1. Corticosteroids

4. Basal secretions Group Hormone Daily secretions Glucocorticoids
Cortisol
Corticosterone
5 – 30 mg
2 – 5 mg
Mineralocorticoids
Aldosterone
11- deoxycorticosterone
5 – 150 μg
Trace
Sex Hormones
Androgen
Progestogen
Oestrogen
DHEA
Progesterone
Oestradiol
15 – 30 mg
0.4 – 0.8 mg
From Essential of Pharmacotherapeutics, ed. FSK Barar. P.351

5. Oestriol Andro-stenedione Oestrone 11- Desoxy- cortisol
Cholesterol
ACTH
Oestriol
17-α- Hydroxy pregnenolone
Pregnenolone
Dehydro-epi androsterone
Progesterone
17- Hydroxy progesterone
Andro-stenedione
Oestrone
21,β hydroxylase
11-Desoxy-corticosterone
11- Desoxy- cortisol
Corticosterone
11,β hydroxylase
18-Hydroxy- corticosterone
ALDOSTERONE
CORTISOL
TESTOSTERONE
OESTRADIOL

6. Glucocorticoid Analogues

7. Pharmacological Actions
Direct (Intended) Actions
Anti-inflammatory
Anti-allergy
Anti-immunity
Permissive Actions
Lipolytic effects
Effect on bp
Effect on bronchial muscles
(e.g.,sympathomimetic amine)

8. Pharmacological Actions
Negative feedback mechanism.
Steroids and drugs designed to mimic them are directly gene-active.
Glucocorticoids (e.g., prednisolone) used to suppress inflammation, allergy and immune responses.
Anti-inflammatory therapy is used in many illnesses (e.g., RA, UC, BA, eye and skin inflammations).
-Useful in, say, tissue transplantation and lymphopoiesis (leukemias and lymphomas).
Striking improvements can be obtained, but severe adverse, but highly predictable, effects are ensue.

10. Pharmacological Actions
For most clinical purposes, synthetic glucocorticoids are used because they have a higher affinity for the receptor, are less activated and have little or no salt-retaining properties.
Hydrocortisone used for: orally for replacement therapy, i.v. for shock and asthma, topically for eczema (ointment) and enemas (ulcerative colitis).
Prednisolone the most widely used drug given orally in inflammation and allergic diseases.

11. Pharmacological Actions
Betamethasone and dexamethasone: very potent, w/o salt-retaining properties; thus, very useful for high-dose therapies (e.g., cerebral edemas).
Beclometasone, diproprionate, budesonide: pass membranes poorly; more active when applied topically (severe eczema for local anti-inflammatory effects) than orally; used in asthma, (aerosol).
Triamcinolone: used for severe asthma and for local joint inflammation (intra-articular inj.).

12. Stress and The Adrenal Glands

13. Actions: Carbohydrate and protein metabolism
Negative nitrogen balance and hyperglycemia
Gluconeogenesis
Peripheral actions (mobilize aas and glucose and glycogen)
Hepatic actions
Peripheral utilization of glucose
Glycogen deposition in liver
(activation of hepatic glycogen synthase)

14. Redistribution of Fat Promote adipokinetic agents activity
Actions: Lipid metabolism
Redistribution of Fat
Buffalo hump
Moon face
Promote adipokinetic agents activity
(glucagon, growth hormone, adrenaline, thyroxine)

15. Actions: Electrolyte and water balance
Aldosterone is more important
Act on DT and CD of kidney
Na+ reabsorption
Urinary excretion of K+ and H+
Addison’s disease ??
Na+ loss
Shrinkage of ECF
Cellular hydration
Hypodynamic state of CVS
Circulatory collapse, renal failure, death

16. ICP (pseudotumor cerebri) - Rare
Actions: CNS
Direct:
Mood
Behaviour
Brain excitability
Indirect:
maintain glucose, circulation and electrolyte balance
ICP (pseudotumor cerebri) - Rare

17. Aggravate peptic ulcer. May be due to: Acid and pepsin secretion
Actions: Stomach
Aggravate peptic ulcer. May be due to:
Acid and pepsin secretion
immune response to H.Pylori

18. Actions: Calcium metabolism
Intestinal absorption
Renal excretion
Excessive loss of calcium from spongy bones (e.g., vertebrae, ribs, etc)

19. Preparations 1 1.0 0.8 4 5 0.3 Intermediate acting 10 - 15 7 Drug
Anti-inflam.
Salt retaining
Topical
Cortisol 1
1.0
Cortisone
0.8
Prednisone 4
Prednisolone 5
0.3
Methylpredni- solone
Intermediate acting
Triamcinolone
Paramethasone 10 -
Fluprednisolone 15 7

20. Preparations Long acting 25-40 10 30 Mineralocorticoids 250 20 Drug
Anti-inflam.
Salt retaining
Topical
Long acting
Betamethasone
25-40 10
Dexamethasone 30
Mineralocorticoids
Fludrocortisone
250
DOCA 20

21. Examples of Corticosteroids available
hydrocortisone
prednisolone
dexamethasone
beclomethasone
budesonide
fluticasone

22. Uses Corticosteroids are used:
to reduce inflammation (asthma, arthritis) and swelling (cerebral oedema)
to suppress the immune response (systemic lupus erythematosis)
to reduce nausea and vomiting (as in cancer chemotherapy)
to reduce terminal pain (associated with cancer)
as replacement therapy (in Addisons disease)

23. Unwanted Effects Metabolic: hypertension hypokalaemia
growth suppression
diabetes mellitus
muscle wasting
osteoporosis
fat redistribution
skin atrophy
hirsutism
acne
hypertension
hypokalaemia
menstrual irregularities
adrenal suppression

24. Unwanted Effects Other: Withdrawal infection
emotional disturbances (psychosis, depression, mania)
cataract, glaucoma
GI bleeding, perforation
Withdrawal
Addisonian crisis
raised intracranial pressure
arthralgia/myalgia
pustular rash

25. How corticosteroids work
Gross (metabolic) actions:
glucose: diabetogenic
(glucose uptake and utilisation; gluconeogenesis)
fat: Cushing’s syndrome
(redistribution, lipolysis)
protein: muscle wasting
(catabolism, anabolism)
minerals: hypertension (mineralocorticoid effect)

26. How corticosteroids work
Cellular (nuclear)* level:
anti-inflammatory and immunosuppressive actions:
 number and activity of leucocytes,
proliferation of blood vessels,
activity of mononuclear cells,
activity of cytokine secreting cells,
production of cytokines,
generation of eicosanoids and PAF,
complement components in blood,
histamine release
*Effect through gene transcription (lipocortin synthesis, inhibition of COX-2 synthesis). THIS TAKES TIME!

27. Avoiding unwanted effects of corticosteroids
Modification of dose/dose regimen
Use short courses/low doses if possible
Use steroid sparing drugs
Withdraw ‘chronic’ steroids slowly
Give dose once daily and in morning
Give on alternate days if possible
Give prophylactics if possible
Give product locally
Remember contraindications
Enrol help of patient

28. Avoiding unwanted effects of corticosteroids
Steroid Selection:
remember, their effects can differ with regard to their mineralocorticoid and anti-inflammatory actions and duration of effect eg as parenteral products
or as topical products (creams)
hydrocortisone - mild
clobetasone but. - moderately potent
betamethasone - potent
clobetasol prop. - very potent

29. Giving products locally can still cause problems!
systemic dosing can occur
local toxicity can develop -
skin: infection, thinning, bruising.
eye: viral infection, cataract, glaucoma.
inhalation: fungal infection, hoarseness
joints: infection, necrosis