Classification
Corticosteroids naturally produced by cortex of adrenal glands 2 types:
- Mineralocorticoids
- aldosterone - concerned with salt and fluid retention / balance
- Glucocorticoids
- cortisol (hydrocortisone) - concerned with carbohydrate and protein metabolism also have some mineralocorticoid properties
- anti-inflammatory, anti allergic & immunosuppressive actions
Functions of cortisol (in health)
- essential for life
- inhibit protein synthesis, stimulate protein breakdown => amino acids => glucose (via process of gluconeogenesis)
- stimulates deposition of glycogen in liver and skeletal muscles, glucose release from liver, inhibition of peripheral uptake of glucose
- stimulates lipolysis - fats => free fatty acids + glycerol for subsequent conversion to glucose
- SO- raises blood sugar, prevents hypoglycaemia during fasting
Control of endogenous steroid production
- release governed by negative feedback loop involving hypothalamus and pituitary
- Hypothalamus releases corticotrophin releasing hormone (CRH) => pituitary
- Pituitary releases adrenocorticotrophin (ACTH) => adrenal cortex. Adrenal cortex releases corticosteroids
- HPA axis
HPA axis and actions of adrenal corticosteroids
- Suppression of this system can occur with exogenous steroids
- occurs early but soon reverses after a single dose or short course
- becomes more significant and much slower to reverse with prolonged or over frequent administration
- body unable to “switch production back on” quickly => period of steroid deficiency => serious, potentially fatal
- need to tail off steroid dosage slowly after prolonged administration to let the bodys control system re-adapt
Mechanism of action of steroids
- steroid diffuses into cells, activates cytoplasmic receptor
- which then diffuses into nucleus and initiates protein synthesis
Glucocorticoid (anti-inflammatory) effect -
mechanism of action
- modify transcription of certain genes
- reduce production of prostaglandin in inflammatory cells
- exogenous glucocorticoids inhibit cyclo-oxygenase (COX-2) by gene inhibition
- also induce anti-inflammatory mediator - Lipocortin
Corticosteroids
actions
Reduced inflammation and immunosuppression achieved by action on blood vessels, inflammatory cells, inflammatory mediators involving:
- vasoconstriction of small blood vessels
- production of anti-inflammatory mediators - lipocortins
- inhibition of macrophage, delaying phagocytosis, fibroblast activity and ultimately repair
- reduction of
- fluid exudation
- leucocyte infiltration
- production of inflammatory mediators
- permeability of the synovial membrane
- migration of leucocytes
- activity of mononuclear cells
- proliferation of blood vessels
- fibrosis
Corticosteroids uses in musculoskeletal medicine
- Arthritis - especially inflammatory
- Capsulitis
- Bursitis
- Tenosynovitis
- Tendinosis
- mechanism of action:
- element of low grade inflammation
- pain relief - allows more normal use and other therapies
- collagen effects
Corticosteroids
EFFECT
- All aspects of inflammatory response depressed
- acute (reduced pain, heat, redness, swelling)
- chronic (proliferation and modelling affected)
- Not suitable for acute inflammation
- protective aspects inhibited
- delay in fibre formation
- some exceptions (bursitis)
- chronic inflamatory phase - the balance of collagen synthesis is interrupted with inflammation and proliferation continuing side by side. Corticosteroid can be beneficial in reducing/abolishing the low grade inflammatory component.
- The unwanted effect on collagen synthesis in the proliferation and remodelling phase is disrupted in:
- topical steroids
- long term large doses suppress collagen
- intermittent doses - no effect
- intralesional corticosteroids
- keloid regression - inhibition of fibroblast activity
- decreased collagen synthesis
Corticosteroids commonly used in MSM
Generic name
Trade name
Dosage pr. ml.
Presentation
Hydrocortisone acetate
Hydrocortistab
25 mg/ml
1 ml. ampoule
Prednisolone acetate
Deltastab
25 mg/ml
1 ml. ampoule
Methylpredisolone acetate
Depo-medrone
40mg/ml
1,2,&3 ml. vials
Triamcinolone acetonide
Adcortyl
10 mg/ml
1 ml. ampoule
Triamcinolone acetonide
Kenalog
40 mg/ml
1 ml. vial
Relative potency
1 Hydrocortisone
4 Prednisolone
5 Methylprednisolone
5 Triamcinalone
Duration of action
Hydrocortisone
Prednisolone acetate
Betamethasone
Dexamethasone
Triamcinolone acetenoide
Metylprednisolone acetate
Corticosteroids
Pharmacokinetics
Absorption
- Absorption:
- oral
- topical
- nasal
- rectal
- injection
- IV
- IM
- Intralesional
- will get systemic absorption after injection
- Metabolised in liver
- Metabolites excreted in urine
SIDE EFFECTS/COMPLICATIONS
LOCAL
- Post injection flare, transient post injection pain 12-24 hours
- subcutaneous fat atrophy
- skin depigmentation (use hydrocortisone)
- infection (1:14.000-50.000) (complication of procedure)
- poor technique
- adjacent infections
- haematogenous spread
- previous trauma
- contaminated
- Tendon weakening/rupture
- steroid atrophathy
- more from oral steroids
SIDE EFFECTS/COMPLICATIONS
SYSTEMIC
- Flushing
- Impaired diabetic control
- Mood changes
- Menstrual disturbance
With repeated high doses:
- immunosuppression
- Hypothalamic-pituitary-adrenal axis(HPA-axis) suppression
- Iatrogenic Cushing´s syndrome
- Allergic reactions & anaphylaxis (more with LA)
Corticosteroids
Drug interactions
- Antagonise
- the effect of hypoglycaemic agents including insulin
- the action of anti-hypertensive agents and diuretics
- Enhance
- the potassium lowering effectof acetazolamide (Diamox) loop diuretics and thiazides
- warfarin (bleeding risks increased)
- gastric irritation more with oral steroids, especially if also taking NSAIDs
- increased risk of tendon rupture with steroids and some antibiotics and maybe with statins.
Kenalog
Triamcinalone acetonide
- Squibb recommends for intra articular and intra muscular use and also for bursitis epicondylitis and tenosynovitis
- Comes in 1ml vials. Squibb do not recommend mixing with other medicinal products e.g.LA
- Has duration of 2-3 weeks
- Physiological dosage equates to 1x40mg injection every 3 weeks
- Systemic absorption after intra-articular or intra-lesional injection is small/slow
Methylprednisolone
Depo-medrone
- equi-potent with triamcinalone
- suspension, but precipitates out more quickly
- slightly longer duration of action in 3 weeks
- can be obtained premixed with lidocaine
