Antianginal & Antiarrhythmic Drugs - Exam-Oriented Made Easy

(Based on Priyanka Sachdev-style approach using standard pharmacology)

Note: The library does not carry Priyanka Sachdev's book directly. The content below is drawn from Lippincott Illustrated Reviews: Pharmacology (the standard exam-oriented reference) and Katzung's Basic & Clinical Pharmacology, which closely align with Sachdev's teaching approach. All high-yield points, mnemonics, uses, and contraindications are included.

PART 1: ANTIANGINAL DRUGS

Types of Angina - Quick Recap

Four Classes of Antianginal Drugs

• Beta-blockers
• Organic nitrates
• Ranolazine (late Na+ channel blocker)
• Nifedipine/CCBs (Calcium Channel Blockers)

1. ORGANIC NITRATES

Drugs

• Short-acting: Sublingual nitroglycerin (NTG), NTG spray
• Long-acting: Isosorbide dinitrate (ISDN), Isosorbide mononitrate (ISMN)
• Transdermal: NTG patch/ointment

Mechanism

• Primarily dilates large veins → ↓ preload → ↓ myocardial O2 demand
• Also dilates coronary vessels → ↑ blood supply

Uses

• Acute angina attack (sublingual NTG = drug of choice, onset 1 min)
• All 3 types of angina (stable, unstable, Prinzmetal)
• Acute MI (IV nitroglycerin)
• Acute heart failure / hypertensive emergencies (IV NTG)

Adverse Effects - Mnemonic: "3 H's + T"

• Headache (most common)
• Hypotension (postural)
• Heart rate ↑ (reflex tachycardia)
• Tolerance (develops rapidly)

Contraindications

• Co-administration with PDE-5 inhibitors (sildenafil, tadalafil, vardenafil) - causes severe dangerous hypotension
• Severe aortic stenosis
• Hypertrophic obstructive cardiomyopathy (HOCM)
• Raised intracranial pressure

Tolerance

• Develops with continuous use (desensitization of vessels)
• Overcome by "nitrate-free interval" of 10-12 hours (usually overnight)

2. BETA-BLOCKERS (Class II Antianginals)

Drugs

Mechanism

Uses

• First-line in stable angina (unless contraindicated)
• Post-MI (reduces death + re-infarction)
• Angina with HFrEF (carvedilol, metoprolol, bisoprolol)
• Angina + hypertension
• Effort-induced angina (reduce exercise-induced tachycardia)

Contraindications - Mnemonic: "ABCDE"

• Asthma / COPD (non-selective agents - cause bronchospasm)
• Bradycardia / heart block
• Cardiogenic shock (severe HF with low output)
• Diabetes with frequent hypoglycemia (masks hypoglycemia signs)
• Excessive peripheral vascular disease (Raynaud's - non-selective)

Important: Avoid in Prinzmetal (vasospastic) angina - can worsen coronary spasm
Avoid agents with ISA (intrinsic sympathomimetic activity) like pindolol - reduce antianginal benefit

Never stop abruptly - taper over 2-3 weeks (risk of rebound angina, MI, hypertension)

3. CALCIUM CHANNEL BLOCKERS (CCBs)

Two Subclasses:

• Nifedipine/Amlodipine = peripheral (N = Naughty peripheral vessel dilators)
• Diltiazem = intermediate
• Verapamil = most cardiac (V = Very cardiac)

Mechanism

Uses

• Prinzmetal (vasospastic) angina - drug of choice (both DHP and non-DHP)
• Stable angina (second-line to beta-blockers, or when beta-blockers are contraindicated)
• Angina + hypertension: Amlodipine preferred
• Angina + arrhythmias: Verapamil or Diltiazem preferred
• Angina + asthma/COPD: CCBs preferred (safe; no bronchospasm)

Contraindications

• Verapamil/Diltiazem (non-DHP): avoid in HF with reduced ejection fraction (negative inotropic effect)
• Verapamil: avoid with beta-blockers (additive bradycardia + heart block)
• Verapamil/Diltiazem: avoid in 2nd/3rd degree heart block, sick sinus syndrome

4. RANOLAZINE

• Blocks late Na+ channels → prevents Na+ overload → prevents secondary Ca2+ overload
• Reduces myocardial oxygen demand without affecting HR or BP
• Used when other antianginal agents are inadequate (add-on therapy)
• Less effective in women
• Prolongs QT interval - use caution

Antianginal Drug Choice by Patient Profile (High-Yield)

PART 2: ANTIARRHYTHMIC DRUGS

Vaughan Williams Classification

CLASS I - SODIUM CHANNEL BLOCKERS

Subdivisions:

• Quinidine
• Procainamide
• Disopyramide

• Lidocaine
• Mexiletine
• Phenytoin

• Flecainide
• Propafenone

Class IA Drugs

Quinidine

• Uses: AF conversion, WPW syndrome, ventricular arrhythmias
• Adverse effects: "Cinchonism" (tinnitus, headache, blurred vision), Torsades de pointes, diarrhea, thrombocytopenia
• Contraindications: Prolonged QT, Torsades, HF

Procainamide

• Uses: Acute ventricular arrhythmias, AF
• Adverse effects: Drug-induced Lupus (with antinuclear antibody / anti-histone antibodies), agranulocytosis
• Mnemonic: "Procaine LUPUS"

Disopyramide

• Strongest anticholinergic side effects (urinary retention, dry mouth, constipation)
• Avoid in elderly men (urinary retention) and in HF (negative inotrope)

Class IB Drugs

Lidocaine

• IV only (significant first-pass metabolism orally)
• Use: Ventricular arrhythmias (especially post-MI), VT, VF
• Acts preferentially on ischemic/depolarized tissue (useful in MI)
• Adverse effects: CNS toxicity (confusion, seizures, tinnitus) - dose-dependent
• Drug of choice for ventricular arrhythmias in acute MI

Mexiletine

• Oral analog of lidocaine
• Use: Chronic ventricular arrhythmias

Phenytoin

• Used for digoxin-induced arrhythmias

Class IC Drugs

Flecainide & Propafenone

• Most potent Na+ channel blockers
• Uses: AF/flutter in structurally normal hearts, SVT
• CONTRAINDICATED in structural heart disease (post-MI, HF) - risk of pro-arrhythmia
• Propafenone also has weak β-blocking and Ca2+ channel blocking activity
• Propafenone may cause bronchospasm (avoid in asthma)

CLASS II - BETA-BLOCKERS

• Tachyarrhythmias due to increased sympathetic activity
• Atrial flutter and fibrillation (rate control)
• AV nodal reentrant tachycardia (AVNRT)
• Post-MI ventricular arrhythmias (life-saving)
• Esmolol: short-acting IV - used in perioperative tachyarrhythmias and acute situations

CLASS III - POTASSIUM CHANNEL BLOCKERS

• Sotalol
• Dofetilide
• Amiodarone (+ Dronedarone, Ibutilide)

Amiodarone (Most Important Class III Drug)

• Refractory ventricular tachycardia / fibrillation
• AF (both rate and rhythm control)
• WPW syndrome
• First-line in cardiac arrest (pulseless VT/VF)

• Very long half-life: 40-55 days
• Extensive tissue distribution
• Contains 37% iodine by weight
• Oral bioavailability variable

• Hypothyroidism or Hyperthyroidism (most common thyroid effect = hypothyroidism)
• Arrhythmia (Torsades - pro-arrhythmic)
• Liver toxicity (hepatotoxicity)
• Thyroid dysfunction
• Treatment-resistant (long washout)
• Interstitial lung disease / pulmonary toxicity (most serious)
• Photosensitivity + bluish-gray skin discoloration
• Sight (corneal microdeposits - reversible; optic neuropathy - rare but serious)

Sotalol

• Both Class II (beta-blocking) and Class III (K+ channel blocking) activity
• Uses: AF, ventricular arrhythmias
• Adverse effects: Torsades de pointes, bradycardia
• Must monitor QTc
• Avoid in renal failure (renally excreted)

Ibutilide

• IV only; used for acute conversion of AF/flutter
• Risk of Torsades

Dofetilide

• Oral; AF/flutter
• Requires in-hospital initiation due to Torsades risk

CLASS IV - CALCIUM CHANNEL BLOCKERS (Non-DHP)

• AVNRT (AV nodal reentrant tachycardia) - drug of choice
• AF/flutter rate control
• Atrial tachycardias
• Prinzmetal angina (discussed above)

• Ventricular arrhythmias (contraindicated - can cause hemodynamic collapse)
• WPW syndrome with AF (can accelerate conduction via accessory pathway)
• Sick sinus syndrome, 2nd/3rd degree AV block
• HF with reduced EF
• Never combine verapamil with beta-blockers IV (fatal bradycardia + asystole)

OTHER ANTIARRHYTHMIC DRUGS

Adenosine

• Drug of choice for acute termination of PSVT/AVNRT
• Mechanism: Activates K+ channels → hyperpolarizes AV node → briefly blocks AV conduction
• Very short half-life: < 10 seconds (metabolized in red blood cells)
• Administration: Rapid IV bolus (otherwise inactivated before reaching the heart)
• Adverse effects: Transient chest tightness, dyspnea, flushing, brief asystole
• Contraindicated in asthma (can cause bronchospasm)
• Theophylline blocks adenosine (antagonist)
• Dipyridamole enhances adenosine (blocks its uptake)

Digoxin

• Mechanism: Inhibits Na+/K+ ATPase → ↑ intracellular Ca2+ → positive inotropy; also increases vagal tone → ↓ AV conduction
• Uses: AF rate control, HF
• Narrow therapeutic index
• Toxic effects: Nausea, vomiting, yellow-green vision, arrhythmias
• Toxicity enhanced by: Hypokalemia, hypomagnesemia, hypercalcemia
• Toxicity treated with: Digoxin-specific antibody fragments (Fab)

Magnesium Sulfate

• Used in: Torsades de pointes (drug of choice), digoxin toxicity arrhythmias

Master Summary Table - Antiarrhythmics

High-Yield Exam Points - Quick Fire

1. Sublingual NTG = drug of choice for acute angina attack (onset 1 min)
2. Beta-blockers = first-line in stable angina (except Prinzmetal)
3. CCBs = drug of choice for Prinzmetal (vasospastic) angina
4. Nitrates + PDE-5 inhibitors = absolute contraindication (severe hypotension)
5. Amiodarone = most effective antiarrhythmic but most side effects; preferred in cardiac arrest
6. Lidocaine = drug of choice for ventricular arrhythmias in acute MI (IV only)
7. Adenosine = drug of choice for acute PSVT/AVNRT (rapid IV bolus only)
8. Class IC drugs (flecainide/propafenone) = contraindicated post-MI (CAST trial)
9. Procainamide = drug-induced lupus (anti-histone antibodies)
10. Verapamil + IV beta-blocker = never combine (fatal bradycardia)
11. WPW + AF = avoid adenosine, digoxin, verapamil (can → VF via accessory pathway)
12. Torsades de pointes → give IV magnesium sulfate
13. Quinidine → Cinchonism (tinnitus + headache)
14. Disopyramide → most anticholinergic class I drug
15. Nitrate tolerance → prevent with 10-12 hour nitrate-free interval

ANTIANGINAL + ANTIARRHYTHMIC DRUGS

"Formula-Based" Super Summary

═══ ANTIANGINAL DRUGS ═══

🧮 MASTER FORMULA

ANGINA = O2 DEMAND > O2 SUPPLY
All antianginals fix this equation ↓

┌─────────────────────────────────────────────────────┐
│                                                     │
│   ANGINA RELIEF = ↓ Demand  OR  ↑ Supply           │
│                                                     │
│   ↓ Demand = ↓ HR  +  ↓ Contractility  +  ↓ Load  │
│   ↑ Supply = Coronary vasodilation                  │
│                                                     │
└─────────────────────────────────────────────────────┘

FORMULA 1 - NITRATES

NTG → NO → ↑cGMP → Vasodilation
           │
           ▼
    Veins >> Arteries
    ↓ Preload   +   ↓ Wall stress   =   ↓ O2 demand
                +   Coronary dilation  =  ↑ O2 supply

ROUTE × SPEED FORMULA:

  Sublingual NTG    →  1 min onset   →  ACUTE ATTACK
  IV NTG            →  1-2 min       →  ICU/Emergency
  Patch/Ointment    →  30-60 min     →  PREVENTION only
  ISMN oral         →  30 min        →  PROPHYLAXIS

TOLERANCE FORMULA:
  Continuous use → Tolerance
  Fix:  10-12 hr NITRATE-FREE INTERVAL (at night)

DANGER FORMULA:
  NTG + Sildenafil/Tadalafil = SEVERE HYPOTENSION ❌
  (Both ↑cGMP → additive vasodilation → crash BP)

FORMULA 2 - BETA-BLOCKERS

β1 blocked → ↓HR × ↓Contractility = ↓ Cardiac Work = ↓ O2 demand

Selectivity Formula:
  Cardioselective (β1 only)  = Metoprolol, Atenolol, Bisoprolol
  Non-selective (β1 + β2)    = Propranolol (prototype)
  α + β blocker              = Carvedilol, Labetalol

WHICH ANGINA WORKS?
  Stable angina    ✅  FIRST LINE
  Post-MI angina   ✅  FIRST LINE (reduces mortality)
  HFrEF + angina   ✅  Carvedilol / Metoprolol / Bisoprolol
  Prinzmetal       ❌  AVOID (worsens coronary spasm)
  Asthma + angina  ❌  AVOID (β2 blockade → bronchospasm)

STOP FORMULA:
  Never stop abruptly!
  Taper over 2-3 weeks
  Abrupt stop → Rebound angina + MI + HTN crisis

FORMULA 3 - CALCIUM CHANNEL BLOCKERS

L-type Ca2+ blocked → Smooth muscle relaxes → Vasodilation
                    → Cardiac muscle → ↓HR, ↓ conduction

PERIPHERAL ──────────────────────────► CARDIAC
Amlodipine  >  Diltiazem  >  Verapamil
(DHP)           (BZD)          (PAP)
Vessels only    Both          Heart mostly

ANGINA TYPE FORMULA:
  Prinzmetal        → DHP (Nifedipine/Amlodipine) FIRST CHOICE
  Stable + HTN      → Amlodipine (dual benefit)
  Stable + AF/SVT   → Verapamil or Diltiazem
  Stable + Asthma   → Any CCB (safe - no bronchospasm)

AVOID FORMULA:
  Verapamil/Diltiazem + HFrEF   ❌  (negative inotropy)
  Verapamil + IV beta-blocker   ❌  (asystole/bradycardia)
  Non-DHP + heart block         ❌  (worsen block)

FORMULA 4 - RANOLAZINE

Late Na+ channel blocked
→ Less Na+ entry
→ Less secondary Ca2+ overload
→ Less myocardial tension = ↓ O2 demand

NO change in HR or BP
→ Safe as add-on when HR already low
→ Prolongs QT → avoid with other QT-prolonging drugs

ANTIANGINAL MASTER DECISION FORMULA

PATIENT TYPE              BEST DRUG
─────────────────────────────────────────────
Acute attack         →    Sublingual NTG
Stable angina        →    Beta-blocker (1st)
Post-MI              →    Beta-blocker (must)
Prinzmetal           →    CCB + Nitrate
Angina + asthma      →    CCB (never BB)
Angina + bradycardia →    CCB-DHP (Amlodipine)
Angina + HFrEF       →    BB (Carvedilol)
On PDE-5 inhibitor   →    Never nitrates

═══ ANTIARRHYTHMIC DRUGS ═══

MASTER ACTION POTENTIAL FORMULA

    Phase 0   = Na+ RUSH IN    → Class I blocks this
    Phase 2   = Ca2+ in        → Class IV blocks this
    Phase 3   = K+ RUSH OUT    → Class III blocks this
    Phase 4   = Na+ slow leak  → Class II (BB) slows this

    ┌──────────────────────────────────────────────┐
    │  Channel blocked = Class number              │
    │  Na+  →  Class I  (1 letter before K)        │
    │  β    →  Class II                            │
    │  K+   →  Class III (3 letters in "ion")      │
    │  Ca2+ →  Class IV  (4 letters in "calci")    │
    └──────────────────────────────────────────────┘

FORMULA - CLASS I (Na+ Blockers)

All Class I: Slow Phase 0 = Slow conduction = ↑ Refractory period

SUBCLASS FORMULA  =  What happens to Action Potential Duration?

    IA → ↑ APD (Prolongs)     → blocks Na+ AND K+
    IB → ↓ APD (Shortens)     → blocks Na+ only (ischemic tissue)
    IC → No change APD        → Severely slows conduction only

DRUGS FORMULA - remember by effect:

  CLASS IA: "Queens Play Dirty"
    Q = Quinidine
    P = Procainamide
    D = Disopyramide

  CLASS IB: "Lie, Mex, Phen"
    L = Lidocaine
    M = Mexiletine
    P = Phenytoin

  CLASS IC: "Flee, Pro"
    F = Flecainide
    P = Propafenone

UNIQUE TOXICITY FORMULA:
  Quinidine    →  Cinchonism (tinnitus + headache) + Torsades
  Procainamide →  Drug-induced LUPUS (anti-histone Ab)
  Disopyramide →  Anticholinergic (dry mouth, urinary retention)
  Lidocaine    →  CNS (confusion → seizure → coma)
  Phenytoin    →  Digoxin arrhythmia antidote
  Flecainide   →  CAST trial ❌ post-MI mortality ↑

STRUCTURAL HEART DISEASE FORMULA:
  Class IC + Post-MI / HF  =  PRO-ARRHYTHMIA + DEATH ❌
  (CAST trial proved this)
  Safe ONLY in structurally NORMAL hearts

FORMULA - CLASS II (Beta-Blockers)

β1 blocked → ↓ Phase 4 depolarization → ↓ Automaticity + ↓ AV conduction

BEST USES:
  Sympathetic tachycardia  ✅
  AF/Flutter rate control  ✅
  AVNRT                    ✅
  Post-MI VT prevention    ✅  (life-saving)

KEY DRUGS:
  Metoprolol  = oral, most used
  Esmolol     = IV only, ultra-short (plasma esterases)
                use in perioperative/emergency arrhythmias

FORMULA - CLASS III (K+ Blockers)

K+ channel blocked → Delayed repolarization → ↑ Action potential duration
                  → ↑ Refractory period → Prevents reentry

DRUGS: "A-S-D-I"
  A = Amiodarone   (most important)
  S = Sotalol      (also Class II)
  D = Dofetilide
  I = Ibutilide    (IV only, acute AF/flutter)

AMIODARONE MASTER FORMULA:

  Structure:  Contains 37% IODINE → resembles thyroxine

  Action:     Class I + II + III + IV + α blockade (ALL-IN-ONE)

  Half-life:  40-55 DAYS (longest of all antiarrhythmics)

  TOXICITY FORMULA  =  "HALT + PS"
    H = Hepatotoxicity
    A = Arrhythmia (Torsades - paradoxical)
    L = Lungs (pulmonary fibrosis - most SERIOUS)
    T = Thyroid (hypo OR hyper - most COMMON organ affected)
    P = Photosensitivity + bluish-gray skin
    S = Sight (corneal microdeposits - common but reversible)

SOTALOL FORMULA:
  Class II + Class III = β-blockade + K+ blockade
  Complication: Torsades de pointes
  Avoided in: Renal failure (renally cleared)

FORMULA - CLASS IV (Ca2+ Blockers)

Ca2+ blocked in AV node → ↓ Automaticity → ↓ AV conduction → ↓ HR

DRUGS: Verapamil, Diltiazem (non-DHP only)

BEST FOR:
  AVNRT              ✅ Drug of CHOICE
  AF/flutter          ✅ Rate control
  Atrial tachycardia  ✅

NEVER USE IN:
  Ventricular arrhythmias   ❌ (hemodynamic collapse)
  WPW + AF                  ❌ (blocks AV node → forces all conduction via accessory pathway → VF)
  With IV beta-blockers      ❌ (asystole)
  HFrEF                     ❌

FORMULA - OTHER DRUGS

ADENOSINE FORMULA:
  Activates K+ channels → Hyperpolarizes AV node → Briefly BLOCKS it
  Half-life: < 10 seconds (fastest washout of any drug)
  Given as: RAPID IV BOLUS (slow injection = inactivated in plasma)

  USE:     PSVT / AVNRT  = Drug of CHOICE
  AVOID:   Asthma (bronchospasm)
  BLOCKED by: Theophylline (caffeine too)
  ENHANCED by: Dipyridamole

TORSADES FORMULA:
  Cause: Prolonged QT → early afterdepolarization → Torsades
  Drugs that CAUSE Torsades:
    Class IA (Quinidine), Class III (Sotalol, Ibutilide, Dofetilide)
    Amiodarone (least common among class III)

  TREATMENT FORMULA:
    Step 1: IV Magnesium sulfate  (drug of choice)
    Step 2: ↑ HR (overdrive pacing or isoproterenol) to shorten QT
    Step 3: NEVER give more antiarrhythmic

WPW + AF FORMULA:
  Drugs that BLOCK AV node → dangerous (force bypass tract conduction)
  AVOID: Adenosine, Digoxin, Verapamil, Diltiazem, Beta-blockers
  USE:   Procainamide or Ibutilide (block accessory pathway)

ANTIARRHYTHMIC MASTER DECISION FORMULA

ARRHYTHMIA TYPE            DRUG OF CHOICE
─────────────────────────────────────────────────────
Acute PSVT / AVNRT    →    Adenosine (IV bolus)
Chronic AVNRT         →    Verapamil / Diltiazem
AF rate control       →    Metoprolol / Verapamil / Diltiazem / Digoxin
AF rhythm control     →    Amiodarone / Flecainide (normal heart)
Acute VT/VF (arrest)  →    Amiodarone (first-line)
VT post-MI (acute)    →    Lidocaine (IV)
VT prevention post-MI →    Metoprolol (oral)
Torsades              →    IV Magnesium sulfate
WPW + AF              →    Procainamide / Ibutilide
Digoxin arrhythmia    →    Phenytoin / Mg sulfate
Perioperative tachy   →    Esmolol (IV)

COMBINED MASTER GRID

CLASS │ BLOCKS   │ APD      │ DRUG           │ #1 USE          │ KILL COMBO
──────┼──────────┼──────────┼────────────────┼─────────────────┼───────────────
IA    │ Na+ K+   │ ↑        │ Quinidine      │ AF, VT          │ Prolonged QT
IB    │ Na+      │ ↓        │ Lidocaine      │ VT post-MI      │ -
IC    │ Na++     │ NC       │ Flecainide     │ AF (normal ❤️)  │ Structural HD
II    │ β1       │ ↓ phase4 │ Metoprolol     │ Post-MI VT, AF  │ Asthma
III   │ K+       │ ↑↑       │ Amiodarone     │ VT/VF, all AF   │ Thyroid disease
IV    │ Ca2+     │ ↓ slope  │ Verapamil      │ AVNRT, AF rate  │ WPW+AF, VT
Other │ AV block │ seconds  │ Adenosine      │ Acute PSVT      │ Asthma

All formulas based on Lippincott Illustrated Reviews: Pharmacology and Katzung's Basic & Clinical Pharmacology, 16th Ed, structured in Priyanka Sachdev's exam-oriented framework.

ANTIANGINAL DRUGS - Simple & Easy

First, understand ONE thing about angina:

NITRATES (like Nitroglycerin)

• Sudden angina attack - put the tablet under the tongue, it works in 1 minute
• All three types of angina - stable, unstable, and Prinzmetal
• Works in Prinzmetal because it also relaxes coronary arteries directly

• Headache is the most common
• Blood pressure drops, especially when you stand up
• Heart beats faster as a reflex

BETA-BLOCKERS (like Metoprolol, Atenolol)

• First choice drug for stable angina
• Must use after a heart attack - they save lives post-MI
• Good when patient also has high blood pressure or heart failure

• Patient has asthma - beta-blockers tighten the airways
• Patient has a very slow heart rate already
• Patient has Prinzmetal (vasospastic) angina - they can actually make the spasm worse

CALCIUM CHANNEL BLOCKERS (CCBs)

• Prinzmetal angina - use either type, they are the drug of choice here
• Angina with hypertension - use Amlodipine, it handles both
• Angina with asthma - use any CCB, they do not affect airways at all
• Angina with arrhythmias - use Verapamil or Diltiazem

• Patient has heart failure with reduced ejection fraction - they weaken the heart further
• Patient is already on a beta-blocker injection - combining both intravenously can cause the heart to stop
• Patient has heart block

RANOLAZINE

Quick memory rule for which drug in which angina:

ANTIARRHYTHMIC DRUGS - Simple & Easy

First, understand ONE thing:

CLASS I - Sodium Channel Blockers

CLASS II - Beta-Blockers

CLASS III - Potassium Channel Blockers

CLASS IV - Calcium Channel Blockers

OTHER IMPORTANT DRUGS

Simple memory for which drug for which arrhythmia: