June 15 – 28, 2009 The Vomiting Patient: Four Important Questions. AAHA National Staff Meeting Webcast. The Vomiting Patient: Four Important Questions June 15 - 28, 2009 By David C. Twedt, DVM, Diplomate ACVIM AAHA gratefully acknowledges the following for their sponsorship of this Web Conference : Diagnosis and Management of the Vomiting Patient David C. Twedt, DVM, Diplomate ACVIM “Jake” 10 yr C/M WWT • Owner’s complaint: 2 years duration of chronic vomiting • Referred for a vomiting work-up 1
June 15 – 28, 2009 The Vomiting Patient: Four Important Questions. AAHA National Staff Meeting Webcast. The Patient • Adopted 2 years ago • Little history prior to adoption except a “reported” episode of pancreatitis • On heartworm prevention • Since owners obtained Jake he would vomit • Jake has as been treated with a variety of medications The Four Important Questions 1. Is the animal really vomiting? 2. What is the vomiting history? 3. How should I direct my work-up? 4. When should I consider antiemetic therapy, and if so which one? The Vomiting History 2
June 15 – 28, 2009 The Vomiting Patient: Four Important Questions. AAHA National Staff Meeting Webcast. The Vomiting History 1. Is the patient actually vomiting? • Nausea • Salivation • Swallowing • Retching • Expulsion of gastric material The Vomiting History 1. Is the patient actually vomiting? 2. Detailed vomiting history • Determine D’FACTs: – Duration – Frequency – Association with eating – Character – Treatments The Vomiting History 1. Is the patient actually vomiting? 2. Detailed vomiting history 3. Diet and drug history 3
June 15 – 28, 2009 The Vomiting Patient: Four Important Questions. AAHA National Staff Meeting Webcast. The Vomiting History 1. Is the patient actually vomiting? 2. Detailed vomiting history 3. Diet and drug history 4. Other signs or symptoms associated with the vomiting Jake’s History • Vomiting: – 2-3 X a week – Contains predominately bile • Occurs almost always during the night or early morning – Occasionally has a gurgling stomach – Sometimes vomits heartworm pills up to 12-18 hours after given Jake’s History • Additional history: – Senior premium diet feed once a day – Good appetite, no weight loss • Past therapy: – Several specialty GI diets – Antibiotics – Famotidine 4
June 15 – 28, 2009 The Vomiting Patient: Four Important Questions. AAHA National Staff Meeting Webcast. Physical Examination • 9 kg bw, BCS - 5/9 • Active and responsive • T - 100º F, Pulse - 102 bpm • GI - normal abdominal palpation • Review of other systems - WNL • Rectal exam - WNL and normal stool Would you consider prescribing an antiemetic as part of Jake’s treatment plan? a. Yes b. No c. Need more information Rational Use of Antiemetics • First, always treat primary disease • Indications would be……. – To prevent fluid and electrolyte loss – Patient comfort from nausea and vomiting – Fear of aspiration pneumonia • Benefit….. – Possibly an early return to nutrition • Contraindications….. – GI obstructions 5
June 15 – 28, 2009 The Vomiting Patient: Four Important Questions. AAHA National Staff Meeting Webcast. Rational Use of Antiemetics • Common uses: – Motion sickness – Uremia – Parvovirus – Pancreatitis – Acute gastroenteritis – Cancer chemotherapy – Undetermined causes and no etiology What Antiemetic? Serotonin antagonists Metoclopramide Butorphanol Phenothiazines NK 1 antagonists Antihistamines Anticholinergic drugs Pathophysiology of Vomiting 6
June 15 – 28, 2009 The Vomiting Patient: Four Important Questions. AAHA National Staff Meeting Webcast. The Pathophysiology of Vomiting Remember all vomiting is a CNS initiated reflex Vestibular CNS Emetic CRTZ Center Vagal (X) CN IX Sympathetic Peripheral Sensory Receptors 2 - adenergic NK1 5-HT 1 Cat H 1 Histimergic Emetic Vestibular CRTZ Center Dog Vagal Afferents NK1 2 - NK1 adenergic 5-HT 1A/3 Cat H 1 Histimergic Emetic Vestibular Phenothiazines CRTZ Center Dog Chlorpromazine 2 adenergic (dog?) D 2 dopaminergic H 1 histiminergic (weak) Vagal M 1 cholinergic (weak) Afferents Sedation / Hypotension NK1 Seizure threshold 7
June 15 – 28, 2009 The Vomiting Patient: Four Important Questions. AAHA National Staff Meeting Webcast. 2 - NK1 adenergic 5-HT 1A/3 H 1 Histimergic Emetic Vestibular CRTZ Antihistamines Center Diphenhydramine H 1 histiminergic M 1 cholinergic Vagal Motion sickness Afferents Vestibular disease NK1 Sedation / dry mouth Effectiveness? 2 - NK1 adenergic 5-HT 1A/3 H 1 Histimergic Anticholinergics Emetic Vestibular CRTZ Isopropamide Center M 1 cholinergic Peripheral afferent cholinergics Generally not indicated Vagal Dry mouth Afferents GI secretions NK1 GI motility 2 - NK1 adenergic 5-HT 1A/3 Cat H 1 Histimergic Dopamine Antagonist Emetic Vestibular CRTZ Metoclopramide Center Dog D 2 dopaminergic (cats?) 5HT 3 serotonergic ( dose) Rapid metabolism - CRI Vagal CNS excitement, with Afferents phenothiazines NK1 GI motility 8
June 15 – 28, 2009 The Vomiting Patient: Four Important Questions. AAHA National Staff Meeting Webcast. 2 - NK1 adenergic 5-HT 1A/3 Cat Serotonin Antagonist H 1 Histimergic Ondansetron Emetic Vestibular Dolasetron CRTZ Center Dog 5HT 3 antagonists Uses: Chemotherapy Vagal Severe vomiting Afferents GI motility NK1 2 - NK1 adenergic 5-HT 1A/3 Cat Maropitant H 1 Histimergic NK 1 Antagonist Emetic Vestibular Vomiting/nausea CRTZ Center Dog Chemotherapy Motion sickness ( dose) Hepatic metabolism Vagal Dose accumulates > 5 Afferents days NK1 Maropitant Mechanism of Action • Blocks Substance P (a neuropeptide) at NK1 receptor P P MAROPITANT 9
June 15 – 28, 2009 The Vomiting Patient: Four Important Questions. AAHA National Staff Meeting Webcast. Maropitant • Oral (16, 24, 60, 160 mg tabs) – 2 mg/kg PO q 24 hr - vomiting – 8 mg/kg PO q 24 hr - motion sickness • Injectable (10 mg/ml) – 1 mg/kg SQ q 24 hr Efficacy - Prevention of Vomiting Central vs. Peripherial Least Squares Mean Number of Emetic Events No Emetic Events 2.5 Ipecac Apomorphine 2 1.5 Peripheral Central 1 0.5 0 Pfizer Study Review of Experience At CSU May 14 to July 26, 2007 • We used 19 bottles in 2 months • >85 cases have been treated with Maropitant • A review of first 50 clinical cases – 46 dogs – 3 cats – 1 ferret 10
June 15 – 28, 2009 The Vomiting Patient: Four Important Questions. AAHA National Staff Meeting Webcast. First 50 Cases 7 Parvovirus 7 Other conditions: 11 Gastroenteritis 2 peritonitis 4 Pancreatitis 2 neurological disease 2 Renal disease 1 vestibular 2 Liver disease disease 17 Oncology 1 rattlesnake bite 15 chemotherapy 1 unknown 2 tumor related First 50 Cases • Treatment response: – 30/50 had treatment response recorded in record – 29/30 cases showed a positive response to therapy – 1 case (abdominal cancer) failed to respond with continued vomiting First 50 Cases • Adverse effects - first 50 cases – 4 clinicians reported stinging at injection site • Cases subsequent to first 50 – Bassett hound getting chemotherapy developed gastric dilatation – Pancreatitis case developed gastric atony and required gastric suction 11
June 15 – 28, 2009 The Vomiting Patient: Four Important Questions. AAHA National Staff Meeting Webcast. Parvovirus: 7 Cases • Vomiting & nausea are a major complication • Ability to begin early oral nutrition improves recovery • Maropitant appears to decrease hospital time by almost one day Motion Sickness Acepromazine Maropitant • Maropitant had a 84% to 93% efficacy in dogs with a history of motion sickness • Give 2 hours before the trip Conder GA: Efficacy and safety of maropitant for prevention of vomiting due to motion sickness. J. Vet. Pharmacol Dec 2008 Does Maropitant Effect GI Motility? • SmartPill™ evaluation of GI motility in dogs given placebo vs Maropitant 12
June 15 – 28, 2009 The Vomiting Patient: Four Important Questions. AAHA National Staff Meeting Webcast. Does Maropitant Effect GI Motility? • Maropitant appears to have no effect on GI motility (ACVIM Forum 2009) Antiemetics in Cats • Antihistamines - poor for motion sickness • Metoclopramide - a poor choice • Maropitant QuickT ime™ and a are needed to see this picture. decompressor – Not yet approved for cats – 0.5-1 mg/kg q 24 h SQ or PO – Motion sickness 1 mg/kg PO Hickman: Safety, pharmacokinetics of maropitant for prevention of vomiting and Milton motion sickness in cats. J Vet Pharmacol Therap 31;220, 2008 Maropitant • Off label use: – IV in several cases – Dogs under 16 weeks – Dogs for longer than 5 days SQ • Cautions: – Liver disease – Prolonged use 13
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