Med Chem 2 Exam 4: Glucocorticoids and Mineralocorticoids

The major functions of hormones include the

regulation of energy, storage, production, and utilization; the adaptation to new environments or conditions of stress; the facilitation of growth and development; and the maturation and function of the reproductive system

An inner core (medulla) secretes

catecholamines

the shell/cortex of the adrenal glands synthesize

steroids, corticosteroids and androgens

Corticosteroids act by binding to specific receptor proteins in target tissues, which regulate

the expression of corticosteroid-responsive genes and alter the types and levels of proteins produced by these cells

Zona fasciculata

cortisol synthesis

Zona glomerulosa

aldosterone

Corticosteroids have numerous effects

Alterations in carbohydrate, protein, and lipid metabolism

Maintenance of fluid and electrolyte balance

Preservation of normal function of the cardiovascular system, the immune system (anti-inflammatory), the kidney, skeletal muscle, the endocrine system, and the nervous system

Capacity to resist stressful and noxious stimuli and environmental changes

In the absence of adequate secretion of corticosteroids from the adrenal cortex,stresses such as

infection, trauma, and extremes in temperature can be fatal

mineralocorticoids

electrolyte balance-regulating activity

glucocorticoids

carbohydrate metabolism-regulating activity

what differentiate glucocosteriods and mineralcorcosteriods

their relative potencies in Na + retention and effects on carbohydrate metabolism

main glucocorticoid

cortisol

physiologic mineralocorticoid

aldosterone

excess of cortisol (glucocorticoid excess) circulating in the body for a prolonged period

Cushing's syndrome.

what are corticosteroids derived from

cholesterol

The receptors for corticosteroids are members of the

nuclear receptor family of transcription factors

GRs/MRs reside predominantly in the

cytoplasm in an inactive form complexed with other proteins

Steroid binding results in receptor

activation and translocation to the nucleus

GRs are essentially

ubiquitous (everywhere)

MRs are expressed in epithelial tissues involved in

electrolyte transport

synthetic glucocorticoids and can be grouped according to their salt retention activity as:

Mineralocorticoids

Glucocorticoids with moderate to low salt retention

Glucocorticoids with very little or no salt retention

Mineralocorticoids drug

Fludrocortisone

Fludrocortisone is a mineralocorticoid used to treat

adrenocortical insufficiency and salt-losing adrenogenital syndrome

Fludrocortisone is used with hydrocortisone to replace missing

endogenous corticosteroids in patients with adrenal insufficiency

thought to be crucial to its mineralocorticoid potency

Fluorination

Fludrocortisone acts on the kidneys to increase

sodium reabsorption and potassium excretion

When fludrocortisone binds to mineralocorticoid receptors causes alterations to DNA transcription and

translation of proteins that result in an increased density of sodium channels on the apical side of renal tubule cells and an increased density of Na + -K +-ATPase on the basolateral side (more NA in more K out)

Glucocorticoids-moderate-low salt retention drugs

Cortisol, Prednisolone, Prednisone, and Methylprednisolone

It is used to treat immune, inflammatory, and neoplastic conditions

Cortisol

otic solutions of cortisol are indicated for

infections of the external auditory canal caused by susceptible organisms and with inflammation

tablet verison of cortisol are indicated for

certain endocrine, rheumatic, collagen, allergic, ophthalmic, respiratory, hematologic, neoplastic, edematous, gastrointestinal, and other conditions; enema is indicated for ulcerative colitis

structurally cortisol contains

a,b unsaturated ketone and an ester

it is indicated to treat endocrine, rheumatic, and hematologic disorders; collagen, dermatologic, ophthalmic, respiratory, and gastrointestinal diseases

Prednisolone

contains a double sided a,b-unsaturated ketone

Prednisolone

It is biologically inert and converted to prednisolone in the liver by CYP3A4

Prednisone

anti-inflammatory or immunosuppressive

intra-articular and soft tissue injections are indicated for short term treatment of acute gouty arthritis, acute and subacute bursitis

Methylprednisolone acetate

In the outbreak ofCOVID-19, low dose ___________ -based therapy was successful in treating COVID-19-associated pneumonia

methylprednisolone

structurally methylprednisolone contains an extra

methyl group

It is a long-acting corticosteroid with immunosuppressive and anti-inflammatory properties.

Betamethasone

betamethasone can be used topically to manage inflammatory skin conditions like

eczema

Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial on 16 June 2020, __________ was recommended for use in COVID-19 patients with severe respiratory symptoms

dexamethasone

It is also usually found in combination with antibiotics for example with ciprofloxacin, neomycin, tobramycin

dexamethasone

Beclomethasone is a prodrug of

beclomethasone 17-monopropionate (17-BMP)

beclomethasone 17-monopropionate (17-BMP) acts on the GR to

mediates its therapeutic action

Beclomethasone by itself possesses

weak glucocorticoid receptor binding affinity and is rapidly converted into 17-BMP upon administration

reported to be less irritating to the nasal mucosa with a longer duration of action when administered intranasally

beclomethasone

It is a corticosteroid that presents a high lipophilicity

Fluocinolone

Fluocinolone is used in what preparations

dermatological and implantable corticosteroid devices as in Retisert

what does fluocinolone contain

acetonide that is a protective group

this type of device containing fluocinolone acetonide was developed by TaroPharmaceuticals and approved for

intravitreal, diabetic macular edema

is a nonfluorinated corticosteroid anti-inflammatory agent used topically for dermatoses

Desonide

indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses

Amcinonide

Flurandrenolide

relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses, particularly dry, scaling localized lesions

indicated in the treatment of allergic and inflammatory conditions (eye drops) and as topically in the treatment of various skin disorders

Fluorometholone

It is a mix of epimers used to treat inflammatory conditions of the lungs and intestines such as asthma, COPD, Crohn's disease, and ulcerative colitis.

Budesonide

extended-release capsules of budesonide are indicated for the treatment of

Crohn's disease, colitis and to reduce proteinuria in adults with IgA nephropathy

inhaled products of budesonide

treat prophylactic therapy in asthma and to reduce exacerbations of COPD

structurally budesonide contains an acetonide with

a large alkyl chain

it is indicated for the treatment of nasal symptoms associated with seasonal and perennial allergic rhinitis in adults and adolescents 12 years of age and older

Ciclesonide

Ciclesonide is a prodrug that is hydrolyzed to

C21-desisobutyryl-ciclesonide following intranasal application

which has higher affinity for GR as an anti-inflammatory effect, ciclesonide or desciclesonide

desciclesonide

clobetasol and halobetasol contain

the halogen Cl

It is indicated to treat moderate to severe plaque psoriasis and eczema as well as inflammatory and pruritic manifestations of corticosteroid responsive dermatoses

Clobetasol

As cream and ointment are indicated in the treatment of inflammatory and pruritic corticosteroid responsive dermatoses

Halobetasol

due to its high potency, Halobetasol it is mainly prescribed in the treatment

of severe plaque psoriasis and corticosteriod responsive dermatoses

structure differences between halobetasol and clobetasol

clobetasol: ester and one less F atom

halobetasol: OH and another F atom

Halcinonide

indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses, psoriasis and is distributed as a cream, solution and ointment

Triamcinolone

allergic rhinitis to acute exacerbations of multiple sclerosis

first line as a topical treatment of corticosteroid responsive dermatoses

Triamcinolone

Triamcinolone is seen as

hexacetonide, acetonide, and diacetate

it is used as anti-inflammatory and immunosuppressant in the management of Duchenne muscular dystrophy (DMD)

Vamorolone

The onset of DMD is

typically begins around age four, with rapid progression

Vamorolone acts as what at the GR

partial agonist

Vamorolone acts as what at the MR

antagonist

Glucocorticoids induced

osteoporosis and steroid myopathy

steroids induce

myopathy and osteonecrosis (death of bone tissue)

Corticosteroids increase levels of glucose inducing

diabetes and cushing syndrome

Corticosteroids can lead to cardio effects like

Hypertension and fluid. retention

Corticosteroid derma/eye side effects

skin thinning, facial erythema; cataracts

Corticosteroid GI side effects

GI bleeding, gastritis, gastric ulcers

Corticosteroid Neuropsychiatric side effects

mild euphoria, anxiety, and depression

Agonist to GR and MR, have play important therapeutic role including in

immunosuppression, as anti-inflammatory agents, and antiallergic activity.