This document provides a comprehensive overview of essential pharmacology and immunology principles relevant to antimicrobial therapy and immune re
This document provides a comprehensive overview of essential pharmacology and immunology principles relevant to antimicrobial therapy and immune responses. It details pharmacokinetic and pharmacodynamic concepts, profiles high-yield antibiotic classes regarding their mechanisms, spectrums, and toxicities, and explains mechanisms of antimicrobial resistance. Furthermore, it differentiates between innate and adaptive immunity, outlines key immune cells and their functions, and clarifies the roles of MHC molecules, antibodies, and the complement system. Key Points Pharmacokinetics (PK) encompasses how the body processes drugs through absorption, distribution, metabolism, and excretion, while pharmacodynamics (PD) describes how drugs interact with pathogens, guiding dosing strategies. Antibiotic classes vary significantly in their mechanisms of action, covering a wide range of bacterial types, but often carry specific toxicities such as nephrotoxicity, ototoxicity, and drug interactions. Antimicrobial resistance (AMR) arises through diverse mechanisms like enzymatic inactivation (e.g., beta-lactamases), target modification (e.g., MRSA), and efflux pumps, frequently spread via gene transfer. The immune system relies on both innate (rapid, non-specific) and adaptive (slower, specific, memory-driven) branches, employing specialized cells and molecular mechanisms like MHC-I and MHC-II for antigen presentation. Detailed Notes PK/PD ESSENTIALS What the Body Does to the Drug (PK) Absorption : IV = 100% bioavailability. High oral bioavailability: fluoroquinolones , metronidazole , linezolid , doxycycline , trimethoprim . Distribution : High Vd (good tissue penetration) = fluoroquinolones , macrolides , tetracyclines , metronidazole . Low Vd (stays in plasma) = vancomycin , aminoglycosides . Metabolism : Liver ( CYP450 ). Rifampicin = potent inducer (reduces levels of warfarin, OCP, antiretrovirals). Azoles/macrolides/metronidazole = inhibitors (increase drug levels). Excretion : Mostly renal → dose adjust aminoglycosides , vancomycin , beta-lactams in renal failure. Nitrofurantoin — AVOID in renal impairment. What the Drug Does to the Bug (PD) Parameter Drug Strategy --- --- --- Time MIC Beta-lactams Frequent dosing / prolonged infusion Cmax/MIC Aminoglycosides Once daily high dose AUC/MIC Vancomycin, fluoroquinolones Optimise total exposure PAE ( Post-antibiotic effect ) = continued suppression after levels drop below MIC → aminoglycosides , fluoroquinolones have long PAE → supports once daily dosing. GRAM +ve vs GRAM -ve — MUST KNOW Feature Gram +ve Gram -ve --- --- --- Peptidoglycan Thick, outer Thin, inner Outer membrane Absent Present (LPS/endotoxin) Gram stain Purple Pink Vancomycin works? Yes No (too large) Endotoxin/septic shock No Yes (LPS) ANTIBIOTIC CLASSES — HIGH-YIELD ONLY Beta-Lactams MOA : Inhibit PBPs → block cell wall crosslinking → bactericidal , time-dependent. Resistance : beta-lactamases , altered PBPs ( MRSA = mecA → PBP2a ). Penicillin allergy cross-reactivity with cephalosporins = ~1–2% (much less than once thought). Drug Key Point --- --- Flucloxacillin MSSA only Co-amoxiclav Broad + anaerobes; bites, abscesses Piperacillin-tazobactam Pseudomonas cover Ceftriaxone Meningitis, gonorrhoea; once daily Ceftazidime Pseudomonas; no Gram+ Meropenem Broadest; CNS safe Ertapenem Once daily; NO Pseudomonas/Acinetobacter Aztreonam Gram-negative only; safe in penicillin allergy Vancomycin MOA : Binds D-Ala-D-Ala → blocks cell wall synthesis. Gram-positive only . IV for systemic; oral ONLY for C. difficile (not absorbed systemically). TDM : AUC/MIC 400–600 ; trough 10–20 mg/L. Side effects : nephrotoxicity , Red Man Syndrome (histamine release — NOT allergy, slow infusion), ototoxicity . VanA = resistant to vancomycin + teicoplanin; VanB = vancomycin resistant, teicoplanin susceptible. Aminoglycosides (Gentamicin, Amikacin) MOA : Irreversibly bind 30S → bactericidal , concentration-dependent. INACTIVE against anaerobes (need O₂ for uptake). Once daily dosing (Hartford nomogram). Toxicities : nephrotoxicity (reversible), ototoxicity — cochlear (irreversible hearing loss) + vestibular (vertigo). Synergistic with beta-lactams. Macrolides (Azithromycin, Clarithromycin, Erythromycin) MOA : Bind 23S rRNA (50S) → bacteriostatic ; excellent intracellular penetration. Uses : atypicals ( Mycoplasma, Chlamydia, Legionella ), CAP , H. pylori (clarithromycin), pertussis . Side effects : GI upset, QT prolongation , hepatotoxicity, CYP inhibitors → drug interactions. Azithromycin: long t½ → 3–5 day course only. Tetracyclines (Doxycycline, Tigecycline) MOA : Bind 30S reversibly → bacteriostatic . Chelate divalent cations → avoid with dairy, antacids, iron. Uses : atypicals , Chlamydia, Lyme, Rickettsia , acne, malaria prophylaxis, MRSA soft tissue . Avoid : pregnancy, children <8 (teeth/bone), renal failure (except doxycycline). Side effects : photosensitivity , oesophageal ulceration, pseudotumour cerebri. Fluoroquinolone