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Pharmacology

      Drugs that Affect the
       Endocrine System
Topics
•   Pituitary Drugs
•   Parathyroid/Thyroid Drugs
•   Adrenal Drugs
•   Pancreatic Drugs
•   Reproductive Drugs
•   Sexual Behavior Drugs
Functions
• Regulation
• Control
Glands
Exocrine            Endocrine

• Secrete enzymes   • Secrete hormones
• Close to organs   • Transport via
                      bloodstream
                    • Require receptors
Nervous             Endocrine



     Wired               Wireless

Neurotransmitters       Hormones

 Short Distance       Long Distance

   Closeness        Receptor Specificity

  Rapid Onset         Delayed Onset

 Short Duration     Prolonged Duration

Rapid Response          Regulation
Mechanism of Action
Hypothalamus
Hypothalamic Control Pituitary
Posterior Pituitary
           Target     Actions


Oxytocin   Uterus     ↑ Contraction
           Mammary    ↑ Milk
                      let-down
ADH        Kidneys    ↑ Water
                      reabsorption
Anterior Pituitary
           Target        Action
GH         Most tissue   ↑Growth
TSH        Thyroid       ↑TH
                         secretion
ACTH       Adrenal       ↑Cortisol
           Cortex        secretion
Anterior Pituitary
           Target    Action


FSH        Ovaries   Follicles
           Testes    Estrogen
                     Sperm
LH         Ovaries   Ovulation
           Testes    Progesterone
                     Testosterone
Anterior Pituitary
            Target    Action



Prolactin   Mammary   Milk
            Gland     production
Pituitary Hormones
Thyroid
Thyroid
                 Target       Action


Thyroxine        Most cells   ↑ BMR
Triiodothyronine
Calcitonin       Mostly bone ↓ Calcium
Hypothyroidism
Hyperthyroidism
Parathyroid
Parathyroid
              Target     Action

Parathyroid   Bone       ↑Calcium
(PTH)         Kidney
              GI Tract
Calcium Regulation
Pancreas
Pancreas
• Alpha cells: glucagon
• Beta cells: insulin
Pancreas
           Target    Action

Glucagon   Liver     ↑Glucose

Insulin    General   ↓Glucose
Glucose Regulation
Adrenal
Endrocrine drugs
Endrocrine drugs
Adrenal Medulla
         Target    Action



Norepi   Heart     Prolongs
Epi      Blood     SNS Effects
         vessels
         Liver
Adrenal Cortex
           Target      Action
Aldosterone Kidney     ↑Na
                       reabsobtion
                       ↑Water
                       retention

Cortisol   Most Tissue ↑Glucose
                       ↓inflammation
Anterior Pituitary Drugs
   Inadequate Growth           Excessive Growth
        Hormone                      Hormone
• Dwarfism                •   Acromegaly
• somatrem (Protropin®)   •   Gigantism
• homatropin              •   Surgical removal 1º
  (Humatrope®)            •   octreotide
                              (Sandostatin®)
Posterior Pituitary Drugs
• Oxytocin
• ADH
  – Diabetes insipidus
  – Nocturnal enuresis
• vasopressin (Pitressin®)
• desmopressin (Stimate®)
• lypressin (Diapid®)
Parathyroid Diseases
• Hypoparathyroidism
  – Inadequate calcium levels
     • TX: increased dietary calcium
• Hyperparathyroidism
  – Excessive calcium levels
     • TX: surgical removal
Thyroid Disease
• Hypothyroidism
  – Hormone replacement
  – levothyroxine (Synthroid®)
• Hyperthyroidism
  – Thyrotoxicosis
  – Surgical removal
  – propylthiouracil (PTU)
Adrenal Cortex
 ACTH Hypersecretion                  ACTH Hyposecretion
   Cushing’s Disease                   Addison’s Disease
• Surgical removal                •   Replacement therapy
• Inhibit adrenal                 •   Cortisone (Cortistan®)
  secretion                       •   Hydrocortisone
    –   ketoconazol (Nizoral ®)       (SoluCortef®)
•    Symptomatic tx:              •   Fludrocortisone
    –   Antihypertensives             (Florinef Acetate®)
Pancreas

                 Blood
               Potassium




            Blood
           Glucose
Insulin Preparations
• Regular Insulin
  – Natural insulin
• Modified Insulin
  – Increased duration of action
  – NPH (neutral protamin Hagedorn)
     • Natural plus protamin
  – Lente
     • Attached to zinc to prolong absorption
Oral Hypoglycemic Agents
      Sulfonylureas               Alpha-glucosidase
⇑ insulin secretion                      inhibitors
tolbutamide (Orinase®)        • Delay carbohydrate
chlorpropamide (Diabinese®)
                                metabolism
                              acarbose (Precose®)
glipizide (Glucotrol®)
                              miglitol (Glyset®)
glyburide (Micronase®)

         Biguanides               Thiazolidinediones
metformin (Glucophage®)       ⇑ Insulin effectiveness
⇓ Glucose synthesis           troglitazone (Rezulin®)
⇑ Glucose uptake
Hyperglycemic Agents

• Glucagon              • diazoxide
    ⇑ gluconeogenesis     (Proglycem®)
                          – Inhibits insulin release

• D50W
Estrogens & Progestins
• Estrogens used for       • Progestin
  post-menopausal            – Diminish side effects
  hormone replacement          of estrogen therapy
  therapy.                   – Nausea, fluid retention,
  – estradiol (Estrace®)       breast tenderness
  – conjugated estrogens     – medroxyprogesterone
    (Premarin®)                acetate (Provera®)
  – estropipate (Ogen®)      – norethindrone acetate
                               (Aygestin®)
Oral Contraceptives
• Combination of estrogen and progestin
  – Loestrin®, Levora®, Nordette®, Ovocon®,
    Norinyl® plus many others
• Minipill: progestin only
  – Micronor®, Nor-Q.D.®, Orvette®


• Prime side effect: ⇑ risk of
  thromboembolism
Uterine Stimulants &
Relaxants
• Stimulants (Oxytocics)   • Relaxants (tocolytics)
∀ ⇑ uterine contraction    • Relax uterine smooth
• Indication:                muscle
   – Induce labor
                           • Beta2 agonists
   – Postpartum
     hemorrhage               – terbutaline (Brethine®)
• oxytocin (Pitocin®)         – ritodrine (Yuptopar®)
• ergonovine
  (Ergotrate®)
Infertility Agents
• Promote maturation of ovarian follicles
• clomiphene (Clomid®)
• urofollitropin (Metrodin®)
Male Reproductive Agents
• Testosterone Replacement
  – methyltestosterone (Metandren®)
  – fluoxymesterone (Halotestin®)
• Benign Prostatic Hypertrophy
  – Surgery
  – finasteride (Proscar®)
Sexual Behavior
• Most are side effects from other
  medications
  – Antihypertensives & psychoactive drugs
• sildenafil (Viagra®)

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Endrocrine drugs

  • 1. Pharmacology Drugs that Affect the Endocrine System
  • 2. Topics • Pituitary Drugs • Parathyroid/Thyroid Drugs • Adrenal Drugs • Pancreatic Drugs • Reproductive Drugs • Sexual Behavior Drugs
  • 4. Glands Exocrine Endocrine • Secrete enzymes • Secrete hormones • Close to organs • Transport via bloodstream • Require receptors
  • 5. Nervous Endocrine Wired Wireless Neurotransmitters Hormones Short Distance Long Distance Closeness Receptor Specificity Rapid Onset Delayed Onset Short Duration Prolonged Duration Rapid Response Regulation
  • 9. Posterior Pituitary Target Actions Oxytocin Uterus ↑ Contraction Mammary ↑ Milk let-down ADH Kidneys ↑ Water reabsorption
  • 10. Anterior Pituitary Target Action GH Most tissue ↑Growth TSH Thyroid ↑TH secretion ACTH Adrenal ↑Cortisol Cortex secretion
  • 11. Anterior Pituitary Target Action FSH Ovaries Follicles Testes Estrogen Sperm LH Ovaries Ovulation Testes Progesterone Testosterone
  • 12. Anterior Pituitary Target Action Prolactin Mammary Milk Gland production
  • 15. Thyroid Target Action Thyroxine Most cells ↑ BMR Triiodothyronine Calcitonin Mostly bone ↓ Calcium
  • 19. Parathyroid Target Action Parathyroid Bone ↑Calcium (PTH) Kidney GI Tract
  • 22. Pancreas • Alpha cells: glucagon • Beta cells: insulin
  • 23. Pancreas Target Action Glucagon Liver ↑Glucose Insulin General ↓Glucose
  • 28. Adrenal Medulla Target Action Norepi Heart Prolongs Epi Blood SNS Effects vessels Liver
  • 29. Adrenal Cortex Target Action Aldosterone Kidney ↑Na reabsobtion ↑Water retention Cortisol Most Tissue ↑Glucose ↓inflammation
  • 30. Anterior Pituitary Drugs Inadequate Growth Excessive Growth Hormone Hormone • Dwarfism • Acromegaly • somatrem (Protropin®) • Gigantism • homatropin • Surgical removal 1º (Humatrope®) • octreotide (Sandostatin®)
  • 31. Posterior Pituitary Drugs • Oxytocin • ADH – Diabetes insipidus – Nocturnal enuresis • vasopressin (Pitressin®) • desmopressin (Stimate®) • lypressin (Diapid®)
  • 32. Parathyroid Diseases • Hypoparathyroidism – Inadequate calcium levels • TX: increased dietary calcium • Hyperparathyroidism – Excessive calcium levels • TX: surgical removal
  • 33. Thyroid Disease • Hypothyroidism – Hormone replacement – levothyroxine (Synthroid®) • Hyperthyroidism – Thyrotoxicosis – Surgical removal – propylthiouracil (PTU)
  • 34. Adrenal Cortex ACTH Hypersecretion ACTH Hyposecretion Cushing’s Disease Addison’s Disease • Surgical removal • Replacement therapy • Inhibit adrenal • Cortisone (Cortistan®) secretion • Hydrocortisone – ketoconazol (Nizoral ®) (SoluCortef®) • Symptomatic tx: • Fludrocortisone – Antihypertensives (Florinef Acetate®)
  • 35. Pancreas Blood Potassium Blood Glucose
  • 36. Insulin Preparations • Regular Insulin – Natural insulin • Modified Insulin – Increased duration of action – NPH (neutral protamin Hagedorn) • Natural plus protamin – Lente • Attached to zinc to prolong absorption
  • 37. Oral Hypoglycemic Agents Sulfonylureas Alpha-glucosidase ⇑ insulin secretion inhibitors tolbutamide (Orinase®) • Delay carbohydrate chlorpropamide (Diabinese®) metabolism acarbose (Precose®) glipizide (Glucotrol®) miglitol (Glyset®) glyburide (Micronase®) Biguanides Thiazolidinediones metformin (Glucophage®) ⇑ Insulin effectiveness ⇓ Glucose synthesis troglitazone (Rezulin®) ⇑ Glucose uptake
  • 38. Hyperglycemic Agents • Glucagon • diazoxide ⇑ gluconeogenesis (Proglycem®) – Inhibits insulin release • D50W
  • 39. Estrogens & Progestins • Estrogens used for • Progestin post-menopausal – Diminish side effects hormone replacement of estrogen therapy therapy. – Nausea, fluid retention, – estradiol (Estrace®) breast tenderness – conjugated estrogens – medroxyprogesterone (Premarin®) acetate (Provera®) – estropipate (Ogen®) – norethindrone acetate (Aygestin®)
  • 40. Oral Contraceptives • Combination of estrogen and progestin – Loestrin®, Levora®, Nordette®, Ovocon®, Norinyl® plus many others • Minipill: progestin only – Micronor®, Nor-Q.D.®, Orvette® • Prime side effect: ⇑ risk of thromboembolism
  • 41. Uterine Stimulants & Relaxants • Stimulants (Oxytocics) • Relaxants (tocolytics) ∀ ⇑ uterine contraction • Relax uterine smooth • Indication: muscle – Induce labor • Beta2 agonists – Postpartum hemorrhage – terbutaline (Brethine®) • oxytocin (Pitocin®) – ritodrine (Yuptopar®) • ergonovine (Ergotrate®)
  • 42. Infertility Agents • Promote maturation of ovarian follicles • clomiphene (Clomid®) • urofollitropin (Metrodin®)
  • 43. Male Reproductive Agents • Testosterone Replacement – methyltestosterone (Metandren®) – fluoxymesterone (Halotestin®) • Benign Prostatic Hypertrophy – Surgery – finasteride (Proscar®)
  • 44. Sexual Behavior • Most are side effects from other medications – Antihypertensives & psychoactive drugs • sildenafil (Viagra®)

Hinweis der Redaktion

  1. Regulation of: Metabolism Water and Electrolyte balance Red Blood Cell Production Control of: Reproduction Smooth, sequential growth and development
  2. Oxytocin: Uterine contraction Milk ejection from Mammary gland Release stimulated by delivery and infant suckling Vasopressin (Antidiuretic Hormone): Enhances water retention by kidneys (hence antidiuretic) Major regulation of urinary water loss and overall water balance Causes contraction of arteriolar smooth muscle (vessel pressor effect) Little normal control of blood pressure Released via hypothalmic osmoreceptors when an increase in osmolarity is dected (ie, a decrease in plasma levels)
  3. Growth Hormone (GH) responsible for regulating growth and development important in regulating metabolism (increases use of stored fats, decreases glucose utilization) Thyroid-Stimulating Hormone (TSH) Increases metabolic rate acting on thyroid gland Adrenocorticotropic Hormone (ACTH) Increases cortisol secretion by adrenal cortex Promotes growth of adrenal cortex Follicle-Stimulating Hormone (FSH) Males: required for sperm production Females: stimulates growth and devlopment of ovarian follicles Luteinizing Hormone (LH) Males:responsible for secretion of testosterone by testes Females: responsible for ovulation, secretion of estrogen and progesterone by ovaries Prolactin (PRL) Females: Enhances breast development and milk production
  4. Thyroid Hormone: Effects virtually ever body tissue Increases the body’s overall basal metabolic rate or “idling speed” Increases Oxygen consumption and energy expenditure Slow action, long duration Increases heat production via increased metabolic rate (Calorigenic Effect) Sympathomimetic Effects with increased thyroid stimulation increased production of catecholmine receptors
  5. Cretinism Exhibits signs of dwarfism because skeleton fails to grow or mature Severe Mental retardation In adult onset, causes Myxedma S/S: facial swelling, bradycardia, decreased body temperature, weakness, leathergy Treatment aimed at thyroid replacement
  6. Exophthalmos Grave’s Disease Increased metabolism, tachycardia , heat intolerance, increased sweating, weight loss despite good apetite, insomnia, nervousness Treatment: surgical removal of part of thyroid gland or radiation therapy to destroy part of thyroid
  7. Parathyroid hormone: Increases Calcium concentration in plasma and, therefore, ECF. Complete lack of parathyroid hormone leads to death within several days, usually due to hypocalcemic spasm of respiratory muscles
  8. Alpha cells: glucagon Opposes action of insulin Increases blood sugar levels by: decreasing glycogen synthesis increasing glycogen breakdown into glucose Beta cells: insulin Decreases blood sugar by: Promotes glucose transport into most cells by increasing the number of glucose-transporter proteins available on cell membrane. Brain doesn’t require insulin for transport Increases glucogenesis (creation of glucose) Increases glycogenolysis (breakdown of glycogen) Delta cells: somatostatin Inhibits production and release of both glucogon and insulin
  9. Medulla Epinephrine and Norepinephrine Part of SNS, responsible for catecholmine release which prolongs fight or flite response Cortex: Glucocorticoids, mineralocorticoids Glucocorticoids: increase blood glucose levels prevent inflammation are released in response to stress