Endocrine Test 2

What are the second generation drug forms of sulfonylurea hypoglycemic agents? (less side effects with this generation)

-Glyburide (Diabeta, Micronase) -Glipizide (Glucotrol) -Gliclazide (Diamicron) -Glimepiride (Amaryl)

What are the 7 adverse effects of Sulfonylureas?

1. Hypoglycemia: due to over production of endogenous insulin (related to too high of dose or prolonged fasting) and typically found in elderly with liver/kidney dysfunction causing a reduction in clearance. 2. Weight Gain: due to insulin stimulation of glucose uptake into fat cells for storage 3. Bone marrow suppression: leads to aplastic anemia due to hematopoietic stem cell damage 4. N/V, Vasomotor flushing, and antidiuresis(increased ADH) 5. Drug-Drug interactions: due to significant plasma protein binding 6. First generation drugs cross placenta and get into breast milk. Avoid use in pregnant mothers, however, second generation are safe (glyburide 2nd line in gestational) 7. Light to moderate alcohol use increases action of drug, to lower blood glucose levels, while heavy drinking has a negative effect on blood glucose levels (increases glucose levels)

What are 3 forms of male contraception?

1. combined testosterone and progestin to suppress LH secretion and spermatogenesis 2. Condoms 3. Spermicides

Sulfonylureas are hypoglycemic agents for type 2 diabetics only, because they require the presence of insulin, so they do not work in IDDM patients. How do sulfonylureas work?

1. stimulate insulin release by blocking K+ channel in β-cells 2. increase sensitivity of tissues to insulin. 3. increase insulin affinity to insulin-receptors

What are 6 possible treatments for neuropathic pain?

1. α-lipoic acid 2. Opioids 3. Botulinum Toxin A 4. Emoxypine (Mexidol or Mexifin) 5. Reflexology 6. Thai foot massage

When taken orally, testosterone is rapidly first-pass metabolized in GI mucosa & liver to what inactive metabolites?

17-ketosteroids: androsterone & etiocholanone

What was the first orally active androgen that is 10 fold better than testosterone and is also effective sublingually?

17α-methyltestosterone

Some examples of estradiol esters include?

17β-valerate & 17β-cyclopentylpropionate (cypionate). Formulated in oil vehicle (cottonseed, castor, sesame oils)

The liver contains approximately 400-500 kcal of glycogen stores and the muscle approximately 1000-2000kcal. The glycogen stores in both the liver and the muscle can provide enough fuel for the body for how long?

3-8 hours, depending on the level of physical activity.

Desogestrel is rapidly metabolized in the intestine to what active progestin metabolite?

3-ketodesogestrel (etonogestrel)

What is the metabolite of tamoxifen that has 25-50 times higher affinity for estrogen receptors than tamoxifen?

4-hydroxy tamoxifen

Hypoglycemia can lead to decreased mental function, coma, and death. Most individuals show symptoms of hypoglycemia such as dizziness, confusion, hunger, nausea, etc. when blood glucose levels drop below what level?

45mg/dl However, some diabetic patients can tolerate (display no symptoms) much lower blood glucose levels.

What is the most potent endogenous androgen?

5α-dihydrotestosterone (5α-DHT)

What enzyme converts testosterone to dihydrotestosterone?

5α-reductase

Finasteride and Dutasteride are examples of?

5α-reductase inhibitors

What percent of the islets of langerhans are insulin-producing cells?

60%

Glucose homeostasis is a highly sensitive and regulated system, despite large fluxes due to eating and exercise. This system maintains blood glucose levels between?

70-150mg/dL

Testosterone is secreted in a pulsatile manner and is highest about what time?

8am because it is also diurnal

What is the percentage of efficacy for a combination oral contraceptive containing estrogen and progestin?

99.9%

What 2 hormones control the process for spermatogenesis? A. FSH B. LH C. Testosterone D. Estrogen E. Aldosterone

A. FSH C. Testosterone

Which of the following has equal amounts of FSH and LH? A. Menotropin B. Urofollitropin C. rFSH

A. Menotropin

Which one of the following testosterone preparations has more hepatotoxicity? A. Methyltestosterone B. Testosterone C. Testosterone cypionate D. Testosterone enanthate

A. Methyltestosterone

Which of the following are side effects of bromocriptine? A. Nausea B. Acne C. Postural Hypotension D. Pruritus

A. Nausea C. Postural Hypotension

GnRH agonist therapy can be used effectively in the treatment of which of the following? A. Precocious Puberty B. Acne C. Polycystic Ovarian Disease D. Cervicitis

A. Precocious Puberty B. Acne C. Polycystic Ovarian Disease

Which drug has LH-like activity and is used to treat infertility in men and women, and to induce ovulation for in vitro fertilization (IVF)? A. Pregnyl B. Pergonal C. Metrodin

A. Pregnyl (hCG)

When sperm is being produced, what is the name of the supporting cells surrounding them? They deal with tight junctions and synthesize/release inhibin which via feedback inhibits gonadotropin. A. Sertoli Cells B. Leydig Cells C. Supporter Cells D. Sustentacular Cells

A. Sertoli Cells D. Sustentacular Cells

Exemestane is an inhibitor of? A. aromatase B. desemolase C. 5α-reductase D. 17-hydroxysteroid dehydrogenase

A. aromatase

Spermatogenesis occurs in ___ and the sperms are matured in ____. A. seminiferous tubules; epididymis B. epididymis; seminiferous tubules C. Leydig cells; Sertoli cells D. Sertoli cells; Leydig cells

A. seminiferous tubules; epidiymis

How can hyperglycemia lead to peripheral vascular disease?

Advanced atherosclerosis in extremities can result in the destruction of major vascular beds and lead to tissue destruction, infection and gangrene. Unregulated diabetes can result in the amputation of limbs, particularly the legs.

Flutamide, Bicalutamide, and Nilutamide are examples of?

Androgen Receptor Antagonists

Other side effects of OHSS include associations of abnormal imprinting that increase the risk of developmental syndromes such as?

Angelman's and Beckwith-Wiedemann syndrome

Fulvestrant is indicated for breast cancer, and is what type of drug?

Anti-Estrogens

GnRH is a decapeptide synthesized and secreted by the hypothalamus, governed by a neural pulse generator in an aggregation of neurons called?

Arcuate Nucleus

What enzyme converts testosterone to estradiol?

Aromatase (CYP19)

Exemestane, Anastrozole, and Letrozole are all examples of?

Aromatase Inhibitors

Which of the following synthetic progestins have a long duration and is used parenterally? A. 17α-acetoxyprogesterone B. 17α-hydroxyprogesterone caproate

B. 17α-hydroxyprogesterone caproate

Estradiol is generated by enzyme ___ from testosterone. A. 17-hydroxysteroid dehydrogenase (17-OH-SDH) B. Aromatase (CYP19) C. Desmolase D. 5α-reductase

B. Aromatase (CYP19)

Insulin is an anabolic hormone that is produced when there is high blood glucose, which ultimately lowers those glucose levels. Which of the following are effects insulin has on the liver? A. Increase glycogenolysis B. Decrease gluconeogenesis C. Increases glycogen synthesis D. Decreases triglyceride synthesis

B. Decrease gluconeogenesis C. Increases glycogen synthesis

What drug is approved for prostate cancer treatment and is not associated with systemic allergic reactions? A. Ketoconazole B. Degarelix C. Abarelix

B. Degarelix deplete testicular androgens; medical castration

What is the most potent endogenous estrogen with high receptor affinity when used parenterally? A. Estrone B. Estradiol C. Estriol D. 16α-hydroxyestrone

B. Estradiol

The follicular phase is day 1-14 of the menstrual cycle where the egg develops into a follicle. What hormone stimulates this process? A. LH B. FSH C. Estrogen D. Testosterone

B. FSH

Which insulin formulation can also be given IV? A. Rapid-Acting B. Short-Acting C. Intermediate-Acting D. Long-Acting E. Ultra Long-Acting

B. Short-Acting

Steroid hormones are effectors. They directly maintain and stimulate sex characteristics of sex organ development. Once steroid hormones bind to a receptor, they move into the nucleus and activate protein synthesis producing a new effect. This determines the efficacy of the steroid hormone which is typically how long compared to peptide hormones? A. Quicker/Shorter B. Slower/Longer lasting

B. Slower/Longer lasting

Which of the following bypass initial hepatic catabolism and are more lipophilic? A. 17α-alkylated androgens B. Testosterone Esters C. Methyltestosterone D. Testosterone enanthate

B. Testosterone Esters D. Testosterone enanthate

What 2 drugs are more potent and orally active hydroxylated analogs of 17α-methyltestosterone?

Oxymesterone (Oranabol) & Oxymetholone (Anadrol, Anapolon).

Flutamide is a drug that is used for prostate cancer but it can also be used for what in women?

hirsutism

GnRH and GnRH agonists are used to treat what with regards to infertility?

hypogonadtropic hypogonadism and GnRH-dependent precocious puberty

What inhibits GnRH neuronal activity following ovulation?

increased progesterone levels

Another group of neurons in the hypothalamus, anteroventral periventricular nucleus, can stimulate GnRH production (positive feedback). This neuron can release one peptide that binds its receptor in endocrine cells and increase GnRH. What is this peptide?

kiss1

All of the following are metabolites of testosterone. Which ones are active metabolites? A. Dihydrotestosterone B. Androsterone C. Estradiol D. Etiocholanolone

A. Dihydrotestosterone C. Estradiol

T/F. Mestranol is 3-O-methyl ether prodrug analog of ethinyl estradiol which immediately O-demethylated to its parent ethinyl estradiol.

T.

What are the first generation drug forms of sulfonylurea hypoglycemic agents?

-Chlorpropamide (Diabinese) -Tolbutamide (Orinase) -Tolaziamide (Tolinase) -Acetohexamide (Dymelor)

What happens to all of the following regarding glycosylation due to hyperglycemia? 1. Red blood cells: 2. Hemoglobin: 3. Albumin: 4. Antibodies: 5. Lens of Eye: 6. Clotting Factors:

1. Red blood cells: Increases Clearance (of rbc's due to damage which can lead to anemia) 2. Hemoglobin: decreases O2 exchange greatly (in a normal person this is measured by HbA1C which is a marker for % of glycosylation of hemoglobin and normal is 4 or 5 and can go up to 12 or 13 in diabetics) 3. Albumin: decreased transport function (a lot of drugs/hormones are carried by this protein) 4. Antibodies: Decreased immune function and decreased resistance to disease. 5. Lens of Eye: Cataracts (lens becomes opaque instead of clear; these patients can go blind) 6. Clotting Factors: increase clotting time (because clotting factors don't work)

Often borderline diabetes displays full blown diabetes during pregnancy. Glucose crosses the placenta, so hyperglycemia can result in an oversized baby. What serious developmental problems can result due to hyperglycemia?

1. delayed lung maturation: 6X increase in respiratory distress syndrome. 2. hyperviscosity of blood (increased thrombus formation) 3. increased organ malformation (3X increase, accounts for ½ of infant deaths of diabetic mothers. Heart disease incidence increased 5X) 4. caudal regression syndrome (reduced size of lower body)

Hypoglycemia can be an adverse reaction to insulin due to what possible factors?

1. excessively large dose, mismatched therapy. 2. failure to eat after administration of therapy. 3. excessive exercise 4. adrenal and pancreatic insufficiency

What are 3 goals of therapy for diabetes mellitus?

1. prevent hyperglycemia 2. prevent ketoacidosis 3. prevent polydipsia/polyuria (water & electrolyte imbalance)

T/F. PR-B binds through its DNA binding domain (DNA-BD) to the progesterone response element (PRE) on the promoter, and function as activator of progesterone response genes.

T.

Ulipristal can be used for ____. A. Emergency contraception. B. Termination of early pregnancy. C. Hormone therapy for postmenopausal women. D. Treatment of infertility in anovulatory women.

A. Emergency Contraception

With regards to the SAR of progestins, match each of the following to its activity effect. A. Enhanced activity B. Prolongs activity C. Retains activity D. Required for Oral Activity 1. removal of C-19 Me gives norethindrone (norethisterone) 2. Acetylation of C-17 and/or C-3 OH 3. Replacement of C-3 ketone with OH 4. C-6 or C-7 α-Halogen 5. Further ring B or C unsaturation 6. Adding Me group at C-18 (norgestrel) 7. 17α-ethinyl, Me, Ethyl 8. C-19-nor methyl + C-21 chlorination block C-21 metabolic inactivation

A-1,4,5,6,8 B-2 C-3 D-7

Islet of Langerhans are cells in the pancreas. Match each cell of the islet of langerhans to its correct secretion. A. Alpha Cell B. Beta Cell C. Delta Cell 1. insulin 2. glucagon 3. somatostatin

A-2 B-1 C-3

Match the following insulin preparations to the correct formulation. A. Rapid-Acting B. Short-Acting C. Intermediate-Acting D. Long-Acting E. Ultra Long-Acting 1. Insulin degludec/Tresiba 2. lispro/HumaLog, aspart/NovoLog, glusine/Apidra 3. glargine/Lantus, detemir/Levemir 4. regular insulin/Humulin R and Novolin R 5. neutral protamine Hagedorn (NPH)/Humulin N and Novolin N

A-2 B-4 C-5 D-3 E-1

Match the correct segment of alpha estrogen receptors to its function. A. AF-1 B. AF-2 C. C domain 1. ligand binding, dimerization, and ligand-dependent transaction 2. DNA binding 3. active transcription independently of ligand

A-3 B-1 C-2 Beta estrogen receptors do not contain a functional AF-1, and are highly expressed in prostate and ovaries

Which of the following slows hepatic catabolism and can lead to hepatotoxicity? A. 17α-alkylated androgens B. Testosterone Esters C. Methyltestosterone D. Testosterone enanthate

A. 17α-alkylated androgens C. Methyltestosterone

Which of the following estradiol metabolites will be direct substrate for COMT metabolism? A. 2-Hydroxy estradiol B. Estrone C. 2-Methoxy estradiol D. Estriol

A. 2-Hydroxy estradiol

Flutamide is an antagonist of___ and can be used for ___ treatment. A. ARs; prostate cancer B. PRs; BHP C. ERs; breast cancer D. GPCRs; prostate cancer

A. ARs; prostate cancer

What layer of the uterus is has both a basal layer as well as a functional layer that is responsive to sex hormones and produces menstruation? A. Endometrium B. Myometrium C. Perimetrium

A. Endometrium

Which of the following estradiol esters will have the longest parenteral duration? A. Estradiol cyclopentyl propionate (8 C's) B. Estradiol validate (5 C's) C. Estradiol acetate (2 C's) D. Estradiol butyrate (4 C's)

A. Estradiol cyclopentyl propionate (8 C's)

Tamoxifen selectively blocks the _____ to inhibit breast cancer growth; ___ is the option for breast cancer resistant to tamoxifen. A. Estrogen receptor (ER-α); Fulvestrant B. ER-β; Fulvestrant C. ER-α; Clomiphene D. ER-β; Clomiphene

A. Estrogen receptor (ER-α); Fulvestrant

Which of the following is incorrect? A. For sexual infantilism, if fertility is the goal, using sex steroid (estrogen/progesterone in female, testosterone in male) is standard therapy. B. Induction of sex maturation using sex steroid is standard therapy for sexual infantilism. C. Infertility is a failure to conceive after 12 months of unprotected intercourse. D. The presence of hCG can be detected for pregnancy within a few days after a woman's first missed menstrual period.

A. For sexual infantilism, if fertility is the goal, using sex steroid

OHSS is a side effect in ___ and resulted from ___: A. Gonadotropins treatments; increased secretion of ovary B. Hormone replace therapy; increased secretion of ovary C. Clomiphene treatments; increased secretion of peritoneal membrane D. Bromocriptine treatment; decreased secretion of prolactin.

A. Gonadotropins treatments; increased secretion of ovary

Where in the female reproductive system is progesterone produced? A. Granulosa Cells B. Endometrium C. Ovarian Follicles D. Corpus Luteum

A. Granulosa Cells D. Corpus Luteum

Which of the following are effects insulin has on the muscle and fat? A. Increases glucose uptake B. Decrease glycogen synthesis C. Increases triglyceride synthesis

A. Increases glucose uptake C. Increases triglyceride synthesis

What drug blocks steroid hormone synthesis by inhibition of desmolase (CYP11A1) and 17α-hydroxylase (CYP17), thereby decreasing testosterone and cortisol? A. Ketoconazole B. Degarelix C. Mifepristone D. Bromocriptine E. Etomidate

A. Ketoconazole

During pregnancy, the placenta will synthesize hCG which will replace what hormone? A. LH B. FSH C. Estrogen D. Testosterone E. Norepinephrine

A. LH

With regards to the SAR of estrogen, match each of the following to its activity effect. A. Essential for Activity B. Increases Activity C. Reduces Activity D. Small effect 1. distance between C-3 and C-17 oxygens is 10.3 -12.1 A° 2. Aromatic ring A & C-3 OH 3. Substitution at C-1 4. C-3 & C-17 O 5. C-2 & C-4 substituents 6. C-17α-ethinyl or vinyl 7. C-17β-hydroxy & planar hydrophobic molecule 8. C-17 epimer (α-OH) 9. Unsaturation at ring B 10. C-6, C-7, & C-11 OH 11. 11βOMe & 11β-Ethyl

A.-1, 2, 4, 7 B.-6,11 C.-3, 8, 9, 10 D.-5

Which of the following are therapeutic uses for estrogen, progesterone, and/or testosterone? A. osteoporosis B. prostate cancer C. medical abortion D. menopausal therapy E. contraception

All of them are therapeutic uses.

What are some of the benefits of using estrogen in menopausal hormone therapy (MHT) or (HRT)?

Amelioration of vasomotor symptoms (hot flashes, sweating), prevention of osteoporosis, and urogenital atrophy.

Gluconeogenesis is a biochemical process mainly in the liver and kidneys by which glucose is produced from non-carbohydrate sources such as?

Amino acids, lactate, pyruvate, and glycerol

Ovulation is day 14 of the menstrual cycle, what happens?

An LH surge (increase) causes the oocyte to be released from the follicle into the abdominal cavity where it can be picked up by fimbria of the fallopian tube, with a survival of about 24 hours.

Spermatogenesis occurs in what part of the testes and represents what percentage of testicular volume? A. Epididymis, 75% B. Seminiferous tubules, 80% C. Tubulus rectus, 80% D. Seminiferous tubules, 55% E. Tubulus rectus, 55%

B. seminiferous tubules, 80%

GnRH antagonist are used in a regimen for fertility to ____. A. enhance FSH for follicle maturation B. suppress LH release C. enhance FSH and E2 D. induce LH release

B. suppress LH release

What drug is an inhibitor of aldosterone receptors that is also a weak inhibitor of the androgen receptor and a weak inhibitor of testosterone synthesis? A. Flutamide B. Spironolactone C. Cyproterone D. Nilutamide E. Bicalutamide

B. Spironolactone

The major source of estrogen for postmenopausal women is ___ and it is converted from androgen by _____. A. ovary; aromatase. B. adipose tissue; aromatase. C. adrenal gland; aromatase. D. ovary; 17-OH-SDH. E. adipose tissue; 17-OH-SDH

B. adipose tissue; aromatase.

What drug can induce masculinization of female fetuses if used in pregnancy?

Dimethisterone

Which of the following is the correct order of biological potency? A. testosterone>dihydrotestosterone>dehydroepiandrosterone B. dihydrotestosterone>testosterone>dehydroepiandrosterone C. dehydroepiandrosterone>testosterone>dihydrotestosterone D. dihydrotestosterone>dehydroepiandrosterone>testosterone

B. dihydrotestosterone>testosterone>dehydroepiandrosterone

Ganirelix and Cetrorelix decrease LH and FSH levels, what type of drugs are they?

GnRH antagonists, with these there is no initial increase in LH and FSH like in GnRH agonists

Which drug blocks the conversion of testosterone to dihydrotestosterone and is used to treat benign prostatic hyperplasia? A. Flutamide B. Finasteride C. Spironolactone D. Dutasteride E. Nilutamide

B. Finasteride

What drug is used to treat male pattern baldness, where effectiveness only persists as long as the drug is taken? A. Flutamide B. Finasteride C. Spironolactone D. Dutasteride E. Nilutamide

B. Finasteride it can also be used for hirsutism in women

The most common side effect of gonadotropin therapy in males is ___, which presumably reflects increased production of estrogens due to the induction of ____. A. Prepubertal testes; 17 α-dehydrogenase B. Gynecomastia; aromatase C. Enlarged testes; aromatase D. gynecomastia; 17 α-dehydrogenase

B. Gynecomastia; aromatase

Which of the following have tropic effects which is the stimulation of target tissue for proliferation/enlargement? A. Testosterone B. LH C. FSH D. Estrogen

B. LH C. FSH Steroids don't have this effect. This tropic effect helps the development of gonads (testes, ovaries) to maturity. However steroids can regulate gonadotropin synthesis via feedback regulation.

What type of cells secrete androgens? A. Sertoli Cells B. Leydig Cells C. Sustentacular Cells D. Interstitial Cells

B. Leydig Cells D. Interstitial Cells

Which of the following steroids has the best oral/metabolic stability & androgenic/anabolic potency? A. Testosterone B. Methyltestosterone C. Ethyltestosterone D. Propyltestosterone

B. Methyltestosterone

Which drug is recombinant human LH, has both LH and FSH activity, and is used as a fertility drug to enhance follicle development? A. Pregnyl B. Pergonal C. Metrodin

B. Pergonal (Menotropin)

Why does acarbose have side effects such as diarrhea, gas, liver enzyme elevations?

Because acarbose is non-absorbable so it functions exclusively in the intestine. alpha-glucosidase inhibitors side effects due to inhibition of enzymatic digestion of carbohydrates

Why is it critical for diabetic patients to eat meals to maintain blood glucose when on insulin therapy?

Because once insulin is injected, hormone will act to lower blood glucose, and it keeps working, so if the patient doesn't eat, he can become hypoglycemic.

Tissues with the greatest concentration of insulin-receptors are most responsive to the hormone (ex: liver, adipose, muscle). What are 2 examples of insulin insensitive tissues?

Brain and gonads

The basal level for blood glucose is around 90-100mg/dL. During a meal blood glucose shoots up and insulin follows it instantly (its tightly regulated). After a meal in the nonfasted state, what is the brain using for fuel and what are other tissues using for fuel?

Brain is using 100% glucose as fuel and other tissues are using >90% glucose as fuel

12-48 hours after a meal there's increased secretion of GH and cortisol, decreased conversion of T4 to T3, and decreased basal metabolic rate. This is the fasting state (acute starvation), what are the brain and tissues using for fuel?

Brain is using 50% glucose and 50% ketone bodies as fuel. Other tissues using fatty acid and ketone bodies as primary fuel source.

What drug can be used to treat a prolactin-secreting pituitary adenoma?

Bromocriptine, a dopamine agonist that activated D2 receptors

Many GI hormones stimulate insulin release and include, gastrin, secretin, cholecystokinin (CCK) and vasoactive intestinal peptide (VIP). There is a reciprocal relationship between insulin and glucagon. Insulin directly inhibits alpha cell function and decreases glucagon secretion. How does glucagon indirectly inhibit insulin secretion?

By stimulating somatostatin release, which inhibits both insulin and glucagon, but effect on glucagon is transient. Net effect is glucagon indirectly inhibits insulin secretion.

What makes ethinyl estradiol 15-20 fold more orally active than estradiol?

C-17 β-OH was metabolically protected through inserting appropriate substituents, ethinyl C≡CH group at C-17

On progestins, blocking hydroxylation of what carbon using a methyl analog increases oral stability and lipid solubility?

C-6

What drug is used for prostate cancer with metastases, for which there is no other treatment options? A. Ketoconazole B. Degarelix C. Abarelix

C. Abarelix (GnRH antagonist) discontinued in U.S. due to higher incidence of severe allergic reactions

A patient with PCOS is experiencing hypogonadotropic hypogonadism. What should be used first for ovulation induction? A. Estrogen B. Gonadotropins C. Clomiphene D. Bromocriptine E. Progesterone

C. Clomiphene gonadotropins can be used after a trial of clomiphene

What drug is a progestin and weak antiandrogen by virtue of binding to the androgen receptor; it is effective in reducing hirsutism, but is not approved for use in the U.S? A. Flutamide B. Spironolactone C. Cyproterone D. Nilutamide E. Bicalutamide

C. Cyproterone

Which hormone has positive feedback effects on GnRH? A. Progesterone B. Testosterone C. Estradiol D. LH

C. Estradiol

Which of the following androgens has the most progestational potency? A. Testosterone B. Methyltestosterone C. Ethinyltestosterone D. Propyltestosterone

C. Ethinyltestosterone

Which one of the following hormones is the major determinant for maintaining pregnancy? A. High level of LH. B. High level of FSH. C. High level of progesterone. D. Low level of Estradiol. E. Low level of hCG.

C. High level of progesterone.

Which of the following steroids has the most anabolic and least androgenic potency? A. Testosterone B. Methyltestosterone C. Methandrostenolone D. Fluoxymesterone

C. Methandrostenolone

Which drug has FSH-like activity and is used to develop follicles? A. Pregnyl B. Pergonal C. Metrodin

C. Metrodin (Urofollitropin)

What 2 structures of the female reproductive system produces estradiol? A. Granulosa Cells B. Endometrium C. Ovarian Follicles D. Corpus Luteum

C. Ovarian Follicles D. Corpus Luteum

Which of the following statements is incorrect? A. LH and FSH are synthesized and secreted by gonadotropes in anterior pituitary. B. GnRH signals through a specific GPCR that stimulates the PLC-IP3-Ca2+ pathway, resulting in increased synthesis and secretion of LH and FSH. C. Ovarian estradiol always negatively feedback regulates the synthesis and secretion of gonadotropins. D. The gonadotropins include LH and FSH E. Testosterone can negatively feedback regulates GnRH and LH and FSH.

C. Ovarian estradiol always negatively feedback regulates the synthesis and secretion of gonadotropins.

When hormones such as gonadotropins bind to receptors, it will chemically modify the effectors quickly via what process? A. Hydrolysis B. Dealkylation C. Phosphorylation D. Dephosphorylation

C. Phosphorylation

The role of the C-17 ethinyl functionality in ethinyl estradiol is? A. Extend the duration of activity via prodrug effect B. Protect against COMT metabolic inactivation C. Protect agains C-17 metabolic oxidation/inactivation D. Increase the water solubility for IV use

C. Protect agains C-17 metabolic oxidation/inactivation

Finasteride is used for treatments of benign prostatic hyperplasia and male pattern baldness, because it can: A. enhance activity of aromatase in tissues. B. enhance 5α-reductase type 2 in tissues. C. reduce levels of dihydrotestosterone in particular tissues. D. Reduce levels of testosterone in particular tissues.

C. reduce levels of dihydrotestosterone in particular tissues.

What enzyme converts Cholesterol to pregnenolone?

CYP450

Which metabolites can exhibit mild to moderate activities when binding to estrogen receptors?

Catechol & methyl-O-catechol metabolites

What drug increases FSH by 50% and thereby enhances follicular maturation?

Clomiphene

What drug is a potent anti-estrogen used for the treatment of anovulation in situations like polycystic ovarian syndrome?

Clomiphene

The luteal phase is day 15-28 of the menstrual cycle. The corpus luteum develops from the exploded follicle and produces progesterone as well as estrogen. Progesterone stimulates the uterus to be ready for a fetus, if there is no pregnancy, what does the corpus luteum degenerate into?

Corpus Albicans

In response to hypoglycemia, what hormone acts to raise blood glucose levels by shifting metabolism to burn protein as fuel and is involved with maintenance of levels during acute and chronic starvation?

Cortisol

The testes are descended to the scrotum 1 month prior to birth through the inguinal canal. What is the term used to describe when testes do not descend to the scrotum after birth (still in pelvic cavity)? This is a risk factor testicular cancer and is a direct reason for infertility. Surgery can correct it at a young age (<2years).

Cryptorchidism

Which of the following is NOT a human metabolite of megesterol acetate? A. Megesterol B. Megesterol Sodium Sulfate C. 22-Hydroxymegesterol D. 21-Hydroxymegesterol

D. 21-Hydroxymegesterol

What structure of the fallopian tube is where an oocyte gets fertilized? A. Isthmus B. Fimbriae C. Infundibulum D. Ampulla

D. Ampulla

Which of the following functional groups in estradiol will be a favorite target for sulfating, phase-II conjugation metabolism? A. C-6 hydroxylated, then conjugated B. C-16 hydroxylated, then conjugated C. C-17 OH D. C-3 phenolic OH

D. C-3 phenolic OH

C-3/C-17 oxygens are essential for estrogen activity with a required 10-12 A° distance, why is this optimal distance critical? A. Enhances oral activity B. Enhances metabolic stability C. Minimizes binding at androgens receptor D. Encourages binding at the receptor via formation of water bridge between both oxygens, enhancing the binding affinity

D. Encourages binding at the receptor via formation of water bridge between both oxygens, enhancing the binding affinity

The route of estrogen administration affects the potency. What is the order of oral administration? A. Estradial>estrone>estriol B. Estriol>estrone>estradiol C. Estradial>estriol>estrone D. Estriol>estradiol>estrone

D. Estriol>estradiol>estrone (A is the potency of SC route)

Aromatase is an enzyme that converts androstenedione to ____ and converts testosterone to ____. A. Progesterone, Estradiol B. Estradiol, Estrone C. DHEA, Progesterone D. Estrone, Estradiol E. Cholesterol, Estradiol

D. Estrone, Estradiol

Which of the following steroids has the most anabolic and androgenic potency with significant sodium retention side effects? A. Testosterone B. Methyltestosterone C. Methandrostenolone D. Fluoxymesterone

D. Fluoxymesterone

Which one of the following analogs can decrease the levels of GnRH and gonadotropins without transiently increase of gonadotropin secretion and sex steroid biosynthesis? A. Goserelin B. Nafarelin C. Leuprolide D. Ganirelix E. Triptorelin

D. Ganirelix

Which one of the following hormones secretes higher levels in luteal phase than in follicular phase? A. LH B. FSH C. Estradiol D. Inhibin

D. Inhibin

FSH stimulates the growth of developing ovarian follicles, induces the expression of __ receptors and regulates the expression of __ to stimulate the production of estradiol. A. GnRh; aromatase B. FSH; 17α-hydroxylase C. LH; 17α-hydroxylase D. LH; aromatase

D. LH; aromatase

Increases in insulin, fat deposition, and LDL, and reduction of HDL are metabolic effects of which drug? A. Exemestane B. Tamoxifen C. Fulvestrant D. Medroxyprogesterone acetate (MPA) E. Raloxifene

D. Medroxyprogesterone acetate (MPA)

For a healthy and normal day-night shift man, the highest levels of testosterone are in ______, at ____ time of a day. A. Testes; night B. Prostate; morning C. Peripheral system; morning D. Testes; morning

D. Testes; morning

Hyperglycemia can result in changes in the skin due to thickening of capillary beds to the skin resulting in vascular insufficiency and ultimately destruction of the skin and lesions. What is the term used to describe this?

Dermopathy

How does hyperglycemia result in retinopathy?

Destruction of vessels in the retina results in hemorrhage, scarring, retinal damage and blindness. Also this damage stimulates glial cell proliferation over retinal cells and reduces vision

How can hyperglycemia result in cardiomyopathy?

Diabetics have high incidence of heart failure due to glycosylation of actin and myocin filaments of the myocardium, resulting in decreased contractility.

How do GLP-1 agonists work? And what side effects do they have?

Drugs bind to GLP receptors. GPL-1 is a hormone that lowers blood glucose by slowing gastric emptying and increasing insulin secretion. These drugs also directly decrease glucagon secretion. They induce nausea, diarrhea, vomiting and weight loss due to making enticing food undesirable.

Continuous administration of long-acting GnRH agonists (Goserelin) can result in all of the following except? A. Down-regulation of GnRH receptors on pituitary gonadotropes. B. Decreased serum level of FSH. C. Decreased serum level of LH. D. Decreased serum level of testosterone or estradiol. E. Continuously increased levels of gonadotropins.

E. Continuously increased levels of gonadotropins.

In what structure of the male reproductive system does sperm maturation occur? A. Seminiferous tubules B. Leydig Cells C. Rete Testis D. Vas Deferens E. Epididymis

E. Epididymis

The synthesis and secretion of gonadotropins in gonadotropes are regulated by all of the following, except? A. GnRH B. Testosterone C. Estradiol D. Inhibin E. LH

E. LH

Which of the following statements is incorrect? A. The actions of LH and hCG on target tissues are mediated by the LH receptor. B. LH is required for the rupture of the dominant follicle during ovulation. C. The initial signs of puberty are breast development in girls and testes enlargement in boys. D. Leuprolide depot can be used to determine precocious puberty is central or peripheral. E. Leuprolide can be used for peripheral precocious puberty.

E. Leuprolide can be used for peripheral precocious puberty.

Which one of the following hormone is the major determinant maintaining the higher levels of testosterone of male fetus during pregnancy? A. Fetal pituitary LH. B. Fetal pituitary FSH. C. High level of progesterone. D. Low level of Estradiol. E. Placental hCG.

E. Placental hCG

What drug is used primarily for the prevention and treatment of osteoporosis? A. Exemestane B. Tamoxifen C. Fulvestrant D. Toremifene E. Raloxifene

E. Raloxifene

Which of the following statements is incorrect? A. Before puberty, CNS via opiod, dopamine and GABA inhibits Arcuate nucleus release GnRH. B. Both ERs are estrogen-dependent nuclear transcription factors. C. Deacetylation of histones alters chromatin conformation and reduces the ability of the general transcription apparatus to initiate transcription. D. PR-A strongly inhibits the transactivation of PR-B and is also a transcription inhibitor of other steroid receptors. E. The circulating levels of testosterone are constant before and after puberty.

E. The circulating levels of testosterone are constant before and after puberty.

Which of the following statements is incorrect? A. Before puberty, CNS via opiod, dopamine and GABA inhibits Arcuate nucleus release GnRH. B. Both ARs are androgen-dependent nuclear transcription factors. C. Dihydrotestosterone has higher affinity binding to and activating ARs than testosterone. D. Coactivators including steroid-receptor co-activator-1 are tissue specific. E. The circulating levels of testosterone in males are approximately 2-times higher than in females.

E. The circulating levels of testosterone in males are approximately 2-times higher than in females.

Estradiol is mainly generated from ___ in women before menopause. A. gonadotropes B. Leydig cells C. Sertoli cells D. cells of Arcuate nucleus. E. thecal cells and granulosa cells F. Corpus luteum

E. thecal cells and granulosa cells

17α-Hydroxyprogesterone activity is enhanced by what substituents, which prevent metabolic reduction/inactivation of both C-3 & C-20 progesterone skeleton ketones and prevents metabolic oxidation at C-6?

Enhanced by Δ6,7 unsaturation & C-6α-methyl or halogen, C-11 Me

Endogenous estrogens are inter-convertible via what enzyme?

Estradiol dehydrogenase

NuvaRing is a month-long contraceptive vaginal insert ring that is FDA approved and includes what drug combination?

Ethinyl estradiol and etonogestrel

What was the first synthetic progestin without a C-17 side chain, originally synthesized from androstanes for oral use?

Ethisterone (17α-ethinyl testosterone)

In combination oral contraceptives, what is the estrogen in most preparations?

Ethyl estradiol -few preparations contain mestranol

Incretin mimetic insulin secretagogues such as glucagon-like peptide (GLP-1) agonists stimulate glucose-dependent insulin release, what 5 drugs are GLP-1 agonists?

Exenatide, Liraglutide, Taspoglutide, Albiglutide, and Dulaglutide. (*Even though t's called GLP it doesn't have glucagon effects, it stimulates glucose release which is the opposite effect.)

T/F. Ethinyl analogs are indicated for long-term IM estrogen therapy, unlike Estradiol Esters.

F. Estradiol Esters are indicated for long-term IM estrogen therapy, unlike ethinyl analogs.

T/F. Finasteride is an antagonist of 5α-reductase I & II whereas Dutasteride is only an antagonist of 5α-reductase II.

F. Finasteride is an antagonist of 5α-reductase II whereas Dutasteride is an antagonist of 5α-reductase I & II.

T/F. In the basal hypothalamus, neurons in the arcuate and periventricular nuclei are always associated with positive feedback of gonadotropin secretion.

F. In the basal hypothalamus, neurons in the arcuate and periventricular nuclei are always associated with negative feedback of gonadotropin secretion.

T/F. Insulin can only be taken in IV and SC forms.

F. Insulin can be inhaled. Afrezza is a fast acting inhaled insulin. Single use, rapid acting cartridges filled with white powder containing insulin that is administered with oral inhaler. When patient inhales through the device, the powder is aerosolized and delivered to the lungs. Amount delivered to lungs is variable and dependent on patient and their physical condition.

T/F. Oral bioavailability of progesterone is high, hence it doesn't need to be administered parenterally.

F. Oral bioavailability of progesterone is poor, hence it should be used parenterally.

T/F. PR-B strongly inhibits the action of PR-A.

F. PR-B binds through its DNA binding domain (DNA-BD) to the progesterone response element (PRE) on the promoter, and function as activator of progesterone response genes. PR-A strongly INHIBITS this action of PR-B.

T/F. Estrogen-mediated decreases in GnRH pulse frequency suppresses gonadotropin release: it's the major mechanism of action of contraceptives.

F. Progesterone-mediated decreases in GnRH pulse frequency suppresses gonadotropin release: it's the major mechanism of action of progestin-containing contraceptives.

T/F. Estrogens are highly bound to albumin & SHBG. This causes non-linear pharmacokinetics, especially when used with ethinyl estradiol, which enhances binding capacity of SHBG.

F. Progestins are highly bound to albumin & SHBG. This causes non-linear pharmacokinetics, especially when used with ethinyl estradiol, which enhances binding capacity of SHBG

T/F after the oocyte is released during ovulation at day 14, the primary follicle becomes the corpus luteum which keeps the endocrine function and synthesizes estrogen and progesterone.

F. after the oocyte is released during ovulation at day 14, the Graffian follicle becomes the corpus luteum which keeps the endocrine function and synthesizes estrogen and progesterone.

T/F. For testosterone 17β-esters the higher the carbon number of acylating fatty acid, the shorter the duration.

F. the lower the carbon number of acylating fatty acid, the shorter the duration

What hormone is used in in-vitro fertilization (IVF)?

FSH

What hormone stimulates spermatogenesis, follicle development in ovaries, estrogen production and secretion by granulosa cells of the ovary and sertoli cells of testes?

FSH

What drug can cause edema through increase of Na+ retention?

Fluoxymesterone (correlated with mineralocorticoidal side effect since it has the 9α-F)

What drug may be useful in a tamoxifen-resistant cancer?

Fulvestrant

What hormone acts to raise blood glucose levels in response to hypoglycemia, is an acute effect that lasts 1-2 hours and only has action in the liver causing increases in both glycogenolysis and gluconeogenesis?

Glucagon

How is atherosclerosis a result of hyperglycemia?

Glucose stimulates cholesterol synthesis. Also insulin increases LDL-receptors and enhances LDL clearance from blood. Lack of insulin results in elevations in blood cholesterol and increased risk of cardiovascular disease. Also, insulin stimulates lipase activity and clears blood of triglycerides. Lack of insulin increases triglycerides blood levels.

For each menstrual cycle only 1 follicle will be selected and developed from a primordial follicle to primary, then secondary and to a mature follicle. What is another name for a mature follicle?

Graffian Follicle

What hormone, in response to hypoglycemia, acts to raise blood glucose levels by shifting metabolism to burn fat as fuel as well as preventing nocturnal hypoglycemia 6-10 hours following a meal and during acute starvation?

Growth Hormone (GH)

What is the most common side effect of gonadotropin therapy in males?

Gynecomastia

What is common in older patients, resulting from dehydration and leads to suppression of CNS function, confusion, seizures, coma and eventually death?

Hyperosmolar Coma

What 3 parts of the body control the menstrual cycle?

Hypothalamus, pituitary, and ovaries

A side effect of using gonadotropins is ovarian hyper stimulation syndrome (OHSS) which can lead to?

Hypovolemia, electrolyte abnormalities, acute respiratory distress syndrome, thromboembolic events and hepatic dysfunction

A possible mechanism of action for bromocriptine is that it: (fill in blank with decrease or increase) ______dopaminergic activity in the morning ______sympathetic activity ______serotonergic activity

INCREASES dopaminergic activity in the morning DECREASES sympathetic activity DECREASES serotonergic activity

When should patients avoid taking viagra?

If patients use nitrate drugs for chest pain or heart problems (ex: nitroglycerin, isosorbide denigrate, isosorbide mononitrate) because together it can cause a sudden and serious decrease in blood pressure.

Dipeptidyl peptidase (DPP)-4 inhibitors (gliptins) are also incretin mimetic insulin secretagogues. What is their mechanism of action and what side effects do they have?

Increase blood levels of the incretins GLP-1 and GIP, which inhibit glucagon release, by blocking their metabolism and degradation. Side effects include severe join pain. If pain occurs discontinue use of drug.

48 hours to 2 weeks after a meal, this stage is the fasted state (chronic starvation). Brain is using 10% glucose and 90% ketone bodies fuel and other tissues are using fatty acids and ketone bodies as a primary fuel source. What happens in the body? (what's secreted, deceased, etc.)

Increased secretion of GH and cortisol Decreased conversion of T4 to T3 Decreased basal metabolic rate Behavioral changes associated with decreased activity Decrease mental function, eventually leading to coma and death

6-12 hours after a meal, glucose used is approximately equal to glucose produced, where 1/4 glucose is produced via gluconeogenesis and 3/4 produced by glycogenolysis. This stage is the acute fasting state where the brain uses >90% glucose as fuel and other tissues use >75% glucose as fuel. What hormones are being increased/decreased in this stage?

Increased secretion of epinephrine and glucagon Decreased secretion of insulin

Another alpha-glucosidase inhibitor is miglitol (Glyset) which may exert effects in various cell types of the body, but generally has the same side effects as acarbose, however it differs from acarbose in that it?

Is absorbable

How does sildenafil treat erectile dysfunction?

It acts by inhibiting cGMP-specific phosphodiesterase type 5 (PDE5), an enzyme that promotes degradation of cGMP, to increase cGMP, relax muscles in the walls of blood vessels and increases blood flow to particular areas of the body (penis, pulmonary arterial)

Testosterone replacement therapy is used for male hypogonadism to induced normal virilization in prepubertal boys and men who became hypogonadal as adults. However, what can testosterone accelerate?

It can accelerate epiphyseal maturation, leading initially to a growth spurt but then to epiphyseal closure and permanent cessation of linear growth

Biguanides are hypoglycemic agents for type 2 diabetics. An example is metformin (Glucophage). It is the most commonly used agent for type 2 diabetes in children and teenagers. Among common diabetic drugs, metformin is the only widely used oral drug that does not cause weight gain. How does this drug work?

It reduces hepatic glucose output and increases uptake of glucose by the periphery, including skeletal muscle.

For methyltestosterone, what will increasing the length/carbon number of the C-17α-side chain do to the activity?

It will decrease the activity: Me>Ethyl>Propyl

What will a constant infusion of gonadorelin do?

It will initially increase LH and FSH, but after that it will induce downregulation of pituitary GnRH-receptors and decrease LH and FSH, which can decrease sex characteristics.

How is testosterone formed? (what enzyme/process)

It's formed via the stereoselective reduction of the C-17 ketone of androstenedione by 17β-hydroxysteroid dehydrogenase.

What are some adverse effects of SGLT2 inhibitors?

Ketoacidosis (associated with drug induced hypoglycemia), UTIs, and hypoglycemia.

How does hyperglycemia result in nephropathology?

Kidneys become enlarged, with increased GFR due to glycosylation of glomerulus resulting in leaky filtration and decreased kidney function. Observed in approximately 50% of all diabetics.

Progestins are compounds with biological activities similar to those of progesterone. What hormone via its g-protein coupled receptor stimulates progesterone recreation during the normal cycle?

LH

What hormone stimulates androgen production by Leydig cells in testes and Theca cells in ovaries?

LH

Which hormone induces ovulation?

LH

Metformin has many side effects including diarrhea, bloating, stomach pain, heartburn, gas, indigestion, constipation, headache, muscle pain, rash, chest pain, as well what rare side effect that lowers blood pH?

Lactic Acidosis (rare): blood lactate increases with metformin because it decreases uptake of lactate by liver, resulting in a lowering of blood pH.

In women, how can low levels of estradiol and progesterone inhibit gonadotropin production?

Largely through opioid action on the neural pulse generator. Low levels of estradiol have negative regulation on gonadotropins because the arcuate nucleus can release opioids to control neuron endocrine cells in the hypothalamus.

Glycogenolysis is the breakdown of glycogen stores to form glucose that can be used as a fuel source from what parts of the body?

Liver and muscle

With regards to glucose homeostasis what is autoregulation?

Liver is sensitive to changes in blood glucose levels and will initiate gluconeogenesis and glycogenlysis independent of hormone stimulation.

What is the name of the GnRH pump that delivers GnRH in a pulsatile manner, which is more natural and its use is associated with few complications?

Lutrepulse

What is an example of recombinant human LH?

Lutropin alfa (Luveris)

Removal of norethindrone C-3 ketone gives what drug, which is a potent progestin that's free of androgenic activity?

Lynestrenol

When a patient has hyperglycemia, glycosylation of proteins occurs, which is adding a sugar moiety to proteins and can result in altered protein structure and function. This glycosylation occurs primarily on what amino acid residues?

Lysine and Valine

What 2 drugs have a double bond at C-6,7 and are used for breast & endometrial carcinoma, as an appetite stimulant, and as a contraceptive (combined with estrogens)?

Megestrol acetate (Megace) & chlormadinone acetate

What drug is metabolized by CYP3A4 mono & di-N-demethylation & terminal hydroxylation of the 17-propynyl side chain?

Mifepristone (Mifeprex) Has anti-glucocorticoidal activity, unlike onapristone, with much less anti-glucocorticoidal activity.

Leuprolide, Goserelin, Histrelin, Nafarelin, and Triptorelin are all GnRH agonists. How have they been modified to enhance potency and prolonged duration of action as compared to natural GnRH?

Modified in position 6 and C-terminus

Hyperglycemia can result in neuropathology. What is polyneuropathology and what symptoms does it result in?

Multiple nerves affected. Symptoms include motor dysfunction, numbness, tingling, burning and/or lightning pain. Loss of stretch reflexes.

Bromocriptine (Cycloset) is a dopamine receptor agonist that binds to D2 receptors. It is formulated as quick-release tablet, not interchangeable with other bromocriptine products. It can be used for type 2 diabetes mellitus, what is its mechanism of action?

No effect on insulin secretion, and the mechanism of action for improving glycemic control is unknown.

What drug is a strong progestin with weak estrogenic activity and is used as oral contraceptives?

Norethindrone (Norlutin)

What is the cyclic regimen for menopausal hormone therapy?

Oral, low-dose conjugated equine estrogen-medroxyprogesterone acetate (CEE-MPA)

Diethylstilbestrol (DES) is a nonsteroidal estrogen that causes neoplasia in offspring if used during pregnancy and used for?

Prostate cancer (no longer used in women)

T/F. Insulin preparations are made in mixtures that combine intermediate and short acting forms of insulin.

T. It simplifies insulin treatment plan Ex: Novolog 70/30 Humalog 75/25 Humalog 50/50 Humulin 70/30 Novolin 70/30

Nervous regulation of insulin secretion occurs via the autonomic nervous system. What is the parasympathetic (vagus) and sympathetic effect on insulin?

Parasympathetic (Vagus): Ach stimulates β-cell and increases insulin secretion. Sympathetic: NE stimulation of α1- and β2- adrenergic receptors on b-cells inhibits insulin secretion.

Explain the glucose tolerance test.

Patient fasts at least 12 hours prior to test. Baseline glucose levels are measured, then the patient drinks a glucose solution. In a normal patient glucose levels go up and then go back down with a little dip past baseline then remains normal. A diabetic patient's baseline is much higher to begin with and will go up and stay high for a long period of time.

GnRH suppression of reproductive function is reversible and is referred to as what?

Pharmacological castration

What part of the estradiol structure is responsible for receptor binding?

Phenolic A ring

T/F. Colesevelam works by decreasing hepatic bile, which increases diacylglycerol conversion, thus increases insulin sensitivity, and ultimately decreases plasma glucose. (based on animal model)

T.

T/F. Estrogens are weakly active orally due to first pass intestinal conjugation & hepatic oxidation metabolism.

T.

What is the most common hormone replacement therapy in the U.S. and is a water soluble natural conjugated metabolite obtained from the urine of female horses?

Premarin

Onapristone, Mifepristone, and Ulipristal are what type of drugs?

Progesterone Receptor Antagonists

Novarel, Pregnyl, and Profasi are all forms of?

hCG

Hyperglycemia can lead to foot syndrome, what does this result from?

Results from combination of vascular insufficiency and decreased nerve function. Glycosylated nerves have decrease pain perception. Also there is breakdown of skin, loss of ability to sweat, dry skin, inflammation, cracking, and decrease ability to heal wounds. Ultimately leads to ischemia, ulcers and even gangrene.

What drug is used to treat pulmonary arterial hypertension (PAH) and to improve exercise capacity?

Revatio (another brand of sildenafil)

Sodium glucose cotransporter inhibitors (SGLT-inhibitors or gliflozin) such as canagliflozin, dapagliflozin, and empagliflozin, work by what mechanism of action? (for type 2 diabetes mellitus)

SGLT-2 is Na-dependent glucose transporter in the kidney and responsible for 90% of glucose reabsorption in the kidney. Inhibition of SGLT-2 prevents glucose reabsorption and elimination in the urine and may help to reduce body weight and blood pressure.

T/F. For insulin, both alpha and beta chains are required for binding and activation of insulin-receptors. It's not bound to plasma proteins, giving a short half-life (5-6 minutes)

T.

T/F. Insulin-receptor exist as a dimer and is classified as a "receptor tyrosine kinase"

T.

Tamoxifen, Raloxifene, and Toremifene are indicated for breast cancer and/or breast cancer prophylaxis. All of these are what type of drugs?

Selective Estrogen Receptor modulators (SERMs)

T/F. Testosterone 17β-esters are prodrug oil solutions.

T

How does thyroxine work in response to chronic hypoglycemia?

There is a reduction in 5'-deiodinase activity which decreases conversion of T4 to T3, which causes a decrease in basal metabolism which conserves calories thus sparing glucose.

Thiazolidinediones (aka glitazones) bind to PPARγ, a type of nuclear regulatory protein involved in transcription of genes regulating glucose and fat metabolism. What do these PPARs act on and what is the result?

These PPARs act on Peroxysome Proliferator Responsive Elements (PPRE), which influence insulin sensitive genes (work downstream from receptor), and therefore enhance production of mRNAs of insulin dependent enzymes (increase glucose pumps; glycogen synthesis). The final result is better use of glucose by the cells (and decreased levels).

Bile Acid Sequestrants such as colesevelam (Welchol) are drugs that are taken orally and can be used for type 2 diabetes mellitus, but the mechanism by which drug lowers blood glucose is unclear, what is its mechanism of action? And what are the side effects?

These drugs are not absorbed and act in the gut to bind bile acids and blocking their reabsorption. As bile stores become depleted, the liver upregulates LDL receptors to take in more cholesterol from the blood for synthesis of bile, thus lowering blood cholesterol levels. Side effects include GI distress (gas, constipation, diarrhea, abdominal pain, N/V, etc)

Pramlintide is an amylin agonist. It can induce nausea, but it is a transient (short) effect. How do amylin agonists work?

They slow gastric emptying and suppress glucagon secretion. Has all the action of incretins but these drugs do NOT stimulate insulin secretion.

Which formulation (dosage form) is for physiological effects on uterus locally while systemic estradiol levels are low due to rapid liver metabolism?

Transdermal patch

What type of diabetic patients average 1 hypoglycemic episode/week due to excessive insulin dose, decreased compensatory mechanisms and/or imperfect therapy replacement?

Type 1 - Insulin dependent diabetes mellitus (IDDM)

Which type of diabetes includes all forms in which exogenous insulin is required to prevent ketoacidosis, regardless of etiology?

Type 1 or Insulin Dependent Diabetes Mellitus (IDDM) Type I or juvenile onset diabetes is a form of IDDM, but applies only to autoimmune destruction of beta cells in pancreas.

What type of diabetes includes all forms of diabetes in which endogenous insulin is sufficient to prevent ketoacidosis, and Beta cells present and insulin levels in blood are normal or higher than normal. Problem is tissue resistance to insulin (defect in insulin receptor) and relative deficiency in insulin secretion?

Type 2 or non-insulin dependent diabetes mellitus (NIDDM)

What type of diabetes has a very strong genetic link, and has poor association with autoimmune disease, but primary environmental risk factor is excessive food intake or obesity. Obesity increases insulin resistance. (obesity does not cause diabetes, it exacerbates it)

Type 2/NIDDM

Mumps, rubella, retroviruses, drugs such as streptozocin, alloxan, poisons such as vacor, and nitrosamines are all environmental influences that can lead to what type of diabetes?

Type1/IDDM All cause changes in MHC and induce autoimmune response and destruction of b-cells in pancreas. Type I diabetes is commonly and most often caused by environmental factors.

Genistein, Zeranol, Mehoxychlor, and Bisphenol A are all examples of?

Xenoestrogens, which are environmental estrogens that have 1-10% of estradiol activity

Epinephrine acts to raise blood glucose levels in response to hypoglycemia, its direct action is β-adrenergic receptor mediated causing an increase in glycogenolysis and increase gluconeogenesis in muscle and liver. What is epinephrine's indirect action?

a. α-adrenergic receptor mediated: decreases insulin secretion. b. β-adrenergic receptor mediated: stimulates glucagon secretion

LH and hCG share the same alpha subunit, but differ in the beta subunit in what way?

hCG has 30 more amino acids in its beta subunit, and extra carbohydrates that prolong its half life.

What is a side effect of ketoconazole?

hepatotoxicity

Alpha-glucosidase inhibitors such as acarbose (Precose/Glucobay) is used to treat type 2 diabetes mellitus (off-label use in type 1 diabetes mellitus). How does this drug work?

decreases G.I. absorption of carbohydrates. It is a starch blocker which reduces blood glucose and induces weight loss. These may work better in obese patients, but not recommended in patients of normal weight.

Hyperglycemia can result in neuropathology. What happens with regard to autonomic nerve dysfunction?

defects can occur in baroreceptor response (hypotension), sexual dysfunction, impotence, motility disturbances in bladder and GI tract, and arrhythmias.

Progestin-only contraceptives are available as?

norethindrone pill and levonorgestrel implants

In combination oral contraceptives, what is the progestogen in most preparations?

norethisterone and levonorgestrel.

Hyperglycemia can result in neuropathology. What is mononeuropathology and what does it result in?

one nerve is effected (femoral, sciatic, ulner, cranial 3,4,6), which can result in wristdrop, foot drop, paralysis, atrophy, pain, and fasciculations.

Combination oral contraceptives can be biphasic or triphasic pills. One drug is fixed and the other is increased for each phase. Which drug, estrogen or progestin, changes?

progestin

Insulin Secretagogues (meglitinides) are hypoglycemic agents for type 2 diabetics only. These are short-acting and stimulate insulin production by pancreas. Act by inhibiting K+ channels, inducing increase intracellular Ca+2 levels and thereby increasing insulin secretion. What are 2 examples of secretagogues and what are some possible adverse reactions?

repaglinide (Prandin) nateglinide (Starlix) Adverse reactions include weight gain and hypoglycemia.

Pioglitazone (Actos) is used for type 2 diabetes mellitus, what are its side effects?

side effects include edema, weight gain, bladder cancer, melanoma and non-Hodgkin lymphoma. Cancer is associated with carcinogen-like effects.

Rosiglitazone (Avandia) is used for type 2 diabetes mellitus, but what are some side effects of it?

side effects include increased risk of heart attack due to accumulation of fluid (edema) that can lead to heart failure.

Human Chorionic Gonadotropin (hCG) is secreted by what structure of the placenta during pregnancy?

syncytiotrophoblast (syntrophoblast)

What are the 5 dipeptidyl peptidase-4 inhibitors?

vildagliptin, sitagliptin, alogliptin, linagliptin, saxagliptin