2026/2027 COMPLETE WEEKS 1–8 EDITION • NR 565 / NURS 6521 / FNP & APRN / PHARM.D / LEHNE’S &
ROSENTHAL ALIGNED
ADVANCED PHARMACOLOGY FUNDAMENTALS MASTER
GUIDE
Pharmacokinetics, Prescribing Laws, Cardiovascular, Endocrine, Respiratory, GI, Opioid MME & Board-Style Clinical
Rationales
1. PHARMACOKINETICS (ADME), CYP450 & CONTROLLED Weeks 1 & 2: Core
SUBSTANCE PRESCRIBING Prescribing Principles
Principle / Rule Mechanism / Clinical Impact on Active vs. High-Yield Exam Traps &
Pharmacokinetic Equation Prodrug Special Populations
First-Pass & Hepatic portal & gut wall High first-pass requires much Cirrhosis / Portal
Bioavailability (F) CYP3A4/P-gp extraction prior higher PO vs. IV dose (e.g., Hypertension: Shunts blood
to systemic circulation; IV F = Propranolol, Morphine, past liver → dramatically
100% Nitroglycerin, Verapamil) increases PO bioavailability,
risking acute toxicity.
Protein Binding & Acidic drugs bind Albumin Hypoalbuminemia (malnutrition, Phenytoin / Sulfonylurea +
Distribution (Vd) (Warfarin, Phenytoin, cirrhosis, burns, nephrotic Sulfonamide or Aspirin:
Valproate, NSAIDs); Only syndrome, pregnancy) increases Displaces drug from albumin →
unbound (free) drug is active free fraction acute free-drug toxicity
despite normal total serum
level.
Half-Life (t1/2) & t1/2 = (0.693 × Vd) / Cl Loading dose rapidly achieves Zero-Order (Saturation)
Steady State • Steady state reached in 4 target Cp based on Vd; Kinetics ("PEA"): Phenytoin,
to 5 half-lives (94%–97%) Maintenance dose is governed Ethanol, Aspirin (high dose)
strictly by Clearance (Cl) eliminate a constant amount per
hour → small dose increase
causes exponential toxicity.
CYP450 Inducers Carbamazepine, Rifampin, • Active Drug: ↑ Metabolism → Upregulates enzyme synthesis
("CRAP GPS") Alcohol (chronic), Phenytoin, therapeutic failure. over 1–2 weeks. Rifampin or
Griseofulvin, Phenobarbital, St. • Prodrug: ↑ Conversion → St. John's Wort causes
John's Wort / Smoking increased active metabolite breakthrough pregnancy on
toxicity. OCPs, transplant rejection
(Cyclosporine), and
subtherapeutic Warfarin INR.
CYP450 Inhibitors Sodium valproate, Isoniazid, • Active Drug: ↓ Metabolism → Immediate onset (<24 hrs).
("SICKFACES.COM") Cimetidine, Ketoconazole, life-threatening toxicity. • Clopidogrel (Prodrug) +
Fluconazole, Alcohol • Prodrug: Blocks activation → Omeprazole (CYP2C19
(acute)/Amiodarone, loss of clinical efficacy. inhibitor): Blocks antiplatelet
Clarithromycin, Erythromycin, activation → stent thrombosis
Sulfonamides, Cipro, (use Pantoprazole instead).
Omeprazole, Metronidazole + • Codeine (Prodrug) +
Grapefruit CYP2D6 Inhibitor: Zero
analgesia.
Geriatric Beers Age-related ↓ GFR (even with Fat-soluble drugs (Diazepam) Always calculate Cockcroft-
Criteria & Renal Cl "normal" serum Cr due to low have prolonged t1/2; water- Gault CrCl in elderly. Avoid 1st-
muscle mass), ↓ hepatic blood soluble drugs (Digoxin, Lithium) gen antihistamines
flow, ↓ total body water, ↑ body reach higher peak concentrations (Diphenhydramine), TCAs,
fat sliding-scale insulin,
Nitrofurantoin (if CrCl <30), and
long-acting sulfonylureas
(Glyburide).
DEA Schedules (I– Schedule based on abuse • C-II: Opioid agonists • C-II Prescriptions: ZERO
V) liability vs. medical utility (Oxycodone, Morphine, Fentanyl, refills permitted; cannot be
Hydrocodone), ADHD Stimulants. phoned in (except 72-hr
Advanced Pharmacology Fundamentals Master Guide (2026/2027) • PK/PD, CYP450 & Prescribing Law Page 1 of 25
, 2. CARDIOVASCULAR & RENAL PHARMACOTHERAPY (HTN, HF, Weeks 3 & 4: Cardiology
DYSLIPIDEMIA & ANTICOAGULANTS) & Nephrology
Drug Class & Mechanism of Action Compelling Indications & Adverse Effects, Contraindications
Agents Clinical Pearls & Monitoring
ACE Inhibitors (- • ACEi: Blocks ACE (↓ First-line for HTN with Diabetes, • Bradykinin Effects (ACEi): Dry,
prils) Ang II, ↓ Aldosterone, ↑ Diabetic Nephropathy hacking cough (10–20%) & life-
Lisinopril, Enalapril, Bradykinin). (proteinuria), CKD (dilates threatening Angioedema (switch to
Ramipril, Captopril • ARB: Blocks AT1 efferent arteriole → reduces ARB after cough; avoid both if severe
ARBs (-sartans) receptor directly (no intraglomerular pressure), HFrEF, angioedema).
Losartan, Valsartan, bradykinin accumulation). and Post-MI. • Electrolyte/Renal: Hyperkalemia
Irbesartan • Losartan: Uricosuric (lowers (K+ >5.0), acute Cr bump (≤30% rise is
uric acid; best in Gout). acceptable; >30% suggests bilateral
renal artery stenosis — strictly
contraindicated).
• Black Box: Fetal toxicity /
Teratogen (stop immediately in
pregnancy; use Labetalol, Nifedipine
ER, or Methyldopa). Never combine
ACEi + ARB + Aliskiren.
ARNI Neprilysin inhibitor (↑ First-line GDMT replacement for • Mandatory 36-Hour Washout when
Sacubitril / BNP/natriuretic peptides) ACEi/ARB in symptomatic HFrEF switching from an ACEi to Entresto to
Valsartan (Entresto) + ARB (EF ≤40%); reduces CV death & prevent fatal angioedema (no washout
HF hospitalization. needed when switching from an ARB).
Calcium Channel • DHPs: Vascular smooth • DHPs: HTN (first-line in Black & • DHPs: Dose-dependent peripheral
Blockers muscle L-type Ca2+ elderly patients), Raynaud pedal edema (caused by precapillary
DHP (-dipines): blockade (vasodilation). phenomenon, Prinzmetal angina. arteriolar dilation, NOT fluid overload
Amlodipine, • Non-DHPs: Cardiac • Non-DHPs: Atrial → do not treat with loop diuretics; add
Nifedipine SA/AV node Ca2+ fibrillation/flutter rate control, SVT, an ACEi/ARB to dilate postcapillary
Non-DHP: blockade (↓ HR, ↓ chronic stable angina. venules), flushing, reflex tachycardia,
Verapamil, contractility). gingival hyperplasia.
Diltiazem • Non-DHPs: Severe constipation
(Verapamil), bradycardia, AV block,
contraindicated in HFrEF & with β-
blockers.
Beta-Blockers Block catecholamine • The ONLY 3 Beta-Blockers • β2 Blockade Traps: Non-selective
β1-Selective (A– binding at β1 (↓ HR, ↓ Proven to Reduce Mortality in agents cause fatal bronchospasm in
M): Metoprolol, contractility, ↓ renin HFrEF: 1. Metoprolol Succinate Asthma/COPD (use cardioselective β1
Atenolol, Bisoprolol, release) and/or β2 (XL) (NOT Tartrate), 2. if required) and mask adrenergic
Esmolol (bronchial & vascular Carvedilol, 3. Bisoprolol. symptoms of hypoglycemia (tremor,
Non-Selective (N– smooth muscle) • Start only when patient is tachycardia, palpitations) in diabetics
Z): Propranolol, euvolemic (stable); start low and while sparing diaphoresis (sweating).
Nadolol titrate every 2 weeks. • Black Box: Never discontinue
α1 + β: Carvedilol, abruptly → rebound upregulation of β1
Labetalol receptors precipitates acute angina,
NO-Donor β1: MI, or hypertensive crisis (taper over
Nebivolol 1–2 weeks).
Diuretics • Thiazides: Inhibit • Chlorthalidone: Preferred over • Thiazide + Loop Adverse Effects
Thiazides: Na+/Cl− cotransporter in HCTZ for HTN (longer t1/2, ("HyperGLUC" + Hypo-K/Mg/Na):
Chlorthalidone, DCT. superior CV outcome data); HyperGlycemia, HyperLipidemia,
HCTZ • Loops: Inhibit decreases urinary Ca2+ excretion HyperUricemia (precipitates acute
Loops: Na+/K+/2Cl− in thick (protects bone density in Gout), HyperCalcemia (Thiazides
Furosemide, ascending loop. osteoporosis). only; Loops lose Ca2+).
Bumetanide, • MRAs: Aldosterone • Loops: Required for acute • Loops: Ototoxicity (especially
Torsemide receptor antagonists in pulmonary edema/HF volume Ethacrynic acid or rapid IV Furosemide
K+-Sparing / MRA: collecting duct. overload & when CrCl <30 + Aminoglycosides), severe
Spironolactone, mL/min (Thiazides fail if GFR hypokalemia (triggers Digoxin toxicity).
Eplerenone <30, except Metolazone). • Spironolactone: Hyperkalemia,
• Spironolactone/Eplerenone: endocrine effects (gynecomastia,
Mortality reduction in HFrEF (EF mastodynia, impotence — switch to
Advanced Pharmacology Fundamentals Master Guide (2026/2027) • Cardiovascular, Renal & Anticoagulants Page 2 of 25
ROSENTHAL ALIGNED
ADVANCED PHARMACOLOGY FUNDAMENTALS MASTER
GUIDE
Pharmacokinetics, Prescribing Laws, Cardiovascular, Endocrine, Respiratory, GI, Opioid MME & Board-Style Clinical
Rationales
1. PHARMACOKINETICS (ADME), CYP450 & CONTROLLED Weeks 1 & 2: Core
SUBSTANCE PRESCRIBING Prescribing Principles
Principle / Rule Mechanism / Clinical Impact on Active vs. High-Yield Exam Traps &
Pharmacokinetic Equation Prodrug Special Populations
First-Pass & Hepatic portal & gut wall High first-pass requires much Cirrhosis / Portal
Bioavailability (F) CYP3A4/P-gp extraction prior higher PO vs. IV dose (e.g., Hypertension: Shunts blood
to systemic circulation; IV F = Propranolol, Morphine, past liver → dramatically
100% Nitroglycerin, Verapamil) increases PO bioavailability,
risking acute toxicity.
Protein Binding & Acidic drugs bind Albumin Hypoalbuminemia (malnutrition, Phenytoin / Sulfonylurea +
Distribution (Vd) (Warfarin, Phenytoin, cirrhosis, burns, nephrotic Sulfonamide or Aspirin:
Valproate, NSAIDs); Only syndrome, pregnancy) increases Displaces drug from albumin →
unbound (free) drug is active free fraction acute free-drug toxicity
despite normal total serum
level.
Half-Life (t1/2) & t1/2 = (0.693 × Vd) / Cl Loading dose rapidly achieves Zero-Order (Saturation)
Steady State • Steady state reached in 4 target Cp based on Vd; Kinetics ("PEA"): Phenytoin,
to 5 half-lives (94%–97%) Maintenance dose is governed Ethanol, Aspirin (high dose)
strictly by Clearance (Cl) eliminate a constant amount per
hour → small dose increase
causes exponential toxicity.
CYP450 Inducers Carbamazepine, Rifampin, • Active Drug: ↑ Metabolism → Upregulates enzyme synthesis
("CRAP GPS") Alcohol (chronic), Phenytoin, therapeutic failure. over 1–2 weeks. Rifampin or
Griseofulvin, Phenobarbital, St. • Prodrug: ↑ Conversion → St. John's Wort causes
John's Wort / Smoking increased active metabolite breakthrough pregnancy on
toxicity. OCPs, transplant rejection
(Cyclosporine), and
subtherapeutic Warfarin INR.
CYP450 Inhibitors Sodium valproate, Isoniazid, • Active Drug: ↓ Metabolism → Immediate onset (<24 hrs).
("SICKFACES.COM") Cimetidine, Ketoconazole, life-threatening toxicity. • Clopidogrel (Prodrug) +
Fluconazole, Alcohol • Prodrug: Blocks activation → Omeprazole (CYP2C19
(acute)/Amiodarone, loss of clinical efficacy. inhibitor): Blocks antiplatelet
Clarithromycin, Erythromycin, activation → stent thrombosis
Sulfonamides, Cipro, (use Pantoprazole instead).
Omeprazole, Metronidazole + • Codeine (Prodrug) +
Grapefruit CYP2D6 Inhibitor: Zero
analgesia.
Geriatric Beers Age-related ↓ GFR (even with Fat-soluble drugs (Diazepam) Always calculate Cockcroft-
Criteria & Renal Cl "normal" serum Cr due to low have prolonged t1/2; water- Gault CrCl in elderly. Avoid 1st-
muscle mass), ↓ hepatic blood soluble drugs (Digoxin, Lithium) gen antihistamines
flow, ↓ total body water, ↑ body reach higher peak concentrations (Diphenhydramine), TCAs,
fat sliding-scale insulin,
Nitrofurantoin (if CrCl <30), and
long-acting sulfonylureas
(Glyburide).
DEA Schedules (I– Schedule based on abuse • C-II: Opioid agonists • C-II Prescriptions: ZERO
V) liability vs. medical utility (Oxycodone, Morphine, Fentanyl, refills permitted; cannot be
Hydrocodone), ADHD Stimulants. phoned in (except 72-hr
Advanced Pharmacology Fundamentals Master Guide (2026/2027) • PK/PD, CYP450 & Prescribing Law Page 1 of 25
, 2. CARDIOVASCULAR & RENAL PHARMACOTHERAPY (HTN, HF, Weeks 3 & 4: Cardiology
DYSLIPIDEMIA & ANTICOAGULANTS) & Nephrology
Drug Class & Mechanism of Action Compelling Indications & Adverse Effects, Contraindications
Agents Clinical Pearls & Monitoring
ACE Inhibitors (- • ACEi: Blocks ACE (↓ First-line for HTN with Diabetes, • Bradykinin Effects (ACEi): Dry,
prils) Ang II, ↓ Aldosterone, ↑ Diabetic Nephropathy hacking cough (10–20%) & life-
Lisinopril, Enalapril, Bradykinin). (proteinuria), CKD (dilates threatening Angioedema (switch to
Ramipril, Captopril • ARB: Blocks AT1 efferent arteriole → reduces ARB after cough; avoid both if severe
ARBs (-sartans) receptor directly (no intraglomerular pressure), HFrEF, angioedema).
Losartan, Valsartan, bradykinin accumulation). and Post-MI. • Electrolyte/Renal: Hyperkalemia
Irbesartan • Losartan: Uricosuric (lowers (K+ >5.0), acute Cr bump (≤30% rise is
uric acid; best in Gout). acceptable; >30% suggests bilateral
renal artery stenosis — strictly
contraindicated).
• Black Box: Fetal toxicity /
Teratogen (stop immediately in
pregnancy; use Labetalol, Nifedipine
ER, or Methyldopa). Never combine
ACEi + ARB + Aliskiren.
ARNI Neprilysin inhibitor (↑ First-line GDMT replacement for • Mandatory 36-Hour Washout when
Sacubitril / BNP/natriuretic peptides) ACEi/ARB in symptomatic HFrEF switching from an ACEi to Entresto to
Valsartan (Entresto) + ARB (EF ≤40%); reduces CV death & prevent fatal angioedema (no washout
HF hospitalization. needed when switching from an ARB).
Calcium Channel • DHPs: Vascular smooth • DHPs: HTN (first-line in Black & • DHPs: Dose-dependent peripheral
Blockers muscle L-type Ca2+ elderly patients), Raynaud pedal edema (caused by precapillary
DHP (-dipines): blockade (vasodilation). phenomenon, Prinzmetal angina. arteriolar dilation, NOT fluid overload
Amlodipine, • Non-DHPs: Cardiac • Non-DHPs: Atrial → do not treat with loop diuretics; add
Nifedipine SA/AV node Ca2+ fibrillation/flutter rate control, SVT, an ACEi/ARB to dilate postcapillary
Non-DHP: blockade (↓ HR, ↓ chronic stable angina. venules), flushing, reflex tachycardia,
Verapamil, contractility). gingival hyperplasia.
Diltiazem • Non-DHPs: Severe constipation
(Verapamil), bradycardia, AV block,
contraindicated in HFrEF & with β-
blockers.
Beta-Blockers Block catecholamine • The ONLY 3 Beta-Blockers • β2 Blockade Traps: Non-selective
β1-Selective (A– binding at β1 (↓ HR, ↓ Proven to Reduce Mortality in agents cause fatal bronchospasm in
M): Metoprolol, contractility, ↓ renin HFrEF: 1. Metoprolol Succinate Asthma/COPD (use cardioselective β1
Atenolol, Bisoprolol, release) and/or β2 (XL) (NOT Tartrate), 2. if required) and mask adrenergic
Esmolol (bronchial & vascular Carvedilol, 3. Bisoprolol. symptoms of hypoglycemia (tremor,
Non-Selective (N– smooth muscle) • Start only when patient is tachycardia, palpitations) in diabetics
Z): Propranolol, euvolemic (stable); start low and while sparing diaphoresis (sweating).
Nadolol titrate every 2 weeks. • Black Box: Never discontinue
α1 + β: Carvedilol, abruptly → rebound upregulation of β1
Labetalol receptors precipitates acute angina,
NO-Donor β1: MI, or hypertensive crisis (taper over
Nebivolol 1–2 weeks).
Diuretics • Thiazides: Inhibit • Chlorthalidone: Preferred over • Thiazide + Loop Adverse Effects
Thiazides: Na+/Cl− cotransporter in HCTZ for HTN (longer t1/2, ("HyperGLUC" + Hypo-K/Mg/Na):
Chlorthalidone, DCT. superior CV outcome data); HyperGlycemia, HyperLipidemia,
HCTZ • Loops: Inhibit decreases urinary Ca2+ excretion HyperUricemia (precipitates acute
Loops: Na+/K+/2Cl− in thick (protects bone density in Gout), HyperCalcemia (Thiazides
Furosemide, ascending loop. osteoporosis). only; Loops lose Ca2+).
Bumetanide, • MRAs: Aldosterone • Loops: Required for acute • Loops: Ototoxicity (especially
Torsemide receptor antagonists in pulmonary edema/HF volume Ethacrynic acid or rapid IV Furosemide
K+-Sparing / MRA: collecting duct. overload & when CrCl <30 + Aminoglycosides), severe
Spironolactone, mL/min (Thiazides fail if GFR hypokalemia (triggers Digoxin toxicity).
Eplerenone <30, except Metolazone). • Spironolactone: Hyperkalemia,
• Spironolactone/Eplerenone: endocrine effects (gynecomastia,
Mortality reduction in HFrEF (EF mastodynia, impotence — switch to
Advanced Pharmacology Fundamentals Master Guide (2026/2027) • Cardiovascular, Renal & Anticoagulants Page 2 of 25
