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Hypoglycemic agent and Thyroid hormone lecture notes-Dr.Jibachha Sah
- 1. Welcome to MY Lecturer Notes www.jibachhavet.com 1 AUTONOMIC AND SYSTEMIC PHARMACOLOGY SIXTH SEMESTER Hypoglycemic agents and thyroid hormones DR.JIBACHHA SAH, LECTURER, M.V.Sc (Veterinary Pharmacology) College of Veterinary Science Nepal polytechnic, Bhojard, Chitwan, Nepal Email:jibachhashah@gmail.com;Mobile:00977-9845024121
- 3. 1 INTRODUCTION Drugs used in diabetes treat Diabetes mellitus by lowering the glucose level in blood With the exceptions of insulin, exenatide, liraglutide and pramlintide all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents
- 4. 1 2 3 4 5 6 Table of Contents Introduction Hypoglycemic agent / Thyroid hormone Administration & dosage Route of drug administration Classification Hypoglycemic agent and thyroid hormone Mechanism of action Pharmacological effect after drug bind in body Pharmacokinetic Movement of drugs within the body. Availability Form of drugs www.jibachhavet.com 4
- 5. Anti-diabetic medication Oral hypoglycemic agent Type 1 diabetes (T1D), also known as juvenile diabetes, is a form of diabetes in which very little or no insulin is produced by the pancreas Type -1 diabetes Diabetes mellitus type -1 Juvenile diabetes, Insulin dependent diabetes www.jibachhavet.com 5
- 6. www.jibachhavet.com 6 The management of type 2 diabetes relies on a series of changes in diet and physical activity with the purpose of reducing blood sugar levels to normal ranges and increasing insulin sensitivity.Biguanides such as metformin are also used as part of the treatment along with insulin therapy. Type 2 diabetes This form of diabetes usually are a combination of insulin resistance and impaired insulin secretion
- 7. Pancreas Its head section connects to the first part of the small intestine (duodenum). Anatomically divided into……. Head Neck Body and tail When blood glucose levels are low, alpha cells secrete glucagon, which increases blood glucose levels. When blood glucose levels are high beta cells secrete insulin to decrease glucose in blood. Delta cells in the islet also secrete somatostatin which decreases the release of insulin and glucose. www.jibachhavet.com
- 8. Diabetes in Dogs Diabetes is a chronic disease that can affect dogs and cats and other animals (including apes, pigs, and horses) as well as humans. • Insulin-deficiency diabetes—This is when the dog’s body isn’t producing enough insulin. This is the most common type of diabetes in dogs. • Insulin-resistance diabetes—This is when the pancreas is producing some insulin, but the dog’s body isn’t utilizing the insulin as it should. This type of diabetes can especially occur in older, obese dogs. www.jibachhavet.com 8
- 9. Symptoms Excessive thirst Increased urination Weight loss. The dog may drink frequently and empty the water bowl more often. Increased urination (and increased thirst) happens because the body is trying to get rid of excess sugar by sending it out through urine. The dog can lose weight despite eating normal portions. www.jibachhavet.com 9
- 10. Other & advance stage symptoms are Loss of appetite, Lack of energy, Depressed attitude, vomiting Ketoacidosis a potentially life-threatening acute condition that can be accompanied by rapid breathing, dehydration, lethargy, vomiting, or sweet-smelling breath. www.jibachhavet.com 10
- 12. Mechanism of action of sulphonyl ureas (first generation) Stimulate the release of insulin from pancreatic B-cells (can only be used in patients with some B-cell function) ATP-dependent potassium channels (on B-cells) contain the sulfonylurea receptor – binding inhibits these channels and alters the resting potential of the cell – this leads to calcium moving into the cell and insulin being secreted www.jibachhavet.com 12
- 14. www.jibachhavet.com 14 CLASSIFICATION OF ORAL HYPOGLYCEMIC AGENTS 1.Sulphonyl ureas – first generation (tolbutamide, chlorpropamide); second generation – (glibenglamide, glipizide, gliclazide, glimiperide) 2.Biguanides – metformin 3Meglitinides – repaglinide, nateglinide 4.Thiazolidine diones – rosiglitazone, pioglitazone 5.Alpha glucosidase inhibitors – acarbose, miglitol 6.Dipeptidyl peptidase-4 (DPP-4) inhibitors – sitagliptin 7.Glucagon like peptide (GLP-1) analogue – exenatide
- 15. Side effect www.jibachhavet.com Hypoglycemia Most common side effect; occurs more often in long-acting sulfs (chloropropamide glyburide and glimepiride) 15
- 18. Thyroid hormones www.jibachhavet.com 18 Thyroid hormones are two hormones produced and released by the thyroid gland, namely triiodothyronine (T3) and thyroxine (T4). FUNCTION The thyroid hormones act on nearly every cell in the body. They act to increase the basal metabolic rate, affect protein synthesis, help regulate long bone growth (synergy with growth hormone) and neural maturation, and increase the body's sensitivity to catecholamines (such as adrenaline) by permissiveness. These hormones also regulate protein, fat, and carbohydrate metabolism, affecting how human cells use energetic compounds. This plays an important role in the hibernation cycles of mammals and the moulting behaviour of birds. One effect of administering the thyronamines is a severe drop in body temperature.
- 20. Causes of Primary Hypothyroidism in dog www.jibachhavet.com 20 Diagnosis: Combination of elevated serum TSH and decreased T4 or fT4 has a specificity of 98% for diagnosis of hypothyroidism. Serum TSH concentration greater than 0.6 ng/ml is consistent with hypothyroidism. T3 is a poor gauge of thyroid gland function and should not be used to diagnose hypothyroidism.
- 21. Production www.jibachhavet.com 21 Thyroid hormones (T4 and T3) are produced by the follicular cells of the thyroid gland and are regulated by TSH made by the thyrotropes of the anterior pituitary gland.
- 22. Mechanism of action www.jibachhavet.com 22 The thyroid hormones function via a well-studied set of nuclear receptors, termed the thyroid hormone receptors. These receptors, together with corepressor molecules, bind DNA regions called thyroid hormone response elements (TREs) near genes. This receptor-corepressor-DNA complex can block gene transcription. Triiodothyronine (T3), which is the active form of thyroxine(T4), goes on to bind to receptors.
- 23. Related diseases www.jibachhavet.com 23 Both excess and deficiency of thyroxine can cause disorders.
- 33. Myxedema www.jibachhavet.com 33 Severe form of hypothyroidism Myxedema occurs because of severe hypothyroidism that is not diagnosed or is not treated successfully. When thyroid hormone levels become extremely low, a person may experience symptoms such as drowsiness, confusion, and hypothermia, as well as changes to the skin.
- 34. Myxedema One life-threatening complication of hypothyroidism is myxedema coma. This complication is also known as myxedema crisis www.jibachhavet.com
- 35. Goiter in animal www.jibachhavet.com Hypothyroidism Goiter in calf Hoffman's syndrome(proximal weakness and pseudohypertrophy of muscles.), hypothyroidism, myopathy Goiter in horse laminitis, a grave hoof condition; anhidrosis, (an inability to sweat;) tying up, or exertional rhabdomyolysis; fertility problems Hypothyroidism in dog Excessive weight loss Increased appetite Frequent urination and increased thirst, Vomiting Hypothyroidism in dog Hyperthyroidism is rarer in dogs than hypothyroidism, and it usually results from an aggressive thyroid tumor. Symptoms Symptoms 35 Symptoms
- 36. Symptoms www.jibachhavet.com 36 Myxedema is a serious condition. A person with myxedema may notice swelling in their face, legs, or tongue. Their skin may also become dry and pale. Other symptoms of severe hypothyroidism can include: ●intolerance to cold ● tiredness ● weight gain ● drooping eye ● Shock ● decreased breathing ● Confusion ● apathy or depression ● Psychosis ● constipation ● coarse hair ● goiter ● low energy ● seizures ● reduced mobility ● coma ● low body temperature
- 37. Medical use Both T3 and T4 are used to treat thyroid hormone deficiency (hypothyroidism). They are both absorbed well by the gut, so can be given orally. Levothyroxine is the pharmaceutical name of the manufactured version of T4, which is metabolized more slowly than T3 and hence usually only needs once-daily administration www.jibachhavet.com 37
- 38. Antithyroid agent www.jibachhavet.com 38 The main antithyroid drugs are carbimazole (in the UK), methimazole (in the US), and propylthiouracil/PTU. A less common antithyroid agent is potassium perchlorate. Adverse effects The most common side effects are rash and peripheral neuritis. These drugs also cross the placenta and are secreted in breast milk. Lugol's iodine is used to block hormone synthesis before surgery. An antithyroid agent is a hormone antagonist acting upon thyroid hormones.
- 43. Treatment in dog www.jibachhavet.com 43 Surgical excision of tumor. External beam radiation therapy. Chemotherapy.