Glucocorticoids

Question 1

Synth of steroids

Answer 1

Membranes⇒Cholesterol⇒Pregnelone

Minerallocorticoids:

Pregnelone→Progesterone⇒⇒⇒Aldosterone

Glucocorticoids:

Pregnelone⇒17 OH Pregnenolone⇒17 OH Progesterone⇒11 deoxycortisol⇒cortisol

Sex steroids:

Pregnelone⇒17 OH Pregnenolone→DHEA→→Test.⇒Estradiol

P450 rxn: ⇒

Non P450 rxn: →

Question 2

Mech of steroids

Answer 2

1. Steroids enter cell
2. Bind to cytoplasmic receptor
3. Dimerize
4. Enter nucleus
5. Bind to steroid response element

• This can enhance or suppress gene transcription
  
  • Transactivation or transreppression
• Effects not immediate
• Given any route due to lipid content

Question 3

Specific mech. of glucocorticoids

Answer 3

Binds a receptor

Lipocortin 1 in induced

Lipocortin 1→inh. activity of phospholipase A2

PLA2 responsible for synth of arachadonic acid

Arachadonic acid is precursor for PGs and leukotrienes

Lipocortin 1 induced→inh. synth of many cytokines

Result: Immune suppression

Question 4

Cortisone

+

Hydrocortisone

Answer 4

Immunosuppressive potency=1

Relative minerallocorticod activity=1

Duration: 8-12hrs

Cortisone is a prodrug:

• Must be metab by P450 (in liver)
• Not effective topically

Question 5

Prednisone

+

Prednisolone

Answer 5

Immunosuppressive potency=4

Relative minerallocorticod activity=.25

Duration: 18-36hrs

Prednisone is a prodrug:

• Must be metab by P450 (in liver)
• Not effective topically

Question 6

Triamcinolone

Answer 6

Immunosuppressive potency=4

Relative minerallocorticod activity=.25

Duration: 18-36hrs

Question 7

-methasone

Answer 7

Dexamethasone

Betamethasone

Immunosuppressive potency=15

Relative minerallocorticod activity=<.01

Duration: 36-54hrs

Question 8

Topical use and GCs

Answer 8

Topical use can lead to systemic absorption and SE

Factors:

• Dose
• Duration
• Potency
• Size of area
• Occlusive dressings
• Skin damage
• Thickness of skin
  
  • More absorption at thin skin

Question 9

Solution

Answer 9

Homogenous dissolution in H2O

Question 10

Lotion

Answer 10

Suspension of powder in H2O

Question 11

Cream

Answer 11

Emulsion of oil in H2O

Question 12

Gel

Answer 12

Oil in H2O in cross linking carrier

Holds drug on skin longer

Question 13

Ointment

Answer 13

H2O in oil base (more oil than H2O)

Increases absorption

Longer duration→increase efficacy of drug

Question 14

Addison’s vs Cushing’s disease

Answer 14

Addison’s:

Deficiency of cortisol production

Weight loss

Low BP

Muscle weakness

Cushing’s:

Excess cortisol production

Question 15

SE of glucocorticoids

Answer 15

Metabolic changes

• Weight gain
• Increase gluconeogenesis
• Decrease glc by mm cells
• Increase protein breakdown
• Decrease protein synth.
• Altered lipolysis+ Fat redistribution
  
  • Abdomen
  • Moon face
  • Buffalo hump

Growth

• Muscle wasting
  
  • Thin arms and legs
• Growth inh. in children
• Bone damage
  
  • Osteoporosis
  • Osteonecrosis
  • Decrease bone growth

Ocular

• Cataracts
• Glaucoma

Cardiovascular

• Stroke
• MI
• Heart failure
• Hypertension
• Increase intracranial pressure

GI

• PGs necessary for mucus and bicarb. production
  
  • Ulcers
  • Gastritis
  • Bleeding

Skin

• Bruising (thin skin)
• Acne
• Increase infections
• Poor wound healing

Behavioral

• Euphoria or depression
• Psychosis
• Emotional lability

Cataracts, glaucoma

Ulcer

Skin thins/suppression of HPA

Hypertension

Infections

Necrosis of muscle

Gain wt/redistribution

Bone loss

Acne

Diabetes

Moonface

Depression/euphoria