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149 Cards in this Set

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gonadorelin (Lutrepulse)
Gonadorelin (Lutrepulse)

Class: GnRH
MOA: regulate FSH/LH pulsatile secretion
Use: Central Amenorrhea (Replacement Therapy IV), Idiopathic hypogonadotropic hypogonadism
AE: ovarian hyperstim, anaphylaxis
Contra:
Interaction:
Admin: parental
Leuprolide (Lupron)
Leuprolide (Lupron)

Class: GnRH analog
MOA: long acting, downregulate GnRH ^decrease LH/FSH
Use: ovulation supression, prostate/breast cancer, endometriosis, idiopathic precocius puberty
AE: Androgen-like effects
Contra: pregnancy, lactation, osteoporosis
Interaction:
Admin: SQ/IM
Goserelin (Lupron)
Goserelin (Lupron)

Class: GnRH analog
MOA: long acting, downregulate GnRH ^decrease LH/FSH
Use: ovulation supression, prostate/breast cancer, endometriosis, idiopathic precocius puberty
AE: Androgen-like effects
Contra: pregnancy, lactation, osteoporosis
Interaction:
Admin: SQ/IM
Naferelin (Synarel)
Nafarelin (Synarel)

Class: GnRH analog
MOA: long acting, downregulate GnRH ^decrease LH/FSH
Use: ovulation supression, prostate/breast cancer, endometriosis, idiopathic precocius puberty
AE: Androgen-like effects
Contra: pregnancy, lactation, osteoporosis
Interaction:
Admin: SQ/IM
Ganirelix (Antagon)
Ganirelix (Antagon)

Class: GnRH antag
MOA: rapid reversibile suppressor LH/FSH
Use: prevent premature LH surge (control ovarian hyperstimulation)
AE: ab pain, headache, ovarian hyperstimulation syndrome
Contra: pregnancy, lactation
Interaction:
Admin: SQ
Sermorelin (Geref)
Sermorelin (Geref)

Class: GHRH analog
MOA: pulsatile release, stim IGF, indirect anabolic/growth promotion
Use: GH def, GH def diag
AE: facial flushing, N/V
Contra:
Interaction: drugs affect secretion GH - insulin, glucocorticoids, NSAIDS.... increase GH level - Clonidine, levodopa... decrease response GHRH - antimuscarinic drugs
Admin:
Octreotide (Sandostatin)
Octreotide (Sandostatin)

Class: somatostatin analog
MOA: inhibit secretion GI/pit horm (more selective)
Use: acromegaly, hyperfxn endocrine tumors (GI secreting, VIP secreting tumors & carcinoid tumor)
AE: supress insulin release, gallstone, abd pain, diarrhea, N/V
Contra:
Interaction: decreased bioavailability cyclosporine.. additive beta and Ca channel blockers
Admin:
Bromocriptine (Parlodel)
Bromocriptine (Parlodel)

Class: D2 receptor antag
MOA: inhib prolactin release - ant pit
Use: hyperprolactinemia, acromegaly, parkinson's
AE: N/V, dizzy, ORTHO HTN, seizures, arrhythmias, stroke
Contra: sev ischemic disease, HTN, toxemia of pregnancy
Interaction: drugs that increase prolactin - phenothiazine (chlorpromazine) - antag + butyrophenone (haloperidol) - antag + MAOI.... AntiHTN agent - additive hypotensive effect
Admin:
Human chorionic gonadotropin (Pregnyl)
Human chorionic gonadotropin (Pregnyl)

Class: Gonadotropin prep
MOA: produced by placenta, isolated in urine from pregnant... contain LH
Use: Infertility - Induce ovulation, hypogonadism
AE: ovarian enlargement - hyperstim, thromboembolism
Contra:
Interaction:
Admin: IM
Menotropin (Pergonal, Repronex)
Menotropin (Pergonal -IM, Repronex -SQ)

Class: Gonadotropin prep isolated in urine from menopausal women (contain FSH/LH)
MOA:
Use: infertility - induce ovulation, hypogonadism
AE: ovarian enlargment - hyperstim, thromboembolism
Contra:
Interaction:
Admin: IM/SQ
Urofollitropin (Metrodin)
Urofollitropin (Metrodin)

Class: pure FSH
MOA:
Use: induce ovulation in women with PCO
AE: ovarian enlargment - hyperstimulation, thromboembolism
Contra:
Interaction:
Admin:
Somatropin (Humatrope)
Somatropin (Humatrope)

Class: recomb GH
MOA: IGF effect longer than drug 1/2 life, slow induction/clearance IGF
Use: replacement therapy 4 GH def, Turner's syndrome for girls, AIDS wasting or cachexia
AE: headache, intracranial HTN, muscle pain, mild hyperglycemia, ab production to GH, leukemia
Contra: when epiphyses closed
Interaction: corticosteroid, sex steroid
Admin: IM/SQ
Somatrem (Protropin)
Somatrem (Protropin)

Class: recomb GH analog
MOA: IGF effect longer than drug 1/2 life, slow induction/clearance IGF
Use: replacement therapy 4 GH def, Turner's syndrome in girls, AIDS wasting or cachexia
AE: headache, intracranial HTN, muscle pain, mild hyperglycemia, ab production to GH, leukemia
Contra: when epiphyses closed
Interaction: corticosteroid, sex steroid
Admin: IM/SQ
Arginine Vasopressin (Pitressin)
Arginine Vasopressin (Pitressin)

Class: made hypo, post pit horm
MOA: antidiuretic, increase resorption H2O renal collecting ducts (increase bv), stim contraction vasc sm (increase bp)
USE: diabetes insipidus, hemophilia A, vonWillebrands, enuresis
AE: H2O INTOX, vasoconstriction
Contra: chronic nephritis
Interaction: (+) carbamazepine, chlorpropamide, tricyclic (increase bp HTN crisis) ...(-) Li, heparin, epi, etoh
Admin: IM/SQ
Desmopressin (DDAVP)
Desmopressin (DDAVP)

Class: vasopressin synthetic analog (minimal vasoconst effect than AVP)
MOA: antidiuretic, increase resorption H2O renal CD (increase bv), stim contraction vasc sm (increase bp)
USE: diabetes insipidus, hemophilia A,vonWillebrands, enuresis
AE: H2O INTOX, vasoconstrict
Contra:
Interaction: (+ - inappropriate ADH - directly stimulate ADH secretion centrally by carbamazepine, chlorpropamide, tricyclic (increase bp HTN crisis) ...(- interfere with cellular axn of ADH in collecting ducts) Li, heparin, epi, etoh
Admin: IM/SQ/oral/nasal
*nasal drug of choice for CAD*
Oxytocin (Pitocin)
Oxytocin (Pitocin)

Class: post pit
MOA: released by reflex - dilation uterus/sucking
USE: IV - induce/enhance uterine contract... IM - prevent postpartum hemorrhage... Nasal - stim milk letdown
AE: arrhythmias, CNS stim, excessive uterine contraction, hyponatremia
Contra: abn fetal presentation, premature, cephalopelvic disproportion
Interaction:
Admin:
Thyrotropin (TSH, Thyropar)
Thyrotropin (TSH, Thyropar)

CLASS: TSH from bovine ant pit
MOA: stim synthesis/release T3/T4 and I- transport
USE: hypothyroid diag - diff btw primary and secondary.... thyroid carcinoma - enhance uptake of 131I by thyroid
AE: N/V, headahce, fever, sinus tachy, a fib
CONTRA: CAD, adrenal insuff
INTERACTION: sympthomimetics - additive effect... hepatic enzyme inducers - barbs, rifampin, carbamazepine... estrogens increase levels of TBG
ADMIN: IM/SQ
Recombinant TSH (Thyrogen)
Recombinant TSH (Thyrogen)

CLASS: recombinant TSH
MOA: stim synthesis/release T3/T4 and I- transport
USE: hypothyroid diag - diff btw primary and secondary.... thyroid carcinoma - enhance uptake of 131I by thyroid
AE: N/V, headahce, fever, sinus tachy, a fib
CONTRA:
INTERACTION: sympthomimetics - additive effect... hepatic enzyme inducers - barbs, rifampin, carbamazepine... estrogens increase levels of TBG
ADMIN: IM/SQ
Levothyroxine Na (T4, Synthroid)
Levothyroxine Na (T4, Synthroid)

CLASS: Thyroid hormone
MOA:
USE: hypothyroid, TSH suprression, nodular thyroid disease
AE: headache, insomnia, diarrhea, tachy, arrythmia, wt loss, amenorrhea, fever, tremors
CONTRA: heart disease, adrenal insufficiency
INTERACTION: increase anticoag activity of warfarin... Increase TBG binding - estrogen, tamoxifen... Decrease TBG binding - aspirin, phenytoin, furosemide, androgens, carbamazepine... Hepatic enzyme inducers - barbs, rifampin, carbamazepine... bound by cholestyramine in GI
ADMIN:
Liothyronine (T3 Cytomel)
Liothyronine (T3 Cytomel)

CLASS: Thyroid hormone
MOA: t1/2=1 day, faster onset, more express, need freq dosing
USE: hypothyroidism, TSH suppress
AE: diarrhea, wt loss, tachy, headache, tremor, arrythmias, fever, amenorrhea, insomnia
INTERACTION: increase anticoag activity warfarin... increase TBG binding - estrogens, tamoxifen... decrease TBG binding - carbamazepine, aspirin, pheny, furosemide, androgens... Hepatic enzyme inducer - barb, rifampin, carbamazepine... bound by cholestyramine in GI tract
Liotrix (T3/T4 Thyrolar)
Liotrix (T3/T4 Thyrolar)

CLASS: Combo thyroid horm
MOA:
USE: hypothyroidism, TSH suppression
AE: headache, tremors, fever, tachy, arrythmias, insomnia, amenorrhea, weight loss, diarrhea
CONTRA:
INTERACTION: increase activity of warfarin... increase binding TBG - estrogens, tamoxifen... decrease binding TBG - aspirin, phenytoin, carbamazepine, furosemide, androgens... hepatic enzyme inducers - rifampin, carbamazepine, barb
ADMIN:
Propylthiouracil (PTU, Propylthyracil)
Propylthiouracil (PTU, Propylthyracil)

CLASS: Thioureylene (anti-thyroid)
MOA: inhibit periph conversion T4/T3, inhibit MIT/DIT coupling, inactivate oxidized thyroid peroxidase
USE: hyperthyroid, graves, hyperfxn thyroid nodules, thyroid storm (DOC)
AE: headache, vertigo, edema, N/V, Rash: urticaria, puritus, alopecia
CONTRA:
INTERACTION: reduces response to oral anticoag, shorter life, plasma bound protein
ADMIN: oral
Methimazole (Tapazole)
Methimazole (Tapazole)

CLASS: thioureylene (anti-thyroid)
MOA: inactivate oxidation thyroid peroxiase, inhib MIT/DIT coupling
USE: hyperthyroidism, graves, hyperfxning thyroid nodules, thyroid storm
AE: headache, vertigo, edema, N/V, rash: urticaria, puritus, alopecia; AGRANULOCYTOSIS, APLASTIC ANEMIA
CONTRA:
INTERACTION: reduces response to oral anticoag
ADMIN: oral, once a day
Lugol's solution (Strong I-)
Lugol's Solution (Strong I-)

CLASS: iodide solution
MOA: inhib synth further secretion, [] dependent, high dose prevent incorporation I into thyroid hormone
USE: hyperthyroidism, preop period in prep for surgery, thyroid storm
AE: N/V, diarrhea, acneiform rash, hypersensitivity (III), angioedema, hemorrhage, induction of goiter and myxedema
CONTRA:
INTERACTION: alters free Li []
ADMIN: oral
Ipodate (Oragrafin Sodium); Iopanoic Acid (Telepaque)
Ipodate (Oragrafin Sodium); Iopanoic Acid (Telepaque)

CLASS: Contrast agent
MOA: inhib T4-->T3 in periphery, euthyroid in 3 days, suppress T4, inhib release of horm
USE: hyperthyroidism and thyroid storm
AE: Few - well tolerated.. resemble iodides
CONTRA: toxicity in preg
INTERACTION: none
ADMIN: oral
Diatrizoate (Hypaque)
Diatrizoate (Hypaque)

CLASS: Contrast Agent
MOA: inhibit T4--> T3 periphery, euthyroid 3 days, suppress T4, inhib release of horm
USE: hyperthyroidism, thyroid storm
AE: few - well tolerated - sim to I
CONTRA: toxicity in preg
INTERACTION:
ADMIN: IV
Potassium Iodide (Thyro-Block)
Potassium Iodide (Thyro-Block)

CLASS: Iodide solution
MOA: rapid inhib release thyroid horm, limit transport I --> thyroid, inhib MIT/DIT synth
USE: hyperthyroidism, preop period for surgery, thyroid storm
AE: N/V, diarrhea, acneiform rash, hypersensitivity (III), angioedema, hemorrhage, induction goiter and myxedema
CONTRA:
INTERACTION: alter free Li []
ADMIN: oral
131 I (Iodotope)
131 I (Iodotope)

CLASS: Radioactive iodide
MOA:
USE: hyperthyroidism in poor surgical subjects, additional rx when subtotal thyroidectomy ineffective, toxic nodular goiter
AE: high incidence delayed hypothyroidism, long rx period
CONTRA: preg
INTERACTION:
ADMIN:
adjunctive therapy for thyroid? (3)
Beta Adrenergic Antag - propanolol/atenolol antagonizes sympathomimetic effects

CCB - Diltiazem controls tachy (decrease incidence)

Corticosteroids - Dexamethazone inhib periph conversion T4-->T3; antipyretic
ACTH regulates?
glucocorticoids
hypothal --(__)-- ant pit --(__)-- adrenal cortex --(__)-- negative feedback to (x3) --_____ positive feedback to (x2)
hypothal --(_CRH_)-- ant pit --(_ACTH_)-- adrenal cortex --(_CORTISOL_)-- negative feedback to (HYPOTHAL, ANT PIT, IMMUNE SYS) --___IL-1, 2, 6, TNFa__ positive feedback to (HYPOTHAL, ANT PIT)
__-> Glucocorticoid --(__)--> ___

how released?
when released most?
_CH_-> Glucocorticoid --(11-B OH IN MITOCH)--> CORTISOL

pulsatile release
highest levels in morning
metabolic axns of glucocorticoids
increase glycogenolysis, gluconeogenesis, protein catabolism... decrease protein synth, osteoclast formation & activity, Ca absorption in GI tract, TSH secretion
physical axn of glucocorticoids
anti-inflamm (decrease production PG, cytokine, IL)

decrease prolif and migration of lymphocyte and macrophages

*inhibit accumulation neutrophils and monocytes at infection site and suppress activity
Cortisol, Hydrocortisone (Cortef)
Cortisol, Hydrocortisone (Cortef)

CLASS: short acting glucocort
MOA:
USE: *REPLACEMENT THERAPY* replace cortisol hyperfxn (cushing, congenital adrenal hyperplasia); hypofxn (addisons)... anti-inflamm (allergic rxn, infection, transplants... adjuvant... diagnostic dexamethasone suppression, fetal lung maturation
AE: suppress HPA; increased physiological response
CONTRA:
INTERACTION: many
ADMIN: IM/IV/ORAL
Prednisone (Deltasone); Prednisolone (Delta-Cortef)
Prednisone (Deltasone)

CLASS: intermed acting glucocort
MOA:
USE: *INFLAMMATION*
replacement, anti-infl... collagen dz, vasculitis, GI inflammatory dz, renal autoimmune dz, bronchial asthma, COPD
AE: suppress HPA, increase physiological response
CONTRA: liver dysfxn
INTERACTION: many
ADMIN: oral; IV/IM
**1st choice chronic use**
Methyl Prednisone (A-Methapred)
Methyl Prednisone (A-Methapred)

CLASS: long acting gluco
MOA:
USE: replacement, anti-inflamm... collagen dz, vasculitis, GI inflamm, renal autoimmune dz, bronchial asthma, copd
AE: suppress HPA, increase physiological response
CONTRA:
INTERACTION: many
ADMIN:
Dexamethasone (Decadron); Betamethasone (Celestone)
Dexamethasone (Decadron); Betamethasone (Celestone)

CLASS: long acting gluco
MOA:
USE: septic shock, brain edema *max anti-inflamm*
AE: b/c long 1/2 life, pronounced growth/bone suppression
CONTRA:
INTERACTION: many
ADMIN: IM/ORAL/TOPICAL/IV; ORAL TOPICAL INHALE

**BEST USED ACUTELY**
Mifepristone (RU-486)
Mifepristone (RU-486)

CLASS: glucocorticoid antag @ higher doses
MOA: block receptor, interfere with regulation HPA axis, increase ACTH & cortisol
USE: hypercorticism
AE: precipitate acute adrenal insufficiency
CONTRA:
INTERACTION:
ADMIN:
LONG TERM GLUCOCORTICOID RX SIDE EFFECT/TOXICITY?
BONE: children/women high risk... decrease osteoblast activity, increase Vit D --> 1, 25 OH but block ability to reabsorb (hypocalcemia, increase PTH release, bone absorption

Glucose - hyperglycemia

GUT - increased peptic ulcer

CNS - increased arousal/euphoria but prolonged=depression/sleep disturbances/psychosis
WAT IS THE DOC FOR HYPOPARATHYROIDISM?
dihydrotachysterol
what is a fatal side effect of Vit D?
hypercalcemia
what drug interaction can increase the risk of Vit D side effect?
Thiazides decrease Ca excretion and increase serum Ca levels
mech axn Vit D?
INCREASES SERUM Ca
1) increase bone resorption by increase osteoclast activity
2) increase GI absorption of Ca and P
3) decrease renal excretion Ca and P
4) inhibit PTH secretion (by increasing serum Ca)
mech axn parathyroid horm?
INCREASES serum Ca
1) increase GI absorption Ca but decreases absorption P
2) stimulate Vit D formation
3) stim bone resorption
mech axn calcitonin?
DECREASES SERUM Ca
1) inhibits bone resorption
2) decreases GI absorption Ca
3) increases renal excretion of Ca and P
mech axn bisphosphonates??
what drug is in this class?
alendronate
1) inhibit bone resorption -inhibit osteoclast activity
2) inhibit formation, aggregation, dissolution hydroxyapetite
AE associated with first generation bisphosphonates?
inhibit mineralization - cause osteomalacia
pharmacokinetics of bisphosphonates?
poor intestinal absorption
cannot take with food
excreted unchanged in urine
AE of Vit D?
hypercalcemia, hyperphosphatemia
AE calcitonin
hypersensitivity rxn
hypocalcemia
GI disturbances
AE etidronate
osteomalacia
GI disturbances
AE alendronate
GI disturbances, rash, musculoskeletal pain
what non-hormonal drug is used to rx osteoporosis?
alendronate
mech Sulfonylureas?
glipizide, glyburide

STIM insulin release
mech Biguanides?
metformin

increase insulin BINDING to receptor
mech ThiazolidinedioneS?
"TRPS"
risoglitazone, pioglitazone

increase SENSITIVITY of TARGET TISSUE to insulin
mech Alpha glucosidase Inhibitors?
arabose

prevent ABSORPTION of glucose, starch, dextrin, disaccharides in intestine
what is a short acting insulin
SHILis NIL LU
humalog, insulin, lisipro
what are intermediate acting insulins?
SHILis NIL LU

NPH, lente
what are long acting insulins?
SHILis NIL LU

ultralente
what are insulin's axns?
Carb metab: increase glycogen synthesis, pentose shunt, glucose oxidation, facilitates glucose transport via GLUT 4... decrease gluconeogenesis

Lipid metab: increases FA transport and TG synthesis... decrease lipolysis

Protein metab: increases aa transport, protein synthesis... decreases protein degredation
why lispro and not insulin?
liSpRo
more RAPID onset
SHORTER duration axn
prevents SPIKING + rebound hypoglycemia
therefore better pt compliance + tighter regulation of plasma glucose concentrations
what drugs/hormones stimulate insulin release normally?
Nutrients - glucose, aa, FA, ketone bodies

Hormones - secretin, gastrin, VIP, GIP

Drugs - beta 2 agonist, muscarinic cholinergic agonist, sulfonylureas
what hormones/drugs inhibit insulin release?
*all work DIRECTLY on beta cells in pancreas*

hormones - somatostatin, glucagon

drugs - alpha 2 agonists
complications from insulin therapy?
ALLERGIC RXN - IgE mediated... Rx by switching to human insulin or desensitization

RESISTANCE - IgG mediated... resensitizing with thiazolidinedione
1st generation sulfonylureas vs 2nd generation sulfonylureas
1st gen sulfonylureas -
variable t1/2 (2-48hrs)

2nd gen sulfonylureas -
10-100x greater potency
t1/2 = 24 hrs
binds tighter to plasma binding proteins

BOTH - bind plasma binding proteins
AE of oral antidiabetic agents?
hypoglycemia

acarbose causes flatulence
contraindications of sulfonylureas?
no insulin, pregnancy/lactation, hepatic renal insuffiency
drug interactions of sulfonylureas?
SALICYLATES displace sulfonylureas from binding proteins

SALICYLATES, PROBENECID, SULFONAMIDES decrease urinary excretion of sulfonylureas

MAOI, CHLORAMPHENICOL, PHENYLBUTAZONE reduce hepatic metab of sulfonylureas
contra of biguanides?
hepatic/renal disorder - increases risk for lactic acidosis
contra of thiazolidinedione
none
contra of alpha glucosidase inhibitors?
none
human GnRh vs long-acting GnRH analog?
gonadorelin (human GnRH) - short t1/2, used for replacement therapy (amenorrhea, hypogonadism

leuprolide, goserelin, nafarelin - longer t1/2, down regulates receptor, used to suppress hormone production (breast/prostate cancer, endometriosis, precocius puberty, ovulation suppression
native somatostatin vs somatostatin analog
native - limited by short t1/2, also rebound hypersecretion GH

analog (octreotide) - resistant to enzymatic degradation, longer t1/2, oral, more selective for inhibiting GH
ganirelix mech?
GnRH antag

rapid reversible suppression LH/FSH
ganirelix clinical use?
controlled ovarian hyperstimulation - prevent premature LH surge
ganirelix AE?
ovarian hyperstimulation syndrome
bromocriptine AE during initiation of rx?
orthostatic hypotension, N/V, dizziness
what drugs potentiate bromocriptine effect?
antihypertensive agents
what drugs inhibit bromocriptine effect
drugs that increase prolactin - phenothiazines, butyrophenones, MAO
why do the effects of somatropin (GH) outlast drug's t1/2?
IGF effect is longer than t 1/2 b/c it has

IGF has slow induction and clearance
what is the DOC in CAD
desmopressin
desmopressin AE?
water intoxification
what potentiates desmopressin?
siADH drugs - directly stimulate ADH secretion centrally

carbamazepine, chlorpropamide, tricyclics
what inhibits desmopressin?
drugs that interefere with ADH axns in Collecting duct

Li, heparin, epi, etoh
what is the DOC for thyroid preparations?
levothyroxine

takes 4-6 weeks to reach steady state plasma [ ]

must be converted to T3
how do you dose T4 for pregnant pt?
increase dosage

high estrogen levels during pregnancy stimulate increased production TBG

less T4 available
thyrotropin use?
hypothyroidism diagnosis (differentiates btw primary/secondary , thyroid carcinoma

enhances iodine uptake into thyroid gland

use in conjuction with 131 I
propylthiouracil vs methimazole mech?
THIOUREYLENE
propylthiouracil - inhibits peripheral conversion T4 -> T3

both
1)inhibit thyroid perixidase mediated iodination (irreversibly inactivates oxidized form of thyroid peroxidase)
2) inhibit MIT/DIT coupling
propylthiouracil vs methimazole AE?
both:
rash, GI upset, headache

methimazole: agranulocytosis, aplastic anemia
how do you rx thyroid storm?
1) iodide w/in 24 hrs (inhibits release of hormones)

2) propylthiouracil (longer t1/2, longer time to get effect) - used b/c inhibits peripheral conversion

3) for symptom - also give propanolol
what is thyroid storm?
life threatening thyrotoxicosis
AE associated with hyperthyroidism rx with radioactive iodine?
high incidence of delayed hypothyroidism
what are short acting glucocorticoids?
8-12 hrs

hydrocortisone, cortisol
what are intermediate acting glucocorticoids?
18-36

prednisolone, prednisone
what are long acting glucocorticoids?
1-3 days

betamethasone, dexamethasone
what is cortisol and hydrocortisone used for?
rx allergic rxn

suppress immune sys

anti-inflamm
what is prednisone and prednisolone used for?
anti-inflamm to rx
asthma,
COPD,
renal autoimmune disease,
GI inflamm disease, vasculitis,
collagen diseases
what is the clinical use of dexamethasone and betamethasone?
dexamethasone suppression test
septic shock
edema
lymphatic cancer (lymphotoxic nature)
chronic vs alternate day glucocorticoid therapy
chronic - some pt don't respond

alternate day - adv
prolonged anti-inflammatory effects
minimize HPA suppression
facilitate HPA recovery
minimizes reduction in bone growth
minimizes risk 4 hypercortisolism (Cushing-like syndrome)

abrupt switching can lead to hypocortisolism (tired, N/V, hypotension)
AE to glucocorticoid therapy?
bone - increased bone loss
decreased bone growth

glucose - hyperglycemia due to blockade of insulin effects
increased synthesis of glucose

gut - increased ulcers
increased HCl secretion
reduced formation of mucus lining

CNS - first: arousal/euphoria
later: depression/psychosis

HPA: Suppression of your own HPA axis
inability to synthesize your own cortisol

immune system - suppression
increased risk 4 infection
which drug is a glucocorticoid antag?
mifepristone

anti-progestin

@ higher doses blocks glucocortisol receptor

rx hypercortisolism
MOA and uses for mitotane
MOA: similar to DDT, unknown mech

use: adenocortical carcinoma
MOA and uses for aminoglutethimide
moa: inhib P450-scc (P450-11 beta @ high doses)

use: cushing's
ACTH hypersecretion
breast cancer (aromatase inhibition)
MOA and uses for ketoconazole
MOA: inhib P450-17 alpha
(P450-scc @ high doses)

use: cushings *MOST EFFECTIVE*
MOA and uses for trilostane
MOA: inhib 3 beta hydroxysteroid dehydrogenase

use: cushings
physiological mech of mineralocorticoids
salt retention - increase Na reabsorption, excrete K

aldosterone binds to response element on DNA

induces formation AIP, which increase cycling and change permeability

activates and inserts Na channels/pumps into
1) basolateral membrane(increase Na pump axn)

2) lumenal membrane (increase Na conduct activity, make (-), drive H & K to lumen)

in DCT and CD
AE of mineralocorticoid agonist?
Na retention

hypertension

@ high doses elicit symptoms resembling adrenal hypersecretion
AE Mitotane?
anorexia,

N,

lethargy
AE Aminoglutethimide
GI,

neurological,

signs of adrenal insufficiency
AE Ketoconazole
hepatic dysfxn

decrease metab of antihistamines -> prolong QT interval
AE Trilostane
adrenal insufficiency
why are natural estrogens given only parentally?
extensive first pass effect
what forms of estrogen can be given orally?
conjugated and synthetic estrogens

conjugated estrogens are hydrolyzed in intestine to estrogen and have less first pass effect

C17 substitution decrease hepatic metabolism of synthetic estrogen
what forms of estrogen are commonly used in postmenopausal therapy?
conjugated estrogens
where are conjugated estrogens derived from?
premarin - female horse urine

Cenestin - yam and soy
benefits of estrogen therapy in postmenopausal women
inhibit bone resorption in osteoporosis

decrease vasomotor symptoms

prevent cardiovascular dz (increase HDL/LDL ratio)
AE of estrogen replacement therapy in postmenopausal women
N

migrane

mood lability

thromboembolism

gallbladder dz

HTN
oral vs transdermal estrogens for postmenopausal hormone replacement therapy
oral
increase SSBG levels, increase secretion of CH to bile, increase exposure of liver to high [] of estrogens, relieves vasomotor symptoms, protects against blood loss, CV benefits

transdermal
decreased beneficial changes in plasma lipoproteins, skin rxn to patches, relieves vasomotor symptoms and protects against bone loss, consistent blood levels
raloxifine MOA?
Selective estrogen receptor modulator

decreases bone resorption and remodeling
where does raloxifine have estrogen vs anti-estrogen effects?
estrogen effects:
bone + lipid metabolism

anti-estrogen effects:
breast + uterus
why are progestins included in postmenopausal hormone replacement therapy?
addition of progestins limits endometrial hyperplasia and risk of endometrial cancer
MOA of antiestrogens?
antag @ estrogen receptor

blocks binding of estrogen to its receptor
what confirmation of antiestrogens are responsible for antiestrogenic activity
trans
clinical uses of antiestrogens
clomiphene - induce ovulation

tamoxifen + toremifine - breast cancer

anastrozole and exemestane - advanced breast cancer in postmenopausal women

GnRH analog + Ganirelix - suppress preovulatory surges - controlled ovarian hyperstimulation
clomiphene vs tamoxifen pharmacokinetics
both -
extensive plasma protein binding
enterohepatic recirc
accumulation in fatty tissues

tamoxifen has an active metabolite that is more potent than itself
AE of toremifene vs tamoxifen
both:
N/V
hot flashes
menstral irregularities
PE
increased risk of endometrial cancer

tamoxifen only - hyperlipidemia

TOREMIFINE PREFERRED IN PT WITH CV OR HIGH CH
current clinical uses for mifepristone in Great Britain
medical abortion in first trimester
MOA and use of aromatase inhibitors
anastrozole - nonsteroidal, competitive aromatase inhib

exemestane - steroidal, irreversible aromatase inhib

*BOTH RX ADVANCED BREAST CANCER IN POSTMENOPAUSAL WOMEN*
how to administer testosterone so give good absorption and CONSISTENT blood levels?

what do you do this to rx?
scrotal patches - mimics circadial rhythm

rx hypogonadism
how does methyl sub @ C17 of testosterone alter pharm axns and administration
decreases hepatic metabolism

longer t1/2

allow oral administration
why should testosterone derivatives (fluoxymesterone NOT be used to rx hypogonadism?
associated with hepatotoxicity and liver cancer with prolonged use
MOA nilutamide
irreversible androgen receptor antag

used in combo with orchiectomy
MOA flutamide vs bicalutamide
both competitive antag

use in combo with GnRH agonist or radiation rx for metastatic prostate cancer
DOC 4 endometriosis?
Danazol
what Danazol use?
*ENDOMETRIOSIS*, hereditary angioneurotic edema
AE Danazol
masculinization,

acne,

hirsutism,

menstrual irregularities
what drugs used to rx prostatic cancer & MOA?
GnRH analog - suppress HPT axis, downregulate system

ketoconazole - block CP-450 enzymes involved in steroid biosynthesis

flutamide and bicalutamide - nonsteroidal, competitive receptor antag

Nilutamide - nonsteroidal irreversible androgen receptor antag
what drug commonly used to rx benign prostatic hyperplasia
finasteride
use finasteride?
male pattern baldness

*NO USE IN WOMEN B/C TERATOGEN*
finesteride MOA?
inhib 5-alpha reductase

competitive inhibitor test -> DHT
Fludrocortisone (Florinef)
Fludrocortisone (Florinef

CLASS: Mineralocort agonist
MOA:
USE: hypoaldosteronism
AE: salt retention, HTN
CONTRA:
INTERACTION: high doses resemble glucocorticoids (adrenal hypersecretion)
ADMIN:
Spironolactone (Aldactone)
Spironolactone (Aldactone)

CLASS: Mineralocort antag
MOA: no bind DNA so no AIP
USE: hyperaldosteronism, refractory edema
AE: Hyperkalemia
CONTRA:
INTERACTION: sailcylates - block secretion of active metabolite
ADMIN: poor bioavailability
Aminoglutethimide (Cytadren)
Aminoglutethimide (Cytadren)

CLASS: Corticosteroid synthesis inhib
MOA: inhib P450 scc (rate limiting enzymes for all steroid)
USE: Cushings, breast cancer, hypersecretion ectopic production ACTH
AE: GI distress, neurological, adrenal insufficiency, shut down body cortisol
CONTRA:
INTERACTION: many - induces P450 CYP3A
ADMIN:
Ketoconazole (Nizoral)
Ketoconazole (Nizoral)

CLASS: Corticosteroid synthesis inhib
MOA: inhib P450 17 alpha, 11 beta, scc
USE: *MOST EFFECTIVE FOR CUSHINGS*
AE: hepatic dysfxn, PVC
CONTRA:
INTERACTION: second generation antihistamine - increase QT interval
ADMIN:
Trilostane (Modrastane)
Trilostane (Modrastane)

CLASS: Corticosteroid synthesis inhib
MOA: inhib 3 beta OH steroid dehydrogenase (block pregnenolone to progest)
USE: Cushings
AE: Adrenal insufficiency
CONTRA:
INTERACTION: ?
ADMIN:
Metyrapone (Metopirone)
Metyrapone (Metopirone)

CLASS: corticosteroid synthesis inhib
MOA:
USE: HPA testing
AE: HTN, hirsutism
CONTRA:
INTERACTION:
ADMIN: no longer available in US
Mitotane (Lysodren)
Mitotane (Lysodren)

CLASS: Corticosteroid Synthesis inhib
MOA:
USE: adrenocortical carcinoma (hypersecretion cortisol)
AE: anorexia, lethargy, nausea
CONTRA:
INTERACTION: unknown
ADMIN: