ENDOCRINE PHARMACOLOGY

1. ENDOCRINE PHARMACOLOGY

2. Drugs Affecting the Pituitary Gland • Anterior Pituitary Gland • Conditions treated are those of abnormal growth, specifically: * Dwarfism * Acromegaly * Gigantism

3. Anterior Pituitary Drugs • Dwarfism • Somatrem (protropin) • Somatropin (hymatrope) • Both are similar to endogenous growth hormone • Side effects include: * Pain * Redness at injection site

4. Anterior Pituitary Drugs • Acromegaly & Gigantism • Treatment of choice is surgical removal of the tumor • Octreotide (sandostatin) * Synthetic drug similar to somatostatin. * Inhibits the release of growth hormone * Side effects include: bradycardia, diarrhea and stomach distress

5. Posterior Pituitary Drugs • Two posterior hormones are oxytocin and antidiuretic hormone. • Antidiuretic analogues are used to treat diabetes insipidus, nocturnal enuresis (bedwetting). • ADH can cause vasoconstriction and increased BP. • Other names: Vasopressin (pitressin), desmopressin (stimate), lypressin (diapid)

6. Drugs Affecting the Parathyroid & Thyroid Glands • Parathyroid glands regulate calcium levels. • Thyroid gland produces thyroid hormones. Play a role in regulating growth, maturation, and metabolism. • Hyperparathyroidism, results from a tumor and treatment is surgical removal of all or part of the glands.

7. Hypothyroidism • Treatment is aimed at thyroid hormone replacement. • Prototype drug: levothyroxine (Synthroid) • No significant side effects in therapeutic doses. • Overdose could lead to thyrotoxicosis or thyroid storm.

8. Goiter • Not common in developed countries. • AKA Hashimoto’s disease • Chronic autoimmune disease • Treatment is aimed at supplementing the inadequate iodine.

9. Hyperthyroidism • Typically a result of tumors • Most common cause is Grave’s Disease • Treatment is typically surgical removal of all or part of the gland. • Radioactive iodine may be given • Propylthiouracil (PTU), may be given alone or in conjunction with radiation

10. Drugs Affecting the Adrenal Cortex • Adrenal cortex secretes 3 classes of hormones: • Glucocorticoids • Mineralocorticoids • Androgens • Two diseases associated with the adrenal cortex: • Cushing’s Disease • Addison’s disease

11. Cushing’s Disease • Treatment is typically surgical. • Pharmacologic intervention with a antihypertensives: • Spironolactone (Aldactone) • ACE inhibitors – Captopril (Capoten)

12. Addison’s Disease • Therapy is aimed at replacement therapy. • Cortisone (cortistan) and hydrocortisone (solucortef) are the drugs of choice. • Fludrocortisone (florinef acetate) is a mineralocorticoid that is also available for use

13. Drugs Affecting the Pancreas • Insulin Preparations • Three Sources: • Beef • Pork • Human • Differ primarily in their onset and duration of action and incidence of allergic reaction. • Preparations may be short acting, intermediate acting or long acting. (table 9-10)

14. Insulin Preparations • Also classified as nature (regular) or modified. • Natural insulins are used as they occur in nature. • Insulin can also be modified to increase their duration of action, decreasing the number of administrations necessary

15. Insulin Preparations • Modified insulin preparations include: • Neutral Protamine Hagedorn (regular insulin attached to a large protein to delay absorption) • Lente (attached to zinc) • Insulin preparations derived from beef or pork, lentes, may lead to allergic reactions. • Natural human insulin preparations do not have allergic reactions.

16. Oral Hypoglycemic Agents • Used to stimulate insulin secretion from the pancreas is patients with NIDDM. • Four Pharmacologic classes: • Sulfonylureas • Biguanides • Alpha-glucosidase inhibitors • Thiazolidinediones

17. Sulfonylureas • First class of oral hypoglycemics. • Drugs include: • Tolbutamide (Orinase) • Chlorpropamide (Diabinese) • Glipizide (Glucotrol) • Glyburide (Micronase) • Increase insulin secretion from the pancreas. • Side effect: hypoglycemia

18. Biguanide • Metformin (Glucophage) • Decreases glucose synthesis and increases glucose uptake. • Does not stimulate release of insulin. • Side effects: nausea, vomiting, decreased appetite

19. Alpha-glucosidase Inhibitors • Acarbose (precose) • Miglitol (glyset) • Delay carbohydrate metabolism • Side effects: flatulence, cramps, diarrhea, abdominal distention

20. Thiazolidinediones • New class of oral hypoglycemic agents. • Troglitazone (Rezulin) • Promotes tissue response to insulin, making available insulin more effective • Has no major side effects

21. Hyperglycemic Agents • Two agents: • Glucagon • Diazoxide (proglycem) • Increase blood glucose levels.

22. Glucagon • Given IM when IV live is unobtainable • Converts glycogen stores into glucose • Side effects: N/V, allergic reactions (rare)

23. Diazoxide • Inhibits insulin release • Typically used for patient with hyperinsulin secretion from pancreatic tumors • Not indicated for treating diabetes-induced hypoglycemia

24. D50 • Sugar solution given intravenously for acute hypoglycemia. • Primary side effect is local tissue necrosis if infiltration occurs

25. Generic Name: Brand Name: Classification: Dextrose 50% None Hyperglycemic DEXTROSE 50%

26. DEXTROSE 50%Actions • Rapidly increases serum glucose levels • Provides short-term osmotic diuresis

27. DEXTROSE 50%Indications • Coma of unknown origin • Hypoglycemia • Status Epilepticus

28. DEXTROSE 50%Contraindications • Intracranial hemorrhage • Delirium tremens • Use with caution in acute alcoholism - ineffective without thiamine; may make thiamine deficiency more severe • Severe pain (paradoxical excitement may occur) • Know or suspected CVA unless hypoglycemia is documented

29. DEXTROSE 50%Adverse Reactions • Extravasation leads to tissue necrosis

30. DEXTROSE 50%Dose: • Adult: 25-50 g IV bolus • Pediatric: 25% dextrose, 2-4 ml/kg IV bolus

31. DEXTROSE 50%Incompatible Reactions • Sodium bicarbonate • Coumadin

32. DEXTROSE 50%Notes • Onset: Immediate • Peak: Variable • Duration: Variable

33. Generic Name: Brand Name: Classification: Glucose (oral) Glucola, Insta-Glucose Hyperglycemic GLUCOSE

34. GLUCOSEActions • A quickly absorbed form of glucose to increase blood glucose levels

35. GLUCOSEIndications • Hypoglycemia • Conscious patients

36. GLUCOSEContraindications: • Decreased level of consciousness • Nausea/vomiting

37. GLUCOSEPrecautions: • Assure that the airway is patent

38. GLUCOSEDose: • ADULT: sipped slowly by the patient until a feeling of improvement is reported. It is not essential to administer the entire bottle. • PEDIATRIC: Same as adult

39. GLUCOSENotes: • Onset: Minutes • Peak: Variable • Duration: Variable • Glucola - 300 ml bottles • Glucose pastes and gels also available in various forms

40. Generic Name: Brand name: Classification: Glucagon None Hyperglycemic GLUCAGON

41. GLUCAGONActions • Protein secreted by the alpha cells of the pancreas (islets of Langerhans) • Causes a breakdown of stored glycogen to glucose (glycogenesis); increases circulating blood glucose • Unknown mechanism of stabilizing cardiac rhythm in beta-blocker overdose

42. Actions • Positive inotropic and chronotropic • Decreases GI motility and secretions, pancreatic secretions, and blood pressure

43. GLUCAGONIndications • Hypoglycemia • Beta-blocker overdose

44. GLUCAGONContraindications • Hyperglycemia • Known hypersensitivity

45. GLUCAGONAdverse Reactions • Hypersensitivity (protein-based drug) • Nausea/vomiting

46. GLUCAGONPrecautions • Caution with administration to patients with a history of cardiovascular or renal disease

47. GLUCAGONDose • ADULT: 0.5-1.0 mg IV; repeat 1-2 times if no response within 20 minutes • PEDIATRIC: Not used

48. GLUCAGONIncompatible/Reactions • Incompatible in solution with most other substances

49. GLUCAGONNotes • Onset: 1 minute • Peak: 30 minutes • Duration: Variable • Should always be used in conjunction with D5W • Must be reconstituted before administration. Must be used or refrigerated after reconstitution.

50. Generic Name Brand Name Classification Thiamine (Vitamin B) Betalin Vitamin THIAMINE