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Adrenal Steroids - Coggle Diagram
Adrenal Steroids
Cortisol
Axis
CRH (Hypothalamus)
ACTH (Ant Pitutary)
Cortisol (Adrenal cortex)
Pharmacokinetics
Bound to plasma protein - Corticosteroid binding globulin (CBG), and Albumin
Liver
Reduction and conjugation to glucuronic acid - inactivation
Converted to inactive cortisone by
11-β-hydroxysteroid dehydrogenase 2
MOA
Crosses plasma membrane of cell
Binds to Glucocorticoid receptor
Receptors form homodimers and is transported into the nucleus
Binds
GC response elements (GRE) in the promoter regions
of genes
Activation or suppression of gene transcription
Addisons
Primary
Autoimunne cortex destruction due to T-cell
TB infections
Deficiences of glucocorticoids, aldosterone, sex steroids
Secondary
Pituitary gland disease
Exogenous GC therapy withdrawal
Aldosterone not ffected
Symptoms
Fatigue, Muscle weakness, depression, poor appetite, anorexia, hypoglycaemia, darkening of skin, low BP, renal loss of salt + water
Treatment
Replacement combination GCs (hydrocortisone) and MCs (fludrocortisone)
Cushings
Causes
Pituitary ACTH adenoma / adrenal cortex adenoma
Chronic GC therapy
Signs / Symptoms
Mood swings, muscle wasting, thin skin, hypertension, oedeam, weight gain, hyperglycaemia
Immunosuppressive Effects (6)
Inhibits Inflammation
Early Stage:
Heat
Pain
Redness
Late Stage:
Healing
Repair
Inhibit
Inflammatory
Cells
Decreases pro-inflammatory
cytokine
release
Antibody archer - B cells
T knight - T cell
Helper T squire - Helper T cells
Eo-slingshot - Eosinophils
N-Flame Kross Bow
NF-kB
Transcription factor for pro-inflammatory cytokines is inhibited
Decreases
Prostanoid
,
Leukotriene
,
Histamine
production
Upregulation of expression of
Annexin
A1
Directly inhibits
Phospholipase A2 (PLA2)
cataPuLt A2 Phospholipase A2
Prostaglandin Pro-Slugger Bat by COX
Leukotrien lacross stick by LOX
Decreases
leukocyte
migration and activation
Decreases
complement
components in plasma
Metabolic Effects (4)
Protein :muscle::skin-tone-2:
Decreased synthesis
Increases breakdown (wasting)
Lipid :white_circle:
Decreased synthesis
Increases lypolysis
Buffalo hump
Moon face
Carbohydrate :candy:
Incerases gluconeogenesis + Glycogenesis
Hyperglycaemia
Calcium balance :skull_and_crossbones:
Decreased GI absorption
Increased renal excretion
Osteoporosis
Fractured bone table leg - Osteoporosis
Pharmacological Glucocorticoids
Hydrocortisone (cortisol)
Prednisolone
Prednisone
Dexamethasone
Beclomethasone
Fluticasone
Adverse Effects of GC Admin
Adrenal Gland Atrophy
Suppressed capacity to synthesis cortisol - HPA shutdown
Acute adrenal insufficiency
Sudden withdrawal
Adrenal crisis
Definition
Circulatory collapse, normally after a stressful event
Risk
More likely in:
GA
Infection
Surgery
Pain
Stress
Symptoms
Abdominal pain
Confusion :thinking_face:
Fatigue :sleeping:
BP drop :arrow_down::tent:
Rapid weak pulse
Tachypnea :arrow_up::wind_blowing_face:
Loss of conciousness
Shock, coma, death :skull_and_crossbones:
Metabolic
Fractures / osteoporosis : Calcium
Muscle wasting : Protein
Weight gain, diabetes, Hyperglycaemia : Insulin + carbs
Impaired growth
Immunological
Immunsuppresion: Oppertunist / latent infections
Poor wound healing
Peptic ulceration
Other
Cushing's syndrome
Psychosis
Odeama / hypertension - MC actions
Aldosterone
MOA
Binds to nuclear receptor within renal
collecting ducts and distal tubules
Increases gene expression of
Na+ channels
and
Na+/K+ ATPase
Increases Na+ resporption
Increased water and K+ loss
Conn's Syndrome
Excess aldosterone secretion
Cause
Adenoma
Symptoms
Na+ and Water retention
Hypokalaemia :arrow_down::banana:
Hypotension :arrow_down::tent:
Addison's Disease
Decreased Aldosterone secretion
Symptoms
Na+ loss :peanuts:
Reduced extracellular fluid :desert:
K+ retention :banana:
Hypotention :arrow_down::tent:
Clinical Use
Flucrocortisone
Oral
High mineralocorticoid receptor potency compared to GC
Increases Na+ reabsorption :peanuts:
Loss of K+ and H+
Analogues used in replacement therapy
Addison's
In combo with GCs
Hydrocortisone
MOA
Synthetic cortisol analogue
Effects both GC and MC receptors
Pharmacokinetics
Effects within 2-8h
Same potency and DOA as cortisol
Use
Addison's replacement therapy :knife_fork_plate:
Dermalogical disorders - psoriasis :hand:
Routes of Admin of Steroids
Topical
Ointments / Creams
Treats:
Dermalogical disorders
Atopic dermatitis
Psoriasis
Drugs:
Hydrocortisone
Dexamethasone
Prednisolone
High dose topically, low systemic levels
Inhaled
Treats:
Asthma
Drugs:
Fluticasone
Beclomethasone
Budesonide
High delivery dose, low systemic effects
Systemic / Parental
Intramuscular
Avoids repeated oral GCS
Treats:
Systemic Inflammation
Intra-articular
Drugs:
Methylprednisolone
Treats:
Rheumatoid or Gout
Epidural
Treats:
Herniated disc pain
Oral
Most effective route
Dexamethasone
MOA
Cortisol Analogue
Very little MC receptor effects
Pharmokinetics
18x more potent than cortisol
Much longer t1/2 than cortisol
Use
Diagnostic Test for HPA axis
ACTH or Cortisol hypersecretion
Failure to supress : Cushing's
Adrenal Hormones
Cortex
Zona fasiculata
Glucocorticoids (Cortisol) :candy:
Zona reticularis
Sex Steroids (Androgens) :peach:
Zona Glomerulosa
Mineralcorticoids (aldosterones) :pick:
Medulla
Catecholamines (Adrenaline / noradrenaline)
Prednisone
Pharmacokinetics
Prodrug
Converted in the liver to
Prednisolone
Prednisolone 5x more potent than cortisol
Longer half life than cortisol
MOA
High GC effects relative to MC receptors
Cortisol analogue
