Synthetic corticosteroids

Synthetic corticosteroids 

Synthetic corticosteroids mimic the actions of naturally occurring corticosteroids and may be used to replace corticosteroids in people with adrenal glands that are unable to produce adequate amounts of corticosteroids, however, they more often are used in higher-than-replacement doses to treat diseases of immunity, inflammation or salt and water balance.

 Examples of synthetic corticosteroids include:

1. bethamethasone, (Celestone)
2. Prednisone (Prednisone Intensol)
3. Prednisolone (Orapred, Prelone)
4. Triamcinolone (Aristospan Intra-Articular, Aristospan Intralesional, Kenalog)
5. Methylprednisolone (Medrol, Depo-Medrol, Solu-Medrol)
6. Dexamethasone (Dexamethasone Intensol, DexPak 10 Day, DexPak 13 Day, DexPak 6       Day).
7. Fludrocortisone (Florinef)

Relative potencies	Glucocorticoid	Mineralocorticoid
Hydrocortisone	1	1
Cortisol	1.25	1
Prednisolone	4	0.8
Methylprednisolone	5	minimal
Dexamethasone	30	minimal
Fludrocortisone	15	150

• prednisolone is standard choice for anti-inflammatory therapy. Can be given orally or IM.
• methylprednisolone used for IV pulsed therapy.
• dexamethasone longer acting.
• fludrocortisone used to replace aldosterone where the adrenal cortex has been destroyed.
• beclomethasone and budesonide used by inhalation for asthma. About 90% of inhalation dose is swallowed and inactivated by first-pass hepatic metabolism (steroids listed above are protected from this by protein binding). The rest, which is absorbed from the mouth and lungs gives very low systemic plasma concentrations. Although risk of HPA axis suppression is very low it can happen.

Pharmacokinetics

1. Administration: PO/IM/IV/intra-articular/topical/inhaled. Absorption after oral administration is rapid. Maximum biological effect seen after 2-8 h
2. Distribution: high plasma protein binding (95% in case of hydrocortisone) to transcortin and when this is saturated to albumin (80% in the case of hydrocortisone). Concentration of transcortin is increased by oestrogens (eg pregnancy, oral contraceptives). In patients with very low serum albumin doses should be reduced due to reduced binding capacity
3. Elimination: hepatic and renal.t_1/2 of most steroids 1-3 h. Prolonged in renal and hepatic disease and shortened by hepatic enzyme induction to an extent that may be clinically important

Adverse effects

1. In general serious unwanted effects are unlikely if daily dose is < 50 mg hydrocortisone or 10mg of prednisolone or equivalent
2. 
   
3. iatrogenic Cushings
4. avascular necrosis of bone
5. depression and psychosis
6. peptic ulceration
7. others include cataract (chronic use), glaucoma (prolonged use of eye drops), raised ICP and convulsions, blood hypercoagulability, menstrual disorders, fever
8. immunosuppression
9. HPA axis suppression: dependent on steroid used, dose, duration of administration and time of administration. Single morning dose of <20mg prednisolone does not usually cause suppression while 5mg in evening suppresses early morning activation of HPA axis