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Endocrine Pharmacology - MBBS 2nd Year Complete Notes

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Overview of Endocrine Pharmacology Topics (MBBS 2nd Year)

1. Thyroid & Antithyroid Drugs
2. Insulin & Oral Antidiabetic Drugs
3. Glucocorticoids & Mineralocorticoids
4. Sex Hormones & Oral Contraceptives
5. Anterior Pituitary Hormones

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UNIT 1: THYROID AND ANTITHYROID DRUGS

1.1 Thyroid Physiology (Quick Recap)

• The thyroid secretes T3 (triiodothyronine) and T4 (thyroxine). T4 contains 65% iodine; T3 contains 59% iodine.
• Daily iodide requirement: 150 mcg (200 mcg in pregnancy/lactation).
• T3 is the more active form; T4 is peripherally converted to T3 by deiodinase enzymes.

1. Iodide trapping via NIS (sodium/iodide symporter) - inhibited by thiocyanate, perchlorate, pertechnetate
2. Iodide transport to apical membrane via pendrin (SLC26A4)
3. Oxidation by thyroid peroxidase (TPO) → iodine
4. Organification - iodination of tyrosine residues on thyroglobulin → MIT, DIT
5. Coupling - MIT + DIT → T3; DIT + DIT → T4
6. Proteolysis → release of T3 and T4 into blood

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1.2 Thyroid Hormone Preparations (Hypothyroidism Treatment)

• Decreased absorption: Calcium carbonate, antacids, omeprazole, iron salts, cholestyramine (separate by 4 hours)
• Increased metabolism: Rifampicin, phenytoin, carbamazepine

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1.3 Antithyroid Drugs (Hyperthyroidism Treatment)

A. Thioamides (Thiocarbamides)

• Inhibit thyroid peroxidase (TPO) → block organification and iodine incorporation
• Block coupling of iodotyrosines (MIT+DIT → T3, DIT+DIT → T4)
• PTU only - also inhibits peripheral conversion of T4 → T3 (deiodination)
• Do NOT block iodide uptake

• Longer half-life → once-daily dosing
• Safer hepatic profile (PTU has black box warning for severe/fatal hepatitis)
• Preferred except in 1st trimester of pregnancy and thyroid storm

• First trimester of pregnancy (methimazole teratogenic - aplasia cutis, choanal atresia)
• Thyroid storm (also blocks T4→T3 peripheral conversion)

• Maculopapular pruritic rash (4-6%) - most common
• Nausea, GI distress
• Agranulocytosis (0.1-0.5%) - most dangerous; patient must stop drug immediately if sore throat/fever; cross-sensitivity ~50% between PTU and methimazole
• PTU: hepatotoxicity (black box warning - rare but fatal)
• Methimazole: cholestatic jaundice, altered taste/smell
• Rare: vasculitis, lupus-like reaction, exfoliative dermatitis

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B. Iodides (High-Dose Iodine)

• Inhibit organification (Wolff-Chaikoff effect)
• Inhibit hormone release
• Reduce vascularity and size of hyperplastic thyroid gland

• Pre-operative preparation for thyroidectomy (given 10-14 days before surgery)
• Thyroid storm (given 1 hour AFTER thioamides to prevent organification of excess iodine)
• Radiation emergency (KI protects thyroid from radioactive iodine uptake)
• Jod-Basedow phenomenon: excess iodide → hyperthyroidism in susceptible patients (multinodular goiter)

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C. Radioactive Iodine (¹³¹I)

• Emits beta rays (mainly) + gamma rays
• Taken up by thyroid → destroys follicular cells
• Treatment of choice for Graves' disease in non-pregnant adults
• Contraindicated in pregnancy and breastfeeding
• May worsen ophthalmopathy (15-20% risk, especially in smokers)
• Results in permanent hypothyroidism in most patients → needs levothyroxine replacement

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D. Anion Inhibitors

• Perchlorate (ClO₄⁻), pertechnetate (TcO₄⁻), thiocyanate (SCN⁻)
• Competitively inhibit iodide transport (NIS)
• Potassium perchlorate used in amiodarone-induced hyperthyroidism
• Rarely used - risk of aplastic anemia

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E. Beta-Blockers (Propranolol)

• Controls symptomatic relief of thyrotoxicosis (palpitations, tremor, anxiety, heat intolerance)
• Propranolol at high doses also inhibits peripheral T4 → T3 conversion
• Key role in thyroid storm management

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1.4 Thyroid Storm Management

1. Propranolol IV/oral - controls cardiovascular symptoms
2. PTU (500-1000 mg loading dose, then 250 mg every 4h) - blocks synthesis AND peripheral conversion
3. Iodide (SSKI/Lugol's) - given 1 hour AFTER PTU - blocks hormone release
4. Hydrocortisone 50 mg IV every 6h - anti-shock + blocks T4→T3 conversion

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UNIT 2: INSULIN & ANTIDIABETIC DRUGS

2.1 Insulin

• Hypoglycemia (most important)
• Lipodystrophy at injection site (lipoatrophy or lipohypertrophy)
• Weight gain
• Hypokalemia (insulin drives K⁺ into cells)

• Type 1 DM (mandatory)
• Type 2 DM (when oral agents fail)
• Diabetic ketoacidosis (regular insulin IV)
• Hyperkalemia (insulin + dextrose IV)
• Gestational diabetes

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2.2 Oral Antidiabetic Drugs

A. Biguanides - Metformin

• MOA: Activates AMPK → inhibits hepatic gluconeogenesis; increases insulin sensitivity; does NOT cause hypoglycemia (anti-hyperglycemic)
• Drug of choice for Type 2 DM (especially overweight patients)
• No weight gain, may reduce weight; no hypoglycemia monotherapy
• ADRs: GI upset (most common), lactic acidosis (rare but serious - avoid in renal impairment, hepatic failure, hypoxia)
• Contraindications: eGFR <30, IV contrast studies (hold 48h)

B. Sulfonylureas

• MOA: Close ATP-sensitive K⁺ channels on β-cells → depolarization → Ca²⁺ influx → insulin secretion (require functional β-cells)
• ADRs: Hypoglycemia (main risk, especially with glibenclamide), weight gain
• Chlorpropamide: longest acting, antabuse-like reaction with alcohol, SIADH

C. Meglitinides (Glinides)

• Similar MOA to sulfonylureas (K⁺ channel closure) but shorter-acting
• Taken before meals; control postprandial hyperglycemia
• Less hypoglycemia than sulfonylureas

D. Thiazolidinediones (Glitazones)

• MOA: Activate PPAR-γ nuclear receptor → improve insulin sensitivity in muscle, fat, liver
• ADRs: Weight gain, fluid retention/edema, heart failure (contraindicated in heart failure), fractures, bladder cancer risk (pioglitazone)
• Rosiglitazone: increased cardiovascular risk (withdrawn in many countries)

E. Alpha-Glucosidase Inhibitors

• MOA: Inhibit intestinal alpha-glucosidase → delay carbohydrate digestion/absorption → reduce postprandial hyperglycemia
• ADRs: GI - flatulence, bloating, diarrhea (most common reason for discontinuation)
• No hypoglycemia monotherapy; if hypoglycemia occurs with combination therapy → treat with glucose (NOT sucrose)

F. DPP-4 Inhibitors (Gliptins)

• MOA: Inhibit dipeptidyl peptidase-4 → prevent GLP-1 degradation → increased insulin secretion (glucose-dependent) + decreased glucagon
• Weight-neutral; low hypoglycemia risk
• ADRs: Nasopharyngitis, urinary tract infections, rare pancreatitis

G. GLP-1 Receptor Agonists

• MOA: Mimic GLP-1 → stimulate insulin secretion (glucose-dependent), suppress glucagon, slow gastric emptying, reduce appetite
• Weight loss benefit; cardiovascular benefit (liraglutide, semaglutide)
• ADRs: Nausea, vomiting (most common); rare pancreatitis; thyroid C-cell tumors in animals
• Given by subcutaneous injection (semaglutide also available orally)

H. SGLT-2 Inhibitors (Gliflozins)

• MOA: Inhibit SGLT-2 in proximal tubule → block glucose reabsorption → glycosuria
• Weight loss, BP reduction; cardiovascular and renal protection
• ADRs: Genital mycotic infections, UTI, polyuria; Euglycemic DKA (rare); Fournier's gangrene; do NOT use in eGFR <30

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Summary Table: Oral Antidiabetics

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UNIT 3: GLUCOCORTICOIDS & MINERALOCORTICOIDS

3.1 Glucocorticoids

• Diffuse through cell membrane → bind cytoplasmic glucocorticoid receptor (GR)
• GR-steroid complex → translocates to nucleus → binds GRE (glucocorticoid response elements) → gene transcription
• Anti-inflammatory: inhibit phospholipase A₂ (via lipocortin/annexin) → ↓ arachidonic acid → ↓ prostaglandins, leukotrienes
• Immunosuppressive: inhibit NF-κB, IL-1, IL-2, TNF-α; reduce T-cell proliferation; reduce neutrophil migration

• Carbohydrate: ↑ gluconeogenesis, insulin resistance → hyperglycemia
• Protein: catabolic (muscle wasting, skin thinning)
• Fat: redistribution → central obesity (buffalo hump, moon face, truncal obesity)
• Calcium: ↓ intestinal Ca absorption, ↑ renal Ca excretion → osteoporosis
• Immune: anti-inflammatory, immunosuppressive

• Replacement therapy: Addison's disease, CAH (congenital adrenal hyperplasia)
• Anti-inflammatory: asthma, COPD, rheumatoid arthritis, IBD
• Immunosuppression: organ transplant, SLE
• Cerebral edema (dexamethasone)
• Antenatal: betamethasone/dexamethasone for fetal lung maturity (preterm labor)
• Thyroid storm (hydrocortisone)
• Septic shock (hydrocortisone)
• Dexamethasone suppression test (diagnosis of Cushing's syndrome)
• Allergy/anaphylaxis (adjunct)

• HPA axis suppression (never stop abruptly - taper gradually)
• Cushing-like syndrome: moon face, buffalo hump, striae, obesity
• Hyperglycemia / precipitates DM
• Osteoporosis (long-term use)
• Peptic ulcer (combined with NSAIDs = very high risk)
• Growth retardation in children
• Cataracts, glaucoma
• Psychiatric effects: euphoria, psychosis
• Opportunistic infections
• Hypertension, hypokalemia, sodium/water retention (mineralocorticoid effects)

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3.2 Mineralocorticoids

• MOA: Acts on mineralocorticoid receptor in renal collecting duct → ↑ Na⁺ reabsorption, ↑ K⁺ excretion, ↑ H⁺ excretion
• Use: Addison's disease (primary adrenal insufficiency) - combined with hydrocortisone; orthostatic hypotension

• Used in: hyperaldosteronism (Conn's syndrome), heart failure, hypertension
• Spironolactone ADRs: gynecomastia, menstrual irregularities (anti-androgen effect)
• Eplerenone: more selective, less anti-androgen effects

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UNIT 4: SEX HORMONES & ORAL CONTRACEPTIVES

4.1 Estrogens

• Hormone replacement therapy (menopause)
• Oral contraceptives (combined with progestin)
• Dysfunctional uterine bleeding
• Osteoporosis prevention
• Hypogonadism

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4.2 Progestins

• Combined OCP, Progestin-only pill (POP/"mini-pill")
• Threatened/habitual abortion
• Endometriosis, endometrial carcinoma
• Contraception (DMPA injections, Norplant implants, Mirena IUD)

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4.3 Oral Contraceptives

1. Inhibit ovulation (suppress LH surge via negative feedback on GnRH/LH/FSH)
2. Thicken cervical mucus (sperm-hostile)
3. Thin endometrium (unfavorable for implantation)
4. Impair tubal motility

• Nausea, breast tenderness, breakthrough bleeding
• Thromboembolic disease (DVT, PE, stroke) - estrogen component
• Hypertension
• Headache, migraine
• Decreased libido
• Chloasma (skin pigmentation)

• Levonorgestrel (Plan B): 1.5 mg single dose within 72 hours (up to 120 h)
• Ulipristal acetate (EllaOne): within 120 h; progesterone receptor modulator
• Copper IUD: within 5 days - most effective emergency contraception

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4.4 Androgens & Antiandrogens

• Uses: Male hypogonadism, anemia, catabolic states, delayed puberty
• ADRs: Virilization in females, hepatotoxicity (17α-alkylated forms), polycythemia

• Finasteride: 5-alpha reductase inhibitor → blocks DHT → BPH, male-pattern baldness
• Spironolactone: Mineralocorticoid/androgen antagonist → hirsutism, PCOS
• Flutamide, Bicalutamide: Androgen receptor blockers → prostate cancer
• Cyproterone acetate: Antiandrogen → hirsutism, precocious puberty

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UNIT 5: ANTERIOR PITUITARY HORMONES

Clinically Important Preparations

• Dopamine D2 agonist → inhibits prolactin secretion
• Used in: prolactinoma, hyperprolactinemia, Parkinson's disease, type 2 DM (novel use), acromegaly
• ADRs: Nausea, postural hypotension, nasal congestion

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HIGH-YIELD EXAM POINTS

Compare Methimazole vs. PTU

Wolff-Chaikoff Effect vs. Jod-Basedow Phenomenon

Drugs Causing Thyroid Dysfunction

• Amiodarone: Contains 37% iodine → both hypo and hyperthyroidism; also inhibits T4→T3 conversion
• Lithium: Inhibits hormone release → hypothyroidism, goiter
• Interferon-alpha: Autoimmune thyroiditis
• Tyrosine kinase inhibitors: Hypothyroidism

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Quick Memory Aids

• "PTU first in thyroid storm" - P for Propranolol, T for thioamide (PTU), U for Umbilical (iodide 1 hour AFTER), hydrocortisone
• Sulfonylureas need beta cells - do not work in Type 1 DM
• Metformin = weight neutral/loss, no hypoglycemia - first choice T2DM
• SGLT2i = glucose excreted in urine = glycosuria (treat genital infections proactively)
• GLP-1 agonists = "lose weight, protect heart"
• Dexamethasone = most potent glucocorticoid, zero mineralocorticoid activity, crosses placenta, fetal lung maturity
• Fludrocortisone = pure mineralocorticoid for Addison's
• Levonorgestrel emergency contraception within 72 hours; Copper IUD most effective (up to 5 days)
• Finasteride = 5-alpha reductase inhibitor → reduces DHT → BPH + male pattern baldness

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🧬 ENDOCRINE PHARMACOLOGY

MBBS 2nd Year - Easy English Notes (KD Tripathi Style)

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💡 How to use these notes: Think of the endocrine system as a boss and worker system. The brain (hypothalamus + pituitary) is the boss. The glands (thyroid, adrenal, pancreas) are the workers. Drugs either mimic, block, or modify this communication.

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CHAPTER 1: THYROID & ANTITHYROID DRUGS

🔑 First, Understand the System Simply

• The brain sends orders via TRH (from hypothalamus) → TSH (from pituitary) → Thyroid makes T3 & T4
• T3 and T4 then go back and tell the brain "enough, stop ordering" - this is called negative feedback

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How Thyroid Makes Hormones (Step-by-Step - VERY IMPORTANT for Exams)

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PART A: DRUGS FOR HYPOTHYROIDISM (Under-active thyroid)

Patient is "slow" - tired, weight gain, cold intolerance, constipation, slow pulse

🚨 Why Take Levothyroxine on Empty Stomach?

🔍 How to Monitor: Check TSH after 6-8 weeks

Special Case - Myxedema Coma (life-threatening hypothyroidism):

• Give IV liothyronine (T3) - faster acting
• Plus IV hydrocortisone (because adrenal function may be suppressed too)

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PART B: ANTITHYROID DRUGS (For Hyperthyroidism)

Patient is "fast" - weight loss, sweating, palpitations, diarrhea, bulging eyes (in Graves' disease)

Four Types of Antithyroid Treatment:

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1. THIOAMIDES (Most Important Drug Class!)

Think of thioamides as blocking the TPO enzyme (the machine that activates iodine). No active iodine = no hormone made.

• Block TPO → block organification → no T3/T4 made
• Block coupling of MIT + DIT
• PTU ONLY: Also blocks peripheral T4 → T3 conversion (extra benefit!)
• ❌ They do NOT block iodide uptake into the gland

Methimazole vs PTU - KD Tripathi Favourite Comparison!

Adverse Effects of Thioamides:

• Most common: Maculopapular itchy rash (4-6%), nausea
• Most dangerous: Agranulocytosis (0.1-0.5%) - sudden drop in WBC → fever + sore throat = STOP DRUG immediately!
• Cross-sensitivity between PTU and methimazole = 50% → don't switch if serious reaction
• PTU: Fatal hepatitis (rare but black box)
• Methimazole: altered taste/smell, cholestatic jaundice

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2. IODIDES (High-Dose Iodine) - Paradoxical Effect!

• Wolff-Chaikoff Effect: Large iodide → blocks organification → reduces T3/T4 synthesis
• Reduces vascularity and size of the thyroid (useful before surgery)
• Reduces hormone release

• Pre-operative prep for thyroidectomy (given 10-14 days before operation to shrink gland)
• Thyroid storm (given 1 hour AFTER thioamides! Never before!)
• Radiation emergency - protects thyroid from radioactive fallout

⭐ The Jod-Basedow vs Wolff-Chaikoff - HIGH YIELD!

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3. RADIOACTIVE IODINE (¹³¹I) - The "Radiation Bomb"

• Contraindicated in pregnancy and breastfeeding
• Usually causes permanent hypothyroidism → needs lifelong levothyroxine
• Can worsen thyroid eye disease (ophthalmopathy) - especially in smokers
• Give 1 week AFTER stopping antithyroid drugs

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4. BETA-BLOCKERS (Symptomatic Relief Only)

• Controls palpitations, tremor, sweating, anxiety, heat intolerance
• Propranolol at HIGH doses also inhibits peripheral T4 → T3 conversion (unlike other beta-blockers)
• Does NOT treat the cause - only relieves symptoms
• Also used in thyroid storm

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5. ANION INHIBITORS

• Rarely used clinically (risk of aplastic anemia with perchlorate)
• Potassium perchlorate: used in amiodarone-induced hyperthyroidism

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🔥 THYROID STORM - High Yield Protocol

🧠 Memory trick: "P-T-I-S" = Propranolol, Thioamide (PTU), Iodide (1 hr later), Steroids

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Drugs That Affect Thyroid Function (Important Exam Topic!)

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CHAPTER 2: INSULIN & ANTIDIABETIC DRUGS

First, Understand Diabetes Simply

• Fasting glucose ≥ 126 mg/dL
• 2-hr post-meal glucose ≥ 200 mg/dL
• HbA1c ≥ 6.5% (reflects 3 months of average sugar)
• Prediabetes: fasting 100-125 mg/dL, HbA1c 5.7-6.4%

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INSULIN

Types of Insulin - Read the Graph!

Insulin Types - Easy Comparison Table

How Regular Insulin is Different from Analogs:

• Regular insulin = crystalline zinc insulin = clear, given 30 min BEFORE meals
• Rapid analogs (Lispro, Aspart) = amino acid sequence modified → faster absorbed → give 15 min before or immediately after meal
• NPH = regular insulin + protamine + zinc = cloudy, intermediate
• Glargine = modified to precipitate at neutral pH (subcutaneous) → slow, no peak = "peakless basal insulin"

Mechanism of Action of Insulin:

Insulin binds to insulin receptor (tyrosine kinase receptor) on cell surface → signals GLUT-4 transporters to move to surface → glucose enters the cell

• ↑ glucose uptake (muscle, fat)
• ↑ glycogen synthesis (liver, muscle)
• ↑ protein synthesis
• ↑ fat storage (lipogenesis)
• ↓ gluconeogenesis, glycogenolysis, lipolysis
• Drives K⁺ INTO cells (used in hyperkalemia treatment!)

Adverse Effects of Insulin:

• Hypoglycemia - most common and important!
• Weight gain - promotes fat storage
• Lipodystrophy at injection site - lipoatrophy (fat loss) or lipohypertrophy (fat buildup)
• Hypokalemia - insulin pushes K⁺ into cells
• Insulin allergy (rare)

Special Uses of Insulin:

• Type 1 DM: MANDATORY (no beta cells = no choice)
• Type 2 DM: when oral drugs fail
• DKA (Diabetic Ketoacidosis): IV regular insulin
• Hyperkalemia: IV insulin + dextrose → drives K⁺ into cells (rapid fix)
• Gestational diabetes

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ORAL ANTIDIABETIC DRUGS (OADs)

🧠 Simple way to remember all OAD classes: "B-S-M-T-A-D-G-S" (Biguanides, Sulfonylureas, Meglitinides, TZDs, Alpha-glucosidase inhibitors, DPP-4 inhibitors, GLP-1 agonists, SGLT-2 inhibitors)

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1. BIGUANIDES - METFORMIN ⭐ (DRUG OF CHOICE FOR TYPE 2 DM)

• Activates AMPK enzyme in liver → shuts down gluconeogenesis
• Also increases insulin sensitivity in muscle
• Does NOT stimulate insulin release → does NOT cause hypoglycemia alone

• ✅ No weight gain (actually may reduce weight)
• ✅ No hypoglycemia when used alone
• ✅ Cheap, proven, safe
• ✅ Cardiovascular benefit (UKPDS study)

• GI effects (nausea, diarrhea, metallic taste) - most common; take with food to reduce
• Lactic acidosis - rare but serious, especially in renal failure
• Reduces B12 absorption (long-term use)

• eGFR < 30 (severe kidney disease) - lactic acidosis risk
• Liver failure, alcohol abuse
• Hold before IV contrast dye (48 hours before and after)
• Hypoxic states (heart failure, respiratory failure)

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2. SULFONYLUREAS ⭐ (Second Most Important)

Block ATP-sensitive K⁺ channels on beta cells → K⁺ can't leave → cell depolarizes → Ca²⁺ enters → insulin granules released!

• 1st generation (older): Tolbutamide, Chlorpropamide, Glibenclamide
• 2nd generation (better, preferred): Glipizide, Glibenclamide (Glyburide), Glimepiride

• Hypoglycemia - most important! (Because they stimulate insulin even when glucose is normal/low)
• Weight gain (due to insulin release)
• Sulfa allergy cross-reactivity (rare)

• Longest acting sulfonylurea
• Causes disulfiram-like reaction with alcohol (flushing, nausea)
• Causes SIADH (water retention)
• Not preferred now due to prolonged hypoglycemia

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3. MEGLITINIDES (Glinides)

• Much faster onset, shorter duration
• Taken just before each meal
• Controls postprandial (after-meal) glucose
• Less hypoglycemia risk than sulfonylureas
• Do NOT combine with sulfonylureas (same mechanism = double risk of hypoglycemia)

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4. THIAZOLIDINEDIONES (TZDs / Glitazones)

Activate PPAR-γ (nuclear receptor) in fat/muscle/liver → cells become more insulin sensitive → glucose uptake improves

• Do NOT cause hypoglycemia alone
• Need 2-3 months to show full effect
• Need insulin to be present to work

• Weight gain + edema (fluid retention)
• Heart failure - CONTRAINDICATED in heart failure!
• Osteoporosis + fractures (especially in women)
• Pioglitazone: slight risk of bladder cancer (long-term)
• Rosiglitazone: cardiovascular concerns → mostly withdrawn

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5. ALPHA-GLUCOSIDASE INHIBITORS

Inhibit intestinal alpha-glucosidase enzyme → delay CHO breakdown → slow glucose absorption → reduce postprandial hyperglycemia

• Gas, flatulence, bloating, diarrhea (very common - undigested CHO ferments in colon)
• No hypoglycemia alone
• ⭐ Important: If hypoglycemia occurs (due to combination therapy) → treat with pure glucose (NOT sucrose/table sugar) because sucrose needs the same enzyme that is blocked!

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6. DPP-4 INHIBITORS (Gliptins)

Inhibit DPP-4 enzyme → GLP-1 and GIP levels rise → glucose-dependent insulin secretion increases + glucagon decreases

• Insulin release only when glucose is high → minimal hypoglycemia
• Weight neutral
• Safe in elderly

• Upper respiratory infections, nasopharyngitis
• Urinary tract infections
• Rare: pancreatitis, joint pain

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7. GLP-1 RECEPTOR AGONISTS (Incretins)

• ↑ insulin secretion (glucose-dependent)
• ↓ glucagon secretion
• ↓ gastric emptying (food stays longer → feel full)
• ↓ appetite (act on brain)
• → Significant weight loss

• Cardiovascular protection (liraglutide, semaglutide - proven in trials)
• Renal protection (semaglutide)

• Nausea, vomiting (most common - improves with time)
• Rare: pancreatitis
• Thyroid C-cell tumors in animal studies (caution in MEN-2, thyroid cancer history)
• Given as subcutaneous injection (semaglutide also available as oral pill)

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8. SGLT-2 INHIBITORS (Gliflozins) - Newest & Trendy!

Block SGLT-2 transporter in proximal tubule of kidney → glucose not reabsorbed → glycosuria (glucose in urine)

• Weight loss (glucose = calories wasted in urine)
• Blood pressure reduction (osmotic diuresis)
• Heart failure benefit - reduces hospitalizations!
• Kidney protection - reduces CKD progression

• Genital fungal infections (glucose in urine = food for fungi) - most common!
• Urinary tract infections
• Polyuria
• Euglycemic DKA (DKA even when glucose is normal - rare but dangerous)
• Fournier's gangrene (necrotizing fasciitis of genitals - rare)
• ❌ Do NOT use if eGFR < 30

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📊 Master Summary Table - All Oral Antidiabetics

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CHAPTER 3: GLUCOCORTICOIDS

Think of Glucocorticoids as the Body's "Stress Hormone"

Natural vs Synthetic Glucocorticoids

⭐ Dexamethasone = most potent glucocorticoid + ZERO mineralocorticoid activity = perfect when you want only anti-inflammatory effect (cerebral edema, fetal lung maturity)

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Mechanism of Action (Simple Version)

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Effects of Glucocorticoids on the Body

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Clinical Uses of Glucocorticoids

• Addison's disease (adrenal insufficiency): hydrocortisone + fludrocortisone
• Congenital adrenal hyperplasia (CAH)

• Asthma, COPD (budesonide inhaler, prednisolone)
• Rheumatoid arthritis, SLE
• Inflammatory bowel disease
• Allergic reactions, anaphylaxis (adjunct)
• Organ transplant rejection prevention

• Cerebral edema: Dexamethasone (no mineralocorticoid = no Na/water retention!)
• Fetal lung maturity (preterm labor): Betamethasone or Dexamethasone given to mother at 24-34 weeks
• Thyroid storm: Hydrocortisone (blocks T4→T3 + prevents shock)
• Septic shock: Hydrocortisone (relative adrenal insufficiency)
• Cushing's syndrome diagnosis: Dexamethasone suppression test

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Adverse Effects - "Cushing's Syndrome in a Box"

🧠 Memory trick: "WASHED"

• Weight gain, moon face, buffalo hump
• Adrenal suppression (never stop abruptly!)
• Sugar raised (hyperglycemia, steroid diabetes)
• Hypertension + Hypokalemia
• Eyes (cataracts, glaucoma)
• Decreased immunity + Delayed wound healing + Depression/psychosis

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⭐ Steroid Withdrawal - Never Stop Abruptly!

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MINERALOCORTICOIDS

• Acts on mineralocorticoid receptor in kidney collecting duct
• ↑ Na⁺ reabsorption, ↑ K⁺ excretion, ↑ H⁺ excretion → retains sodium and water
• Used in: Addison's disease (combined with hydrocortisone), orthostatic hypotension

• Block aldosterone receptor
• Used in: Conn's syndrome (hyperaldosteronism), heart failure, hypertension
• Spironolactone ADRs: gynecomastia, menstrual irregularities (also has anti-androgen effect)
• Eplerenone: more selective, fewer hormonal side effects

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CHAPTER 4: SEX HORMONES & ORAL CONTRACEPTIVES

ESTROGENS

• OCP (combined with progestin)
• Hormone replacement therapy (HRT) for menopause symptoms
• Hypogonadism in females
• Osteoporosis prevention
• Dysfunctional uterine bleeding

• Nausea, breast tenderness
• Thromboembolism (DVT, PE, stroke) - most dangerous!
• Hypertension
• Endometrial hyperplasia/cancer (if used alone without progestin)
• Breast cancer risk (long-term)

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PROGESTINS

• OCP, Progestin-only pill (POP / mini-pill)
• Threatened/habitual abortion
• Endometriosis
• Contraception (DMPA injection = Depo-Provera, Mirena IUD)

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ORAL CONTRACEPTIVES - VERY IMPORTANT FOR EXAMS!

Combined OCP (Estrogen + Progestin)

1. Inhibits ovulation - suppresses LH surge via negative feedback on GnRH → no egg released (main mechanism)
2. Thickens cervical mucus - sperm cannot swim through
3. Thins endometrium - even if fertilized, egg cannot implant

Types of Combined OCP:

• Monophasic: Same dose every day (e.g., Yasmin - ethinyl estradiol + drospirenone)
• Biphasic/Triphasic: Varying doses across the cycle

Adverse Effects of OCP:

• Nausea (most common early complaint)
• Breast tenderness
• Breakthrough (irregular) bleeding
• Thromboembolism - estrogen increases clotting factors → DVT/PE/stroke risk
• Hypertension
• Headache, migraine
• Chloasma (dark skin patches, especially with sun exposure)
• Reduced libido

Absolute Contraindications of OCP ("FACH rule"):

• Family history of VTE / Previous DVT or PE
• Age >35 + Smoker (5-10x VTE risk)
• Cardiovascular disease, ischemic heart disease, stroke history
• Hepatitis/liver disease, breast cancer, migraine with aura, pregnancy

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Progestin-Only Pill (POP / Mini-Pill)

• No estrogen → safer in breastfeeding mothers, smokers >35, hypertension patients
• Works mainly by thickening cervical mucus
• Must be taken at SAME TIME every day (less forgiving than combined OCP)

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EMERGENCY CONTRACEPTION ("Morning After Pill")

⭐ Copper IUD = most effective emergency contraceptive (>99% effective!)

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ANDROGENS & ANTIANDROGENS

Antiandrogens - High-Yield Table:

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CHAPTER 5: ANTERIOR PITUITARY HORMONES - Quick Reference

Key Point - GnRH Agonists (Leuprolide, Goserelin):

• Pulsatile use → stimulates FSH/LH → used in infertility
• Continuous use → DOWNREGULATES receptors → SUPPRESSES FSH/LH → like "medical castration"
• Used in: prostate cancer, endometriosis, precocious puberty, uterine fibroids

Bromocriptine (Dopamine D2 agonist):

• Inhibits prolactin secretion
• Used in: prolactinoma, hyperprolactinemia, Parkinson's, type 2 DM (Cycloset)
• ADRs: nausea, postural hypotension, nasal congestion

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🏆 EXAM POWER SUMMARY - One Liner Facts

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