Corticosteroids (CSs) and DMARDs Practice Flashcards

A set of practice flashcards covering the medicinal chemistry, pharmacophore structures, and classifications of corticosteroids and disease-modifying antirheumatic drugs (DMARDs).

How many carbon atoms are typically found in the structure of a corticosteroid?

21

Which class of corticosteroids is responsible for regulating carbohydrate, lipid, and protein metabolism?

Glucocorticoids

Which class of corticosteroids is responsible for influencing salt balance and water retension?

Mineralocorticoids

What are all corticosteroids biosynthesized by?

Cholesterol

In humans, which specific corticosteroid is considered the primary glucocorticoid?

Hydrocortisone (cortisol)

Which substance is identified as the main mineralocorticoid in humans?

Aldosterone

What are the four fused rings in the corticosteroid pharmacophore designated as?

A, B, C, D

At what position is a ketone located for corticosteroids on ring A?

3

What group is located at position 3 of corticosteroids?

Ketone

At what position is a double bond located for corticosteroids?

4 & 5

What is located at position 4 & 5 of corticosteroids?

Double bond

At what position is a hydroxyl located for corticosteroids?

11

What is located at position 11 of corticosteroids?

Hydroxyl group

At which position is the ketone located on the side chain of a corticosteroid structure?

20

Where is the additional double bond located affecting potency and bioavailability of corticosteroids?

1 & 2

What is located at position 1 & 2 affecting potency and bioavailability of corticosteroids?

Double bond

What is added at position 6, 9 or 21 affecting potency and bioavailability of corticosteroids?

Halide

What what positions is are halides added affecting potency and bioavailability of corticosteroids?

6, 9, or 21

What are groups that increase lipophilicity of corticosteroids?

Halogen, ketal

At what position is resistance of the molecule to biotransformation occurs for corticosteroids?

16

What groups is used to block position 16 of corticosteroids?

Methyl or ketal

What happens at position 16 of corticosteroids?

Resistance to biotransformation occurs

What group in hydrocortisone acetate makes it have an increased stability and longer duration of action?

Ester

The ester group in hydrocortisone acetate helps with increased stability and what?

Longer duration of action

How is hydrocortisone acetate administered?

IM

What group in hydrocortisone sodium phosphate makes it extremely water-soluble?

Phosphate ester

Which systemic corticosteroid is given for emergency conditions?

Hydrocortisone sodium phosphate

What is the prodrug of hydrocortisone?

Hydrocortisone acetate

What does prednisolone have that increases potency by 3-4 times compared to hydrocortisone?

double bond at 1,2

What group is located at position 16 of dexamethasone?

Methyl group

What is located at position 9 of dexamethasone?

Halogen

Which potency corticosteroids have a modest anti-inflammatory effect and safest for chronic application?

Low

What do most low potency corticosteroids have?

No halogens

What does Desonide have at position 16 & 17?

Ketal moiety

At what positions does dexamethasone have substitutions to increase stability and improve bioavailability?

9 & 16

What do medium potency corticosteroids have?

Halogens and ketal moieties

What group does not lead to longer duration of action?

Phosphate ester

What group increases stability and leads to longer duration of action?

Ester

What must steroids with 11-keto group must be enzymatically reduced to what derivative before they are biologically active?

11b-hydroxy

What happens when 11-keto is not enzymatically reduced?

Severe hepatic failure and cortisone reductase deficiency

What is the prodrug of prednisolone?

Prednisone

What is biologically active corticosteroids?

Unbound fraction

How are synthetic corticosteroids excreted?

Urine

What are synthetic corticosteroids excreted as?

Glucuronide conjugates

What is located at position 20 of corticosteroids?

ketone group

How are systemic corticosteroids may be administered?

iv, oral, solution

To which plasma proteins do systemic corticosteroids bind in a proportion greater than $90\%$?

Transcortin and albumin

What percentage of systemic corticosteroids bind to plasma proteins?

90%

How are synthetic corticosteroids excreted similarly to?

Endogenous adrenocorticoids

What rapidly converts corticosteroids to inactive metabolites?

Hepatic oxidative metabolism

What makes Hepatic oxidative metabolism prevent harm on?

HPA-suppressive effects

Where is systemic corticosteroids primarily metabolized?

Liver

Are topical corticosteroids able to be systemically absorbed?

Yes

Are topical corticosteroids lipophilic or hydrophilic?

Lipophilic

Do inhaled & intranasal corticosteroids have long or short half-life?

Short

Which type of corticosteroid lack active metabolites?

Inhaled & Intranasal Corticosteroids

Do topical corticosteroids have long or short duration of action?

Long

What does inhaled and intranasal corticosteroids lack?

Active metabolites

How are synthetic DMARDS administered?

Orally

What do DMARDs prevent?

Joint damage

How are biologic DMARDS administered?

IV or SQ

What class does hydroxychloroquine belong to?

4-aminoquinoline

Is hydroxychloroquine water soluble?

Yes

What is sulfasalazine?

Prodrug

Direct administration of what is irritating to gastric mucosa?

5-ASA

How is the azo link cleaved?

Colonic bacteria

What does colonic bacteria cleave?

Azo link

How much of sulfapyridine is absorbed in the colon?

60-80%

How much of 5-ASA is absorbed in the colon?

25%

Where is sulfapyridine & 5-ASA absorbed in?

Colon

What drug is an analog of folic acid?

Methotrexate

What type of inhibitor is methotrexate?

Potent competitive inhibitor

What is methotrexate a potent competitive inhibitor of what?

DHFR

What enzyme does leflunomide interferes with?

Dihydroorotate dehydrogenase

What is Leflunomide metabolized to?

Active & stable metabolite

What is azathioprine?

Prodrug

What is the active metabolite of azathioprine?

6-mercaptopurine

Is cyclosporine lipophilic?

Yes

What is cyclosporine made of?

Cyclic peptides

How many amino acids are made of cyclosporine?

11

How is hydroxychloroquine metabolized?

N-dealkylation