Pharmacology for APNs-Endocrinology
Endocrine- pituitary/adrenal
* Pharmacologic application of hormone replacement vs. antagonists
o Replacement therapy for hormone deficiency states . e
o Antagonists for diseases caused by excess production of + Posteror Pitry POSTCFOT POV !
pituitary hormones. T ot
° Growth hormone "“lfi::"flh""f anterior piwitary, and target organ
o Required for normal growth, regulator of lipid/carb
metabolism throughout adulthood
o Deficiency tx:
= Somatropin used in children/adults
= Children w/ genetic diseases associated w/ short
stature
o Excess tx:
= Somatostatin analogs - octreotide, lanreotide
o Treatment of deficiency/excess
¢ Prolactin
o Principal hormone for lactation
o Hyperprolactinemia
= Etiologies
¢ Medications: SSRIs, Haldol, reglan, dopamine antagonists
* Prolactin-secreting adenomas
* dopamine agonists bromocriptine (parlodel)
o definition, symptoms, etiologies, treatment
* Vasopressin/ADH- effects, deficiency
* Oxytocin- effect, clinical uses
¢ Glucocorticoids/mineralcorticoids
o Glucocorticoids: effects metabolism, catabolism, immune responses,
inflammation
= Stimulated by ACTH
0Mineralocorticoids: regulate Na and K reabsorption in collecting tubules of
kidney
* Organ and tissue effects of glucocorticoids
o Metabolic effects
= Glucocorticoids stimulate gluconeogenesis and glycogen synthesis >
inc. BG, fat deposition, insulin resistance when too much!
= Regulate carb/protein/fat metabolism
= Release of amino acids via muscle catabolism
= Inhibition of peripheral glucose uptake
o Immunosuppressive effects
= Inhibits cell-mediated immunologic functions
* inc. neutrophils, dec.
lymphocytes/eosinophils/basophils/monocytes
* Inhibits leukocyte migration
= Does not interfere with the development of normal acquired immunity
o Catabolic effects
= Decreased muscle mass, thinning skin, osteoporosis, limited growth in
children
o Other effects
, = CNS - behavioral (“roid rage”, depression)
= Gastric acid secretion - lead to ulcers
= CVintegrity and contractility
e Cortisol (hydrocortisone)
o
= When you are more stressed or sick, more ACTH will be excreted!
0 Metabolized in liver, renally excreted
¢ Clinical uses of corticosteroids
o Adrenal disorders: dx and tx of adrenal dysfunction
= Dexamethasone suppression test
= Replacement in adrenal insufficiency
o Non-adrenal disroders
= r/t ability to suppress inflammatory/immune responses
= stimulation of lung maturation in fetus
* How corticosteroids used for diagnosis of adrenal disorders
Short cosyntropin-stimulation test Dexamethasone suppression tes
FAddison’s discase Diagnosis of Cushing syndrome.
cosyntropin IVorIM + 1 mg dexamethasone orally
(synthetic ACTH) @lipm
+ Plasma cortisol measured at0, + Plasma cortisol measured @
30,60 mi Sam
‘Lo for specificincreasein
cortisal level to o AT
o . § e/ indicativeof
Cushing’s syndrome
* Adrenocortical insufficiency, Addison’s Disease- symptoms, treatment, stress dosing,
side effects
o S/S
- ftigue, weakness + Hyperpigmentation of skin, mucosa
. depression + Saltcraving
+ Anorexia, weight loss - Pallor
- Dizziness, orthostatic - Amenorhea, decreased libido,
hypotension impotence
bdominl cramps.
yponateemia
- Hypoglycemia yed
« Hyperkatemia puberty
Iymphocytosis, cosinophilia
o Tx:
e Combined glucocorticoid & mineralocorticoid activity
s Adrenal crisis: demands parenteral glucocorticoids
= Don't forget stress dosing
= ADE:
* Hyperglycemia, glycosuria, Na retention w/ edema or HTN,
hypokalemia, peptic ulcer, osteoporosis, hidden infections
Glucocorticoids: indications that are non-adrenal related
* Hypercortisolism- adrenal hyperactivity- Cushing’s Typical Findings in Cushing Syndrome
Syndrome ——
o Resulting from chronic exposure to excessive _nf 3
circulating levels of glucocorticoid
o Typical signs, symptoms, exam findings
o Diagnosis
= 24-hour urine cortisol level HIGH
= Check ACTH levels
o Treatment
= Surgical removal of ACTH-producing tumor -
irradiation of pituitary tumor
, = 4 agents use preoperatively or as adjunctive therapy postop
* Steroidogenesis inhibitors, adrenolytic agents,
neuromodulators of ACTH release, glucocorticoid-receptor
blocking agents
o Ketoconazole: inhibits glucocorticoid synthesis at high
doses
o Mifepristone: glucocorticoid receptor antagonist
o synthesis inhibitors and antagonists
* Side effects of giving exogenous corticosteroids look like typical findings in Cushing
syndrome
s Corticosteroid weaning
o Abrupt cessation/withdrawal cause symptoms of adrenal insufficiency
o Wean anyone on...
= dose comparable w/ 20mg of prednisone a day for > 3 wks
= nighttime dose > 5mg of prednisone for more than a few weeks
= a cushingoid appearance
¢ Mineralocorticoids = Aldosterone
o Promotes reabsorption of Na from renal tubules
e Hyperaldosteronism
o S/S: hypokalemia, metabolic alkalosis, inc. plasma volume, HTN
o Treatment options:
¢ Fludrocortisone
o Potent steroid with glucocorticoid and mineralocorticoid activity
o Used for...
= Orthostatic hypotension
o Adrenal insufficiency in some instances (not always needed)
* Mineralcorticoid antagonists
Endocrine- Thyroid
s Thyroid
o Important for maintaining thermogenic and metabolic homeostasis
e Thyroid hormones
o Thyroxine T4
o Triiodothyronine T3
* understand thyroid regulation/HPT axis
0 negative feedback loop between
s thyroid hormone effects
o iodine = essential for thyroid hormone production!!
o Nontoxic goiter global prevalence b/c of low iodine in developing countries
o Need iodine supplementation, well absorbed
s Thyroid function tests - check Free T4 and T3, check TSH
¢ Hypothyroidism:
o incidence/prevalence: 1% of general population, 5% if >60 yrs
* more common in women than men
o Primary vs. secondary hypothyroidism
= Primary: due to thyroid gland (HIGH TSH, LOW FT4)
= Secondary: due to lack of pituitary TSH (LOW TSH, HIGH FT4)
o Causes
= Hashimoto thyroiditis*** e‘Symptoms of Hypothyroidisn
ring 1 Stoang down!
Endocrine- pituitary/adrenal
* Pharmacologic application of hormone replacement vs. antagonists
o Replacement therapy for hormone deficiency states . e
o Antagonists for diseases caused by excess production of + Posteror Pitry POSTCFOT POV !
pituitary hormones. T ot
° Growth hormone "“lfi::"flh""f anterior piwitary, and target organ
o Required for normal growth, regulator of lipid/carb
metabolism throughout adulthood
o Deficiency tx:
= Somatropin used in children/adults
= Children w/ genetic diseases associated w/ short
stature
o Excess tx:
= Somatostatin analogs - octreotide, lanreotide
o Treatment of deficiency/excess
¢ Prolactin
o Principal hormone for lactation
o Hyperprolactinemia
= Etiologies
¢ Medications: SSRIs, Haldol, reglan, dopamine antagonists
* Prolactin-secreting adenomas
* dopamine agonists bromocriptine (parlodel)
o definition, symptoms, etiologies, treatment
* Vasopressin/ADH- effects, deficiency
* Oxytocin- effect, clinical uses
¢ Glucocorticoids/mineralcorticoids
o Glucocorticoids: effects metabolism, catabolism, immune responses,
inflammation
= Stimulated by ACTH
0Mineralocorticoids: regulate Na and K reabsorption in collecting tubules of
kidney
* Organ and tissue effects of glucocorticoids
o Metabolic effects
= Glucocorticoids stimulate gluconeogenesis and glycogen synthesis >
inc. BG, fat deposition, insulin resistance when too much!
= Regulate carb/protein/fat metabolism
= Release of amino acids via muscle catabolism
= Inhibition of peripheral glucose uptake
o Immunosuppressive effects
= Inhibits cell-mediated immunologic functions
* inc. neutrophils, dec.
lymphocytes/eosinophils/basophils/monocytes
* Inhibits leukocyte migration
= Does not interfere with the development of normal acquired immunity
o Catabolic effects
= Decreased muscle mass, thinning skin, osteoporosis, limited growth in
children
o Other effects
, = CNS - behavioral (“roid rage”, depression)
= Gastric acid secretion - lead to ulcers
= CVintegrity and contractility
e Cortisol (hydrocortisone)
o
= When you are more stressed or sick, more ACTH will be excreted!
0 Metabolized in liver, renally excreted
¢ Clinical uses of corticosteroids
o Adrenal disorders: dx and tx of adrenal dysfunction
= Dexamethasone suppression test
= Replacement in adrenal insufficiency
o Non-adrenal disroders
= r/t ability to suppress inflammatory/immune responses
= stimulation of lung maturation in fetus
* How corticosteroids used for diagnosis of adrenal disorders
Short cosyntropin-stimulation test Dexamethasone suppression tes
FAddison’s discase Diagnosis of Cushing syndrome.
cosyntropin IVorIM + 1 mg dexamethasone orally
(synthetic ACTH) @lipm
+ Plasma cortisol measured at0, + Plasma cortisol measured @
30,60 mi Sam
‘Lo for specificincreasein
cortisal level to o AT
o . § e/ indicativeof
Cushing’s syndrome
* Adrenocortical insufficiency, Addison’s Disease- symptoms, treatment, stress dosing,
side effects
o S/S
- ftigue, weakness + Hyperpigmentation of skin, mucosa
. depression + Saltcraving
+ Anorexia, weight loss - Pallor
- Dizziness, orthostatic - Amenorhea, decreased libido,
hypotension impotence
bdominl cramps.
yponateemia
- Hypoglycemia yed
« Hyperkatemia puberty
Iymphocytosis, cosinophilia
o Tx:
e Combined glucocorticoid & mineralocorticoid activity
s Adrenal crisis: demands parenteral glucocorticoids
= Don't forget stress dosing
= ADE:
* Hyperglycemia, glycosuria, Na retention w/ edema or HTN,
hypokalemia, peptic ulcer, osteoporosis, hidden infections
Glucocorticoids: indications that are non-adrenal related
* Hypercortisolism- adrenal hyperactivity- Cushing’s Typical Findings in Cushing Syndrome
Syndrome ——
o Resulting from chronic exposure to excessive _nf 3
circulating levels of glucocorticoid
o Typical signs, symptoms, exam findings
o Diagnosis
= 24-hour urine cortisol level HIGH
= Check ACTH levels
o Treatment
= Surgical removal of ACTH-producing tumor -
irradiation of pituitary tumor
, = 4 agents use preoperatively or as adjunctive therapy postop
* Steroidogenesis inhibitors, adrenolytic agents,
neuromodulators of ACTH release, glucocorticoid-receptor
blocking agents
o Ketoconazole: inhibits glucocorticoid synthesis at high
doses
o Mifepristone: glucocorticoid receptor antagonist
o synthesis inhibitors and antagonists
* Side effects of giving exogenous corticosteroids look like typical findings in Cushing
syndrome
s Corticosteroid weaning
o Abrupt cessation/withdrawal cause symptoms of adrenal insufficiency
o Wean anyone on...
= dose comparable w/ 20mg of prednisone a day for > 3 wks
= nighttime dose > 5mg of prednisone for more than a few weeks
= a cushingoid appearance
¢ Mineralocorticoids = Aldosterone
o Promotes reabsorption of Na from renal tubules
e Hyperaldosteronism
o S/S: hypokalemia, metabolic alkalosis, inc. plasma volume, HTN
o Treatment options:
¢ Fludrocortisone
o Potent steroid with glucocorticoid and mineralocorticoid activity
o Used for...
= Orthostatic hypotension
o Adrenal insufficiency in some instances (not always needed)
* Mineralcorticoid antagonists
Endocrine- Thyroid
s Thyroid
o Important for maintaining thermogenic and metabolic homeostasis
e Thyroid hormones
o Thyroxine T4
o Triiodothyronine T3
* understand thyroid regulation/HPT axis
0 negative feedback loop between
s thyroid hormone effects
o iodine = essential for thyroid hormone production!!
o Nontoxic goiter global prevalence b/c of low iodine in developing countries
o Need iodine supplementation, well absorbed
s Thyroid function tests - check Free T4 and T3, check TSH
¢ Hypothyroidism:
o incidence/prevalence: 1% of general population, 5% if >60 yrs
* more common in women than men
o Primary vs. secondary hypothyroidism
= Primary: due to thyroid gland (HIGH TSH, LOW FT4)
= Secondary: due to lack of pituitary TSH (LOW TSH, HIGH FT4)
o Causes
= Hashimoto thyroiditis*** e‘Symptoms of Hypothyroidisn
ring 1 Stoang down!
