PHAR 502 Adrenal

b

A patient with Cushing syndrome has an overproduction of ____________. a. mineralocorticoids b. glucocorticoids c. androgens d. aldosterone

d

Eplerenone has minimized side effects compared to spironolactone. Which of the following best describes why is this the case? a. has reduced binding to aldosterone receptors b. the drug is given in lower doses than spironolactone c. it is a selective aldosterone agonist d. has reduction of the progestational and antiandrogenic actions

pregnane, androstane

Fill in the Blank: mineralcorticoid and glucocorticoids are derivatives of _______________; androgens are derivatives of _____________

A

If the hydrogen in the 5 position in androstane is flipped from alpha to beta, which of the following structures would be the result?

c

In theory, what would be the best drug of choice to target specifically a cortisol overproduction problem? a. osilodrostat b. aminoglutethimide c. metyrapone d. trilostane

b

Prednisolone/prednisone has about 4x more anti-inflammatory activity compared to cortisol/cortisone. which of the following best explains why? a. addition of a fluorine changed the metabolic profile, therefore increasing drug half-life b. addition of a double bond at the 1 position (1-ene) increased activity via flattened boat conformation c. prednisone is metabolized via glucoronidation leading to increase activity d. inductive effect of the 11β-OH group on prednisolone increases potency

B

Relative to the steroid background, which highlighted portion is 'anti' connected?

A

Relative to the steroid background, which highlighted portion is 'trans' connected?

true

T of F? cAMP facilitates both the rapid and chronic responses in steroid biosynthesis

false, expressed in many tissues

T or F? glucocorticoid receptors are only expressed in the adrenal gland

true

T or F? in you replace a hydrogen with "F" in the 9 position, you will increase both glucocorticoid and mineralocorticoid activity

false, it will significantly impair mineralocorticoid activity

T or F? insertion of a bulky substituent on the α-side will abolish mineralocorticoid activity

false, it has a longer half-life

T or F? predisolone has a shorter half life compared to cortisol do to changes in its metabolic profile

c

To determine whether a patient has cushings syndrome due to a pituitary adenoma or a tumor in the adrenal gland, which lab level would we want to draw? a. cortisol b. aldosterone c. ACTH d. angiotensin

1: hypoglycemia, hypotension, fever, trauma, surgery 2: corticoid releasing hormone (CRH) 3: ACTH 4: cortisol

fill in the missing components of the regulation system

11β-hydroxysteroid dehydrogenase type 2 (11β-HSD) converts cortisol to cortisone to prevent binding

how do the kidneys prevent cortisol from binding to the mineralocorticoid receptor?

a

if we inhibit the cortisol forming enzyme 11β-hydroxylase, which enzyme will most likely also be effected? a. aldosterone synthase b. P450 side cleaving enzyme c. 17,20-lyase d. no enzymes will be effected

methylprednisolone sodium succinate

if we wanted to administer this medication IV, which one would we use?

d

inhibiting which of the following enzymes would likely have the most off target side-effects? a. 11β-hydroxylase b. 17,20-lyase c. aldosterone synthase d. cholesterol side chain cleavage enzyme

glucocorticoid activity

insertion of bulky substituents on the β-side will abolish which corticocosteroid activity?

c

ketoconazole inhibits the which of the following adrenal steroid enzymes? a. P450scc b. P450 c. 11β-hydroxylase and P450c17 d. aldosterone synthase

e

mineralocorticoid receptors are expressed all of the following tissues EXCEPT? a. colon b. kidneys c. sweat glands d. salivary glands e. hypothalamus

a

mitotane affects enzymes in the ___________? a. mitochondria b. endoplasmic reticulum c. nucleus d. cytosol

A: 19 B: 18

number the labeled substituents

d

steroid biosynthesis occurs in what two major organelles? a. mitochondria and nucleus b. nucleus and smooth endoplasmic reticulum c. nucleus and lysosomes d. endoplasmic reticulum and mitochondria

Mitotane

this drug is really only used when we want to destroy the adrenal gland in cases of adrenal cancer?

-mineralocorticoids -glucocorticoids with moderate/low salt retention -glucocorticoids with little/no salt retention

what are the three major groups that adrenal steroids and drugs can be classified into?

aldosterone and cortisol

what are the two main corticosteroids?

increase lipid solubility to increase absorption in dosage forms like nasal sprays or inhalers

what is most likely the purpose of this chemical modification? example?

c

what is the driving factor that determines where a hormone will bind to a nuclear receptor? a. amino acid palindrome sequence b. number of nucleotides between palindrome c. number of nucleotides between palindrome and amino acid palindrome sequence d. DNA binding domain

use of glucocorticoids to treat other diseases (exogenous)

what is the most common cause of cushing's syndrome?

-surgery with selective tumor resection -radiation

what is the treatment of chose for ACTH-independent (cushings syndrome)?

-surgery with selective tumor resection -radiation

what is the treatment of chose for excessive secretion of ACTH (cushings disease)?

c

what prevents the glucocorticoid pathway from producing mineralocorticoids? a. zona fasciculata lacks P450 activity b. it is synthesized from cholesterol c. lack aldosterone synthase expression d. occurs only in the endoplasmic reticulum

b

what prevents the mineralocorticoid pathway from producing glucocorticoids or androgens? a. zona reticularis lacks P450c17 expression b. zona glomerulosa lacks P450c17 expression c. mineralocorticoid biosynthesis only happens in the mitochondria d. mineralocorticoid biosynthesis only happens in the endoplasmic reticulum

b

where is the side chain cleaving enzyme responsible for the activation of steroid synthesis located? a. cytosol b. mitochondria c. nucleus d. ECF

at the 16α or 6α position

where would we add substituents if we wanted to decrease salt retention?

a

which class of adrenocorticoids is used for treatment of adrenal insufficiency? a. mineralocorticoids b. glucocorticoids with moderate/low salt retention c. glucocorticoids with little/no salt retention

Glucocorticoids (cortisol)

which class of corticosteroids would most likely be used in response to an inflammatory or immune response?

a

which drug inhibits 3β-hydroxysteroid dehydrogenase? a. triolstane b. aminoglutethimide c. ketoconazole d. osilodrostat

b

which drug inhibits P450scc? a. triolstane b. aminoglutethimide c. ketoconazole d. osilodrostat

Osilodrostat

which drug inhibits aldosterone synthase?

d

which of the following about aminoglutethimide is FALSE? a. inhibits P450scc activity b. used in treatment of Cushing syndrome c. inhibits aromatase activity in peripheral tissues d. it is an allosteric modulator of the estrogen receptor

d

which of the following about the adrenal gland is FALSE? a. the adrenal glands are located near the kidney b. the medulla and cortex are combined in mammals c. we can survive without the medulla but not without the cortex d. we cannot survive without the medulla

d

which of the following can inhibit 11β-hydroxylase? a. metyrapone b. ketoconazole c. osilodrostat d. all of the above

b

which of the following enzymes has the same physiologic activity as a desmolase? a. hydroxylase b. lyase c. hydroxysteroid dehydrogenase

b

which of the following enzymes would catalyze this rxn? a. 21-hydroxylase b. 17α-hydroxylase c. 3β-hydroxysteroid dehydrogenase d. 11β-hydroxylase

c

which of the following enzymes would catalyze this rxn? a. 21-hydroxylase b. 17α-hydroxylase c. 3β-hydroxysteroid dehydrogenase d. 11β-hydroxylase

d

which of the following hormones is correctly matched with its functional zone? a. aldosterone/z. reticularis b. cortisol/z. reticularis c. dehydroepiandrosterone/z. glomerulosa d. aldosterone/z. glomerulosa e. cortisol/z. glomerulosa

d

which of the following is NOT a type of metabolism that is affected by glucocorticoids? a. carbohydrates b. fat c. protein d. potassium/sodium

a

which of the following is NOT a way glucocorticoids block an inflammatory response? a. increased permeability of capillaries b. depression of phagocytosis c. suppression of interleukin-1 d. suppression of thymus-derived lymphocytes

d

which of the following is a major pathway in adrenocorticoid metabolism? a. side chain cleavage b. reduction to 5β and conjugated via sulfation c. they are excreted unchanged due to being hydrophilic d. reduction to alcohol and conjugated via sulfation/glucuronidation

c

which of the following is a mineralocorticoid? a. cortisol b. dehydroepiandrosterone c. aldosterone d. angiotensin

b

which of the following is most likely responsible for the side effects from taking spironolactone? a. spironolactone is a potassium sparing diuretic b. it stimulates and progesterone receptor and inhibits androgen receptor c. it acts on the distal convoluted tubule d. inhibits aldosterone synthase

a, b

which of the following is regulated by ACTH? choose all that apply a. cortisol (glucocorticoid? b. dehydroepiandrosterone (androgen) c. aldosterone (mineralcorticoid) d. angiotensin

d

which of the following is used to treat cushings syndrome? a. metyrapone b. ketoconazole c. osilodrostat d. all of the above

a

which of the following is/are a major site of adrenalcorticoid inactivation? a. liver and kidneys b. kidneys alone c. pituitary gland d. hypothalamus

c

which of the following proteins is responsible for mobilizing cholesterol into the mitochondria? a. IP3 b. LDL c. StAR protein d. ACTH

d

which of the following regarding fludrocortisone is FALSE? a. used for oral treatment in addison's disease b. has very potent mineralocorticoid activity c. prevents metabolic oxidation of 11β-OH group d. increased glucocorticoid activity by 10x and decreased mineralocorticoid activity by 300x

d

which of the following regarding steroid biosynthesis is FALSE? a. cAMP is a facilitator in the acute rapid response b. LDL binds to lipoproteins for cholesterol to be stored in cells c. the StAR protein catalyzes the rate limiting step in rapid response d. the StAR protein catalyzes the transport of Ca2+ into the mitochondria

C

which of the following steroids would be a precursor to aldosterone?

C

which of the following steroids would be a precursor to cortisol?

d

which of the following ways would serve as a negative feedback loop for aldosterone secretion? a. decreased renal arterial pressure b. increased gluconeogenesis c. decreased ACTH d. decreased extracellular potassium

c

which of the following would likely lead to increase in cortisol secretion? a. hyperglycemia b. cold intolerance c. hypoglycemia d. decreased corticoid releasing hormone

c

which of the following would most likely NOT be the result of administration of a glucocorticoid? a. increased amino acid levels in blood b. increased supply of glucose c. decreased concentration of glycerol in the blood d. increase mobilization of fatty acids

a, c

which of the following would most likely be secreted from the adrenal medulla? choose all that apply a. epinephrine b. tyrosine c. norepinephrine d. aldosterone

b

which plane is substituent C18 in? a. alpha b. beta c. anti d. trans

d

which rings are most important for structure-activity relationships in adrenocorticoid receptor recognition? a. A ring only b. A and B ring c. B and C ring d. C and D ring e. D ring only

17α-hydroxylase and 17,20-lyase

which steroid enzymes are included in P450c17?

16α-methyl

which substituent on dexamethasone is responsible for eliminating salt retention?

Aldosterone circulates in a free state and is rapidly cleared. Most circulating cortisol is bound to plasma proteins

why are cortisol plasma levels significantly higher than aldosterone plasma levels?

they have no mineralocorticoid activity

why are dexamethasone and betamethasone not used in treatment of addison's disease?

cortisone is interconverted to cortisol by 11β-HSD (reversible rxn)

why can we give cortisone but still have cortisol activity?

c

why does methylprednisolone have a longer half-life compared to prednisolone? a. prevents CYP oxidation at C9 b. slows metabolism via addition of fluorine group c. prevents CYP oxidation at C6 d. addition of 1-ene

a

with respect to the individual zones in the cortex, predict which secretion would be in majority? a. cortisol b. mineralocorticoid c. androgens d. dehydroepiandrosterone