9 Bovine GI Drugs

• Drugs covered affect the abomasum or are antibiotics selected for calf diarrhea
• Emily Reppert is a Doctor of Veterinary medicine, holds a Masters of Science and is a Diplomate of the American College of Veterinary Internal Medicine

Outline

• Abomasal diseases where pharmacologic intervention is possible include:
  • Abomasal ulceration
  • Clostridial abomasitis
  • Abomasal atony

AMDUCA

• The Animal Medicinal Drug Use Clarification Act allows veterinarians to prescribe extra-label uses of approved animal and human drugs under certain conditions
• Food animal regulations dictate that prescriptions require no approved animal drug labeled for the use and with the same active ingredient
• A veterinarian must make a diagnosis, establish withdrawal periods, ensure the animal is identified, and enforce appropriate withdrawal times before prescribing

Holstein Cow Case Study

• A 4-year-old Holstein cow, fresh for 3 weeks, presented with acute loss of appetite, decreased milk production, and a ping sound on the left side of the abdomen
• The cow was confirmed to have a Left Displaced Abomasum (LDA)
• Exploratory laparotomy with omentopexy revealed a heavy abomasum and painful manipulation
• Immediately post-operation, symptoms included mild colic and anorexia
• 24 hours post-operation, the cow exhibited tachypnea, tachycardia, pale mucous membranes, melena, and recumbency

Abomasal Ulceration

• Ulceration is defined as the penetration of mucosa, possibly extending through the submucosa, muscularis externa, and serosa
• Erosion is defined as discrete mucosal defects without penetration of the muscularis mucosa

Abomasal Ulceration Prevalence

• Beef calves: 0.2-5.7%
• Healthy veal calves: 32-76%
• Healthy dairy cows: 1.0-2.6%
• Healthy beef cows: 1.8%
• Feedlot cattle: 1.6%

Four Types of Abomasal Ulceration

• Type 1: Non-perforating, with minimal intraluminal hemorrhage
• Type 2: Non-perforating, with severe blood loss
• Type 3: Perforating, with local peritonitis
• Type 4: Perforating, with diffuse peritonitis

Normal Protective Mechanisms of the Abomasum

• Mucous barrier
• Blood flow
• Gastric motility
• Prostaglandins
• Pyloric sphincter
• PGE2 and PGI2 decrease acid secretion, stimulate mucus-bicarb phospholipid bilayer, increase blood flow, accelerate mucosal healing, and decrease mast cell activation

Ulcer Development

• Acid secretion or impaired protective barriers lead to ulcer development
• Mucosal epithelial trauma
• Decreased luminal pH
• Decreased blood flow
• Decreased prostaglandins

Predisposing Factors for Ulcers

• Calves/Young: Stress, microorganism invasion, abrasion, mineral deficiencies
• Adults: Stress, diet, lymphosarcoma, drugs

Diagnosing Abomasal Ulceration

• Fecal occult blood test
• Abdominocentesis
• Abdominal ultrasound
• Abomasocentesis

Treatment for Abomasal Ulceration

• Reduce stress
• Restore appetite
• Enhance normal protective mechanisms of abomasal mucosa via manipulation of abomasal pH
• Provide RBCs

Enhancing Normal Protective Mechanisms

Neutralization of Acid

• Oral antacids are used for neutralization
  • Aluminum hydroxide binds pepsin and bile acids
  • Magnesium hydroxide binds bile acids

Prevention of Acid Secretion

• H2 receptor antagonists
• Proton pump inhibitors
• Prostaglandin analogs

Protection for Damaged Mucosa

• Sucralfate is used to protect damaged mucosa

Oral Antacids

• Aluminum hydroxide directly absorbs pepsin and binds bile acids
• Magnesium hydroxide binds bile acids
• Both aluminum hydroxide and magnesium hydroxide are weak bases that neutralize acid

Esophageal Groove Closure

• Esophageal Groove Closure bypasses the rumen
• This Closure increases oral drug absorption
• Drugs used include IV vasopressin and oral hypertonic saline

Preventing Acid Secretion with H2 Receptor Antagonists

• H2 Receptor Antagonists are selective, competitive antagonists of histamine receptors on parietal cells
• Cimetidine dosage is 50-100 mg/kg PO every 8 hours
• Ranitidine dosage is 10-50 mg/kg PO every 8 hours
• Famotidine dosage is 0.4 mg/kg IV every 24 hours

Preventing Acid Secretion with Proton Pump Inhibitors

• Proton Pump Inhibitors permanently bind and block K+/H+ ATPase "proton pump" on parietal cells
• Omeprazole dosage is 4 mg/kg PO every 24 hours
• Pantoprazole dosage is 1.1 mg/kg IV every 24 hours or 2.2 mg/kg SQ every 24 hours

Manipulation of Ruminant Abomasal pH

• Oral therapies for manipulation of ruminant abomasal pH are minimally effective in adults because they become diluted in the rumen
• Intravenous H2-antagonists like ranitidine and possibly famotidine are more effective
• Intravenous proton pump inhibitors like pantoprazole and possibly esomeprazole are more effective

Beef Calf Case Study

• A 2-week-old mixed breed heifer calf presented with mastitis and signs of colic
• Bottle baby, reluctant to nurse.
• Elevated heart rate of 176 bpm and a temperature of 101.4 degrees was observed
• CRT was 3s
• Moderate scleral injection and mild abdominal distention were noted
• Splash auscultated on abdominal succussion and the calf was reluctant to stand, intermittently kicking at its belly

Beef Calf Case Study: Diagnostics

• Rumen fluid analysis
• Gram stain
• Blood work
• Abdominal ultrasound.

Abomasitis Considerations

• Calves complete ruminant development occurs between 8-12 weeks
• Birth to 3 weeks: Calf is non-ruminant
• 3-8 weeks: Calf in transition
• 8 weeks and beyond: Calf is mature ruminant

Abomasitis Etiology

• Potential causes are Clostridium perfringens Type A and Sarcina sp

Abomasitis Clinical Signs

• Primarily affects milk-fed calves between 2-4 weeks old
• Acute onset of bloat and anorexia
• Depression, potentially leading to recumbency
• Signs of shock
• Possible diarrhea
• Colic
• Abdominal distention

Abomasitis Diagnosis

• Blood gas analysis showing acidosis and lactatemia
• Chemistry panel indicating azotemia and hypochloremia
• CBC showing immature and toxic neutrophils
• Abdominal ultrasound revealing abomasal distention and intramural emphysema

Abomasitis Treatment

• Supportive care includes intravenous fluids and a warm environment
• Antibiotics with good gram + spectrum
• Anti-toxin with C & D antitoxin
  • Calves: 10 mL SQ or IV
  • Adults: 30 mL SQ or IV

C. perfringens Toxins

• Type A: Alpha toxin, associated with abomasal tympany/abomasitis
• Type B: Alpha, Beta, and Epsilon toxins; associated with enterotoxemia in sheep/goats
• Type C: Alpha and Beta toxins; associated with necrotic enteritis
• Type D: Alpha and Epsilon toxins; associated with enterotoxemia ("overeating" disease)
• Type E: Alpha and Iota toxins; associated with enteritis in rabbits

Beef Calf Follow Up

• The calf recovered and went home initially
• However, the calf returned 6 months later, laterally recumbent with crepitation palpable under all large muscle groups
• The calf died from clostridial myositis

Calf Case Study

• A 10-day-old female mixed breed beef calf presented with a 3-day history of diarrhea, reluctance to nurse, and weakness
• Physical examination revealed a temperature of 104.5 F, scleral injection, hyperemic mucous membranes, CRT approximately 4 seconds, and depressed mentation

Goals of Antibiotic Treatment

• Treat bacteremia
• Decrease number of coliform bacteria in the small intestine

Antibiotic Selection Considerations

• Route of administration
• Spectrum of activity
• Static vs. cidal action
• Drug elimination pathway

Historically Labeled Antibiotics for Calf Diarrhea

• Oxytetracycline
• Amoxicillin
• Chlortetracycline
• Neomycin
• Streptomycin
• Sulfamethazine
• No peer-reviewed info shows that these drugs when labeled work in the setting of naturally acquired calf diarrhea

Available Antibiotics

• Ampicillin: 10 mg/kg IM or IV every 12 hours
• Florfenicol
• Tulathromycin

Guidelines for Antibiotic Use

• Antibiotics are recommended if the diarrheic calf shows systemic signs of disease such as depression, fever, young age, and comorbidity
• Antibiotics are NOT recommended if the diarrheic calf presents as normal with appetite, activity level, rectal temperature, hydration status, or other comorbidities

No-Tag Calf Case Study

• A 3-week-old female Simmental calf presented with a 2-day history of diarrhea
• Physical examination revealed: HR: 80, RR: 32, T: 101.5, CRT <2s