Biomedical Sciences Viva Anticoagulants and Antibiotics

Biomedical Sciences Viva Anticoagulants and AntibioticsDevinda Jayewardene

Pharmacology General TipsPASTQUESTIONSPASTQUESTIONSPASTQUESTIONSType A vs Type B ADRsAntibiotics Learn them now!

Case 152 year old woman, sudden SOB D3 post lap cholecystectomy. 1. PDx and DDx2. Important historical features?3. Important examination findings?4. Ix?5. Compare/contrast the heparins and warfarin.

HeparinsMoA UFH effects thrombin and Xa, LMWH just effects XaADRsType A haemorrhage (major ICH, GIT, minor epistaxis, bruising)Type B HITS (Ig vs heparin and PF4 complex), hyperkalaemiaMonitoring UFH APTT, LMWH Anti Factor XaPharmacokinetics Liver and kidney UFH preferred in CKD (both renal)UFH reversal with protamineDosageProphylactic (UFH 5000U SC 2-3/day, Enoxaparin 20 mg BD/40 mg OD)Therapeutic (UFH 5000U bolus + 30,000U/day adjust to APTT, Enoxa 1mg/kg BD/ 1.5 mg/kg daily)

WarfarinMoA inhibits quinine reductase and Vit K epoxide reductase interfering Vit K metabolism (coenzyme for II, VII, IX, X, protein C and S)ADRsType A HaemorrhageType B teratogen, skin necrosis, zillions of interactionsMonitoring INRPK liver (P450) and excreted by kidneyReversal prothrombinex, FFP, Vit KCover with heparin in initial stagesDosage 5 mg OD for 2 days, adjust to INR (2-3 unless heart valves),

NOACsXa Inhibitors have xa in name (rivaroxaban, apixaban)Direct thrombin inhibitors dabigatranDont need monitoringNo antidote

Case 40 F12 days febrile, cough productive of little sputum, malaise, lethargyVS HR 120, BP 140/90, RR 26 Temp 37.8Creps over all lung fieldsSees GP, given Amoxicillin and sent home

Pdx? Ddx?How would you judge if she needs admission?Ix?

Antimicrobials - TargetsCell Wall B Lactams, VancomycinRibosomal 30S Aminoglycosides, Tetracyclines, 50S Chloramphenicol, Erythromycin and macrolides, Lincosamides Buy AT 30 CEL at 50DNANucleotide synthesisDNA

Wall InhibitorsMoA?Examples?Spectrum of Activity?ADRs?

Wall Inhibitors Mechanisms and SpectrumMoABeta Lactams: Carboxy- and transpeptidases -> enzymes -> deathVancomycin - binding D-alanine D-alanine portion of cell wall precursors Spectrum Pencillins G+, Neiserria meningitidis, syphilisAmpicillin/Amoxicillin G- coverage (HELPSS kill Enterococci - HiB, E. Coli, Listeria, Proteus, Salmonella, Shigella, Enteroccoci)Penicillinase Resistance di/flucloxacillin, +clav/tazobactamAnti-Pseudomonal tic- or piperacillinVancomycin G+ (MRSA), Enterococci, C. Diff

Wall Inhibitors Spectrum (2)Cephalosporins Penicillinase Resistant1st Gen. Ceph G+, (PEcK - Proteus, E. coli, Klebsiella)2nd Gen Ceph (cefuroxime) Uncommonly used, G+, mild G- coverage (HEN PEcKS - HiB, Enterobacter, Neisseria)3rd Gen Ceph G+ and G-4th Gen Ceph (cefepime) Anti-pseudomonalCarbopenems Nukes

Wall Inhibitors PD and PKADRsType A- Diarrhoea, Nausea, Abdominal Pain, Opportunistic InfectionsType B- Anaphylaxis/Allergy (immediate usually a lincosamide or vanc, non-immediate cephalosporin)Vancomycin nephro- and ototoxic, thrombophlebitis, red man syndrome, monitoringInteractionsBeta-Lactams clotting drugs (prolongs BT)Cephalosporins increase aminoglycoside nephrotoxicityPKPartial hepatic metabolism, mainly kidney excretion, ceftriaxone 40% biliary

Protein Synthesis InhibitorsMoA?Examples?Spectrum of Activity?ADRs?

Protein Synthesis InhibitorsBuy AT 30 CEL at 50AminoglycosidesInhibits initiation complex, mRNA misreading, blocks translocationNephrotoxic, Ototoxic, TeratogenicMonitoring >48 hours or with PK alteration trough levels or AUCRenal excretionMacrolidesPrevents translocation (macroSLIDES) 50SA: GIT distress, candida, B: MACRO motility issues, arrhythmia (QTc), Rash, EosinophiliaHalf-life Erithro 90 min, Clarith 270 min, Azithro 12-24 hoursElimination in bile after inactivation in liver

Microbes - Morphology6 Clinically Relevant G+Cocci SA, StrepRods Spore Forming (Bacillus and Clostridium), Non-Spore Forming (Listeria, Corynebacterium)G-Only one G- Coccus (Neisseria - diplococcus)Rods coccoids (Hib, Pertussis), or normal rods (Others)Strange Organisms mycobacterium, spirochetes, mycoplasma

What are potential aetiologies of pneumonia? How do you treat it?

Aetiologies of PneumoniaTypical Strep. Pneumoniae, HiB, SA, Moraxella CatarrhalisAtypical viral, mycoplasma pneumonia, legionella, chlamydia

Tests come back positive for mycoplasma is amoxicillin appropriate? Why? What other options are there?

Antibiotic Management of PneumoniaDependent on type and severity, usually covers both typical and atypical unless mild

CAPOutpatient amoxi/doxy/clarith, Mild inpatient IV Benpen + PO Doxy/Clarith, Severe IV ceft OR benpen AND gent as well as azithro

HAP (unlikely atypical, likely resistant)amoxi (low risk), ceftriaxone (intermediate), tazocin/timentin (high risk)

Aspiration (anaerobes) IV benpen and metronidazole

Antibiotics Targeting DNA TrimethoprimSulfonamidesFluoroquinolonesMetronidazoleNitrofurantoin (among other things)

Trimethoprim and Sulfonamides

TrimethoprimSulfonamidesMoAdihydrofolic acid analogueparabenzoic acid (PABA) analogueADRsA: teratogenic, marrow suppression, (megaloblastic anaemia, leucopoenia, granulocytopoenia)B: hyperkalaemia, rashB: Hypersensitivity, rash, nephrotoxic, photosensitivity, displaces drugs attached to albumin (e.g. warfarin), haemolysis in G6PDPKGood PO absorption, crosses BBB, high conctrations in lungs and urine, eliminated by kidney

Fluroquinolones (-floxacins)MoA Inhibit DNA gyrase and topoisomerase IV impairing DNA organisation after divisionADRsA: GI distress, superinfectionB: tendonitis and rupture (e.g. Achilles), rashes, headache, dizziness, some may prolong QT intervalPK Good PO availability, only ofloxacin crosses BBB, Cipro- and Nor- eliminated partly by P450 and partly renal, while Ofloxacin renal. Resistance DNA gyrase mutations and efflux pumps

MetronidazoleMoA forms free radicals that damage DNAIndications anaerobes, protozoa (giardia, trichomonas), and H. PyloriADRsA: GI distress, C. DiffB: Disulfiram-like reaction with EtOH, headache, metallic taste