Endocrine drugs Flashcards
Drug that is purified from the urine of postmenopausal women and is used to promote spermatogenesis
Urofollitropin
A 3 year old boy with failure to thrive and metabolic disturbance was found to have an inactivating mutation in the gene that encodes the growth hormone receptor. Which drug will most likely improve his metabolic function and promote its growth
Mecasermin
- a combiantion of recombinant IGF-1 and the binding protein that protects IGF-1 from immediate destruction
An important difference between leuprolide and ganirelix is that ganirelix _____
immediately reduces gonadotropin secretion
- Leuprolide
- agonist of GnRH receptors
- about 1 week of sustained activity
- Ganirelix
- GnRH antagonist
used to treat the amenorrhea-galctorrhea syndrome
Bromocriptine
- dopamine receptor agonist
- drug should not be used in patients with a history of schizophrenia or other forms of psychotic illness
Patient is a known case of turner syndrome. Which drug will allow her to achive a higher adult height
Somatropin
- recombinant human GH
- Turner syndrome or chronic renal failure
- ACTH
- used in diagnosisng adrenal insuffciency
- CRH
- distringuish cushing’s syndrome from ectopic ACTH secretion
Most appropriate drug to treat precocius puberty
Leuprolide
- GnRH agonist
Pharmacologic treatment for acromegaly
Octreotide
- somatostatin analog. has some efficacy in reducing the excess GH production
The 2nd step in ovulation induction is the administration of a drug with FSH activity.
Follitropin
- Recombinant FSH
- hCG - LH analog
treatment for pituitary diabetes insipidus
Desmopressin
- V2 receptor
Somatropin
Recombinant human GH. Actis through GH receptors to icnrease the production of IGF-1
Replacement in GH deficienct. Icnreased final adult height in children with certain conditions associated with short stature. Wasting in HIV infection. Short bowel syndrome
SQ injection
SE: In children, pseudotumor cerebri, slipped capital femoral epiphysis, progression of scoliosis, edema ,and hyperglycemia. In Adults, peripheral edema, myalgia,and arthralgias. Risk os asphyxia in severely obese patients with Prader Willi syndrome and upper airway obstruction or sleep apnea
Mecasermin
IGF-1 agonist
Replacement of IGF-1 deficiency that is not responsive to exogenous GH
SQ injection
SE: hypoglycemia, intracranial hypertension, increased liver enzymes
Octreotide
Lantreotide: long acting formulation for Acromegaly
Somatostanin receptor agonist
Used in Acromegaly an several other homone secreting tumors. Acute control of bleeding from esophageal varices
SC or IV injection. Long acting formualtion injected IM
SE: GI disturbances, galsstone, bradycardia, cardiac conduction anomalies
Pegvisomant
Blocks GH receptor signalling
USed in acromegaly
SC injection
Increased liver enzymes
Follitropin alfa
FSH receptor agonist
Used in controlled ovulation hyperstimualtion in women. Infertility due to hypogonadotropic hypogonadism in men
SC injection
SE: ovarian hyperstimulation syndrome and multiple pregnancies in women. Gynecomastia in men. Headache, depression, edema, in both sexe
Recombinant product with the same peptide sequence as follitropin alfa but differs in its carbohydrate side chains
Follitropin beta
Human FSH purified from the urine of postmenopausal women
Urofollitropin
Extract of the urine of postmenopausal women; contains both FSH and LH activity
Menotropins (hMG)
hCG
LH receptor agonist
Initiation of final oocyte maturation and ovulation during controlled ovarian stimulation. Male hypogonadotropic hypogonadism
IM or SC injection
SE: ovarian hyperstimualtion syndrome, multiple pregnancies in women. Gynecomastia in men, headache, depression, edema in both sexes
Recombinant fom of hCG
choriogonadotropin alfa
Recombinant form of human LH
Lutropin
Leuprolide
GnRH receptor agonist
Used in ovarian suppresion. Controlled ovarian stimulation. Central precocious puberty in some transgender early pubertal adolescents. Advanced prostate cancer
Adminsitered IV, SC, IM, or intranasally. Depot formulations are available
SE: headache, light headedness, nausea, injection site reactions, with continuous treatment symptoms of hypogonadism
Synthetic human GnRH
Gonadorelin
Ganirelix
Antagonist of GnRH receptors
Prevention of premature LH surges during controlled ovarian stimualtion
SC injection
SE: nausea and vomiting
GnRH receptor antagonists approved for prostate cancer
Degarelix, abarelix
Bromocriptine
Dopaine D2 receptor agonist
Used in hyperprolactinemia, Parkinson’s disease
Administered orally or for hyperprolactemia, vaginally
SE; GI disturbances, orthostatic hypotention, headache, psychiatric disturbances, vasopasm and pulmonary infiltrates in high doses
OXytocin
Oxytocin receptor agonist
Used in induction and augmentation of labor. Control of uterine hemorrhage after delivery
IV infusion
SE: fetal distress, placental abruption, uterine rupture, fluid retetion, hypotension
Atosiban
Antagonist of oxytocin receptor
Tocolysis for preterm labor.
IV infusion
SE: concern about rates of infant death. not FDA approved
Desmopressin
Agonist of vasopressin V2 receptors
used in pituitary diabetes insipidus. Hemophilia A and vWF
Oral, IV, SC, or intranasal adminsitration
SE: GI disturbances, headache, hyponatremia, allergic reactions
Used in treatment of DI and sometimes used to control bleeding from esophageal varices?
Vasopressin
Conivaptan
Antagonist of vasopressin V1a and V2 receptors
used in hyponatremia in hospitalized patients.
Administered as an IV infusion
Infusion site reactions
- Tolvaptan - silimar but more selective for V2 receptors; oral administration limited to 30 day treatment due to hepatoxicity
In grave’s disease, the cause of the hyperthyroidism is the production of an antibody that ___________
Activatesthe thyroid gland TSH receptor and stimulates thyroid hormone synthesis and release
Methimazole reduces serum concentration of T3 by primarily ____________
Preventing the addition of iodine to tyrosine residues on thyroglobulin
A rare but serious toxicity associated with the thioamides
Agranulocytosis
A 56 year old woman presented to the emergency deparment with tachycardia, shortness of breath, and chest pain. She had shortness of breath and diarrhea for the last 2 days and was sweating and anxious. a relative reported that the patient had run out of methimazole 2 weeks earlier. The diagnosisof thyroid storm was made. What drug that is sueful adjuvant in the treatment of thyroid storm?
Propanolol
What drug can be administered for 10-14 days before surgery to reduce the vasuclarity of the thyroid gland?
Lugol’s solution
When initiating T4 therapy for an elderly patient with long standing hypothyroidism, it is important to begin with small dosesto avoid ______
overstimulating of the heart
What hormone is produced in the peripheral tissues when levothyroxine is administered??
T3
A 62 year old woman presents with complaints of fatigue sluggishness and weight gain. She needs to nap several times. She has been taking T4 for the past 15 years without significant problem regarding her energy level. Her recent history is significant of arrythmia and she is currently taking an anti arrythmic drug. What is the most likely cause of her current situation?
Amiodarone
A 25 year old woman presents with insomnia and fears she may habe something wrong with her heart. She describes her heart jumping out of her chest. She feel healthy otherwise and reports she has lots of energy. Lab tests confirms hyperthyroidism. What drug that produces permanent reduction activity?
131I
Thyroid preparations
(Levothyroxine, Liothyronine)
Activation of nuclear receptors results in gene expression with RNA formulation and protein synthesis.
Hypothyroidism
MAximum effect seen after 6-8 weeks of therapy. T4 is converted to T3 in target cells, the liver and the kidneys. T3 is 10x more potent than T4
Thiomides
(PTU, methimazole)
Inhibit thyroid peroxidase reactions, iodine organification and peripheral conversion of T4 to T3
Hyperthyroidism
Oral administration, delayed onset of activity
SE: nausea, GI disturbancs, rash, agranulocytosis, hepatitis (PTU-warning). hypothyroidism
Lugol’s solution, potassium iodide
Inhibit iodine organification and hormone release. Reduce size and vascularity of thyroid gland
Preparation for surgical thyroidectomy
Oral adminsitration, acute onset of activity within 2-7 days
Radioactive Iodine
Radiation-induced destruction of thyroid parenchyma
Used in hyperthyroidism. Patient should be euthyroid or on B-blockers before RAI. Avoid in pregnancy and in nursing mothers
Oral adminsitration
SE: sore throat, hypothyroidism
Beta blockers
(Propanolol, other beta blcokers lacking partial agonist activity)
Inhibition of B receptors; Inhibition of conversion of T4 to T3(propanolol only)
Used in thyroid storm. adjunct to control tachycardia, hypertension, and atrial fibrillation
Rapid onset of activity
SE: asthma, AV blockade, hypotension, bradycardia
What is the pharmacologic effect of exogenous glucocorticoids in asthma?
Inhibition of leukotriene synthesis
One of the adverse metabolic effects of long term glucocorticoid therapy is the ______ of bone, which can result to ________
Net loss
Osteoporosis
A patient is a known case of cushing’s syndrome due to adrenal tumor. What drug woul be expected to reduce the signs and symptoms of the patient?
Ketoconazole
- Inhibits many types of cytochrome P450
- reduce the unregulated overproduction of corticosteroids by adrenal tumors
Describes the therapeutic effect of glucocorticoid administration in patients with 21a-hydroxylase activity
Suppresion of ACTH secretion
Describes a glucocorticoid response element
A specific nucleotide sequence that is recognized by steroid hormone receptor-hormone complex
Gradual tapering of a glucocorticoid is required for recovery of _________
The hypothalamic-pituitary-adrenal system
Most pont antiinflammatory steroid?
Dexamethasone
a 54 year old man has developed signs of severe acute adrenal insufficiency. The patient should be treated immediately with this combination
Cortisol and fludrocortisone
Drug that in high doses blocks the glucocorticoid receptor
Mifepristone
- Competitive antagonist of glucocorticoid and progesterone receptors
Prednisone
Activation of glucocorticoid receptor alters gene transcription
Used in may inflammatory conditions, organ transplantation, hematologic cancers
Druration of activity is longer than pharmacokinetic half life of drug owing to gene transcription effects
SE: adrenal suppression, growth inhibtion, muscle wasting, osteoporosis, salt retention, glucose intolerance, behavioral changes
Fludrocortisone
Strong agonist at mineralocorticoid receptors and moderate activation of glucocorticoid receptors
Used in Adrenal insufficiency (Addison’s disease)
Lonh duration of action
SE: salt and fluid retention, congestive heart failure, signs and symptoms of glucocorticoid excess
Mifepristone
Pharmacologic antagonist of glucocorticoid and progesterone receptors
Used in MEdical abortion, and very rarely Crushing’s syndrome
Oral administration
SE: Vaginal bleeding in women, abdominal pain, GI upset, diarrhea, headcahe
Spironolactone
Pharmacologic antagonist of mineralocorticoid receptor, weak antagonism or androgen receptors
Used in aldosteronism from any cause, hypokalemia due to other diuretics, post MI
Slow onset and offset of effect. DUration: 24-48h
SE: hyperkalemia, gynecomastia (spironolactone, not eplerenone), additive interaction with other K-retaining drugs
Eplerenone
More selective for mineralocorticoid receptor
similar to spironolactone
Ketoconazole
Blocks fungal and mammalian CYP450 enzymes.
Inhibits mammalian steroid hormone synthesis and fungal erogosterol syntesis
Oral, topical administration
SE: hepatic dysfunctio, many drug-dryg CYP450 interactions
Beclomethasone and budesonide
readily pentrates the airway mucosa but have short half lives after they enter the bloodm so systemic effects and toxicity are greatly reduced
A teenager seeks postcoital contraception. What drug will be effective for this purpose?
Mifepristone
- antagonist at progesterone and glucocorticoid receptors
- has lutelolytic effect
A 23 year old woman desires a combine oral contraceptive for pregnancy protection. What patient factor would lead a health professional to recommend alternative form of contraception?
History of migraine headache that is well controlled by sumatriptan
- estrogen containing hormonal contraceptives increases the risk of migraine headcahes
Men who uses large doses of anabolic steroids are at increased risk of
Cholestatic jaundice and elevation of AST in the blood
A 50 year old woman with a positive mammogram undergoes lumpectomy and a small carcinoma is removed. Biochemical analysis of the cancer reveals the presence of estrogen and progesterone receptors. What drug is recommended for the patient?
Tamoxifen
A 60 year old man is found to have a prostate lump and an elevated prostate specific antigen blood test. MRI suggests several enlarged LN in the lower abdomen. and an xray reveals 2 radiolcuent lesions in the bony pelvis. This patient is likely to be treated with ______
Leuprolide
- GnRH agonist used in the treatment of men with prostate cancer
- To prevent tumor flares – add flutamide
Most appropriate treatment for endometriosis
Medroxyprogesterone acetate by intramusculat injection
DEWS should never be used in pregnant women because it is associated with _____
Infertility and developmenmy of vaginal cancer in female offsprine
Unique property of SERMs
Act as agonsits in some tissues adn antagonists in other
Finasteride has efficacy in the prevention of male-pattern baldness by virtue of its ability to do which of the following?
Reduce the production of dihydrotestosterone
- 5a-reductase inhibitor
In patients with a strong family of breast cancer ______ may be a better choice than a full estrogen agonist
Raloxifene
Ethinyl estradiol
Activation of estrogen receptors leads to changes in the rates of transcription of estrogen-regulated genes
USed in hypogonadism in girls, oral and parenteral contraceptive
Oral, parenteral, or transdermal adminsitration. metabolism relies on cytochrome P450 systems. Enterohepatic recirculation occurs
Side Effects:
- Moderate toxicity
- Breakthrough bleeding, nasuea, breast tenderness
- Serious toxicity
- thromboembolism, gallbladder disease, hyperTG, migrane headache, hypertension, depression
- In post menopausal women
- Breast cancer, endometrial hyperplasia(unopposed estrogen)
- Combination with cytochrome P450 inducer can lead to breakthrough bleeding and reduced contraceptive efficacy
Prodrug that is converted ti ethinyl estradiol, contained in some contraceptives
Mestranol
Long acting estrogens administered IM and used for hypogonadism un young females
Estrogen Esters (Estradiol cypionate)
Norgestrel
Activaion of progesterone receptors leads to changes in the rate of transcription of progeterone-regulated genes
used in parenteral contraception, postcoital contraceptive
Oral, parenteral or transdermal administration, metabolism relies on cytochrome P450. Enterohepatic recirculation occurs
SE: weigh gaine, reversible decrease in bone mineral density (high doses)
Drospirenone
Spironolactone derivative of norgestrel
Tamoxifen
Estrogen antagonist actions in breast tissue and CNS. estrogen agonist effects in liver and bone
Used in prevention and adjuvant treatment of hormone-responsice breast cancer
Oral administration
SE: Hot flushes, thromboembolism, endometrial hyperplasia
approved for osteoporosis and prevention of breast cancer in selected patients.
Antagonist effect in breast, CNS, and endometrium
Agonist effects in the liver
Raloxifene
Approved for treatment of menopausal symptoms and prophylaxis of postmenopausal osteoporosis in combiantion with conjugated estrogens
Bazedoxifene
Partial agonist at estrogen receptor; used for ovulation inductionl antagonis effect in pituitary increases gonadotropin secretion
Clomiphene
Fulvrestant
Estrogen receptor antagonist in ALL tissues
Used in adjuvant treatment of homone-responsive Breast cancer that is resistant to first-line antiestrogen therapy
IM adminsitration
SE: hot flushes, headaches, injection site reactions
Anastrozole
Reduces estrogen synthesis by inhibiting aromatase enzyme
Used in adjuvant treatment of hormone responsive breast cancer
Oral administration
SE: hot flushes, MSK disorders, reduce bone mineral density
Irreversible aromatase inhibitor
Exemestane
Danazol
Weak cytochrome p450 inhibitor and partial agonist of progestin and androgen receptors
Used in endometriosis, fibrocystic breast disease
Oral administration. Drug interactions due to cytochrome P450 inhibition
SE: acne, hirsutism, weigh gain, menstrual disturbance, heaptic dysfunction
Mifepristone
Progestin and glucocorticoid receptor antagonist
Used in combination with prostaglandin for medical abortion
Oral
SE: GI disturbances (mostly due to misoprostol). vatginal bleeding, atypical infection
testosterone
Androgen receptor agonist
Used in male hypogonadism. weigh gain in patients with wasting syndromes
Transdermal, buccal, SQ implant
SE: In females, virilization. In men, high doses can cause gynecomastia, testicular shrinkage, infertility
Long acting androgens for parenteral administration
Testosterone esters (testosterone cypionate)
Anabolic steroids
Oxandrolone, nandrolone decanoate
Increased ration of anabolic to androgenic activity in laboratory animals. cholestatic jaundice, liver toxicity
Finasteride
Inhibition of 5a-reductase enzume that converts tetosterone to DHT
USed in BPH, male pattern hair loss
Oral adminisration
SE: rarely, impotence, gynecomastia
Flutamide
Competitive inhibition of androgen receptor
Usedin advance prostate cancer
Oral
SE: gynecomastia, hot flushes, impotence, hepatotoxicity
similar to flutamide but lower risk of hepatotoxicity
Bicalutamide, nilutamide
Mineralocorticoid receptor antagonist used mainly as potassium sparing diuretic; also gas androgen receptor antagonist, used for the treatment of hirsutism
Spironoalctone
Ketoconazole
inhibition of cytochrome p450 enzymes involved in andrigen synthesis
Ued in advanced prostate cancer that is resistant to first line-antiandrogen drugs
Oral
SE: interferes with synthesis of other steroids. MAny drug interactions due to cytochrome p450 inhibition
most likely complication of insulin adminsitration?
hypoglycemia
Tight control regimen
Establish a basal level of insulin with a small amount of along acting preparation (Insulin glargine) and supplemeting the insulin levels, when called for by food intake, with short acting insluin (lispro).
Lest tight control may be achieved with 2 injections of intermediate acting insulin per day.
Glipizide is a second generation ___________ that promotes insulin release by closing potassium channels in the pancreatic B cells
Sulfonylureas
Improtant effect of glucose
Increased glucose transport into cells
a 54 year old obese patient with type 2 diabetes has a history of alcoholism. In this patient, metformin should either be avoided or used with extreme caution because metformin and ethanol can increase the risk of
Lactic acidosis
Drug that is taken during the first part of a meal for the purpose of delaying the absorption of dietary carbohydrates?
Acarbose
The PPAR-y receptors that is activated the TZD increases tissue sensitivoty to insulin by___________
Regualting transcription of genese involved in glucose utilization
_________ is useful in the treatment of B-blocker induced cardiac depression
Glucagon
Rapid acting insulin
Lispro, aspart, glulisine
Intermediate actibg insulin
NPH
Long acting insulin
Detemir, glargine, degludec
Metformin
Decreased endogenous glucose production
Used in type2 DM
Oral administration
SE: GI distubances, lactic acidosis
Glipizide
Secretagogues
Increases insulin secretion from pancreatic beta cells by closing ATP sensitive potassium channels
Used in T2DM
Oral
SE: hypoglycemia, weight gain
Sulfonylureas with intermediate duration of action
Glyburide, glimepiride
Fast acting insulin secretatgouges
Repaglinide, nateglinide
Acarbose
Alpha glucosidase inhibitors
used in T2DM
oral
SE: GI disturbances
Thiazolidinediones
(Rosiglitazone)
Regulatesgene expression by binding to PPAR-y
used in type 2 DM
Oral administration
SE: fluid retention, edema, anemia, weigh gain, bone fracture in women, may worsen heat disease and increase risk of MI
Exanatide
Analog of glucagon-like peptide-1 (GLP-1) ParenterGLP-1 Receptors
used in T2DM
Parenteral
SE: Gi disturbances, headache, pancreatitis
Sitagliptin
Inhibitor of the DPP-4 that degrades GLP-1 and other incretins
Used in T2DM
Oral
SE: rhiitis, URTI, Rare allergic reactions
Pramlintide
Amylin analog
used in T1DM and T2DM
Parenteral adminsitration
SE: GI disturbances, hypoglycemia, headache
Glucagon
Activates glucagon receptors
Used in severe hypoglycemia and B-blocker overdose
PArenteral administation
SE: Gi disturbances, hypotension
SGLT2 inhibitors
(Canaglifozin, dapaglifozin)
Inhibit renal glucose absorption via SGLT2
used in T2DM
Oral
SE: Osmotic diuresis, genital and urinary tract infections
What drug is routinely added to calcium supplements?
Cholecalciferol
Most useful for the treatment of hypercalcemia in Paget’s disease
Pamindronate
- Biphosphonates and calcitonin are first line treaments
- Paminodranate can be given pareneterally
The active metabolites of vitamin D act through a nuclear receptor to produce this effect
Increase the absorption of calcium from the gastrointestinal tract
_________ increases bone formation and bone resoprion
Teriparatide
Should not be used longer than 2 years due to risk of osteosarcoma.
Long erm therapy 0f ___________ is assocaited with reduction in bone mineral density and an increased risk of fractures
Glucocorticoids
Oral biphosphontes can cause ___________
erosive esophagitis
_________ is a peptide hormone that prevents bone resorption. Can be given as nasal spray
Calcitonin
(Salmon calcitonin is available as nasal spray)
In aptients with chronic kidney disease that requires dialysis, the impaired priduction of active vitamin D metabolities with elevated serum phosphate due to renal impairment leads to secondary hypePTH. Administration of ___________ is necessary
Calcitriol
_________ is an analog of 1,25 dihydroxyvitamin D3 that lowers serum PTH at doses that rarely precipitate hypercalcemia
Paricalcitol
MOA of cincalcet as PTH lowering agent
Activating the serum sensing receptor in PTH cells
Vitamin D metabolites, analogs
(Cholecalciferol, ergocalciferol)
Regulates gene transcription via the vitamin D receptor to produce the effect
Used in vitamin D deficiency, osteoporosis, osteomalacia, psoriasis
Oral adminsitration.requires metabolism in the liver or kindey to active forms
SE: hypercalcemia, hyperphosphatemia, hypercalciuria
Used for management of secondary hyperPTH in patients with chronic kidney disease and for management of hypercalcemia in patients with hypoPth.
Cacitriol
this drug is in its active form
an analog of calcitriol approved for psoriasis
Calcipotriene
Alendronate
Suppresses the activity of osteoclasts and inhibits bone resorption
Used in Osteoporosis, Paget’s disease
Oral adminsitration daily or weekly
SE: adynamic bone, esophageal irritation, osteonecrosis of the jaw (rare)
Teriparatide
PTH analog
Acts throught PTH receptors to produce a netr increase in bone formation
Used in Osteoporosis
SQ inhection
SE: hypercalcemia, hypercaliuria, osteosarcoma in experimental animals
full length rhPTH used for hypoPTH
Natpara
Calcitonin
Acts through calcitonin receptors to inhibit bone resorption.
Used in osteoporosis
SQ or intranasal
SE: rhinitis with the nasal spray
Raloxifene
Estrogen agonist effect in bone. Estrogen antagonist effects in breast and endometrium
Osteoporosis in post menopausal women
Oral adminsitration
SE: Hot flushes, Thromboembolism
Denosumab
Binds to TANKL an prevents it from stimulating osteoclasts differentiation and function
Used in osteoporosis
SQ every 6 months
SE: may increase risk of infections, osteonecrosis of the jaw (rare)
Cinacalcet
Actiavates the calcium sensing receptor
Used in hyperparathyroidism
Oral adminsitration
SE: nausea, hypocalcemia, adynamic bone
Minerals
(calcium phosphate strontium)
Strontium suppresses bone resorption and phosphate required for bone mineralization
Used in osteoporosis, osteomalacia, calcium or phosphate deficiencies
Oral and parenteral
SE: ectopic calcification
