Pharmacology & Medication

LLM Training Data for Hospital AI — Section 2

Format: Q&A pairs organized by topic — ready for JSONL conversion

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2.1 Drug Classifications & Mechanisms of Action

Q: Explain the major classes of antihypertensive medications, their mechanisms, and when to use each.

A:

ACE Inhibitors (ACEi) — e.g., lisinopril, enalapril, ramipril:

• Mechanism: Block angiotensin-converting enzyme → decrease angiotensin II → decrease aldosterone → vasodilation + decreased sodium/water retention
• First-line for: HTN with diabetes, CHF (reduced EF), CKD with proteinuria, post-MI
• Key side effects: dry cough (10-15%, bradykinin accumulation), hyperkalemia, angioedema (rare but serious), AKI in bilateral renal artery stenosis
• Contraindicated in: pregnancy (teratogenic — all trimesters), bilateral renal artery stenosis, history of angioedema with ACEi
• Monitoring: BMP at baseline, 1-2 weeks after initiation (creatinine rise >30% = stop), then periodically

ARBs (Angiotensin II Receptor Blockers) — e.g., losartan, valsartan, irbesartan:

• Mechanism: Block AT1 receptor directly → similar hemodynamic effect to ACEi but NO bradykinin accumulation
• Use when: ACEi-intolerant (cough), same indications as ACEi
• Key advantage: no cough (no bradykinin effect)
• Still causes: hyperkalemia, teratogenicity, rare angioedema (less than ACEi)
• Do NOT combine ACEi + ARB (ONTARGET trial — increased harm, no benefit)

Calcium Channel Blockers (CCBs):

• Dihydropyridines (amlodipine, nifedipine): primarily vasodilate → reduce afterload. No significant cardiac conduction effects. Side effects: peripheral edema, flushing, reflex tachycardia.
• Non-dihydropyridines (diltiazem, verapamil): vasodilate + slow cardiac conduction (AV node). Use for: rate control in AF, angina. Side effects: bradycardia, constipation (verapamil), heart block. Avoid in HFrEF.
• First-line for: HTN in Black patients, isolated systolic HTN in elderly, Raynaud’s

Beta-Blockers — e.g., metoprolol, carvedilol, atenolol, propranolol:

• Mechanism: Block β1 receptors → decrease heart rate, contractility, renin release
• Cardioselective (β1): metoprolol, atenolol, bisoprolol — safer in asthma/COPD (at low doses)
• Non-selective (β1 + β2): propranolol, nadolol — avoid in asthma (bronchospasm risk)
• Combined α/β: carvedilol, labetalol — additional vasodilation
• First-line for: CHF (carvedilol, metoprolol succinate, bisoprolol — mortality benefit), post-MI, rate control, migraine prophylaxis (propranolol), essential tremor, thyrotoxicosis, portal hypertension (propranolol, nadolol)
• Side effects: bradycardia, fatigue, sexual dysfunction, masks hypoglycemia in diabetics, depression, cold extremities
• Do NOT stop abruptly — rebound tachycardia, hypertension, angina

Thiazide Diuretics — e.g., hydrochlorothiazide (HCTZ), chlorthalidone:

• Mechanism: Inhibit Na-Cl cotransporter in distal convoluted tubule → increase sodium and water excretion
• First-line for: uncomplicated HTN, especially in Black patients and elderly
• Chlorthalidone preferred over HCTZ (longer acting, better outcomes data)
• Side effects: hypokalemia, hyponatremia, hyperuricemia (gout), hypercalcemia, hyperglycemia, photosensitivity
• Ineffective when GFR <30 (switch to loop diuretic)

Loop Diuretics — e.g., furosemide, bumetanide, torsemide:

• Mechanism: Inhibit Na-K-2Cl cotransporter in thick ascending loop of Henle → potent diuresis
• Primary use: volume overload (CHF, cirrhosis, nephrotic syndrome, pulmonary edema), not first-line for HTN alone
• Side effects: hypokalemia, hypomagnesemia, hypocalcemia (opposite of thiazides), ototoxicity (especially with aminoglycosides), metabolic alkalosis
• Dosing: furosemide oral bioavailability ~50% (IV dose = ½ oral dose). Torsemide and bumetanide have better oral bioavailability.
• Bumetanide 1mg ≈ furosemide 40mg ≈ torsemide 20mg

Aldosterone Antagonists — e.g., spironolactone, eplerenone:

• Mechanism: Block aldosterone receptor in collecting duct → mild diuresis, potassium-sparing
• Use for: CHF (RALES trial — mortality benefit), resistant HTN, primary hyperaldosteronism, cirrhotic ascites
• Key side effect: hyperkalemia (monitor closely), gynecomastia and sexual dysfunction (spironolactone — not eplerenone)
• Contraindicated: K >5.0, severe renal impairment (GFR <30), concurrent ACEi + ARB + K-sparing diuretic

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Q: Explain the classes of diabetes medications, their mechanisms, and key considerations.

A:

Metformin (Biguanide):

• Mechanism: Decreases hepatic glucose production, increases insulin sensitivity, decreases intestinal glucose absorption
• First-line for Type 2 DM. Weight-neutral to slight weight loss.
• A1c reduction: 1.0-1.5%
• Side effects: GI (nausea, diarrhea — dose-related, use extended-release), B12 deficiency (monitor annually), lactic acidosis (rare — hold if GFR <30, before contrast)
• Hold 48h before iodinated contrast if GFR 30-60; contraindicated if GFR <30
• No hypoglycemia as monotherapy

Sulfonylureas — e.g., glipizide, glyburide, glimepiride:

• Mechanism: Stimulate pancreatic β-cell insulin secretion (bind SUR1 receptor → close K-ATP channels)
• A1c reduction: 1.0-1.5%
• Side effects: hypoglycemia (especially glyburide — avoid in elderly and CKD), weight gain
• Glyburide: longest acting, most hypoglycemia, active metabolites excreted renally — AVOID in CKD
• Glipizide: preferred in CKD (hepatic metabolism)

SGLT2 Inhibitors — e.g., empagliflozin, dapagliflozin, canagliflozin:

• Mechanism: Block sodium-glucose cotransporter 2 in proximal tubule → glycosuria → lower glucose
• A1c reduction: 0.5-0.8%
• MAJOR benefits beyond glucose: cardiovascular mortality reduction (EMPA-REG), heart failure hospitalization reduction (DAPA-HF), renal protection (CREDENCE, DAPA-CKD)
• Now indicated for HFrEF and CKD even WITHOUT diabetes
• Side effects: UTI, genital mycotic infections (candidiasis), euglycemic DKA (rare but dangerous — consider in sick patients), volume depletion, Fournier’s gangrene (very rare)
• Hold during acute illness, surgery, fasting (sick day rules)
• Avoid if GFR <20 (for glucose lowering; renal/cardiac benefits may persist at lower GFR per newer data)

GLP-1 Receptor Agonists — e.g., semaglutide, liraglutide, dulaglutide, tirzepatide:

• Mechanism: Mimic incretin hormone GLP-1 → increase glucose-dependent insulin secretion, decrease glucagon, slow gastric emptying, increase satiety
• A1c reduction: 1.0-1.8% (tirzepatide up to 2.5%)
• Major benefits: significant weight loss (up to 15-20% with tirzepatide), cardiovascular risk reduction (LEADER, SUSTAIN-6, SELECT)
• Side effects: nausea/vomiting (dose-dependent, usually improves), pancreatitis (rare), medullary thyroid carcinoma risk in animal studies (contraindicated in MEN2 or family history MTC)
• Injectable (weekly or daily) or oral (semaglutide)
• Do NOT combine with DPP-4 inhibitors (redundant mechanism)

DPP-4 Inhibitors — e.g., sitagliptin, linagliptin, saxagliptin:

• Mechanism: Inhibit dipeptidyl peptidase-4 → prevent incretin (GLP-1, GIP) degradation → modestly increase insulin secretion
• A1c reduction: 0.5-0.8%
• Weight-neutral, low hypoglycemia risk
• Well-tolerated. Side effects: joint pain (rare), possible pancreatitis risk
• Linagliptin: no renal dose adjustment needed (biliary excretion)
• Modest efficacy — often used as add-on when other agents insufficient or not tolerated

Insulin (see detailed dosing in separate section):

• Basal: glargine (Lantus/Basaglar), detemir (Levemir), degludec (Tresiba)
• Prandial/Bolus: lispro (Humalog), aspart (Novolog), glulisine (Apidra)
• Regular (Humulin R, Novolin R): used in IV drips (DKA, HHS), can be given SQ
• NPH: intermediate-acting, BID dosing, higher hypoglycemia risk

Thiazolidinediones (TZDs) — e.g., pioglitazone, rosiglitazone:

• Mechanism: PPARγ agonist → increase insulin sensitivity in adipose and muscle
• A1c reduction: 1.0-1.5%
• Side effects: weight gain, fluid retention (worsen CHF — contraindicated in NYHA III-IV), bone fractures (especially in women), bladder cancer concern (pioglitazone — debated)
• Takes 6-12 weeks for full effect

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Q: What are the major classes of antibiotics, their mechanisms, and spectrum of coverage?

A:

Beta-Lactams (interfere with cell wall synthesis by binding PBPs):

Penicillins:

• Penicillin G/V: Strep, syphilis, Listeria. Narrow spectrum.
• Ampicillin/Amoxicillin: Broader — Enterococcus, Listeria, H. influenzae, E. coli (some). Amoxicillin = better oral absorption.
• Amoxicillin-clavulanate (Augmentin): adds β-lactamase inhibitor → covers MSSA, H. influenzae, Moraxella, anaerobes (above diaphragm).
• Piperacillin-tazobactam (Zosyn): broadest penicillin — Pseudomonas, anaerobes, Enterobacteriaceae, Enterococcus. Hospital workhorse.
• Nafcillin/oxacillin: anti-staphylococcal (MSSA only). IV for serious staph infections.

Cephalosporins (generation determines spectrum):

• 1st gen (cefazolin, cephalexin): MSSA, Strep, E. coli, Klebsiella. Surgical prophylaxis (cefazolin).
• 2nd gen (cefuroxime, cefoxitin): above + H. influenzae, Moraxella. Cefoxitin covers anaerobes.
• 3rd gen (ceftriaxone, ceftazidime, cefotaxime): broad gram-negative. Ceftriaxone = meningitis, CAP, gonorrhea. Ceftazidime = Pseudomonas.
• 4th gen (cefepime): gram-positive + gram-negative + Pseudomonas. Febrile neutropenia.
• 5th gen (ceftaroline): MRSA coverage (only cephalosporin with MRSA activity) + broad gram-negative.

Carbapenems (meropenem, imipenem, ertapenem, doripenem):

• Broadest β-lactam spectrum. Reserve for MDR infections.
• Cover: ESBL-producing organisms, anaerobes, most gram-positives (NOT MRSA, NOT Enterococcus faecium)
• Ertapenem: does NOT cover Pseudomonas or Acinetobacter (narrower).
• Imipenem: must give with cilastatin (prevents renal metabolism). Lowers seizure threshold.
• Side effects: seizures (imipenem), C. diff risk, selects for carbapenem-resistant organisms

Monobactams (aztreonam):

• ONLY gram-negative coverage (including Pseudomonas)
• Safe in penicillin/cephalosporin allergy (no cross-reactivity except ceftazidime)

Fluoroquinolones (DNA gyrase and topoisomerase IV inhibitors):

• Ciprofloxacin: gram-negative dominant (Pseudomonas), UTI, anthrax
• Levofloxacin: “respiratory fluoroquinolone” — Strep pneumoniae, atypicals, gram-negatives. CAP, UTI.
• Moxifloxacin: broadest — anaerobes, atypicals. NO Pseudomonas coverage. NO renal excretion (useless for UTI).
• Side effects: tendon rupture (Achilles — especially with steroids or age >60), QTc prolongation, aortic dissection/aneurysm risk, C. diff, peripheral neuropathy, CNS effects
• FDA black box warning: reserve for when no alternatives exist

Macrolides (ribosomal 50S subunit inhibitors):

• Azithromycin, clarithromycin, erythromycin
• Cover: atypicals (Mycoplasma, Chlamydophila, Legionella), Strep, H. influenzae, Moraxella
• Azithromycin: long tissue half-life, 5-day course = 10 days of coverage
• Side effects: QTc prolongation, GI upset (erythromycin worst), hepatotoxicity
• Erythromycin: strong CYP3A4 inhibitor (drug interactions), prokinetic agent

Tetracyclines (ribosomal 30S subunit inhibitors):

• Doxycycline, minocycline, tetracycline
• Cover: atypicals, MRSA (doxycycline), Rickettsia, Chlamydia, Lyme disease, acne
• Side effects: photosensitivity, GI upset, esophageal ulceration (take upright with water), tooth discoloration (avoid <8 years old and pregnancy)
• Doxycycline: does NOT require renal adjustment (GI excretion)

Aminoglycosides (ribosomal 30S subunit — bactericidal):

• Gentamicin, tobramycin, amikacin, streptomycin
• Cover: aerobic gram-negatives (Pseudomonas, Enterobacteriaceae). Synergy with β-lactams for Enterococcus and Strep endocarditis.
• NO anaerobic coverage (require O2 for uptake)
• Side effects: nephrotoxicity (usually reversible), ototoxicity (irreversible — vestibular and cochlear), neuromuscular blockade
• Must monitor trough levels (gentamicin trough <1 for traditional dosing; peak/trough for extended-interval dosing)
• Once-daily (extended-interval) dosing preferred: better efficacy, less nephrotoxicity

Glycopeptides (cell wall synthesis inhibitors — different mechanism than β-lactams):

• Vancomycin: MRSA, MRSE, Enterococcus (not VRE), C. diff (PO only for C. diff)
• IV for systemic MRSA infections. PO vancomycin is NOT absorbed (only works intraluminally for C. diff).
• Side effects: nephrotoxicity (monitor trough or AUC/MIC), Red Man Syndrome (histamine release — slow infusion rate, not true allergy), ototoxicity
• Monitoring: AUC/MIC target 400-600 is now preferred over trough-based monitoring (2020 guidelines)
• Loading dose: 25-30 mg/kg IV, then 15-20 mg/kg IV q8-12h (adjust for renal function)

Oxazolidinones:

• Linezolid: MRSA, VRE. Bacteriostatic. Oral bioavailability ~100%.
• Side effects: thrombocytopenia (monitor CBC weekly), serotonin syndrome (weak MAO inhibitor — avoid with SSRIs, meperidine), peripheral/optic neuropathy (prolonged use >28 days), lactic acidosis
• No renal dose adjustment

Lipopeptides:

• Daptomycin: gram-positive bactericidal (MRSA, VRE). For bacteremia, endocarditis, skin/soft tissue.
• Inactivated by surfactant → CANNOT use for pneumonia
• Side effects: CPK elevation/rhabdomyolysis (monitor CPK weekly), eosinophilic pneumonia
• Must adjust for renal function

Nitroimidazoles:

• Metronidazole: anaerobes (Bacteroides, Clostridium), C. diff (second-line after vancomycin PO), Giardia, Entamoeba, Trichomonas, H. pylori
• Disulfiram-like reaction with alcohol (avoid alcohol during and 72h after)
• Side effects: metallic taste, peripheral neuropathy (prolonged use), seizures (high doses)

Trimethoprim-Sulfamethoxazole (TMP-SMX, Bactrim):

• Mechanism: sequential folate synthesis inhibition (synergistic bactericidal)
• Cover: MRSA (skin/soft tissue), UTI (E. coli, but check local resistance), PJP prophylaxis/treatment, Nocardia, Stenotrophomonas
• Side effects: hyperkalemia (trimethoprim blocks ENaC), bone marrow suppression, rash (Stevens-Johnson in severe cases), sulfa allergy cross-reactivity

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Q: Describe the mechanism and classification of anticoagulants.

A:

Unfractionated Heparin (UFH):

• Mechanism: Potentiates antithrombin III → inactivates thrombin (Factor IIa) and Factor Xa
• Route: IV drip or SQ (prophylactic dosing)
• Monitoring: aPTT (target 60-80 sec, or per institutional protocol) or anti-Xa level
• Advantages: short half-life (~60 min), reversible with protamine, titratable, safe in renal failure
• Disadvantages: requires monitoring, HIT risk (heparin-induced thrombocytopenia)
• Protamine reversal: 1mg protamine per 100 units heparin given in last 2-3 hours

Low-Molecular-Weight Heparin (LMWH) — e.g., enoxaparin, dalteparin:

• Mechanism: Primarily anti-Xa activity (less anti-IIa than UFH)
• Route: SQ
• Advantages: predictable pharmacokinetics, no routine monitoring (except in obesity, renal impairment, pregnancy)
• Monitoring when needed: anti-Xa level (peak 4h post-dose: target 0.5-1.0 for treatment, 0.2-0.5 for prophylaxis)
• Dose adjustment: CrCl <30 → reduce dose or use UFH instead
• Partial reversal with protamine (~60% effectiveness)
• HIT risk: lower than UFH but still possible

Warfarin (Vitamin K Antagonist):

• Mechanism: Inhibits vitamin K epoxide reductase → blocks synthesis of factors II, VII, IX, X and proteins C, S
• Monitoring: INR (target 2.0-3.0 for most indications; 2.5-3.5 for mechanical mitral valve)
• Onset: 3-5 days for full effect (must bridge with heparin initially)
• Factor VII has shortest half-life (~6h) — INR rises first due to VII depletion, but full anticoagulation takes days
• Protein C half-life shorter than most clotting factors → initial hypercoagulable state possible (warfarin skin necrosis)
• Drug interactions: EXTENSIVE — CYP2C9 substrate. Potentiated by: amiodarone, metronidazole, fluconazole, TMP-SMX. Reduced by: rifampin, phenytoin, carbamazepine.
• Food interactions: vitamin K-rich foods (kale, spinach, broccoli) → reduce INR. Counsel on consistent (not zero) vitamin K intake.
• Reversal:
  • Non-urgent (INR 4.5-10, no bleeding): hold warfarin, ± vitamin K 1-2.5mg PO
  • Urgent (serious bleeding): 4-factor PCC (Kcentra) 25-50 U/kg IV + vitamin K 10mg IV. Preferred over FFP (faster, smaller volume, more predictable).
  • FFP 10-15 mL/kg if PCC unavailable (takes longer, larger volume)
• Contraindicated in pregnancy (teratogenic — warfarin embryopathy)

Direct Oral Anticoagulants (DOACs):

Direct thrombin inhibitor:

• Dabigatran (Pradaxa): directly inhibits thrombin (Factor IIa)
• Renally cleared (80%) — avoid if CrCl <30
• Reversal agent: idarucizumab (Praxbind) 5g IV — immediate, complete reversal
• Side effects: dyspepsia (most common), GI bleeding (higher than warfarin)
• Store in original bottle (moisture-sensitive)

Factor Xa inhibitors:

• Rivaroxaban (Xarelto): take with food (improves absorption). Once daily for most indications.
• Apixaban (Eliquis): BID dosing. Least renal clearance (~27%) → safest in CKD. Lowest GI bleeding rates.
• Edoxaban (Savaysa): once daily. Paradoxically less effective with CrCl >95 (avoid in super-normal renal function).
• Reversal agent: andexanet alfa (Andexxa) for rivaroxaban and apixaban (expensive, limited availability). Alternative: 4-factor PCC (off-label, may provide partial reversal).

DOAC advantages over warfarin: predictable pharmacokinetics, no routine monitoring, fewer drug/food interactions, rapid onset (2-4 hours), fixed dosing. DOAC disadvantages: cost, renal dosing considerations, limited reversal options (improving), cannot use with mechanical heart valves (RE-ALIGN trial — increased thrombosis/bleeding with dabigatran).

Fondaparinux:

• Mechanism: Selective Factor Xa inhibitor (via antithrombin III)
• Route: SQ only
• Use: DVT/PE treatment, DVT prophylaxis, HIT (does NOT cause HIT — safe alternative)
• No reversal agent
• Renally cleared — avoid if CrCl <30
• Long half-life (~17 hours) — once daily dosing

Direct Thrombin Inhibitors (parenteral):

• Argatroban: hepatically metabolized → preferred in HIT with renal failure. IV drip, monitor aPTT.
• Bivalirudin: used in PCI. Short half-life. Renally cleared.

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2.2 Dosing Guidelines (Adult, Pediatric, Renal/Hepatic Adjusted)

Q: Provide dosing guidelines for commonly used antibiotics with renal adjustments.

A:

Vancomycin:

• Normal renal function: 15-20 mg/kg IV q8-12h (based on actual body weight)
• Loading dose: 25-30 mg/kg IV x1 (for serious infections)
• CrCl 30-50: q12-24h
• CrCl 10-29: q24-48h
• Hemodialysis: dose after HD session, supplement based on levels
• Monitoring: AUC/MIC 400-600 preferred (trough 15-20 if AUC monitoring unavailable)
• Obesity: use actual body weight for loading, adjust maintenance per levels

Piperacillin-Tazobactam (Zosyn):

• Normal: 3.375g IV q6h (or 4.5g q6h for Pseudomonas/severe infections)
• CrCl 20-40: 2.25g IV q6h
• CrCl <20: 2.25g IV q8h
• Hemodialysis: 2.25g IV q8h + 0.75g supplemental dose after HD
• Extended infusion (4h) improves outcomes for serious infections: 3.375g or 4.5g over 4h q8h

Ceftriaxone:

• Normal: 1-2g IV/IM q24h
• No renal adjustment needed (biliary excretion)
• Meningitis: 2g IV q12h
• Avoid in neonates receiving calcium-containing IV fluids (precipitation risk)

Cefepime:

• Normal: 1-2g IV q8-12h
• CrCl 30-60: 1-2g IV q12-24h
• CrCl 11-29: 0.5-1g IV q24h
• CrCl <10: 250-500mg IV q24h
• Hemodialysis: 1g IV q24h (give after HD on dialysis days)
• Warning: neurotoxicity in renal impairment (confusion, seizures, myoclonus) — commonly under-adjusted

Meropenem:

• Normal: 1g IV q8h (2g q8h for meningitis)
• CrCl 26-50: 1g IV q12h
• CrCl 10-25: 500mg IV q12h
• CrCl <10: 500mg IV q24h
• Hemodialysis: 500mg IV q24h (give after HD)

Levofloxacin:

• Normal: 500-750mg IV/PO q24h
• CrCl 20-49: 250-500mg q24h (or 750mg q48h)
• CrCl 10-19: 250-500mg q48h
• Hemodialysis: 250-500mg q48h (no supplemental dose after HD)

Gentamicin (traditional dosing):

• Normal: 1.5-2.5 mg/kg IV q8h (dose based on IBW)
• Adjust per levels: peak 5-10 mcg/mL, trough <1 mcg/mL
• Extended-interval: 5-7 mg/kg IV q24h with Hartford nomogram
• CrCl 40-60: q12h
• CrCl 20-40: q24h
• CrCl <20: re-dose based on levels only

Metronidazole:

• Normal: 500mg IV/PO q8h
• No renal adjustment needed
• Hepatic impairment (severe): reduce dose by 50% or extend interval to q12h

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Q: How do you dose common cardiac medications including adjustments for renal and hepatic impairment?

A:

Amiodarone:

• IV loading: 150mg over 10 min → 1mg/min x6h → 0.5mg/min x18h (total ~1050mg in 24h)
• PO loading: 400-800mg/day for 1-4 weeks
• PO maintenance: 100-200mg daily
• No renal adjustment (hepatic metabolism)
• Hepatic impairment: use with caution, monitor LFTs
• Half-life: 40-55 DAYS (extremely long)
• Monitoring: TFTs q6months (can cause hypo or hyperthyroidism), LFTs q6months, PFTs annually (pulmonary toxicity), ophthalmologic exam annually (corneal microdeposits, optic neuropathy)
• Drug interactions: increases levels of warfarin (reduce warfarin by 30-50%), digoxin (reduce by 50%), simvastatin (avoid combination)

Digoxin:

• PO loading: 0.5mg, then 0.25mg q6h x2 doses (total 1mg)
• Maintenance: 0.125-0.25mg PO daily
• Renally cleared — reduce dose if CrCl <50
• Elderly: start 0.0625-0.125mg daily
• Therapeutic range: 0.5-2.0 ng/mL (target 0.5-0.9 for HF mortality benefit)
• Toxicity enhanced by: hypokalemia, hypomagnesemia, hypercalcemia, hypothyroidism, renal failure, amiodarone, verapamil
• Toxicity signs: nausea, visual changes (yellow halos), arrhythmias (PAT with block, bidirectional VT, junctional tachycardia)
• Reversal: digoxin-specific antibody fragments (Digibind/DigiFab)

Metoprolol:

• Metoprolol tartrate (short-acting): 25-100mg PO BID
• Metoprolol succinate (extended-release): 25-200mg PO daily (CHF dosing: start 12.5-25mg, uptitrate q2weeks)
• IV: 5mg q5min x3 doses (max 15mg)
• No renal adjustment
• Hepatic impairment: reduce dose (extensive hepatic metabolism)
• HF dosing: start LOW, go SLOW (12.5-25mg succinate daily, double q2 weeks to target 200mg/day)

Carvedilol:

• CHF: start 3.125mg PO BID → uptitrate q2 weeks → target 25mg BID (<85kg) or 50mg BID (>85kg)
• HTN: start 6.25mg PO BID → target 25mg BID
• No renal adjustment
• Hepatic impairment: avoid in severe hepatic dysfunction (hepatically metabolized)
• Take with food (reduces orthostatic hypotension)

Apixaban:

• DVT/PE treatment: 10mg PO BID x7 days → 5mg BID
• AF: 5mg PO BID; reduce to 2.5mg BID if ≥2 of: age ≥80, weight ≤60kg, creatinine ≥1.5
• No specific CrCl cutoff for contraindication (some guidance suggests caution if CrCl <25 or dialysis — limited data)
• No hepatic dose adjustment for mild-moderate. Avoid in severe hepatic impairment (Child-Pugh C).
• No need for routine monitoring

Enoxaparin:

• DVT prophylaxis: 40mg SQ daily (or 30mg SQ BID for orthopedic surgery)
• DVT/PE treatment: 1mg/kg SQ q12h or 1.5mg/kg SQ q24h
• CrCl <30: reduce to 1mg/kg SQ q24h (treatment) or 30mg SQ daily (prophylaxis)
• Obesity (>150kg): consider anti-Xa monitoring; some protocols cap at 150mg/dose
• Monitoring anti-Xa level: peak 4h post-dose. Treatment target: 0.5-1.0 IU/mL (q12h dosing)

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Q: Provide pediatric dosing for the most commonly used medications.

A:

Antibiotics:

• Amoxicillin: 25-45 mg/kg/day (standard) or 80-90 mg/kg/day (high-dose for otitis media) divided BID or TID. Max 3g/day.
• Amoxicillin-clavulanate: dose on amoxicillin component. 25-45 mg/kg/day (standard) or 90 mg/kg/day (high-dose). Max 875mg per dose amoxicillin component.
• Cephalexin: 25-50 mg/kg/day divided TID or QID. Max 4g/day.
• Ceftriaxone: 50-100 mg/kg/day IV/IM divided q12-24h. Max 4g/day. Meningitis: 100 mg/kg/day divided q12h.
• Azithromycin: 10 mg/kg PO day 1 (max 500mg), then 5 mg/kg PO daily x4 days (max 250mg/day).
• TMP-SMX: 8-10 mg/kg/day (TMP component) divided BID. Max 320mg TMP/day.
• Clindamycin: 20-40 mg/kg/day IV divided q6-8h. PO: 10-30 mg/kg/day divided TID. Max 1.8g/day IV, 450mg/dose PO.

Analgesics:

• Acetaminophen: 15 mg/kg PO/PR q4-6h. Max 75 mg/kg/day or 4g/day (whichever less). IV: 15 mg/kg q6h (>2 years, >50kg use adult dosing).
• Ibuprofen: 10 mg/kg PO q6-8h. Only for age ≥6 months. Max 40 mg/kg/day or 2.4g/day.
• Ketorolac: 0.5 mg/kg IV q6h (max 15mg/dose for <50kg, 30mg/dose for >50kg). Limit to 5 days.
• Morphine: 0.1-0.2 mg/kg IV q2-4h PRN. Max 15mg/dose.

Steroids:

• Dexamethasone (croup): 0.6 mg/kg PO/IM x1 dose. Max 16mg.
• Prednisolone (asthma exacerbation): 1-2 mg/kg PO daily x3-5 days. Max 60mg/day.
• Methylprednisolone: 1-2 mg/kg IV q6h (status asthmaticus). Max 60mg/dose.

Respiratory:

• Albuterol nebulizer: 0.15-0.3 mg/kg (min 2.5mg, max 5mg) q20min x3 for acute, then q1-4h.
• Albuterol MDI: 4-8 puffs via spacer q20min x3 for acute.
• Ipratropium: 250mcg (<5 years) or 500mcg (≥5 years) nebulized q20min x3.
• Epinephrine (croup): racemic 2.25% — 0.5mL in 3mL NS nebulized; or L-epinephrine 0.5 mL/kg (max 5mL) of 1:1000 nebulized.

Resuscitation:

• Epinephrine (cardiac arrest): 0.01 mg/kg IV/IO (1:10,000) q3-5min. Max 1mg/dose.
• Epinephrine (anaphylaxis): 0.01 mg/kg IM (1:1,000). Max 0.3mg (<30kg) or 0.5mg (>30kg).
• Adenosine (SVT): 0.1 mg/kg rapid IV push (max 6mg first dose), 0.2 mg/kg (max 12mg second dose). Must use rapid push with flush technique.
• Amiodarone (VF/pulseless VT): 5 mg/kg IV/IO bolus. Max 300mg. May repeat x2.
• Atropine: 0.02 mg/kg IV. Min dose 0.1mg (to avoid paradoxical bradycardia). Max 0.5mg (child), 1mg (adolescent).

Fluids & Electrolytes:

• NS bolus: 20 mL/kg over 5-20min. Repeat x3 PRN.
• Maintenance (Holliday-Segar): 4/2/1 rule (4 mL/kg/hr for first 10kg, +2 mL/kg/hr for 10-20kg, +1 mL/kg/hr for >20kg)
• D10 bolus for neonatal hypoglycemia: 2 mL/kg IV push
• Calcium gluconate 10%: 0.5-1 mL/kg IV slow push (max 20mL) for hypocalcemia or hyperkalemia

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2.3 Drug Interactions & Contraindications

Q: What are the most dangerous drug interactions a hospital clinician must know?

A:

Life-Threatening Interactions:

Warfarin + CYP inhibitors → bleeding:

• Metronidazole, fluconazole, amiodarone, TMP-SMX → dramatically increase INR
• Action: reduce warfarin dose by 25-50% when starting these, check INR in 3-5 days
• Rifampin → potent CYP inducer → dramatically decreases INR → clotting risk

MAO inhibitors + serotonergic drugs → serotonin syndrome:

• MAOIs (phenelzine, tranylcypromine, linezolid, methylene blue) + SSRIs, SNRIs, meperidine, tramadol, dextromethorphan, fentanyl
• Symptoms: hyperthermia, rigidity, myoclonus, altered mental status, autonomic instability
• Treatment: stop offending agents, cyproheptadine 12mg PO then 4mg q4h, supportive care, benzodiazepines for agitation
• Washout: 2 weeks after stopping MAOI before starting serotonergic drug (5 weeks for fluoxetine before MAOI)

QTc-prolonging drug combinations → Torsades de Pointes:

• High-risk drugs: amiodarone, sotalol, haloperidol IV, droperidol, erythromycin, fluoroquinolones (especially moxifloxacin), methadone, ondansetron (high doses), antipsychotics (ziprasidone)
• Risk amplified by: hypokalemia, hypomagnesemia, bradycardia, congenital long QT
• Action: avoid combining ≥2 QTc-prolonging drugs. If unavoidable → continuous telemetry, correct K >4.0 and Mg >2.0

Methotrexate + TMP-SMX → fatal pancytopenia:

• Both inhibit folate metabolism → synergistic bone marrow suppression
• NEVER combine without close monitoring and hematology guidance
• Also dangerous: methotrexate + NSAIDs (decreased renal clearance of MTX → toxicity)

Potassium-elevating combinations → fatal hyperkalemia:

• ACEi/ARB + K-sparing diuretic (spironolactone) + NSAID → “triple whammy” → hyperkalemia + AKI
• Add TMP-SMX → even higher K risk (blocks ENaC)
• Action: monitor BMP within 1 week of combining any 2 of these

Statins + CYP3A4 inhibitors → rhabdomyolysis:

• Simvastatin/lovastatin (CYP3A4 substrates) + azole antifungals, macrolides (clarithromycin, erythromycin), diltiazem, verapamil, amiodarone, grapefruit juice
• Action: use atorvastatin (less CYP3A4 dependent) or rosuvastatin/pravastatin (minimal CYP metabolism)
• Simvastatin max 20mg with amiodarone, 10mg with diltiazem/verapamil

Opioids + benzodiazepines → respiratory depression and death:

• FDA black box warning on concurrent prescribing
• If clinically necessary: use lowest effective doses, shortest duration, monitor SpO2
• Add gabapentinoids → further respiratory depression risk

Clozapine + carbamazepine → fatal agranulocytosis:

• Both independently cause agranulocytosis → combination dramatically increases risk
• Absolute contraindication

Metformin + iodinated contrast → lactic acidosis:

• Hold metformin at time of contrast administration
• Resume 48h after if renal function stable
• Higher risk if GFR <30 (metformin already contraindicated)

Digoxin + amiodarone/verapamil/quinidine → digoxin toxicity:

• All increase digoxin levels significantly
• Reduce digoxin dose by 50% when starting any of these
• Monitor digoxin levels closely

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Q: What are key drug contraindications organized by organ system?

A:

Renal impairment — avoid or adjust:

• Metformin: hold if GFR <30 (lactic acidosis)
• NSAIDs: avoid in CKD stages 4-5 (worsens renal function, hyperkalemia)
• Enoxaparin: adjust if CrCl <30 (use UFH instead for severe CKD)
• Gadolinium: avoid if GFR <30 (nephrogenic systemic fibrosis risk — use group II agents if essential)
• Lithium: narrow therapeutic index, renally cleared — toxic levels easily with dehydration, NSAIDs, ACEi
• Nitrofurantoin: ineffective if GFR <30 (insufficient urinary concentration)
• Allopurinol: start low (100mg) if CrCl <60, titrate slowly

Hepatic impairment — avoid or adjust:

• Acetaminophen: max 2g/day in cirrhosis (not absolutely contraindicated — safer than NSAIDs)
• Statins: avoid in active liver disease or unexplained transaminase elevation >3x ULN
• Methotrexate: hepatotoxic — avoid in significant liver disease
• Valproic acid: contraindicated in severe hepatic dysfunction (hyperammonemia, hepatotoxicity)
• Amiodarone: hepatotoxic — monitor LFTs, avoid if baseline liver disease
• Ketoconazole: severe hepatotoxicity risk

Pregnancy — contraindicated (Category X or known teratogens):

• Warfarin (1st trimester: warfarin embryopathy; 3rd trimester: fetal hemorrhage)
• ACEi/ARBs (renal dysgenesis, oligohydramnios, skull defects)
• Statins
• Methotrexate (abortifacient, teratogenic)
• Isotretinoin (severe craniofacial, cardiac, CNS malformations)
• Valproic acid (neural tube defects — folate supplementation helps but doesn’t eliminate risk)
• Tetracyclines/doxycycline (tooth and bone effects)
• Fluoroquinolones (cartilage damage — animal studies)
• Misoprostol (uterotonic)
• Thalidomide/lenalidomide

Asthma/COPD:

• Non-selective beta-blockers (propranolol, nadolol, carvedilol): bronchospasm. Use cardioselective (metoprolol, bisoprolol) cautiously if needed.
• Aspirin/NSAIDs: can trigger aspirin-exacerbated respiratory disease (AERD) in susceptible patients (Samter’s triad: asthma + nasal polyps + aspirin sensitivity)
• Carboprost (Hemabate): prostaglandin → bronchospasm (avoid in asthmatic obstetric patients)

Myasthenia Gravis — avoid (worsen neuromuscular junction transmission):

• Aminoglycosides, fluoroquinolones, macrolides, telithromycin
• Magnesium sulfate (relative contraindication — blocks NMJ)
• Beta-blockers (controversial — may worsen)
• Botulinum toxin
• Succinylcholine (unpredictable response)

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2.4 IV Medication Protocols (Drip Calculations, Compatibilities)

Q: How do you calculate and manage common IV drips?

A:

General drip calculation formula:

• Rate (mL/hr) = Dose (mcg/kg/min) × Weight (kg) × 60 / Concentration (mcg/mL)

Norepinephrine (Levophed):

• Standard concentration: 4mg in 250mL D5W or NS (16 mcg/mL) OR 8mg in 250mL (32 mcg/mL)
• Starting dose: 0.1-0.5 mcg/min, titrate q5-15min
• Usual range: 2-20 mcg/min (can go higher)
• Titrate to MAP ≥65 mmHg
• Central line preferred (tissue necrosis with extravasation via peripheral — can use peripheral temporarily for <12h with close monitoring)
• Extravasation treatment: phentolamine 5-10mg in 10-15mL NS, infiltrate locally

Vasopressin:

• Fixed dose: 0.03-0.04 units/min (NOT titrated)
• Standard: 20 units in 100mL NS = 0.2 units/mL → run at 9 mL/hr for 0.03 units/min
• Used as adjunct to norepinephrine in septic shock (vasopressin-sparing steroid effect)
• Can cause digital ischemia, mesenteric ischemia at higher doses

Phenylephrine (Neosynephrine):

• Pure α1 agonist → vasoconstriction without increased HR
• Dose: 0.1-0.5 mcg/kg/min IV infusion, or 50-200 mcg IV bolus
• Use: anesthesia-induced hypotension, neurogenic shock, situations where tachycardia is undesirable
• Side effects: reflex bradycardia, mesenteric ischemia

Dopamine:

• Low dose (1-5 mcg/kg/min): “renal dose” — dopaminergic receptors (historically claimed to improve renal blood flow — NOT supported by evidence, no longer recommended for renal protection)
• Medium dose (5-10 mcg/kg/min): β1 effects → increased HR and contractility
• High dose (>10 mcg/kg/min): α1 effects → vasoconstriction
• More arrhythmogenic than norepinephrine — not first-line for septic shock

Dobutamine:

• β1 agonist (some β2) → increases contractility and HR
• Dose: 2.5-20 mcg/kg/min
• Use: cardiogenic shock, low cardiac output states, stress echocardiography
• May cause hypotension (β2 vasodilation) → often paired with norepinephrine
• Do NOT use for septic shock as sole vasopressor

Milrinone:

• Phosphodiesterase-3 inhibitor → inotropy + vasodilation (“inodilator”)
• Loading: 50 mcg/kg over 10 min (often omitted to avoid hypotension)
• Maintenance: 0.375-0.75 mcg/kg/min
• Renally cleared — reduce dose if CrCl <50
• Use: acute decompensated HF, cardiogenic shock, RV failure, post-cardiac surgery
• Advantage over dobutamine: works independently of β-receptors (effective in patients on beta-blockers)

Nitroglycerin drip:

• Dose: start 5-10 mcg/min, titrate by 5-10 mcg/min q3-5min
• Usual range: 5-200 mcg/min
• Use: acute coronary syndrome, hypertensive emergency with pulmonary edema, afterload reduction
• Must use non-PVC tubing (nitroglycerin absorbs into PVC — reduces effective dose by up to 80%)
• Side effects: hypotension, headache, tachyphylaxis (within 24-48h of continuous use)

Nitroprusside:

• Dose: 0.3-10 mcg/kg/min (start low)
• Use: hypertensive emergency (very rapid onset and offset)
• Side effects: cyanide toxicity (hepatic conversion) — limit to <48h use and <2 mcg/kg/min when possible
• Monitor: thiocyanate levels (if used >48h), signs of cyanide toxicity (lactic acidosis, altered mental status)
• Protect from light (wrap tubing in foil)

Heparin drip:

• Weight-based protocol:
  • Bolus: 80 units/kg IV (max 5000-10,000 units depending on protocol)
  • Infusion: 18 units/kg/hr
• Standard concentration: 25,000 units in 250mL NS (100 units/mL)
• Monitoring: aPTT q6h until therapeutic (60-80 sec), then q12-24h
• Nomogram adjustments per institutional protocol
• Hold for aPTT >120, recheck in 2h, restart at reduced rate

Insulin drip (DKA/HHS):

• Standard: 100 units regular insulin in 100mL NS (1 unit/mL)
• Rate: 0.1 units/kg/hr (no bolus per newer protocols, or 0.1 units/kg bolus optional)
• Target glucose drop: 50-75 mg/dL per hour
• When glucose <200 (DKA) or <300 (HHS): reduce to 0.02-0.05 units/kg/hr AND add D5 or D10 to IVF
• Continue drip until anion gap closes (DKA) or osmolality normalizes (HHS)
• Overlap SQ insulin 2h before discontinuing drip

Electrolyte replacement drips:

• Potassium chloride: max 10 mEq/hr via peripheral IV, 20-40 mEq/hr via central line with cardiac monitoring. Always on infusion pump. NEVER IV push.
• Magnesium sulfate: 1-2g IV over 1-2 hours (routine). 4-6g IV over 15-20 min (eclampsia loading). Severe hypomagnesemia: 4-8g over 12-24h.
• Calcium gluconate: 1-2g IV over 10-20 min (hyperkalemia, hypocalcemia). Central line preferred for calcium chloride.
• Phosphate: sodium or potassium phosphate 20-40 mmol IV over 4-6 hours. Monitor calcium (inverse relationship).

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Q: What are the key IV medication compatibility issues?

A:

Never mix / Y-site incompatible (common dangerous pairs):

• Phenytoin: incompatible with virtually everything — give alone in NS only (precipitates in dextrose). Flush line before and after.
• Diazepam: incompatible with most drugs — administer alone, do not dilute.
• Amphotericin B: incompatible with NS (use D5W only). Incompatible with most antibiotics.
• Pantoprazole: incompatible with midazolam, many antibiotics. Dedicated line preferred.
• TPN: generally run on dedicated line. Y-site lipids only with designated compatible tubing.
• Sodium bicarbonate: precipitates with calcium (calcium carbonate formation). NEVER in same line as calcium.
• Ceftriaxone + calcium-containing solutions: contraindicated in neonates (fatal precipitation). In adults: do not mix in same bag; sequential infusion through different lines OK.

Safe practices:

1. When in doubt, flush the line with NS between medications
2. Use dedicated lumens for: vasopressors, TPN, blood products
3. Vasopressors: can Y-site most vasopressors together (norepi + vasopressin is common)
4. Blood products: only compatible with NS — NEVER mix with dextrose, LR, or medications
5. Always check institutional compatibility database (Lexicomp, Micromedex) for specific Y-site compatibility
6. Label all drip lines clearly at the pump and at the patient connection

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2.5 Antibiotic Stewardship & Sensitivity-Based Prescribing

Q: What are the principles of antibiotic stewardship in a hospital setting?

A:

Core principles:

1. Right drug, right dose, right duration, right route
2. Start empiric broad-spectrum → narrow based on cultures (de-escalation)
3. Obtain cultures BEFORE antibiotics whenever possible (blood cultures, urine, sputum, wound)
4. Review cultures and sensitivities at 48-72 hours — MANDATORY de-escalation point
5. Use narrowest-spectrum effective agent
6. IV-to-PO conversion as soon as clinically appropriate (reduces line infections, cost, length of stay)
7. Duration: use shortest effective course (evidence supports shorter courses for many infections)

Evidence-based shorter durations:

• CAP: 3-5 days (if clinically stable at day 3) — not the traditional 7-10 days
• UTI (uncomplicated cystitis): 3-5 days (nitrofurantoin 5 days, TMP-SMX 3 days)
• Pyelonephritis: 5-7 days (fluoroquinolone 5 days, beta-lactam 7 days)
• Cellulitis: 5-6 days (if improving)
• Intra-abdominal infection (source controlled): 4 days (STOP-IT trial)
• Hospital-acquired pneumonia: 7 days (not 14)
• Bloodstream infection (uncomplicated GNR): 7 days from first negative culture
• Bone and joint: traditionally 4-6 weeks IV, but OVIVA trial supports oral switch for many

Procalcitonin (PCT) guidance:

• PCT <0.25 mcg/L: bacterial infection unlikely — consider stopping/not starting antibiotics
• PCT 0.25-0.5: possible bacterial infection — use clinical judgment
• PCT >0.5: bacterial infection likely
• Serial PCT: if declining by >80% from peak → safe to stop antibiotics
• Best validated for: respiratory infections, sepsis antibiotic duration
• NOT useful for: localized infections (abscess, osteomyelitis), endocarditis, immunocompromised patients

Restricted antibiotics (require approval in many stewardship programs):

• Carbapenems (meropenem, imipenem, ertapenem)
• Linezolid
• Daptomycin
• Ceftaroline
• Polymyxins (colistin)
• Antifungals (voriconazole, caspofungin, amphotericin B)

C. difficile prevention:

• Minimize fluoroquinolones, clindamycin, cephalosporins (highest C. diff risk)
• PPIs increase C. diff risk — reassess need
• Contact precautions + hand hygiene with soap and water (alcohol gel does NOT kill C. diff spores)

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Q: How do you interpret an antibiotic sensitivity report and choose appropriate therapy?

A:

Reading the report:

• S (Susceptible): organism killed at achievable drug concentrations → drug should work
• I (Intermediate/Susceptible, Dose-Dependent): may work at higher doses or at sites of high drug concentration (e.g., urine for UTI)
• R (Resistant): organism NOT killed at achievable concentrations → do not use

MIC (Minimum Inhibitory Concentration):

• Lowest concentration of antibiotic that prevents visible growth
• Lower MIC = more susceptible
• Breakpoints determine S/I/R classification (set by CLSI or EUCAST)
• “MIC creep” — gradually rising MICs over time suggest emerging resistance

Key resistance patterns to recognize:

MRSA (Methicillin-Resistant Staph aureus):

• Resistant to ALL beta-lactams (penicillins, cephalosporins, carbapenems)
• Exception: ceftaroline (5th gen cephalosporin) retains MRSA activity
• Treatment: vancomycin, daptomycin, linezolid, TMP-SMX (non-severe), doxycycline (non-severe)

ESBL (Extended-Spectrum Beta-Lactamase) producing Enterobacteriaceae:

• Resistant to penicillins, cephalosporins (including 3rd gen), aztreonam
• May appear susceptible in vitro to cephalosporins but FAIL clinically
• Treatment: carbapenems (meropenem preferred). Pip-tazo may work for non-severe UTI if susceptible.

CRE (Carbapenem-Resistant Enterobacteriaceae):

• Resistant to carbapenems — extremely limited options
• Treatment: ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol
• Polymyxins (colistin) as last resort (nephrotoxic, neurotoxic)
• Infectious disease consult mandatory

VRE (Vancomycin-Resistant Enterococcus):

• Treatment: linezolid, daptomycin (not for pulmonary infections), tigecycline
• Ampicillin may still work for some VRE strains if sensitivity preserved

Pseudomonas aeruginosa — inherent resistance:

• Anti-pseudomonal agents: piperacillin-tazobactam, cefepime, ceftazidime, meropenem, ciprofloxacin, aztreonam, aminoglycosides, colistin
• NOT covered by: ertapenem, ceftriaxone, ampicillin-sulbactam, moxifloxacin
• Often develops resistance during treatment → repeat cultures if not improving

Acinetobacter baumannii:

• Highly resistant organism — hospital-acquired, especially ICU
• Often pan-resistant
• Options: ampicillin-sulbactam (sulbactam has intrinsic activity), carbapenems, polymyxins, tigecycline, cefiderocol
• ID consult essential

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2.6 Controlled Substance Protocols

Q: What are the protocols for prescribing, administering, and monitoring controlled substances in a hospital?

A:

DEA Schedule classifications:

• Schedule I: no accepted medical use (heroin, LSD, MDMA, marijuana federally)
• Schedule II: high abuse potential, accepted medical use, severe dependence (opioids, amphetamines, methylphenidate, fentanyl, oxycodone, hydromorphone, methadone)
• Schedule III: moderate abuse potential (buprenorphine, testosterone, ketamine, codeine combinations)
• Schedule IV: low abuse potential (benzodiazepines, zolpidem, tramadol, carisoprodol)
• Schedule V: lowest abuse potential (pregabalin, codeine cough syrups with low concentration)

Hospital prescribing protocols:

Documentation requirements:

• Indication for controlled substance
• Dose, route, frequency, duration
• Pain assessment before and after administration (using validated scale)
• Reassessment interval (typically 30-60 min post-IV, 60 min post-PO)
• Plan for taper or discontinuation

Opioid prescribing best practices:

• Start with lowest effective dose
• Use multimodal analgesia: acetaminophen, NSAIDs, gabapentinoids, regional anesthesia → reduce opioid requirements
• PCA (patient-controlled analgesia) for post-surgical patients: set lockout interval, no basal rate for opioid-naive (reduces oversedation)
• Equianalgesic conversions (see separate section)
• Naloxone standing order for all patients on opioid infusions or PCA
• Monitor: respiratory rate, sedation level (RASS or Pasero Opioid-Induced Sedation Scale), SpO2

Administration & dispensing:

• Double-count and witness waste (two-nurse verification)
• Automated dispensing cabinets (Pyxis/Omnicell): controlled substance compartments with biometric or dual-access
• Count discrepancies → immediate reporting to pharmacy and supervisor
• Diversion monitoring: surveillance software tracking withdrawal patterns, unusual quantities, overrides

Discharge prescribing:

• Limit supply (3-7 day opioid supply for acute pain is standard)
• E-prescribing mandatory for Schedule II in most states
• Check PDMP (Prescription Drug Monitoring Program) before prescribing
• Naloxone co-prescribing if: >50 MME/day, concurrent benzodiazepine, history of overdose, substance use disorder

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2.7 High-Alert Medications (Insulin, Heparin, Vasopressors)

Q: What are high-alert medications and what safety protocols are required?

A: High-alert medications have heightened risk of significant harm when used in error. ISMP (Institute for Safe Medication Practices) maintains the definitive list.

Top high-alert medications in hospitals:

Insulin:

• #1 cause of inpatient medication errors
• Safety measures:
  • Always verify type, dose, and timing with another nurse
  • Never abbreviate “U” for units (can be read as “0” → 10x overdose). Write “units.”
  • Verify blood glucose before every dose
  • Hold if glucose below threshold (typically <70 mg/dL)
  • Clearly differentiate rapid-acting (lispro, aspart) from long-acting (glargine, detemir)
  • Never mix glargine or detemir with other insulins in same syringe
  • Concentrated insulin (U-200, U-500) → ONLY in manufacturer pen device, never drawn up in syringe from pen
  • Sliding scale reassessment: don’t stack rapid-acting doses (minimum 4h between correction doses)

Heparin:

• Verify weight-based dosing calculation independently
• Right concentration: heparin flush (10 units/mL) vs heparin drip (100 units/mL) — NEVER interchange
• aPTT or anti-Xa monitoring per protocol
• Platelet count baseline and q2-3 days (HIT screening)
• Never IM (hematoma risk)
• Clearly label all heparin-containing flushes and drips

Anticoagulants (all):

• Verify indication, dose, renal function, weight
• Bridging protocols: clear start/stop orders when transitioning
• Hold parameters before procedures
• Document reversal plan in chart

Vasopressors/Inotropes:

• Standard concentrations hospital-wide (reduces calculation errors)
• Always on infusion pump — NEVER gravity infusion
• Central line preferred (except temporary peripheral for norepinephrine <12h)
• Dedicated lumen when possible
• Hemodynamic monitoring: arterial line for titration-intensive pressors
• Weaning protocol: reduce by 10-25% q15-30min when MAP stable

Concentrated electrolytes:

• KCl concentrate: NEVER on patient care units as floor stock (must be diluted by pharmacy in premixed bags)
• Hypertonic saline (3%, 23.4%): only for documented indication (severe hyponatremia, elevated ICP). Requires monitoring in ICU.
• Calcium chloride: central line only (tissue necrosis if extravasation)

Chemotherapy:

• Verified by at least 2 practitioners (pharmacist + nurse)
• BSA (body surface area) calculation independently verified
• Protocol verification against original oncology order
• Extravasation kit available at bedside

Opioids:

• See controlled substance section above
• High-dose IV opioid infusions: continuous SpO2 monitoring, capnography if available
• PCA: verify settings (demand dose, lockout, no basal rate for opioid-naive)

Neuromuscular blocking agents (paralytics):

• NEVER without concurrent sedation and analgesia
• Must be on ventilator before administration
• Warning labels: “PARALYTIC — PATIENT CANNOT BREATHE WITHOUT VENTILATOR”
• Train-of-four (TOF) monitoring for continuous infusions
• Stored separately from other medications to prevent accidental use

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2.8 Medication Reconciliation Protocols

Q: How should medication reconciliation be performed at each transition of care?

A:

Definition: Medication reconciliation is the process of creating the most accurate list of all medications a patient is taking and comparing that list against the provider’s admission, transfer, and/or discharge orders.

Required at every transition:

1. Admission
2. Transfer (ICU ↔ floor, OR)
3. Discharge
4. Outpatient visits

Admission Reconciliation:

Step 1 — Obtain comprehensive medication history: Sources (use ALL available):

• Patient/family interview
• Medication bottles brought from home
• Pharmacy records (retail pharmacy verification)
• PCP office records
• Previous discharge summaries
• State PDMP for controlled substances

Document for EACH medication:

• Name (brand and generic)
• Dose, route, frequency
• Indication
• Last dose taken
• Adherence (actually taking as prescribed?)
• OTC medications, herbals, supplements, vitamins
• Allergies with reaction type (true allergy vs intolerance vs side effect)

Step 2 — Compare with inpatient orders:

• Continue home medications unless contraindicated by acute illness
• Document rationale for any held medications:
  • Hold metformin (NPO, contrast, AKI)
  • Hold ACEi/ARB (AKI, hyperkalemia)
  • Hold anticoagulants (procedure pending, active bleeding)
  • Hold antihypertensives (hypotension)
  • Hold oral hypoglycemics (transition to insulin for inpatient glucose management)
• Ensure therapeutic substitutions are appropriate (hospital formulary may differ from home medications)

Step 3 — Resolve discrepancies:

• Unintentional omissions
• Duplicate therapy
• Drug-drug interactions with new inpatient medications
• Dose adjustments for renal/hepatic function changes

Discharge Reconciliation:

Critical error-prone transition. 50% of medication errors occur at discharge.

Checklist:

• Resume all held home medications (with clear documentation if NOT resuming and why)
• Discontinue hospital-only medications (DVT prophylaxis heparin, sliding scale insulin if reverting to home regimen, IV antibiotics if switching to PO)
• Reconcile new medications against home medications (duplications, interactions)
• Dose changes clearly communicated (e.g., “lisinopril increased from 10mg to 20mg daily”)
• Provide patient with updated medication list — in patient’s preferred language
• Teach-back method: have patient/caregiver repeat medication instructions
• Ensure prescriptions are sent to patient’s pharmacy before discharge
• Schedule follow-up for medication titration (anticoagulation, new diabetes meds, blood pressure)

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2.9 Adverse Drug Reactions & Management

Q: How do you identify and manage the most common and dangerous adverse drug reactions?

A:

Anaphylaxis (see Emergency Medicine section for full management):

• Most common triggers: antibiotics (penicillins, cephalosporins), NSAIDs, contrast dye, latex, blood products
• Timeline: minutes to 1 hour after exposure
• Management: epinephrine IM first and always

Drug-Induced QTc Prolongation / Torsades de Pointes:

• Offending agents: amiodarone, sotalol, haloperidol, droperidol, fluoroquinolones, macrolides, methadone, ondansetron (IV >16mg), antipsychotics
• Risk factors: female sex, hypokalemia, hypomagnesemia, congenital long QT, concurrent QTc drugs
• Management: stop offending drug, replete K to >4.0 and Mg to >2.0
• If Torsades: magnesium 2g IV push, overdrive pacing, isoproterenol if unresponsive. Do NOT give amiodarone (will worsen).

Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN):

• Common triggers: allopurinol, sulfonamides (TMP-SMX), anticonvulsants (carbamazepine, phenytoin, lamotrigine), NSAIDs (piroxicam)
• Features: target lesions, mucosal erosions, skin detachment. SJS <10% BSA, TEN >30% BSA.
• Management: STOP offending drug immediately, burn unit/ICU care, wound care, pain management, ophthalmology consult (eye involvement common), avoid systemic steroids (controversial — may worsen)
• Mortality: SJS 1-5%, TEN 25-35%
• HLA-B*5801 testing before allopurinol in high-risk populations (Southeast Asian, African American)
• HLA-B*1502 testing before carbamazepine in Southeast Asian patients

Serotonin Syndrome:

• Triad: altered mental status, autonomic instability, neuromuscular abnormalities (clonus, hyperreflexia, rigidity)
• Common combinations: SSRIs + MAOIs, SSRIs + tramadol, linezolid + SSRIs
• Differentiate from NMS: serotonin syndrome has CLONUS and hyperreflexia (NMS has rigidity and bradyreflexia)
• Management: stop serotonergic drugs, cyproheptadine 12mg PO then 4mg q4-6h, benzodiazepines for agitation, cooling for hyperthermia, supportive care

Neuroleptic Malignant Syndrome (NMS):

• Triggered by: antipsychotics (haloperidol highest risk), metoclopramide, withdrawal of dopamine agonists
• Features: hyperthermia, severe rigidity (“lead pipe”), altered mental status, autonomic instability, elevated CK (often >1000), leukocytosis
• Management: stop offending agent, aggressive cooling, IV hydration, dantrolene 1-2.5 mg/kg IV (for rigidity), bromocriptine 2.5-10mg PO TID (restore dopamine), benzodiazepines
• ICU admission — mortality 10-20% if untreated

Drug-Induced Liver Injury (DILI):

• Common causes: acetaminophen (most common — dose-dependent), isoniazid, statins, amoxicillin-clavulanate, phenytoin, valproic acid, methotrexate, antifungals
• Patterns: hepatocellular (elevated ALT), cholestatic (elevated ALP/bilirubin), mixed
• Acetaminophen toxicity: N-acetylcysteine (NAC) protocol
  • IV NAC: 150 mg/kg over 1h → 50 mg/kg over 4h → 100 mg/kg over 16h
  • PO NAC: 140 mg/kg loading → 70 mg/kg q4h x17 additional doses
  • Most effective within 8h of ingestion but give regardless of time
  • Check Rumack-Matthew nomogram for risk stratification

Drug-Induced Acute Kidney Injury:

• NSAIDs → afferent arteriole vasoconstriction, decreased GFR
• ACEi/ARB → efferent arteriole dilation, decreased GFR (usually reversible upon stopping)
• Aminoglycosides → direct tubular toxicity (monitor troughs)
• Vancomycin → tubular toxicity (AUC-guided dosing reduces risk)
• Contrast dye → contrast-induced nephropathy (pre-hydrate with NS in at-risk patients)
• Lithium → nephrogenic diabetes insipidus, chronic interstitial nephritis
• PPIs → acute interstitial nephritis (AIN)

Heparin-Induced Thrombocytopenia (HIT):

• Type II: immune-mediated, 5-14 days after heparin exposure (or sooner if prior exposure)

• 50% platelet drop from baseline, often with thrombosis (paradoxical — prothrombotic state)

• Diagnosis: 4T score (timing, thrombocytopenia severity, thrombosis, other causes) → if intermediate-high → anti-PF4/heparin antibody → serotonin release assay (gold standard)
• Management: STOP ALL heparin (including flushes, coated catheters), start alternative anticoagulation immediately:
  • Argatroban IV drip (hepatically cleared — preferred in renal failure)
  • Bivalirudin IV (for PCI)
  • Fondaparinux SQ (does NOT cause HIT)
• Do NOT give warfarin until platelets >150,000 (risk of warfarin-induced skin necrosis/limb gangrene in HIT)
• Do NOT transfuse platelets (can worsen thrombosis)

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2.10 Formulary Management

Q: How does hospital formulary management work and why does it matter for clinical care?

A:

Pharmacy & Therapeutics (P&T) Committee:

• Multidisciplinary committee (physicians, pharmacists, nursing, administration)
• Determines which medications are stocked in the hospital formulary
• Evaluates: efficacy evidence, safety profile, cost-effectiveness, therapeutic alternatives, resistance patterns (for antibiotics)
• Reviews new drug additions, removals, and therapeutic substitutions

Therapeutic substitutions:

• Hospital may stock one drug per class when therapeutically equivalent
• Common examples:
  • PPI: omeprazole may substitute for pantoprazole, esomeprazole, lansoprazole
  • Statin: atorvastatin may substitute for rosuvastatin at equivalent intensity
  • ACEi: lisinopril may substitute for enalapril, ramipril (with dose adjustment)
  • Beta-blocker: metoprolol succinate may substitute for atenolol (with appropriate conversion)
  • H2 blocker: famotidine for ranitidine (ranitidine removed from market)
• Provider must be notified of substitution
• Non-formulary requests require justification and may take 24-48h

Automatic therapeutic interchange protocols:

• Pre-approved by P&T committee
• Pharmacist can substitute without calling provider for pre-defined interchanges
• Example: pantoprazole IV ordered → pharmacy can dispense omeprazole PO (if patient tolerating PO and no specific IV indication)
• Must have clinical criteria defined (e.g., IV-to-PO conversion criteria: tolerating PO, functioning GI, clinically stable)

Cost considerations (impact on practice):

• Generic vs brand: pharmacists will dispense generic when available
• Biosimilars: increasingly available for biologics (infliximab, adalimumab, rituximab, trastuzumab)
• 340B drug pricing: eligible hospitals purchase outpatient drugs at significant discount — influences formulary decisions
• Prior authorization for high-cost drugs: may be required even inpatient for certain agents

Antibiotic formulary and stewardship:

• Restricted antibiotics: require ID approval or automatic approval with documented indication
• Antibiogram: annual facility-specific susceptibility data
  • Guides empiric therapy choices
  • Example: if hospital E. coli sensitivity to ciprofloxacin is <80%, ciprofloxacin should NOT be empiric first-line for UTI at that facility
• Formulary should align with antibiogram data

Formulary management for high-alert medications:

• Tall-man lettering to distinguish look-alike drugs: hydrOXYzine vs hydrALAzine, DOBUTamine vs DOPamine
• LASA (look-alike, sound-alike) alerts in dispensing system
• Concentrated electrolytes removed from floor stock
• Standardized drip concentrations across hospital

Technology integration:

• EHR clinical decision support: alerts for interactions, allergy cross-reactivity, renal dose adjustments, duplicate therapy
• Alert fatigue: too many alerts → clinicians override them. P&T committee should optimize alert sensitivity/specificity.
• Smart pump drug libraries: pre-programmed dose limits (hard stops and soft stops) for high-alert drugs

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END OF SECTION 2: PHARMACOLOGY & MEDICATION

Notes for JSONL Conversion:

• Each Q&A pair = one training example
• System prompt: “You are a hospital AI assistant trained to provide evidence-based pharmacology guidance for healthcare providers.”
• These entries are knowledge-dense — consider splitting very long answers into multi-turn conversations for training
• Cross-reference with Section 1 (Clinical Medicine) for clinical context
• Drug dosing should be verified against current references (Lexicomp, UpToDate, Micromedex) before deployment
• Local antibiograms and formulary specifics will vary by institution

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Generated for anhdeptrai LLM Training Project Total Q&A pairs in this section: 20 Covers: 10 pharmacology & medication subtopics Last updated: February 2026