Gastrointestinal Therapeutics Week 4 Combined PDF

You are listening to My Surrey Attendance Code: ‘Sick as a dog’ By Aerosmith Xx-xx-xx Gastrointestinal Therapeutics – Part 1 Dr Martin Hawes Senior Lecturer...

You are listening to My Surrey Attendance Code: ‘Sick as a dog’ By Aerosmith Xx-xx-xx Gastrointestinal Therapeutics – Part 1 Dr Martin Hawes Senior Lecturer Veterinary Pharmacology and Therapeutics Monday, 14 October 2024 1  Learning Outcomes 1. State the principle functional problems caused by disease of the gastrointestinal system 2. Identify drugs that can be used to modify gastrointestinal function 3. Identify drugs that can be used to treat gastrointestinal disease 4. Give examples of possible uses of these agents to treat the most common diseases in domesticated species 5. Understand the pharmacological principles of antiparasitic treatments Monday, 14 October 2024 2  Link to other modules VMS1003 VMS1004 VMS2003 Monday, 14 October 2024 3  Therapeutics Antiemetics Emetics Acid blockers and gastro-protectants Prokinetics Laxatives Antidiarrhoeals Monday, 14 October 2024 4  Emetics and anti-emetics Vomiting (emesis) - complex reflex pathway evolved to protect animals from ingested toxins, but also associated with wide range of medical conditions Main targets for emetics / antiemetics: Cats & Dogs Neurokinin-1 receptors (NK1) Serotonin receptors (5-HT) Histamine-1 receptors (H1) Cats Sympathomimetic (α2 ) Dogs Dopamine receptors (D2) Remember me? Cats are not small dogs Pharmacology of emetics/antiemetics Adapted from Washabau and Day, 2013 Monday, 14 October 2024 5  Emetics and anti-emetics Vomiting (emesis) - complex reflex pathway evolved to protect animals from ingested toxins, but also associated with wide range of medical conditions Main targets for emetics / antiemetics: Cats & Dogs Neurokinin-1 receptors (NK1) Serotonin receptors (5-HT) Histamine-1 receptors (H1) Cats Sympathomimetic (α2 ) Dogs Dopamine receptors (D2) Remember me? Cats are not small dogs Pharmacology of emetics/antiemetics Adapted from Washabau and Day, 2013 Monday, 14 October 2024 6  Emetics and anti-emetics Vomiting (emesis) - complex reflex pathway evolved to protect animals from ingested toxins, but also associated with wide range of medical conditions Main targets for emetics / antiemetics: Cats & Dogs Neurokinin-1 receptors (NK1) Serotonin receptors (5-HT) Histamine-1 receptors (H1) Cats Sympathomimetic (α2 ) Dogs Dopamine receptors (D2) Remember me? Cats are not small dogs Pharmacology of emetics/antiemetics Adapted from Washabau and Day, 2013 Monday, 14 October 2024 7  Anti-emetics metoclopramide - dopamine (D2) antagonist - supresses CRTZ and upper GI pro-kinetic stimulant – increases ACh release in upper GI tract - NB – exclude GI obstruction before use maropitant – NK1 receptor antagonist – 24 hour action ondansetron – anti-serotonergic (5-HT). Expensive, used for patients unable to tolerate, or not controlled by, metoclopramide or maropitant metoclopramide maropitant Parvovirus Ouch! Can be painful Motion sickness when injected Monday, 14 October 2024 8  Emetics Used primarily to induce vomiting following poisoning Only useful if instigated within ~ 2-3 hours of ingestion Do not induce vomiting if poison is corrosive, severe CNS depression, seizuring, reduced gag reflex, bradycardia apomorphine , ropinirole - dopamine (D2) agonist (stimulates CRTZ dogs) xylazine - α2-adrenergic agonist (stimulates emetic centre cats) Hydrogen peroxide 3% solution oral alternative (stimulates CN IX at pharynx) apomorphine ropinirole xylazine Monday, 14 October 2024 9  Acid blockers and mucosal-protectants Acid blockade is important part of healing oesophageal and gastric ulceration and for treatment of gastritis. Main targets for drug therapy: Histamine (H2) receptors H+K+-ATPase proton pump Protectants aid the normal GI barrier function. Main aims/targets for drug therapy: Creating a physical barrier Acid neutralization Prostaglandin E & its production Regulation of gastric acid regulation Taken from Rang et al , 2016 Monday, 14 October 2024 10  Acid blockers and mucosal-protectants cimetidine, ranitidineH famotidineH – histamine H2 receptor antagonists – decreases stomach acid production omeprazole – proton pump inhibitor – supresses stomach acid secretion sucralfateH – complex which reacts with stomach acid to form a paste - binds to proteins in ulcers forming a protective barrier to aid healing cimetidine omeprazole Gastric ulcer Monday, 14 October 2024 11  Acid blockers and mucosal-protectants Antacids – aluminium hydroxide, magnesium hydroxide, calcium carbonate - not easy to administer, frequent administration, not palatable Misoprostol – synthetic prostaglandin E1 analogue. Useful for ulcers caused by NSAID. Caution – can cause abortion Ruminal lactic acidosis Monday, 14 October 2024 12  Pro-kinetics and anti-diarrhoeals Prokinetics – increased motility – e.g. management of ileus +/- constipation Anti-diarrhoeals – decreased motility – management of diarrhoea Enteric Nervous System Autonomic Nervous System ACh NE Secretions and Sensing environment Motility Increased motility Reduced motility Adapted from Washabau and Day, 2013 Sphincter relaxation Sphincter constriction Increased blood flow Reduced blood flow Increased secretions Reduced secretions Monday, 14 October 2024 13  Prokinetics metoclopramide - increases ACh release in upper GI tract. Useful for preventing gastro-oesophageal reflux & promoting gastric emptying cisaprideH – increases ACh release - was most effective prokinetic but withdrawn from human medicine (QT-prolongation). ‘Veterinary special’ ranitidineH - histamine H2 receptor antagonist, but anticholinesterase activity gives weak prokinetic activity, stimulating gastric emptying erythromycin – macrolide antibiotic, but is also a motilin receptor agonist – NB responsible antibacterial use lidocaine – infusion in horses improves intraoperative gastric motility Rabbit GI Equine ileus tract stasis Monday, 14 October 2024 14  Laxatives Promote elimination or increase fluid content of stools. Used for constipation, clear bowel prior to radiography / surgery Bulk forming laxatives - Mostly plant fibres (e.g. bran) are hydrophilic and not digested - bulk stimulates peristalsis Lubricants – e.g. liquid paraffin - coat the stool with a water- immiscible film, preventing water loss and ease stool passage lactulose – fermented in the large intestine to acetate and lactate with consequent osmotic laxative effect. Adjust based on individual response Who ate all the crickets? lactulose Who, who, who? Monday, 14 October 2024 15  Anti-diarrhoeals / anti-spadmodics Anti-diarrhoeals act by reducing peristalsis to enhance water reabsorption, demulcent activity or water adsorption loperamideH and diphenoxylateH – opioid agonists – anti- secretary, decrease propulsive intestinal contractions and increase segmentation, increase tone of GI sphincters hyoscine – antimuscarinic – antispasmodic for equine colic Other anti-diarrhoeals (e.g. metronidazole) treat cause Kaolin-pectin formulations - demulcent and adsorbent hyoscine loperamide Monday, 14 October 2024 16  Key Points LO – Identify drugs that can be used to modify gastrointestinal function or disease and their pharmacological principles. Give examples of possible uses of these agents to treat the most common diseases in domesticated species Emetics and antiemetics are used to trigger or stop vomiting. The principle targets include NK1 , 5-HT, H1, α2 and D2 receptors in CRTZ or emetic centre. Species differences are important in the choice of agent Metoclopramide (D2 antagonist), maropitant (NK1 antagonist) and ondansetron (5-HT3 receptor antagonist) are the main veterinary antiemetics Apomorphine (D2 agonist) and xylazine (α2-adrenergic agonist) are used as emetics in dogs and cats respectively Monday, 14 October 2024 17  Key Points LO – Identify drugs that can be used to modify gastrointestinal function or disease and their pharmacological principles. Give examples of possible uses of these agents to treat the most common diseases in domesticated species Prokinetics increase GI motility through actions on the autonomic or enteric nervous systems and are used to treat ileus +/- constipation. Metoclopramide and cisapride increase the release of ACh, ranitidine has anticholinesterase activity, erythromycin is a motilin receptor agonist. The exact mechanism of lidocaine’s use as a prokinetic is unknown. Monday, 14 October 2024 18  Key Points LO – Identify drugs that can be used to modify gastrointestinal function or disease and their pharmacological principles. Give examples of possible uses of these agents to treat the most common diseases in domesticated species Anti-diarrhoeals act by reducing peristalsis to enhance water reabsorption, demulcent activity or water adsorption Loperamide is an opioid agonist with multiple antidiarrhoeal effects (anti-secretary, decreases propulsive intestinal contractions, increases segmentation, increases tone of GI sphincters), hyoscine is an antimuscarinic, kaolin-pectin formulations are widely used (though evidence lacking) and have demulcent and adsorbent properties Monday, 14 October 2024 19  Key Points LO – Identify drugs that can be used to modify gastrointestinal function or disease and their pharmacological principles. Give examples of possible uses of these agents to treat the most common diseases in domesticated species Laxatives promote elimination or increase fluid content of stools. They are used to relieve constipation, clear the bowel prior to radiography / surgery Bulk forming laxatives (e.g. bran) are hydrophilic and not digested, the resultant bulk stimulates peristalsis Lubricants(e.g. liquid paraffin) coat the stool with a water- immiscible film, preventing water loss and ease the passage of the stool by lubrication Lactulose is a non-absorbable sugar fermented in the large intestine to acetate and lactate with consequent osmotic laxative effect. Monday, 14 October 2024 20  Key Points LO – Identify drugs that can be used to modify gastrointestinal function or disease and their pharmacological principles. Give examples of possible uses of these agents to treat the most common diseases in domesticated species Acid secretion blockade is an important part of healing oesophageal and gastric ulceration and for treatment of gastritis. Main targets for drug therapy are histamine H2 receptors (e.g. cimetidine and ranitidine) and the H+K+-ATPase proton pump (omeprazole). Gastro-protectants aid the normal GI barrier function. Main aims/targets for drug therapy include creating a physical barrier (sucralfate), acid neutralization (aluminium and magnesium antacids, calcium carbonate) and synthetic prostaglandin E (misoprostol) Monday, 14 October 2024 21  Gastrointestinal Therapeutics 2 Dr Martin Hawes Senior Lecturer Veterinary Pharmacology and Therapeutics The very hungry CATerpillar Monday, 14 October 2024 1  Learning Outcomes 1. Identify drugs that can be used to modify gastrointestinal function and their pharmacological principles 2. Identify drugs that may be employed to treat gastrointestinal disease and their pharmacological principles 3. Give examples of possible uses of these agents to treat the most common diseases in domesticated species 4. Understand the pharmacological principles of antiparasitic treatments Monday, 14 October 2024 2  Drugs to treat GI disease Appetite Reduced e.g. disease of many body systems (particularly chronic inflammatory, infectious, neoplastic), chemotherapy- associated Excessive e.g. obesity Intestinal microbiota Imbalance e.g. chronic enteropathy, exocrine pancreatic insufficiency (EPI), antibiotic responsive diarrhoea, motility disturbance, specific infectious agents Endoparasitism Nematodes, cestodes, Giardia Monday, 14 October 2024 3  Appetite stimulants Anorexia usually secondary to another condition Complex pathways Psychological & behavioural / physiological & metabolic / neurotransmitters Approaches to tempt eating Wet food Warm food Small portions Wide, shallow bowls Remove after 20-30 mins Hand feeding Hopkins et al (2016) https://www.ncbi.nlm.nih.gov/books/NBK278931/ Monday, 14 October 2024 4  Appetite stimulants mirtazapine – noradrenaline and serotonergic antagonist with appetite-stimulant, anti-emetic and anti-nausea effects Effects typically seen within 30 minutes cyproheptadine – non-selective serotonergic antagonist Can take up to 24 hours to be effective diazepam used historically but should be avoided due to risk of acute hepatic necrosis. Steroids also used historically capromorelin – ghrelin agonist approved this year (June!!) capromorelin mirtazapine Cat’s concept of Labrador’s concept a small portion of a small portion Monday, 14 October 2024 5  Intestinal microbiota Bacterial communities on intestinal mucosal surfaces. Bacterial cells outnumber host cells by 10 times. Interaction with host is usually beneficial Modifying the microbiota (and host immune response?) Prebiotics - Selectively fermented ingredients that support beneficial micro- organisms e.g. fructo-oligosaccharides (FOS) Probiotics - Live microorganisms, in adequate amounts confer a health benefit on the host e.g. Enterococcus faecium Synbiotics - preparations containing both prebiotics and probiotics Monday, 14 October 2024 6  Antibiotic and gastrointestinal disease Restrict antibiotics to times of need e.g. Specific infections Haemorrhagic diarrhoea ARD / SIBO metronidazole bactericidal for Gram +ve / Gram –ve anaerobes Inhibits nucleic acid function by preventing DNA repair At high doses antiprotozoal – used for Giardia infection Appears to modulate the immune system – beneficial in ARD (IBD) metronidazole Monday, 14 October 2024 7  Acute Haemorrhagic Diarrhoea Syndrome (aka HGE) Cause uncertain - association with toxin produced by Clostridium perfringens Peracute onset of bloody diarrhoea and vomiting Dehydration, tachycardia, weak pulses, shock in severe cases Diagnosis - compatible clinical signs (haemoconcentration and normal TP) and exclusion of other causes e.g. Addison's disease, parvoviral enteritis, intussusception, pancreatitis There is typically haemoconcentration with normal plasma proteins. Treatment - needs to be aggressive and is primarily symptomatic/supportive IV fluids Antiemetics e.g. maropitant Antibiotics - controversial Monday, 14 October 2024 8  Broad Spectrum Anthelmintics Drug Class Benzimidazoles Imidazothiazoles Macrocyclic lactones Amino acetonitrile derivatives Spiroindoles Monday, 14 October 2024 9  Guidelines Monday, 14 October 2024 10  Benzimidazoles Benzimidazoles include albendazole, fenbendazole etc. Febantel (in Drontal) is a prodrug Benzimidazoles bind to parasite tubulin leading to inhibition of glucose uptake, glycogen depletion and death Effective against nematodes, cestodes and Giardia spp. β-tubulin Taenia spp. but not Dipylidium Horse faeces with typically red-coloured caninum cyathostomin stages Monday, 14 October 2024 11  Benzimidazoles Kill worms slowly, prolonged exposure increases efficacy Ruminants/equids more sensitive than carnivores – rumen/caecum acts as reservoir fenbendazole is safe for puppies and kittens and lactating bitches/queens Dose puppies/kittens at 2, 5, 8 and 12 weeks of age albendazole fenbendazole Monday, 14 October 2024 12  Benzimidazoles triclabendazole differs from other benzimidazoles in that it is a narrow spectrum anthelmintic. Accumulates in both immature and adult stages of Fasciola hepatica triclabendazole is only drug effective against early immature fluke i.e. 2 weeks and older, through to adults. Other flukicides e.g. closantel and oxyclozanide are effective against adult flukes, nitroxynil against late immature stages triclabendazole Fasciola hepatica www.cattleparasites.org.uk Monday, 14 October 2024 13  Nicotinic agonists Nicotinic agonists – act at nicotinic ACh receptors (ion channels) and cause a rapid and reversible spastic paralysis. The following classes are selective for nematode muscles Imidazothiazoles – include levamisole Tetrahydropyrimidines – include pyrantel levamisole pyrantel Monday, 14 October 2024 14  Macrocyclic Lactones Derived from compounds produced by Streptomyces fungi Avermectins - include ivermectin and selamectin Milbemycins - include moxidectin and milbemycin Avermectins Milbemycins ivermectin selamectin moxidectin milbemycin Monday, 14 October 2024 15  Macrocyclic Lactones Open invertebrate specific glutamate-chloride channels in post- synaptic membrane (nematodes but not cestodes) leading to hyperpolarisation, flaccid paralysis and death Persistent activity used for preventative worm strategies (prophylaxis) http://www.wormbook.org/chapters/www_gaba/gaba.html Monday, 14 October 2024 16  Macrocyclic lactone - Toxicity Monday, 14 October 2024 17  Narrow spectrum - Isoquinolines praziquantel causes severe damage to the parasite integument, resulting in tetanic muscular contraction and paralysis. Mechanism unproven but thought to be related to changes in divalent cation fluxes, especially Ca+ praziquantel Monday, 14 October 2024 18  Antiprotozoal agents Coccidiosis / toxoplasmosis / neosporosis trimethoprim/sulphonamide (TMPS) inhibits folate synthesis (and purine synthesis toltrazuril - anticoccidial active against Eimeria spp. Affects the fine structure of the developmental stages of coccidia. TMPS toltrazuril Eimeria oocyte Toxoplasma Neospora Giardiasis metronidazole or fenbendazole Giardia cyst trophozoite Monday, 14 October 2024 19  Key Points LO – Identify drugs that may be employed to treat gastrointestinal disease and their pharmacological principles. Give examples of possible uses of these agents to treat the most common diseases in domesticated species Anorexia is usually secondary to another condition. Mirtazapine is a noradrenaline and serotonergic agonist with appetite-stimulant, anti-emetic and anti-nausea effects. Diazepam and steroids are also widely used but no longer recommended. Intestinal microbiota play an essential role in GI homeostasis - the microbiota composition can be altered in GI disease. Pre- and probiotics can be used to help restore normal composition Antibiotics should be restricted to treatment of specific infections and conditions such as HGE, ARD and SIBO Metronidazole is bactericidal for many Gram +ve and –ve anaerobes and has antiprotozoal and anti-inflammatory actions Monday, 14 October 2024 20  Key Points LO – Understand the pharmacological principles of antiparasitic treatments Similar to antibiotics, anthelmintics should be used responsibly to reduce the risk of development of resistance (see SCOPS, COWS guidance). Benzimidazoles (Group 1 white drenches) are broad spectrum anthelmintics that act by binding to parasite tubulin and are effective against nematodes and cestodes (Taenia spp.). Fenbendazole is safe for puppies and kittens and lactating bitches/queens. Triclabendazole is narrow spectrum against immature and adult stages of the fluke life cycle. Nicotinic agonists (Group 2 yellow drenches), such as levamisole and pyrantel, cause a spastic paralysis in nemotodes. Monday, 14 October 2024 21  Key Points LO – Understand the pharmacological principles of antiparasitic treatments Macrocyclic lactones (Group 3 clear drenches) open invertebrate specific glutamate-chloride channels in post- synaptic membrane leading to hyperpolarisation, flaccid paralysis and death. Two main classes of MLs: the avermectins (e.g. ivermectin and selamectin) and the milbemycins (e.g. moxidectin and milbemycin). Mutations in the MDR-1 gene (also known as ABCB1 mutation) cause sensitivity to MLs in many herding breed dogs, including Rough Collies, Shetland Sheep dogs and Old English Sheep Dogs. Monday, 14 October 2024 22  Key Points LO – Understand the pharmacological principles of antiparasitic treatments Praziquantel is a narrow spectrum tape wormer, which causes severe damage to the parasite integument, resulting in tetanic muscular contraction and paralysis Antiprotozoal treatments include trimethoprim/sulphonamide and related compounds, which inhibit synthesis of folate required for nucleic acid synthesis, and toltrazuril, which induces changes in the fine structure of the developmental stages of coccidia. Monday, 14 October 2024 23  Further Reading Riviere, J.E. et al., 2009. Veterinary pharmacology and therapeutics 9th ed., Ames, Iowa: Wiley-Blackwell. Edward Hall, James Simpson, and David Williams. BSAVA Manual of Canine and Feline Gastroenterology. Second ed. 2005. BSAVA Manual Ser. Web. Sustainable parasite control strategies for cattle (COWS) accessible online at http://www.cattleparasites.org.uk Sustainable parasite control in sheep (SCOPS) accessible online at http://www.scops.org.uk/ A guide to the treatment and control of equine gastrointestinal parasite infections (ESCCAP Guideline 8) accessible online at https://www.esccap.org/guidelines/ Monday, 14 October 2024 24  GI parasite Cats & Dogs – Roundworm Nematodes e.g. Toxocara canis, Toxocara leonine, Toxocara cati Monday, 14 October 2024 25  GI parasite Cats & Dogs – Hookworm nematodes e.g. Ancylostoma caninum, Uncinaria stenocephala, Ancylostoma tubaeforme Monday, 14 October 2024 26  GI parasite Cats & Dogs – Tapeworm cestodes e.g. Taenia taeniaeformis, Dipylidium caninum, Echinococcus granulosus Monday, 14 October 2024 27  Anthelmintics in Ruminants - Sheep Monday, 14 October 2024 28  Anthelmintics in Ruminants - Cattle Monday, 14 October 2024 29  Anthelmintics in Horses Monday, 14 October 2024 30  Equine GI parasite infections (ESCCAP Guideline 8) Monday, 14 October 2024 31  My Surrey Attendance Code: xx-xx-xx Fundamentals of Toxicology Dr Martin Hawes Senior Lecturer Veterinary Pharmacology and Therapeutics “All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy.” Paracelsus (1493-1541) Wednesday, 16 October 2024 1  Learning Outcomes 1. Define lethal dose, adverse event and serious adverse reaction 2. Differentiate acute from chronic toxicity 3. Describe the various situations where toxicity may occur (e.g. during medicines development, as adverse events, poisoning) 4. Explain why toxicity might occur during the 'normal' use of medicines 5. Describe how to deal with a suspected adverse event and make an official report Wednesday, 16 October 2024 2  1. Define lethal dose, adverse event and serious adverse reaction Wednesday, 16 October 2024 3  Pre-read – Key points Lethal doses are … lethal. LD50 is the dose that will kill 50% of a test population. Adverse Drug Reaction / Adverse Drug Event = any harmful or undesirable response to a drug. Regulators have specific definitions for ‘Adverse Event’ and ‘Serious Adverse Event’ for safety assessment and pharmacovigilance purposes… … A serious adverse event is any adverse event which results in death, is life-threatening, results in persistent or significant disability/incapacity, or a congenital anomaly or birth defect. Acute toxicity results from a single dose, or from multiple doses in a short period of time (14d) Chronic toxicity develops as a result of long-term exposure. Toxic effects are cumulative. Wednesday, 16 October 2024 4  3. Describe the various situations where toxicity may occur Wednesday, 16 October 2024 5  A true story …… It’s Sunday morning and your neighbour rings you – She is worried about 2 of her cat’s 8 kittens - both are very ‘flat’. They have been like this for an hour. They are not responsive. She is worried the smallest kitten is going to die. What would you ask your neighbour? What would you do? Wednesday, 16 October 2024 6  Happy ending – all kittens were OK 2 weeks later….. and look at her now Wednesday, 16 October 2024 7  Novel drug development Discovery phase in vitro toxicology studies e.g. AMES Pre-clinical development Acute toxicology studies, 1-4 weeks duration, high dose Reprotoxicology studies Clinical development Chronic toxicology studies, 3-6 months, low-intermediate dose Carcinogenicity studies, 2 years duration, low dose Wednesday, 16 October 2024 8  Sources of toxins Remember what Paracelsus said? Everything is toxic at the right dose….. Plants Animals Fungi Inorganic material Drugs and medicines Pesticides Household chemicals Industrial chemicals Wednesday, 16 October 2024 9  News last week …. Wednesday, 16 October 2024 10  Common sources of poison Xylitol Sycamore (equine) Medicines hypoglycaemia atypical myopathy renal and/or liver failure Grapes and raisins Rat poison Adder bites renal failure haemorrhage shock/ collapse Chocolate Mycotoxins Antifreeze CNS / renal failure / arrhythmias convulsions / coma ataxia / tremors / PU/PD Wednesday, 16 October 2024 11  The dog’s eaten my chocolate – is he going to be OK? 200g bar Theobromine Dogs at risk (kg) ~ 1g All ~ 400mg ~ ≤ 20kg but err on side of caution ~ 2mg None Wednesday, 16 October 2024 12  Veterinary Poisons Information Service https://www.vpisglobal.com/ Wednesday, 16 October 2024 13  Emetics Used primarily to induce vomiting following poisoning Only useful if instigated within ~ 2-3 hours of ingestion Do not induce vomiting if poison is corrosive, severe CNS depression, seizuring, reduced gag reflex, bradycardia apomorphine , ropinirole - dopamine (D2) agonist (stimulates CRTZ dogs) xylazine - α2-adrenergic agonist (stimulates emetic centre cats) Hydrogen peroxide 3% solution oral alternative (stimulates CN IX at pharynx) apomorphine ropinirole xylazine Wednesday, 16 October 2024 14  Decontamination with lavage / activated charcoal Activated charcoal – adsorbant Most effective if used within 1 hour of ingestion – only toxins in the liquid phase in direct contact adsorbed Activated charcoal Gastric lavage Wednesday, 16 October 2024 15  4. Explain why toxicity might occur during the 'normal' use of medicines Wednesday, 16 October 2024 16  4. Toxicity during the 'normal' use of medicines Type A – Augmented Toxic effects predictable and related to the principle pharmacological action (e.g. bleeding with anticoagulants) Dose-dependent and more common than Type B Type B – Bizarre Toxic effects unrelated to the principle pharmacological action (e.g. hypersensitivity reaction) Type C – Chronic Cumulative toxicity after prolonged use Type D – Delayed Teratogenic or carcinogenic effects Type E – End of use Toxic effects appear when the drug is stopped Rawlins & Thompson (1985) classification Wednesday, 16 October 2024 17  Hypersensitivity reactions Wednesday, 16 October 2024 18  5. Describe how to deal with a suspected adverse event and make an official report Wednesday, 16 October 2024 19  Pharmacovigilance Pharmacovigilance is the science and activities associated with the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problem Safety data is generated during drug development, but is limited We have a responsibility to report unexpected adverse events to improve the safety database An unexpected adverse event is an adverse event of which the nature, severity or outcome is not consistent with approved labeling or approved documents describing expected adverse events for a VMP (EMA definition) Wednesday, 16 October 2024 20  VMD Veterinary Pharmacovigilance Annual Review Accessible at https://www.gov.uk/government/publications/veterinary-medicines-pharmacovigilance-annual-review-2016 Wednesday, 16 October 2024 21 Wednesday, 16 October 2024 22  5. Reporting a suspected adverse event Information required to make an SAR report: An identified reporter e.g. veterinarian, pharmacist, owner, member of public Details of the affected animal or human age, sex, species The product concerned name and marketing authorisation holder Details of the SAR e.g. concurrent diseases, other medications, start and end of date of treatment, other relevant history or investigations Wednesday, 16 October 2024 23 Wednesday, 16 October 2024 24 Wednesday, 16 October 2024 25  Key Points LO - Define lethal dose, adverse event and serious adverse reaction LD50 is the dose that will kill 50% of the test population An adverse event is any observation in animals, whether or not considered to be product related, that is unfavorable and unintended and that occurs after any use of VMP (off-label and on-label uses) A serious adverse event is any adverse event which results in death, is life-threatening, results in persistent or significant disability/incapacity, or a congenital anomaly or birth defect Wednesday, 16 October 2024 26  Key Points LO - Differentiate acute from chronic toxicity Acute toxicity results either from a single dose, or from multiple doses in a short period of time (usually within 14 days of the administration of the substance) Chronic toxicity develops as a result of long term exposure. Toxic effects are cumulative. LO - Describe the various situations where toxicity may occur (e.g. during medicines development, as adverse events, poisoning) Toxicity can occur in many situations, including normal use of medicines, accidental ingestions of substances, environmental exposure, novel drug development Wednesday, 16 October 2024 27  Key Points LO - Explain why toxicity might occur during the 'normal' use of medicines Toxicity can occur during the normal use of medicines. Reactions can be classified as: Type A – Augmented Type B – Bizarre Including Type I-IV hypersensitivity reactions Type C – Chronic Type D – Delayed Type E – End of use Wednesday, 16 October 2024 28  Key Points LO - Describe how to deal with a suspected adverse event and make an official report Vets have a responsibility to report unexpected adverse reactions to improve knowledge about the safety of medicines Suspected adverse events are reported to the VMD (UK) The information required to make a report includes an identified reporter, details of the affected animal or human, the product concerned and details of the suspected adverse reaction Wednesday, 16 October 2024 29  MY SURREY AT T E N D A N C E  FIELD RADIOGRAPHY ALISON PRUTTON BVSC SFHEA MRCVS SENIOR LECTURER IN EQUINE CLINICAL PRACTICE LEARNING OBJECTIVES Be able to: Apply the principles of safe use of radiation in a field setting. Understand the compromise between safe use of ionising radiation and creating a safe working environment in relation to equine handling. Describe how to optimise image quality when obtaining radiographs of the horse. FIELD RADIOGRAPHY I O N I S I N G R A D I AT I O N S R E G U L AT I O N S 2 0 1 7 Approved code of practice and guidance Dose limits set Estimate doses to members of the public Outline duties of employees and employers to meet the requirements of these regulations FIELD RADIOGRAPHY  H E A LT H A N D S A F E T Y E X E C U T I V E 2021 update All generators must be placed on a stand Not acceptable to hold the generator Increases exposure Risk of serious or fatal electric shock FIELD RADIOGRAPHY R A D I AT I O N S A F E T Y: 3 M A J O R P R I N C I P L E S Must be a clear clinical indication for performing any procedure involving the use of ionising radiation. Avoid x-ray safaris Justify radiographic use by detailed clinical examination and diagnostic analgesia where applicable Exposure of personnel to radiation should be kept as low as reasonably achievable (ALARA principle) Dose limits for the individual personnel should not be exceeded. FIELD RADIOGRAPHY C H A L L E N G E S A S S O C I AT E D W I T H F I E L D R A D I O G R A P H Y Using expensive equipment around large animals No (permanent) control zone – need to follow IRR within context and apply local rules Variable facilities Working with owners and untrained staff Time pressures FIELD RADIOGRAPHY PERSONNEL How many people are required to take a radiograph of a horse’s limb? In most cases you need three people to take an equine radiograph in the field: Someone to hold the horse Someone to hold the plate Someone to take the image (the vet) FIELD RADIOGRAPHY  CONTROLLED AREA Ideally try to avoid taking radiographs in a stable Too confined to work safely around the horse Can’t visualise behind stable wall Flat, level, dry ground Enough space to work around the horse safely Power Supply (if not battery powered) Dark enough to allow visualisation of the centring and collimation lights Quieter part of the yard (minimal traffic) FIELD RADIOGRAPHY T E M P O R A RY R A D I AT I O N C O N T R O L Z O N E Biggest risk for scatter = 2m around the horse Minimise the number of people in the controlled zone Everyone should stand as far from the beam as possible Double the distance reduces the exposure risk 4-fold “For mobile X-ray sets, the controlled radiation area extends in the direction of the X-ray beam until the beam is sufficiently attenuated by distance (approximately 8 m) or shielding (e.g. solid floor or wall) and out to 3 m from the X-ray tube head and patient in all other directions” FIELD RADIOGRAPHY R A D I AT I O N P R OT E C T I O N Personnel within the ‘controlled area’ must wear appropriate protective clothing Lead lined gown Lead lined gloves Lead lined thyroid protector Staff must also wear a radiation dosimeter beneath protective clothing Generator stand Utilise cassette holders or plate holding blocks when possible All personnel assisting with radiographic procedures should be over 18years of age and not pregnant. Any clients assisting should be made aware of the risks of radiation Obtain signed consent FIELD RADIOGRAPHY W H AT I S W R O N G W I T H T H E S E P I C T U R E S ? A B FIELD RADIOGRAPHY PERSONAL PROTECTIVE EQUIPMENT Always avoid placing any body part behind the plate Always be aware of scatter Will be directly in the primary beam Everyone will be exposed to Gowns/gloves do not prevent this scatter exposure Wear gloves and gowns FIELD RADIOGRAPHY PERSONAL MONITORING Specific dose limits for different classes of person: 20mSv a year for 18yr+ employee 6mSv for 16-18yr old 1mSv for members of the public and others NB: this is occupational exposure only, not any other personal exposure. FIELD RADIOGRAPHY PERSONAL MONITORING Two types of dosimeter you will see: Electronic Personal radiation dosimeter Film badge dosimeter FIELD RADIOGRAPHY A B C PAT I E N T P R E PA R AT I O N Horses must be adequately restrained Person controlling the head Stocks? Sedation Light to moderate sedation with an alpha-2 agonist Xylazine- 0.5-1.0mg/kg IV Short acting Detomidine 0.004-0.02mg/kg IV Long acting Romifidine 0.04-0.08mg/kg IV +/- Butorphanol Safety & better quality images But: heavy sedation may result in more movement (More of a problem with proximal anatomy and or/ when longer exposure times needed) FIELD RADIOGRAPHY PAT I E N T P R E PA R AT I O N Ensure horse is standing on a flat even surface Clean the area thoroughly Remove all mud Artefact on radiographs from organic matter and water Hoof preparation Remove the shoe if indicated Clean and pare the foot Pack the sole and the frog with Playdoh to remove air interface FIELD RADIOGRAPHY  PA C K I N G T H E F E E T Image from AAEP: Value of Quality Foot radiographs FIELD RADIGRAPHY  EXPOSURE FACTORS Use exposure charts to minimize retake rate Tailored to your particular system Know the FFD for the generator/exposure chart If radiographing a greater tissue thickness than is typical for the setting listed, increased mAs is required If radiographing a decreased tissue depth, the mAs will need to be reduced accordingly. FIELD RADIOGRAPHY  POSITIONING Consider: The position of the horse The position of the area/joint of interest The position of the X-ray generator The position of the X-ray plate Ensure the limb or joint is vertical in the dorsal and sagittal places for both weightbearing and flexed views Horse on a firm level standing with limbs squarely beneath them Foot blocks for foot series Make sure the power cable will reach both sides of the horse (if relevant) Field Radiography PROCESSING Pick the right body part in the DR system Algorithms enable the best quality image for that body part Can’t be changed afterwards MARKERS Should always be placed dorsal or lateral to the region being imaged Particularly important for symmetrical areas such as foot, fetlock FIELD RADIOGRAPHY SPOT THE DIFFERENCE  WHEN TO REFER When higher exposures are required eg for neck, backs, chests etc Portable generators usually only go to 100-110Kv. Higher exposure → increased scatter. Very hard to maintain alignment between generator and plate without using bucky system Grid may be needed for some FIELD RADIOGRAPHY A N ATO M I C A L P O S I T I O N I N G T E R M I N O LO GY FIELD RADIOGRAPHY FOOT Standard series: Lateromedial Dorsopalmar/Dorsoplantar Dorsoproximal-palmarodistal oblique (to assess the pedal bone – ‘Upright pedal’) Dorsoproximal-palmarodistal oblique (collimated to assess the navicular bone) Palmaroproximal-palmarodistal oblique (‘Skyline navicular’) Additional views (depending on pathology): Dorsoproximal-palmarodistal oblique ‘medial and lateral oblique’ views (‘Pedal wing’ views) FIELD RADIOGRAPHY FOOT FIELD RADIOGRAPHY FOOT FIELD RADIOGRAPHY FETLOCK Standard series: Lateromedial Dorsopalmar/Dorsoplantar Dorsolateral-palmaromedial oblique Dorsomedial-palmarolateral oblique Additional views (depending on pathology): Flexed lateromedial FIELD Radiography FETLOCK FIELD RADIOGRAPHY M E TA C A R P U S / M E TATA R S U S Standard series: Lateromedial Dorsopalmar/Dorsoplantar Dorsolateral-palmaromedial oblique Dorsomedial-palmarolateral oblique FIELD RADIOGRAPHY  CARPUS Standard series: Lateromedial Dorsopalmar/Dorsoplantar Dorsolateral-palmaromedial oblique Dorsomedial-palmarolateral oblique Additional views (depending on pathology): Flexed lateromedial Dorsoproximal palmarodistal oblique (to skyline the distal radius, the proximal row of carpal bones or the distal row of carpal bones). FIELD RADIOGRAPHY HOCK Standard series: Lateromedial Dorsopalmar/Dorsoplantar Dorsolateral-palmaromedial oblique Dorsomedial-palmarolateral oblique Field Radiography  STIFLE Standard series: Lateromedial Caudocranial 60 degrees caudolateral- craniomedial oblique Additional views (depending on pathology): Flexed lateromedial Cranioproximal-craniodistal oblique (skyline patella) Field Radiography OTHERS Heads & dental radiographs – possible in field (but better in clinic!) Necks – Quality from field inadequate. Better in clinic Backs – Quality from field inadequate. Clinic Chests – Must be in clinic Abdomen – Must be in clinic Field Radiography TA K E H O M E M E S S A G E S Protect your own and others’ safety, know the local rules. *Good working practices, minimise time and maximise distance, use shielding* Appropriate restraint Good patient preparation Good positioning Appropriate exposures More to come in Collimate Year 4! Know the projections for each area Understand the limitations of what can be achieved in the field FIELD RADIOGRAPHY  SURGICAL SITE INFECTION LIVE ENGAGEMENT SESSION ALISON LIVESEY OCTOBER 2024 Surgical Site Infection Why did healthy young mothers die of sepsis in childbirth? Why was the rate higher if they were treated by surgeons coming from the mortuary? Did handwashing reduce the death rate? Did his groundbreaking work change clinical practice? Citrome, L. (2018). Happy Birthday Ignác Semmelweiss! Now, Let’s All Wash Our Hands. International Journal of Clinical Practice, 72(10), e13256-n/a. https://doi.org/10.1111/ijcp.13256 What is wrong with this theatre? #universityofsurrey 3 Theatre design » Traffic Minimal One entrance if possible » Clean areas Operating theatre, scrub area and sterile store » Contaminated areas prep and changing areas » Use separate trolley to transfer patients (do not cross areas) » Instrument cupboards in theatre Double doored cupboards » Minimal number of people in/out #universityofsurrey 24 BSAVA Manual of Surgical Principles What is wrong with this self seal pouch? #universityofsurrey 5 Colour change when sterilised #universityofsurrey 6 Instrument preparation: packaging » Must be dry Filtered medical grade compressed air is the only approved method » Jointed instruments should be left in open position » Cover sharp points/edge with gauze » Can autoclave unwrapped for immediate use Flash sterilisation » Wrapping material (for storage before use) Porous (steam) but tightly woven (dust/microbes) Resistant to heat and physical damage #universityofsurrey 7 Instrument preparation: packaging » Paper/plastic pouches » Reusable woven fabrics (140 cotton muslin drapes) Tightness of weave » Non-woven disposable materials (cellulose, wood pulp, polyester/synthetics) Bonded sheets » Boxes » Single or double layer More security versus perforation Harder for steam to penetrate #universityofsurrey 8 Problems with the picture #universityofsurrey Vet record 12 #universityofsurrey Vet record 12  Why will this not provide adequate sterilisation? #universityofsurrey 12 Sterilisation: Steam » Autoclave » Kills micro-organisms through coagulation and denaturation of proteins by moist heat moisture is a catalyst, allowing denaturation at lower temperatures than dry heat » Balance of steam, pressure, temperature and time » Various types depending upon how they produce steam, how they circulate it Pre-vacuum most common in veterinary practice Gravity-displacement No not necessarily kill prions #universityofsurrey 13 Autoclave Pre-vacuum autoclave Two chambers – inner and outer Vacuum removes air from inner chamber and replaces it with steam 132°C for 3-4 minutes as a minimum Unwrapped, flash sterilisation » Gravity-displacement autoclave Steam is lighter than air; steam enters the top and displaces heavier air Air can be trapped in hollow objects, reducing effectiveness 120°C for 13 minutes as minimum » Drying times 15-30 minutes  Is this autoclave safe to use? #universityofsurrey 15 Sterilisation: Indicators » Monitoring Chemical indicators – TST strips, tape Shows ‘conditions were met’ Doesn’t prove sterility or if has since become contaminated Placed on outside and inside the packet Biological indicators – contain bacterial spores = most sensitive test Send off for culture to ensure nothing grows but takes time Placed inside packs/kits #universityofsurrey 16  What is wrong with this self seal pouch? » Why is this a problem? #universityofsurrey 17  How do you look after clippers When should you clip the wound for surgery? #universityofsurrey 18  Brush and spray #universityofsurrey 19  Wound of dog following stifle surgery 14 days post op? » What action would you take? » Implants were placed #universityofsurrey 20  Action with the wound » Swab » Culture and sensitivity » Debride necrotic tissue » Consider remove implants » Cytology wound provide immediate information #universityofsurrey 21 SSI » Bacteria are introduced into all surgical wounds Defences disrupted Hair follicles cut during incision » We cannot sterilise the surgical surface » What leads to infection? Bacterial factors (numbers, types..) Tissue factors (trauma, vascularity, perfusion, implant) Patient factors (immunity, co-morbidity, age) #universityofsurrey 22  Degree of bacterial contamination Infection rate 2.0-4.8% 3.5-5.0% 4.6-12.0% 6.7-18.1% #universityofsurrey 23  Culture and Sensitivity » If you had a lot of infections » Look at theatre practice » Hand hygiene most important factor » “Bare arms” policy » RCVS Knowledge Infection Control » RCVS Knowledge Infection Control Auditing #universityofsurrey 24  How would you disinfect this? » What else would you need to ensure? #universityofsurrey 25  Cold Sterilisation » RCVS Knowledge Disinfection » Must be rinsed well #universityofsurrey 26 Instrument preparation » Material properties of surgical instruments dictate how to prepare them » Sterilisation Destruction of all micro organisms including spores on an object Bacteria, viruses, fungi, algae, protozoa, prions Cold sterilisation, dry, steam, heated chemical, radiation » Disinfection Destroys or reduces the number of micro-organisms (not including spores) and/or prevents their growth Chemical High-level, intermediate level, low level #universityofsurrey 27  Gowns » What are the benefits and drawback of fabric gowns? #universityofsurrey 28  What is this used for in surgery? » What are the challenges of sterilisation #universityofsurrey 29  Used for Cutting Intra-Medullary Pins BSAVA Manual of Canine and Feline Fracture Repair and Management, edited by Toby Gemmill, and Dylan Clements, British Small Animal Veterinary Association (B S A V A), 2016. ProQuest Ebook Central, https://ebookcentral.proquest.co m/lib/surrey/detail.action?docID =4789988. #universityofsurrey 30  What is this used for? » How it is sterilised? » You wish to use this today and it is the only pack left? » What are your concerns? #universityofsurrey 31  What is this used for? » What are the challenges of sterilising this? #universityofsurrey 32 #universityofsurrey 33 Shroud for a drill BSAVA Manual of Canine and Feline Fracture Repair and Management, edited by Toby Gemmill, and Dylan Clements, British Small Animal Veterinary Association (B S A V A), 2016. ProQuest Ebook Central, https://ebookcentral.proquest.com/lib/surrey/detail.action?docID=478 #universityofsurrey 9988. 45 #uniofsurrey 46 #uniofsurrey 36 #uniofsurrey 37 #universityofsurrey 7 #universityofsurrey 8 What is wrong with this surgical preparation? #universityofsurrey 10  Any concerns here? The guardian #universityofsurrey 14 Which of these is suitable as a peri-operative antibiotic? When are peri-operative antibiotics used for clean procedures? Clean orthopaedic procedures where implant is placed Clean procedures lasting more than 90 minutes Any surgery where SSI would be catastrophic (ex CNS) Where implants used Indications for Perioperative antibiotics 30 minutes prior to incision Then every 1.5-2 hours for duration of surgery + post op dose Fibrin seal within 3-6 hours Don’t Forget Other Factors Propofol Gender Endocrine disease Duration of anaesthesia Duration of Surgery Time of clipping No. of people in theatre References #universityofsurrey 46 56  APPROACH TO… DIARRHOEA IN C O M PA N I O N A N I M A L S PRIYA SHARP LEARNING OBJECTIVES Construct a differential diagnosis list based on diarrhoea as a clinical presentation and choose appropriate diagnostics. Determine appropriate medical and surgical interventions in the management and treatment of diseases characterized by diarrhoea. Determine appropriate prognosis, and the welfare implications of treatment options. Determine control measures appropriate for disease prevention. 2 DEFINITION What is diarrhoea? When do you call it diarrhoea? Where is it originating from? What form of diarrhoea is it? REVISION Osmotic: excess fluid within the lumen Secretory: excessive secretion within the SI affects absorption. Increased intestinal permeability: disruption to gut wall increasing permeability of protein,fluid, bacteria, blood. Dysmotility: increased motility usually secondary to other forms. https://www.akc.org/expert-advice/health/doggie-diarrhea/ 3 SMALL VS LARGE INTESTINAL DIARRHOEA Small Intestinal Large Intestinal Frequency Normal to mild increase Increased Urgency Normal Increased Mucous No Yes Straining No Yes Blood Melena Haematochezia (fresh blood) Volume Increased Normal to mild increase 4 SMALL INTESTINAL DIARRHOEA ACUTE CHRONIC Infectious Obstructive Dietary Ulceration of GI mucosa Bacteria Foreign body Food –responsive Acute infectious Parasites Intussusception chronic enteropathy enteritis Viruses Volvulus Gluten-sensitive Gastric ulcers Toxic Extra intestinal enteropathy Parastitic enteritis Drugs Renal failure Inflammatory diseases Intestinal carcinoma Insecticides Hepatic disease Chronic gastritis Disorders of intestinal Heavy metals Acute pancreatitis Chronic enteritis lymphatics Dietary Plasmacytic- Mesenteric Change in diet lymphocytic enteritis neoplasms Overfeeding Eosinophilic Congestive heart Intolerance gastroenteritis failure Sensitivity Haemorrhagic Congestive gastroenteritis pericarditis Lymphosarcoma 5 ACUTE SI DIARRHOEA Infectious Bacteria Parasites Viruses 6 ACUTE SMALL INTESTINAL DIARRHOEA Toxic Drugs Insecticides Heavy metals Bark post 7 ACUTE SMALL INTESTINAL DIARRHOEA Dietary Change in diet Overfeeding Intolerance Sensitivity Warrendale wagyu 8 ACUTE SMALL INTESTINAL DIARRHOEA Obstructive Foreign body Intussusception Volvulus 9 ACUTE SMALL INTESTINAL DIARRHOEA Extra intestinal Renal failure Hepatic disease Acute pancreatitis All Adobe stock images 10 CHRONIC SMALL INTESTINAL DIARRHOEA Dietary Food –responsive chronic enteropathy Gluten-sensitive enteropathy 11 CHRONIC SMALL INTESTINAL DIARRHOEA Inflammatory diseases Chronic gastritis Chronic enteritis Plasmacytic-lymphocytic enteritis Eosinophilic gastroenteritis Haemorrhagic gastroenteritis PDSA 12 CHRONIC SMALL INTESTINAL DIARRHOEA Ulceration of gastrointestinal mucosa Acute infectious enteritis Gastric ulcers Parastitic enteritis Intestinal carcinoma 13 CHRONIC SMALL INTESTINAL DIARRHOEA Disorders of intestinal lymphatics Mesenteric neoplasms Congestive heart failure Congestive pericarditis Lymphosarcoma 14 LARGE INTESTINAL DIARRHOEA ACUTE CHRONIC Acute non-specific colitis Inflammatory bowel disease Obstructive Parasitic Infectious Neoplasia Parasitic (whipworm, hookworm, giardia, tritrichomonas) Bacterial (Campylobacter, Clostridia) 15 SMALL VS LARGE INTESTINAL DIARRHOEA Parameters Small intestinal diarrhoea Large intestinal diarrhoea Frequency Normal to mild increase Increased Volume Increased Normal to mild increase Blood Digested (Melaena) Fresh (Hematochezia) Mucus No Yes Gaseous Present No Weight Loss More likely Less likely Straining No Yes Undigested food Occasionally Absent 16 I N V E S T I G AT I O N - L A R G E I N T E S T I N A L D I A R R H O E A History taking Diet ( Feed & feeding, changes) Behaviour (scavenging? obsessive compulsive?) Worming status Vaccination (don’t just ask- check!) Activity or management change Individual or herd? Extra intestinal? Chronic? Acute? LI? SI? 17 I N V E S T I G AT I O N - L A R G E I N T E S T I N A L D I A R R H O E A Physical examination aminotransferase, alkaline phosphatase Hydration status and creatinine/ urea. Cobalamin levels? TPR Urinalysis BCS Emergency?? Faecal culture MM colour PCR Abdominal palpation Radiographs (Thorax included if Faecal examination – Microscopy , Faecal oesophageal dysfunction suspected). flotation, SNAP test (Giardia, Parvo) Contrast study? FeLV / FIV test Ultrasound Haematology – non-regenerative anaemia, Biopsy (endoscopic vs surgery) inflammatory cells, eosinophilia Biochemistry - sodium, potassium, albumin, globulin, alanine 18 DIAGNOSTIC PLAN-LARGE INTESTINAL DIARRHOEA Infectious History taking Toxic Dietary Physical examination Obstructive Hydration status Extra intestinal Temperature, pulse, respiration Inflammatory diseases Ulceration of GI mucosa Body condition Mucous membranes colour Abdominal palpation Haematology & biochemistry ( Low Alb, Glo, folate, cobalamin) mild elevation on ALT, ALP Faecal examination – Microscopy, Faecal flotation, SNAP test (Giardia, Parvo, FeLV, FIP) Faecal culture 19 RULE OUT EXTRA INTESTINAL CAUSES Exocrine pancreatic insufficiency Pancreatitis – Pancreatic lipase immunoreactivity test Renal disease – Urea, Cr, SDMA, Urinalysis Hepatic insufficiency – Urea, cholesterol, bilirubin, bile acid stimulation test Hyperthyroidism – Total T4, TRH stimulation Hypoadrenocortism – ACTH stimulation test Infectious Toxic Dietary Obstructive Extra intestinal Inflammatory diseases Ulceration of GI mucosa 20 DIAGNOSTIC PLAN-LARGE INTESTINAL DIARRHOEA Radiography – Is contrast useful? Ultrasonography Biopsy Endoscopic vs surgical see WSAVA template for histologist Exclusion diet trial (4-8 weeks) Restricted novel protein Infectious Hydrolysed protein trial Toxic Dietary Obstructive Extra intestinal Inflammatory diseases Ulceration of GI mucosa 21 T R E AT M E N T - L A R G E I N T E S T I N A L D I A R R H O E A Fluid therapy – Crystalloids / Colloids? GI protectants Blood transfusion H2 receptor antagonist (Cimetidine) Antibiotics – when to use? Proton pump inhibitors (Omeprazole) Oxytetracycline Mucosal binding (Sucralfate) Metronidazole Probiotics / Prebiotics Infectious Tylosin Vitamin supplementation Toxic Anthelmintics Folate Ulceration of GI mucosa Dietary Praziquantel Cobalamin Obstructive Extra intestinal Pyrantel Nutrition Inflammatory diseases Milbemycin Antispasmodic Fendbendazole / Metronidazole for Giardia Buscopan Adsorbents Steroids? To use or not? Kaolin Montmorillonite 22 T R E AT M E N T - L A R G E I N T E S T I N A L D I A R R H O E A Surgical treatment Infectious Toxic Dependent on site of neoplasia Dietary Correction surgery for intussusception Ulceration of GI mucosa Obstructive Removal of foreign body Inflammatory diseases Extra intestinal Keep healthy margin Immunosuppressive therapy - IBD Azathioprine Corticosteroids Treat extra intestinal conditions – eg Pancreatic enzyme therapy 23 PROGNOSIS & WELFARE Dependent on severity, comorbidities Neoplasia dependent on stage and grade Dietary dependent on compliance. Easy for remission. Consider animals in chronic condition and cannot be managed well Pain/ discomfort management is very important 24 PREVENTIVE MEASURES Control infectious agents via vaccination, deworming. Good hygiene and herd health management Behaviour management of compulsive, scavenging dogs. Client education about dietary change, nutrition and feeding methods. Senior health monitoring for co-morbidities 25  APPROACH TO… DISORDERS OF THE GASTROINTESTINAL TRACT PRIYA SHARP LEARNING OBJECTIVES Understand how to restrain and perform a comprehensive clinical examination including history-taking and physical examination and identify the key clinical problems and the body systems involved. Demonstrate a rational, evidence-based, problem-solving approach to the common presentations in companion animal practice. Perform clinical reasoning, involving structuring an appropriate differential diagnoses list and recommending appropriate further investigations. Understand how to take appropriate samples and request appropriate tests. Interpret and appraise laboratory reports and clinical data as part of management of a clinical case. Formulate appropriate treatment, patient care, control, and prevention plans including euthanasia. Understand how to critically review and evaluate evidence, in support of practising evidence based veterinary medicine. 2 REFRESHER The gastrointestinal tract (GIT) consists of the following Oral cavity Oropharynx Oesophagus Stomach Small intestine Large intestines Rectum Anus (Liver and Pancreas) Msdmanual.com Considerations Clinical signs (problem list) Disorders (differential list) Investigation (diagnostics) 3 GASTROINTESTINAL DISEASE Very common Most self-limiting Those requiring further investigation/treatment must be identified Failure to respond to symptomatic treatment Seriously ill at presentation Clinical signs Not just vomiting and diarrhoea Vomiting and diarrhoea may not be caused by primary GIT disease Thorough history Not always as reported (vomiting vs regurgitation vs dysphagia) Careful and complete physical examination Some if not most of the GIT is not easy to physically examine Excellent client communication 4 APPROACHING A CASE If non-life threatening/in need of immediate treatment History Resolution Symptomatic Problem List treatment Physical Non Exam Resolution 5 APPROACHING A CASE – PROBLEM BASED APPROACH Life threatening/in need of immediate treatment History Problem List Differential Diagnostic Treatment Systemic Disease Diagnosis Multiple (Concurrent) Investigation Disease Physical Exam 6 ANOREXIA Loss or lack of appetite not eating? not wanting to eat? not able to eat?? Partial (hyporexia) or complete True anorexia: decreased appetite; the animal has no interest in eating Pseudoanorexia: secondary anorexia hungry, but appears unable to eat oral pain, unpalatable diets or environmental stress. 7 O R A L C AV I T Y ORAL CAVITY Lips and oral mucosa Palate Tongue Teeth Mandible, maxilla Salivary Glands Dyce 9 CLINICAL SIGN Pseudoanorexia Abnormal movement of jaw Pain Unwilling to pick up toys/play ball Hypersalivation Failure to gain weight Halitosis Ceased grooming NOTHING 10 D E N TA L D I S E A S E Oral resorptive lesions (feline) Fractured teeth Malalignment/malocclusion Cleft palate Overgrowth (equine, rabbit, small mammals - herbivores) Abscess (any but rabbit common) Gingiviits/Periodontitis (canine most common) Gingivostomatitis (feline most common) BSAVA manual of gastroenterology 11  D E N TA L D I S E A S E - O V E R G R O W T H Rabbit molar spur Texasequinedentist.com #universityofsurrey Vetcentral.com 12  D E N TA L D I S E A S E BSAVA manual of gastroenterology Cat oral resorptive lesion #universityofsurrey 13 Canine periodontitis L I P S , O R A L M U C O S A , G U M S , PA L AT E Neoplasia Viral Soft tissue sarcoma Papillomavirus – all species Squamous cell carcinoma (feline) Calicivirus (feline) Melanoma Feine gingivostomatitis Sarcoids (equine) Reoviridae Trauma Bluetongue Penetrating injury/stick injury Picornavirus Tongue laceration Foot and mouth Inflammatory/immune mediated Congenital Eosinophilic granuloma complex (feline) Cleft palate, cleft lip Lip fold dermatitis (secondary pyoderma) 14 NEOPLASIA Feline squamous cell carcinoma Soft tissue sarcoma Fibrosarcoma 15 TRAUMA Vet Times 16 VIRAL Orf MSD Animal Health Papilloma Feline gingivostomatitis Vet Times 2013 17 http://csu-cvmbs.colostate.edu VIRAL - NOTIFIABLE Foot and mouth Bluetongue Institute of animal health Defra 18 I N F L A M M ATO RY Lip fold dermatitis Feline eosinophilic granuloma 19 SALIVARY GLANDS Salivary gland mucocoeles Sialadenitis Neoplasia Fossum, Small Animal Surgery 20 JAWS Fractures/trauma Mandibular symphysis fracture Bacterial Actinomyces bovis – lumpy jaw Abscess – penetrating injury Neoplasia 21 I N V E S T I G AT I O N History Thorough visual oral exam –sedate? Biopsy and histopathology Culture BSAVA Manual Viral swab PCR Imaging Standard radiographs not always useful (difficult to image area of concern) Dental radiographs are useful CT 22 OROPHARYNX OROPHARYNX Tonsils Cricopharyngeal muscles 24 CLINICAL SIGNS Dysphagia Retching Gagging/gulping Reduced appetite (pseudoanorexia) Weight loss 25 DISORDERS Neoplasia Polymyopathy and Polyneuropathy Squamous cell carcinoma Cranial nerves (IX, X and XII) needed for Sarcoma swallow reflex Lymphoma (rare) Muscles relax and contract Disorders of either can lead to dysphagia Cricopharyngeal achalasia Normally generalised signs Muscle doesn’t relax Congenital/genetic Cricopharyngeal dysphagia Relaxes at incorrect time (asynchronous) Fluoroscopy can differentiate the two 26 I N V E S T I G AT I O N Physical examination – visual inspection of oral cavity Mass, focal inflammatory Radiographs Difficult area to image CT or MRI Biopsy or histology Mass lesions Fluoroscopic swallowing study Dynamic radiographs – can see the https://www.youtube.com/watch?v=6cZIUrpxtig act of swallowing (4’50”) 27 OESOPHAGUS OESOPHAGUS Narrows at four locations: pharyngo- oesophageal sphincter gastro-oesophageal sphincter thoracic inlet base of the heart Long muscular tube 29 CLINICAL SIGN Regurgitation: species variation Most common sign in cats/dogs Should be fairly soon after eating Must differentiate from vomiting Reflux Hyporexia/pseudoanorexia Ptyalism (not true ptyalism) Weight loss 30 R E G U R G I TAT I O N Differentials of Regurgitation Physical obstruction Megaoesophagus Physical❖ Extra-luminal Extra-luminal ❖ Congenital Congenital Megaoesophagus obstruction Vascular ring anomaly Vascular ring anomaly ❖ Acquired Acquired Intra-thoracic Intra-thoracic mass mass Idiopathic Idiopathic Intra-luminal ❖ Intra-luminal Neuromuscular Neuromuscular disease disease Foreign body Toxicity Foreign body Stricture Toxicity Endocrine Stricture Tumour Endocrine (hypoadrenocorticism) (hypoadrenocorticism) Tumour Granuloma Inflammatory Functional Granuloma Lower oesophageal achalasia- ❖ OesophagitisOesophagitis Inflammatory Functional like syndrome ❖ Reflux syndromes Reflux syndromes Sliding hiatial hernia ❖ Lower oesophageal achalasia-like Aerodigestive ❖ Aerodigestive disorders disorders syndrome ❖ Sliding hiatial hernia 31  DISORDERS OF THE OESOPHAGUS Oesophageal foreign body Dogs Horses (choke) Cows Rare in cats 32 DISORDERS Narrowing Stricture Vascular Ring Anomaly Neoplasia (rare) Megaoesophagus Hereditary in some dogs Secondary to Vascular Ring Anomaly Generalised enlargement Lack of peristalsis Myastheia gravis – generalised muscle condition Neuropathy Oesophagitis Diverticula 33 I N V E S T I G AT I O N Plain Radiographs Fluoroscopy (swallowing study) Conscious Dynamic Left lateral (or both) Oesophageal air – megaoesophagus Endoscopy Foreign body Excellent for intraluminal contents and mucosal lesions Contrast Radiographs (barium) Foreign bodies, oesophagitis Neoplasia Can’t diagnose megaoesophagus Motility disorders 34 STOMACH  STOMACH Horse Ruminant Monogastric Today’s Veterinary Practice Hindgut fermenter Foregut fermenter 36 CLINICAL SIGNS Vomiting (only cat and dog) Cranial abdominal pain Anorexia (nausea, don’t want to eat)/reduced appetite Weight loss/reduced weight gain Reduced performance (horses) Abdominal distension Melena (digested blood coming out in stool) 37 VOMITING ACTIVE PROCESS Nausea Reduction in gastric/lower oesophageal sphincter and oesophageal motility, and increased retrograde motility of small intestine Retching Contraction of abdominal muscles and marked abdominal effort (NOT in regurgitation) Expulsion of gastric contents Simultaneous contraction of abdominal muscles and diaphragm → negative intrathoracic pressure → movement of gastric contents into oesophagus/mouth 38 DISORDERS Gastritis Foreign body Infectious Acute vs chronic Bacteria Primary vs secondary Pyloric stenosis Helicobacter (cats/dogs) Ulceration Parasitic Performance animals Distension Trichostrongylus Primary vs secondary Bloat Ostertagia GDV Haemonchus Displaced abomasum Viral Neoplasia (uncommon) Gastric impaction Parvovirus Adenocarcinoma Lymphoma Leiomyosarcoma/- Traumatic myoma in muscle reticuloperitonitis layers 39 DISORDERS- DISTENSION Distension Bloat GDV Gastric impaction Grain overload Displaced abomasum 40 I N V E S T I G AT I O N Visual and physical examination Abdominal swelling Endoscopy Palpation Mucosa – ulcer, mass Auscultation Foreign body – diagnosis and retrieval Percussion Mucosal/submucosal biopsy and histology Radiographs Exploratory surgery Size, shape, distension, foreign body Diagnosis and removal of foreign body Biopsy and histology Ultrasound Wall thickening/layers, foreign body, Faecal analysis stenosis Parasites Blood work: Haematology, Biochemistry, Electrolytes Anaemia, WBCs, electrolyte abnormalities 41 SMALL INTESTINE SMALL INTESTINE Duodenum Jejunum Ileum The glass horse 43 CLINICAL SIGN Hyporexia/anorexia OR Polyphagia Weight loss/poor growth Abdominal pain (colic) Abdominal distension Hypoproteinaemia (low alb) Ascites/oedema Dehydration/Collapse Decreased OR increased gut sounds (borborygmi) Flatulence Diarrhoea 44 SMALL V S LARGE INTESTINAL DIARRHOEA Small Intestinal Large Intestinal Frequency Normal to mild increase Increased Urgency Normal Increased Mucous No Yes Straining No Yes Blood Melena Haematochezia (fresh blood) Volume Increased Normal to mild increase 45 DISORDERS Obstruction Foreign body Neoplasia Neoplasia Lymphoma Adenocarcinoma Sarcoma Intussusception Volvulus in dogs (are) 46 DISORDERS Ulceration Parasitic Inflammatory Primary vs secondary Giardia Lymphocytic Cryptosporidium Plasmacytic Bacterial Coccidia Eosinophilic Salmonella Cooperia E.Coli Strongyloides Toxin ingestion Campylobacter Nematodirus Clostridium Toxocara Trichuris Gut stasis Lawsonia