Adrenal Corticosteroid Drugs Flashcards
Pharmacologic uses of [corticosteroids]
- Treat patients with [immunologic, inflammatory and allergic disorderd]
- Establish the diagnosis and cause of Cushings
- Tx adrenal insufficiency
- Tx CAH
What are adrenal corticosteroids?
Ligand-activated TF that modulate gene expression.
Aldosterone and Cortisol bind to MR receptor with ______ affinity
EQUAL
What are 3 active steroids?
- 1. Cortisol
- 2. Corticosterone
- 3. Prednisolone
What are 3 inert steroids?
- Cortisone
- 11-dehydrocorticosterone
- Prednisone
What is required for an inert steroid => active?
11 B-HSD1
(11-ketoreductase)
What is required for an active steroid => inert?
11B-HSD2
(11B-dehydrogenase)
2 short- acting glucocorticoids (8-12 hours) and equivalent dose
- Hydrocortisone (Cortisol) = 20 mg
- Cortisone acetetate = 25 mg
Intermediate-acting glucocorticoids (12-36 hours) and equiv doses
- Prednisone = 5mg
- Prednisolone = 5mg
- Methylprednisolone = 4mg
- Triamcinolone = 4mg
Long-Acting (36 - 72 hours) Glucocorticoids
- Betamethasone = 0.75 mg
- Dexamethasone = 0.6 mg
Therapeutic effects of Glucocorticoids on [immune cells, tissues and organs]
- Immunosuppression
- Anti-inflammatory
- Anti-allergy
- Secondary Pain Relief (in addition to primary meds)
What factors influence the therapeutic and AE of Corticosteroids?
- Potency
- Pharmakokinetics
- Daily dose and timing
- Differnce in metabolism
- Duration of treatment
Corticosteroids are derived from _____
Cholesterol
How should [Corticosteroids] be given for medical emergencies?
- High doses can be given for a FEW days with little risk, but no more than a few.
- NEVER replace/ delay more specific primary treatments (ABX for septic shock).
How should Corticosteroids be given for Chronic Treatment?
-
HIGHLY consider the evidence and how it should be used because it cannot be given chronically W/O adverse effects
- Dose/frequency
- Route of aministration
- Disease index to assess its therapeutic efficacy
Corticosteroids cannot be given chronically without _____
AE.
What are the guidlines for pharmocologic corticosteroid therapy?
- Give only if there is published evidence of therapetic benefit ONLY give after all other txs fail
- ID a specific therapetic objective and monitor the response to treatment. If none= stop taking
- Make sure take long enough to have a desired response, but no longer than necessary to have desired response.
When should you STOP taking corticosteroids?
- Objective therapeutic benefit is not observed
- Complications
- Max benefit is acheived
Treatment for Primary Adrenal insufficiency (Addisons Disease) and Congenital Adrenal Hyperplasia
Hydrocortisone + Fludrocortisone
When should corticosteroids be given for immunosuppresion?
- After organ/BM transplant
- AI disease
- Leukemia (Hematologic cancerS)
When should corticosteroids be given for Inflammatory and Allergic conditions?
- RA
- IBD
- Asthma/COPD
- Allergic Rhinitis
- Skin disease (Psoriasis)/Hypersensitivity Reaction
List 4 ways that glucocorticoids effect the immune system and inlammation
- ↓ production of prostaglandins, leukotrienes, cytokines and receptors
- ↓ production and ↑ apoptosis of immune cell types
- ↓ expression of cell adhesion molecules
- ↓ transmigration of neutrophils and macrophages from blood –> tissue
What are consequences of Glucocorticoids?
- Immunosuprresion
- ↓ inflammation and consequences
- ↓ allergic/hypersensitivity reactions
How do Glucocorticoids affect Carbohydrate Metabolism
-
Has anti-insulin actions, causing hyperglycemia due to
- ↓ glucose uptake
- ↑ gluconeogenesis
- ↑ Glucose output
- ↑ glycogen synthesis
How does glucocorticoids affect liver, skeletal muscle and adipose tissue?
- Liver: ↑ gluconeogenesis
-
Skeletal muscle (3)
- ↓ glucose uptake
- ↓ glycogen synthetase
- ↑ proteolysis
-
Fat:
- ↓ glucose uptake
- ↑ lipolysis
When treating DB patients with corticosteroids, what additional medication should you consider?
Pramlintide + insulin: anti-DB med that can help to control blood sugar
↓ activity/ inhibition of 11B HSD2 (11β-hydroxysteroid-dehydrogenase) = ________
↑ active cortisol => ↑ binding onto MR
What are known inhibitors of 11β-hydroxysteroid-dehydrogenase type 2?
- Glycyrrhizin (licorice root extract)
- Carbenoxolone (UK med to tx esophageal ulcers)
What is the downstream effect following inhibition of 11β-hydroxysteroid-dehydrogenase type 2 by substances such as glycyrrhizin (licorice root extract)?
- ↑ (+) of MR receptor by cortisol
- ↑ Na/H20 retention; ↑ K+ loss
- ↑ BP
Which patients should we be cautious in adrenal corticosteroids?
- Immunocompromised (HIV/AIDS)
- DB
- Pts with infection, peptic ulcers, CV diseases, psychiatric condition
- Post-menopausal women with osteoporosis
- Children
AE with of corticosteroids occur with _______ and can cause _____
Prolonged use of high doses
Cushing disease
How do we dose adrenocorticoid drugs?
- Lowest concentration for shortest time possible
- Try to avoid putting into systemic circulation: use topical or inhalation routes
- Give single dose in the morning (AM)
- Alternate day, short-course therapy
- Dose tapering to allow HPA axis to recovery when reach theraptic benefit
When dose-tapering off of glucocorticoids, what is important?
Measure the integrity of the HPA axis with
1. Morning serum cortisol
2. ACTH test
3. CRH test
Drug used to treat adrenal cortical carcinoma (cancer in adrenal glands)
Mitotane
Which drug has the strongest anti-inflammatory activity, relatie hydrocortisone? Weakest?
Strongest = dexamethasone and betamethasone
Weakest= cortisone acetate (0.8)
Prednisolone
MOA:
Clinical applications:
Pharmokinetics:
AE:
- Glucorticoid AGO => + GR => alter gene transcription
- Inflammatory conditions, organ transplant, hematologic cancers
- Duration of activity is longer than 1/2 life bc it affects gene transciption
- Adrenal suppresion
Mifepristone
- MOA:
- Clinical applications:
- Pharmokinetics:
- AE:
- Glucocorticoid/progesterone R ANT
- Abortions (and rarely Cushings)
- Taken orally
- Vaginal bleeding
Fludrocortisone
- MOA:
- Clinical applications:
- Pharmokinetics:
- AE:
- Mineralocorticoid***/glucocortioid AGO
- Adrenal Insuffiency (Addisons disease)
- LONG duration of action
- AE (3)
- Na+/H20 retention,
- CHF
- Signs of Glucocorticoid excess
2 Mineralcorticoid-R ANT
1. Spironolactone
2. Eplerenone
Spironolactone
- MOA:
- Clinical applications:
- Pharmokinetics:
- AE:
- Mineralcorticoid ANT; weak androgen R ANT
-
Treats
- Aldosteronism,
- Hypokalemia due to diuretic effect,
- Post-MI
- Slow onset and offset (lasts 24-48 hrs)
-
AE
- Hyperkalemia
- Gynecomastia
- Ineration with other K+ retaining drugs
Eplerenone
MOA:
Clinical applications:
Pharmokinetics:
AE:
- Mineralcorticoid R ANT
- Treats HTN to lower BP.
- Short half life (3-6 hours) bc broken down by CYP3A4
- AE
- Hyperkalemia
- ↑ Cr
What is the Corticosteroid Synthesis Inhibitor?
Ketoconazole
Ketoconazole
- MOA
- Clinical Applications
- Pharmacokinetics
- AE
- Blocks corticosteroid synthesis by blocking fungal/mammilian CYP450
- Prevents steroid hormone and funal ergosterol synthesis
- Taken oral or topically
- Many drug-drug CYP450 interactions
