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
- Glucocorticoid insufficiency
- Allergy & Anaphylaxis
- Asthma
- Autoimmune disease
- 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
- Antiinflammatory effect via
- Hyperglycaemia
- Anti-insulin effect
- Carbohydrate
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
- Author: Krisoula Zahariou