Medications Affecting the Endocrine System by Linda Self

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Medications Affecting the Endocrine Systemby
Linda Self
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Review

• Endocrine glands
• Hormoneschemical messengers
• Water-soluble, protein derived hormones have
  short duration of action
• Lipid-soluble steroid and thyroid hormones have
  longer mechanism of action
• Endocrine and nervous systems interconnected
• Circadian cycles-ACTH, cortisol and GH

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Major Hormones and Their Functions

• Anterior pituitary hormones-GH, corticotropin,
  TSH, FSH, LH, prolactin
• Posterior pituitary hormones-ADH (vasopressin)
  and oxytocin
• Adrenal cortex hormonescortisol and aldosterone
• Thyroid hormonesT3 (triiodothyronine) and T4
  (thyroxine)

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Hormones cont.

• Parathyroid hormonePTH
• Ovarian hormonesestrogens and progesterone
• Testicular hormonetestosterone
• Placental hormones-chorionic gonadotropin,
  estrogen, progesterone, human placental lactogen

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Non-Endocrine Hormones

• Cholecystokinin
• Erythropoietin
• WBCs which produce cytokines
• Prostaglandins and leukotrienes
• Sometimes neoplasms

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Hormone Pharmacokinetics

• Three mechanisms
• Inactivated by liver and kidney enzymes
• Sometimes conjugated by the liver and excreted in
  bile or urine
• Inactivated at receptor sites by enzymes

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Hormonal Dysfunction

• Hypofunction-Type 1 diabetes, Addisons
• HyperfunctionCushings, Graves, Gigantism

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Hypothalamic and Pituitary Hormones

• Hypothalamus releases inhibitory and releasing
  hormones
• Corticotropin releasing hormonereleased during
  sleep. Increased by vasopressin and decreased by
  somatostatin
• Growth-hormone releasing hormoneaffected by
  dopamine, norepinephrine, epinephrine, GABA,
  acetylcholine and serotonin. Is blocked by
  somatostatin

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Hypothalamic and Pituitary Hormones

• Somatostatin decreases the release of growth
  hormone, CCK, vasoactive intestinal peptide, TRH,
  others
• TRH causes release of TSH
• GRH (gonadotropin releasing hormone) causes
  release of FSH and LH
• Prolactin-releasing factor active during
  lactation
• Prolactin inhibitory factor active at times other
  than lactation

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Anterior Pituitary Hormones

• Two act directly on target organsgrowth hormone
  and prolactin
• Five act indirectly by stimulating target organs
  to produce hormones
• Corticotropin ACTH
• TSH
• FSH

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Anterior Pituitary Hormones

• Luteinizing hormonegonadotropin, maturation and
  rupture of ovarian follicle produces corpus
  luteum in men, affects Leydigs cells and
  testosterone
• Melanocyte stimulating hormone

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Posterior Pituitary Hormones

• Antidiuretic hormonevasopressin, affects renal
  tubules to regulate water balance
• Oxytocinuterine contractions and movement of
  milk from breast glands to nipples

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Hypothalamic Hormones

• Equivalent to GnRH
• Zoladex (goserelin)
• Vantas (histrelin)
• Lupron (leuprolide)
• Synarel (nafarelin)
• Initially stimulate LH and FSH with chronic
  administration, inhibits stimulation
• Results in equivalent to castration in males and
  menopause in women
• Cannot be given orally

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Hypothalamic Hormones

• Octreotide- Sandostatin pharmacologically
  similar to somatostatin
• Use for acromegalyreduces GH and insulin like
  growth factor
• Useful in vasoactive intestinal peptide tumors
• AIDS

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Anterior Pituitary Hormones

• Cortrosyn (cosyntropin)synthetic ACTH is used to
  test for adrenal insufficiency IV or IM
• Humatrope (growth hormone)-for growth failure,
  Turners, renal failure growth retardation.
  Monitor ephiphyses.
• Chorex (HCG)-luteinizing hormone. In men to
  evaluate ability of Leydigs (testosterone) Tx
  hypogonadism in pituitary problems and in
  cryptorchidism

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Anterior Pituitary Hormones

• Ovidrel (HCG alpha) used w/ menotropins to induce
  ovulation
• Pergonal (menotropins)-contains FSH and LH
  obtained from urine of menopausal women
• Somavert (pegvisomant)GH receptor antagonist.
• Follistim (follitropin beta)drug preparation of
  FSH used sequentially with HCG

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Posterior Pituitary Hormones

• DDAVP (desmopressin) and Pitressin
  (vasopressin)ADH used in neurogenic DI,
  hemostasis in Von Willebrands
• Pitocin (oxytocin)-induction of labor, control
  postpartum bleeding

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Abuse of Growth Hormone

• Does not increase muscle mass or strength greater
  than seen with exercise alone
• Not indicated for anti-aging formula
• Adverse effects includeacromegaly, diabetes,
  hypertension, increased risk of cardiovascular
  disease, tumor growth and cancer

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Corticosteroids

• Glucocorticoids or steroids
• Adrenal cortical secretion
• Corticotropin releasing hormonegtgtcorticotropingtgtgtgt
  cortisol
• With stress, increase in norepi, epi and
  cortisol negative feedback system overruled
• Prototype is hydrocortisone
• Mineralocortocoid activity is intermediae in
  hydrocortisone, prednisolone and low in newer
  agents

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Effects of Glucocorticoids

• Increased glucose production
• Decreased cellular use of glucose 2ndary to
  decreased effect of insulin
• Increased breakdown of protein into amino acids
• Decreased rate of protein formation
• Increased breakdown of adipose tissue
• Decreaed inflammatory response by decreasing
  production of inflammatory chemicals, decreases
  numbers of antibodies, s of lymphocytes

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Effects of Glucocorticoids

• Modifies vascular smooth muscle tone increasing
  pressor effects of catecholamines
• Stimulates renal glucocorticoid and
  mineralocorticoid receptors
• Can cause muscle atrophy
• Decrease bone formation, growth and increase bone
  breakdown
• Opens airways
• Stabilize mast cells
• Decrease viscosity of gastric mucous

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Mineralocorticoids

• Class of steroids affecting fluid and electrolyte
  balance
• Conserve sodium and eliminate potassium
• Controlled by kidney function/Renin-angiotensin
  system
• Inadequate secretion causes hyperkalemia,
  hyponatremia and ECF deficit
• Excessive secretion causes hypokalemia,
  hypernatremia and ECF excess

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Adrenal Sex Hormones

• Male androgens
• Female estrogens and progesterone
• Are secreted by both sexes
• Secondary sexual characteristics in men
• Affect libido and hair growth in women excessive
  amounts can cause masculizing effects in women

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Disorders of the Adrenal Cortex

• Addisons Disease
• Secondary adrenocortical insufficiency
• Cushings disease
• Hyperaldosteronism

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Actions of Exogenous Corticosteroids

• Inhibits arachidonic acid metabolism thus
  affecting prostaglandins and leukotrienes
• Stabilizes biologic membranes also affecting
  prostaglandins and leukotrienes
• Inhibits production of interleukin 1, TNF and
  other cytokines
• Impairs phagocytosiscells cant move to injured
  site
• Impairs functioning of lymphocytes
• Inhibit growth of tissues thus delay wound healing

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Indications for use of steroids

• Allergic or hypersensitivity disorders
• Collagen disorders-lupus, scleroderma and
  periarteritis
• Dermatologic
• Endocrine disorders
• Inflammatory bowel disorders
• Neoplastic diseasesuppress lymphocytes
• Neurologic disorders-cerebral edema, myasthenia
  gravis

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Indications cont.

• Asthma and COPD
• Arthritisif three or fewer joint, can give joint
  injections no more than three per year
• Chemotherapy induced emesisstrong anti-emetic
  effect, mechanism unknown. Usually give dose with
  serotonin antagonist and Reglan.

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Contraindications to Use

• Systemic fungal infections
• Hypersensitivity
• Those at risk for infections
• Diabetes mellitus (be cautious)
• Peptic ulcer disease
• Heart failure
• Renal insufficiency (can accumulate and cause s/s
  of hypercorticism)

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Steroid Preparations

• Beconase-beclamethasone nasally
• Nasonex (mometasone)
• Celestone-(betamethasone) orally
• Decadron (dexamethasone) po or IM
• HydrocortisoneIV, IM, rectally
• Solu-Medrol (methylprednisolone)po, IM, IV
• Kenalog(triamcinolone)IM or topical
• Florinef (fludrocortisone)mineralocorticoid

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Caution

• Daily administration of 15-20mg of hydrocortisone
  or its equivalent for 2 weeks suppresses the HPA
  axis
• MUST taper down

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Thyroid and Antithyroid Drugs

• Thyroid produces three hormones thyroxine,
  triidothyronine and calcitonin
• T3 more potent but with a shorter duration of
  action
• Production of thyroid hormones is dependent on
  iodine and tyrosine (needed to form
  thyroglobulin)
• Control rate of cellular metabolism, linear
  growth, brain function, dentition, bone
  development and neural development

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Physiologic Effects of Thyroid Hormones

• Inhibition of pituitary release of TSH
• Increassesd fat metabolism
• Increased carbohydrate metabolism
• Increased heart rate, force of contraction and
  cardiac output
• Increase rate of cellular metabolism and oxygen
  consumption

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Hypothyroidism

• Common causes include Hashimotos thyroiditis,
  secondary to treatment for hyperthyroidism
• Treatment with amiodarone, lithium or iodine
  preparations
• Congenitalcretinism
• Myxedema can progress to coma

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Signs and Symptoms of hypothyroidism

• Bruising
• Decreased cardiac output
• Decreased heart rate
• Cardiomegaly
• ASHD
• Apathy, lethargy
• Forgetfulness
• Drowsiness
• Cold intolerance
• Constipation
• Fatigue
• Puffiness
• Increased susceptibility to infections
• Increased sensitivity to narcotics, barbiturates,
  anesthetics

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Hyperthyroidism

• Excessive production of thyroid hormone
• Associated with Graves Disease, nodular goiter,
  thyroiditis, overtreatment with thyroid drugs,
  pituitary adenoma or thyroid cancer
• Subclinicalreduced TSH but normal T3/T4
• Can result in osteoporosis
• Thyroid storm aka thyrotoxicosis
• Have been reported cases of iodine-induced
  hyperthyroidism

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Signs and Symptoms of Hyperthyroidism

• Tachycardia
• Increased cardiac output
• Increased BP
• Dysrhythmias
• Heart failure
• Nervousness, restlessness, insomnia
• Heat intolerance
• Weight loss
• Diarrhea
• Weakness
• Tremors
• Amenorrhea
• Increased susceptibility to infection
• exophthalmos

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Drugs for Hypothyroidism

• Prototype and drug of choice is Synthroid,
  Levothroid (levothyroxine)
• Maximum absorption if taken on empty stomach
• Is T4
• TSH (0.5 to 4.2 microunits/L) desired level
• Goal is euthyroid with TSH level
• Most drugs given will have prolonged effect
• Lifelong therapy is indicated

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Drugs for Hyperthyroidism

• Thioamide derivatives-- Propylthiouracil and
  methimazole. Used before radioactive iodine
  therapy
• Results may not be apparent for 3 months or
  longer

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Combination therapy before Surgery

• Thioamide preparation to achieve euthyroid state
• Then Iodine preparationsLugols and SSKI
• Iodine preparations may be used to reduce size
  and vascularity of thyroid before surgery
• Can cause goiter, hyperthyroidism, benefits are
  temporary
• Radioactive iodine cannot be used effectively for
  prolonged time in those who have received iodine
  preparations (insufficient uptake thereafter)
• OK TO GIVE THIOAMIDE THEN IODINE PREPARATION BUT
  NOT IODINE THEN THIOAMIDE

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Special Populations

• Thyroid disorders change metabolism of other
  drugs
• Children w/congenital hypothyroidism, tx should
  be started within 6 weeks of birth
• Drug of choice is levothyroxine
• Monitor ht. and wt.
• If hyperthyroid, can use PTU or methimazole,
  discourage radioactive iodine in children

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Special Populations cont.

• s/s of thyroid disorders may mimic other
  disorders in older adults
• Thorough PE and diagnostic workup
• Levothyroxine is appropriate
• Start with small doses, may increase in small
  increments monthly
• Monitor vitals closely
• For hyperthyroidism, use PTU or methimazole. May
  use radioactive iodine.

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Special Populations

• Thyrotoxicosis manage in intensive care