---

CORTICOSTEROIDS - Complete Pharmacology Notes

(KD Tripathi style - 2nd Year MBBS)

---

PART 1: CLASSIFICATION OF CORTICOSTEROIDS

CORTICOSTEROIDS
│
├── GLUCOCORTICOIDS (affect carbohydrate, protein, fat metabolism + anti-inflammatory)
│   ├── Short-acting (t½ < 12 hrs)
│   │   ├── Hydrocortisone (cortisol) – 1x potency reference
│   │   └── Cortisone – prodrug, converted to cortisol in liver
│   │
│   ├── Intermediate-acting (t½ 12–36 hrs)
│   │   ├── Prednisolone – 4x potency
│   │   ├── Prednisone – prodrug, 4x potency
│   │   ├── Methylprednisolone – 5x potency
│   │   └── Triamcinolone – 5x potency
│   │
│   └── Long-acting (t½ > 36 hrs)
│       ├── Dexamethasone – 25x potency
│       └── Betamethasone – 25x potency
│
└── MINERALOCORTICOIDS (affect salt and water balance)
    ├── Aldosterone – natural, most potent
    ├── Fludrocortisone – used therapeutically
    └── Deoxycorticosterone acetate (DOCA) – obsolete

---

PART 2: MECHANISM OF ACTION

A. Genomic (Main) Mechanism

Corticosteroid enters cell
         ↓
Binds cytoplasmic glucocorticoid receptor (GCR)
         ↓
Hormone-receptor complex formed
         ↓
Dissociation of heat-shock proteins (Hsp90, Hsp70)
         ↓
Complex translocates to nucleus
         ↓
Binds Glucocorticoid Response Elements (GRE) on DNA
         ↓
    ┌────────────────┬─────────────────────┐
    ↓                ↓                     ↓
Transactivation   Transrepression      Suppress NF-κB
(synthesis of     (inhibit AP-1,       and AP-1 transcription
anti-inflam-      NF-κB)               factors
matory proteins)
    ↓                ↓
Lipocortin-1      ↓ IL-1, IL-2,
(annexin-1)       IL-6, TNF-α
synthesis          COX-2, iNOS

B. Non-Genomic Mechanism (rapid - minutes)

• Interaction with membrane-bound receptors
• Direct membrane effects at high doses
• Explain rapid anti-shock and anti-edema effects

---

PART 3: ANTI-INFLAMMATORY ACTION

Mechanism of Anti-Inflammatory Effect

GLUCOCORTICOID
        ↓
Induces synthesis of LIPOCORTIN-1 (Annexin-1)
        ↓
Inhibits PHOSPHOLIPASE A2
        ↓
↓ Release of Arachidonic Acid from membrane phospholipids
        ↓
   ┌────────────┐
   ↓            ↓
↓ COX pathway  ↓ LOX pathway
↓ PGs, TXA2    ↓ Leukotrienes
↓ Prostacyclin  ↓ LTB4, LTC4, LTD4

All Anti-Inflammatory Effects:

---

PART 4: IMMUNOSUPPRESSANT ACTION

GLUCOCORTICOIDS → IMMUNOSUPPRESSION
│
├── CELLULAR IMMUNITY (mainly affected)
│   ├── ↓ T-lymphocyte proliferation (block IL-2)
│   ├── ↓ Cytotoxic T-cell generation
│   ├── ↓ Delayed hypersensitivity reactions
│   └── Lymphocytopenia (redistribution to lymphoid tissue)
│
├── HUMORAL IMMUNITY (less affected at standard doses)
│   ├── ↓ Antibody production at high doses
│   └── ↓ B-cell function at pharmacological doses
│
└── PHAGOCYTE EFFECTS
    ├── ↓ Monocyte/macrophage function
    ├── ↓ Fc receptor expression
    └── ↓ Complement proteins

---

PART 5: THERAPEUTIC USES

Full List of Therapeutic Uses

THERAPEUTIC USES OF GLUCOCORTICOIDS
│
├── ENDOCRINE DISORDERS
│   ├── Addison disease (primary adrenal insufficiency) - hydrocortisone + fludrocortisone
│   ├── Congenital adrenal hyperplasia (CAH) - suppress excess ACTH
│   ├── Acute adrenal crisis - IV hydrocortisone 100 mg
│   └── Subacute thyroiditis
│
├── ALLERGIC/ANAPHYLACTIC CONDITIONS
│   ├── Anaphylactic shock (after epinephrine)
│   ├── Angioedema
│   ├── Drug hypersensitivity reactions
│   └── Urticaria (severe)
│
├── RHEUMATIC/AUTOIMMUNE DISEASES
│   ├── Rheumatoid arthritis
│   ├── SLE (Systemic Lupus Erythematosus)
│   ├── Polymyositis / Dermatomyositis
│   ├── Vasculitis
│   └── Temporal arteritis (high-dose)
│
├── RESPIRATORY DISEASES
│   ├── Bronchial asthma (inhaled: beclomethasone, budesonide, fluticasone)
│   ├── Severe asthma / Status asthmaticus (IV hydrocortisone)
│   ├── COPD (short course in acute exacerbation)
│   └── Croup (single dose dexamethasone)
│
├── RENAL DISEASES
│   ├── Nephrotic syndrome (prednisolone 1–2 mg/kg/day)
│   └── Rapidly progressive glomerulonephritis
│
├── GASTROINTESTINAL DISEASES
│   ├── Inflammatory bowel disease (Crohn's, UC)
│   └── Autoimmune hepatitis
│
├── HEMATOLOGICAL CONDITIONS
│   ├── Idiopathic thrombocytopenic purpura (ITP)
│   ├── Autoimmune hemolytic anemia
│   ├── Acute lymphoblastic leukemia (ALL)
│   └── Multiple myeloma (part of regimens)
│
├── NEUROLOGICAL CONDITIONS
│   ├── Cerebral edema (dexamethasone - tumor, post-op)
│   ├── Bacterial meningitis (reduce inflammation)
│   └── Multiple sclerosis (acute relapse)
│
├── OCULAR CONDITIONS
│   ├── Uveitis, iritis
│   ├── Allergic conjunctivitis
│   └── Optic neuritis
│
├── DERMATOLOGICAL CONDITIONS
│   ├── Eczema / Atopic dermatitis
│   ├── Pemphigus vulgaris (high-dose systemic)
│   ├── Psoriasis (topical)
│   └── Contact dermatitis
│
├── TRANSPLANTATION
│   └── Prevention/treatment of organ rejection
│
└── MISCELLANEOUS
    ├── Diagnostic: dexamethasone suppression test (Cushing's)
    ├── Preterm labor (betamethasone for fetal lung maturity)
    └── Spinal cord injury (methylprednisolone)

Four Important Therapeutic Indications (Exam Question)

1. Addison's Disease (Adrenal Insufficiency) - Replacement therapy with hydrocortisone 20 mg morning + 10 mg evening + fludrocortisone for mineralocorticoid replacement.
2. Severe Bronchial Asthma / Status Asthmaticus - IV hydrocortisone 100–200 mg every 6 hours; controls life-threatening bronchospasm and inflammation.
3. Nephrotic Syndrome - Prednisolone 1–2 mg/kg/day for 4–6 weeks (full dose), then taper; induces remission especially in minimal change disease.
4. Organ Transplant Rejection Prevention - Combined with calcineurin inhibitors (cyclosporin) to prevent T-cell-mediated graft rejection.

---

PART 6: ADVERSE EFFECTS

ADVERSE EFFECTS OF GLUCOCORTICOIDS
(Mnemonic: "CUSHINGOID")
│
C - Cushingoid features (moon face, buffalo hump, central obesity)
U - Ulcer (peptic ulcer - ↑ acid, ↓ mucus)
S - Suppression of HPA axis
H - Hyperglycemia / Diabetes
I - Infections (mask signs, reactivate TB, fungal, bacterial)
N - Na+ and H2O retention → Hypertension, Edema
G - Growth retardation (children)
O - Osteoporosis / Osteonecrosis (avascular necrosis of femoral head)
I - Iatrogenic Cushing syndrome
D - Depression / Psychosis / Cataract / Glaucoma

Detailed ADR Table:

---

PART 7: FOUR CONTRAINDICATIONS

1. Active Peptic Ulcer Disease - Steroids increase gastric acid secretion, decrease mucus production, and impair mucosal healing; can cause GI perforation and bleeding.
2. Active Systemic Infections (especially TB, fungal infections) - Immunosuppression can allow fulminant spread. Uncontrolled sepsis is a contraindication except in septic shock (with appropriate antibiotics).
3. Uncontrolled Diabetes Mellitus - Glucocorticoids cause significant hyperglycemia, insulin resistance, and can precipitate diabetic ketoacidosis.
4. Osteoporosis - Steroids inhibit osteoblasts, promote osteoclast activity, reduce GI calcium absorption, and increase urinary calcium loss; can rapidly worsen existing bone loss and cause fractures.

---

PART 8: TOPICAL CORTICOSTEROIDS IN DERMATOLOGICAL CONDITIONS

Classification by Potency (UK 4-Group / US 7-Group system)

TOPICAL STEROIDS - POTENCY CLASSIFICATION
│
├── VERY POTENT (Group 1 / Super-high)
│   ├── Clobetasol propionate 0.05% (Temovate)
│   └── Betamethasone dipropionate 0.05% (augmented)
│
├── POTENT (Group 2-3 / High)
│   ├── Betamethasone valerate 0.1%
│   ├── Betamethasone dipropionate 0.05%
│   ├── Mometasone furoate 0.1%
│   └── Fluocinonide 0.05%
│
├── MODERATELY POTENT (Group 4-5 / Medium)
│   ├── Triamcinolone acetonide 0.1%
│   ├── Fluocinolone acetonide 0.025%
│   └── Betamethasone valerate 0.025%
│
└── MILD (Group 6-7 / Low)
    ├── Hydrocortisone 1% (OTC)
    ├── Hydrocortisone acetate 0.5-1%
    └── Desonide 0.05%

Dermatological Indications

Vehicles (Formulations) for Topical Steroids

VEHICLES
│
├── OINTMENT - Most occlusive, highest penetration, best for dry/lichenified lesions
├── CREAM - Less occlusive, suitable for moist/weeping lesions, cosmetically acceptable
├── LOTION/SOLUTION - Scalp, hairy areas, large areas
├── GEL - Face, hair-bearing areas
└── FOAM - Scalp, hairy sites

Topical Steroid Adverse Effects

Finger Tip Unit (FTU) - Clinical Application

• 1 FTU = strip of cream from tip of index finger to first crease = ~0.5 g
• Enough to cover an area twice the size of an adult palm
• Used to guide appropriate quantity for different body areas

---

PART 9: GLUCOCORTICOIDS - PHARMACOLOGICAL ACTIONS IN DETAIL

1. Carbohydrate Metabolism

• Gluconeogenesis increased (liver) - raises blood glucose
• Peripheral glucose utilization decreased (insulin antagonism)
• Result: Hyperglycemia, "steroid diabetes"

2. Protein Metabolism

• Catabolic effect on peripheral tissues (muscle, skin, bone)
• Negative nitrogen balance
• Amino acids diverted to gluconeogenesis
• Causes: muscle wasting, thin skin, poor wound healing

3. Fat Metabolism

• Lipolysis in extremities (mobilizes fat)
• Lipogenesis centrally (trunk, face, neck)
• Net redistribution: moon face, buffalo hump, truncal obesity

4. Electrolyte and Water Balance

• Mineralocorticoid activity (more with hydrocortisone/cortisone):
  • Na+ retention
  • K+ excretion (hypokalemia)
  • H2O retention
  • Hypertension, edema

5. Cardiovascular Effects

• Increase cardiac output
• Maintain vascular responsiveness to catecholamines
• Essential for hemodynamic stability in stress

6. Skeletal Effects

• Inhibit osteoblast activity
• Increase RANKL (stimulate osteoclasts)
• Decrease intestinal calcium absorption
• Increase renal calcium excretion
• Result: Osteoporosis, fractures

7. CNS Effects

• Euphoria → depression with long-term use
• Psychosis (high doses)
• Lowered seizure threshold
• Increased appetite

8. Hematological Effects

• Neutrophilia (increased from bone marrow + decreased margination)
• Lymphocytopenia (redistribution)
• Eosinopenia
• Monocytopenia
• Thrombocytosis, erythrocytosis (mild)

9. Anti-inflammatory Effects

• (detailed in Part 3 above)

10. Growth Effects

• Suppress growth hormone secretion
• Inhibit IGF-1 effects
• Inhibit chondrocyte proliferation
• Cause growth retardation in children

---

PART 10: PRECAUTIONS FOR GLUCOCORTICOID USE

PRECAUTIONS
│
├── BEFORE STARTING
│   ├── Screen for active infections (TB - CXR + Mantoux)
│   ├── Blood glucose (DM screening)
│   ├── Bone density (DEXA scan for long-term use)
│   ├── Blood pressure measurement
│   └── Ophthalmic examination (IOP, lens)
│
├── DURING THERAPY
│   ├── Never stop abruptly (risk of adrenal crisis)
│   ├── Use lowest effective dose
│   ├── Alternate-day dosing if possible (preserves HPA axis)
│   ├── Give in the morning (mimics diurnal cortisol peak)
│   ├── Add calcium + Vitamin D supplementation
│   ├── Consider PPI/H2 blocker for GI protection
│   ├── Monitor blood glucose regularly
│   └── Stress dosing during illness/surgery
│
└── SPECIAL POPULATIONS
    ├── Children: monitor growth (height/weight)
    ├── Elderly: extra vigilance for osteoporosis, DM, infection
    ├── Pregnancy: use hydrocortisone/prednisolone (not flucinolone)
    └── Liver failure: use prednisolone (not prednisone - needs liver conversion)

HPA Axis Suppression and Withdrawal

PROLONGED STEROID USE
         ↓
  HPA Axis Suppressed
         ↓
   ABRUPT WITHDRAWAL
         ↓
ACUTE ADRENAL INSUFFICIENCY
(Addisonian crisis)
├── Hypotension / Shock
├── Hyponatremia
├── Hyperkalemia
├── Nausea, vomiting
└── Death if untreated

PREVENTION:
• Taper dose slowly over weeks-months
• Duration of tapering ∝ duration of therapy
• Increase dose during physical stress (surgery, illness)

---

PART 11: SUMMARY FLOWCHART - CORTICOSTEROID MECHANISM TO EFFECTS

CORTICOSTEROID
       │
       ▼
Enters cell → binds GCR → nuclear translocation
       │
       ▼
┌──────────────────────────────────────────────────┐
│              NUCLEAR EFFECTS                      │
│  ┌─────────────────┬────────────────────────────┐│
│  │  TRANSACTIVATION │  TRANSREPRESSION           ││
│  │  ↑ Lipocortin-1  │  ↓ NF-κB, AP-1            ││
│  │  ↑ IκB           │  ↓ COX-2, iNOS            ││
│  │  ↑ Annexin       │  ↓ IL-1,2,4,5,6,8, TNF-α ││
│  └─────────────────┴────────────────────────────┘│
└──────────────────────────────────────────────────┘
       │                              │
       ▼                              ▼
↓ Phospholipase A2             Immunosuppression
       │                       (↓ T-cell, lymphocytes)
       ▼
↓ Arachidonic Acid
  ↓ Prostaglandins
  ↓ Leukotrienes
       │
       ▼
ANTI-INFLAMMATORY EFFECTS
(↓ Edema, ↓ Pain, ↓ Redness, ↓ Vascular permeability)

---

PART 12: CONTRAINDICATIONS (Comprehensive)

---

PART 13: QUICK REVISION TABLE

---

INHALED CORTICOSTEROIDS (ICS) - Special Group

---

MNEMONICS SUMMARY

---

---

1. Classification - Glucocorticoids (short/intermediate/long-acting) + Mineralocorticoids, with potency table
2. Anti-inflammatory mechanism - Lipocortin-1 → Phospholipase A2 inhibition → ↓ PGs and LTs; + direct cytokine suppression via NF-κB inhibition
3. Immunosuppressant mechanism - Mainly T-cell/cellular immunity; humoral at high doses
4. Therapeutic uses - Full categorized list across all organ systems
5. Four exam indications - Addison's, Status Asthmaticus, Nephrotic Syndrome, Transplant rejection
6. Adverse effects - CUSHINGOID mnemonic + detailed system-wise table
7. Four contraindications - Peptic ulcer, Active infection/TB, Uncontrolled DM, Osteoporosis
8. Topical steroids in dermatology - Potency classification (very potent to mild), indications per condition, vehicles, local + systemic ADRs, Finger Tip Unit
9. Glucocorticoid pharmacological actions - All 10 systems (carbohydrate, protein, fat, CVS, bone, CNS, blood, etc.)
10. Precautions - Before/during/special populations; HPA suppression and withdrawal flowchart
11. Flowcharts - Mechanism, HPA suppression, anti-inflammatory cascade, immunosuppression