PHARMACOTHERAPEUTIC MANAGEMENT OF INFECTIOUS DISEASES Semester 2 — Complete Must-Know Notes --- OUTLINE Section 1: Introduction to Chemotherapy & Immune System
Got it — you want the pharmacology notes reformatted to match the exact styling of the vascular pathology notes I just wrote (the ones from document 7) — meaning: - Bold section headers with - Bullet points with for narrative points - Tables with --- formatting - Bold key terms inline - Practice questions at the end - Summary table at the end Let me redo the full pharmacology notes in that exact style now. --- Summary This comprehensive document covers the pharmacotherapeutic management of infectious diseases, spanning antibiotic principles, antimicrobial resistance, drug classes targeting bacterial cell walls and ribosomes, antimycobacterials, antifungals, antivirals, antiparasitic agents, HIV management, and the pharmacotherapy of acne. Key Points Selective toxicity is the foundational principle of chemotherapy — drugs must harm the pathogen while sparing the host, exploiting differences between microbial and human biochemistry. Antimicrobial resistance (AMR) is driven by enzymatic inactivation, target site mutation, efflux pumps, and reduced permeability, and spreads most importantly via conjugation (plasmid transfer). Beta-lactams inhibit penicillin-binding proteins (PBPs) to block peptidoglycan cross-linking; resistance via beta-lactamases is countered by beta-lactamase inhibitor combinations. Vancomycin is the drug of choice for MRSA but carries risks of red man syndrome, nephrotoxicity, and ototoxicity; therapeutic drug monitoring is essential. Aminoglycosides are concentration-dependent bactericidal agents with irreversible ototoxicity and nephrotoxicity as dose-limiting toxicities. Fluoroquinolones inhibit DNA gyrase and topoisomerase IV and are contraindicated in children, pregnant women, and patients with myasthenia gravis due to tendinopathy and cartilage toxicity. First-line TB therapy (RIPE) targets multiple stages of mycobacterial metabolism; rifampicin is a potent CYP450 inducer with clinically critical drug interactions. HIV management relies on combination ART targeting multiple steps of the viral replication cycle; preferred first-line regimen is TDF + 3TC + DTG with a treatment goal of viral load sum of individual effects Beta-lactam + aminoglycoside Additive Combined effect = sum of parts — Antagonism Combined effect erythromycin azithromycin) Hearing loss At high doses 50S Inhibitors — Chloramphenicol Mechanism: bind 50S ribosomal subunit → inhibit peptidyl transferase → block peptide bond formation → bacteriostatic Broad spectrum; excellent CNS and intracellular penetration Rarely used systemically due to serious toxicity Side effects: Side Effect Details --- --- Grey baby syndrome Neonates lack UDP-glucuronyl transferase → drug accumulates → cardiovascular collapse, abdominal distension, grey skin discolouration, death Aplastic anaemia Idiosyncratic, dose-independent, irreversible — rare but potentially fatal; limits systemic use Reversible BM suppression Dose-dependent; anaemia, leucopenia, thrombocytopenia Current uses: topical eye drops (conjunctivitis); meningitis/typhoid in resource-limited settings 50S Inhibitors — Clindamycin Mechanism: bind 50S ribosomal subunit → block peptide bond formation → bacteriostatic Active against: Gram-positive cocci (MSSA, streptococci) + anaerobes (especially below diaphragm — Bacteroides fragilis) Excellent bone and joint penetration Key Use Details --- --- Skin/soft tissue infections MSSA, streptococcal Dental infections Penicillin-allergy alternative Osteomyelitis Excellent bone penetration Toxin-mediated infections Inhibits toxin production in TSS (Toxic Shock Syndrome) and necrotising fasciitis Anaerobic infections Intra-abdominal, pelvic Malaria In combination (clindamycin + quinine) Side effects: C. difficile colitis — highest risk of all antibiotics; GI upset; diarrhoea; rash 50S Inhibitors — Oxazolidinones (Linezolid) Mechanism: bind 50S ribosomal subunit at a unique site (23S rRNA) → prevent formation of the 70S initiation complex → block the very start of translation → bacteriostatic Active against MRSA, VRE, drug-resistant streptococci ; used in XDR-TB Side effects: Side Effect Details --- --- Myelosuppression Thrombocytopenia most common; also anaemia; monitor FBC weekly during treatment Serotonin syndrome Linezolid is a weak MAO inhibitor → avoid SSRIs, SNRIs, TCAs, pethidine Peripheral neuropathy Prolonged use ( 4 weeks) Optic neuropathy Prolonged use → visual disturbance; monitor vision Advantage: no dose adjustment required in renal or hepatic failure --- SECTION 7 — QUINOLONES & FOLIC ACID ANTAGONISTS Fluoroquinolones Mechanism: inhibit DNA gyrase (topoisomerase II) and topoisomerase IV → prevent DNA supercoiling/relaxation → DNA strand breaks → inability to replicate/repair DNA → bactericidal Concentration-dependent killing — maximise Cmax; once or twice daily dosing Excellent oral bioavailability (near-complete absorption — oral = IV for most indications) Drug Spectrum Key Clinical Use --- --- --- Ciprofloxacin Best Gram-negative (including Pseudomonas); limited Gram +ve UTI, GI infections (Salmonella, Shigella, Campylobacter), anthrax, Pseudomonas infections Levofloxacin Broad; good Gram +ve + atypicals CAP, UTI, TB (second-line), healthcare-associated infections Moxifloxacin Broadest; excellent Gram +ve, atypicals + anaerobes; NO Pseudomonas CAP, TB (second-line), intra-abdominal infections Ofloxacin Broad UTI, STIs, TB (second-line) Nalidixic acid Gram-negative only Uncomplicated UTI (largely obsolete now) Side effects: Side Effect Details --- --- Tendinopathy/tendon rupture Especially Achilles tendon; risk ↑ with corticosteroids + elderly + renal failure QT prolongation Risk of torsades de pointes; avoid with other QT-prolonging agents CNS effects Headache, dizziness, confusion, hallucinations, seizures; ↑ risk if combined with NSAIDs Phototoxicity Avoid prolonged sun exposure Cartilage damage Growing joint cartilage — contraindicated in children and pregnancy C. difficile Significant risk with broad-spectrum fluoroquinolones Drug interactions Inhibit CYP1A2 → ↑ theophylline levels; chelation with antacids/iron/calcium reduces absorption Contraindicated in: children · pregnancy · myasthenia gravis (worsen neuromuscular blockade) Folic Acid Antagonists — Sulfonamides Mechanism: structural analogue of para-aminobenzoic acid (PABA) → competitive inhibition of dihydropteroate synthase → ↓ dihydrofolic acid synthesis → ↓ purines and pyrimidines → bacteriostatic Humans obtain folate exogenously (diet) — bacteria must synthesise it; this is the basis of selective toxicity Drug Key Use --- --- Sulfamethoxazole (+ trimethoprim = co-trimoxazole) UTI, PCP prophylaxis/treatment, Toxoplasma, Nocardia Sulfadiazine Toxoplasmosis (with pyrimethamine) Silver sulfadiazine Topical — burns wound management Sulfadoxine-pyrimethamine Malaria (IPTp in pregnancy) Side effects: Side Effect Details --- --- Hypersensitivity Rash, Stevens-Johnson syndrome, toxic epidermal necrolysis Crystalluria Maintain adequate fluid intake to prevent renal stone formation Haemolytic anaemia In G6PD deficiency — check before prescribing Kernicterus Sulfonamides displace bilirubin from albumin in neonates → avoid in pregnancy (3rd trimester) and neonates Bone marrow suppression Megaloblastic anaemia, pancytopenia Folic Acid Antagonists — Trimethoprim Mechanism: inhibit dihydrofolate reductase (DHFR) → ↓ tetrahydrofolate → ↓ purines and DNA synthesis → bacteriostatic Co-trimoxazole (TMP-SMX) = trimethoprim + sulfamethoxazole — sequential blockade of the folate pathway at two steps → synergistic; often bactericidal in combination Key uses of co-trimoxazole: Indication Details --- --- Uncomplicated UTI First-line in many settings PCP treatment + prophylaxis Pneumocystis jirovecii pneumonia — high-dose IV treatment; prophylaxis when CD4 200 on ART): Fluconazole 200 mg/day Other Antifungals Drug Mechanism Use Side Effects --- --- --- --- Griseofulvin Disrupts microtubule polymerisation → inhibits mitosis in derm