Pharmacology and Antibiotic Therapy

Pharmacology

Drug-Drug Interactions

Substrates (Drugs metabolized by the enzyme)

  • CYP450 3A4 substrates: Sildenafil, Atorvastatin, Simvastatin, Venlafaxine, Alprazolam.
  • CYP450 activity decreases by ~30% after age 70.

Inhibitors (Block enzyme function, increasing drug concentration)

  • Macrolides (Clarithromycin, Erythromycin) → Risk of substrate-induced toxicity (e.g., Atorvastatin 20mg could behave like 300mg).
  • Antifungals (Ketoconazole, Fluconazole).
  • Cisapride (Propulsid – withdrawn in the U.S.).
  • Cimetidine (Tagamet).
  • Citalopram (Celexa).
  • Grapefruit → Affects statins, erythromycin, calcium channel blockers, antivirals, amiodarone, benzodiazepines, cisapride, carbamazepine, buspirone.

Activators (Enhance enzyme function, lowering drug levels)

  • St. John’s Wort → Lowers levels of antiretrovirals, contraceptives, and cyclosporine.
    • May trigger serotonin syndrome if taken with SSRIs or SNRIs.

Pharmacology Basics

Pharmacokinetics

  • How the body processes a drug: Absorption, distribution, metabolism, and elimination.

Pharmacodynamics

  • How the drug affects the body and disease processes (remains unchanged with aging).

First-Pass Effect

  • Orally ingested drugs → Absorbed in the small intestine → Enter portal circulation → Processed in the liver (CYP450 biotransformation).
  • Extensive first-pass metabolism drugs cannot be taken orally.
    • Example: Insulin.
  • CYP450 enzyme can be induced (faster metabolism) or inhibited (slower metabolism).
  • Other biotransformation sites: Kidneys, GI tract, lungs.

NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)

  • Avoid in:Heart failure, GI bleeding, kidney disease.
    • Mechanism: Inhibits prostaglandin synthesis, which is essential for normal physiological functions.
  • Long-term use requires patient consent (due to increased risk of MI, stroke, embolism, GI bleeding, acute kidney failure).
  • Consider co-prescribing: PPI, H2RA, Misoprostol (for GI protection).

Miscellaneous Facts

  • Capsaicin cream → Used for trigeminal neuralgia and postherpetic neuralgia.
  • Aspirin (ASA) → Irreversibly suppresses platelet function for up to 7 days.

Narrow Therapeutic Index (NTI) Drugs (Require close monitoring)

DrugMonitoring Parameters
WarfarinINR (interacts with sulfa drugs, “G” herbs, and leafy greens/mayo).
DigoxinDigoxin levels, EKG, electrolytes (K+, Mg+, Ca+, creatinine).
TheophyllineBlood levels.
Tegretol & DilantinBlood levels.
LevothyroxineTSH levels.
LithiumBlood levels, TSH.

Safety Considerations

  • PPIs → Increase fracture risk. (Example: Prilosec interacts with Warfarin.)
  • TZDs (Thiazolidinediones) → May cause/exacerbate CHF.
  • Bisphosphonates → Risk of erosive esophagitis.
  • Statins → Avoid grapefruit juice.
  • Clindamycin → High risk for C. difficile infection.
  • Thiazide diuretics → Contraindicated in sulfa allergy.
    • Chlorthalidone is preferred over HCTZ (longer-acting).
  • Spironolactone → May cause gynecomastia.
  • ACEIs/ARBs → Discontinue if pregnant; excreted in breast milk.
  • Alpha-blockers → First-line therapy only for men with both HTN & BPH.

Antibiotic Therapy

Principles of Empiric Antimicrobial Therapy

  • Decision-making process based on infection characteristics and site.
  • Key considerations:
    • What are the most likely pathogens?
    • Will this antibiotic effectively target them?
    • Likelihood of resistance?
    • Severity of consequences if treatment fails?
    • Optimal safe dose?
    • Shortest effective duration?

Tetracyclines

  • Coverage: Gram-negative, Atypicals, MRSA.
  • Contraindications: Pregnancy, children <9 years (risk of permanent tooth discoloration & skeletal defects if used in late pregnancy).
  • Acne Treatment:
    • Start around age 13-14 (after full tooth eruption).
    • Mild comedones: OTC topicals (salicylic acid, benzoyl peroxide).
    • Moderate: Try Rx topicals first (Benzamycin, Retin-A, Azelaic Acid) for 2-3 months before oral tetracyclines.
  • Adverse Effects:
    • Photosensitivity → Avoid prolonged sun exposure.
    • Esophageal ulcers → Take with full glass of water.
    • Take on an empty stomach for best absorption.
    • May reduce birth control effectiveness.
    • Expired tetracyclines can cause nephropathy—discard old pills.

Lincosamides – Clindamycin

  • Coverage: Gram-positive, Aerobes, Anaerobes.
  • Adverse Effect: High risk of C. difficile infection.

Gram-Positive Bacteria

  • Common organisms:
    • Streptococcus
    • Staphylococcus
    • Enterococcus

Gram-Negative Bacteria

  • H. influenzae treatment:
    • Cephalosporins, Augmentin, Macrolides, Respiratory Fluoroquinolones, Doxycycline.
  • Everything else: Requires specific coverage based on pathogen.

Macrolides

  • Coverage: Atypical pathogens.
  • Risks:
    • QT prolongation → ↑ risk of CV death.
    • Contraindicated in Myasthenia Gravis (can cause respiratory failure).
    • Drug interactions: Anticoagulants, Digoxin, Theophylline, Statins.
    • GI upset common with erythromycin.
  • Macrolide allergy alternatives: Doxycycline, Quinolones.

Cephalosporins (Beta-lactams, classified by generation)

GenerationCoverageExamplesIndications
1st GenGram +Cephalexin (Keflex), CefadroxilGroup A Strep, MSSA (not MRSA), pregnancy UTI, cellulitis, impetigo
2nd GenGram +/- (broader)Ceftin, CefzilOtitis media, rhinosinusitis, CAP, chronic bronchitis
3rd GenGram – (weak Gram +)CefiximeVarious Gram-negative infections
Extended 3rd GenGram +/- (broad)Rocephin, CefdinirGonorrhea, PID, Pyelonephritis, Otitis Media
  • Cross-reactivity: 1st gen cephalosporins have highest PCN allergy cross-reactivity.

Risk Factors for Antibiotic Resistance

  • Age <2 or >65.
  • Recent antibiotic use (last 1 month, 3 months for pneumonia).
  • Hospitalization in past 5 days.
  • Comorbidities or immunocompromised status.

Penicillins

  • Side Effects: Diarrhea, C. Diff, Vaginitis, Stevens-Johnson Syndrome.
  • Avoid Amoxicillin in Mononucleosis → Can cause generalized rash.
  • Specific Uses:
    • Dicloxacillin: Mastitis, impetigo.
    • Anaphylaxis & angioedema → IgE-mediated Type 1 reaction.
  • PCN Allergy Alternative: Macrolides.

Augmentin (Amoxicillin + Clavulanate)

  • Coverage: Gram +/-, Beta-lactamase producing bacteria (NO MRSA).
  • High-dose (3-4g/day) needed for Drug-Resistant Strep Pneumoniae (DRSP).
  • Clavulanate → Beta-lactamase inhibitor allowing Amoxicillin to work on:
    • H. influenzae, M. catarrhalis.

Fluoroquinolones

DrugCoverage
CiprofloxacinGram-negative, Atypicals
Levofloxacin (Levaquin)Gram +/- , Atypicals, DRSP
  • Black Box Warning: Achilles Tendon Rupture (↑ risk with steroids).
  • Contraindications:
    • Children <18, Pregnancy, Breastfeeding.
    • Myasthenia Gravis (can cause respiratory failure).
  • Adverse Effects:
    • QT prolongation.
    • Hypoglycemia risk.

Antibiotic Therapy/Pharmacology

Sulfonamide

  • Effective against Gram-negative bacteria and MRSA but lacks activity against Streptococcus and E. coli.
  • Not recommended for:
    • Individuals with G6PD deficiency due to risk of hemolysis.
    • Infants younger than two months.
  • HIV patients face an elevated risk of Stevens-Johnson syndrome.

Medications Necessitating Eye Examinations

  • Digoxin: May cause color vision disturbances (yellow-green tint), blurry vision, or halos if levels become excessive.
  • Ethambutol & Linezolid: Can lead to optic neuropathy.
  • Corticosteroids: Associated with cataracts, glaucoma, and optic neuritis.
  • Fluoroquinolones: May increase risk of retinal detachment.
  • Phosphodiesterase inhibitors (Viagra, Cialis, Levitra): Linked to cataracts, blurred vision, and ischemic optic neuropathy.
  • Isotretinoin (Accutane): May cause cataracts and impaired night vision.
  • Topiramate (Topamax): Can trigger acute angle-closure glaucoma, raised intracranial pressure, and pupil dilation.
  • Hydroxychloroquine (Plaquenil): Risk of neuropathy and permanent vision impairment.

Cultural Considerations: Southeast Asian Patients

  • Includes Vietnamese, Hmong, and Filipino populations.
  • Patients may be hesitant to ask questions about treatments.
  • Family consultation is often part of major medical decisions.
  • May not disclose non-adherence to prescribed treatments.
  • Show high respect for physicians and rarely express disagreement openly.
  • Health beliefs often center around balancing hot and cold (yin/yang).
  • The male head of the household typically makes decisions.
  • Alpha thalassemia is more prevalent in these populations.
  • Surgery is usually considered a last resort.
  • Infants and young children may wear protective amulets.

Beta-Lactam Antibiotics

  • Penicillins: Includes penicillin, amoxicillin, dicloxacillin, and ampicillin.
  • Cephalosporins: Recognized by “ceph-” or “cef-” prefixes.
  • Carbapenems: Imipenem is commonly administered with cilastatin.
  • Monobactams: Example includes aztreonam.
  • Notable for a high incidence of allergic reactions.

Specific Antimicrobials

  • Nitrofurantoin: Primarily used for urinary tract infections.
  • Metronidazole (Flagyl): Targets anaerobic organisms.

Food & Drug Interactions

  • Tetracycline: Avoid dairy as it interferes with absorption.
  • MAOIs: Must not be combined with high-tyramine foods (e.g., fermented items).
  • Heart-healthy choices:
    • Omega-3-rich fish like salmon.
    • Plant sterols and stanols to lower cholesterol.
  • Vitamin K sources: Collard greens.
  • Blood pressure-lowering minerals:
    • Magnesium: Found in nuts, beans, wheat, and laxatives.
    • Potassium: Present in fruits, leafy greens, and nuts.
  • Non-dairy calcium options: Tofu, spinach, and sardines.
  • Celiac disease:
    • Avoid gluten-containing grains like wheat, rye, barley, and oats.
    • Gluten-free alternatives include corn, rice, potatoes, quinoa, tapioca, and soybeans.

Herbal Remedies & Their Effects

  • Echinacea: Supports immune function.
  • Black cohosh & roasted soybeans: Some estrogen-like effects.
  • Kava Kava: Used for anxiety relief.
  • St. John’s Wort: Helps with depression but interacts with oral contraceptives, cyclosporine, and certain antiretrovirals.
  • Saw Palmetto: Often taken for benign prostatic hyperplasia (BPH).
  • Fish oil & ginseng: Increase bleeding risk.
  • Milk thistle: May benefit liver function, cholesterol levels, and diabetes management.

Vitamin D Deficiency

  • Plays a role in cell regulation, calcium-phosphorus balance, and inflammation reduction.
  • Sun exposure is the most effective way to produce vitamin D.
  • Phenytoin users require 2–5 times more vitamin D.
  • Symptoms include:
    • Rickets, osteomalacia, and muscle weakness.
  • Measurement: 25-hydroxyvitamin D blood test.
  • Recommended intake:
    • Infants: 400 IU daily (equivalent to 32 oz of milk per day).
    • Ages 1–70: 600 IU daily.
    • Over 70: 800 IU daily.
  • Risk factors for deficiency:
    • Darker skin tones (reduced synthesis).
    • Frequent sunscreen use.
    • Liver or kidney disease, post-gastric bypass.
  • Preferred supplementation: Vitamin D3.
    • High-dose therapy: 50,000 IU weekly for eight weeks.
    • Maintenance: 1,000–2,000 IU daily.

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