Adrenal Corticosteroid Drugs Flashcards
(43 cards)
1
Q
Pharmacologic uses of [corticosteroids]
A
- Treat patients with [immunologic, inflammatory and allergic disorderd]
- Establish the diagnosis and cause of Cushings
- Tx adrenal insufficiency
- Tx CAH
2
Q
What are adrenal corticosteroids?
A
Ligand-activated TF that modulate gene expression.
3
Q
Aldosterone and Cortisol bind to MR receptor with ______ affinity
A
EQUAL
4
Q
What are 3 active steroids?
A
- 1. Cortisol
- 2. Corticosterone
- 3. Prednisolone
5
Q
What are 3 inert steroids?
A
- Cortisone
- 11-dehydrocorticosterone
- Prednisone
6
Q
What is required for an inert steroid => active?
A
11 B-HSD1
(11-ketoreductase)
7
Q
What is required for an active steroid => inert?
A
11B-HSD2
(11B-dehydrogenase)
8
Q
2 short- acting glucocorticoids (8-12 hours) and equivalent dose
A
- Hydrocortisone (Cortisol) = 20 mg
- Cortisone acetetate = 25 mg
9
Q
Intermediate-acting glucocorticoids (12-36 hours) and equiv doses
A
- Prednisone = 5mg
- Prednisolone = 5mg
- Methylprednisolone = 4mg
- Triamcinolone = 4mg
10
Q
Long-Acting (36 - 72 hours) Glucocorticoids
A
- Betamethasone = 0.75 mg
- Dexamethasone = 0.6 mg
11
Q
Therapeutic effects of Glucocorticoids on [immune cells, tissues and organs]
A
- Immunosuppression
- Anti-inflammatory
- Anti-allergy
- Secondary Pain Relief (in addition to primary meds)
12
Q
What factors influence the therapeutic and AE of Corticosteroids?
A
- Potency
- Pharmakokinetics
- Daily dose and timing
- Differnce in metabolism
- Duration of treatment
13
Q
Corticosteroids are derived from _____
A
Cholesterol
14
Q
How should [Corticosteroids] be given for medical emergencies?
A
- 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).
15
Q
How should Corticosteroids be given for Chronic Treatment?
A
-
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
16
Q
Corticosteroids cannot be given chronically without _____
A
AE.
17
Q
What are the guidlines for pharmocologic corticosteroid therapy?
A
- 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.
18
Q
When should you STOP taking corticosteroids?
A
- Objective therapeutic benefit is not observed
- Complications
- Max benefit is acheived
19
Q
Treatment for Primary Adrenal insufficiency (Addisons Disease) and Congenital Adrenal Hyperplasia
A
Hydrocortisone + Fludrocortisone
20
Q
When should corticosteroids be given for immunosuppresion?
A
- After organ/BM transplant
- AI disease
- Leukemia (Hematologic cancerS)
21
Q
When should corticosteroids be given for Inflammatory and Allergic conditions?
A
- RA
- IBD
- Asthma/COPD
- Allergic Rhinitis
- Skin disease (Psoriasis)/Hypersensitivity Reaction
22
Q
List 4 ways that glucocorticoids effect the immune system and inlammation
A
- ↓ 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
23
Q
What are consequences of Glucocorticoids?
A
- Immunosuprresion
- ↓ inflammation and consequences
- ↓ allergic/hypersensitivity reactions
24
Q
How do Glucocorticoids affect Carbohydrate Metabolism
A
-
Has anti-insulin actions, causing hyperglycemia due to
- ↓ glucose uptake
- ↑ gluconeogenesis
- ↑ Glucose output
- ↑ glycogen synthesis
25
How does **glucocorticoids** affect liver, skeletal muscle and adipose tissue?
1. **Liver**: ↑ gluconeogenesis
2. **Skeletal muscle (3)**
1. ↓ glucose uptake
2. ↓ glycogen synthetase
3. ↑ proteolysis
3. **Fat:**
1. ↓ glucose uptake
2. ↑ lipolysis
26
When treating **DB** patients with corticosteroids, what additional medication should you consider?
**Pramlintide + insulin**: anti-DB med that can help to control blood sugar
27
↓ activity/ inhibition o**f 11B HSD2** (11β-hydroxysteroid-dehydrogenase) = \_\_\_\_\_\_\_\_
**↑ active cortisol =\> ↑ binding onto MR**
28
What are **known inhibitors** of **11β-hydroxysteroid-dehydrogenase type 2?**
1. - **Glycyrrhizin** (licorice root extract)
2. - **Carbenoxolone** (UK med to tx esophageal ulcers)
29
What is the downstream effect following **inhibition of 11β-hydroxysteroid-dehydrogenase type 2** *by* substances such as **glycyrrhizin** (licorice root extract)?
1. ↑ (+) of MR receptor by cortisol
2. ↑ Na/H20 retention; ↑ K+ loss
3. **↑ BP**
30
Which patients should we be cautious in a**drenal corticosteroids?**
1. **Immunocompromised (HIV/AIDS)**
2. **DB**
3. Pts with infection, peptic ulcers, CV diseases, psychiatric condition
4. **Post-menopausal women** with osteoporosis
5. **Children**
31
AE with of corticosteroids occur with _______ and can cause \_\_\_\_\_
**Prolonged use of high doses**
**Cushing disease**
32
How do we **dose** adrenocorticoid drugs?
1. **Lowest concentration** for **shortest** **time** possible
2. Try to **avoid putting into systemic circulation:** use topical or inhalation routes
3. Give **single dose in the morning (AM)**
4. **Alternate day, short-course therapy**
5. Dose tapering to allow HPA axis to recovery when reach theraptic benefit
33
When dose-tapering off of glucocorticoids, what is important?
Measure the integrity of the HPA axis with
## Footnote
**1. Morning serum cortisol**
**2. ACTH test**
**3. CRH test**
34
Drug used to treat **adrenal cortical carcinoma** (cancer in adrenal glands)
**Mitotane**
35
Which drug has the **strongest anti-inflammatory activity,** relatie hydrocortisone? **Weakest**?
**Strongest** = dexamethasone and betamethasone
**Weakest**= cortisone acetate (0.8)
36
**_Prednisolone_**
## Footnote
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**
37
**_Mifepristone_**
* MOA:
* Clinical applications:
* Pharmokinetics:
* AE:
* **Glucocorticoid/progesterone R ANT**
* Abortions (and rarely Cushings)
* Taken orally
* Vaginal bleeding
38
**_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
39
2 M**ineralcorticoid-R ANT**
**1. Spironolactone**
**2. Eplerenone**
40
**_Spironolactone_**
* MOA:
* Clinical applications:
* Pharmokinetics:
* AE:
* **Mineralcorticoid ANT**; weak androgen R ANT
* **Treats**
1. Aldosteronism,
2. Hypokalemia due to diuretic effect,
3. Post-MI
* **Slow onset and offset (lasts 24-48 hrs)**
* **AE**
1. Hyperkalemia
2. Gynecomastia
3. Ineration with other K+ retaining drugs
41
**_Eplerenone_**
## Footnote
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
1. Hyperkalemia
2. ↑ Cr
42
What is the **Corticosteroid Synthesis Inhibitor?**
**Ketoconazole**
43
**_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**
