U2i / 20B03 / 17A10: Describe the pharmacology of hydrocortisone

20B03: Exam Report

Describe the pharmacology of hydrocortisone.

69% of candidates passed this question.

Hydrocortisone is a level 1 drug in the syllabus. Most answers were well structured, many used key headings. In general, detailed information specific to hydrocortisone was lacking. Answers that focused on the mechanism of action, pharmacodynamic effects and pharmacokinetics effects which were detailed and accurate scored well. It was expected that significant detail be included in the sections with relevance to clinical practice for example, the mechanism of action and pharmacodynamic effects including the side effect profile. An indication/appreciation of the timelines of such was also represented in the marking template.

17A10: Exam Report

Describe the pharmacology of hydrocortisone.

54% of candidates passed this question.

Hydrocortisone is listed as a Class A drug in the syllabus and as such knowledge of its pharmacokinetics is expected. No marks were awarded for generic pharmacokinetic statements such as: “average bioavailability”, “moderate protein binding”, “bioavailability 100% for IV preparation” etc.

U2i / 20B03 / 17A10: Describe the pharmacology of hydrocortisone

Glucocorticoid

Chemical

Glucocorticoid – Natural, Short Acting

Use

  1. Glucocorticoid insufficiency
  2. Allergy & Anaphylaxis
  3. Asthma
  4. Autoimmune disease
  5. Eczema & dermatitis

Presentation

Tablets

IV soln for injection

Glucocorticoid Potency

1.0

Mineralocorticoid Potency

1.0

Dose

100-500mg qid

Route

PO/IV

Onset

Peaks 1-2hrs

DoA

t1/2 8-12h

MoA

Glucocorticoids diffuse into cells → react with cytoplasmic receptors to form a complex → promote gene transcription → ­ mRNA synthesis and ribosomal translation

PD

  • Metabolic
    • Carbohydrate
      • Anti-insulin effect
        • Hyperglycaemia
          • ­↑ gluconeogenesis
          • ↓ glucose utilisation by all cells
          • ↓ glucose uptake
          • ↑­ protein catabolism to ­↑ gluconeogenesis
        • Protein
          • ↑­ catabolism
          • ­ ↑aminoacid transport into hepatocytes → ↑­ gluconeogenesis
        • Fat
          • ­↑ lipolysis
          • ↓fatty acid synthesis
        • CNS Feedback inhibition
          • Hypothalamus to ↓ CRH
          • Anterior pituitary to ↓ ACTH
        • Neuro
          • ­ ↑excitability of CNS – absence causes depression, apathy, Irritability
        • Haematological
          • ­ ↑RBC, platelets, neutrophils
          • ↓ lymphocytes, eosinophils
        • GIT
          • ↑­acid, pepsin secretion → peptic ulceration
          • ↓ prostaglandin synthesis to maintain mucosal barrier
        • CVS:
          • ­ ↑reactivity of peripheral blood vessels to catecholamines. ↑­ no of a1 adrenoreceptors. ­ ↑contractility, ­ ↑vasoconstriction
        • Bone:
          • ­ ↑osteoporosis: ↓ collagen synthesis by osteoblast + ­ ↑collagen breakdown
        • Immune:
          • Antiinflammatory effect via
            • Stabilising lysosomal membranes → ↓ proteolytic enzymes
            • ↓ capillary permeability → ↓ capillary leakage and diapedesis → ↓ bradykinin + ↓ histamine release
          • Inhibition of phospholipase A2 → ↓prostaglandin, ↓thromboxane, ↓leukotrienes

PK

A

OBA 50%

D

90% PPB

Albumin &

Corticosteroid-binding hormone (most)

Vd 0.3-0.5L/kg

M

Liver to inactive glucuronide and sulphate metabolites

CYP3A4

E

Metabolites in urine

Adverse Effects

Cushing’s syndrome (acute withdrawal)

Proximal myopathy

Cataracts
Altered glucose tolerance

­ ↑peptic ulcer disease

Thyroid dysfunction