Endocrine Med Chem Flashcards
Which of the following are Adrenocorticoids? (Select All)
A. Mineralocorticoids
B. Estrogen
C. Andorgen
D. Glucocorticoids
E. Progestogens
A, D
Which of the following are Gonadal Steroids? (Select All)
A. Androgens
B. Glucocorticoids
C. Estrogens
D. Mineralocorticoids
E. Progestogens
A, C, E
What is the precursor for ALL steroidal hormones such as Adrenocorticoids and Gonadal Steroids?
A. Glucose
B. Pyruvate
C. Cholesterol
D. Pyrimidines
C
Based on the picture provided what is the common precursor of Hydrocortisone and Aldosterone?
A. 17a-Hydroxyprogesterone
B. 21-Hydroxyprogesterone
C. Progesterone
D. 17a-Hydroxypregnolone
E. Pregnolone
E. Pregnolone
Based on the structure of cholesterol, which of the following statements are true? (Select All)
A. Hydroxyl group on carbon 3
B. Double bond between carbons 4-5
C. Double bond between carbons 5-6
D. Hyrdroxyl group on carbon 11
A. Hydroxyl group on carbon 3
C. Double bond between carbon 5-6
Remember how to number the structure of cholesterol
When comparing the structure of Pregnolone to 17a-Hydroxypregnonlone, what statment is true?
A. 17a-Hydroxypregnolone gains a double bond betwen carbons 4-5
B. Carbon 3 hyroxyl group is reduced to a ketone in 17a-Hydroxypregnolone
C. Hydroxyl group is added to the carbon 17 in 17a-Hydroxypregnolone
D. No difference in structures
C. hydroxyl group is added to the carbon 17 in 17a-Hydroxypregnolone
When comparing the structures of 17a-Hydroxypregnolone and 17a-Hydroxyprogesterone, which of the following statments is true? (select all)
A. 17a-Hydroxyprogesterone has a ketone functionality at carbon 5 due to a reduction reaction
B. 17a-Hydroxyprogesterone has a ketone functionality at carbon 3 due to a reduction reaction
C. 17a-Hydroxprogesterone undergoes an isomerization reaction and shifts its double bond to carbons 4-5
D. 17a-Hydroxyprogesterone has a ketone functionality at carbon 3 due to an oxidation reaction.
C. 17-Hydroxyprogesterone undergoes an isomerization reaction and shifts its double bond to carbons 4-5
D. 17a-Hydroxyprogesterone has a ketone functionality at carbon 3 due to an oxidation reaction
Remember OIL RIG
Oxidation Is Loss of Hydrogen
Based on the reaction occuring between 11-Deoxycortisol to Hydrocortisone, what is the name of the enzyme responsible for this?
A. 17B-Hydroxylase
B. 10B-Hydroxylase
C. 12B-Hydroxylase
D. 11B-Hydroxylase
D. 11B-Hydroxylase
It makes sense that it is an “11B” enzyme because it is hydroxylating carbon number 11. Hence the name 11B-Hydroxylase
Based on the structures provided what are the similarites between the two? (select all)
A. Both have ketone groups at carbon 3
B. Both have double bonds betwen carbons 5-6
C. Both have hydroxyl groups at carbon 11
D. Both have hydroxyl groups at carbon 17
E. Both have double bonds betwen carbons 4-5
A. Both have ketone groups at carbon 3
C. Both have hydroxyl groups at carbon 11
E. Both have double bonds between carbons 4-5
Know that the CHO group on aldosterone is an aldehyde group
The picture provided shows the different ester forms that hydrocortisone can be manufactured in. Which of the following statements is true when comparing Hydrocortisone to Hydrocortisone Sodium Phosphate?
A. Hydrocortisone sodium phosphate is more lipophilic and has better oral bioavailability
B. Hydrocortisone sodium phosphate is more charged and is better given as IM or IV injections
C. Hydrocortisone sodium phosphate is more charged and thus has a much longer half-life in the body
D. Hydrocortisone sodium phosphate is more charged and is used as a topical formulation.
B. Hydrocortisone sodium phosphate is more charged and is better given as IM or IV injections
The picture provided shows the different ester forms that hydrocortisone can be manufactured in. Which of the following statements is true regarding the difference between Hydrocortisone and Hydrocortisone Cypionate?
A. Hydrocortisone Cypionate is very lipophilic and as a result is absorbed more slowly from the GI tract and has a longer half life.
B. Hydrocortisone Cypionate is very lipophilic and as a result is given as a topical solution.
C. Hydrocortisone Cypionate is very hydrophilic and as a result is given IM or IV and has a shorter half-life
D. Hydrocortisone Cypionate is very hydrophilic and as a result is given as a topical solution
A. Hydrocortisone Cypionate is very lipophilic and as a result is absorbed more slowly from the GI tract and has a longer half life.
The picture provided shows the different ester forms that hydrocortisone can be manufactured in. Which of the following statements is true when comparing Hydrocortisone to Hydrocortisone Butyrate?
A. Hydrocortisone Butyrate is more Hydrophilic and is given as a topical solution
B. Hydrocortisone Butyrate is more Lipophilic and is given as an IM or IV solution
C. Hydrocortisone Butyrate is more Lipophilic and is given as an extended release oral dosage form
D. Hydrocortisone Butyrate is more Lipophilic and is given as a topical solution.
D. Hydrocortisone Butyrate is more Lipophilic and is given as a topical solution.
Remember that butyrate is not given orally but instead topically. Same goes for valerate (not shown in picture).
What kind of reaction is occuring in the conversin of Hydrocortisone (cortisol) to Cortisone?
A. Reduction reaction
B. Oxidation reaction
C. Hydroxylation reaction
D. Esterification
B. Oxidation Reaction
Remember OIL RIG
Oxidation Is Loss of Hydrogen
In the given picture what type of reaction is occuring from Hydrocortisone (cortisol) to 5B-Dihydrocortisol?
A. Oxidation reaction
B. Reduction Reaction
C. Hydroxylation
D. Esterification
B. Reduction Reaction
Remember OIL RIG
Reduction is Gain of Hydrogen
When comparing the structure of Fludrocortisone and Hydrocortisone, which of the following statments is true? (Select all)
A. Fluoro group added at carbon 6 on Fludrocortisone
B. Fluoro group added at carbon 9 on Fludrocortisone
C. Fluoro group increases mineralocorticoid activity of Fludrocortisone in comparison to Hydrocortisone
D. Fluoro group increase hydrophilicity of Fludrocortisone
E. Fluoro group increases the Lipophilicity of Fludrocortisone
B. Fluoro group added at carbon 9 on Fludrocortisone
C. Fluoro group increases mineralocorticoid activity of Fludrocortisone in comparison to Hydrocortisone
E. Fluoro group increases the Lipophilicity of Fludrocortisone
When comparing the structure of Hydrocortisone to Prednisolone, which of the following statements is true? (Select All)
A. Prednisolone has an additional double bond between carbons 1-2, decreaseing Glucocorticoid activity.
B. Prednisolone has an additional double bond between carbons 1-2, increasing Glucocorticoid activity
C. All exposed OH groups are succeptible to Esterification
D. All Ketone groups are succeptible to Esterification
B. Prednisolone has an additional double bond between carbons 1-2, increasing Glucocorticoid activity
C. All exposed OH groups are succeptible to Esterification
The additional double bond at the C 1-2 INCREASES glucocorticoid activity
Based on the picture provided, what kind of reaction is occuring in the metabolism of Prednisolone to 20a/B-Hydroxyprednisolone?
A. Oxidation
B. Reduction
C. Hydroxylation
D. Esterification
B. Reduction
Also when you see the squiggly line conncecting the OH on carbon 20, that means the OH group can be either in the alpha or the beta orientation. Alpha points away (dashed line) and beta points towards you (solid line)
What type of reaction is occuring in the metabolism of Prednisolone to 6B-Hydroxyprednisolone?
A. Hydroxylation at carbon 8
B. Reduction at carbon 8
C. Hydroxylation at carbon 6
D. Reduction at carbon 6
C. Hydroxylation at Carbon 6
What type of reaction is occuring in the metabolism of Prednisolone to 16a-Hydroxyprednisolone?
A. Hydroxylation at carbon 15
B. Hydroxylation at carbon 16
C. Reduction at carbon 16
D. Reduction at carbon 15
B. Hydroxylation at carbon 16
When comparing the structures of Hydrocortisone to Triamcinolone, which of the following statements are true? (Select All)
A. Triamcinolone has an additional double bond between C 1-2.
B. Triamcinolone has a double bond between carbons 5-6 and Hydrocortisone has a double bond between carbons 4-5.
C. Triamcinolone has an additional OH group at carbon 15
D. Triamcinolone has an additional OH group at carbon 16
E. Triamcinolone has a fluoro group at carbon 9
A. Triamcinolone has an additional double bond between C 1-2.
D. Triamcinolone has an additional OH group at carbon 16
E. Triamcinolone has a fluoro group at carbon 9
Also triamcinolone has more glucocorticoid activity than hydrocortisone due to the double bond at 1-2 and yet it somehow has LESS mineralocorticoid activity than Hydrocortisone, despite having a fluoro group??
When comparing the structures of Dexamethasone to Triamcinolone, which of the following statements is true?
A. Dexamethasone is more lipophilic than Triamcinolone due to the alpha CH3 substitution at carbon 16
B. Triamcinolone is more lipophilic than Dexamethasone due to the additional OH group at carbon 16
C. Triamcinolone has a longer half-life due to its higher lipophilicity in comparison to Dexamethasone
D. Dexamethasone is more lipophilic than Triamcinolone due to the beta CH3 substitution at carbon 16
A. Dexamethasone is more lipophilic than Triamcinolone due to the alpha CH3 substitution at carbon 16
Remember that if there is a dashed line that means it is an alpha carbon and is facing away from you.
Alpha = Away = Dashed
Also the only difference between Betamethasone and Dexamethasone is that in Betamethasone the CH3 at carbon 16 is in the beta configuration.
The medication ___ is an Antimineralocorticoid receptor antagonist and ___ is an Antiglucocorticoid receptor antagonist.
A. Spironolactone, Mifepristone
B. Mifepristone, Spironolactone
A. Spironolactone, Mifepristone
Also Mifepristone is a progestin antagonist as well.
The mechanism of action of Metyrapone is to inhibit the enzyme 11B-Hydroxylase. If this medication is given you would expect to see a(n) ____ in Hydrocortisone (cortisol) levels.
A. Increase
B. Decrease
B. Decrease
What enzyme is responsible for converting Androgens to Estrogens?
A. 5a-Reductase
B. Aromatase
C. Hydroxylase
D. Reductase
B. Aromatase
What enzyme is responsible for converting Testosterone to Dihydrotestosterone (DHT)?
A. 5a-Reductase
B. Aromatase
C. Reductase
D. Hydroxylase
A. 5a-Reductase
The picture provided shows the derivatives of testosterone. Cypionate and Enanthate can be added onto the structure of testosterone in order to ___ lipophilicity and ___ duration of action (DOA).
A. Increase, Decrease
B. Decrease, Increase
C. Decrease, Decrease
D. Increase, Increase
D. Increase, Increase
When comparing the structures of 17a-Methyltestosterone and Fluoxymesterone, which of the following statements is true? (Select All)
A. The fluoro group on carbon 9 of Fluoxymesterone increases hydrophilicity of the drug.in comparison to 17a-Methyltestosterone.
B. The fluoro group on carbon 9 of Fluoxymesterone greatly increases the activity of the drug in comparison to 17a-Methyltestosterone
C. The fluoro group on carbon 9 of Fluoxymesterone decreases the oxidative metabolism even further.
D. The fluoro group on carbon 9 of Fluoxymesterone can possibly increase side effects such as water and sodium retention.
B. The fluoro group on carbon 9 of Fluoxymesterone greatly increases the activity of the drug in comparison to 17a-Methyltestosterone
D. The fluoro group on carbon 9 of Fluoxymesterone can possibly increase side effects such as water and sodium retention.
Because of the increased activity due to the fluoro group the side effects can be much higher.
All of the folowing statments regarding Finasterade and Dutasteride are true EXCEPT:
A. Finasteride is much more lipophilic than Dutasteride
B. The MOA of Finasteride and Dutasteride is the inhibition of 5a-Reductase
C. These medications alter the biosynthesis of steroid molecules
D. The blue groups circled in each drug are known as Lactam groups
E. Both are known as “azosteroids”
A. Finasteride is much more lipophilic than Dutasteride
Dutasteride is more lipophilic due to the large ring and two fluoro groups attached to it.
The blue groups are known as Lactams NOT lactones
They are known as azosteroids because they have the steroid core structure (rings) and a nitrogen group which adds the “Azo” to the name.
The following picture shows how Dutasterade and Finasteride inhibit 5a-Reductase. They do this by ___ binding to NADPH and forming an ___ bond.
A. Ionically, Reversible
B. Covalently, Reversible
C. Ionically, Irreversible
D. Covalently, Irreversible
D. Covalently, Irreversible
The enzyme 5a-Reductase requires the cofactor NADPH in order to convert Testosterone to DHT and as a result the enzyme binds to the NADPH in order to carry out the reaction. However, Dutasteride and Finasteride will permenantly bind to the NADPH and thus renders the enzyme useless as well since it is now a part of the Finasteride-NADPH complex. That is why the lactam group in these drugs are very crucial for activity.
What key functional group do all the Androgen receptor antagonists have in common?
A. Fluoro groups
B. Nitrogen groups
C. Sulfer groups
D. Amide groups
D. Amide groups
They all contain amide groups hence the drug names ending in “amide”
Bicalutamide, Flutamide, Nilutamide
Dont forget an amide looks like an ester group but instead of an O linking two carbons its a nitrogen.
Of the three drug molecules displayed, which of the following is the correct labeling of each?
Estriol=____
Estradiol=____
Estrone=____
Estriol=Green (Three OH groups=triol)
Estradiol=Red (Two OH groups=diol)
Estrone=Blue (One OH and one Ketone= one)
Also you can identify an estrogen from an androgen by looking at Ring A. The estrogen will be a phenyl ring with 3 double bonds. Androgens will only have one or two double bonds in Ring A.
The following picture illustrates how estradiol is easily metabolized in two steps. The first step (red) is done through ___ and the second step (blue) is done through ____.
A. Reduction, Oxidation
B. Hydroxylation, Methylation
C. Hydroxylation, Hydroxylation
D. Reduction, Reduction.
B, Hydroxylation. Methylation
OH group is added at the 2nd or 4th carbon on estradiol. Then they are methylated by the addition of the methyl group. The enzyme responsible for the methylation is called COMT.
When comparing the structures of Estradiol to Ethynyl Estradiol, which of the following statements is true? (Select All)
A. Addition of the Ethynyl group at Carbon 17 increases oral bioavailability.
B. Addition of the Ethynyl group at Carbon 17 increases hydrophilicity and shortens half life
C. Addition of the Ethynyl group at Carbon 17 increases drug half-life
D. Addition of the Ethynyl group at Carbon 17 changes the alcohol into a tertiary alcohol, making it more succeptible to oxidation.
A. Addition of the Ethynyl group at Carbon 17 increases oral bioavailability.
C. Addition of the Ethynyl group at Carbon 17 increases drug half-life
What was the purpose of adding the Methyl group in Mestranol to the OH group on ring A?
A. Increases oral bioavailability
B. Converts the medication into a prodrug
C. Makes the OH group less succeptible to glucuronidation and sulfation
D. All of the above
D. All of the above
By adding the methyl group it changed ethynyl estradoil into the prodrug Mestranol. As a result when it is metabolized in the body it converts back into ethynyl estradiol and is activated.
OH groups are also succeptible to Glucuronidation and Sulfation but by adding a CH3 group to the OH on carbon 3 it makes it less succeptible.
Diethylstilbestrol (DES) was known as a Nonsteroidal estrogen because it lacked the steroid structure that Estradiol has. However it still had similar function to estradiol, why is this?
A. Both structures contained two complete phenyl rings
B. Both structures were completely cyclic in nature
C. The orientation of the OH groups were very similar between both molecules
D. None of the above
C. The orientation of the OH groups were very similar between both molecules
The similar orientatino of the OH groups allowed them to bind to estrogen receptors similarly. Also if you superimpose the structure on each other you can see how similar they are.
The medication Tamoxifen is similar to the structure DES and acts as an estrogen ____ in breast tissue and an estrogen ___ in the uterus.
A. Agonist, Agonist
B. Agonist, Antagonist
C. Antagonist, Agonist
D. Antagonist, Antagonist
C. Antagonist (breast), Agonist (uterus)
Also remember that the drug Tamoxifen is in the Z orientation!
Regarding the picture provided, what is the reaction that is occuring between Tamoxifen and Desmethyltamoxifen?
A. Demethylation
B. Oxidation
C. Reduction
D. Hydroxylation
A. Demethylation
Remember: Desmethyl means one less methyl.
Based on the picture provided the enzyme CYP2D6 is required to convert Tamoxifen to its metabolites 4-Hydroxytamoxifen and Edoxifen. Both of these metabolites have ___ activity than the active parent drug Tamoxifen.
A. More
B. Less
A. More
The metabolites 4-hydroxytemoxifen and Endoxifen have MUCH MORE potency than the normal parent drug Tamoxifen and as a result most of the activity comes from these active metabolites.
Based on the picture provided, what will happen if a patient taking Tamoxifen is given medications that inhibit CYP2D6 or is a poor CYP2D6 metabolizer? (Select All)
A. Increased overall activity of the drug Tamoxifen
B. Decreased overall activity of the drug Tamoxifen
C. Increased serum concentrations of 4-Hydroxytamoxifen and Endoxifen
D. Elevated levels of the parent drug Tamoxifen or Desmethyltamoxifen
E. Decreased serum concentrations of 4-hydroxytamoxifen and Endoxifen
B. Decreased overall activity of the drug Tamoxifen
D. Elevated levels of the parent drug Tamoxifen or Desmethyltamoxifen
E. Decreased serum concentrations of 4-hydroxytamoxifen and Endoxifen
Remember: Since most of Tamoxifen’s activity comes from its active metabolites, less of those metabolites will mean less overall activity.
Answer the following question provided in the picture below:
C. Dutasteride
practice on identifying what the MOAs are for the other answer choices.
Of these two aromatase inhibitors, which is the triazole inhibitor?
A. Red
B. Blue
A. Red
The way you can tell a triazole aromatase inhibitor apart from the steroidal aromatase inhibitor is the triazole will have 3 nitrogens in a cyclic ring (hence Tri=3, Azole= Nitrogen). The steroidal agent has a steroid core structure.
When comparing Triazole aromatase inhibitors to Steroidal aromatase inhibitors (Exemestane), which of the following statements is true? (Select All)
A. Exemestane will irreversibly bind to aromatase and inhibit it.
B. Triazole aromatase inhibitors will competitively and reversibly bind to aromatase and inhibit it
C. Both Triazole and Steroidal aromatase inhibitors compete with the natural substrates estrogen and Progestin
D. Both Triazole and Steroidal aromatase inhibitors compete with the natural substrates Testosterone and Androstendione
A. Exemestane will irreversibly bind to aromatase and inhibit it.
B. Triazole aromatase inhibitors will competitively and reversibly bind to aromatase and inhibit it
D. Both Triazole and Steroidal aromatase inhibitors compete with the natural substrates Testosterone and Androstenedione
Based on the picture provided you can see that the natural substrates of aromatase are testosterone and Androstenedione.
The ___ nitrogen of the triazole ring in triazole aromatase inhibitors will interact with the ____ atom of the aromatase enzyme
A. N-4, Heme Iron
B. N-2, Heme Iron
C. N-1, Heme Iron
A. N-4, Heme Iron
The nitrogen on the 4th position of the cyclic triazole group will bind to the iron heme in aromatase and reversibly inhibit the aromatase enzyme.
Based on the picture provided which metabolic reactions are occuring with progesterone? (Select All)
A. Reduction
B. Hydroxylation
C. Esterification
D. Methylation
A. Reduction
B. Hydroxylation
Upper right and lower left are both reductions. Bottom right reaction is Hydroxylation
