Corticosteroids (1 of 2) Steroids the Sleaziest of Drugs

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Corticosteroids (1 of 2)
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Steroids the Sleaziest of Drugs
Steroids are fast catching up with antibiotics as
the most abused class of drugs in doctor's black
bag.
High doses of corticosteroids and other
immunosuppressive agents cause AIDS Mohammed Ali
Al-Bayati Ph.D
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Corticosteroids

• History
• Synthesis
• Pharmacological Actions
• Pharmacokinetics
• Preparations
• Therapeutic principles
• Dosage schedule Steroid withdrawal

• Uses
• Therapeutic
• Diagnostic
• Adverse reactions
• Contraindications
• Precautions during therapy
• Glucocorticoid antagonists

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History

• 1855 Addison's disease
• 1856 Adrenal glands essential for life
• 1930 Cortex gt medulla
• 1932 Cushings syndrome
• 1949 Hench et al (Steroids in rheumatoid
  arthritis)
• 1952 Aldosterone

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From Essential of Pharmacotherapeutics, ed. FSK
Barar. P.351
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ACTH
Cholesterol
Oestriol
17-a- Hydroxy pregnenolone
Dehydro-epi androsterone
Pregnenolone
Progesterone
17- Hydroxy progesterone
Andro-stenedione
Oestrone
21,ß hydroxylase
11-Desoxy-corticosterone
11- Desoxy- cortisol
Corticosterone
11,ß hydroxylase
18-Hydroxy- corticosterone
TESTOSTERONE
OESTRADIOL
ALDOSTERONE
CORTISOL
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Pharmacological Actions

• Direct Actions
• Permissive Actions

• Lipolytic effects
• Effect on BP
• Effect on bronchial muscles
• (e.g.,sympathomimetic amine)

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Pharmacological Actions

• Carbohydrate
• Protein
• Lipid
• Electrolyte water
• CVS
• Sk. Muscle
• CNS

• Stomach
• Blood
• Anti-inflammatory
• Immunosuppressant
• Respiratory system
• Growth Cell Division
• Calcium metabolism

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Actions Carbohydrate and protein metabolism
Negative nitrogen balance hyperglycaemia

• Gluconeogenesis
• Peripheral actions (mobilize AA glucose and
  glycogen)
• Hepatic actions
• Peripheral utilization of glucose
• Glycogen deposition in liver
• (activation of hepatic glycogen synthase)

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Actions Lipid metabolism

• Redistribution of Fat
• Buffalo hump
• Moon face
• Promote adipokinetic agents activity
• (glucagon, growth hormone, adrenaline, thyroxine)

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Actions Electrolyte and water balance

• Aldosterone is more important
• Act on D.T. C.D. of kidney
• Na reabsorption
• Urinary excretion of K and H
• Addisons disease ??

• Na loss
• Shrinkage of ECF
• Cellular hydration
• Hypodynamic state of CVS
• Circulatory collapse, renal failure, death

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Actions Cardiovascular system

• Restrict capillary permeability
• Maintain tone of arterioles
• Myocardial contractility

Mineralocorticoid induced hypertension ??
Na sensitize blood vessels to the action of
catecholamines angiotensin
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Actions Skeletal Muscles
Needed for maintaining the normal function of Sk.
muscle

• Addison's disease weakness fatique is due to
• Prolonged use

inadequacy of circulatory system
Steroid myopathy
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Actions CNS

• Direct
• Mood
• Behaviour
• Brain excitability
• Indirect
• maintain glucose, circulation and electrolyte
  balance

ICP (pseudotumor cerebri) - Rare
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Pseudotumor cerebri (Intracranial hypertension)

• Glucocorticoids
• Mineralocorticoids
• Amiodarone
• Vitamin A
• Oral contraceptives
• Tetracyclines

From Harrison. 15th edition, volume 1, page 435
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Actions Stomach

• Aggravate peptic ulcer. May be due to
• Acid pepsin secretion
• immune response to H.Pylori

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Actions Blood

• RBC Hb RBC content
• (erythrophagocytosis )
• WBC Lymphocytes, eosinophils, monocytes,
  basophils
• Polymorphonucleocytes

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Actions Anti-inflammatory

• Recruitment of WBC monocyte- macrophage
  into affected area elaboration of chemotactic
  substances
• Lipocortin
• ELAM1 ICAM-1 in endothelial cells
• TNF from phagocytic cells
• IL1 from monocyte-macrophage
• Formation of Plasminogen Activator
• Action of MIF fibroblastic activity
• Expression of cyclooxygenase II

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Corticosteroids
Return
Lipocortin
Phospholipids
Phospholipase A2
Arachidonic acids
Cycylooxygenase
lipoxygenase
Prostaglandins, Thromboxane Prostacyclins
Leukotriene
PAF by lipocortin
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Anti-inflammatory actions of corticosteroids
Corticosteroid inhibitory effect
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Immunosuppressive anti-allergic actions

• Suppresses all types of hypersensitivity
  allergic phenomenon
• At High dose Interfere with all steps of
  immunological response
• Causes greater suppression of CMI (graft
  rejection delayed hypersensitivity)
• Transplant rejection antigen expression from
  grafted tissues, delay revascularization,
  sensitisation of T lymphocytes etc.

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Actions Growth Cell division

• Inhibit cell division or synthesis of DNA
• Delay the process of healing
• Retard the growth of children

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Actions Calcium metabolism

• Intestinal absorption
• Renal excretion
• Excessive loss of calcium from spongy bones
  (e.g., vertebrae, ribs etc)

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Actions Respiratory system

• Not bronchodilators
• Most potent and most effective anti-inflammatory
• Effects not seen immediately (delay 6 or more
  hrs)
• Inhaled corticosteroids are used for long term
  control

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To be Continued in the next Class
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Synthesis
Aldosterone
Cortisol Adrenal androgens
Adrenaline Nor-adrenaline