Pharmacology Mastery

Pharmacology Mastery for USMLE Step 1

Master pharmacology with free flashcards and spaced repetition to reinforce critical drug mechanisms, side effects, and clinical applications. This comprehensive lesson covers pharmacokinetics, pharmacodynamics, drug-receptor interactions, and major drug classes—essential concepts for USMLE Step 1 success and clinical practice.

Welcome to Pharmacology Mastery 🎯

Pharmacology represents one of the most high-yield subjects on USMLE Step 1, accounting for approximately 10-15% of exam questions. Understanding drug mechanisms, adverse effects, and clinical applications is crucial not only for exam success but also for safe, effective patient care throughout your medical career.

This lesson takes you through the fundamental principles that govern how drugs work in the body, from absorption to elimination, and from receptor binding to therapeutic effects. We'll explore the major drug classes you'll encounter repeatedly on Step 1, with emphasis on mechanism of action (MOA), side effects, contraindications, and clinical pearls that help you think like a physician.

💡 Study Tip: Pharmacology is best learned through active recall and spaced repetition. Use the embedded flashcards throughout this lesson to reinforce key concepts immediately after learning them.

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Core Concepts in Pharmacology 💊

Pharmacokinetics: What the Body Does to the Drug

Pharmacology begins with understanding pharmacokinetics—the journey of a drug through your patient's body. Remember the acronym ADME:

Absorption 🔺

Bioavailability (F) is the fraction of administered drug that reaches systemic circulation unchanged. IV drugs have 100% bioavailability by definition, while oral drugs must survive the GI tract and first-pass metabolism.

First-pass metabolism occurs when drugs absorbed from the GI tract travel through the portal circulation to the liver before reaching systemic circulation. Drugs with high first-pass metabolism (like nitroglycerin, morphine, propranolol) have significantly reduced oral bioavailability.

💡 Clinical Pearl: This is why nitroglycerin is given sublingually—it bypasses first-pass metabolism by entering systemic circulation directly through the oral mucosa.

Distribution 🌍

Once absorbed, drugs distribute throughout the body. The volume of distribution (Vd) tells you how extensively a drug distributes into tissues:

• Low Vd (4-8 L): Drug stays in plasma (large/charged molecules like heparin)
• Medium Vd (~40 L): Drug distributes to extracellular fluid
• High Vd (>100 L): Drug extensively distributes to tissues (lipophilic drugs like chloroquine)

Protein binding also affects distribution. Only unbound (free) drug is pharmacologically active. Drugs highly bound to plasma proteins (like warfarin at 99%) have more potential for drug interactions when displaced.

⚠️ Important: In hypoalbuminemia (malnutrition, liver disease, nephrotic syndrome), there's less protein binding, leading to increased free drug and potentially toxic effects.

Metabolism 🧪

Most drug metabolism occurs in the liver through Phase I and Phase II reactions:

Phase	Process	Enzyme System	Result
Phase I	Oxidation, Reduction, Hydrolysis	Cytochrome P450 (CYP)	Adds functional group (-OH, -NH₂)
Phase II	Conjugation	Transferases (glucuronyl, sulfate, acetyl)	Makes drug more polar/water-soluble

Cytochrome P450 enzymes are crucial for Step 1. Key facts:

• CYP3A4: Metabolizes ~50% of all drugs (substrates include statins, macrolides, calcium channel blockers)
• CYP2D6: Metabolizes codeine to morphine, tamoxifen to active form
• CYP2C9: Metabolizes warfarin, NSAIDs, phenytoin
• CYP2E1: Metabolizes alcohol, acetaminophen (produces toxic NAPQI)

🧠 Mnemonic for CYP450 Inducers (increase metabolism, decrease drug levels): "CRAP GPS induces my rage"

• Carbamazepine
• Rifampin
• Alcohol (chronic)
• Phenytoin
• Griseofulvin
• Phenobarbital
• St. John's Wort

🧠 Mnemonic for CYP450 Inhibitors (decrease metabolism, increase drug levels): "SICKFACES.COM"

• Sodium valproate
• Isoniazid
• Cimetidine
• Ketoconazole
• Fluconazole
• Acute alcohol
• Ciprofloxacin
• Erythromycin/macrolides
• Sulfonamides
• Chloramphenicol
• Omeprazole
• Metronidazole

Excretion ⚡

The kidneys are the primary route of drug elimination. Key concepts:

• Clearance (CL): Volume of plasma cleared of drug per unit time
• Half-life (t½): Time for plasma concentration to decrease by 50%
• Steady state: Achieved after ~4-5 half-lives of continuous dosing

Loading dose = (Vd × Target concentration) / Bioavailability

Maintenance dose = (CL × Target concentration × Dosing interval) / Bioavailability

💡 Clinical Application: In renal failure, drugs eliminated by kidneys (like gentamicin, digoxin, lithium) accumulate and require dose adjustment.

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Pharmacodynamics: What the Drug Does to the Body

Pharmacodynamics describes the biochemical and physiological effects of drugs and their mechanisms of action.

Drug-Receptor Interactions 🎯

Most drugs work by binding to specific receptors. Key terms:

• Affinity: How tightly a drug binds to its receptor
• Efficacy: Maximal effect a drug can produce (related to intrinsic activity)
• Potency: Dose required to produce effect (related to EC₅₀ or ED₅₀)

Drug Type	Receptor Binding	Effect	Example
Full Agonist	Binds and activates	100% maximal response	Morphine (μ-opioid receptor)
Partial Agonist	Binds and partially activates	<100% maximal response	Buprenorphine (μ-opioid receptor)
Antagonist	Binds but doesn't activate	Blocks agonist effect	Naloxone (μ-opioid receptor)
Inverse Agonist	Binds and produces opposite effect	Decreases baseline activity	Some benzodiazepines

Competitive antagonists (like atropine at muscarinic receptors) can be overcome by increasing agonist concentration. They shift the dose-response curve to the right without changing maximal efficacy.

Non-competitive antagonists (like phenoxybenzamine at α-adrenergic receptors) cannot be overcome. They decrease maximal efficacy.

Dose-Response Relationships 📊

The ED₅₀ (effective dose for 50% of population) and TD₅₀ (toxic dose for 50%) define the therapeutic index (TI):

Therapeutic Index = TD₅₀ / ED₅₀

• High TI (safe drugs): Penicillin (TI > 100)
• Low TI (narrow therapeutic window): Warfarin, digoxin, lithium, phenytoin, theophylline (require monitoring)

⚠️ Critical Concept: Drugs with low therapeutic index require therapeutic drug monitoring (TDM) to maintain levels within the narrow safe range.

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Autonomic Pharmacology 🧠

Autonomic drugs are heavily tested on Step 1. Understanding sympathetic and parasympathetic receptor subtypes is essential.

Adrenergic Receptors (Sympathetic)

Receptor	Location	Effect When Activated	Agonist Example
α₁	Vascular smooth muscle	Vasoconstriction, ↑ BP	Phenylephrine
α₂	Presynaptic terminals, CNS	↓ NE release, ↓ BP (central)	Clonidine
β₁	Heart	↑ HR, ↑ contractility, ↑ CO	Dobutamine
β₂	Bronchioles, vessels, uterus	Bronchodilation, vasodilation	Albuterol
β₃	Adipose tissue	Lipolysis	(Less clinically relevant)

🧠 Mnemonic for β-receptor effects: "1 heart, 2 lungs" (β₁ = cardiac, β₂ = pulmonary)

Epinephrine (EPI) acts on ALL adrenergic receptors:

• Low dose: β₂ vasodilation predominates → ↓ diastolic BP
• High dose: α₁ vasoconstriction predominates → ↑ systolic and diastolic BP

Cholinergic Receptors (Parasympathetic)

Receptor Type	Location	Agonist	Antagonist
Muscarinic (M)	Smooth muscle, cardiac muscle, glands	Bethanechol, Pilocarpine	Atropine, Scopolamine
Nicotinic (Nₙ)	Autonomic ganglia	Nicotine	Mecamylamine
Nicotinic (Nₘ)	Neuromuscular junction	Succinylcholine	Tubocurarine

🧠 Mnemonic for Muscarinic effects: "DUMBBELSS"

• Diarrhea
• Urination
• Miosis (pupil constriction)
• Bronchospasm
• Bradycardia
• Excitation (CNS)
• Lacrimation
• Salivation
• Sweating

⚠️ Atropine toxicity: "Red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare"

• Flushed skin (vasodilation)
• No sweating (anhidrosis) → hyperthermia
• Mydriasis (dilated pupils)
• Confusion/delirium
• Fever

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Cardiovascular Pharmacology ❤️

Cardiovascular drugs are among the most commonly tested on Step 1.

Antihypertensives

Diuretics:

• Thiazides (hydrochlorothiazide): Block Na⁺/Cl⁻ cotransporter in DCT

  • Side effects: Hypokalemia, hypercalcemia, hyperglycemia, hyperlipidemia, hyperuricemia
  • 🧠 Mnemonic: "Hyperglycemia, Hyperlipidemia, Hyperuricemia, HyperCalcemia" (all HYPER except K⁺)

• Loop diuretics (furosemide): Block Na⁺/K⁺/2Cl⁻ cotransporter in thick ascending limb

  • Side effects: Hypokalemia, hypocalcemia, ototoxicity, dehydration
  • ⚠️ Watch for interaction with aminoglycosides (additive ototoxicity)

• K⁺-sparing diuretics:

  • Spironolactone: Aldosterone receptor antagonist → gynecomastia, hyperkalemia
  • Amiloride/Triamterene: Block ENaC channels → less gynecomastia than spironolactone

ACE Inhibitors (-pril: captopril, enalapril, lisinopril):

• MOA: Inhibit ACE → ↓ angiotensin II, ↓ aldosterone, ↑ bradykinin
• Benefits: Renoprotective (↓ proteinuria), beneficial in HF and post-MI
• Side effects: Cough (from bradykinin), angioedema, hyperkalemia, acute renal failure (especially with bilateral renal artery stenosis), teratogenic

ARBs (-sartan: losartan, valsartan):

• MOA: Block AT₁ receptors
• Similar benefits to ACE inhibitors but no cough (don't affect bradykinin)
• Same contraindication in pregnancy (teratogenic)

Calcium Channel Blockers:

• Dihydropyridines (-dipine: amlodipine, nifedipine): Vascular-selective
  • Effect: Vasodilation → ↓ BP, reflex tachycardia, peripheral edema
• Non-dihydropyridines (verapamil, diltiazem): Cardiac-selective
  • Effect: ↓ HR, ↓ contractility, ↓ AV conduction
  • ⚠️ Contraindicated with β-blockers (risk of heart block)

β-Blockers (-olol: metoprolol, propranolol, atenolol):

• MOA: Block β₁ receptors → ↓ HR, ↓ contractility, ↓ renin release
• Indications: HTN, angina, HF (selected agents), post-MI, arrhythmias
• Side effects: Bradycardia, AV block, bronchospasm (non-selective agents), mask hypoglycemia, fatigue
• ⚠️ Never stop abruptly → risk of rebound hypertension/angina

Antiarrhythmics (Vaughan Williams Classification)

Class	MOA	Drugs	Use	Key Side Effect
IA	Block Na⁺ channels (moderate)	Quinidine, Procainamide, Disopyramide	Atrial/ventricular arrhythmias	↑ QT → torsades
IB	Block Na⁺ channels (weak)	Lidocaine, Mexiletine	Ventricular arrhythmias post-MI	CNS effects (seizures)
IC	Block Na⁺ channels (strong)	Flecainide, Propafenone	SVT in normal hearts	Proarrhythmic (CAST trial)
II	β-blockers	Metoprolol, Esmolol	SVT, rate control	Bradycardia, bronchospasm
III	Block K⁺ channels	Amiodarone, Sotalol, Ibutilide	Atrial/ventricular arrhythmias	↑ QT, torsades
IV	Ca²⁺ channel blockers	Verapamil, Diltiazem	SVT, rate control	Bradycardia, AV block

💡 Special Note on Amiodarone: Most effective antiarrhythmic but multiple toxicities:

• Pulmonary fibrosis (most serious)
• Thyroid dysfunction (hyper or hypo—contains iodine)
• Hepatotoxicity
• Corneal deposits (reversible)
• Blue-gray skin discoloration
• ↑ QT interval

🧠 Mnemonic for torsades de pointes causes: "PACE Quinidine"

• Procainamide
• Amiodarone
• Class IA and III drugs
• Erythromycin
• Quinidine

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Antimicrobial Pharmacology 🦠

Antimicrobial agents are extensively tested. Focus on mechanism, spectrum, and resistance.

β-Lactam Antibiotics

Mechanism: All β-lactams inhibit bacterial cell wall synthesis by binding penicillin-binding proteins (PBPs) and preventing peptidoglycan cross-linking. They are bactericidal and work best against actively dividing bacteria.

Penicillins:

• Penicillin G/V: Streptococci, syphilis (T. pallidum), actinomyces
• Aminopenicillins (ampicillin, amoxicillin): Extended spectrum → HELPSS bugs
  • H. influenzae, E. coli, Listeria, Proteus, Salmonella, Shigella
• Antistaphylococcal (nafcillin, oxacillin, dicloxacillin): MSSA
• Antipseudomonal (piperacillin, ticarcillin): Pseudomonas + others

β-Lactamase Inhibitors (clavulanic acid, sulbactam, tazobactam):

• Often combined with penicillins (e.g., amoxicillin-clavulanate, piperacillin-tazobactam)
• Extend spectrum to β-lactamase-producing organisms

Cephalosporins (organized by generation):

Generation	Examples	Coverage	Clinical Use
1st	Cefazolin, Cephalexin	Gram+ (MSSA), PEcK (Proteus, E. coli, Klebsiella)	Surgical prophylaxis
2nd	Cefuroxime, Cefoxitin	Enhanced Gram-, anaerobes (cefoxitin)	Community pneumonia
3rd	Ceftriaxone, Cefotaxime, Ceftazidime	Serious Gram- infections, meningitis	Meningitis, gonorrhea, Lyme
4th	Cefepime	Pseudomonas + Gram+	Hospital-acquired infections
5th	Ceftaroline	MRSA + others	MRSA skin infections

🧠 Mnemonic for generations: "1st generation—Greater Gram-positive. 3rd generation—Greater Gram-negative."

Carbapenems (imipenem, meropenem, ertapenem):

• Broadest spectrum β-lactams
• Cover Gram+, Gram-, anaerobes
• ⚠️ Imipenem: Given with cilastatin (inhibits renal dehydropeptidase) to prevent drug breakdown
• Side effect: Seizures (especially imipenem)
• Resistance: Carbapenemases (KPC, NDM-1) → "superbugs"

Monobactam (aztreonam):

• Only Gram- coverage (including Pseudomonas)
• No cross-reactivity with other β-lactams → safe in penicillin-allergic patients

Protein Synthesis Inhibitors

30S Ribosomal Subunit:

• Aminoglycosides (gentamicin, tobramycin, amikacin):

  • MOA: Irreversibly bind 30S → misreading of mRNA
  • Bactericidal, require O₂ (ineffective against anaerobes)
  • Synergy with β-lactams (enhance penetration)
  • Side effects: Nephrotoxicity, ototoxicity (irreversible)
  • ⚠️ Requires therapeutic drug monitoring

• Tetracyclines (doxycycline, tetracycline):

  • MOA: Reversibly bind 30S → block tRNA binding
  • Bacteriostatic
  • Use: Rickettsial diseases (Rocky Mountain spotted fever), Lyme, Chlamydia, Mycoplasma
  • Side effects: Tooth discoloration/bone growth inhibition in children, photosensitivity, GI upset
  • ⚠️ Contraindicated in pregnancy and children <8 years

50S Ribosomal Subunit:

• Macrolides (azithromycin, clarithromycin, erythromycin):

  • MOA: Bind 50S → block translocation
  • Use: Atypical pneumonia (Mycoplasma, Legionella, Chlamydia)
  • Side effects: GI upset, ↑ QT interval, CYP450 inhibition (erythromycin > clarithromycin > azithromycin)

• Chloramphenicol:

  • MOA: Inhibits peptidyltransferase at 50S
  • Side effects: Gray baby syndrome (neonates lack glucuronyl transferase), aplastic anemia, bone marrow suppression
  • ⚠️ Rarely used due to toxicity

• Clindamycin:

  • MOA: Blocks translocation at 50S
  • Use: Anaerobic infections (B. fragilis), skin/soft tissue (MRSA community strains)
  • Side effect: C. difficile colitis (pseudomembranous colitis)

🧠 Mnemonic for ribosomal inhibitors: "Buy AT 30, CCEL at 50"

• 30S: Aminoglycosides, Tetracyclines
• 50S: Chloramphenicol, Clindamycin/Erythromycin (macrolides), Linezolid

DNA/RNA Synthesis Inhibitors

Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin):

• MOA: Inhibit topoisomerase II (DNA gyrase) and topoisomerase IV
• Bactericidal
• Broad spectrum: Gram- (especially ciprofloxacin for Pseudomonas), atypicals
• Side effects: Tendon rupture (Achilles), cartilage damage in children, ↑ QT interval
• ⚠️ Avoid in pregnancy and children (except special circumstances)

Metronidazole:

• MOA: Forms toxic free radicals that damage DNA
• Use: Anaerobes (B. fragilis, C. difficile), protozoa (Giardia, Entamoeba, Trichomonas)
• Side effect: Disulfiram-like reaction with alcohol (flushing, nausea)

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Clinical Examples with Detailed Explanations 🏥

Example 1: Drug Interaction Emergency

Clinical Scenario: A 68-year-old man with atrial fibrillation on warfarin (INR stable at 2.5) develops a urinary tract infection. His primary care physician prescribes trimethoprim-sulfamethoxazole. Three days later, the patient presents to the ED with hematuria and an INR of 8.2.

What happened?

Trimethoprim-sulfamethoxazole is a CYP2C9 inhibitor. Warfarin is metabolized by CYP2C9. When the antibiotic inhibited this enzyme, warfarin levels increased dramatically, leading to excessive anticoagulation and bleeding.

Key Learning Points:

1. Always check for drug-drug interactions before prescribing
2. Warfarin has a narrow therapeutic index → small changes in metabolism cause large clinical effects
3. Multiple antibiotics interact with warfarin: macrolides, metronidazole, fluoroquinolones, sulfonamides
4. Management: Hold warfarin, give vitamin K (reverses warfarin), consider fresh frozen plasma for immediate reversal if life-threatening bleeding

💡 Step 1 Pearl: Know which drugs are CYP450 substrates, inducers, and inhibitors. Warfarin + CYP inhibitor = ↑ INR and bleeding risk.

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Example 2: Choosing the Right Antihypertensive

Clinical Scenario: A 55-year-old African American woman with hypertension (BP 168/98), type 2 diabetes, and microalbuminuria needs medication adjustment. Current regimen: metformin only.

Which antihypertensive should you choose?

Answer: ACE inhibitor (or ARB)

Rationale:

1. Renoprotective effect: ACE inhibitors reduce proteinuria and slow progression of diabetic nephropathy by:
   • Dilating efferent arteriole → ↓ intraglomerular pressure
   • Reducing proteinuria independent of BP lowering
2. Microalbuminuria indicates early diabetic kidney disease → ACE inhibitor is first-line
3. ACE inhibitors/ARBs have mortality benefit in diabetic patients

What about thiazides? Thiazides are often first-line in African American patients (who tend to have low-renin hypertension and respond better to diuretics), but the presence of diabetic nephropathy makes ACE inhibitor/ARB the priority.

⚠️ Monitor: Check potassium and creatinine within 1-2 weeks (ACE inhibitors can cause hyperkalemia and acute kidney injury, especially with underlying renal disease)

💡 Step 1 Pearl: ACE inhibitors/ARBs are first-line for hypertension in patients with:

• Diabetes with proteinuria
• Chronic kidney disease
• Heart failure
• Post-myocardial infarction

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Example 3: Antibiotic Selection for Meningitis

Clinical Scenario: A 22-year-old college student presents with severe headache, fever, neck stiffness, and photophobia. LP shows: WBC 2,400 (90% neutrophils), protein 180 mg/dL, glucose 25 mg/dL. Gram stain shows Gram-negative diplococci.

What's the diagnosis and treatment?

Diagnosis: Bacterial meningitis, likely Neisseria meningitidis (Gram-negative diplococci, college student in dorm = risk factor)

Empiric Treatment: Ceftriaxone + Vancomycin

Rationale:

1. Ceftriaxone (3rd generation cephalosporin):

   • Excellent CNS penetration (crosses inflamed blood-brain barrier)
   • Covers N. meningitidis, S. pneumoniae, H. influenzae (most common causes)
   • Bactericidal

2. Vancomycin added empirically because:

   • Rising prevalence of penicillin-resistant S. pneumoniae
   • Ceftriaxone alone may be inadequate for resistant strains

3. Once organism identified as N. meningitidis with sensitivities:

   • Can narrow to penicillin G (most sensitive)
   • Discontinue vancomycin

Additional Management:

• Dexamethasone: Give before or with first antibiotic dose → reduces inflammation, improves outcomes in pneumococcal meningitis
• Prophylaxis for close contacts: Rifampin, ciprofloxacin, or ceftriaxone (to eliminate nasopharyngeal carriage)

💡 Step 1 Pearl: For bacterial meningitis:

• Neonates: Ampicillin + gentamicin (or cefotaxime)
• Children/adults: Ceftriaxone + vancomycin
• Elderly/immunocompromised: Add ampicillin (covers Listeria)

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Example 4: Managing β-Blocker Overdose

Clinical Scenario: A 17-year-old is brought to the ED after ingesting his grandfather's propranolol in a suicide attempt. Vitals: HR 38, BP 75/40, RR 18, O₂ sat 92% on RA. ECG shows sinus bradycardia with widened QRS.

What's your management?

Immediate Actions:

1. ABCs: Airway, breathing, circulation
2. IV access, cardiac monitoring, supplemental O₂
3. Activated charcoal if within 1-2 hours of ingestion

Specific Antidote: Glucagon

Mechanism: Glucagon works through Gs-protein coupled receptors (independent of β-receptors) to:

• ↑ cAMP → ↑ cardiac contractility and HR
• Bypasses the β-receptor blockade

Additional Management:

• IV fluids for hypotension
• Atropine for bradycardia (may have limited effect)
• Calcium (enhances cardiac contractility)
• High-dose insulin + dextrose (euglycemic hyperinsulinemia therapy—emerging treatment)
• Pacing if refractory bradycardia

⚠️ Why not epinephrine alone? Propranolol is a non-selective β-blocker → blocks β₁ and β₂. Giving epinephrine could cause unopposed α-stimulation → severe vasoconstriction and worsening hypertension (though bradycardia and hypotension are usually more concerning).

💡 Step 1 Pearl: Glucagon is the antidote for β-blocker and calcium channel blocker overdose. Mechanism involves bypassing blocked receptors to increase cAMP.

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Common Mistakes to Avoid ⚠️

1. Confusing Drug Classes with Similar Names

❌ Mistake: Mixing up sulfonylureas (diabetes drugs) and sulfonamides (antibiotics)

• Sulfonylureas (glyburide, glipizide): Block K⁺ channels on pancreatic β-cells → ↑ insulin release
• Sulfonamides (sulfamethoxazole): Inhibit folic acid synthesis → antibacterial

✅ Solution: Focus on suffixes and mechanism:

• -ureas: Think "Ur"ea → pancreas → insulin
• -amides: Think antimicrobial

2. Forgetting to Adjust Doses in Renal/Hepatic Impairment

❌ Mistake: Prescribing normal doses of renally-cleared drugs in kidney disease

✅ Key drugs requiring renal dose adjustment:

• Aminoglycosides (gentamicin)
• Vancomycin
• Digoxin
• Lithium
• Metformin (actually contraindicated in renal failure → lactic acidosis risk)
• ACE inhibitors/ARBs
• Many antimicrobials

✅ Key drugs requiring hepatic dose adjustment:

• Benzodiazepines
• Warfarin
• Statins
• Phenytoin

3. Overlooking Contraindications

❌ Mistake: Prescribing β-blockers to asthmatic patients

• Non-selective β-blockers (propranolol) block β₂ → bronchospasm → asthma exacerbation
• Even "cardioselective" β₁-blockers (metoprolol) lose selectivity at higher doses

✅ Other important contraindications:

• ACE inhibitors/ARBs in pregnancy (teratogenic—cause renal agenesis)
• Aminoglycosides with loop diuretics (additive ototoxicity)
• Tetracyclines in children <8 years (tooth discoloration)
• Fluoroquinolones in pregnancy/children (cartilage damage)
• NSAIDs in patients with renal insufficiency or on other nephrotoxic drugs
• Metformin with IV contrast (hold 48 hours before/after → lactic acidosis risk)

4. Missing Drug-Drug Interactions

❌ Mistake: Starting rifampin (potent CYP450 inducer) without adjusting other medications

✅ Critical interactions:

• Rifampin ↓ levels of: oral contraceptives (treatment failure/pregnancy), warfarin, HIV protease inhibitors, many others
• Macrolides/azoles ↑ levels of: statins (rhabdomyolysis risk), warfarin (bleeding)
• SSRIs + MAO inhibitors → serotonin syndrome
• Warfarin + NSAIDs → ↑ bleeding risk
• Digoxin + loop diuretics → hypokalemia → ↑ digoxin toxicity

5. Not Considering Pharmacodynamic Tolerance/Dependence

❌ Mistake: Abruptly stopping chronic benzodiazepines or β-blockers

✅ Drugs requiring gradual taper:

• Benzodiazepines: Abrupt cessation → seizures, anxiety, tremors
• β-Blockers: Rebound tachycardia, hypertension, angina
• SSRIs: Discontinuation syndrome (dizziness, paresthesias, flu-like symptoms)
• Corticosteroids: Adrenal suppression → adrenal crisis
• Alcohol (considered a "drug"): Withdrawal can be life-threatening

6. Ignoring Age-Related Pharmacology Changes

❌ Mistake: Using same adult doses in neonates/elderly

✅ Neonates:

• Immature liver/kidney → ↓ drug clearance
• ↓ protein binding → ↑ free drug
• Example: Chloramphenicol → gray baby syndrome (can't glucuronidate)

✅ Elderly:

• ↓ renal function (↓ GFR with age)
• ↓ hepatic blood flow
• ↑ body fat → ↑ Vd for lipophilic drugs
• Beers Criteria: Lists potentially inappropriate medications in elderly
  • Avoid: First-generation antihistamines (diphenhydramine), benzodiazepines (↑ falls), anticholinergics

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Key Takeaways 🎯

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📚 Further Study

To deepen your pharmacology mastery:

1. Sketchy Pharmacology (https://www.sketchy.com) - Visual mnemonics for drug mechanisms, uses, and side effects. Excellent for retention.

2. First Aid for USMLE Step 1 (https://www.firstaidteam.com) - Gold standard review book with high-yield pharmacology tables and concepts.

3. UWorld USMLE Step 1 Question Bank (https://www.uworld.com) - The most comprehensive question bank with detailed explanations. Essential for board preparation.

Consistent daily review with spaced repetition using flashcards will transform these concepts from memorization to lasting clinical knowledge. Focus on understanding mechanisms—this will help you reason through questions even when you don't immediately recognize the drug. Good luck with your preparation! 🎓