endocrines thyroglobulin is a large protein molecule synthesized by the thyroid gland: tyrosine in...
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ENDOCRINESENDOCRINES
• Thyroglobulin is a large protein Thyroglobulin is a large protein molecule synthesized by the molecule synthesized by the thyroid gland: Tyrosine in this thyroid gland: Tyrosine in this molecule is iodinated and molecule is iodinated and coupled by peroxidase enzymecoupled by peroxidase enzyme
• Tetra-iodothyronine is T4Tetra-iodothyronine is T4• Tri-iodothyronine T3 is the active Tri-iodothyronine T3 is the active
moleculemolecule
THYROID HORMONESTHYROID HORMONES
• ACTIONS ACTIONS • Regulates growth and developmentRegulates growth and development• ^BMR^BMR• ^CHO utilization^CHO utilization• ^ Lipolytic action^ Lipolytic action• Reduces plasma cholesterolReduces plasma cholesterol• Negative feed backNegative feed back• CVS stimulantCVS stimulant• Necessary for normal GH secretionNecessary for normal GH secretion
Thyrotoxicosis: Thyrotoxicosis: TreatmentTreatment
• ClassClass• PropylthiouracilPropylthiouracil• MethimazoleMethimazole
• Lugol’s iodine (5% Lugol’s iodine (5% iodine/10% K iodide)iodine/10% K iodide)
• Beta Blockers:Beta Blockers:• PropranalolPropranalol
• Radioactive iodineRadioactive iodine
• MOAMOA• Peroxidase inhibitor: prevents Peroxidase inhibitor: prevents
peripheral conversion of T4 to T3peripheral conversion of T4 to T3• Side effects: Pruritus/ Dizziness/ Side effects: Pruritus/ Dizziness/
Leukopenia/JaundiceLeukopenia/Jaundice• Dosage:15-60mg/dayDosage:15-60mg/day
• Inhibits release of T3 and T4Inhibits release of T3 and T4
• Reduces T3 activity on target Reduces T3 activity on target organsorgans
• Rapidly concentrates in the gland Rapidly concentrates in the gland and destroys the thyroxine and destroys the thyroxine producing cellsproducing cells
THYROID HORMONESTHYROID HORMONES
• Indications:Indications:• Myxedema therapyMyxedema therapy• Prevents cretinismPrevents cretinism• Goiter managementGoiter management• Thyroid tablets–gland extracts-Thyroid tablets–gland extracts-60 mg60 mg• Levothuyroxine sodium (T4)-Levothuyroxine sodium (T4)-100 mcg100 mcg• Liothyronine (T3)-Liothyronine (T3)-25 mcg25 mcg• Adverse effects: Cardiac side effectsAdverse effects: Cardiac side effects
Adrenal GlandsAdrenal Glands
• Adrenal Cortex: Adrenal Cortex: • Steroid hormones derived from Steroid hormones derived from
cholesterol - "long term response”cholesterol - "long term response”
• Adrenal Medulla :Adrenal Medulla :• Epinephrine - Neuronal release due Epinephrine - Neuronal release due
to stress "short term response"to stress "short term response"
CHRONO BIOLOGICAL RHYTHMSCHRONO BIOLOGICAL RHYTHMS
• CIRCADIANCIRCADIAN• 24 HOUR CYCLE24 HOUR CYCLE• DARK / LIGHTDARK / LIGHT• SLEEP / AWAKESLEEP / AWAKE
PATTERNSPATTERNS• PEAK HOURS OF PEAK HOURS OF • COPRTISOL COPRTISOL
SECRETIONSSECRETIONS• 4 AM - 8 AM4 AM - 8 AM
• ULTRADIANULTRADIAN• 4 - 8 SECRETORY 4 - 8 SECRETORY
“BURSTS” IN 24 HOUR “BURSTS” IN 24 HOUR PERIODPERIOD
• TRIGGERED BY CRH TRIGGERED BY CRH AND ACTH BURSTS AND ACTH BURSTS
• CLUSTERED AT PEAK CLUSTERED AT PEAK CIRCADIAN TIMESCIRCADIAN TIMES
GLUCOCORTICOIDS:‘CORTISONE’GLUCOCORTICOIDS:‘CORTISONE’
• Gluco - regulate blood glucose, CHO Gluco - regulate blood glucose, CHO and Protein metabolismand Protein metabolism
•Cortisol (hydrocortisone) Cortisol (hydrocortisone)
10 - 25 mg / day10 - 25 mg / day•Cortisone – Cortisone –
0.5 - 2 mg / day0.5 - 2 mg / day•Corticosterone –Corticosterone –
30 - 150 mcg / day30 - 150 mcg / day
GLUCOCORTICOIDS GLUCOCORTICOIDS FUNCTIONSFUNCTIONS
Increase liver glycogen storesIncrease liver glycogen stores Increase gluocneogenesisIncrease gluocneogenesis Increase lipolysisIncrease lipolysis CNS mood effects: Depression/EuphoriaCNS mood effects: Depression/Euphoria Assists CVS functions: potentiates NEAssists CVS functions: potentiates NE Increased hemoglobin synthesisIncreased hemoglobin synthesis Inhibits prostaglandins and leukotrenesInhibits prostaglandins and leukotrenes
Glucocorticoid functionsGlucocorticoid functions Anti-inflammatory and Anti-allergic:Anti-inflammatory and Anti-allergic:
•Suppress leukocyte migration Suppress leukocyte migration •Stabilize cell membranesStabilize cell membranes•Decrease fibroblast activityDecrease fibroblast activity•Reverse capillary permeability induced by Reverse capillary permeability induced by histamine releasehistamine release
•Suppress immune response by inhibiting Suppress immune response by inhibiting antibody synthesisantibody synthesis
•Inhibits cell growth and cell divisionInhibits cell growth and cell division
AVOID Pituitary-Adrenal Axis suppression
•Once suppressed it will take more Once suppressed it will take more than 1 year for normal function to than 1 year for normal function to returnreturn
•<25mg of prednisolone /day taken at 8 <25mg of prednisolone /day taken at 8 am for < 10-15 days usually does not am for < 10-15 days usually does not suppresssuppress
•To minimize suppression taper of the To minimize suppression taper of the dose rather than stopping abruptlydose rather than stopping abruptly
GLUCOCORTICOIDSGLUCOCORTICOIDS
Glucocorticoid Anti-inflammatory
Potency
Equivalentoral
Potency
SodiumRetenti
onShort acting (<12 hrs)HydrocortisoneCortisone
1.00.8
2025
2+2+
Intermediate acting(12-24hrs)PrednisolonePrednisoneMethylprednisoloneTriamcinolone
5.04.05.05.0
5544
1+1+00
Long acting (>24 hrs)BetamethasoneDexamethasone
40.030.0
0.60.75
00
MineralocorticoidsMineralocorticoids
• RENAL• electrolyte and water excretion
Na+, Phosphate, Ca+, Bicarbonate Retention
Reduction of Serum K+
Aldostrone:Aldostrone:
•Secreted by adrenal cortexSecreted by adrenal cortex•^ Na tubular reabsorption ^ Na tubular reabsorption •^ serum levels of Na^ serum levels of Na•^K and H ions excretion by ^K and H ions excretion by
kidneyskidneys
Fludrocrotisone ‘Florinef Fludrocrotisone ‘Florinef ‘‘
•Acts on distal tubule -Acts on distal tubule -^reabsorption of Na and K^reabsorption of Na and K
•Side effects-Headaches/HTNSide effects-Headaches/HTN• Indication: Indication: •Addison' s diseaseAddison' s disease
Anti Adrenals:Anti Adrenals:• AminoglutehemideAminoglutehemide• MOA- prevents enzymatic action to convert MOA- prevents enzymatic action to convert
cholesterol to steroidscholesterol to steroids• Inhibits peripheral tissue conversion of anjdrogens Inhibits peripheral tissue conversion of anjdrogens
to estrogens to estrogens
• (useful in breast cancer treatment)(useful in breast cancer treatment)• Side effects: ataxia, dizziness, nausea, Side effects: ataxia, dizziness, nausea,
vomiting,rash, jaundice, bruising vomiting,rash, jaundice, bruising • Trilostane another compound which blocks steroid Trilostane another compound which blocks steroid
synthesissynthesis
• Used in Cushing's syndromeUsed in Cushing's syndrome
PreparationsPreparations
• SystemicSystemic• TopicalTopical• Inhaled varieties – Inhaled varieties –
Beclomethasone Beclomethasone
Budesonide Budesonide
FlunisolideFlunisolide• Risk of: Risk of:
oropharyngeal candidiasis oropharyngeal candidiasis
dysphoniadysphonia
Steroid IndicationsSteroid Indications
• Addison’sAddison’s• Rheumatoid Rheumatoid
arthritisarthritis• Rheumatic Rheumatic
carditiscarditis• Nephrotic Nephrotic
syndromesyndrome• SLESLE• Severe allergySevere allergy
• Ocular Ocular
inflammationinflammation• SkinSkin• IBDIBD• Cerebral edemaCerebral edema• AsthmaAsthma• RhinitisRhinitis
STEROID SIDE EFFECTSSTEROID SIDE EFFECTS
PITUITARY SUPPRESSION
RISK OF INFECTIONPEPTIC ULCERATIONMYOPATHYSTEROID PSYCHOSIS
IN CHILDREN: GROWTH ARREST SUBCAPSULAR CATARACTS
OSTEOPOROSIS – INHIBITS:INHIBITS:
OSTEOBLAST FORMATION OSTEOBLAST FORMATION
INTESTINAL Ca ABSORPTIONINTESTINAL Ca ABSORPTION
HYPERGLYCEMIA
PANCREAS / DIABETESPANCREAS / DIABETES
• 16 million Americans and increasing 16 million Americans and increasing • 77thth leading cause of death leading cause of death• Blindness/ESRD/Limb amputationsBlindness/ESRD/Limb amputations• Insulin(Beta cells) = Insulin(Beta cells) =
GlycogenesisGlycogenesis• Glucagon(Alpha cells)= Glucagon(Alpha cells)=
GlycogenolysisGlycogenolysis
Lack of insulin causes:Lack of insulin causes: Reduced rate of glucose transport Reduced rate of glucose transport across cell membranesacross cell membranes
Reduced enzyme activity in Reduced enzyme activity in converting glucose to glycogenconverting glucose to glycogen
Hyperlipemia, ketonemia, Acidosis Hyperlipemia, ketonemia, Acidosis due to increased lipase activitydue to increased lipase activity
Leads to increased glucagon activity Leads to increased glucagon activity causing increased proteolysis and causing increased proteolysis and uremiauremia
• TYPE I / IDDTYPE I / IDD• < 30 YEARS AGE< 30 YEARS AGE• NONOBESENONOBESE• 10% OF PATIENTS10% OF PATIENTS• LOW / ABSENT LOW / ABSENT
INSULIN LEVELSINSULIN LEVELS• REQUIRES REQUIRES
INSULININSULIN• NORMAL NORMAL
RECEPTORSRECEPTORS• DKADKA
• TYPE II / NIDDMTYPE II / NIDDM• > 35 YEARS AGE> 35 YEARS AGE• OBESEOBESE• 90% OF PATUIENTS90% OF PATUIENTS• NORMAL / HIGH NORMAL / HIGH
INSULIN RESISTANTINSULIN RESISTANT• ORAL AGENTS / ORAL AGENTS /
DIETDIET• DECREASED / DECREASED /
DEFECTIVE RECPETORSDEFECTIVE RECPETORS• NON KETOTICNON KETOTIC
TYPES OF INSULINTYPES OF INSULIN
• SOURCE- BEEF / PORK / HUMANSOURCE- BEEF / PORK / HUMAN
• PORK LESS ALLERGENIC THAN BEEFPORK LESS ALLERGENIC THAN BEEF
• RAPID ACTINGRAPID ACTING
• INTERMEDIATE ACTINGINTERMEDIATE ACTING
• LONG ACTINGLONG ACTING
• COMBINATIONSCOMBINATIONS
TYPE OF INSULIN ONSET OFACTION
(Hr)
PEAKEFFECT
(Hr)
DURATION OFACTION (Hr)
Rapid ActingInsulin lisproRegular Insulin
0.251/2 - 1
12-4
45-7
IntermediateActingIsophaneInsulin Zinc (Lente)
3-41-3
6-128-12
18-2818-28
Long ActingExtended Zincinsulin (Ultralente)
4-6 18-24 36
CombinationIsophane +Regular'Humalin 50/50Isophane +Regular'Humalin 70/30''Novalin 70/30'
1/2
1/2
3
4-8
22-24
24
Emergencies in DiabetesEmergencies in Diabetes
• HYPOGLYCEMIAHYPOGLYCEMIA• INSULIN SHOCKINSULIN SHOCK• SWEATINGSWEATING• ^ANXIETY^ANXIETY• BLURRED VISIONBLURRED VISION• WEAKNESSWEAKNESS• HEADACHEHEADACHE• DROWSINESSDROWSINESS
• HYPERGLYCEMIAHYPERGLYCEMIA• DIABETIC COMADIABETIC COMA• RED DRY SKINRED DRY SKIN• FRUITY ODORFRUITY ODOR• ABD. PAIN NAUSEA ABD. PAIN NAUSEA
VOMITINGVOMITING• RAPID DEEP RAPID DEEP
BREATHINGBREATHING
ORAL ANTI DIABETIC ORAL ANTI DIABETIC AGENTSAGENTS
• SULFONYLUREAS-SULFONYLUREAS-• Chlorpropamide / Glipizide / Chlorpropamide / Glipizide /
GlyburideGlyburide• BIGUANIDES-BIGUANIDES-• MetforminMetformin• ALPHA GLUCOSIDASE INHIBITOR-ALPHA GLUCOSIDASE INHIBITOR-• AcarboseAcarbose
DRUGS TO ^BLOOD SUGAR
• GLUCAGON - GLUCAGON -
0.5-1Mg IV/IM/SC prn every 20 mins0.5-1Mg IV/IM/SC prn every 20 mins• Contraindication: Contraindication:
pheochromocytoma/insulinomapheochromocytoma/insulinoma• DIAZOXIDE - 1 mg/kg every 8hrs (3-DIAZOXIDE - 1 mg/kg every 8hrs (3-
8mg/kg daily) 8mg/kg daily) • contraindication: CHF/HTNcontraindication: CHF/HTN• GLUCOSE- 10-20 gm oral or GLUCOSE- 10-20 gm oral or
50 cc 50% IV50 cc 50% IV
REPRODUCTIVEHORMONESREPRODUCTIVEHORMONES
• FSH - FSH - • OVUM AND SPERNATOGENSISOVUM AND SPERNATOGENSIS• LH (ICSH)- SEX HORMONES LH (ICSH)- SEX HORMONES
PRODUCTIONPRODUCTION• ANDROGENSANDROGENS• ESTROGENSESTROGENS• PROGESTOGENSPROGESTOGENS
FEMALE HORMONESFEMALE HORMONES
• GnRH-’Gonadorelin’ ‘Factrel’- GnRH-’Gonadorelin’ ‘Factrel’- LH/ICSH release - a diagnostic agent LH/ICSH release - a diagnostic agent for hypogonadismfor hypogonadism
• Histrelin - synthetic GnRH agonistHistrelin - synthetic GnRH agonist• Indication-10 mcg/kg/ scIndication-10 mcg/kg/ sc• Precocious puberty - decreases Precocious puberty - decreases
LH/FSH/estrogen/testosterone levelsLH/FSH/estrogen/testosterone levels• AE: vaginal dryness/breast AE: vaginal dryness/breast
edema/hot flashesedema/hot flashes
FEMALE HORMONESFEMALE HORMONES• CHORIONIC GnH: in decreased LH-CHORIONIC GnH: in decreased LH-• Undescended testesUndescended testes• ^Secondary male sex characteristics^Secondary male sex characteristics• Male and female infertilityMale and female infertility• AE:Edema/Depression/Gynecomastia/ AE:Edema/Depression/Gynecomastia/
Aggression/Arterial Aggression/Arterial thromboembolismthromboembolism
• 1000-4000 units IM thrice weekly1000-4000 units IM thrice weekly
FEMALE HORMONESFEMALE HORMONES
• MENOTROPINS: (HMG)- FSH and LH MENOTROPINS: (HMG)- FSH and LH activityactivity
• from urine of post menopausal from urine of post menopausal womenwomen
• Female infertilityFemale infertility• Male infertilityMale infertility• AE: wt gain/ edema/ oligurea / AE: wt gain/ edema/ oligurea /
gynecomastiagynecomastia• 75 units IM daily x 7 days75 units IM daily x 7 days
FEMALE HORMONESFEMALE HORMONES
• Estrogens: atrophic vaginitis/ Estrogens: atrophic vaginitis/ abnormal uterine bleeding/abnormal uterine bleeding/
• Post menopausal states/ Post menopausal states/ OsteoporosisOsteoporosis
• Metastatic breast cancerMetastatic breast cancer• AE:gastric/<libido/edema/AE:gastric/<libido/edema/• breast pain/ thrombophlebitisbreast pain/ thrombophlebitis
FEMALE HORMONESFEMALE 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
Oral ContraceptivesOral Contraceptives• Low dose E & P combination benefits:Low dose E & P combination benefits:• < CVS effects< CVS effects• ^ of MI in smokers and >35 years of age^ of MI in smokers and >35 years of age• <risk of stroke and thromboembolism<risk of stroke and thromboembolism• <ectopic pregnancies<ectopic pregnancies• <ovarain cysts/ ovarain cancer/ <ovarain cysts/ ovarain cancer/
endometrial cancerendometrial cancer• >risk of cervical cancer/liver cancer/>risk of cervical cancer/liver cancer/
breast cancerbreast cancer
Oral ContraceptivesOral Contraceptives• MonophasicMonophasic- fixed ratio x 21 days- fixed ratio x 21 days• Biphasic- different progestin levels- Biphasic- different progestin levels-
low for 7-10 days/high for next 11-14 low for 7-10 days/high for next 11-14 daysdays
• TriphasicTriphasic- simulates normal cycle-- simulates normal cycle-
constant low estrogen level/ constant low estrogen level/ progestin increased 3 times during progestin increased 3 times during 21 days21 days
• LongactingLongacting- progestin only - - progestin only -
Norplant / Depo-Provera/Norplant / Depo-Provera/
Oral ContraceptivesOral Contraceptives
• SELECTION of ‘Right’ ONE:SELECTION of ‘Right’ ONE:• ‘‘SAFe’(18-35)- SAFe’(18-35)-
Low E(30-35mcg)/Low P /NO Low E(30-35mcg)/Low P /NO SMOKINGSMOKING
• Smokers and >35-Smokers and >35-• ^CVA side effects^CVA side effects• Use other methodsUse other methods
Oral ContraceptivesOral Contraceptives
• If Cancer + If Cancer +
(Breast, Uterus, Cervix, Liver)(Breast, Uterus, Cervix, Liver)• CVA, CAD, Thrombosis +CVA, CAD, Thrombosis +• Oral contraception is Oral contraception is
contraindicatedcontraindicated• Use other methodsUse other methods
Oral ContraceptivesOral Contraceptives• Liver impaired, Smokers >35, Liver impaired, Smokers >35,
CVA/HTN/Migraine-CVA/HTN/Migraine-• Use progestin only minipill Use progestin only minipill
(< effective)(< effective)
PROBLEMS: PROBLEMS:
Acne, Oily skin, Wt. Gain Acne, Oily skin, Wt. Gain Breakthrough bleedingBreakthrough bleeding
Drugs for infertilityDrugs for infertility• CLOMIPHENE- CLOMIPHENE- • ESTROGEN COMPETITORESTROGEN COMPETITOR• ^FSH/LH SECRETION^FSH/LH SECRETION• ^CORPUS LUTEUM^CORPUS LUTEUM• AE:HEADACHE /NAUSEA/ AE:HEADACHE /NAUSEA/
VOMITING/DEPRESSION/VOMITING/DEPRESSION/• ^OVARIAN CYST /FIBROIDS^OVARIAN CYST /FIBROIDS• HEPATOTOXICHEPATOTOXIC
• UROFOLLITROPIN :UROFOLLITROPIN :^FSH ^FSH
Labor and DeliveryLabor and Delivery
• ““OXYTOCICS”-Induce stimulation OXYTOCICS”-Induce stimulation of uterine smooth muscle of uterine smooth muscle contractions and spontaneous contractions and spontaneous labor. ERGOT/OXYTOCINlabor. ERGOT/OXYTOCIN
• ““TOCOLYTICS”- TOCOLYTICS”-
Inhibit premature labor and Inhibit premature labor and suppress lactation. TERBUTALINE suppress lactation. TERBUTALINE / RITODRINE/ RITODRINE
OXYTOCICS and TOCOLYTICSOXYTOCICS and TOCOLYTICS• Oxytocin “Syntocinon”Oxytocin “Syntocinon”• Acts on pregnant Acts on pregnant
uterusuterus• Impedes uterine blood Impedes uterine blood
flowflow• Labor/PPH/ ^LactationLabor/PPH/ ^Lactation• 0.5-2mU/min0.5-2mU/min• IV 30-60 minsIV 30-60 mins• AE:Nausea/vomiting/AE:Nausea/vomiting/• tachycardiatachycardia
• Ritodrine/TerbutaliuneRitodrine/Terbutaliune• B2 adrenergic agonist B2 adrenergic agonist
-inhibits uterine -inhibits uterine contractioncontraction
• To prevent unwanted To prevent unwanted labor/premature labor labor/premature labor after 20 weeks after 20 weeks
• ^Heart rate/^BP^Heart rate/^BP• Trembling tremorsTrembling tremors• 50-100 mcg/min 50-100 mcg/min
IV(150-350mcg) then IV(150-350mcg) then oraloral
Male HormonesMale Hormones• TESTOSTERONE: TESTOSTERONE: • 25-50 mg IM thrice weekly25-50 mg IM thrice weekly• Androgen deficiency/Delayed male Androgen deficiency/Delayed male
pubertypuberty• Breast cancerBreast cancer• AnemiaAnemia• AE: abdominal pain/ headaches/jaundice/ AE: abdominal pain/ headaches/jaundice/
edema/breast swelling/ frequent erectionsedema/breast swelling/ frequent erections• Females: oily skin/ deep voice/ hirsuitism/ Females: oily skin/ deep voice/ hirsuitism/
male type baldness/ enlarged clitoris/male type baldness/ enlarged clitoris/
irregular mensesirregular menses
Enlarged ProstateEnlarged Prostate
• Benign: Hytrin is usedBenign: Hytrin is used• Finasteride- inhibits 5 alpha Finasteride- inhibits 5 alpha
reductase and prevents testosterone reductase and prevents testosterone conversion to dihydrotestosterone conversion to dihydrotestosterone which causes prostatic growthwhich causes prostatic growth
• AE: Gynecomastia, back pain, AE: Gynecomastia, back pain, diarrhea, <libido, impotency, diarrhea, <libido, impotency,
< ejaculation qty< ejaculation qty
Altering sexual Altering sexual behaviorbehavior
•HTN- HTN-
aldomet,reserpin, thiazidesaldomet,reserpin, thiazides•Antihistamines- BenadrylAntihistamines- Benadryl•Psychotropics- Psychotropics-
Chlorpromazine, valium, Chlorpromazine, valium, haloperidol, imipramine, haloperidol, imipramine, alcoholalcohol
Altering sexual Altering sexual behaviorbehavior
• Amylnitrite-^male orgasmAmylnitrite-^male orgasm• Viagra- ^Nitric oxide release Viagra- ^Nitric oxide release • ^cGM P <phophodiesterase in penis^cGM P <phophodiesterase in penis• AE: caution with cardiac patients on AE: caution with cardiac patients on
nitratesnitrates• Causes hypotension, headache, Causes hypotension, headache,
nasal congestion, flushing, flu nasal congestion, flushing, flu syndrome, angina, tachycardia, syndrome, angina, tachycardia, priapism , Peyronie’s diseasepriapism , Peyronie’s disease
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