15. Glucocorticoids Flashcards
Pathaway of glucocrticoid release
- Hypothalamus → CRF (corticotropin release factor)
- Hypophysis → ACTH (AdrenoCorticoTropic hormone)
- Adrenal cortex → cortisole
Physiological and pathological effects of glucocorticoids
⋆ Diabetogenic
⋆ Gluconeogenesis increases → hyperglycaemia
⋆ muscle atrophy, weakness
⋆ osteoporosis
⋆ delayed wound healing (Decrease collagen synthesis)
⋆ Skin thinning, alopecia
⋆ Decreased growth
⋆ Polyuria/polydipsia
Pharmacological effects of glucocorticoids
⋆ Antinflammatory
⋆ Antiallergic
⋆ Immunosuppressive
⋆ Antishock
⋆ Neuroprotective
What is the target of glucocorticoids?
Phospholipase A2 (PLA2)
Explain antiiflammatory and immunosupressive effects of glucocorticoids?
⋆ inhibition of PLA2 → COX enzyme expression decrease
⋆ interleukin expression ↓
⋆ TNF (tumor necrosis factor) and IFN (interferon) synthesis ↓
⋆ apoptosis in lymphocytes!! → lymphocytopenia
⋆ neutrophilia (demargination)
Explain antishock effect of glucocorticoids
capillary membrane permeability ↓ → enhancing microcirculation
Explain neuroprotective effect of glucocorticoids
Trauma → bleeding → local vasoconstriction → Ischaemia → lipid peroxidation → ROS → APOPTOSIS, NECROSIS
Glucocorticoids counteract lipidperoxidation and enhance microcirculation
List of important glucocorticoids:
⋆ Cortisol
⋆ Prednisolone
⋆ Methylprednisolone
⋆ Triamcinolone
⋆ Betamethasone
⋆ Dexamethasone
Glucocorticoids that are applied locally
⋆ Beclomethason
⋆ Fluticason
Glucocorticoid that are applied orally?
⋆ Budesonide
Side effects of glucocorticoids
⋆ HT-hypophysis-adrenal cortex axis inhibition
⋆ Gastric ulcers
⋆ Hepatopathy
⋆ Pancreatitis
⋆ Glaucoma, cataracta
⋆ Thinning of skin, delayed wound healing, alopecia
⋆ Polyuria/polydipsia
⋆ Polyphagia
⋆ Remobilizing fats
⋆ Muscle atrophy
⋆ Immunosuppression
3 options of using glucocorticoids
- High dosage, once (IV: e.g. shock, spinal trauma (allergy))
- ADT (alternate day therapy) prednisolone, methylprednisolone
- Long acting injections (depot) only if ADT not possible
Recommended order of indications
- Local usage (atopic dermatitis, otitis externa, mastitis)
- Single injectable dose
- Asthma, RAO → Inhalational usage
- Intraarticular
- ADT
- Depot injections