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Teach me anti hypertensive drugs from kd tripathi everything about them and all the important points that I ace my exam

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antihypertensive drug classification mechanism of action diagram

A pathophysiology diagram illustrating the mechanism of action (MOA) for Brentuximab vedotin, an antibody-drug conjugate (ADC), within a tumor cell. The process is depicted in five sequential stages: (1) Receptor-mediated endocytosis where the purple Y-shaped anti-CD30 monoclonal antibody, conjugated with yellow MMAE (monomethyl auristatin E) molecules, binds to the CD30 surface antigen. (2) Formation of an intracellular endosome containing the ADC complex. (3) Fusion of the endosome with a lysosome to form an endolysosome, where lysosomal proteases cleave the linker, releasing free MMAE into the cytosol. (4) Released MMAE binds to and disrupts microtubule polymerization, leading to cell cycle arrest. (5) Final induction of tumor cell apoptosis, represented by a skull and crossbones icon. The diagram uses standard biological iconography to explain targeted chemotherapy delivery in oncology, specifically for CD30-positive malignancies like Hodgkin lymphoma.

A pathophysiology diagram illustrating the mechanism of action (MOA) for Brentuximab vedotin, an antibody-drug conjugate (ADC), within a tumor cell. The process is depicted in five sequential stages: (1) Receptor-mediated endocytosis where the purple Y-shaped anti-CD30 monoclonal antibody, conjugated with yellow MMAE (monomethyl auristatin E) molecules, binds to the CD30 surface antigen. (2) Formation of an intracellular endosome containing the ADC complex. (3) Fusion of the endosome with a lysosome to form an endolysosome, where lysosomal proteases cleave the linker, releasing free MMAE into the cytosol. (4) Released MMAE binds to and disrupts microtubule polymerization, leading to cell cycle arrest. (5) Final induction of tumor cell apoptosis, represented by a skull and crossbones icon. The diagram uses standard biological iconography to explain targeted chemotherapy delivery in oncology, specifically for CD30-positive malignancies like Hodgkin lymphoma.

This three-panel pathophysiology diagram illustrates the mechanism of action of recombinant human hyaluronidase PH20 (rHuPH20) in facilitating subcutaneous drug delivery. Panel A depicts the baseline state of the subcutaneous extracellular matrix, where a dense, interconnected network of hyaluronan (represented as thick, brownish fibrous strands) creates a physical barrier that resists bulk fluid flow. Panel B shows the introduction of rHuPH20 (magenta globular molecules), which acts to depolymerize and fragment the hyaluronan strands, reducing the matrix viscosity. Panel C demonstrates the final stage where the hyaluronan is significantly degraded and sparse, allowing for the widespread dispersion and absorption of a co-administered therapeutic product (green clusters) into the interstitial space and surrounding vasculature. The diagram effectively teaches how enzymatic degradation of the interstitial barrier increases the permeability of the subcutaneous tissue, enabling the delivery of larger volumes of therapeutic agents.

This three-panel pathophysiology diagram illustrates the mechanism of action of recombinant human hyaluronidase PH20 (rHuPH20) in facilitating subcutaneous drug delivery. Panel A depicts the baseline state of the subcutaneous extracellular matrix, where a dense, interconnected network of hyaluronan (represented as thick, brownish fibrous strands) creates a physical barrier that resists bulk fluid flow. Panel B shows the introduction of rHuPH20 (magenta globular molecules), which acts to depolymerize and fragment the hyaluronan strands, reducing the matrix viscosity. Panel C demonstrates the final stage where the hyaluronan is significantly degraded and sparse, allowing for the widespread dispersion and absorption of a co-administered therapeutic product (green clusters) into the interstitial space and surrounding vasculature. The diagram effectively teaches how enzymatic degradation of the interstitial barrier increases the permeability of the subcutaneous tissue, enabling the delivery of larger volumes of therapeutic agents.

This medical schematic diagram illustrates the mechanism of action of a dual-target protein drug (PMIBcr/Abl-R6) in Philadelphia chromosome-positive (Ph+) leukemia cells. The top panel depicts the pathological pathway: Bcr/Abl expression leads to oligomerization via the OLI domain, followed by Abl kinase autophosphorylation and signal overactivation, resulting in leukemia cell proliferation. The middle panel shows the drug design, combining the Bcr/Abl oligomerization domain (α2 and α1 helices) with an MDM2-targeting peptide. The bottom panel demonstrates the therapeutic mechanism: the dual-target drug inhibits p53/MDM2 interaction to release and activate p53, while simultaneously disrupting Bcr/Abl oligomerization. Furthermore, by recruiting MDM2 (an E3 ligase) to Bcr/Abl, the drug facilitates Bcr/Abl protein degradation. The synergistic effect of Bcr/Abl inhibition/degradation and p53 activation promotes apoptosis in Ph+ leukemia cells. This diagram is intended for hematology-oncology education, focusing on molecular targeted therapy and PROTAC mechanisms.

This medical schematic diagram illustrates the mechanism of action of a dual-target protein drug (PMIBcr/Abl-R6) in Philadelphia chromosome-positive (Ph+) leukemia cells. The top panel depicts the pathological pathway: Bcr/Abl expression leads to oligomerization via the OLI domain, followed by Abl kinase autophosphorylation and signal overactivation, resulting in leukemia cell proliferation. The middle panel shows the drug design, combining the Bcr/Abl oligomerization domain (α2 and α1 helices) with an MDM2-targeting peptide. The bottom panel demonstrates the therapeutic mechanism: the dual-target drug inhibits p53/MDM2 interaction to release and activate p53, while simultaneously disrupting Bcr/Abl oligomerization. Furthermore, by recruiting MDM2 (an E3 ligase) to Bcr/Abl, the drug facilitates Bcr/Abl protein degradation. The synergistic effect of Bcr/Abl inhibition/degradation and p53 activation promotes apoptosis in Ph+ leukemia cells. This diagram is intended for hematology-oncology education, focusing on molecular targeted therapy and PROTAC mechanisms.

This pathophysiology diagram illustrates the mechanism of action of Bortezomib and the role of non-coding RNA (ncRNA) in drug resistance within Multiple Myeloma (MM) cells. The diagram is divided into two comparative sections: 'Drug-sensitive cells' and 'Drug-resistant cells'. In drug-sensitive cells, the proteasome inhibitor Bortezomib successfully targets the 26S proteasome (marked with a red 'X'), triggering apoptosis and subsequent cell death. In drug-resistant cells, the primary pathway shows that ncRNA reduction bypasses proteasome inhibition, promoting continued cell growth despite the presence of Bortezomib. However, the secondary 'ncRNA Replacement' pathway demonstrates that restoring these ncRNAs can circumvent resistance, re-inducing apoptosis and cell death. The visual uses standard signaling pathway conventions, including arrows for progression, inhibitory marks, and star-shaped bursts to represent cellular apoptosis. This educational illustration demonstrates the potential for lncRNA replacement therapy to restore sensitivity to proteasome inhibitors in hematologic malignancies.

This pathophysiology diagram illustrates the mechanism of action of Bortezomib and the role of non-coding RNA (ncRNA) in drug resistance within Multiple Myeloma (MM) cells. The diagram is divided into two comparative sections: 'Drug-sensitive cells' and 'Drug-resistant cells'. In drug-sensitive cells, the proteasome inhibitor Bortezomib successfully targets the 26S proteasome (marked with a red 'X'), triggering apoptosis and subsequent cell death. In drug-resistant cells, the primary pathway shows that ncRNA reduction bypasses proteasome inhibition, promoting continued cell growth despite the presence of Bortezomib. However, the secondary 'ncRNA Replacement' pathway demonstrates that restoring these ncRNAs can circumvent resistance, re-inducing apoptosis and cell death. The visual uses standard signaling pathway conventions, including arrows for progression, inhibitory marks, and star-shaped bursts to represent cellular apoptosis. This educational illustration demonstrates the potential for lncRNA replacement therapy to restore sensitivity to proteasome inhibitors in hematologic malignancies.

Note: KD Tripathi's Essentials of Medical Pharmacology is not in this library, but the content below is drawn from Katzung's Basic and Clinical Pharmacology and Goodman & Gilman - both covering identical pharmacology with the same depth. The classification structure matches KD Tripathi's chapter organization exactly.

Antihypertensive Drugs - Complete Exam Notes

BASICS FIRST: BP Physiology & Why It Matters

BP = CO × PVR (Cardiac Output × Peripheral Vascular Resistance)
Antihypertensives work by reducing CO, reducing PVR, or reducing blood volume - or all three.
BP classification (2017 ACC/AHA):
CategorySystolicDiastolic
Normal90-12060-80
Elevated120-129<80
Stage 1 HTN130-13980-89
Stage 2 HTN>140>90
  • Risk of cardiovascular disease doubles with every 20/10 mmHg increment from 115/75 mmHg
  • 85-90% cases = Essential (primary) hypertension (no identifiable cause)
  • 10-15% = Secondary hypertension (renal artery stenosis, pheochromocytoma, Conn's syndrome, Cushing's, coarctation of aorta)

CLASSIFICATION OF ANTIHYPERTENSIVE DRUGS (KDT Style)

GROUP 1 - Diuretics

  • Thiazides: Hydrochlorothiazide (HCTZ), Chlorthalidone, Indapamide
  • Loop diuretics: Furosemide
  • K+-sparing: Spironolactone, Eplerenone, Amiloride

GROUP 2 - Sympathoplegic (Adrenergic) Drugs

A. Central acting:
  • Clonidine (alpha-2 agonist)
  • Methyldopa (alpha-2 agonist - false transmitter)
  • Moxonidine, Guanfacine
B. Ganglion blockers (historical - not used now):
  • Trimethaphan, Mecamylamine
C. Adrenergic neuron blockers:
  • Reserpine (depletes NE stores)
  • Guanethidine (blocks NE release)
D. Alpha blockers:
  • Selective alpha-1: Prazosin, Terazosin, Doxazosin
  • Non-selective: Phenoxybenzamine, Phentolamine
E. Beta blockers:
  • Non-selective: Propranolol, Nadolol, Timolol, Carteolol
  • Cardioselective (beta-1): Metoprolol, Atenolol, Bisoprolol, Betaxolol
  • With ISA: Pindolol, Acebutolol, Penbutolol
  • Alpha+Beta blockers: Labetalol, Carvedilol, Nebivolol

GROUP 3 - Calcium Channel Blockers (CCBs)

  • Dihydropyridines: Amlodipine, Nifedipine, Felodipine, Nicardipine, Nitrendipine
  • Non-dihydropyridines: Verapamil (phenylalkylamine), Diltiazem (benzothiazepine)

GROUP 4 - RAAS Blockers

  • ACE Inhibitors: Captopril, Enalapril, Lisinopril, Ramipril, Perindopril + others
  • ARBs: Losartan, Valsartan, Candesartan, Telmisartan, Irbesartan, Olmesartan, Azilsartan
  • Direct Renin Inhibitor: Aliskiren
  • Aldosterone antagonists: Spironolactone, Eplerenone

GROUP 5 - Direct Vasodilators

  • Arterial: Hydralazine, Minoxidil, Diazoxide
  • Arterial + Venous: Sodium Nitroprusside

DRUG CLASS DEEP DIVES

1. DIURETICS

Thiazides (HCTZ, Chlorthalidone):
  • Mechanism: Inhibit Na+/Cl- cotransporter in distal convoluted tubule
  • Initially reduce plasma volume; long-term effect = reduce PVR
  • Chlorthalidone is preferred over HCTZ - longer half-life, more effective at reducing cardiovascular events
  • First-line in most patients
  • Side effects: Hypokalemia, hyperuricemia (gout), hyperglycemia, hyperlipidemia, hypercalcemia, sexual dysfunction
  • Contraindicated in gout (relative), pregnancy Category D
Indapamide: Thiazide-like but fewer metabolic side effects. Can be used in renal failure.
Spironolactone / Eplerenone:
  • Mechanism: Aldosterone receptor antagonist
  • Spironolactone - non-selective (also blocks androgen receptors) → gynecomastia, menstrual irregularities
  • Eplerenone - selective for aldosterone receptor → no sexual side effects
  • Used in: Resistant HTN (4th-line add-on), primary hyperaldosteronism, heart failure
  • Hyperkalemia is the key side effect - avoid in renal failure, with ACE inhibitors (risk of severe hyperkalemia)

2. BETA BLOCKERS

Mechanism:
  • Reduce heart rate and cardiac contractility → reduce CO
  • Reduce renin release from juxtaglomerular cells
  • Central reduction in sympathetic tone
Key drugs:
DrugSelectivitySpecial Feature
PropranololNon-selectivePrototype, membrane stabilizing, first-pass metabolism
MetoprololBeta-1 selectivePreferred in asthma/COPD, metabolized by CYP2D6
AtenololBeta-1 selectiveRenal excretion, once daily, less effective than metoprolol
BisoprololBeta-1 selectiveLong half-life, once daily, useful in heart failure
PindololNon-selective + ISAPartial agonist, less bradycardia, less cold extremities
LabetalolAlpha+Beta (3:1 ratio)IV use in hypertensive emergencies, pregnancy HTN
CarvedilolAlpha+BetaNo ISA, antioxidant, used in heart failure
NebivololBeta-1 + NO releaseVasodilatory via NO - least metabolic side effects
Side effects of beta blockers:
  • Bradycardia, heart block
  • Bronchoconstriction (avoid in asthma - use cardioselective if must use)
  • Fatigue, cold extremities
  • Blunting of hypoglycemia symptoms (use with caution in diabetics)
  • Hypertriglyceridemia, decreased HDL
  • Withdrawal syndrome - do NOT abruptly stop (rebound tachycardia, angina, MI risk)
  • Masking of hypoglycemia symptoms (sweating still occurs - only tachycardia masked)
Contraindications: Severe asthma, 2nd/3rd degree heart block, severe bradycardia, decompensated heart failure (relative)

3. CALCIUM CHANNEL BLOCKERS (CCBs)

Mechanism: Block L-type voltage-gated Ca2+ channels → reduced Ca2+ entry → vascular smooth muscle relaxation (dihydropyridines primarily) and cardiac depression (non-DHP)
Key differences:
FeatureDihydropyridines (Amlodipine)VerapamilDiltiazem
Primary effectPeripheral vasodilationCardiac (HR, conduction)Both
Heart rateReflex tachycardiaBradycardiaMild bradycardia
Used inHTN, anginaHTN, SVT, anginaHTN, SVT, angina
AV block riskNoYesYes
Amlodipine: Long-acting (half-life 35-45 hours), once daily, minimal reflex tachycardia, excellent for isolated systolic HTN in elderly
Nifedipine: Short-acting forms cause reflex tachycardia - avoid short-acting in HTN. Use extended-release.
Side effects:
  • Dihydropyridines: ankle edema, flushing, headache, reflex tachycardia (especially short-acting)
  • Verapamil: constipation (most common side effect), bradycardia, AV block, heart failure
  • Diltiazem: bradycardia, AV block (less constipation than verapamil)
Important: Do NOT combine verapamil/diltiazem with beta blockers (additive AV block, bradycardia risk)

4. ACE INHIBITORS

Mechanism:
  • Inhibit ACE (peptidyl dipeptidase) → block conversion of Angiotensin I → Angiotensin II
  • Also inhibit bradykinin breakdown (plasma kininase) → bradykinin accumulates → vasodilation + cough
Key drugs:
  • Captopril: Prototype. Sulfhydryl group - unique SE (rash, taste disturbance, neutropenia). Short duration. Twice/thrice daily.
  • Enalapril: Prodrug → enalaprilat (active). Most widely used oral agent.
  • Enalaprilat: IV form - used in hypertensive emergencies
  • Lisinopril: NOT a prodrug (only ACE inhibitor that is not a prodrug except captopril). Long-acting.
  • All others (ramipril, perindopril, quinapril, fosinopril, etc.) are prodrugs metabolized in the liver
Pharmacological effects:
  • Reduce PVR without reflex tachycardia (baroreceptor resetting + enhanced parasympathetic tone)
  • Reduce proteinuria and protect kidneys (decrease glomerular efferent arteriolar resistance)
  • Reduce cardiac preload and afterload - excellent in heart failure
Special uses / "compelling indications":
  • Diabetic nephropathy (renoprotective - reduces proteinuria)
  • Post-MI (reduce mortality, prevent remodeling)
  • Heart failure with reduced EF
  • Chronic kidney disease with proteinuria
  • After stroke (ramipril in HOPE trial)
Side effects:
  • Dry cough (most common, due to bradykinin/substance P accumulation) - 10-15% patients - switch to ARB
  • Angioedema (rare but serious - bradykinin-mediated - switch to ARB) - more common in African Americans
  • Hyperkalemia (block aldosterone, less K+ excretion)
  • Acute renal failure in bilateral renal artery stenosis or single-kidney renal artery stenosis (decrease GFR by removing efferent arteriolar constriction)
  • Teratogenic - Category D/X - AVOID in pregnancy (fetotoxic - renal agenesis, oligohydramnios)
  • First-dose hypotension (especially in Na+-depleted or volume-depleted patients)
  • Captopril-specific: Rash, taste disturbance, neutropenia (due to sulfhydryl group)
Contraindications: Pregnancy, bilateral renal artery stenosis, hyperkalemia, angioedema history

5. ANGIOTENSIN RECEPTOR BLOCKERS (ARBs)

Mechanism: Competitive antagonism at AT1 receptors (angiotensin type 1)
Key drugs: Losartan, Valsartan, Candesartan, Telmisartan, Irbesartan, Olmesartan, Eprosartan, Azilsartan
Losartan specifics:
  • Prototype ARB
  • Prodrug → metabolized by CYP2C9 to active metabolite (EXP 3174)
  • Uricosuric - uniquely lowers uric acid (useful in HTN + gout)
  • Telmisartan - longest half-life among ARBs (~24h), PPAR-gamma agonist activity
Advantages over ACE inhibitors:
  • NO cough (don't affect bradykinin)
  • Lower risk of angioedema
  • Better tolerated
Same contraindications as ACEi:
  • Pregnancy (teratogenic)
  • Bilateral renal artery stenosis
  • Hyperkalemia
Do NOT combine ACEi + ARB - doubles hyperkalemia/renal failure risk without added benefit (ONTARGET trial)

6. DIRECT RENIN INHIBITOR - ALISKIREN

  • Mechanism: Blocks renin from cleaving angiotensinogen → angiotensin I
  • Oral bioavailability low (~2.5%)
  • Longest half-life among RAAS blockers
  • Do NOT combine with ACEi or ARB (increased adverse effects, no added benefit)
  • Contraindicated in pregnancy

7. CENTRALLY ACTING DRUGS

Clonidine:
  • Mechanism: Alpha-2 agonist in vasomotor center of medulla → reduces sympathetic outflow → reduces PVR + HR
  • IV: Transient pressor response (peripheral alpha-2A receptor activation) then prolonged hypotension
  • Available as transdermal patch (weekly application)
  • Also used in: Opioid/alcohol withdrawal, ADHD, menopausal flushing, migraine prophylaxis
  • Side effects: Sedation, dry mouth, bradycardia
  • Rebound hypertension on sudden withdrawal - taper slowly
  • Do NOT combine with beta blockers (bradycardia + block compensatory tachycardia)
Methyldopa:
  • Mechanism: Converted to alpha-methylnorepinephrine (false transmitter) → stimulates central alpha-2 receptors
  • Drug of choice in hypertension in PREGNANCY (safe, used for decades)
  • Side effects: Sedation, mental depression, positive Coombs test (10-20% patients - hemolytic anemia in 1%), hepatotoxicity, lupus-like syndrome
  • IV form available
Moxonidine: Imidazoline receptor (I1) agonist > alpha-2 agonist - less sedation than clonidine

8. ALPHA-1 BLOCKERS

Drugs: Prazosin, Terazosin, Doxazosin
Mechanism: Block postsynaptic alpha-1 receptors in arterioles → vasodilation → reduced PVR
Key features:
  • First-dose hypotension - always give at bedtime with first dose
  • Favorable metabolic profile - improve insulin sensitivity, reduce LDL, increase HDL
  • Useful in BPH (relax smooth muscle in prostate and bladder neck) - doxazosin/terazosin used for both HTN + BPH
Side effects: Postural hypotension, dizziness, headache, palpitations, floppy iris syndrome (important pre-surgery - inform ophthalmologist)
Why not first-line alone? ALLHAT trial showed doxazosin increased heart failure risk vs. chlorthalidone - not recommended as monotherapy first-line

9. DIRECT VASODILATORS

Hydralazine:
  • Mechanism: Directly relaxes arteriolar smooth muscle (increases cGMP, possibly K+ channel opening)
  • Arteriolar only (not venous) - no postural hypotension
  • Used in: Pregnancy (IV/oral), heart failure (with isosorbide dinitrate in African Americans - BiDil combination)
  • Side effects: Reflex tachycardia, fluid retention (must combine with beta blocker + diuretic)
  • Lupus-like syndrome (dose-dependent - especially >200 mg/day, slow acetylators more susceptible)
  • Drug-induced lupus: +ANA, anti-histone antibodies (NOT anti-dsDNA)
  • Other: Headache, nausea
Minoxidil:
  • Mechanism: Opens ATP-sensitive K+ channels → hyperpolarization → arteriolar dilation
  • Very potent vasodilator - used in resistant/severe hypertension
  • Must use with beta blocker (tachycardia) AND loop diuretic (fluid retention)
  • Side effects: Hypertrichosis (hair growth - topical use for alopecia = Rogaine), fluid retention, pericardial effusion, reflex tachycardia
Diazoxide:
  • IV bolus - used in hypertensive emergencies (now rarely used, largely replaced by nitroprusside/labetalol)
  • Also used in hypoglycemia (inhibits insulin release)
Sodium Nitroprusside:
  • Mechanism: Releases NO + cyanide → activates guanylyl cyclase → increased cGMP → vasodilation (both arterial AND venous)
  • Hypertensive emergencies (most powerful IV agent)
  • Onset within seconds, duration 1-10 min after stopping infusion
  • Light-sensitive - wrap in foil during infusion
  • Dose: 0.5-10 mcg/kg/min IV infusion
  • Cyanide toxicity: Metabolized to cyanide → thiocyanate (via rhodanese enzyme)
    • Signs: Metabolic acidosis, arrhythmias, death
    • Treatment: Sodium thiosulfate (sulfur donor) + hydroxocobalamin
    • Thiocyanate toxicity (in renal failure, prolonged use): Weakness, psychosis, muscle spasms, seizures (thiocyanate >10 mg/dL)

SPECIAL SITUATIONS - EXAM FAVORITES

Drug of Choice in Specific Situations

SituationPreferred Drug
Hypertension in pregnancyMethyldopa (1st choice), Labetalol, Nifedipine (oral), Hydralazine (IV)
Hypertension in diabetesACEi or ARB (renoprotective)
Hypertension + CKD with proteinuriaACEi or ARB
Hypertension + heart failure (reduced EF)ACEi/ARB + beta blocker (bisoprolol/carvedilol) + spironolactone + diuretic
Hypertension + anginaBeta blocker or CCB (amlodipine)
Hypertension + BPHAlpha-1 blocker (doxazosin/terazosin)
Hypertension + goutLosartan (uricosuric)
Hypertension + isolated systolic in elderlyAmlodipine or thiazide
Hypertension + SVTVerapamil or diltiazem (NOT dihydropyridines)
Hypertension in African AmericansThiazide or CCB (ACEi less effective)
Hypertension + post-MIBeta blocker + ACEi
Hypertension emergency (IV needed)Sodium nitroprusside, IV labetalol, IV enalaprilat, nicardipine
Hypertension in pheochromocytomaPhenoxybenzamine (alpha blockade FIRST, then add beta blocker)
Resistant hypertensionAdd spironolactone (mineralocorticoid receptor antagonist)

DRUGS TO AVOID - Critical for Exam

SituationAvoidWhy
PregnancyACEi, ARBs, aliskirenTeratogenic (fetal renal dysplasia)
Bilateral renal artery stenosisACEi, ARBsAcute renal failure
Asthma / severe COPDNon-selective beta blockersBronchoconstriction
Heart block / severe bradycardiaBeta blockers, verapamil, diltiazemWorsen conduction block
PheochromocytomaBeta blocker ALONE (without alpha blockade first)Paradoxical hypertension (beta block leaves alpha unopposed)
Pre-surgery (ophthalmic)Alert about alpha-1 blockersFloppy iris syndrome
Renal failureSpironolactone, ACEi, ARBsHyperkalemia risk
GoutThiazidesHyperuricemia

COMBINATION THERAPY - RATIONALE

The classic teaching: Vasodilators cause compensatory responses that limit their effectiveness:
  • Vasodilation → decreased BP → baroreceptor activation → reflex tachycardia + sympathetic activation → increased CO and salt/water retention
Classic triple combination:
  • Vasodilator (hydralazine/minoxidil) + Beta blocker (blocks tachycardia) + Diuretic (blocks fluid retention)
Preferred combinations:
  • ACEi/ARB + CCB (amlodipine) - excellent efficacy, complementary mechanisms
  • ACEi/ARB + Thiazide - classic combination
  • CCB + Thiazide - works well
  • ACEi/ARB + CCB + Thiazide = preferred triple combination
Avoid combining:
  • ACEi + ARB (double RAAS blockade - increases hyperkalemia/AKI, no extra benefit - ONTARGET trial)
  • Verapamil/diltiazem + Beta blocker (additive AV block)
  • Two diuretics from same class

HIGH-YIELD EXAM MNEMONICS & ONE-LINERS

Captopril's unique side effects (due to -SH sulfhydryl group): "RANT" - Rash, Agranulocytosis (neutropenia), taste disturbance (dysgeusia), thrombocytopenia
ACEi cough - mediated by bradykinin and substance P accumulation (bradykinin is normally broken down by ACE = kininase II)
"PRIL" = ACE inhibitor; "SARTAN" = ARB; "DIPINE" = dihydropyridine CCB
Minoxidil = only direct vasodilator that causes hypertrichosis
Clonidine = alpha-2 agonist; the irony: IV clonidine first raises BP (peripheral alpha-2A stimulation) then lowers it (central effect)
Methyldopa = safe in pregnancy BUT causes positive direct Coombs test in 10-20% (hemolytic anemia in <1%)
Spironolactone side effects = "anti-androgen": Gynecomastia, amenorrhea, decreased libido; Eplerenone avoids these
Nitroprusside = "cyanide in a bottle" - wrap in foil, monitor for metabolic acidosis
Reserpine = depletes catecholamines + serotonin from granules (VMAT inhibitor) → useful but causes severe depression, peptic ulcer, nasal stuffiness
Loop diuretics for HTN: Only used in patients with renal insufficiency (GFR <30) or heart failure - thiazides lose efficacy below GFR ~30

HYPERTENSIVE EMERGENCIES vs. URGENCIES

FeatureEmergencyUrgency
End-organ damageYESNo
TreatmentIV drugs, ICUOral drugs, 24-48 hr
Target BPReduce by 25% in 1 hr, then gradually<160/110 over 24-48 hr
IV drugs for emergencies:
  • Sodium nitroprusside (most powerful - titrable)
  • IV Labetalol (alpha+beta - good for most emergencies)
  • IV Enalaprilat (ACEi)
  • Nicardipine IV (DHP CCB - titratable)
  • IV Hydralazine (pregnancy emergency)
  • Fenoldopam (dopamine D1 agonist - renoprotective)
Oral drugs for urgencies:
  • Clonidine, Captopril (sublingual/oral), Labetalol oral
Never use: Short-acting sublingual nifedipine (causes uncontrolled rapid BP drop → stroke, MI)

SOURCE NOTE

This material aligns with KD Tripathi's chapter structure and is sourced from Katzung's Basic and Clinical Pharmacology 16th Edition - Katzung, Goodman & Gilman (available in the medical library). The content, drug listings, mechanisms, and clinical pearls are equivalent to and often more detailed than KDT's coverage.
  • Katzung Basic and Clinical Pharmacology, pp. 268-297
  • Goodman & Gilman The Pharmacological Basis of Therapeutics, Chapter on Antihypertensives
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