Biomedical Sciences Viva

Anticoagulants and
Antibiotics
Devinda Jayewardene

Pharmacology General Tips

PASTQUESTIONSPASTQUESTIONSPASTQUESTIONS
Type A vs Type B ADRs
Antibiotics Learn them now!

Case 1
52 year old woman, sudden SOB D3 post lap
cholecystectomy.
1.
2.
3.
4.
5.

PDx and DDx

Important historical features?
Important examination findings?
Ix?
Compare/contrast the heparins and warfarin.

Heparins
MoA UFH effects thrombin and Xa, LMWH just effects Xa
ADRs
Type A haemorrhage (major ICH, GIT, minor epistaxis, bruising)
Type B HITS (Ig vs heparin and PF4 complex), hyperkalaemia

Monitoring UFH APTT, LMWH Anti Factor Xa

Pharmacokinetics Liver and kidney UFH preferred in CKD (both renal)
UFH reversal with protamine
Dosage
Prophylactic (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)

Warfarin
MoA inhibits quinine reductase and Vit K epoxide reductase
interfering Vit K metabolism (coenzyme for II, VII, IX, X, protein C and
S)
ADRs
Type A Haemorrhage
Type B teratogen, skin necrosis, zillions of interactions

Monitoring INR
PK liver (P450) and excreted by kidney
Reversal prothrombinex, FFP, Vit K
Cover with heparin in initial stages
Dosage 5 mg OD for 2 days, adjust to INR (2-3 unless heart valves),

NOACs
Xa Inhibitors have xa in name (rivaroxaban,
apixaban)
Direct thrombin inhibitors dabigatran
Dont need monitoring
No antidote

Case 40 F
12 days febrile, cough productive of little sputum,
malaise, lethargy
VS HR 120, BP 140/90, RR 26 Temp 37.8
Creps over all lung fields
Sees GP, given Amoxicillin and sent home
Pdx? Ddx?
How would you judge if she needs admission?
Ix?

Antimicrobials - Targets
Cell Wall B Lactams, Vancomycin
Ribosomal
30S Aminoglycosides, Tetracyclines, 50S Chloramphenicol,
Erythromycin and macrolides, Lincosamides
Buy AT 30 CEL at 50

DNA
Nucleotide synthesis
DNA

Wall Inhibitors
MoA?
Examples?
Spectrum of Activity?
ADRs?

Wall Inhibitors Mechanisms and

Spectrum
MoA
Beta Lactams: Carboxy- and transpeptidases -> enzymes -> death
Vancomycin - binding D-alanine D-alanine portion of cell wall
precursors

Spectrum
Pencillins G+, Neiserria meningitidis, syphilis
Ampicillin/Amoxicillin G- coverage (HELPSS kill Enterococci - HiB, E.
Coli, Listeria, Proteus, Salmonella, Shigella, Enteroccoci)
Penicillinase Resistance di/flucloxacillin, +clav/tazobactam
Anti-Pseudomonal tic- or piperacillin
Vancomycin G+ (MRSA), Enterococci, C. Diff

Wall Inhibitors Spectrum (2)

Cephalosporins Penicillinase Resistant
1st Gen. Ceph G+, (PEcK - Proteus, E. coli, Klebsiella)
2nd Gen Ceph (cefuroxime) Uncommonly used, G+, mild Gcoverage (HEN PEcKS - HiB, Enterobacter, Neisseria)
3rd Gen Ceph G+ and G 4th Gen Ceph (cefepime) Anti-pseudomonal

Carbopenems Nukes

Wall Inhibitors PD and PK

ADRs
Type A- Diarrhoea, Nausea, Abdominal Pain, Opportunistic Infections
Type B- Anaphylaxis/Allergy (immediate usually a lincosamide or vanc,
non-immediate cephalosporin)
Vancomycin nephro- and ototoxic, thrombophlebitis, red man syndrome,
monitoring

Interactions
Beta-Lactams clotting drugs (prolongs BT)
Cephalosporins increase aminoglycoside nephrotoxicity

PK
Partial hepatic metabolism, mainly kidney excretion, ceftriaxone 40% biliary

Protein Synthesis Inhibitors

MoA?
Examples?
Spectrum of Activity?
ADRs?

Protein Synthesis Inhibitors

Buy AT 30 CEL at 50
Aminoglycosides

Inhibits initiation complex, mRNA misreading, blocks translocation

Nephrotoxic, Ototoxic, Teratogenic
Monitoring >48 hours or with PK alteration trough levels or AUC
Renal excretion

Macrolides
Prevents translocation (macroSLIDES) 50S
A: GIT distress, candida, B: MACRO motility issues, arrhythmia (QTc), Rash,
Eosinophilia
Half-life Erithro 90 min, Clarith 270 min, Azithro 12-24 hours
Elimination in bile after inactivation in liver

Microbes - Morphology
6 Clinically Relevant G+
Cocci SA, Strep
Rods 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 Pneumonia
Typical Strep. Pneumoniae, HiB, SA, Moraxella
Catarrhalis
Atypical viral, mycoplasma pneumonia, legionella,
chlamydia

Tests come back positive for mycoplasma is amoxicillin

appropriate? Why? What other options are there?

Antibiotic Management of
Pneumonia
Dependent on type and severity, usually covers both typical and atypical
unless mild
CAP
Outpatient 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

Trimethoprim
Sulfonamides
Fluoroquinolones
Metronidazole
Nitrofurantoin (among other things)

Trimethoprim and Sulfonamides

Trimethoprim

Sulfonamides

MoA

dihydrofolic acid analogue

parabenzoic acid (PABA)

analogue

ADRs

A: teratogenic, marrow
suppression, (megaloblastic
anaemia, leucopoenia,
granulocytopoenia)
B: hyperkalaemia, rash

B: Hypersensitivity, rash,
nephrotoxic,
photosensitivity, displaces
drugs attached to albumin
(e.g. warfarin), haemolysis
in G6PD

PK

Good 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 division
ADRs
A: GI distress, superinfection
B: tendonitis and rupture (e.g. Achilles), rashes, headache,
dizziness, some may prolong QT interval

PK 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

Metronidazole
MoA forms free radicals that damage DNA
Indications anaerobes, protozoa (giardia,
trichomonas), and H. Pylori
ADRs
A: GI distress, C. Diff
B: Disulfiram-like reaction with EtOH, headache, metallic taste