsis or increase segmental contractions, thereby allowing fluid absorption from the intestinal contentsExamples:AnticholinergicsProtectants/adsorbentsOpiate-related agentsAnti-inflammatory drugsProbioticsAntibiotics/ antiparasitic
drugs: MetronidazoleSlide15
Antidiarrheals – Modify Intestinal Motility
Anticholinergics (against Ach)used to treat tenesmus (colitis) and vomiting (colonic irritation)Examples:Atropine (Injectable-SA)Not used oftenanticholinergic, mydriatic, cycloplegiaAminopentamide
(
Centrine
)
Isopropamide
Propantheline
(Pro-
Banthine
) - IBD
Methscopolamine
(Biosol
-M
)
Don’t use in cardiac arrhythmias, tachycardia (cat-hyperthyroidism), ileus,
Side effects
of
anticholinergics
M
ake SI diarrhea worse by
dec. segmental contraction and resistance flowDry
mouthConstipationCNS stimulationTachycardiaPupillary dilationSlide16
Antidiarrheals - AnticholinergicsSlide17
Opiate-related agents (scheduled drugs)Narcotic analgesics control diarrhea by decreasing both intestinal secretions and the flow of feces and
increasing segmental contractionsExamples:Diphenoxylate (Lomotil, lonox, diphenatol). C-VLoperamide (Imodium: OTC): least CNS depressionParegoric (tincture of opium): C-III, older drugSide effects include CNS depression (excitement:horses & cats), ileus, urine
retention,
bloat, constipation and may increase contact time between pathogen and gut!!!
Antidiarrheal – Modify Intestinal MotilitySlide18
Secretions fromEnterotoxinsLeukotrienesPG
Increase affect of Ach or PNSPulls electrolytes and can cause severe dehydration esp. youngCan become exudative diarrhea if GI lumen is compromised >> protein loss, rbc, sugar, fluidAntidiarrheal -Block HypersecretionSlide19
Anti-inflammatory drugsSalicylates (aspirin like compounds)Salicylate: antisecretory by blocking PG
Bismuth in bowel: tarry stool looks like melenaBismuth subsalicylate (bismuth + aspirin-like product)DON’T USE IN CATS (no more than 24 hrs)Not specificPepto bismol, corrective mixture (w/opium): refrigerate to increase palatabilityKaopectate: breaks in gut to bismuth carbonate (coating agent) and salicylateFlunixine
Meglumine
(
Banamine
,
flunixamine
)
Mostly for
colic horses
Calf scours
Not canine/feline: ulcersSulfasalazine (Azulfidine): sulfonamide + salicylate (mesalamine)Antimicrobial (sulfonamide) and mesalamine (anti-inflammatory) Ulcerative colitisCaution in catsSulfa SE: vomiting (give with food),
dec.
tear production
Antidiarrheal -
Block
HypersecretionSlide20
Protectants & AdsorbentsProtectants coat inflamed intestinal mucosa with a protective layer
Adsorbents bind bacteria and/or digestive enzymes and/or toxins to protect intestinal mucosa from damaging effectsExamples:Bismuth subsalicylate (bismuth + aspirin-like product)DON’T USE IN CATSNot specificPepto bismol, corrective mixture (w/opium)Kaolin (adsorb)/pectin (Kao-forte, kaopectilin)
Dec. absorption of some antibiotics and digoxin
New
kaopectate
: 130mg aspirin and 230 mg
(extra strength) >> 1Tbsp >> toxicity 5
lb
cat
Activated
charcoal (toxiban, liqui
-char)
Side effects include constipation
Antidiarrheal -
Adsorbents and ProtectantsSlide21
AntidiarrhealsProbioticsProbiotics seed the GI tract with beneficial bacteria; use is based on the theory that some forms of diarrhea are caused by disruption of the normal bacterial flora of the GI tract
Must be refrigerated to maintain the viability of the bacteriaExamples:Plain yogurt with active culturesVariety of trade-name productsSlide22
Probiotics
Lactobacillus spp.Enterococcus faeciumBifidobacterium
spp.Slide23
AntidiarrhealsMetronidazole (Falgyl)
A theory regarding the development of diarrhea is that anaerobic bacteria may increase due to disruption of normal GI floraOne way to treat this is to use an antibiotic effective against anaerobic bacteriaMetronidazole is an example of an antibiotic and antiparasitic used to treat diarrheaSlide24
Metronidazole
Tablets, suspension
Bitter tasting (cats hate this, foam in the back of mouth), if smash up and put in food, they will stop eating
Narrow margin toxicity:
CNS problems
, ataxiaSlide25
ReferencesRomich, J.A. Pharmacology for Veterinary Technicians, 2nd edition. 2010.Bill, R.L. Clinical Pharmacology and Therapeutics for the Veterinary Technician, 3rd
edition. 2006.