3.2 Steroid Drugs Flashcards
What are the 3 layers of the adrenal coretx and what is secreted from each?
Zona Gomerulosa: mineralocorticoids (aldosterone)
Zona Fasciula: glucocorticoids (cortisol)
Zona Reticularis: androgens/ sex steroids (DHEA)
Corticosteroids are derived from what?
cholesterol
Cortisol = endogenous glucocorticoid
What is the name given to the SAME structure when it is given pharmacologically (exogenous)
Hydrocortisone
Give 2 other glucocorticoids (not cortisol)
Dexamethazone and Prednisolone
Explain the HPA axis
Give 3 metabolic actions of glucocorticoids
1) glycogenolysis and gluconeogenesis ➞ hyperglycaemia and proteinolysis
2) Lipolysis (at low conc)
3) Lipid deposition (at high conc) ➞ Redistribution of fat
Give 4 effects of a glucocorticoid deficiency
- Hypoglycaemia
- Weight loss
- Nausea
- Hypotension
- Underweight
Give 4 effects of a glucocorticoid excess
- Hyperglycaemia
- Weight gain
- Increased appetite
- Hypertension
- Cushingoid
When considering the effect of glucocorticoids, what else MUST we consider and why?
Mineralocorticoid effect!
Glucocorticoids can bind to mineralocorticoid receptors due to their structural similary. This may cause patients to present with symptoms associated with mineralocorticoids AND corticoids
Give 4 effects of a mineralocorticoid deficiency
- Hyponatraemia
- Dehydration
- Hypotension
- Hyperkalaemia
Give 3 effects of a mineralocorticoid excess
- Hypernatraemia
- Hypertension
- Hypokalaemia
Explain what the image below shows
The relative action of specific corticosteroid drugs on the glucocorticoid and mineralocorticoid receptors
Hydrocortisone = 1
➞ normalised effect on both receptors which is used to compare the other drugs
What does the image below show?
Equivalent anti-inflammatory doses of corticosteroids (potency) compared to a 5mg dose of Prednisolone
This table takes no account of mineralocorticoid effects, nor does it take account of variations in duration of action
What 3 similarities can be said about most corticosteroids
1) When taken orally, steroids have similar bioavailability
2) Most metabolised hepatically and cleared renally (renal clearance)
3) Ability for clearance with all steroids, decreases with age
Give 5 routes of administration for corticosteroids and an example of a drug used in each
Give 4 effects of corticosteroids on the immune system
- Inhibition of B and T cell responses
- Inhibition of NF-κB
- Reduced transcription of cytokines
- Reduced expression of cell adhesion molecules
- Reduced phagocytic function
- Immunosuppression
- Reduced inflammation
Steroids are ______ soluble and ______ cross the cell membrane
lipid, can
Steroid diffuses into cell and binds to hormone receptors either in the ______ or the ________.
They then _______ and act as either ______ or ______ of hormone response elements by regulating gene ________.
cytoplasm, nucleus, dimerise, enhancers, inhibitors, transcription
What does HSP and HRE stand for?
HSP – heat shock protein
HRE – hormone response element
What is the role of NF-κB?
Good modulator of the inflammatory response
Give 2 things that occur when a corticosteroid binds to the glucocorticoid receptor
1) transactivation ➞ regulates Annexin 1 which inhibits leukocyte inflammation events
2) transrepression ➞ upregulates CBP which is the inhibtor of NF-κB
These stimulate anti-inflammatory gene transcription
Give 3 negative side effects of glucocorticoids and state why?
1) Repression of gene expression by down regulation of HPA axis
2) Downregulation of osteocalcin ➞ important for osteoblast activity
3) Reduces the amount of keratin ➞ skin thinning
What is CBP and its relevance in corticosteroids? (non-genetic effect)
CBP: cAMP response element binding protein
This is a coactivator molecule. Corticosteroid can bind to this which attacts and complexes to NF-κB. This holds NF-κB in an inactive form which reduces its inflammatory effect.
(Note: this is in additon to the upregulation of NF-κB inhibtors)
Give 4 clinical uses of steroid drugs
- Inflammatory disease
- Immuno-suppression
- Malignancy
- Adrenal insufficiency
- Cushing’s disease diagnosis
Give 3 instances when corticosteroids may be used for replacement therapy
- Deficiency
- Addison’s disease
- Adrenolectomy
What are the 2 main corticosteroids and their dosage used in replacement therapy?
Hydrocortisone 20 – 30 mg daily
Fludrocortisone 50 – 300 μg daily
Give 4 Inflammatory diseases we can use corticosteroids to treat/manage
- Asthma
- GI diseases
- Inflammatory skin conditions
- Nephrotic syndrome
- Rheumatoid arthritis
- Cerebral oedema
What is the use of steroids in preterm birth?
Who are they offered too and when?
Steroid are used to enhance lung maturation. They can cross the placenta and stimulate surfactant production of immature lungs. This reduces the symptoms of respiratory distress syndrome
A single course of antenatal corticosteroids are offered to women, who are at risk of preterm birth, between 24 and 34 weeks of gestation.
Give 2 examples of steroids that can be used for preterm births (incl doses)
Betamethasone 12 mg given IM in two doses
OR
Dexamethasone 6 mg given IM in four doses
Give 3 Mineralocorticoid side-effects (ADRs)
- Fluid retention
- Hypertension
- Hypokalaemia
Give 6 Glucocorticoid side effects
Give 2 Cushingoid features in terms of fat distribution
1) Central obesity
2) Dorso-cervical fat pad
Give 5 Corticosteroid effects on bone
- Inhibition of osteoblast formation
- Increased osteoclast proliferation
- Reduced calcium absorption in gut
- Reduced sex steroid production
- Osteoporosis
All steroid drugs mimic what endogenous steroid hormone?
What is the major risk factor of this for patients?
Cortisol
Adrenal suppression (may persist for years if patient is on long term treatment). Abrupt withdrawal may lead to hypo-adrenal crisis
How long does it take for supression of the HPA axis to occur?
Give an example of a specific drug and dosage that will do this
Suppression of HPA axis occurs after 3 weeks
Prednisolone > 20mg will suppress HPA axis
Give ALL 6 main features/ risks of a Hypoadrenal crisis
- Hypotension
- Hypoglycaemia
- Hyponatraemia
- Hyperkalaemia
- Severe dehydration
- Death if untreated
If a patient who has been on long term prednisolone requires surgery what MUST we do?
Gradually withdraw them off oral prednisolone
How can we identify if a patient is on long term steroids when they are admitted into hospital?
Most will carry a steroid treatment card
