ENDOCRINES

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ENDOCRINES

• Thyroglobulin is a large protein molecule
  synthesized by the thyroid gland Tyrosine in
  this molecule is iodinated and coupled by
  peroxidase enzyme
• Tetra-iodothyronine is T4
• Tri-iodothyronine T3 is the active molecule

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THYROID HORMONES

• ACTIONS
• Regulates growth and development
• BMR
• CHO utilization
• Lipolytic action
• Reduces plasma cholesterol
• Negative feed back
• CVS stimulant
• Necessary for normal GH secretion

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Thyrotoxicosis Treatment

• Class
• Propylthiouracil
• Methimazole
• Lugols iodine (5 iodine/10 K iodide)
• Beta Blockers
• Propranalol
• Radioactive iodine

• MOA
• Peroxidase inhibitor prevents peripheral
  conversion of T4 to T3
• Side effects Pruritus/ Dizziness/
  Leukopenia/Jaundice
• Dosage15-60mg/day
• Inhibits release of T3 and T4
• Reduces T3 activity on target organs
• Rapidly concentrates in the gland and destroys
  the thyroxine producing cells

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THYROID HORMONES

• Indications
• Myxedema therapy
• Prevents cretinism
• Goiter management
• Thyroid tabletsgland extracts-60 mg
• Levothuyroxine sodium (T4)-100 mcg
• Liothyronine (T3)-25 mcg
• Adverse effects Cardiac side effects

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Adrenal Glands

• Adrenal Cortex
• Steroid hormones derived from cholesterol - "long
  term response
• Adrenal Medulla
• Epinephrine - Neuronal release due to stress
  "short term response"

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CHRONO BIOLOGICAL RHYTHMS

• CIRCADIAN
• 24 HOUR CYCLE
• DARK / LIGHT
• SLEEP / AWAKE
• PATTERNS
• PEAK HOURS OF
• COPRTISOL SECRETIONS
• 4 AM - 8 AM

• ULTRADIAN
• 4 - 8 SECRETORY BURSTS IN 24 HOUR PERIOD
• TRIGGERED BY CRH AND ACTH BURSTS
• CLUSTERED AT PEAK CIRCADIAN TIMES

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GLUCOCORTICOIDSCORTISONE

• Gluco - regulate blood glucose, CHO and Protein
  metabolism
• Cortisol (hydrocortisone)
• 10 - 25 mg / day
• Cortisone
• 0.5 - 2 mg / day
• Corticosterone
• 30 - 150 mcg / day

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GLUCOCORTICOIDS FUNCTIONS

• Increase liver glycogen stores
• Increase gluocneogenesis
• Increase lipolysis
• CNS mood effects Depression/Euphoria
• Assists CVS functions potentiates NE
• Increased hemoglobin synthesis
• Inhibits prostaglandins and leukotrenes

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Glucocorticoid functions

• Anti-inflammatory and Anti-allergic
• Suppress leukocyte migration
• Stabilize cell membranes
• Decrease fibroblast activity
• Reverse capillary permeability induced by
  histamine release
• Suppress immune response by inhibiting antibody
  synthesis
• Inhibits cell growth and cell division

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AVOID Pituitary-Adrenal Axis suppression

• Once suppressed it will take more than 1 year
  for normal function to return
• lt25mg of prednisolone /day taken at 8 am for lt
  10-15 days usually does not suppress
• To minimize suppression taper of the dose rather
  than stopping abruptly

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Mineralocorticoids

• RENAL
• electrolyte and water excretion
• Na, Phosphate, Ca, Bicarbonate Retention
• Reduction of Serum K

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Aldostrone

• Secreted by adrenal cortex
• Na tubular reabsorption
• serum levels of Na
• K and H ions excretion by kidneys

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Fludrocrotisone Florinef

• Acts on distal tubule -reabsorption of Na and K
• Side effects-Headaches/HTN
• Indication
• Addison' s disease

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Anti Adrenals

• Aminoglutehemide
• MOA- prevents enzymatic action to convert
  cholesterol to steroids
• Inhibits peripheral tissue conversion of
  anjdrogens to estrogens
• (useful in breast cancer treatment)
• Side effects ataxia, dizziness, nausea,
  vomiting,rash, jaundice, bruising
• Trilostane another compound which blocks steroid
  synthesis
• Used in Cushing's syndrome

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Preparations

• Systemic
• Topical
• Inhaled varieties
• Beclomethasone
• Budesonide
• Flunisolide
• Risk of
• oropharyngeal candidiasis
• dysphonia

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Steroid Indications

• Addisons
• Rheumatoid arthritis
• Rheumatic carditis
• Nephrotic syndrome
• SLE
• Severe allergy

• Ocular
• inflammation
• Skin
• IBD
• Cerebral edema
• Asthma
• Rhinitis

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STEROID SIDE EFFECTS

• PITUITARY SUPPRESSION
• RISK OF INFECTION
• PEPTIC ULCERATION
• MYOPATHY
• STEROID
• PSYCHOSIS

• IN CHILDREN
• GROWTH ARREST SUBCAPSULAR CATARACTS
• OSTEOPOROSIS
• INHIBITS
• OSTEOBLAST FORMATION
• INTESTINAL Ca ABSORPTION
• HYPERGLYCEMIA

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PANCREAS / DIABETES

• 16 million Americans and increasing
• 7th leading cause of death
• Blindness/ESRD/Limb amputations
• Insulin(Beta cells)
• Glycogenesis
• Glucagon(Alpha cells) Glycogenolysis

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Lack of insulin causes

• Reduced rate of glucose transport across cell
  membranes
• Reduced enzyme activity in converting glucose to
  glycogen
• Hyperlipemia, ketonemia, Acidosis due to
  increased lipase activity
• Leads to increased glucagon activity causing
  increased proteolysis and uremia

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• TYPE I / IDD
• lt 30 YEARS AGE
• NONOBESE
• 10 OF PATIENTS
• LOW / ABSENT INSULIN LEVELS
• REQUIRES INSULIN
• NORMAL RECEPTORS
• DKA

• TYPE II / NIDDM
• gt 35 YEARS AGE
• OBESE
• 90 OF PATUIENTS
• NORMAL / HIGH INSULIN RESISTANT
• ORAL AGENTS /
• DIET
• DECREASED / DEFECTIVE RECPETORS
• NON KETOTIC

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TYPES OF INSULIN

• SOURCE- BEEF / PORK / HUMAN
• PORK LESS ALLERGENIC THAN BEEF
• RAPID ACTING
• INTERMEDIATE ACTING
• LONG ACTING
• COMBINATIONS

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Emergencies in Diabetes

• HYPOGLYCEMIA
• INSULIN SHOCK
• SWEATING
• ANXIETY
• BLURRED VISION
• WEAKNESS
• HEADACHE
• DROWSINESS

• HYPERGLYCEMIA
• DIABETIC COMA
• RED DRY SKIN
• FRUITY ODOR
• ABD. PAIN NAUSEA VOMITING
• RAPID DEEP BREATHING

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ORAL ANTI DIABETIC AGENTS

• SULFONYLUREAS-
• Chlorpropamide / Glipizide / Glyburide
• BIGUANIDES-
• Metformin
• ALPHA GLUCOSIDASE INHIBITOR-
• Acarbose

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DRUGS TO BLOOD SUGAR

• GLUCAGON -
• 0.5-1Mg IV/IM/SC prn every 20 mins
• Contraindication pheochromocytoma/insulinoma
• DIAZOXIDE - 1 mg/kg every 8hrs (3-8mg/kg daily)
• contraindication CHF/HTN
• GLUCOSE- 10-20 gm oral or
• 50 cc 50 IV

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REPRODUCTIVEHORMONES

• FSH -
• OVUM AND SPERNATOGENSIS
• LH (ICSH)- SEX HORMONES PRODUCTION
• ANDROGENS
• ESTROGENS
• PROGESTOGENS

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FEMALE HORMONES

• GnRH-Gonadorelin Factrel- LH/ICSH release - a
  diagnostic agent for hypogonadism
• Histrelin - synthetic GnRH agonist
• Indication-10 mcg/kg/ sc
• Precocious puberty - decreases
  LH/FSH/estrogen/testosterone levels
• AE vaginal dryness/breast edema/hot flashes

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FEMALE HORMONES

• CHORIONIC GnH in decreased LH-
• Undescended testes
• Secondary male sex characteristics
• Male and female infertility
• AEEdema/Depression/Gynecomastia/
  Aggression/Arterial thromboembolism
• 1000-4000 units IM thrice weekly

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FEMALE HORMONES

• MENOTROPINS (HMG)- FSH and LH activity
• from urine of post menopausal women
• Female infertility
• Male infertility
• AE wt gain/ edema/ oligurea / gynecomastia
• 75 units IM daily x 7 days

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FEMALE HORMONES

• Estrogens atrophic vaginitis/ abnormal uterine
  bleeding/
• Post menopausal states/ Osteoporosis
• Metastatic breast cancer
• AEgastric/ltlibido/edema/
• breast pain/ thrombophlebitis

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FEMALE HORMONES

• Progesterone endometrial hormone
• complement estrogen effects on uterus/ suppresses
  ovulation/
• relaxes uterine smooth muscle/
• Indications- dysmenorrhea/endometriosis/
• AE wt gain/ edema/breast pain
• Contraindication breast cancer/
• liver disease/thromboembolism

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Oral Contraceptives

• Low dose E P combination benefits
• lt CVS effects
• of MI in smokers and gt35 years of age
• ltrisk of stroke and thromboembolism
• ltectopic pregnancies
• ltovarain cysts/ ovarain cancer/ endometrial
  cancer
• gtrisk of cervical cancer/liver cancer/
• breast cancer

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Oral Contraceptives

• Monophasic- fixed ratio x 21 days
• Biphasic- different progestin levels- low for
  7-10 days/high for next 11-14 days
• Triphasic- simulates normal cycle-
• constant low estrogen level/ progestin increased
  3 times during 21 days
• Longacting- progestin only -
• Norplant / Depo-Provera/

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Oral Contraceptives

• SELECTION of Right ONE
• SAFe(18-35)-
• Low E(30-35mcg)/Low P /NO SMOKING
• Smokers and gt35-
• CVA side effects
• Use other methods

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Oral Contraceptives

• If Cancer
• (Breast, Uterus, Cervix, Liver)
• CVA, CAD, Thrombosis
• Oral contraception is contraindicated
• Use other methods

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Oral Contraceptives

• Liver impaired, Smokers gt35, CVA/HTN/Migraine-
• Use progestin only minipill
• (lt effective)
• PROBLEMS
• Acne, Oily skin, Wt. Gain Breakthrough bleeding

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Drugs for infertility

• CLOMIPHENE-
• ESTROGEN COMPETITOR
• FSH/LH SECRETION
• CORPUS LUTEUM
• AEHEADACHE /NAUSEA/ VOMITING/DEPRESSION/
• OVARIAN CYST /FIBROIDS
• HEPATOTOXIC
• UROFOLLITROPIN FSH

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Labor and Delivery

• OXYTOCICS-Induce stimulation of uterine smooth
  muscle contractions and spontaneous labor.
  ERGOT/OXYTOCIN
• TOCOLYTICS-
• Inhibit premature labor and suppress lactation.
  TERBUTALINE / RITODRINE

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OXYTOCICS and TOCOLYTICS

• Oxytocin Syntocinon
• Acts on pregnant uterus
• Impedes uterine blood flow
• Labor/PPH/ Lactation
• 0.5-2mU/min
• IV 30-60 mins
• AENausea/vomiting/
• tachycardia

• Ritodrine/Terbutaliune
• B2 adrenergic agonist -inhibits uterine
  contraction
• To prevent unwanted labor/premature labor after
  20 weeks
• Heart rate/BP
• Trembling tremors
• 50-100 mcg/min IV(150-350mcg) then oral

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Male Hormones

• TESTOSTERONE
• 25-50 mg IM thrice weekly
• Androgen deficiency/Delayed male puberty
• Breast cancer
• Anemia
• AE abdominal pain/ headaches/jaundice/
  edema/breast swelling/ frequent erections
• Females oily skin/ deep voice/ hirsuitism/ male
  type baldness/ enlarged clitoris/
• irregular menses

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Enlarged Prostate

• Benign Hytrin is used
• Finasteride- inhibits 5 alpha reductase and
  prevents testosterone conversion to
  dihydrotestosterone which causes prostatic growth
• AE Gynecomastia, back pain, diarrhea, ltlibido,
  impotency,
• lt ejaculation qty

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Altering sexual behavior

• HTN-
• aldomet,reserpin, thiazides
• Antihistamines- Benadryl
• Psychotropics- Chlorpromazine, valium,
  haloperidol, imipramine, alcohol

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Altering sexual behavior

• Amylnitrite-male orgasm
• Viagra- Nitric oxide release
• cGM P ltphophodiesterase in penis
• AE caution with cardiac patients on nitrates
• Causes hypotension, headache,
• nasal congestion, flushing, flu syndrome,
  angina, tachycardia, priapism , Peyronies
  disease