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Pharmacology (Semester 6) > 3.2 Steroid Drugs > Flashcards

3.2 Steroid Drugs Flashcards

1
Q

What are the 3 layers of the adrenal coretx and what is secreted from each?

A

Zona Gomerulosa: mineralocorticoids (aldosterone)

Zona Fasciula: glucocorticoids (cortisol)

Zona Reticularis: androgens/ sex steroids (DHEA)

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2
Q

Corticosteroids are derived from what?

A

cholesterol

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3
Q

Cortisol = endogenous glucocorticoid

What is the name given to the SAME structure when it is given pharmacologically (exogenous)

A

Hydrocortisone

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4
Q

Give 2 other glucocorticoids (not cortisol)

A

Dexamethazone and Prednisolone

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5
Q

Explain the HPA axis

A
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6
Q

Give 3 metabolic actions of glucocorticoids

A

1) glycogenolysis and gluconeogenesis ➞ hyperglycaemia and proteinolysis
2) Lipolysis (at low conc)
3) Lipid deposition (at high conc) ➞ Redistribution of fat

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7
Q

Give 4 effects of a glucocorticoid deficiency

A
  1. Hypoglycaemia
  2. Weight loss
  3. Nausea
  4. Hypotension
  5. Underweight
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8
Q

Give 4 effects of a glucocorticoid excess

A
  1. Hyperglycaemia
  2. Weight gain
  3. Increased appetite
  4. Hypertension
  5. Cushingoid
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9
Q

When considering the effect of glucocorticoids, what else MUST we consider and why?

A

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

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10
Q

Give 4 effects of a mineralocorticoid deficiency

A
  1. Hyponatraemia
  2. Dehydration
  3. Hypotension
  4. Hyperkalaemia
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11
Q

Give 3 effects of a mineralocorticoid excess

A
  1. Hypernatraemia
  2. Hypertension
  3. Hypokalaemia
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12
Q

Explain what the image below shows

A

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

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13
Q

What does the image below show?

A

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

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14
Q

What 3 similarities can be said about most corticosteroids

A

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

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15
Q

Give 5 routes of administration for corticosteroids and an example of a drug used in each

A
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16
Q

Give 4 effects of corticosteroids on the immune system

A
  1. Inhibition of B and T cell responses
  2. Inhibition of NF-κB
  3. Reduced transcription of cytokines
  4. Reduced expression of cell adhesion molecules
  5. Reduced phagocytic function
  6. Immunosuppression
  7. Reduced inflammation
17
Q

Steroids are ______ soluble and ______ cross the cell membrane

A

lipid, can

18
Q

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 ________.

A

cytoplasm, nucleus, dimerise, enhancers, inhibitors, transcription

19
Q

What does HSP and HRE stand for?

A

HSP – heat shock protein

HRE – hormone response element

20
Q

What is the role of NF-κB?

A

Good modulator of the inflammatory response

21
Q

Give 2 things that occur when a corticosteroid binds to the glucocorticoid receptor

A

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

22
Q

Give 3 negative side effects of glucocorticoids and state why?

A

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

23
Q

What is CBP and its relevance in corticosteroids? (non-genetic effect)

A

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)

24
Q

Give 4 clinical uses of steroid drugs

A
  • Inflammatory disease
  • Immuno-suppression
  • Malignancy
  • Adrenal insufficiency
  • Cushing’s disease diagnosis
25
Q

Give 3 instances when corticosteroids may be used for replacement therapy

A
  1. Deficiency
  2. Addison’s disease
  3. Adrenolectomy
26
Q

What are the 2 main corticosteroids and their dosage used in replacement therapy?

A

Hydrocortisone 20 – 30 mg daily

Fludrocortisone 50 – 300 μg daily

27
Q

Give 4 Inflammatory diseases we can use corticosteroids to treat/manage

A
  1. Asthma
  2. GI diseases
  3. Inflammatory skin conditions
  4. Nephrotic syndrome
  5. Rheumatoid arthritis
  6. Cerebral oedema
28
Q

What is the use of steroids in preterm birth?

Who are they offered too and when?

A

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.

29
Q

Give 2 examples of steroids that can be used for preterm births (incl doses)

A

Betamethasone 12 mg given IM in two doses

OR

Dexamethasone 6 mg given IM in four doses

30
Q

Give 3 Mineralocorticoid side-effects (ADRs)

A
  1. Fluid retention
  2. Hypertension
  3. Hypokalaemia
31
Q

Give 6 Glucocorticoid side effects

A
32
Q

Give 2 Cushingoid features in terms of fat distribution

A

1) Central obesity
2) Dorso-cervical fat pad

33
Q

Give 5 Corticosteroid effects on bone

A
  1. Inhibition of osteoblast formation
  2. Increased osteoclast proliferation
  3. Reduced calcium absorption in gut
  4. Reduced sex steroid production
  5. Osteoporosis
34
Q

All steroid drugs mimic what endogenous steroid hormone?

What is the major risk factor of this for patients?

A

Cortisol

Adrenal suppression (may persist for years if patient is on long term treatment). Abrupt withdrawal may lead to hypo-adrenal crisis

35
Q

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

A

Suppression of HPA axis occurs after 3 weeks

Prednisolone > 20mg will suppress HPA axis

36
Q

Give ALL 6 main features/ risks of a Hypoadrenal crisis

A
  1. Hypotension
  2. Hypoglycaemia
  3. Hyponatraemia
  4. Hyperkalaemia
  5. Severe dehydration
  6. Death if untreated
37
Q

If a patient who has been on long term prednisolone requires surgery what MUST we do?

A

Gradually withdraw them off oral prednisolone

38
Q

How can we identify if a patient is on long term steroids when they are admitted into hospital?

A

Most will carry a steroid treatment card

Pharmacology (Semester 6) (17 decks)

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