VPHM 142 Lecture 5 .pdf

Gastrointestinal drugs COMMON targets Motility Acidity Others- inflammation, absorption Gastrointestinal drugs Most provide relief/comfort/support But not for treatment, so… Diagnose the condition properly to understand all factors involved. -Is the drug really necessary? -Are you also add...

Gastrointestinal drugs COMMON targets Motility Acidity Others- inflammation, absorption Gastrointestinal drugs Most provide relief/comfort/support But not for treatment, so… Diagnose the condition properly to understand all factors involved. -Is the drug really necessary? -Are you also addressing the primary cause? Which anti-emetic drug would be most appropriate as adjunct in cancer chemotherapy? Why? Pathophysiology of emesis in chemotherapy Types PNS CNS acute Free radicals stimulate enterochromaffin cells 5-HT3 receptors sends impulse which trigger the in GIT which cause release serotonin; vomiting reflex via the nucleus of the solitary serotonin binds to intestinal vagal afferent tract (NTS) and chemoreceptor trigger zone (CTZ) nerves via 5-HT3 receptors in the CNS delayed Release of substance P from neurons Release of substance P from neurons Which binds to neurokinin receptors (NK1) in the CNS October 2, 2017 Nelly Adel, PharmD, BCOP, BCPS Supplements and Featured Publications, Managed Care Considerations in Chemotherapy-Induced Nausea and Vomiting, Volume 23, Issue 14 Serotonin (5-HT3) receptor antagonists Inhibit 5HT3 receptors in the CRTZ e.g. Ondansetron & Dolasetron, Granisteron NK-1 receptor antagonist blocks receptors found in the emetic center, CRTZ and in peripheral afferent nerves Maropitant citrate What type of diarrhea is not treated with anti-motility drugs like loperamide? Why? Narcotic Increase segmentation, decrease secretion Diarrhea Infectious Non-infectious  What are gastroprotectants? Describe their action and use. Gastro- stomach Protectant *protects the stomach/ protects the mucosa How? target cause- acid, toxins (antacids, PPIs, H2blockers, BSubsalicylate) protect mucosa- gastric mucosa protectants (sucralfate, BSubsalicylate) Gastroprotectants An In-Depth Look: The Use of Gastroprotectants in Treating Gastric Ulceration in Dogs Internal MedicineMay 2006 (Vol 28, No 5)byAlicia K. Henderson , DVM ,Cynthia R. L. Webster , DVM , DACVIM Which anti-ulcer drug would be more appropriate for ulcerations due to renal failure? Why? “Chronic administration of acid suppressants to dogs and cats with CKD may not be benign. Prolonged administration of acid suppressants has been associated with derangements in serum calcium and PTH concentrations, osteoporosis, and pathologic fractures in at-risk human populations” There is no evidence to support the prophylactic use of gastroprotectants in dogs and cats with International Renal Interest Society (IRIS) stages 1-3 renal disease. Additional studies are warranted to determine the benefits of acid suppression in animals with IRIS stage 4 renal disease. VPHM 142 Lecture 5 Pharmacology of the Endocrine System Endocrine system by Amoeba sisters Outline: Endocrine system it is composed of organs (glands) or groups of cells that secrete regulatory substances (hormones) directly into the bloodstream Includes regulatory substances that are distributed by diffusion across cell membranes. Feldt-Rasmussen, U., Effraimidis, G., & Klose, M. (2021). The hypothalamus-pituitary-thyroid (HPT)-axis and its role in physiology and pathophysiology of other hypothalamus- pituitary functions. Molecular and Cellular Endocrinology, 525, 111173. https://doi.org/10.1016/j.mce.2021.111173 https://emergencyvet.org/archive-blog/what-is-endocrinology/  Feedback mechanism https://opentextbc.ca/nursingpharmacology/chapter/9-2-endocrine-system-basics/ Applications of endocrine pharmacology A. Treatment of disease/management of clinical signs B. Reproductive physiology Treatment of Disease Common disorders Overproduction/underproduction; Hypersecretion/hyposecretion Receptor malfunction, alteration in tissue responsiveness Disrupted pathways for excretion, feedback mechanisms Genetic anomaly Autoimmune destruction of endocrine tissue Common treatment modalities Surgical intervention Drug treatment Radiotherapy Dietary therapy Hormone replacement therapy  Function: control body’s growth and metabolism Thyroid gland Hormones: inactive thyroxine (T4), active triiodothyronine (T3) Disorder Treatment: thyroid drugs MOA ADR/NOTES Hypothyroidism (common Levothyroxine sodium (optical isomer of Synthetic form of thyroxine polyuria, polydipsia, nervousness, in dogs thyroxine) (T4) to normalize levels panting, tachycardia, weight loss, diarrhea, increase in appetite DOG-Initially, 22–44 micrograms/kg once daily. Adjust the dose after approximately 8 weeks of therapy. CAT-10–20 micrograms/kg daily in divided doses Need for continuous monitoring at 3,6,10,20 weeks then every 3 months and adjust to lowest effective dose Disorder Treatment: Antithyroid drugs MOA ADR/NOTES Hyperthyroidism Carbimazole (prodrug); active form interfere with the synthesis of decrease glomerular filtration (common in cats) is thiamazole) thyroid hormones and must rate with a corresponding be administered at least increase in the plasma-urea and - DOG-10–15 mg daily in divided once daily to control creatinine concentration doses. Increase dose as required to excessive thyroid hormone maintain normal level production CAT- 10–15 mg daily in divided doses for 1 to 3 weeks. Adjust to the lowest effective dose block the release of Iodine, Iodide thyroxine and tri- Not for long-term use because iodothyronine and to reduce effect tends to diminish CAT- by mouth, Aqueous Iodine Oral the vascularity of the thyroid Solution, 3 to 5 drops daily for 7– gland 14 days before thyroidectomy *Propranolol Beta-blocker to address cardiovascular complications CAT- 2.5 to 5.0 mg 3 times daily like tachyarrhythmias and before surgery and for 2 days post- hyperexcitability surgery Reco when there is Radioactive Iodine (131I) intolerance to or owner non- compliance with drug treatment, recurrence following surgery, or surgery is contra-indicated due to the location of the tumor or the condition of the individual patient Need for continuous monitoring at 3,6,10,20 weeks then every 3 months and adjust to lowest effective dose  Function: mediate stress Adrenal gland (suprarenal response, immune response, metabolism, electrolyte gland) balance, and produce sex hormones Disorder Treatment MOA ADR/ NOTES Hypoadrenocorticism Acute case: Glucocorticoid Primary (GCC and MC affected) replacement Addison’s Dx Hydrocortisone sodium succinate 10 mg/kg every 6 hours by intravenous injection or 0.5 mg/kg/hour by IV infusion Dexamethasone sodium phosphate 0.5 to 1.0 mg/kg twice daily by IV injection Fludrocortisone acetate PO, 15–20 micrograms/kg daily. dose may Mineralocorticoid oral synthetic adrenocortical be increased during the first 6 to 18 months replacement steroid with mineralocorticoid of therapy activity *Secondary hypoadrenocorticism (deficiency of ACTH) Disorder Treatment MOA ADR/ NOTES Catabolic disease/critically ill patients Anabolic steroids Synthetic derivatives of Virilism with high Chronic renal failure testosterone to increase doses, hepatopathy, Ethylestrenol testosterone levels (promote possible production of Supportive management of nitrogen retention in very odorous urine in chronic renal failure animals with catabolic cats diseases. They also cause by mouth, 50 micrograms/kg retention of sodium, daily in divided doses if calcium, potassium, chloride, Caution in hepatic possible sulfate, and phosphate impairment; use in stimulate appetite, increase prepubertal animals Nandrolone muscle mass, retain may result in early Supportive management of intracellular water, increase epiphyseal closure; chronic renal failure; some skin thickness, increase operator should wear cases of anemia skeletal mass, close growth gloves when handling plates prematurely, and the product increase production of erythrocytes ) Disorder Treatment MOA ADR/ NOTES Hyperadrenocorticism Mitotane for pituitary cytotoxic drug that selectively Lethargy, anorexia, vomiting, weakness, (Cushing’s syndrome) common dependent destroys the zona fasciculata and diarrhoea, and neurological signs such as in dogs and horses after hyperadrenocorticism zona reticularis of the adrenal ataxia, incoordi- nation, circling, blindness, prolonged administration of Higher dose for adrenal cortex while tending to preserve facial paralysis, and seizures GCC dependent the zona glomerulosa (Use gloves when handling) Lethargy, depression, vomiting, anorexia, hyperkalaemia, diarrhoea, acute pancreatitis, thromboem- bolism, adrenal necrosis, acute Addisonian crisis and corti- competitive inhibitor of 3β- costeroid withdrawal syndrome hydroxysteroid dehydrogenase, Trilostane for pituitary which blocks adrenal synthesis of dependent and adrenal gluco- corticoids, dependent mineralocorticoids, and sex hyperadrenocorticism hormones Disorder Treatment MOA ADR/ NOTES Hyperadrenocorticism (Cushing’s syndrome) Selegiline for pituitary monoamine oxidase inhibitor Not in patients with common in dogs and horses dependent hyperadrenocorticism that inhibits ACTH secretion by concurrent diabetes increasing dopaminergic tone mellitus, pancrreatitis, to the hypothalmic-pituitary cardiac impairment, axis renal impairment, or other severe illness Ketoconazole alternative to reversible inhibitory effect on mitotane in dogs glucocorticoid synthesis while Hepatotoxicity having negligible effects on mineralocorticoid production  Function: (exocrine part produce digestive enzymes; endocrine part regulate blood glucose through Pancreas insulin and glucagon) Disorder Treatment MOA ADR/ NOTES Diabetes mellitus, Diabetes ketosis INSULIN Short-acting Rapid effect lasting to 1-2 hrs Soluble insulin for diabetic emergencies (IV, if given IV IM, SC) Intermediate-acting Effect in 1-2hrs, peak in 6- Insulin Zinc Suspension 12hrs, duration is 18-26 hrs in Isophane insulin (bid) dog Biphasic insulin Long-acting insulin The onset of activity is at 4 to Protamine zinc insulin 6 hours, peak action around Insulin Zinc suspension (crystalline) 14 to 24 hours, and duration of activity of 32 to 36 hours  Pancreas : Disorder Treatment MOA ADR/ NOTES Non-insulin-dependent diabetes mellitus ORAL HYPOGLYCEMIC AGENTS (Sulfonylureas) augment insulin secretion Chlorpropamide therefore are only hypoglycemia, vomiting, effective when some hepatic enzyme induction Glibenclamide residual pancreatic beta- cell activity Glipizide Tolbutamide Hepatopathy, overdosage Causes hypoglycemia, vomiting ( decrease gluconeogenesis hypoglycemia, vomiting, Biguanide) and increase peripheral hepatic enzyme induction Metformin utilization of glucose; also only effective with some residual functioning pancreatic islet cells  Pancreas : Disorder Treatment MOA ADR/ NOTES Acute hypoglycemia 50% glucose IV Provide glucose 1ml/kg Glucagon Hormone that mobilize 20–30 micrograms/kg, IM,SC, IV glycogen stores in the liver non-diuretic Chronic hypoglycemia Prednisolone benzothiadiazine Diazoxide antihyperten- sive drug, which acts primarily by suppressing insulin secretion by the pancreas