ENDOCRINE PHARMACOLOGY

Drugs Affecting the Pituitary GlandAnterior Pituitary GlandConditions treated are those of abnormal growth, specifically:* Dwarfism* Acromegaly* Gigantism

Anterior Pituitary DrugsDwarfismSomatrem (protropin)Somatropin (hymatrope)Both are similar to endogenous growth hormoneSide effects include:* Pain* Redness at injection site

Anterior Pituitary DrugsAcromegaly & GigantismTreatment of choice is surgical removal of the tumorOctreotide (sandostatin)* Synthetic drug similar to somatostatin.* Inhibits the release of growth hormone* Side effects include: bradycardia, diarrhea and stomach distress

Posterior Pituitary DrugsTwo 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)

Drugs Affecting the Parathyroid & Thyroid GlandsParathyroid 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.

HypothyroidismTreatment 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.

GoiterNot common in developed countries.AKA Hashimotos diseaseChronic autoimmune diseaseTreatment is aimed at supplementing the inadequate iodine.

HyperthyroidismTypically a result of tumorsMost common cause is Graves DiseaseTreatment is typically surgical removal of all or part of the gland.Radioactive iodine may be givenPropylthiouracil (PTU), may be given alone or in conjunction with radiation

Drugs Affecting the Adrenal CortexAdrenal cortex secretes 3 classes of hormones:GlucocorticoidsMineralocorticoidsAndrogensTwo diseases associated with the adrenal cortex:Cushings DiseaseAddisons disease

Cushings DiseaseTreatment is typically surgical.Pharmacologic intervention with a antihypertensives:Spironolactone (Aldactone)ACE inhibitors Captopril (Capoten)

Addisons DiseaseTherapy 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

Drugs Affecting the PancreasInsulin PreparationsThree Sources:Beef PorkHumanDiffer 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)

Insulin PreparationsAlso 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

Insulin PreparationsModified 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.

Oral Hypoglycemic AgentsUsed to stimulate insulin secretion from the pancreas is patients with NIDDM.Four Pharmacologic classes:SulfonylureasBiguanidesAlpha-glucosidase inhibitorsThiazolidinediones

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

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

Alpha-glucosidase InhibitorsAcarbose (precose)Miglitol (glyset)Delay carbohydrate metabolismSide effects: flatulence, cramps, diarrhea, abdominal distention

ThiazolidinedionesNew class of oral hypoglycemic agents.Troglitazone (Rezulin)Promotes tissue response to insulin, making available insulin more effectiveHas no major side effects

Hyperglycemic AgentsTwo agents:GlucagonDiazoxide (proglycem)Increase blood glucose levels.

GlucagonGiven IM when IV live is unobtainableConverts glycogen stores into glucoseSide effects: N/V, allergic reactions (rare)

Diazoxide Inhibits insulin release Typically used for patient with hyperinsulin secretion from pancreatic tumorsNot indicated for treating diabetes-induced hypoglycemia

D50Sugar solution given intravenously for acute hypoglycemia.Primary side effect is local tissue necrosis if infiltration occurs

DEXTROSE 50%Generic Name:

Brand Name:

Classification:Dextrose 50%

None

Hyperglycemic

DEXTROSE 50%ActionsRapidly increases serum glucose levelsProvides short-term osmotic diuresis

DEXTROSE 50%IndicationsComa of unknown originHypoglycemiaStatus Epilepticus

DEXTROSE 50%ContraindicationsIntracranial hemorrhageDelirium tremensUse with caution in acute alcoholism - ineffective without thiamine; may make thiamine deficiency more severeSevere pain (paradoxical excitement may occur)Know or suspected CVA unless hypoglycemia is documented

DEXTROSE 50%Adverse ReactionsExtravasation leads to tissue necrosis

DEXTROSE 50%Dose:Adult:25-50 g IV bolus

Pediatric:25% dextrose, 2-4 ml/kg IV bolus

DEXTROSE 50%Incompatible ReactionsSodium bicarbonateCoumadin

DEXTROSE 50%NotesOnset:ImmediatePeak:VariableDuration:Variable

GLUCOSEGeneric Name:

Brand Name:

Classification:Glucose (oral)

Glucola, Insta-Glucose

Hyperglycemic

GLUCOSEActionsA quickly absorbed form of glucose to increase blood glucose levels

GLUCOSEIndicationsHypoglycemiaConscious patients

GLUCOSEContraindications:Decreased level of consciousnessNausea/vomiting

GLUCOSEPrecautions:Assure that the airway is patent

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

GLUCOSENotes:Onset:MinutesPeak:VariableDuration:Variable

Glucola - 300 ml bottlesGlucose pastes and gels also available in various forms

GLUCAGONGeneric Name:

Brand name:

Classification:Glucagon

None

Hyperglycemic

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

ActionsPositive inotropic and chronotropicDecreases GI motility and secretions, pancreatic secretions, and blood pressure

GLUCAGONIndicationsHypoglycemiaBeta-blocker overdose

GLUCAGONContraindicationsHyperglycemiaKnown hypersensitivity

GLUCAGONAdverse ReactionsHypersensitivity (protein-based drug)Nausea/vomiting

GLUCAGONPrecautionsCaution with administration to patients with a history of cardiovascular or renal disease

GLUCAGONDoseADULT: 0.5-1.0 mg IV; repeat 1-2 times if no response within 20 minutesPEDIATRIC: Not used

GLUCAGONIncompatible/ReactionsIncompatible in solution with most other substances

GLUCAGONNotesOnset:1 minutePeak:30 minutesDuration:VariableShould always be used in conjunction with D5WMust be reconstituted before administration. Must be used or refrigerated after reconstitution.

THIAMINEGeneric Name

Brand Name

ClassificationThiamine (Vitamin B)

Betalin

Vitamin

THIAMINEActionsRequired for carbohydrate metabolismDeficiency leads to anemia, polyneuritis, Wernickes encephalopathy, cardiomyopathyAdministration may reverse symptoms of deficiency, but effects are dependent upon duration of illness and severity of disease

THIAMINEIndicationsComa of unknown origin, especially if alcohol may be involvedDelirium tremensOther thiamine deficiency syndromes

THIAMINEContraindicationsKnown hypersensitivity

THIAMINEAdverse ReactionsRare

THIAMINEDoseADULT: 100 mgPEDIATRIC: Rarely used

THIAMINEIncompatible/ReactionsAlkaline solutionsBarbituratesBicarbonateCephalosporinsOther antibiotics

THIAMINENotesOnset:HoursPeak:3-5 daysDuration:UnavailableAny comatose patient, especially those who are suspected to be alcoholic, should receive IV thiamine prior to the administration of D50 or Narcan

INSULINGeneric Name:

Brand Name:

Classification:Insulin

Regular Insulin, Humulin RAntidiabetic

INSULINActionsProtein secreted by beta cells of the Islets of LangerhansResponsible for promoting the uptake of glucose by the cells (muscle, cardiac, CNS, and all other tissue)Necessary for carbohydrate, fat and protein metabolismConverts glycogen to fat

ActionsAllows glucose storage in the liverPromotes fat and protein synthesis while antagonizing fat breakdownProduces intracellular shift of potassium and magnesium to reduce elevated serum levels of those electrolytes

INSULINIndicationsRarely used in the field - blood glucose levels are necessary before administering in an emergency situationIn-hospital use: diabetic ketoacidosis or other hyperglycemic stateHyperkalemia

INSULINContraindicationsHypoglycemiaHypokalemia

INSULINAdverse ReactionsHypokalemiaHypoglycemia

INSULINDoseADULT: Adjusted to relative blood sugar levels. Standard dose for diabetic coma is 10-25 units Regular Insulin IV bolusPEDIATRIC: Adjusted to relative blood sugar levels

INSULINIncompatible/ReactionsIncompatible in solution with all other drugsAntagonizes actions of epinephrine, steroids, estrogens, thyroid hormones, diazoxide, dilantin

INSULINNotesONSETRegular:NPH/Lente:Ultralente:PEAKRegular:NPH/Lente:Ultralente:

MinutesMinutesMinutes

1 hour2 hours6 hours

INSULINNotesDURATIONRegularNPH/LenteUltralente

12 hours24 hours36 hours

INSULINNotesUsually refrigeratedOral hypoglycemics, such as Orinase, Diabinese and Dymelor, are not substitutes for insulin, they stimulate the release of insulin from a sluggish pancreas