1. Diabetes Mellitus (DM)

General Management & Principles

• Lifestyle modifications are essential for all diabetic patients.

• Hypoglycemia is the most common and serious side effect of many antidiabetic drugs. Symptoms include tachycardia, sweating, fatigue.

• Insulin is used for hospitalized diabetic patients. Also indicated in Type 2 DM with progressive beta-cell dysfunction.

• Low-dose Aspirin is indicated for secondary cardioprotection in patients with ischemic heart disease.

• Drugs associated with causing/inducing DM:
  • Beta-cell destruction: Pentamidine, Interferon, Pyriminil.
  • Insulin resistance: Glucocorticoids, Cyclosporine, Nicotinic acid, Growth hormone, Diazoxide, Clozapine, HIV protease inhibitors.
  • Spironolactone is NOT known to cause diabetes.

• DM Prevention: Metformin, Liraglutide, Rosiglitazone, Acarbose, weight reduction, physical exercise are mentioned as preventive. Repaglinide and Glyburide are not used for prevention.

Type 1 Diabetes Mellitus (T1DM)

• Diabetic Ketoacidosis (DKA) Treatment: Requires IV regular insulin (crystalline zinc insulin). Symptoms include coma, hyperglycemia, acidosis, rapid breathing, excessive urination/thirst, nausea/vomiting, ketones in urine.

• Basal-Bolus Regimens: Aim to mimic physiological insulin secretion. Often use a long-acting insulin (e.g., Glargine, Detemir) for basal coverage and a rapid-acting insulin (e.g., Lispro, Aspart, Glulisine) before meals. Lispro has a very short duration of action. Glargine provides basal coverage up to 24 hours.

• Pramlintide:
  • Used as an adjunct for postprandial hyperglycemia when insulin alone is insufficient (erratic control).
  • Decreases gastric emptying, reduces appetite, can cause moderate weight loss and anorexia.
  • Must NOT be mixed in the same syringe with insulin. Should be used prior to meals.

Type 2 Diabetes Mellitus (T2DM)

• Initial Therapy: Metformin is the first-line agent after lifestyle modifications, especially for obese patients (with high insulin levels). It decreases hepatic glucose production and improves insulin sensitivity.

• Non-obese patients: Often treated with insulin secretagogues (e.g., Sulfonylureas).

• Sulfonylureas (e.g., Glyburide/Glibenclamide, Glimepiride):
  • Stimulate insulin release.
  • High risk of hypoglycemia.
  • Avoid in severe renal impairment and caution in the elderly. Glyburide should be discontinued if renal impairment develops. Glibenclamide may be used for normal-weight T2DM with fasting hyperglycemia but is not appropriate for obese patients.

• Metformin:
  • Contraindicated in severe renal impairment, congestive heart failure, metabolic acidosis, respiratory disease, alcoholism (risk of lactic acidosis).
  • Does not cause lipodystrophy. Is not contraindicated in dyslipidemia.

• Thiazolidinediones (TZDs - e.g., Pioglitazone, Rosiglitazone):
  • Improve insulin sensitivity, decrease hepatic glucose production (Pioglitazone).
  • Contraindicated in heart failure due to sodium and fluid retention.
  • Associated with osteoporosis.
  • Not considered first-line treatment.

• GLP-1 Receptor Agonists (e.g., Exenatide, Liraglutide):
  • Stimulate glucose-dependent insulin release, decrease glucagon, slow gastric emptying, reduce appetite, stimulate vagus nerve.
  • Associated with moderate weight loss.
  • Risk of acute pancreatitis (especially Exenatide).
  • Exenatide may increase pancreatic beta-cell mass by decreasing apoptosis. Considered a drug of choice for T2DM with atherosclerotic CVD.

• DPP-4 Inhibitors (e.g., Sitagliptin, Saxagliptin):
  • Inhibit breakdown of incretin hormones, leading to increased insulin secretion and decreased glucagon release.
  • Common side effect: Nasopharyngitis. Hypertension is NOT a side effect.
  • Sitagliptin is considered relatively safe for elderly patients. Can be added if Metformin + SU is insufficient, especially if avoiding TZDs/SGLT2i due to osteoporosis.

• SGLT-2 Inhibitors (e.g., Empagliflozin, Canagliflozin, Dapagliflozin):
  • Inhibit glucose reabsorption in the kidneys.
  • Useful in patients with chronic kidney disease (CKD) (e.g., Empagliflozin).
  • Side effects include hypotension.
  • Associated with osteoporosis (Canagliflozin).
  • GFR 60 is NOT a contraindication. Recurrent UTI is a potential issue but not an absolute contraindication listed.

• Alpha-glucosidase Inhibitors (e.g., Acarbose, Miglitol):
  • Inhibit breakdown of complex carbohydrates in the intestine, decreasing postprandial glucose levels.
  • Side effect: Abdominal distention (Acarbose). Lactic acidosis is NOT associated with Miglitol.

• Meglitinides (e.g., Repaglinide): Stimulate insulin release in a glucose-dependent manner.

• Combination Therapy: Metformin + Rosiglitazone + Exenatide may delay beta-cell failure.

• Specific Comorbidities:
  • Hypertension: Treat with ACE inhibitors (ACEI) or ARBs.
  • Heart Failure: Avoid TZDs (Pioglitazone, Rosiglitazone).
  • Renal Impairment: Avoid Metformin and Sulfonylureas if severe. SGLT-2 inhibitors (Empagliflozin) can be beneficial. Sitagliptin is relatively safe.
  • Osteoporosis: Avoid TZDs and Canagliflozin. Sitagliptin may be a preferred add-on.
  • Atherosclerotic CVD: Exenatide is a preferred agent.
  • Elderly: Sitagliptin is relatively safe. Avoid Glyburide. Amlodipine is a reasonable antihypertensive choice.

Hyperglycemic Crises (DKA/HHS)

• Treatment: IV Regular Insulin (crystalline zinc insulin).

Insulin

• Insulin causes weight gain.

• Hypoglycemia can result from high doses.

2. Hypertension (HTN)

General Management & Principles

• Confirm diagnosis via daily self-monitoring with an approved automated device if suspected based on family history.

• Stage 1 HTN Management: Lifestyle modifications plus one antihypertensive agent.

• First-line agents: ACEI, ARB, Thiazide diuretics, Calcium Channel Blockers (CCB). Alpha-1 blockers are not first-line.

• Lifestyle Modifications: Includes diet rich in fruits/vegetables, reduced saturated/total fat, reducing daily sodium intake to < 1.5g/day. Exercising 120 minutes weekly is incorrect (more is needed). Lifestyle changes can potentially reduce the number of drugs needed.

• Drug-Induced HTN: Agents include oral contraceptives, decongestants (phenylephrine), corticosteroids, NSAIDs, Darbepoetin, cocaine, licorice, Ergots, Bevacizumab. Paracetamol does NOT cause HTN. Rifampin can cause resistance to antihypertensive drugs.

• Monitoring: Serum electrolytes should be monitored with thiazides and ARBs (Valsartan). Heart rate should be monitored with verapamil.

Specific Patient Populations & Comorbidities

• Elderly Patients: Amlodipine (long-acting dihydropyridine CCB) and thiazides (Hydrochlorothiazide) are reasonable choices. Sitagliptin is a safe diabetic drug for the elderly.

• Diabetes Mellitus: ACEI or ARB are preferred. If HTN develops and patient is on thiazide, glycemic control may be disrupted (Hydrochlorothiazide effect). Use beta-blockers with caution if treating HTN in diabetics.

• Chronic Kidney Disease (CKD): ACEI (e.g., enalapril) is used. Dose may need to be increased if BP is not controlled (e.g., BP 155/92, Cr 2.3 on enalapril -> increase enalapril dose).

• Heart Failure with Reduced Ejection Fraction (HFrEF): Indicated combination includes Lisinopril (ACEI), Furosemide (loop diuretic), Bisoprolol (beta-blocker). Spironolactone may be added.

• Coronary Artery Disease (CAD)/Ischemic Heart Disease (IHD): Beta-blockers (e.g., Metoprolol, Bisoprolol) are main drugs.

• Post-Stroke (Recurrent Stroke Prevention): Thiazide diuretics.

• COPD: Avoid non-selective beta-blockers. Lisinopril (ACEI) use was questioned in COPD context (likely okay, but a specific question stated not to use it). ACEI, CCB, Diuretics were listed as options to be avoided in one question (Answer was ACEI). This seems contradictory based on general guidelines but reflects the questions.

• Peripheral Arterial Disease (PAD): Carvedilol is mentioned. Propranolol + hydralazine was flagged as a wrong match.

• Pregnancy: See section "Therapy of Certain Disorders During Pregnancy".

Treatment Strategies & Combinations

• If uncontrolled on one agent (e.g., beta-blocker), add another agent (e.g., ACEI - enalapril). If uncontrolled on multiple agents (e.g., Enalapril, Metoprolol), increase the dose of one agent (e.g., Enalapril) before adding another.

• Stage 2 HTN: Combination therapy often required. Beta-blocker + hydralazine was flagged as a wrong combination.

• Alternative for ACEI/ARBs: Spironolactone + hydralazine; Isosorbide dinitrate + hydralazine.

• Inotropic agent use: Beta-blockers can be given (one question flagged this as incorrect regarding HTN treatment).

Hypertensive Urgencies & Emergencies

• Hypertensive Urgency: Avoid rapid-release/sublingual nifedipine. Labetalol, Clonidine, Captopril are options. Normalize BP over hours to days.

• Hypertensive Emergency: Goal is controlled BP reduction, do NOT decrease BP < 140/90 immediately (except in specific circumstances). Do not reduce to 130. Do not normalize BP within 36 hours in acute ischemic stroke (this statement was flagged as wrong).
  • Good agent choices: Labetalol, Esmolol, Nicardipine, Fenoldopam, Enalaprilat.
  • Nifedipine is NOT a good choice.
  • Specific indications:
    • Renal insufficiency: Fenoldopam (caution: sympathetic activity, glaucoma).
    • Aortic dissection: Esmolol.
    • Myocardial ischemia: Nicardipine.
    • Eclampsia: Hydralazine, Labetalol. Enalaprilat is NOT matched with eclampsia.

• IV Metoprolol should not be used in acute dyspnea with crackles, high JVP (likely acute decompensated HF).

3. Epilepsy

General Principles & Drug Selection

• First-line for generalized tonic-clonic and mixed seizures: Carbamazepine.

• First-line for absence seizures: Ethosuximide.

• First-line for generalized seizures (myoclonic, atonic, absence): Valproic acid.

• Drug of choice for myoclonic epilepsy: Valproic acid.

• Neuropathic pain + generalized tonic-clonic seizures: Gabapentin.

• Elderly Patients: Lamotrigine is often the medication of choice due to hypoalbuminemia, decreased hepatic blood flow, and renal clearance considerations.

• Resistant Epilepsy: If Phenytoin, Valproic acid (VA), and Carbamazepine (CMZ) fail in mixed-seizure epilepsy, Lamotrigine is a next step.

• Liver Disease: Avoid Carbamazepine.

• Pregnancy: See section "Therapy of Certain Disorders During Pregnancy". Lamotrigine is considered relatively safe. Valproic acid has the highest risk.

• Breastfeeding: Zonisamide is contraindicated. Phenytoin, valproic acid, levetiracetam, zonisamide distribute to breast milk.

Adverse Effects

• Common to most AEDs: Impairment of cognition, ataxia, diplopia, GI upset, weight changes, thrombocytopenia. Weight loss and GI upset are listed, but impairment of cognition is highlighted as common.

• Concentration-dependent: Diplopia, gingival hyperplasia (Phenytoin).

• Idiosyncratic: Acute liver failure (Valproic acid), pseudolymphoma (Phenytoin), severe skin reactions (Phenytoin, Lamotrigine).

• Chronic: Osteoporosis (Carbamazepine, Phenytoin - due to Vitamin D metabolism), cerebellar syndrome. GI upset with Ethosuximide is a chronic side effect.

• Specific Drugs:
  • Valproic Acid: Hepatotoxicity (idiosyncratic). Inhibits carbamazepine metabolism.
  • Topiramate: Most cognitive impairment. Carbonic anhydrase inhibitor effect. Can be used for migraine prevention. Inhibits carbamazepine metabolism.
  • Phenytoin: Lower cognitive side effects than carbamazepine (mostly). Causes osteoporosis, gingival hyperplasia, pseudolymphoma. Metabolism affected by estrogen. Increased toxicity with isoniazid. Can cause strong skin reactions (switch to Valproate if this occurs).
  • Carbamazepine: Causes osteoporosis. Metabolized by CYP enzymes (inducer). Metabolism inhibited by valproate. Avoid in liver disease.
  • Lamotrigine: Dose-dependent diplopia. Relatively safe in elderly and pregnancy.
  • Ethosuximide: Chronic GI upset. Used only for absence seizures, not neuropathic pain.
  • Zonisamide: Kidney stones, underweight. Contraindicated in breastfeeding.
  • Gabapentin: Used for neuropathic pain.
  • Benzodiazepines: Drowsiness (increased with ethanol).
  • Phenobarbital: Increases phenytoin concentration.

Monitoring & Dosing

• Monitoring: Drug levels can be useful but therapeutic endpoint is seizure control vs. side effects. Interpret levels in clinical context. Higher concentrations needed for focal dyscognitive vs. tonic-clonic seizures. Monitoring valproic acid at peak is incorrect. Monitoring carbamazepine level was implied as correct if patient develops ataxia/nystagmus at high levels.

• Dose Adjustments: Lower dose if side effects occur (e.g., incoordination with phenytoin). Lower dose again and monitor if symptoms persist.

• Neonates: Require high doses of AEDs (statement flagged as incorrect, suggesting this is false).

• Enzyme Inducers: Carbamazepine, Phenytoin. Valproic acid and Lamotrigine are NOT inducers.

• Enzyme Inhibitors: Valproate, Topiramate.

Drug Interactions

• Valproic acid inhibits carbamazepine metabolism, increasing risk of toxicity (diplopia, ataxia).

• Isoniazid increases phenytoin toxicity.

• Phenobarbital increases phenytoin concentration.

• Phenytoin decreases estrogen metabolism.

• Ethanol increases benzodiazepine drowsiness.

4. Antimicrobial Selection and Prophylaxis

Principles of Selection

• Empirical Therapy: Based on site of infection, likely pathogens, local antibiogram, patient factors. Specimen for culture should ideally be taken before starting empirical therapy. Dependence solely on physician experience is not ideal. Therapy should cover likely organisms.

• Combination Therapy Rationale: Broad-spectrum coverage in severe illness, polymicrobial infections, preventing resistance, decreasing dose-related toxicity. Covering ALL possible organisms is NOT a valid reason.

• Failure of Therapy Causes: Immunosuppression, foreign bodies, cystic fibrosis, short bowel syndrome. Concomitant drug inhibiting antibiotic metabolism is NOT a cause of failure.

• Rational Prescription: Includes taking cultures before antibiotics. Starting antibiotics before culture (e.g., child with UTI) is wrong.

Dose Adjustment

• Both Renal and Hepatic Impairment: Piperacillin, Cefotaxime, Sulfamethoxazole, Nafcillin.

• Severe Hepatic Impairment: Clindamycin, Erythromycin, Metronidazole, Rifampin. Gentamicin does NOT require hepatic adjustment. Cefotaxime requires adjustment.

• Renal Impairment: Hepatic clearance is spared in CKD (statement flagged as wrong, implying some hepatic clearance might be relevant or affected).

Adverse Effects & Interactions

• QT Prolongation: Fluoroquinolones, Macrolides/Azalides. Interaction with Class Ia/III antiarrhythmics. Clindamycin is NOT associated with QT prolongation.

• Photosensitivity: Tetracyclines, Sulfamethoxazole, Trimethoprim, Azithromycin, Quinolones, Pyrazinamide. Gentamicin does NOT cause photosensitivity.

• Clostridium difficile Infection: Associated with Penicillins, Cephalosporins, Carbapenems (Imipenem), Clindamycin, Fluoroquinolones. Amikacin and Metronidazole are NOT known causes. Gentamicin is the least likely cause of superinfection.

• Nephrotoxicity: Aminoglycosides, Amphotericin B, Radiocontrast, NSAIDs, Vancomycin (esp. with radiocontrast). Penicillin is NOT listed as nephrotoxic.

• Ototoxicity/Neuromuscular Blockade: Aminoglycosides (enhanced by loop diuretics like furosemide, neuromuscular blockers like vecuronium).

• Tetracycline Toxicity: Enhanced by antacids, iron, calcium, sucralfate (chelation). Enhances digoxin toxicity.

• Macrolide Toxicity: Enhances digoxin, theophylline toxicity. Decreased gentamicin concentration is a WRONG interaction.

• Metronidazole Toxicity: Enhanced by ethanol (disulfiram-like reaction). Interaction with furosemide enhancing toxicity is incorrect.

• Rifampin: Potent enzyme inducer, increases metabolism of cyclosporine, OCPs, warfarin etc.

• Isoniazid: Enzyme inhibitor, decreases metabolism of carbamazepine, phenytoin. Vitamin B6 prevents neurotoxicity.

• Quinolones: Toxicity enhanced by multivalent cations (antacids, iron etc.).

• TMP-SMX Side Effects: Kidney stones, bone marrow suppression, methemoglobinemia. Hypokalemia is NOT listed.

• Linezolid: Can cause serotonin syndrome. Can cause hypertensive crisis with tyramine-rich foods (cheese).

• Amoxicillin: Liver toxicity is a mismatched side effect.

• NSAIDS: Most serious side effect involves renal dysfunction/peptic ulcer/hypertension (exact answer depends on options, multiple serious effects exist).

Specific Pathogens/Situations

• MRSA: Vancomycin. Linezolid is an alternative.

• Pseudomonas aeruginosa: Requires antipseudomonal coverage. Often two antipseudomonal antibiotics if structural lung disease. Combinations like Meropenem + Ciprofloxacin. Vancomycin + Ciprofloxacin is NOT adequate coverage for pseudomonas in CA-P inpatient settings. Piperacillin-tazobactam.

• Methicillin-Sensitive Staph Aureus (MSSA): Empiric coverage with Piperacillin-tazobactam.

• Acinetobacter: Ampicillin (listed as treatment of choice in one question).

• N. meningitidis Prophylaxis: Ceftriaxone in pregnancy. Rifampin otherwise.

• Group B Streptococcus (Maternal): Drug of choice if penicillin-allergic is Cefazolin.

• Cryptococcus neoformans Meningitis: Amphotericin B + Flucytosine. Terbinafine is NOT used.

• Brain Abscess: Vancomycin + Ceftriaxone (or Cefotaxime) + Metronidazole. Treatment duration is typically 4-8 weeks.

• Neonatal Chlamydia Meningitis: Azithromycin.

• Entamoeba histolytica: Do NOT use Loperamide.

• Mycoplasma: Intrinsically resistant to beta-lactams.

• G6PD Deficiency: Amikacin can be given.

Surgical Prophylaxis

• General Principle: Cefazolin is common, but coverage depends on site/procedure.

• Perforated Appendix: Cefazolin + Metronidazole.

• Appendectomy (non-perforated): Cefazolin. Cefotetan + Metronidazole was listed as correct in one mismatch question. Cefazolin alone was flagged as wrong/insufficient in another. Metronidazole MUST be added if perforation.

• Colorectal Surgery (Elective): Oral neomycin + erythromycin.

• Craniotomy: Cefazolin.

• C-Section: Cefotetan. Using Cefotetan was flagged as wrong for C/S in one mismatch question.

• Rheumatic Fever Prophylaxis: Benzathine penicillin. Cephalosporin use is wrong.

5. Therapy of Certain Disorders During Pregnancy

General Principles

• Drug concentration changes: Maternal serum penicillin concentration decreases. Clearance of aminoglycosides increases. GFR increases. Fat content increases. Albumin decreases. Weak acidic drug concentration may increase.

• Teratogenicity: All antimicrobials are NOT teratogenic. Specific agents are contraindicated.

Constipation & Hemorrhoids

• First line: Increase fiber and fluid intake.

• Second line (safe first choice if fiber fails): Psyllium (bulk-forming).

• Laxatives to AVOID: Castor oil.

GERD (Heartburn)

• Management: Lifestyle/diet modification first.

• Acceptable medications: Ranitidine, Omeprazole, Sucralfate, Aluminum/Magnesium hydroxide mixtures (Maalox/Antacids).

• AVOID: Sodium bicarbonate.

Nausea & Vomiting (N+V)

• Treatment of choice: Pyridoxine (B6) + Doxylamine. Ginger is also an option.

Thromboembolism (VTE/DVT)

• First-line anticoagulation: Low Molecular Weight Heparin (LMWH).

Urinary Tract Infections (UTI) / Pyelonephritis

• Asymptomatic Bacteriuria: Treat with Nitrofurantoin.

• Pyelonephritis: Requires hospitalization and IV antibiotics.
  • Empirical treatment (e.g., E. coli): Ceftriaxone.
  • Cefuroxime is a potential choice.
  • Nitrofurantoin is NOT used for pyelonephritis. Levofloxacin, Co-trimoxazole, Amoxicillin are other options listed but potentially less ideal or contraindicated depending on trimester/resistance.

Gestational Diabetes / Pre-existing Diabetes

• Poorly controlled T2DM (HbA1c 8.5) on metformin/glyburide: Discontinue oral agents and start insulin.

Hypertension / Preeclampsia / Eclampsia

• Chronic HTN: Drugs that should NOT be used: ACE Inhibitors (Lisinopril, Enalapril), ARBs (Losartan, Valsartan). These are absolutely contraindicated and can cause fetal skeletal/renal abnormalities, oligohydramnios.

• Acceptable Antihypertensives: Methyldopa, Labetalol, Hydralazine. Magnesium sulfate is used for eclampsia seizure prophylaxis/treatment.

• Preeclampsia (Elevated BP + proteinuria at >20 weeks): Can use Methyldopa, Labetalol, Hydralazine, Magnesium sulfate. AVOID ACEI/ARBs.

• Eclamptic Seizures: IV Magnesium Sulfate is the best drug.

Preterm Labor

• Concerns/Diagnosis: Regular uterine contractions (e.g., every 3 min), closed/elongated cervix at <37 weeks.

• Management:
  • Corticosteroids (Dexamethasone): Administer to mother near term (e.g., 28 weeks) to prevent Respiratory Distress Syndrome (RDS) in the preterm infant. Typically given over 2 days.
  • Tocolytics: Used to suppress contractions. Options include beta-mimetics (ritodrine - risk of hypokalemia), magnesium sulfate, CCBs (nifedipine - risk of hypotension), NSAIDs. Abnormal vaginal bleeding is a contraindication. Diazepam is NOT used as a tocolytic. Use in 3rd trimester requires caution.

Cervical Ripening / Labor Induction

• Indication: e.g., Post-term pregnancy (42 weeks).

• Agent: Dinoprostone (prostaglandin E2), often given intracervically.

Epilepsy

• Highest Risk AED: Valproic acid. Also Phenytoin, Carbamazepine.

• Relatively Safe AED: Lamotrigine.

• Avoid all AEDs if possible, especially during the first trimester (e.g., if pregnant at 6 weeks, avoid all except maybe carbamazepine - this seems contradictory). Valproic acid is definitely high risk.

Hyperthyroidism

• Treatment: Propylthiouracil (PTU) initially, may switch to Methimazole later.

Group B Streptococcus (GBS) Carrier

• Prophylaxis during labor to prevent neonatal transmission.

• Drug of choice if penicillin-allergic: Cefazolin. (Ampicillin is standard if not allergic).

Other Considerations

• Methotrexate: Must be stopped 3 months (or 6-9 months) before attempting pregnancy.

• Antibiotics Contraindicated: Tetracyclines (teeth staining after 5 months), Trimethoprim (folate antagonism - risk of hemolytic anemia if G6PD deficient), Co-trimoxazole (hemolytic anemia).

• Smoking during pregnancy: Associated with small baby, preterm birth, craniosynostosis, later intellectual issues.

• Thiopental (Anesthesia for Cesarean): Can cause sedation and apnea in the neonate.

• Oral Contraceptives (OCPs):
  • Starting first time: Monophasic.
  • Stop immediately if: Abdominal pain, severe leg pain, retinal problems. Amenorrhea, stroke, B6 deficiency are NOT necessarily immediate stop indications.
  • Breakthrough bleeding: Options include stopping and using non-hormonal method, or giving progestogen with androgen activity (less preferred).
  • Smoking + Migraine after starting OCP: Switch to alternative like DMPA.

• DMPA (Depot Medroxyprogesterone Acetate): Indicated if contraindication to estrogen, breastfeeding after 6 months. Risk of osteoporosis. Inadherence is NOT an indication.

• Drospirenone: Can increase potassium (K+).

• Chronic Peptic Ulcer/Menorrhagia/Iron Deficiency Anemia (Hb 8): Ferrous sulfate 150mg daily for 6 months.

• Epoetin Alfa Precaution: Should not increase Hb by more than 1 g/dL every 2 weeks.

6. Heart Failure (HF)

General Principles & Staging

• Pre-HF (Stage A/B): Patients with risk factors (HTN, DM, Dyslipidemia) but no structural heart disease or symptoms.
  • Stage A management: Manage risk factors.
  • Stage B management (structural disease, no symptoms): Start ACEI (or ARB) + Beta-blocker. Statins are also used if dyslipidemia/CAD present. Example: Patient with HTN but no symptoms -> Bisoprolol + Statin + Valsartan to improve mortality.

• HFrEF (HF with Reduced Ejection Fraction): Systolic dysfunction.
  • Standard therapy cornerstone: ACEI (or ARB), Beta-blocker, Diuretic (loop if fluid overload).
  • Aldosterone Antagonists (Spironolactone): Add if symptoms persist despite ACEI/BB therapy (e.g., symptoms on less than ordinary exertion). Reduces mortality, attenuates fibrosis/atherogenesis, inhibits collagen deposition. Does NOT enhance calcium excretion. Monitor potassium. Incorrect to use high dose in renal impairment.
  • ARNI (Valsartan/Sacubitril): Alternative to ACEI/ARB, especially if symptoms persist. Do NOT add ARNI directly to ACEI therapy.
  • Hydralazine + Isosorbide Dinitrate: Alternative combination if ACEI/ARB are contraindicated.
  • Digoxin: Can be used for symptom control, but does NOT reduce mortality.
  • Drugs NOT used/Contraindicated: Non-dihydropyridine CCBs (Verapamil, Diltiazem), Amlodipine (Dihydropyridine CCB), TZDs (Rosiglitazone). NSAIDs can precipitate HF.

• HFpEF (HF with Preserved Ejection Fraction): Diastolic dysfunction.
  • Management focuses on controlling BP, heart rate, and fluid status.
  • Loop diuretics used at lower doses than HFrEF to avoid hypoperfusion/renal failure/low cardiac output. Reduction of prostaglandin synthesis is NOT the reason for lower doses.
  • Role of RAAS inhibition (ACEI/ARB) is less established than in HFrEF (statement suggesting no role was flagged as incorrect).

• Acute Decompensated HF (ADHF):
  • Symptoms: Acute onset dyspnea, elevated JVP, S3 sound, crackles, maybe chest pain, tachycardia.
  • Drugs NOT to use acutely: IV Beta-blockers (Metoprolol) if signs of cardiogenic shock/decompensation. Carvedilol not used in acute decompensation.
  • Clevidipine mentioned in context of acute HF.

Drugs Causing/Exacerbating HF

• Cardiotoxicity: Bevacizumab, Doxorubicin. Disopyramide, Diltiazem, Propranolol also mentioned but Bevacizumab was the answer. Uzumab mentioned for cardiotoxicity.

• Negative Inotropic Effects: Diltiazem, Verapamil, Flecainide, Beta-blockers (acutely).

• Sodium and Water Retention: TZDs (Rosiglitazone), NSAIDs, Corticosteroids, Ticarcillin disodium.

• Cardiac Decompensation/Heart Block: Diltiazem.

Specific Drug Considerations

• ACE Inhibitors (e.g., Lisinopril): Reduce ventricular remodeling, myocardial fibrosis, norepinephrine release, sodium/water retention. Do NOT reduce vasodilator prostaglandins. Dose may need increasing if HFrEF patient has renal impairment (Cr 2.5) but stable BP.

• Beta-Blockers (e.g., Bisoprolol, Carvedilol): Improve mortality in HFrEF. Contraindicated if patient needs inotropic support. IV BB contraindicated in early cardiogenic shock.

• Ivabradine: Used in HFrEF if contraindication to beta-blockers or heart rate remains high despite BBs. Adverse effects: Atrial fibrillation, vision problems, hypotension.

• Diuretics (Loop - Furosemide; Thiazide; Aldosterone Antag - Spironolactone): Used for symptom relief (fluid retention). Do NOT stop disease progression. Doses for HFpEF are smaller than for HFrEF.

• CCBs: Dihydropyridines (Amlodipine) and Non-dihydropyridines (Verapamil, Diltiazem) are generally avoided in HFrEF. Bradycardia is a side effect differing non-DHP from DHP. Edema, headache, flushing, dizziness common to both.

• Prostaglandin E: Not involved in the pathogenesis of CHF.

7. Acute Coronary Syndromes (ACS)

Initial Management

• Morphine: Used for pain relief. Disadvantage: Slows aspirin absorption. Does not decrease mortality. Does not prevent remodeling.

• Oxygen: If hypoxic.

• Nitrates (e.g., Nitroglycerin): Vasodilator, symptom relief. Does not prevent remodeling. Side effects: Hypotension, bradycardia (mismatched effect).

• Aspirin: Antiplatelet therapy, given immediately. Decreases mortality.

• Beta-Blockers (e.g., Bisoprolol): Decrease mortality, re-infarction. Start within 24 hours if no contraindications. IV beta-blockers are NOT beneficial and potentially harmful in early cardiogenic shock.

• Anticoagulation: Indicated for most ACS patients (fibrinolysis, PCI, no reperfusion, NSTE-ACS).
  • Options/Durations: Bivalirudin (up to 3 days), Enoxaparin (up to 8 days), UFH (2 days). Fondaparinux duration of 21 days is incorrect. Enoxaparin 21 days is incorrect.

Reperfusion Therapy (STEMI)

• Primary Percutaneous Coronary Intervention (PCI): Preferred if available promptly. Aggressive statin before PCI.

• Fibrinolytic Therapy (e.g., Alteplase): Use if PCI unavailable/delayed. Indicated within 12 hours of symptom onset. Not indicated if presentation delayed beyond 24 hours.
  • Contraindications: Active bleeding, recent major surgery, intracranial hemorrhage. History of streptokinase use is NOT a contraindication for alteplase.

Secondary Prevention (Post-MI / Hospital Discharge)

• Essential Medications (proven to decrease mortality, HF, re-infarction, stroke, stent thrombosis):
  • Aspirin (lifelong).
  • P2Y12 Inhibitor (e.g., Clopidogrel): Duration typically 12 months.
  • Beta-Blocker (e.g., Bisoprolol).
  • High-Intensity Statin (e.g., Atorvastatin, Rosuvastatin).
  • ACE Inhibitor (e.g., Lisinopril) or ARB: Especially if LVEF <40%, HTN, DM, CKD. Should be started in patients with LVEF <0.4 within one week AFTER ACS (statement about starting ALL patients one week after was flagged as incorrect).

• Aldosterone Antagonist (Spironolactone): Consider if LVEF ≤40% AND either HF symptoms or DM, provided no significant renal dysfunction or hyperkalemia. Patient must be on ACEI/ARB and beta-blocker. Monitor serum potassium. EF of at least 0.55 is NOT the correct threshold.

• Drugs NOT routinely used for secondary prevention: Organic nitrates, Amlodipine, Verapamil, Loop diuretics (used for symptoms, don't prevent remodeling), Morphine, Non-dihydropyridine CCBs.

8. Pneumonia

Community-Acquired Pneumonia (CAP)

• Outpatient, Otherwise Healthy Adult, No Comorbidities:
  • First-line: Amoxicillin or Doxycycline or Macrolide (e.g., Azithromycin if previously healthy). Amoxiclav + Doxycycline is also an option.

• Outpatient, Comorbidities (e.g., Asthma): Amoxicillin-clavulanate + Azithromycin.

• Inpatient, Non-severe (e.g., patchy interstitial infiltrate): Respiratory fluoroquinolone (Levofloxacin) OR Beta-lactam + Macrolide. Levofloxacin mentioned multiple times. Azithromycin monotherapy is an option for low-risk.

• Inpatient, Severe / Risk Factors for Drug-Resistant Pathogens:
  • Empirical choice: Beta-lactam (e.g., Ceftriaxone) + Macrolide (Azithromycin) OR Beta-lactam + Fluoroquinolone.
  • If Pseudomonas risk: Antipseudomonal beta-lactam (Piperacillin-tazobactam, Cefepime, Meropenem) + Ciprofloxacin or Levofloxacin. Meropenem + Ciprofloxacin specifically mentioned. Combinations NOT covering Pseudomonas: Vancomycin + Ciprofloxacin.
  • If MRSA risk: Add Vancomycin or Linezolid.

• Specific Pathogens:
  • Penicillin-resistant Strep. pneumoniae: Ceftriaxone or Vancomycin or Levofloxacin.
  • Acinetobacter: Ampicillin (listed as treatment choice).

• Aspiration Pneumonia (e.g., neurologic problem, choking): Regimen needs anaerobic coverage. Amoxicillin + Azithromycin + Metronidazole or Clindamycin. Amoxicillin only, Amox/Azithro only, Azithro only are insufficient.

• Treatment Duration (Uncomplicated CAP, immunocompetent): 7-10 days.

• Risk Factors for Drug-Resistant Pathogens: Age > 65, recent hospitalization, COPD. Smoking history is a general risk factor for pneumonia but listed as NOT a risk for drug-resistant pathogens.

Hospital-Acquired / Ventilator-Associated Pneumonia (HAP/VAP)

• Often involves resistant organisms (Pseudomonas, MRSA).

• Empirical Therapy: Broad coverage needed.
  • Antipseudomonal beta-lactam (e.g., Piperacillin-tazobactam) + Antipseudomonal fluoroquinolone (Cipro/Levo) OR Aminoglycoside.
  • Add Vancomycin or Linezolid if MRSA suspected.
  • Example: Patient on ventilator develops VAP, cultures grow MRSA -> Vancomycin.
  • Example: HAP progressing to meningitis -> Cefepime + Vancomycin.
  • Combinations for VAP: Ceftazidime+Levo, Imipenem+Levo, Pip-Tazo+Gentamicin. Clarithromycin+Nafcillin is NOT appropriate.

• Structural Lung Disease: Often requires two antipseudomonal antibiotics.

Other Considerations

• Post-Herpetic Neuralgia: Gabapentin, Acetaminophen, TCA, Sertraline, NSAIDs failed -> Add Oxycodone PRN.

• Isoniazid Neurotoxicity Prevention: Vitamin B6.

• Neonatal Pneumonia (Chlamydia trachomatis): Azithromycin.

• Mycoplasma: Intrinsically resistant to beta-lactams.

9. Schizophrenia

Core Features & Symptoms

• Key Features: Disorganized/bizarre thoughts, delusions, hallucinations, inappropriate affect, impaired psychosocial functioning.

• Positive Symptoms: Delusions, Hallucinations, Disorganized speech.

• Negative Symptoms: Flat affect, Apathy, Alogia, Avolition.

• Cognitive Symptoms: Impaired attention, memory, executive function (associated with negative symptoms).

• Neurotransmitter Dysfunctions: Primarily Dopamine dysregulation. Serotonin and Glutamate also involved.

• Onset: Most common age is early adulthood or adolescence.

Treatment Goals & Approaches

• Acute Psychotic Episode Goals: Reduction of symptoms, normalization of sleep/eating patterns. Complete elimination of symptoms may not be realistic initially.

• Long-Term Goals: Prevent relapse, increase adaptive functioning, avoid adverse effects.

• First-Line Treatment (Acute): Antipsychotic medications.

• Maintenance Treatment: Lifelong antipsychotic treatment recommended for most patients.

• Treatment-Resistant Schizophrenia: Clozapine (an atypical/SGA) is primarily used in this situation.

• Psychosocial Rehabilitation: Important in combination with antipsychotic treatment to manage symptoms and improve daily functioning. Not a sole treatment. Cognitive Behavioral Therapy (CBT) is a key therapy approach.

• Substance Abuse: Common comorbidity, associated with poor response to medications and poor prognosis.

Antipsychotic Medications

• Mechanism: Primarily block dopamine receptors.

• First-Generation (Typical) Antipsychotics (FGAs):
  • Examples: Chlorpromazine, Haloperidol, Thiothixine.
  • Mechanism: Primarily D2 receptor blockade.
  • Higher risk of Extrapyramidal Side Effects (EPS).
  • Chlorpromazine can cause severe hypotension.

• Second-Generation (Atypical) Antipsychotics (SGAs):
  • Examples: Clozapine, Risperidone, Olanzapine, Aripiprazole.
  • Mechanism: Block D2 and 5-HT2A serotonin receptors.
  • Major Advantage: Lower risk of neurologic/motor adverse effects (EPS) compared to FGAs.
  • Higher efficacy in treating positive symptoms, faster onset (these were presented as potential advantages but lower EPS risk is the main one).
  • Higher risk of metabolic adverse effects (weight gain, diabetes, dyslipidemia).
  • Clozapine: Most effective, reserved for treatment resistance due to side effects.
    • Side Effects: Agranulocytosis (requires monitoring), Sedation, Seizures, Weight gain, Metabolic issues. Weight loss is NOT a side effect.
  • Risperidone: Can cause akathisia.
  • Haloperidol: High risk of EPS (e.g., akathisia).

• Adverse Effect Management:
  • Extrapyramidal Side Effects (EPS): Manage with anticholinergic agents like Benztropine. Akathisia (severe restlessness) can occur (e.g., with Haloperidol, Risperidone).
  • Hypotension: Can be severe with Chlorpromazine.

• Drug Selection: Consider the adverse effect profile when choosing an agent. Monotherapy is preferred initially. Avoid high-risk combinations if possible.

Other Considerations

• Medical Conditions Causing Psychosis: HIV/AIDS, Alzheimer's disease, Parkinson's disease.

• Substances Causing Psychosis: Cannabis, Cocaine, Amphetamines, LSD. Nicotine does NOT cause psychosis.

10. Medication Errors

Definition & Scope

• Definition: Any preventable event that may cause inappropriate medication use or patient harm while the medication is in the control of the healthcare professional or patient.

• Impact: Constitute a significant portion of medical errors (though perhaps not two-thirds), lead to significant morbidity and mortality, and decrease patient satisfaction.

• Prevalence: Approximately 6,800 prescription medications available in the US.

• Medication errors are preventable.

• Ranking: Third-leading cause of death in the USA (including all medical errors).

Causes & Contributing Factors

• Point of Occurrence: Most commonly occur at the ordering/prescribing stage (approx. 50%). Administration errors (incorrect route, wrong patient, extra dose) also occur. Monitoring errors (failing to account for renal/liver function, allergies, interactions) happen. Dispensing errors.

• Common Reasons:
  • Failure to communicate drug orders.
  • Illegible handwriting.
  • Confusion over similarly named drugs.
  • Errors involving dosing units or weight.
  • Incorrect drug selection from drop-down menus.
  • Expired products (due to improper storage or use).
  • Incorrect strength (calculation errors, incorrect unit conversion).
  • Accurate use of similar drug names is NOT a reason for errors.

• System Failures:
  • Flawed system: Weak, imperfect, inadequate backup to detect mistakes. Not necessarily overly complex or outdated.
  • Inaccurate order transcription.
  • Poor drug knowledge dissemination.
  • Failing to obtain allergy history.
  • Poor professional communication.
  • Adequate order checking is NOT a system failure.

• Human Errors: Mistakes by physicians, pharmacists, nurses. Judgment errors, mechanical errors, distraction (most common cause for physicians).

• Patient Factors: Interactions involving prescription meds, OTC drugs, health supplements, herbs, alternative medicines.

• Sensitive Populations: Elderly and children. Pregnant women and infants, adults/teenagers, middle-aged/adolescents also mentioned, but elderly/children highlighted.

Prevention Strategies

• Implement medication safety protocols.

• Conduct regular medication reconciliation.

• Enhance patient education on medications.

• Follow established protocols and guidelines.

• Practice effective communication and teamwork.

• Report and learn from errors.

• Avoid unclear prescriptions (e.g., "2.0 mg" is not preferred over "2 mg"). Use leading zeros, avoid trailing zeros. Avoid ambiguous abbreviations.

11. Migraine

Acute (Abortive) Treatment

• First-line: NSAIDs or Triptans. Acetaminophen is NOT recommended/used for mild migraine.

• Triptans (e.g., Sumatriptan, Naratriptan, Frovatriptan):
  • Serotonin 1B/1D agonists.
  • Recommended duration of use for acute attack: 3 days.
  • Contraindications: History of ischemic heart disease, stroke, uncontrolled HTN. Age over 35 is NOT a contraindication.
  • Naratriptan does NOT have a rapid onset of action.
  • Frovatriptan: Has a long duration of action.

• Ergotamine: Older abortive agent. Side effects include hypotension, chest tightness, severe ischemia, nausea/vomiting, rebound headache. Use in combination with triptans in refractory migraine is NOT true.

• Adjunctive Therapy:
  • Antiemetics (e.g., Metoclopramide): For nausea/vomiting. Use every 12 hours was flagged as not true. Increases absorption of other drugs. Can be used in combination to decrease rebound headache (statement flagged as wrong). Used in refractory migraine.
  • Corticosteroids: Can be added to triptans.

• Mild Migraine: Aspirin/caffeine, Diclofenac, Ibuprofen are options. Acetaminophen is not used.

Prophylactic (Preventive) Treatment

• Indication: Frequent or severe migraines.

• Commonly Used Agents:
  • Beta-blockers (Propranolol).
  • Antiepileptics (Topiramate, Valproic acid/Divalproex). Carbamazepine is NOT preventive.
  • Tricyclic antidepressants (Amitriptyline).

• Recommended Agent (based on questions): Topiramate. Also Propranolol. Valproic acid can be used.

• Specific Situations: Patient with asthma, kidney stones, renal problems -> Divalproex. Patient needing prevention + anxiety treatment -> Topiramate.

• CGRP Receptor Antagonists (e.g., Erenumab): Newer class for migraine prevention.

• Duration: Recommended duration for chronic migraine prevention is potentially indefinite, or at least 6-12 months.

• Frovatriptan: Long duration, used for prevention (likely menstrual migraine).

Medication Overuse Headache (MOH)

• Caused by frequent use of abortive medications.

• Metoclopramide is NOT used as a primary drug to treat MOH.

12. Meningitis

Empirical Therapy (Based on Age/Situation)

• Neonate (<1 month): Ampicillin + Cefotaxime (or Gentamicin). Covers GBS, E. coli, Listeria. Vancomycin + Ceftriaxone is NOT standard. Cefepime + Metronidazole is incorrect. Vancomycin + Ampicillin is incorrect.

• Infant/Child/Adult (1 month - 50 years): Vancomycin + Ceftriaxone (or Cefotaxime). Covers S. pneumoniae, N. meningitidis.

• Older Adult (>50 years) or Immunocompromised: Vancomycin + Ceftriaxone (or Cefotaxime) + Ampicillin (to cover Listeria). Example: 55-year-old man -> Vancomycin + Ampicillin + Ceftriaxone. Example: 65-year-old, CSF hazy, no culture -> Vancomycin + Ceftriaxone + Ampicillin.

• Healthcare Worker Exposure: If symptomatic, treat empirically based on likely pathogens (e.g., Vancomycin + Ceftriaxone for 43yo nurse).

• Post-Neurosurgery/Trauma: Broader coverage often needed, including anti-pseudomonal and MRSA coverage.

Pathogen-Specific Therapy

• Penicillin-Resistant Strep. pneumoniae: Vancomycin + Ceftriaxone (or Cefotaxime).

• N. meningitidis: Ceftriaxone. Prophylaxis for contacts (Rifampin, Cipro, or Ceftriaxone - Ceftriaxone if pregnant). No need for rifampin in adult contacts if treating child with G(-) diplococci (wrong statement). No need for prophylaxis for contacts of neonate with G(-) bacilli (mostly true).

• Listeria monocytogenes: Ampicillin or Penicillin G (+ Gentamicin often).

• Group B Streptococcus: Penicillin G or Ampicillin.

• Staph. epidermidis: Vancomycin.

• Hemophilus influenzae: Ceftriaxone.

• E. coli / Gram-negative bacilli: Third-gen cephalosporin (Ceftriaxone/Cefotaxime).

• Cryptococcus neoformans: Amphotericin B + Flucytosine. Terbinafine is NOT used. Corticosteroids can be detrimental. Fluconazole is fungistatic, not ideal alone initially. Affects immunocompromised more but can affect immunocompetent. Amphotericin B remains a key drug.

Duration of Therapy (Mismatches Highlighted)

• Group B Strep: 14-21 days (7-10 days is mismatch).

• H. influenzae: 7-10 days.

• S. pneumoniae: 10-14 days.

• N. meningitidis: 7 days (21 days is wrong).

• Listeria: >= 21 days (14-21 days listed).

• Gram-negative bacilli (E. coli): >= 21 days (2 months is wrong).

• Staph. Epidermidis: 14-21 days.

• Antifungal treatment duration: 5 days is incorrect (much longer needed).

Brain Abscess

• Often polymicrobial.

• Empirical Treatment: Vancomycin + Cefepime (or Ceftriaxone/Cefotaxime) + Metronidazole. (Example: 65yo woman with fever/altered mental status).

• Duration: Usually 4-8 weeks. Treatment duration is not the same for all patients; multiloculated may take longer (statement suggesting less time is wrong).

Other Considerations

• Antibiotic penetration: Levofloxacin penetrates well regardless of inflammation.

• Adjunctive Dexamethasone: May be used in bacterial meningitis (esp. H. influenzae, S. pneumoniae) but controversial.

13. Depression

General Principles

• First-line Treatment for Major Depression: Selective Serotonin Reuptake Inhibitors (SSRIs). TCAs and MAOIs are not first-line.

• Recommended Duration (First Episode): 6 months after remission.

Drug Classes & Specific Agents

• SSRIs:
  • First choice, particularly in the elderly.
  • Adverse effects may appear early, therapeutic effects delayed (not necessarily after 3 weeks).
  • Serotonin Syndrome: Risk when SSRIs interact with other serotonergic agents, such as Linezolid or MAOIs.
  • Wrong statement about SSRIs: adverse effects appear after 3 weeks.

• SNRIs (e.g., Venlafaxine): Can be used.

• Atypical Antidepressants:
  • Bupropion: Used for depression and smoking cessation.
  • Mirtazapine: Sedating, appetite stimulant.
  • Trazodone: Sedating, used for insomnia.

• Tricyclic Antidepressants (TCAs): Not first-line due to side effect profile (anticholinergic, cardiac).

• Monoamine Oxidase Inhibitors (MAOIs - e.g., Phenelzine):
  • Effective but many interactions.
  • Dietary Restrictions: Avoid tyramine-rich foods (e.g., fermented cheese) to prevent hypertensive crisis.

• Smoking Cessation: Bupropion.

Drug-Induced Depression

• Drugs that can cause depression: Methyldopa, Isotretinoin, Steroids, Interferon.

• Drugs that do NOT cause depression (based on options): Triptans, Carbamazepine.

Related Symptoms

• Apathy: Term for loss of interest, motivation, and emotional responsiveness (can be seen in schizophrenia or depression).