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Pharmacological Management of Coronary Artery Disease (CAD)

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A. Drugs for Prognosis (Reduce MI, Death, Stroke)

1. Antiplatelet Agents

• Low-dose aspirin (75-100 mg/day) is the cornerstone antiplatelet for all CAD patients.
• Irreversibly inhibits COX-1, reducing thromboxane A2-mediated platelet aggregation.
• Reduces risk of MI and cardiovascular death in stable CAD.

• DAPT duration after drug-eluting stent: minimum 6-12 months; may extend to 12+ months in high-ischemic/low-bleeding risk patients.
• A 2025 meta-analysis (PMID: 40467090) confirms P2Y12 inhibitor monotherapy after PCI is non-inferior to aspirin monotherapy for some outcomes post-DAPT.

• Used IV in high-risk ACS/PCI settings; block the final common pathway of platelet aggregation.

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2. Statins (HMG-CoA Reductase Inhibitors)

• High-intensity statins (atorvastatin 40-80 mg, rosuvastatin 20-40 mg) are indicated for ALL CAD patients, regardless of baseline LDL-C.
• Goal: LDL-C <1.4 mmol/L (<55 mg/dL) with ≥50% reduction from baseline (European guidelines); high-intensity statin therapy for all (US/ACC/AHA approach).
• In patients with recurrent events within 2 years despite max statin, LDL-C goal <1.0 mmol/L (<40 mg/dL).
• Benefit: plaque stabilization, anti-inflammatory effects, mortality reduction.

• Ezetimibe (10 mg/day): inhibits intestinal cholesterol absorption; IMPROVE-IT trial showed 6.4% relative risk reduction in composite CV events added to statin in post-ACS patients.
• PCSK9 inhibitors (evolocumab, alirocumab): monoclonal antibodies; FOURIER trial showed 15% relative reduction in CV events vs. placebo in patients on max-dose statin; initiated 8-12 weeks after event if LDL goal not met.

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3. Beta-Blockers (β-Adrenergic Antagonists)

• Mechanism: Reduce heart rate, myocardial contractility, and oxygen demand; also antiarrhythmic.
• Indicated: All post-MI patients, especially with LVEF ≤40% or HF (Class I, LOE A).
• For LVEF >40%: Recommended routinely after MI (Class IIa).
• IV Metoprolol: IV then oral in hemodynamically stable STEMI patients undergoing primary PCI (Class IIa). Metoprolol is the IV beta-blocker of choice (unique cardioprotective effect on β1 receptor).
• Carvedilol: Proven mortality reduction in post-MI patients with reduced LVEF (CAPRICORN trial).
• For stable angina: beta-blockers are first-line antianginal AND prognostic agents.

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4. ACE Inhibitors / ARBs / ARNi

• Indicated (Class I): Post-MI with HF, LV systolic dysfunction (LVEF ≤40%), diabetes, or anterior infarct.
• Should be started within 24 hours of STEMI in the absence of contraindications (hypotension, hypersensitivity, pregnancy).
• Consider (Class IIa) in ALL post-MI patients without contraindications.

• Alternative when ACE inhibitors are not tolerated (VALIANT trial for valsartan).

• Added on top of ACE inhibitor + beta-blocker in post-MI patients with LVEF ≤40% AND HF or diabetes (EPHESUS trial).
• Reduces CV mortality and hospitalization.
• Contraindicated if serum creatinine >2.5 mg/dL (men) or >2.0 mg/dL (women), or K+ >5.0 mEq/L.

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B. Antianginal Drugs (Symptom Relief)

5. Nitrates

• Mechanism: Release NO → venodilation → reduced preload → reduced myocardial O2 demand; also coronary vasodilation.
• Tolerance: Nitrate-free interval of 8-12 hours required to avoid tolerance.
• Contraindication: Absolutely contraindicated with PDE5 inhibitors (sildenafil, tadalafil) - risk of severe hypotension; do not use within 24-48 hours.
• Nitrates relieve angina but have not been shown to reduce mortality as monotherapy in CAD.

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6. Calcium Channel Blockers (CCBs)

• Primarily vasodilators; reduce afterload.
• Amlodipine: commonly used, well tolerated, also reduces angina frequency.
• Nifedipine immediate-release: avoid as monotherapy in unstable angina (reflex tachycardia).

• Reduce heart rate AND vasodilate - useful when beta-blockers are contraindicated.
• Avoid in HF with reduced LVEF (negative inotrope).
• Verapamil: most negative chronotropic/inotropic.

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7. Ivabradine

• Mechanism: Selectively inhibits the If (funny) current in the sinoatrial node - pure heart rate reduction without negative inotropy or vasodilation.
• Indicated for stable angina in sinus rhythm when beta-blockers are contraindicated or poorly tolerated, or as add-on.
• Also used in HF with reduced EF + resting HR ≥70 bpm on maximum tolerated beta-blocker.

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8. Ranolazine

• Mechanism: Inhibits late inward sodium current (INa) → reduces intracellular Ca2+ → reduces myocardial oxygen demand; no significant effect on HR or BP.
• Used as add-on antianginal therapy in patients inadequately controlled on beta-blockers and/or CCBs.
• Available in some countries; CARISA trial showed improved exercise tolerance when added to atenolol, amlodipine, or diltiazem.

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9. Other Antianginal Agents

• Nicorandil: Potassium channel opener + nitrate-like effect; reduces both preload and afterload; available in Europe and Asia; not US.
• Trimetazidine: Metabolic agent (inhibits fatty acid oxidation, favors glucose metabolism); used in some countries as add-on; safety in HF uncertain.
• Molsidomine: Nitric oxide donor; alternative to nitrates.

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C. Anticoagulants in ACS

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D. Drug Overview by CAD Setting

Stable Chronic CAD

Acute Coronary Syndrome (STEMI / NSTEMI-UA)

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E. STEMI Pharmacological Timeline

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Recent Evidence Updates (2024-2025)

• PMID 39567875 (2024): Low/moderate statin + ezetimibe combination is comparable in safety and efficacy to high-intensity statin monotherapy - a consideration for statin-intolerant patients.
• PMID 39918465 (2025, JACC): In AF + stable CAD, anticoagulation alone (without antiplatelet) is generally preferred after PCI; combination therapy increases bleeding.
• PMID 40467090 (2025, BMJ): P2Y12 inhibitor monotherapy after PCI is superior to aspirin monotherapy for reducing MACE - may change post-DAPT strategy.
• 2025 ACC/AHA ACS Guideline (PMID 40014670): Updated comprehensive guideline replacing 2013 STEMI and 2014 NSTEMI guidelines.

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Sonya Chawla - Polyclinic Notes: Full Explanation

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📘 TOPIC 1: DIABETES MELLITUS (Days 1, 2 & 10)

1.1 Diagnosis of Diabetes

• Glucometer - NOT used for diagnosis; only used for monitoring/control
• HbA1c - reflects average blood glucose over the last 2-3 months (lifespan of RBC = 120 days); it is attached to glucose molecules on hemoglobin

• Hemolytic anemia (RBCs destroyed faster - falsely low HbA1c)
• Iron deficiency anemia
• Sickle cell disease / hemoglobinopathies

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1.2 Risk Factors for Type 2 Diabetes

• BMI ≥ 25 kg/m², waist > 80 cm (women)
• Age ≥ 28
• Family history
• Previous pregnancy with macrosomia (baby > 4 kg)
• Ethnicity (South Asian, etc.)
• Previous gestational diabetes

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1.3 Pathogenesis of Type 2 Diabetes

1. Adipose tissue - reduced glucose uptake
2. Skeletal muscle - reduced glucose uptake (GLUT-4 dependent)
3. Liver - increased gluconeogenesis (liver keeps making sugar even when not needed)

• Fatty liver disease is BOTH a cause and consequence of insulin resistance
• Treatment: increase physical activity to reduce muscle insulin resistance
• Pioglitazone (thiazolidinedione) acts on GLUT-4 receptors, improves insulin sensitivity

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1.4 Gestational Diabetes

• Placental hormones (progesterone, cortisol, GH, placental lactogen) → increase insulin resistance
• Progesterone also increases aldosterone production → increases BP

• Glucose Tolerance Test (75g in non-pregnant, 100g in pregnant)
• Done at 24-28 weeks gestation
• After 2 hours: target < 7.8 mmol/L
• If 8.5 mmol/L after 2h → abnormal → repeat test

• Fasting: 5.1 mmol/L = borderline
• Fasting 5.1-5.3 = gestational diabetes
• Fasting 5.3-5.6 = also abnormal range

• First 12-14 weeks: control by diet + progesterone
• Check sugar 7 times a day
• Metformin can be used
• If < 36 weeks and need steroids → give corticosteroids (for fetal lung maturity) but they worsen glucose

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1.5 Insulin Therapy

• Total dose: 0.5 units/kg/day
• Long:Short ratio = 50:50 (e.g., 20 units long + 20 units short)
• Never start full dose - start at half dose (10:10)
• Long-acting (Glargine): 10 units morning OR evening

• 1 BU = 12g of carbohydrates
• In the morning: 1.5 units insulin per 1 BU (cortisol + GH spike in morning increases insulin requirement)
• Type 2 DM: 1 BU = 1 unit insulin
• Target blood glucose: 5-6 mmol/L fasting; ≤ 6 after meals

• If cortisol is high → increase dose
• If no food planned → decrease dose
• If increased physical activity → decrease dose

• After breakfast (dose often higher than dinner)
• Before lunch
• After lunch
• Before dinner
• After dinner (target ~6.5)

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1.6 Antidiabetic Drug Classes

① DPP-4 Inhibitors (Gliptins)

• Sitagliptin 100 mg
• Mechanism: Inhibit DPP-4 enzyme → prolong GLP-1 and GIP activity → increase insulin secretion
• Advantage: Do NOT cause hypoglycemia
• Safe in CKD (do not use if GFR < 15)
• Note: May increase risk of lymphogranulomatous disease, sarcoidosis

② Metformin (Biguanide)

• Dose: Start 500 mg, maintenance 1000 mg, max 1800-2200 mg/day
• Mechanism:
  1. Decrease hepatic gluconeogenesis
  2. Increase insulin sensitivity
  3. Decrease gut glucose absorption
• Indications: Type 2 DM, pre-diabetes, PCOS
• Advantages: No hypoglycemia (liver keeps working), no weight gain
• Contraindications: GFR < 30 (use small dose if GFR 30-45), heart failure (severe), liver cirrhosis, alcoholism
• Side effects: Lactic acidosis (rare, in hypoxic states), GI upset, B12 deficiency, anemia
• Stop Metformin 48-72 hours before and after contrast studies (risk of AKI + lactic acidosis)

③ GLP-1 Agonists

• Drugs: Liraglutide, Dulaglutide, Semaglutide, Tirzepatide (dual GLP-1/GIP agonist)
• Mechanism: Mimic GLP-1 → increase insulin secretion, decrease glucagon, slow gastric emptying, reduce appetite
• Benefits: Weight loss, reduce CV events (LEADER trial for liraglutide)
• Side effects:
  • Nausea, vomiting, diarrhea (malabsorption syndrome)
  • Pancreatitis risk
  • Gallstones (biliary stones)
  • Thyroid C-cell tumors (check calcitonin) - contraindicated in medullary thyroid cancer
  • Kidney stones
  • Depression, menstrual irregularity
  • Tachyphylaxis (drug stops working over time)
  • Skin problems
• Tirzepatide: Dual GLP-1/GIP agonist - also causes weight loss, used in DM + obesity

④ Thiazolidinediones (Glitazones)

• Pioglitazone 30 mg
• Mechanism: PPAR-γ agonist → improves insulin sensitivity in fat, muscle, liver
• Benefits: Nephroprotective, treats fatty liver disease (with Vitamin E), not just antidiabetic
• Also used in: Alopecia (hair loss), heart failure management (controversial)
• Side effects: Fluid retention (edema), risk of heart failure, bladder cancer risk, weight gain, arrythmia risk
• Combination: Glargine + Lixisenatide (insulin + GLP-1 combo pen)

⑤ Sulfonylureas

• Better options: Gliclazide, Glimepiride (newer, safer)
• Mechanism: Stimulate pancreatic beta cells to release insulin
• Risk: Hypoglycemia (most dangerous class for hypoglycemia; more dangerous than insulin in some)
• Contraindicated: GFR < 60 (Gliclazide) or GFR < 30 (Glimepiride)

⑥ SGLT-2 Inhibitors (Gliflozins)

• Drugs: Canagliflozin, Empagliflozin (Empa), Dapagliflozin (Dapa)
• Mechanism: Block SGLT-2 transporters in proximal tubule → glucose excreted in urine after meals
• Benefits:
  • Weight loss
  • Reduce CV mortality (especially Empagliflozin - EMPA-REG trial)
  • Nephroprotective (slow CKD progression)
  • Reduce HF hospitalizations
  • Can be used in Type 1 DM (off-label)
• Contraindicated: GFR < 30 (Canagliflozin), GFR < 45 (some)
• Side effects: UTI, genital mycotic infections, DKA (euglycemic DKA), polyuria
• Do NOT cause hypoglycemia (unless combined with insulin/sulfonylurea)

• Finerenone (Kerendia) - Non-steroidal mineralocorticoid antagonist, 10 mg, max dose - used in DM + CKD (GFR ≥ 25); reduces albuminuria and CV events

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1.7 Complications of Diabetes

Acute Complications:

• Dizziness, confusion (like alcohol intoxication)
• Tremors, sweating, vomiting, palpitations
• Nocturnal sweating
• Coma (if severe)
• Can mimic: TB (night sweats), hyperthyroidism (palpitations), cancer, pre-menopause

• Insulinoma (insulin-producing tumor - usually tail of pancreas)
• Sulfonylureas, insulin overdose
• Antipsychotic drugs
• Adrenal insufficiency (cortisol deficiency)
• Liver cirrhosis (liver can't do gluconeogenesis)
• Pituitary adenoma (↓ ACTH → ↓ cortisol)
• Corticosteroids > 2 weeks → don't taper → adrenal insufficiency
• Tumor (intestine/kidney/radiation-induced)
• Liver transplant complications

• Pathogenesis: Insulin deficiency → ketogenesis (β-oxidation of FFA) → ketone bodies → metabolic acidosis
• Triggers: Missed insulin, infection, surgery, pregnancy
• Symptoms: Vomiting, N/V, sweet/fruity breath (ketones), high blood glucose, dehydration
• Management: IV insulin pump + fluids + electrolytes

• No ketones (residual insulin prevents ketosis)
• Extreme hyperglycemia, severe dehydration, altered consciousness

• Causes: Hypoxia + Metformin intake; liver cirrhosis; alcohol toxicity; B12 deficiency anemia; GFR < 30 + Metformin

Chronic Complications:

• Nephropathy (diabetic kidney disease)
• Retinopathy (vision loss)
• Neuropathy (peripheral sensory loss, numbness)

• CVD (coronary artery disease)
• Stroke
• Peripheral arterial disease (PAD)
• Rhabdomyolysis

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📗 TOPIC 2: INFLAMMATORY BOWEL DISEASE (IBD) - Day 13

2.1 Ulcerative Colitis (UC) vs Crohn's Disease (CD)

1. Proctitis (rectum only)
2. Proctosigmoiditis
3. Left-sided colitis
4. Total colitis (pancolitis)

• Number of bloody stools per day
• Temperature
• Heart rate
• Hemoglobin
• ESR/CRP

• Colonoscopy + biopsy (gold standard)
• Mayo score (endoscopic severity)
• Signs on endoscopy: loss of vascular pattern, contact bleeding, superficial ulcers, pseudopolyposis, edema, hyperemia
• Irrigoscopy (barium enema X-ray)
• Capsule endoscopy (NOT done if stenosis/strictures - capsule can get stuck; capsule works for 24h)
• Deep endoscopy (long probe, under anesthesia)
• Hydro MRI (patient drinks mannitol) - good for small bowel
• CT scan

• Hemorrhoids, anal fissure
• Dysentery, Salmonella
• Ischemic colitis (vessel thrombosis)
• Diverticulitis
• Pseudomembranous colitis (C. difficile) - presents with fever
• Colorectal neoplasia
• Microscopic colitis

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2.2 IBD Treatment

• Oral Prednisolone
• Rectal: foam enemas, suppositories

• Oral Prednisolone (reduce dose as improves → stop)
• 5-ASA (mesalazine) for maintenance

• IV steroids from the start

• Azathioprine (immunosuppressant; SE: thrombocytopenia)
• Monitor IBD granule level (thiopurine metabolites)
• Prednisolone course: 12 weeks

• Vedolizumab (anti-integrin - gut specific)
• Ustekinumab (anti-IL-12/23)
• Before giving biologics: check viral hepatitis serology + TB test (Mantoux) + CXR

• Mild: Metronidazole 100 mg 4 times/day orally
• Severe: Vancomycin orally

• 70% affects ileum → risk of Vitamin B12 deficiency (ileum absorbs B12)
• If ileum affected → do genetic test for CD
• Rule out: Celiac disease, Whipple's disease
• Diagnosis of small bowel CD: Duodenoscopy + biopsy

• PSC (Primary Sclerosing Cholangitis) - intrahepatic bile ducts affected
• Erythema nodosum (skin - bluish/red nodules on legs)
• Arthritis (large joints)
• Uveitis (eye)

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📙 TOPIC 3: THYROID DISEASE - Day 23

3.1 Hypothyroidism

• Hashimoto's thyroiditis (autoimmune, antibodies against TPO - anti-TPO)
• Postpartum thyroiditis
• Atrophic thyroiditis
• Pituitary adenoma (secondary hypothyroidism, ↓ TSH)
• Iodine deficiency
• Subacute thyroiditis (after viral infection, starts with thyrotoxicosis → then hypothyroidism)
• Drugs: Amiodarone, Interferon, Lithium, PTU, Methimazole, Tyrosine kinase inhibitors
• Riedel's thyroiditis
• Sarcoidosis, amyloidosis, hemochromatosis

• Accumulation of GAGs (glycosaminoglycans) + hyaluronic acid in tissues → attract water → myxedema (non-pitting edema)
• Diuretics do NOT work in myxedema

• ↓ LDL clearance from blood (liver receptors reduced)
• ↓ Lipoprotein lipase activity
• ↓ Cholesterol breakdown
• ↓ Hepatic metabolism of lipids
• ↓ Fat metabolism overall

• TSH ↑ (primary hypothyroid)
• T3/T4 ↓
• ↑ Cholesterol
• Anemia

• Dose: 1.6 mcg/kg/day (calculate according to weight)
• Start LOW especially in elderly, cardiac patients
• Example: Patient with cardiomyopathy, EF = 15%, atrial fibrillation/ventricular tachycardia → start 6.25 mcg, check after 1 week → increase to 12.5 mcg → titrate up
• If patient given 50 mcg wrongly → drug-induced thyrotoxicosis → stop L-thyroxine → level drops to subclinical hypothyroidism

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3.2 Thyrotoxicosis (Hyperthyroidism)

• Cardiovascular: Tachycardia, paroxysmal AF, palpitations
• Neurological: Tremor, insomnia, anxiety, mood swings, emotional lability
• GI: Belly pain, diarrhea, spastic pains
• Eyes: Exophthalmos, proptosis, dry eyes, vision problems (ophthalmopathy)
• Musculoskeletal: Muscle weakness, myopathy
• Other: Weight loss despite normal appetite, hyperhidrosis

• Atrial fibrillation (Afib) - most common cardiac complication
• Dyshormohal cardiomyopathy, heart failure (hypertrophy of LV walls)
• Thyroid storm (crisis) - can occur after contrast iodine injection (e.g., post coronary angiography)
• HTN (Grade 2)
• Osteoporosis (long-standing thyrotoxicosis)
• Paralysis
• Ophthalmopathy: Proptosis, exophthalmos, retroorbital tissue hyperplasia
• Seizures (low K+)
• Gynecological problems (menstrual irregularity)

• TSH: 2.5 mIU/L
• Start L-thyroxine if: antibody positive + TSH elevated + symptoms

• Methimazole / Carbimazole - total 18 months to 2 years of treatment
• Side effects: Agranulocytosis (if fever → check WBC), anemia, hepatitis
• After treatment: check thyroid size
• Subclinical thyrotoxicosis from subacute thyroiditis: starts with thyrotoxicosis → use NSAIDS first, then Prednisolone if needed

• Start iodine supplements
• If want to get pregnant → give thyroxine even with iodine supplement
• Selenium + Zinc: reduce nodule size, reduce anti-TPO antibodies, reduce thyroid size

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📒 TOPIC 4: CKD (Chronic Kidney Disease) - Day 28

4.1 Why Males Have Higher Risk of CKD

• Men have FEWER nephrons than women to begin with
• Women: lose nephrons after age 20 progressively
• Boys have higher UTI risk after age 11
• Male risk factors: smoking, alcohol, drugs

4.2 Causes / Risk Factors for AKI and CKD Progression

• NSAIDs (nephrotoxic)
• Aminoglycosides (gentamicin)
• Cyclosporine, Antivirals (Tenofovir), Chemotherapy (Cisplatin)
• PPI long-term use
• Radiocontrast agents (toxic → stop Metformin 48-72h before and after contrast)
• Gadolinium (MRI contrast) - toxic in CKD; use only if GFR > 30
• Thiazide diuretics can cause dehydration → AKI
• Uncontrolled DM, uncontrolled HTN, elderly age

4.3 Definition of CKD

• GFR < 60 mL/min for > 3 months, AND/OR
• Albumin/creatinine ratio elevated (albuminuria) even if GFR is normal

4.4 Functions of the Kidney

1. Osmoregulation (water balance)
2. Electrolyte regulation (Na, K, Ca, Phosphate)
3. Filtration (1801 L/day through 25 km of capillaries)
4. Blood pressure regulation (renin, prostaglandins)
5. Erythropoiesis (EPO production) → anemia if CKD
6. Phosphorus-Calcium metabolism
7. Vitamin D activation (1-alpha hydroxylation in kidney → active calcitriol)
8. Fibrinolysis (urokinase, tPA - alteplase given in STEMI)

4.5 CKD Mineral Bone Disease (Vitamin D Pathway)

1. Kidney disease → cannot produce 1-alpha hydroxylase
2. → Cannot convert 25-OH Vitamin D → active 1,25-OH2 Vitamin D
3. → ↓ Ca2+ absorption from gut
4. → ↓ Ca2+ stimulates ↑ PTH (parathyroid hormone) - secondary hyperparathyroidism
5. PTH tries to raise calcium:
   • Pulls Ca2+ from bones → osteoporosis
   • Stimulates phosphate excretion from kidney (but kidney already damaged)
   • → ↑ Phosphate accumulates

• Vitamin D supplements (50,000 IU / 12 weeks) → suppress PTH
• Active Vitamin D (Paricalcitol) = VDR activator; used if GFR < 30
• Phosphate binders (sevelamer) - months to start working; give before meals; check ALP when giving (bone disorder marker)
• Eladetinib (new agent)
• Cinacalcet (calcimimetic) → activates calcium-sensing receptors → suppresses PTH
• Denosumab (if GFR < 30; for osteoporosis)
• Bisphosphonates - contraindicated if GFR < 30

4.6 Anemia of CKD

1. ↓ EPO production by kidney → ↓ RBC production
2. ↑ Hepcidin (acute phase reactant) → traps iron in macrophages → iron-restricted erythropoiesis
3. ↓ Ferroportin → iron cannot exit macrophages
4. ↑ Cytokines (chronic inflammation) → suppress bone marrow

• EPO analogues / ESAs (Erythropoiesis-stimulating agents) - if patient agrees
• Roxadustat (HIF-PH inhibitor) - oral, 2x/week; alternative to EPO injections
• Iron: only if transferrin saturation is low (don't give iron if normochromic ACD without iron deficiency)

4.7 HTN in CKD Treatment

1. RAAS blockade (ACE inhibitor or ARB):
   • If GFR > 15: Telmisartan (ARB - Valsartan is stronger than Losartan)
   • If GFR < 30: be cautious
   • Sacubitril/Valsartan (Neprilysin inhibitor): used in uncontrolled HTN + HF
2. Loop diuretics (GFR < 30)
3. Cardioselective beta-blockers: Carvedilol, Metoprolol (NOT non-selective; avoid non-selective)
4. Spironolactone / Eplerenone / Finerenone - for resistant HTN (caution with K+)
5. Moxonidine 0.3 mg - central alpha-2 agonist; used in last-stage resistant HTN

• Spironolactone, Eplerenone, Finerenone
• ACE inhibitors / ARBs
• Non-selective beta-blockers
• NSAIDs
• Statins (via rhabdomyolysis → cell damage → K+ release)
• ATT (anti-tuberculosis therapy)
• Anti-cancer drugs

• Stop the offending drug if possible
• Diuretics
• Calcium gluconate (IV for cardiac protection - K+ > 6.5-7)
• Patiromer (potassium binder)
• Polystyrene sulphonate (K+ binder)

4.8 Dyslipidemia in CKD

• LDL < 1.8 mmol/L (< 1.2 mmol/L in dialysis)
• TG < 1.7 mmol/L
• HbA1c < 7%

• Fenofibrate: if GFR > 60 (for TG)
• Rosuvastatin 10-20 mg: safe in CKD; before/after dialysis, with meals
• PCSK9 inhibitors (Inclisiran): most potent LDL-lowering option
• Ezetimibe: before/after dialysis

4.9 CKD Diet

• Protein restriction: 0.8 g/kg/day (but not < 0.6/kg - risk of sarcopenia)
• ↓ Sodium (not just ↓ salt)
• Vegetarian diet: creatinine comes out low (vegetarians have less muscle mass) → use Cystatin C for GFR if creatinine is unreliable

4.10 Indications for Dialysis

4.11 Urine Analysis Interpretation (from the lab notes)

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📔 TOPIC 5: HEPATOBILIARY SYSTEM - Day 14

5.1 Chronic Cholecystitis & Biliary Dyskinesia

1. Functional disorder (Biliary dyskinesia): Abnormal motility, contraction, sphincter of Oddi spasm
2. Non-calcular cholecystitis: Inflammation without gallstones

• Biliary pain in right hypochondrium (radiates to right shoulder, back)
• Belt-like pain
• Bitter taste, bloating
• Dyspeptic syndrome (nausea, more epigastric → need to differentiate from cardiac pain)
• Severe episodic pain if stone stuck in GB neck

• Cardiac: pressing, retrosternal, NOT relieved by Nitroglycerin... wait - actually GB pain is NOT relieved by Nitroglycerin (cardiac pain IS relieved by nitro)

• USG: wall thickness > 4-5 mm, dense bile/sludge, polyps
• USG after fatty food (yoghurt/fatty meal) → check GB contraction
• Biliary scintigraphy (IV contrast + fatty food) → assess bile flow
• MRCP / ERCP (for bile duct stones/strictures)

1. Mechanical/Obstructive: All LFTs elevated, ↑ ALP, itching; caused by tumor of pancreas, stone
2. Hemolytic: Indirect bilirubin elevated; reticulocytes high; haemolytic anemia
3. Hepatic: Viral hepatitis, any etiology; ↑ transaminases

5.2 Metabolic Syndrome + Fatty Liver

• Obesity (BMI > 30, or visceral obesity)
• Glucose intolerance / DM
• Dyslipidemia
• HTN (≥ 130/80)

• Grade 1: ALT elevated < 5x normal (Degree 1: mild steatosis)
• Progresses to steatohepatitis → cirrhosis

• Pioglitazone + Vitamin E (improves histology)
• UDCA (ursodeoxycholic acid) - dissolves cholesterol stones, protects liver, 3 months then recheck USG
• Dietary changes + healthy lifestyle + exercise
• Atorvastatin 80 mg (if bad cholesterol / LDL high)
• Hepatoprotectors:
  • Ademetionine (Heptral): 800 mg IV; good for alcoholic hepatitis; also oral 1-2 months
  • Used for cytolytic syndrome (high ALT/AST)
• Antibiotics (if bacterial exacerbation):
  • Mild: Metronidazole (no major side effects)
  • Strong: Ciprofloxacin 500 mg, OR Ceftriaxone (7 days)
  • Intestinal antiseptic (e.g., Rifaximin) for dysbiosis
• Prokinetics: Trimebutine (also helps biliary motility - 2-3 times/day)
• Hemochromatosis (iron overload): improves sphincter of Oddi function; improves bile flow; improves pancreatic flow

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📕 TOPIC 6: HEMATOLOGY - Day 17 (Lab Interpretation)

6.1 Hepatic Syndromes (Lab-based)

6.2 CBC Interpretation & Blood Disorders

• RBC: 4.5-5.5 (men), 4-5 (women) x10¹²/L
• Hb: 130-175 (men), 120-155 (women) g/L
• Color Index (CI): 0.85-1.05
• Reticulocytes: 1-2% (regenerative marker)
• Platelets: 150-400 x10⁹/L
• WBC: 4-9 x10⁹/L

• Stage I: Hb 90-120 (women) / 100-130 (men) - mild
• Stage II: Hb 70-90 - moderate
• Stage III: Hb < 70 - severe

• WBC +++, RBC casts, bacteria +++, mucus +++, cloudy urine

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🔬 CLINICAL CASES DISCUSSED IN NOTES

Case 1 (Page 12) - 42-year-old Track Driver

• Complaints: 2 months fatigue, episodes of loss of consciousness, cramping leg pain, flank pain, poor eating (gastric), going to work, blurry vision, UTI 7 days, on PPI 1 month, NSAIDs for cramps
• Examination: BP 130/90, weight 95 kg, waist 105 cm, HR 80, liver enlarged (4 cm)
• Likely diagnoses:
  • Type 2 DM (polyuria, polydipsia, hyperglycemia signs)
  • Stage 1 HTN
  • Obesity (BMI > 30)
  • Fatty liver disease
  • Peripheral arterial disease (leg pain, vascular examination needed)
  • COPD (smoker, 1 pack/day, 40 years)
  • Polyneuropathy (loss of sensation)
  • Dyspeptic syndrome
• Investigations needed: Blood glucose, HbA1c, TSH, biochemistry (Sr.Cr, AST, ALT, GGT), CBC, urinalysis, Vitamin B12, ECG

Case 2 - Thyroid Cardiomyopathy

• Ejection fraction 15%, cardiomyopathy
• Started on 6.25 mcg L-thyroxine very cautiously due to severe cardiac compromise
• Private clinic had wrongly given 50 mcg → drug-induced thyrotoxicosis → stop → revert to subclinical hypothyroid level

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🩺 PRACTICAL EXAMINATION SKILLS (from Yulia Ma'am - Day 22)

Percussion of Lungs

• Comparative percussion: both sides, 3 times, start from right side
• Zigzag pattern: upper clavicle → on clavicle → 3rd intercostal space → zigzag paravertebral
• Sounds: Resonance (normal lung), Dullness (consolidation, pleural effusion, liver), Tympanic (hollow/air-filled organs)
• Emphysema: Hyperresonance (large thorax, barrel chest)
• Pleural effusion, abscess: Dull sound

Vocal Fremitus (Voice Vibration)

• Patient says "33" (in Russian) while you feel vibration on chest wall
• Pneumonia: ↑ vibration
• Abscess: ↓ vibration (initially), then ↑ when draining
• Bronchus open: ↑ vibration

Cardiac Borders Percussion

• Rt border: Mid-clavicular line (move from lung → dullness = cardiac border)
• Left border: 5th ICS - 2 cm from mid-clavicular line
• Upper border: 3rd ICS, parasternal line
• Parasternally from above/below

Cardiac Auscultation

• Apex (Mitral Valve): 5th ICS, mid-clavicular
• 2nd ICS R (Aortic)
• 2nd ICS L (Pulmonary)
• 4th ICS L (Tricuspid) - Erb's point
• Young people: may have functional murmur (due to connective tissue dysplasia → extra myofibrils, trabeculation)
• Not serious - functional

Pulse Examination

• Check both hands (important for coarctation of aorta, AVblock)
• AF: irregular pulse
• Pulse deficit: AF - difference between apical and radial pulse
• Extrasystole: extra contraction
• Character: regularity, amplitude, shape

BP Measurement

• Cuff above elbow, 2-finger loose placement
• Hand position: palm up, at heart level
• Also in popliteal fossa (leg BP)

Liver Palpation (Kurlov's Method)

• Start from mid-clavicular line
• Find lower border of liver by percussion from umbilicus going up
• Kurlov lines: 10-9-8 cm (normal)
• Palpate during inspiration (hand supports from back)

Gallbladder Points

• Murphy's sign: Inspire + palpate right hypochondrium → pain on inspiration = positive
• McKenzie point: GB intersection with right hypochondrium
• Boas point: 10th-11th vertebrae left (posterior)
• Mayo-Robson point: Pancreatic tail (intersection of spinal cord and 2nd rib at back)

Abdomen

• Superficial palpation: rigidity, tension, pain, mass, hernias
• Compare 9 points: Start from flank
• Go from your right side, cycle around: hypochondrium R → epigastrium → hypochondrium L → etc.

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✅ Summary Table: Key Drug Reminders from Notes

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