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Atherosclerosis - Complete Pathology for MBBS

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1. Definition & Overview

• A soft, friable lipid core (mainly cholesterol, cholesterol esters, necrotic debris)
• Covered by a fibrous cap

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2. Risk Factors

Non-Modifiable (Constitutional)

Modifiable (Major)

Additional Risk Factors

• Inflammation / CRP - CRP is a strong independent marker of risk for MI, stroke, and sudden cardiac death (even in apparently healthy people). CRP levels fall with statins, exercise, and weight loss.
• Hyperhomocysteinemia - Correlates with coronary, peripheral, and cerebrovascular disease
• Metabolic syndrome - Central obesity + insulin resistance + hypertension + dyslipidemia + hypercoagulability
• Lipoprotein(a) [Lp(a)] - Elevated levels independently raise coronary and cerebrovascular risk
• Hemostatic factors - Elevated plasminogen activator inhibitor-1 (PAI-1) predicts MI and stroke

Note: ~20% of cardiovascular events occur in people with none of the classic major risk factors. More than 75% of cardiovascular events in previously healthy females occur with LDL < 160 mg/dL.

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3. Pathogenesis - "Response to Injury" Hypothesis

Step-by-Step Sequence:

Step 1 - Endothelial Injury & Dysfunction

• Endothelial cell (EC) injury is the cornerstone of atherosclerosis
• Early lesions begin at sites of intact but dysfunctional endothelium
• "Dysfunction" = defective vascular tone, impaired barrier function, reduced hemostatic regulation, and enhanced inflammation
• Two most important causes of EC dysfunction:
  1. Hemodynamic disturbances - Turbulent blood flow at ostia, branch points, and posterior abdominal aorta preferentially induces EC injury. Non-turbulent laminar flow induces "atheroprotective" genes - explaining why plaques form at specific anatomical sites
  2. Hypercholesterolemia - Chronic hyperlipidemia directly impairs ECs by increasing reactive oxygen species (ROS), which accelerate nitric oxide (NO) decay, dampening vasodilator activity
• Other triggers: inflammatory cytokines (TNF-α), cigarette smoke toxins, hypertension, immune reactions

Step 2 - Lipoprotein Accumulation & Oxidation

• With chronic hyperlipidemia, LDL enters and accumulates in the intima
• Oxidized LDL (ox-LDL) forms when LDL is oxidized by free radicals from inflammatory cells - this is particularly dangerous:
  • Ox-LDL is toxic to ECs, SMCs, and macrophages
  • It is taken up by macrophages via scavenger receptors (not the normal LDL receptor) - leading to foam cell formation since it cannot be degraded
  • Stimulates release of growth factors, cytokines, and chemokines
  • Recruits more monocytes - creating a vicious cycle

Step 3 - Monocyte Recruitment & Macrophage Activation

• Dysfunctional ECs express adhesion molecules (VCAM-1, ICAM-1, E-selectin) that capture monocytes and T lymphocytes from blood
• Monocytes migrate into the intima via chemokines (e.g., MCP-1) and differentiate into macrophages
• Macrophages engulf oxidized LDL via scavenger receptors → transform into foam cells (lipid-laden macrophages)
• Macrophages also sense cholesterol crystals and free fatty acids via the inflammasome → produce IL-1 → activates ECs, recruits more mononuclear cells
• Activated macrophages produce: ROS (enhance LDL oxidation), growth factors (drive SMC proliferation), and proteases (break down ECM)

Step 4 - Platelet Adhesion

• Exposed intimal components trigger platelet adhesion and activation
• Activated platelets release platelet-derived growth factor (PDGF) and other cytokines

Step 5 - T-Cell Recruitment & Inflammatory Amplification

• T lymphocytes enter the intima and release interferon-γ (IFN-γ) which:
  • Activates macrophages further
  • Activates ECs and SMCs
  • Promotes inflammation (contributing to plaque instability)

Step 6 - Smooth Muscle Cell (SMC) Proliferation & Matrix Synthesis

• Growth factors (PDGF from platelets/macrophages, FGF, TGF-β) recruit SMCs from the media into the intima (phenotypic switch: contractile → synthetic)
• Intimal SMCs proliferate and synthesize ECM (especially collagen) - converting the fatty streak into a mature atheroma
• Collagen deposition forms and stabilizes the fibrous cap
• However, activated macrophages can also induce SMC apoptosis and ECM breakdown → unstable plaques

Step 7 - Lipid Accumulation (Extracellular)

• As foam cells die, lipids spill into the extracellular space → necrotic lipid core forms
• Cholesterol crystals become incorporated into the plaque

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4. Morphology (Lesion Types)

Stage 1 - Fatty Streak (Earliest Lesion)

• Gross: Minute, flat, yellow macules that coalesce into elongated lesions ≥1 cm long
• Microscopy: Intimal lipid-filled foam cells (macrophage-derived) - no significant flow disturbance
• Age: Can appear in the aorta of infants <1 year old; present in virtually ALL children >10 years, regardless of risk factors
• Significance: Not all progress to plaques - but coronary fatty streaks form during adolescence at the same sites that develop plaques later in life

Stage 2 - Atherosclerotic Plaque (Atheromatous Plaque / Fibrous Plaque)

• Gross: White to yellow raised lesions, 0.3-1.5 cm in diameter (may coalesce); eccentric (involves only part of the vessel wall)
• Microscopy: Three key components:
  1. Fibrous cap - Smooth muscle cells, collagen (dense), proteoglycans, elastin; relatively few inflammatory cells
  2. Cellular zone (shoulder region) - Active area with macrophages, foam cells, T lymphocytes, SMCs; most prone to rupture
  3. Necrotic lipid core - Extracellular lipids, cholesterol crystals, necrotic debris, calcification; no collagen

Distribution of Plaques (Descending Frequency):

1. Infrarenal abdominal aorta (most common/severe)
2. Coronary arteries
3. Popliteal arteries
4. Internal carotid arteries
5. Circle of Willis

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5. Stable vs. Vulnerable (Unstable) Plaque

• Macrophage-derived metalloproteinases (MMPs) that digest collagen in the fibrous cap
• T cell IFN-γ inhibiting collagen synthesis by SMCs
• SMC apoptosis from inflammatory signals

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6. Consequences of Atherosclerosis / Acute Plaque Change

1. Plaque Rupture / Erosion / Ulceration

• Exposes highly thrombogenic subendothelial components and lipid core
• Triggers thrombus formation - can cause acute coronary syndrome (unstable angina, STEMI, NSTEMI)
• Most ruptures occur at the shoulder region of the plaque (highest inflammatory cell density, thinnest fibrous cap)

2. Hemorrhage into Plaque

• Rupture of overlying fibrous cap or thin-walled neovessels within the plaque
• Sudden expansion of plaque volume → acute luminal narrowing

3. Atheroembolism

• Plaque rupture can discharge atherosclerotic debris (cholesterol crystals, etc.) into the bloodstream
• Causes microemboli downstream (e.g., "blue toe syndrome")

4. Aneurysm Formation

• Atherosclerosis-induced ischemia of the underlying media with loss of elastic tissue → wall weakening → aneurysmal dilation and rupture
• Most common: infrarenal abdominal aortic aneurysm (AAA)

Atherosclerotic Stenosis (Chronic)

• Critical stenosis: ~70% occlusion is the tipping point in coronary arteries
• At rest: adequate perfusion; with exertion: demand exceeds supply → stable angina
• Chronic arterial hypoperfusion causes: bowel ischemia, chronic IHD, ischemic encephalopathy, intermittent claudication

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7. Major Clinical Consequences

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8. Key High-Yield Points for MBBS Exams

• Response to injury hypothesis (Ross) = the core concept - endothelial injury is the initiating event
• Foam cells = lipid-laden macrophages (and SMCs) formed via scavenger receptor uptake of ox-LDL
• Fatty streak = earliest visible lesion; present in virtually all children >10 years; does NOT obstruct flow
• Fibrous cap = collagen + SMCs; protects against plaque rupture
• Vulnerable plaque = thin cap, large lipid core, heavy inflammation - responsible for ACS
• Most severe atherosclerosis = infrarenal abdominal aorta > coronary > popliteal > internal carotid
• Critical stenosis = 70% in coronary arteries = stable angina threshold
• CRP = strong independent inflammatory marker of cardiovascular risk (not causative)
• Hyperhomocysteinemia - additional risk factor (caused by vit B12/B6/folate deficiency or inborn errors)
• Diabetes = 100-fold increased risk of lower limb gangrene

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Summary Diagram of Pathogenesis (Memorization Framework)

Endothelial Injury (hyperlipidemia, HTN, smoking, turbulence)
        ↓
Endothelial Dysfunction (↑ permeability, ↑ leukocyte adhesion)
        ↓
LDL enters intima → Oxidized LDL (ox-LDL)
        ↓
Monocytes adhere (VCAM-1) → migrate → Macrophages
        ↓
Macrophages engulf ox-LDL via scavenger receptors → FOAM CELLS → FATTY STREAK
        ↓
Platelet adhesion → PDGF released
Macrophages → IL-1, TNF-α, ROS, MMPs
T cells → IFN-γ
        ↓
SMC migration (media → intima) + proliferation + collagen synthesis
        ↓
Fibrous cap forms over lipid core → ATHEROSCLEROTIC PLAQUE
        ↓
Plaque growth → stenosis OR plaque rupture → THROMBOSIS → ACS/Stroke

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Antihypertensive Drugs - Complete Pharmacology for MBBS

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Understanding Blood Pressure First

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Sites of Drug Action - The Big Picture

1. Brain (vasomotor center) - centrally acting drugs
2. Heart - beta blockers
3. Blood vessels - CCBs, alpha blockers, vasodilators, ARBs
4. Kidney - diuretics, beta blockers (↓renin), ACE inhibitors, ARBs

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Classification of Antihypertensive Drugs

ANTIHYPERTENSIVE DRUGS
│
├── 1. DIURETICS
│       ├── Thiazides: Hydrochlorothiazide, Chlorthalidone, Indapamide
│       ├── Loop: Furosemide, Bumetanide, Torsemide
│       └── K⁺-sparing: Spironolactone, Eplerenone, Amiloride, Triamterene
│
├── 2. RENIN-ANGIOTENSIN SYSTEM (RAS) BLOCKERS
│       ├── ACE Inhibitors: Captopril, Enalapril, Lisinopril, Ramipril
│       ├── ARBs: Losartan, Valsartan, Olmesartan, Telmisartan
│       └── Direct Renin Inhibitor: Aliskiren
│
├── 3. CALCIUM CHANNEL BLOCKERS (CCBs)
│       ├── Dihydropyridines (vasodilators): Amlodipine, Nifedipine, Felodipine
│       └── Non-dihydropyridines (cardiac): Verapamil, Diltiazem
│
├── 4. SYMPATHOPLEGIC AGENTS
│       ├── Beta-blockers: Propranolol, Atenolol, Metoprolol, Carvedilol
│       ├── Alpha-1 blockers: Prazosin, Doxazosin, Terazosin
│       ├── Alpha + Beta blockers: Carvedilol, Labetalol
│       └── Central acting: Methyldopa, Clonidine
│
└── 5. DIRECT VASODILATORS
        ├── Oral: Hydralazine, Minoxidil
        └── Parenteral: Sodium Nitroprusside, Diazoxide, Fenoldopam

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CLASS 1: DIURETICS

How They Work

• Initial (first 6-8 weeks): Reduce blood volume and cardiac output → ↓ BP. Peripheral vascular resistance may actually go up initially.
• Long-term: Cardiac output returns toward normal but peripheral vascular resistance falls - this is the sustained mechanism.

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A. Thiazide Diuretics

Memory trick: Thiazides cause "GLUD" - Glucose up, Lipids up, Uric acid up, potassium Down. But calcium goes UP (opposite of loop diuretics).

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B. Loop Diuretics

• Renal insufficiency (GFR < 30-40 mL/min) - thiazides don't work well
• Severe hypertension with multiple sodium-retaining drugs
• Pulmonary edema, cardiac failure, cirrhosis

• Short duration → only once-daily → rebound sodium retention (baroreceptor activation of RAS offsets the diuresis)
• Must be given twice daily; then become too aggressive

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C. Potassium-Sparing Diuretics

• Mechanism: Block mineralocorticoid receptors in the collecting duct → block aldosterone-driven Na⁺ reabsorption / K⁺ secretion
• Use: Resistant hypertension (add-on), heart failure, primary hyperaldosteronism
• Side effects: Hyperkalemia; spironolactone causes gynecomastia (steroidal structure); eplerenone is more selective and avoids this

• Mechanism: Directly block epithelial Na⁺ channels (ENaC) in collecting duct
• Use: Usually combined with thiazides to prevent K⁺ loss; rarely used alone
• Liddle syndrome (genetic ENaC overactivity) responds specifically to amiloride

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CLASS 2: RAS BLOCKERS

Angiotensinogen
     ↓ (Renin - from kidney JG cells)
Angiotensin I (inactive decapeptide)
     ↓ (ACE / Kininase II - in lung endothelium)
Angiotensin II (active octapeptide)
     ↓ acts on AT₁ receptors
→ Vasoconstriction (↑ TPR)
→ Aldosterone release (↑ Na retention → ↑ volume → ↑ BP)
→ ADH release
→ Sympathetic activation

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A. ACE Inhibitors (ACEIs)

1. Blocks conversion of Ang I → Ang II → ↓ vasoconstriction + ↓ aldosterone → ↓ BP
2. Prevents breakdown of bradykinin → bradykinin accumulates → vasodilation (via NO, prostacyclin)

• Diabetic nephropathy: Reduce intraglomerular pressure (dilate efferent arteriole) → reduce proteinuria → protect kidneys
• Heart failure + post-MI: Reduce afterload, prevent cardiac remodeling
• Reduce incidence of new-onset diabetes

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B. Angiotensin Receptor Blockers (ARBs)

Do NOT combine ACEIs + ARBs (dual RAS blockade) - dangerous: risk of acute renal failure, hyperkalemia, hypotension; no additional BP benefit.

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C. Direct Renin Inhibitor

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CLASS 3: CALCIUM CHANNEL BLOCKERS (CCBs)

Two Subgroups - Very Different Clinical Profiles:

• Amlodipine is the most widely used DHP - very long half-life (35-50 hrs), smooth BP control, once daily, well tolerated
• Nifedipine short-acting - should NOT be used for chronic HTN (rapid BP fall → reflex tachycardia → ischemia); only sustained-release forms acceptable
• Verapamil - greatest cardiac depressant; can cause AV block, bradycardia, constipation

• Verapamil/Diltiazem: Heart failure with reduced EF, 2nd/3rd degree AV block, sick sinus syndrome
• Verapamil + beta-blockers: Dangerous combination (additive cardiac depression → heart block)

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CLASS 4: SYMPATHOPLEGIC AGENTS

A. Beta-Blockers (β-Blockers)

• Non-selective: Propranolol (β₁ + β₂), Carvedilol (α₁ + β₁ + β₂), Labetalol (α₁ + β)
• Cardioselective (β₁ preferential): Atenolol, Metoprolol, Bisoprolol

1. ↓ Cardiac output - block β₁ receptors in heart → ↓ heart rate + ↓ contractility
2. ↓ Renin secretion - block β₁ receptors on juxtaglomerular cells → ↓ renin → ↓ Ang II → ↓ aldosterone
3. Central effect - reduce sympathetic outflow from vasomotor center
4. Presynaptic β₂ block - reduce norepinephrine release

• HTN with post-MI: Excellent (reduce mortality)
• HTN with heart failure: Carvedilol, Bisoprolol, Metoprolol
• HTN with angina: Beta-blockers are first-line
• HTN with atrial fibrillation (rate control): Yes
• HTN with aortic aneurysm: Beta-blockers specifically

Current guidelines suggest restricting beta-blockers to patients with compelling indications (heart failure, post-MI, angina, AF) rather than using them as first-line for uncomplicated HTN.

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B. Alpha-1 Blockers

• First-dose phenomenon: Severe postural hypotension after first dose (especially prazosin) - give at bedtime, start low
• Reflex tachycardia
• Sodium and water retention
• Dizziness, nasal stuffiness

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C. Centrally Acting Agents

• Clonidine: Stimulates α₂ receptors in the brainstem vasomotor center → ↓ sympathetic outflow → ↓ heart rate + ↓ BP
• Methyldopa: Converted to α-methylnorepinephrine in the brain → acts as α₂ agonist (same mechanism)

• Sedation, dry mouth (clonidine - most common)
• Rebound hypertension with abrupt withdrawal of clonidine (catecholamine surge) - must taper slowly
• Methyldopa: Drug of choice in pregnancy (proven safety); also causes hemolytic anemia, positive Coombs test, hepatotoxicity, lupus-like syndrome

• HTN emergencies (oral/transdermal)
• Opioid/nicotine/alcohol withdrawal
• ADHD, menopausal flushing

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CLASS 5: DIRECT VASODILATORS

A. Hydralazine

• Severe/resistant hypertension (combined with beta-blocker + diuretic)
• Hypertensive urgency in pregnancy (IV hydralazine is preferred for preeclampsia)
• Heart failure combined with nitrates (BiDil) in patients who cannot tolerate ACEIs/ARBs (especially in Black patients)

• Headache, nausea, flushing, palpitations, tachycardia
• Drug-induced lupus syndrome: At doses ≥400 mg/day; arthralgia, myalgia, rash, fever. No renal damage (unlike true lupus); reverses on stopping drug. More common in slow acetylators.
• Peripheral neuropathy (treat with pyridoxine)
• Reflex tachycardia + angina in patients with coronary artery disease

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B. Minoxidil

• Severe reflex tachycardia, palpitations, angina
• Severe fluid retention, edema
• Hypertrichosis (hair growth on face/body) - problematic especially in women; paradoxically used topically as "Rogaine" for baldness treatment

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C. Sodium Nitroprusside (Parenteral)

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Drug Selection Based on Compelling Indications

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Combination Therapy - Why and What Works Together

• Vasodilators → reflex tachycardia + sodium retention
• Adding a beta-blocker blocks tachycardia; adding a diuretic blocks sodium retention
• All three drugs then work synergistically

• ACEI/ARB + CCB - Excellent (NICE guidelines first choice in most patients): additive vasodilation, CCB-induced edema reduced by ACEI
• ACEI/ARB + Thiazide - Very effective; diuretic activates RAS → more substrate for ACEI to block
• CCB + Thiazide - Complementary mechanisms
• ACE + ARB - Avoid (dual RAS blockade: renal failure, hyperkalemia)
• Beta-blocker + Verapamil/Diltiazem - Avoid (severe bradycardia/AV block)
• Beta-blocker + Alpha-blocker - Avoid (Labetalol/Carvedilol already combine both)

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Hypertensive Emergencies (Quick Reference)

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Summary Memory Framework

BP = CO × TPR

DIURETICS          → ↓ volume → ↓ CO (initial), then ↓ TPR
BETA-BLOCKERS      → ↓ HR and contractility → ↓ CO; + ↓ renin → ↓ Ang II → ↓ TPR
CCBs               → ↓ TPR (DHPs) or ↓ CO + ↓ TPR (non-DHPs)
ACEIs/ARBs         → ↓ Ang II effects → ↓ TPR + ↓ volume (↓ aldosterone)
ALPHA-BLOCKERS     → block NE → ↓ TPR
CENTRAL DRUGS      → ↓ sympathetic outflow → ↓ CO + ↓ TPR
VASODILATORS       → direct ↓ TPR (but cause reflex ↑ CO - need combination)

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High-Yield Exam Points

• ACEIs cause dry cough due to bradykinin; switch to ARB if intolerable
• ACEIs/ARBs are teratogenic - absolutely contraindicated in pregnancy
• Methyldopa = drug of choice in pregnancy
• Thiazides retain calcium (opposite of loop diuretics which waste calcium)
• Clonidine rebound - never stop abruptly; causes sympathetic storm
• Hydralazine slow acetylators → lupus-like syndrome at lower doses
• Minoxidil must be given with beta-blocker + diuretic
• Nitroprusside → cyanide toxicity → treat with sodium thiosulfate
• Beta-blocker first in pheochromocytoma = contraindicated (give alpha-blocker first, always)
• Losartan is uricosuric (useful when patient has both HTN and gout)
• Spironolactone causes gynecomastia (steroid structure) → use eplerenone if this is an issue
• Verapamil + beta-blocker = dangerous combination (severe AV block)
• Bilateral RAS = ACEIs/ARBs contraindicated (GFR depends on Ang II to maintain efferent arteriolar tone)
• Amlodipine = longest acting DHP CCB; preferred in most stable hypertensives

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Antihypertensive Drugs - High-Yield MBBS Summary

The Core Formula

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Classification at a Glance

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Drug-by-Drug: Mechanism + Key Points

1. Thiazide Diuretics (HCTZ, Chlorthalidone)

• MOA: Block Na⁺/Cl⁻ transporter in distal convoluted tubule → ↓ volume → ↓ BP
• Side effects (remember "GLUD + HH"):
  • Glucose↑ (hyperglycemia)
  • Lipids↑ (hyperlipidemia)
  • Uric acid↑ (hyperuricemia → gout)
  • K (potassium) ↓ (hypokalemia)
  • Hypercalcemia (thiazides RETAIN calcium - opposite of loop diuretics)
  • Hyponatremia (can be severe)
• Use: First-line for mild-moderate uncomplicated HTN

2. Loop Diuretics (Furosemide)

• MOA: Block Na⁺/K⁺/2Cl⁻ in loop of Henle
• Use: HTN with renal failure (GFR < 30), heart failure, pulmonary edema
• Side effects: Hypokalemia, hypocalcemia (LOSES calcium - opposite of thiazides), ototoxicity
• Less preferred for HTN alone (short acting → rebound Na retention)

3. Spironolactone / Eplerenone

• MOA: Aldosterone receptor antagonist → blocks Na retention, K loss
• Use: Resistant HTN (4th drug add-on), heart failure, primary hyperaldosteronism
• Side effect: Hyperkalemia; spironolactone → gynecomastia (use eplerenone to avoid this)

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4. ACE Inhibitors

• MOA: Block ACE → ↓ Ang II (↓ vasoconstriction, ↓ aldosterone) + ↑ bradykinin (vasodilation)
• Benefits beyond BP:
  • Renal protection in diabetics (↓ proteinuria)
  • Heart failure, post-MI (↓ remodeling)
• Side effects - HIGH YIELD:

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5. ARBs (Losartan, Valsartan)

• MOA: Block AT₁ receptors directly; Ang II forms but can't act
• Key advantage over ACEIs: No cough, no angioedema (no bradykinin effect)
• Same indications and contraindications as ACEIs
• Do NOT combine ACEI + ARB - dual RAS blockade causes renal failure + hyperkalemia
• Losartan bonus: uricosuric → useful in HTN + gout

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6. Calcium Channel Blockers (CCBs)

• Amlodipine = most preferred DHP (long half-life, once daily, smooth BP control)
• Short-acting nifedipine = AVOID in chronic HTN (reflex tachycardia → ischemia)
• Verapamil + Beta-blocker = DANGEROUS (severe bradycardia/AV block - never combine)

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7. Beta-Blockers

1. Block β₁ in heart → ↓ HR + ↓ contractility → ↓ CO
2. Block β₁ in kidney JG cells → ↓ renin → ↓ Ang II
3. ↓ Central sympathetic outflow

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8. Alpha-1 Blockers (Prazosin, Doxazosin)

• MOA: Block α₁ on vessels → prevent NE-mediated vasoconstriction → ↓ TPR
• Unique use: HTN + BPH (also relaxes urethral smooth muscle)
• First-dose phenomenon: Severe postural hypotension after first dose - give at bedtime, start low

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9. Methyldopa + Clonidine (Central Acting)

• MOA: α₂ agonists in brainstem → ↓ sympathetic outflow → ↓ BP
• Methyldopa: Drug of choice in pregnancy (proven safety record). Also causes hemolytic anemia, positive Coombs test
• Clonidine: Rebound hypertension if stopped abruptly (always taper). Also used for opioid withdrawal, ADHD

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10. Direct Vasodilators

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Drug Selection - Must Know Table

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Top 15 Exam One-Liners

1. ACEIs cause dry cough → bradykinin accumulation → switch to ARB
2. ACEIs/ARBs = teratogenic → absolutely contraindicated in pregnancy
3. Methyldopa = drug of choice in pregnancy
4. Thiazides retain Ca²⁺; Loop diuretics lose Ca²⁺ - opposite effects
5. Spironolactone causes gynecomastia → use eplerenone instead
6. Clonidine rebound → never stop abruptly (taper always)
7. Hydralazine + slow acetylators → lupus-like syndrome at lower doses
8. Minoxidil causes hypertrichosis → topical form used for baldness (Rogaine)
9. Nitroprusside → cyanide toxicity → treat with sodium thiosulfate
10. Verapamil + beta-blocker = dangerous → severe AV block
11. First-dose hypotension → Prazosin (give at bedtime)
12. Pheochromocytoma: Always give alpha-blocker before beta-blocker
13. Losartan is uricosuric → preferred in HTN with gout
14. Short-acting nifedipine → avoid in chronic HTN (reflex tachycardia)
15. ACEI + ARB together → never combine (renal failure + hyperkalemia)

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