Endocrine System Pharm Test 1

Front 1

Effects of GH and IGF

Back 1

Stimulate almost all body tissues to grow
Promote nitrogen metabolism (increased nitrogen retention, aa transport into tissues, protein incorporation)
Carb & lipid metabolism use of lipids for energy instead of carbs
Diabetogenic effect in diabetics
Saves muscle at the expense of fat during stress

Front 2

Growth Hormone
(Somatotropin)
rhIGF-1 (last resort) MOA

Back 2

Activate intracellular tyrosine kinase (JAK2)

Front 3

Role of IGF

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made by liver & other tissues in response to GH & mediates effects

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Uses of IGF and GH

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*Hypopituitary dwarfism
*Idiopathic, non-GH deficient short stature (recently approved)
*AIDS-associated wasting (due to loss of muscle mass)
*Adult onset GH deficiency (lose lean muscle mass, become obese, development of CV problems)
*Short stature associated with Turner’s syndrome
*Anti-aging supplements OTC suggesting contains hGH but really have aa that should release GH

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Side effects of GH and IGF

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*Intracranial HTN & visual changes are possible (fundascopic exam needed)
*Type II Diabetes possible
*Respiratory difficulties in patients with obesity or sleep apnea due to Prader-Willi syndrome
*Possible contamination of human derived GH with Creutzfeldt-Jakob virus (not anymore)

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Leutenizing Hormone (LH) effects

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Promotes ovulation & luteinization of ovarian follicles ovaries
Stimulates synthesis & secretion of estrogen & progesterone from corpus luteum ovaries
Stimulates interstitial (leydig) cells to secrete androgens testis

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Uses of LH

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Infertility (women)
Infertility (men) – not a first line drug

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Side effects of LH

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*Multiple pregnancies
*Ovarian hyperstimulation syndrome (OHS) could occur

Front 9

FSH drugs

Back 9

rhFSH
– follitropin
– urofollitropin

Front 10

FSH MOA

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GONADOTROPIN
Promotes follicular development ovaries
Stimulates testicular growth & maintain seminiferous tubules testes

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Uses for FSH

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Promote Ovulation

Front 12

Side effects of FSH

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*Ovarian hypertrophic syndrome (OHS)
*Multiple pregnancies

Front 13

Chorionic Gonadotropin
(HCG) MOA

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GONADOTROPIN
Stimulate and sustain function of corpus luteum

Front 14

HCG Uses

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*Induction of ovulation
*promote descent of testes in cryptochism
*Presence in urine confirms pregnancy
*restarts testosterone synthesis after using anabolic steroids

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Prolactin MOA

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Lactation causes growth & development of breasts & increased synthesis of milk proteins
Decreases release/effectiveness of gonadotropins

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Uses for Prolactin

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*Promote lactation
*Limit gonadotropin effects

Front 17

Side of Prolactin

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Glactorrhea
Amennorhea
Impotence

Front 18

TSH drugs

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– thyrotropin alpha
– rhTSH

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MOA of TSH

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Stimulation activates Gs which stimulates the thyroid (increase uptake of iodine by thyroid, synthesis & release of hormone & growth of gland)

Front 20

uses for TSH

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*Increase uptake of radioactive iodine
*Diagnostic tool for serum thyroglobulin testing or whole body scanning in follow-up of patients with thyroid cancer (there shouldn’t be any thyroid tissue post surgical removal unless metastasis has occurred)
--Good way to find metastasis

Front 21

Corticotropin drugs

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– ACTH
– Cosyntropin

Front 22

MOA of Corticotropin

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Stimulates adrenal cortex to make & secrete cortisol, corticosterone, & aldosterone (slightly)
Prevents atrophy of adrenal cortex

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Uses of Corticotropin

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*Diagnosis of adrenal insufficiency (not making cortisol, which can be life-threatening)
*Help determine where the problem lies (pituitary, hypothalamus or adrenal glands)
*Infantile spasms (epilepsy associated with mental retardation)

Front 24

Gonadotropin-releasing hormone (gonadorelin) MOA

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Hypothalamic Hormone

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Uses of GnRH

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*Induction of ovulation (sometimes)
*Promote release of LH & FSH

Front 26

Long acting GnRH analogs MOA

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Hypothalamic Hormone
Hyperstimulation of receptors leads to down regulation

Front 27

Uses of long acting GnRH

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PMS
Endometriosis
Prostate CA
Central precocious puberty (turns off testosterone)

Front 28

Long acting GnRH agents

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Histrelin
– LEUPROLIDE
– Gosrelin
– triptorelin
– nafarelin

Front 29

Side effects of GnRH

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Initially an increased gonadotropin release “flare”

Front 30

GnRH Antagonist agents

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– Ganirelix
– cetrorelix

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GnRH Antagonist Uses

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Inhibit LH surges before egg harvesting
Advanced Prostate Cancer

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GnRH Side effects

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Danger of life threatening allergic reaction (4%)

Front 33

Somatostatin
(GH-IH) agents

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– Lanreotide
– Somatuline

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Somatostatin MOA

Back 34

Hypothalamic Hormone
Analog used in treatment
Inhibits GH

Front 35

uses of Somatostatin

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Acromegaly
carcinoid
VIP secreting tumors

Front 36

GHRH agent

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– Semorelin

Front 37

Use of Semorelin

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GH deficiency
*only works in patients with functioning pituitary

Front 38

MOA of (PTU) propylthiouracil

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Anti-Thyroid
Decrease synthesis of thyroid hormones by inhibiting peroxidase
Inhibits peripheral conversion of T4 to T3

Front 39

Uses of PTU

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Hyperthyroidism with pregnancy and thyroid storm

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Side effects for PTU

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Loss of Hair pigment
Agranulocytosis
Do CBC before therapy
hepatotoxicity

Front 41

Methimazole

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Anti Thyroid
Decrease synthesis of thyroid hormones by inhibiting peroxidase

Front 42

Uses of Methimazole

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Hyperthyroidism (chronic use)

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Side effects of Methimazole

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Not in pregnancies
Loss of hair pigment
Agranulocytosis

Front 44

Lugol's Solution (Concentrated Iodide) MOA

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Anti-thyroid
inhibition of release of thyroid hormone
High levels of iodine = inhibition only works a couple weeks

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Uses of Lugol's Solution

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Hyperthyroidism
– give while waiting on methimazole to kick in

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Side effects of Lugol's Solution

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Angioedema, cutaneous hemorrhage
Iodide “escpe

Front 47

X-ray contrast media MOA

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Anti-thyroid
Inhibit conversion to T4 to T3

Front 48

Side effects of Radioactive Iodine 131

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Delayed hypothyroidism
Should not be used in children or pregnant women

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Propranolol MOA

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Non-selective Beta Blocker

Front 50

Radioactive Iodine 131 MOA

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Anti-thyroid
Actively concentrated by thyroid
release of radiation destroys parenchymal cells of thyroid (at high doses)

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Radioactive Iodine 131 Uses

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Diagnosis of thyroid disorders
Tx of Hyperthyroidism

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Use of Propranaolol

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Symptomatic relief from symptoms of excess hormone

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Sodium L-thyroxine MOA

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Synthetic T4

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Sodium L-thyroxine uses

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DRUG OF CHOICE
Replacement therapy
Hypothyroidism (myxedema)
Cretinism
Simple Goiter
Nodular Goiter
TSH-dependent Carcinoma

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Sodium L-thyroxine side effects

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Pre-existing cardiac disease start low dose and gradually increase
Pregnant women require higher doses

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Teriparatide ( rhPTH) MOA

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Stimulates new bone growth
– Only drug to stimulate NEW bone growth!!!!

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Teriparatide (rhPTH) Uses

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Osteoporosis

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Teriparatide (rhPTH) Side effects

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Dizziness or tachyardia after injections
2 year limit or risk of osteosarcoma

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Cinacalet MOA

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Inhibits PTH by binding to Ca++ receptors

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Cinacalet uses

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Secondary HyperParathyroidism

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Fully Active Vit D

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Calcitriol
Paricalcitol
Doxercalciferol

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Fully Active Vit D MOA

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↑ Ca++
Intestine – Increases Ca++ absorption
Kidney – Decreases Ca++ excretion
Bone – Increased Ca++ resorption

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Uses for Fully Active Vit D

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When body CAN'T activate Vitamin D (chronic renal failure)
Hypoparathyroid
Pseudohypoparathyroidism
Rickets and Osteomalacia

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Cholecalciferol (D3) MOA

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↑ Ca++
Intestine – Increases Ca++ absorption
Kidney – Decreases Ca++ excretion
Bone – Increased Ca++ resorption

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Cholecalciferol (D3) Uses

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Hypoparathyroid
Pseudohypoparathyroidism
Rickets and Osteomalacia

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Cholecalciferol Side effects

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CRF patients can't convert to active form

Front 67

Calcitonin MOA

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↓ Ca++
Kidney – Increased Ca++ excretion
Bone – Decrease Ca++ resorption

Front 68

uses for Calictonin

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Hypercalcemia

Front 69

Bisphophonates agents

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all end in -dronates
Zoledronic Acid

Front 70

Bisphophonates MOA

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Bind to the mineral surface of bone and decrease osteoclast-induced resorption of bone
Induces apoptosis of osteoclasts and inhibits mevalonate pathway
Increases mineral density but NO NEW BONE GROWTH

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Uses for Bisphosphonates

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Paget's
Osteoporosis
Hypercalcemia associated with Cancer

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Bisphosphonates side effects

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GI irritation
eye inflammation
bone/join/muscle pain
IV agents give jaw osteonecrosis
-Zoledronic Acid
-pamidronate

Front 73

Glucocorticoids MOA

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Alter bone mineral homeostasis by antagonizing Vitamin D stimulated calcium absorption in the gut as well as stimulateing renal calcium excretion
Decreases calcium absorption and also increases excretion

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Glucocorticoids Uses

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Long term treatment of hypercalcemia due to lymphonas and sacroidosis

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Furosemide MOA

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Increases calcium excretion by blocking reabsorption in the loop of henle

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Furosemide Uses

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Emergency treatment of Hypercalcemia

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Gallium MOA

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Inhibits bone resportion by osteoclasts.

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Gallium uses

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Hypercalcemia of malignancy

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Gallium side effects

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Renal tubular plugs and renal failure

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Estrogens MOA

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Reduce the bone-resorbing action of PTH and by promoting apoptosis in osteoclasts

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Estrogens Uses

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Prevent acccelerated bone loss during immediate post menopausal period

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Thiazides MOA

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Reduce calcium excretion by increasing tubular reabsorption in DCT

Front 83

Uses of Thiazide

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Reduces hypercalciuria and incidence of stone formation in patients with idopathic hypercalcemia

Front 84

Cortisol MOA

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Liver – Anabolic effects
-Gluconeogenesis
-hepatic glycogen
-blood glucose

Muscle – Catabolic Effects
-Negative N balance
-Decreased glucose uptate (hyperglycemia and glycosuria)
-decreased AA uptake
Connective Tissues – Catabolic Effects
-decreased glucose uptake
-matrix broken down
-thinning of skin

Inhibits ACTH
Blocks inflammatory response
Suppressess immune system
Stimulates gastric acid secretion

Front 85

Cortisol uses

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Replacement Therapy
-Primary adrenal insufficiency
-secondary adrenal insufficiency
-Congenital adreneal hyperplasia

Anti-inflammatory Agent

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Cortisol side effects

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None at physiologic doses
Iatrogenic Cushing Syndrome
-Redistribution of body fat
-protein cataoblism
-increased glucose production
-may lead to DM and obesity
-Osteoporosis
-growth suppression with children
-thinning of skin
-impaired wound healing
-peptic ulcer

WEAN PATIENTS OFF THESE DRUGS
ALTERNATE DAY THERAPY WHENEVER POSSIBLE

Front 87

Dexamethasone use

Back 87

Diagnostic Testing
-feedback inhibition of ACTH to trun off adrenal gland

Front 88

Betamethasone uses

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Premature infants to mature lungs before birth

Front 89

Metyrapone MOA

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Inhibits 11-Beta hydroxylation

Front 90

Metyrapone uses

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Severe cortisol excess
compassionate use basis

Front 91

Aminoglutethimide MOA

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Inhibits conversion of Bholesterol to pregnenolone (Desomolase)

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Aminoglutethimide uses

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Functional adrenalectomy
Decrease cortisol synthesis in patients with Cushing's who don't respond to mitotane
Metastatic breast and prostate cancer
– Decrease circulating androgens
Induces microsomal metabolism of dexamethasone

Front 93

Ketoconozole MOA

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Anti-fungal which inhibits multiple enzymes including hydroxypegnalone conversion to DHEA

Front 94

Ketoconozole Uses

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Cushing's

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Mitotane MOA

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Destroys adrenal cells

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Mitotane

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Adrenal tumors
-compassionate use basis

Front 97

Fludrocortisone MOA

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Mineralcorticoid agonist
-Na retention
-K and H ion excretion
-H2O reabsorption

Front 98

Fludrocortisone Use

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Replacement therapy

Front 99

Fludrocortisone side effects

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HTN
Muscle weakness
Hypokalemic alkalosis

Front 100

Eplerenone MOA

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Aldosterone receptor antagonist
– similar to spironolactone

Front 101

Eplerenone Use

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Improves survival in patients with heart failure
HTN