Session 12 Flashcards
Describe bacterial structure
• DNA present in nuclei and
plasmids • Cell membrane and wall • Other specialised features
how anti-microbials work Mechanisms
- 5 main methods
- Inhibiting cell wall synthesis
- Inhibiting nucleic acid synthesis
- Stopping metabolite production
- Inhibiting cell membrane synthesis
- Inhibiting protein synthesis
What’s the difference between bactercidal and bacteriostatic?
• Bactericidal – means destroying, or killing bacteria. • Bacteriostatic – stopping divisions and replication of bacteria, slowing the growth. The bacteria are still alive and rely on body’s usual mechanisms
Classes of antibiotic
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Antibiotic resistance
- Example
- Beta lactamase enzymes
- Efflux pumps • Plasmid DNA can be passed from cell to cell
• Why do we need to monitor?
• Narrow therapeutic window • Maximum effect of antibiotic • Risk of toxicity • Examples: vancomycin and gentamicin • Blood tests at specified time
Time dependent Vs. concentration dependent killing of bacteria
• Minimum inhibitory concentration used needed to kill bacteria • In time dependent – long half
lives beneficial, they spend
longer at the binding sites • In concentration dependent –
levels important, need a
certain concentration at the
binding sites
Why do we use antibiotics?
- Short term management of bacterial infections • Prophylaxis in acute setting
- High risk procedures • Long term prophylaxis
- If suitable
- Local UHL guidelines
- Associated risks
why clavulanic acid and amoxicillin are co
prescribed as co-amoxiclav
• Synergistic effect • Examples: Tazocin, Co-trimoxazole
Co-amoxiclav
Clavulanic acid
Inhibits effect of some β lactamase enzymes so amoxicillin can work better
Amoxicillin
Acts on cell walls of bacteria in usual standard mechanism of action
What determines which antibiotic to give?
- Multiple factors
- What is the likely source of infection?
- Sources lend themselves to common groups of bacteria
- Is the patient in a ‘high risk group’?
- Trends, previous results – including resistance patterns • Special groups
- Hepatic / renal impairment / pregnancy • Allergies and reactions
Anti-microbial stewardship
• Does the patient need antibiotics?
• Effects of overuse – resistance and side effects • Starting broad (empirical treatment) and then narrowing to more
appropriate antibiotics
• Choice rationalised by appropriate samples, blood cultures, swabs etc
• UHL policy – ‘restricted’ antibiotics, need authorisation from
microbiology department
Identify • Isolate • Investigate • Inform • Initiate treatment
• Initiate treatment
A to F A – abroad B – blood born virus C – colonised D – diarrhoea (& vomiting) E – expectorating (cough) F – funny looking rash
When can acyclovir be used in the treatment of
herpes simplex virus?
Aciclovir is anti viral, multiple uses, prevents replication but doesn’t eradicate. Can also be used against varicella zosta virus. Used against herpes simplex type 1.
Haemostasis
Haemostasis – the recapitulation of the recapitulation
• Essential for life
Limits bleeding following injury – adhesion and activation of platelets
and fibrin formation
haemostatic plug + fibrin mesh → stable bleeding control • Thrombosis: pathological haemostasis – in the absence of bleeding
things gone wrong • Thromboembolic diseases are common
- deep vein thrombosis (DVT) and pulmonary embolism (PE)
- transient ischaemic attacks (TIA), ischaemic stroke
- myocardial infarction (MI)
- consequence of atrial fibrillation (AF) • Venous and intracardiac thrombosis driven largely by coagulation
cascade c.f. arterial thrombus mainly platelet rich
The coagulation cascade
• Anticoagulant drugs – prevent thrombus formation and thrombus
growing
Intrinsic pathway - all components within blood
Extrinsic pathway - tissue factor and other factors in endothelium
• Regulation of the coagulation cascade essential to prevent solidification
of all blood • Coagulation factors are present in blood as inactive zymogens
serine proteases and cofactors • Number of intrinsic inhibitors of this pathway including antithrombin III • Vascular endothelium and its regulation of many mediators also critical
for balance in coagulation cascade (and platelet activation) • Calcium is an important cofactor in many of the coagulation cascade
steps (think of chelators used in blood sampling)
.
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Heparin
• First heparin like compound isolated in 1916ish • Heparins produced naturally in mast cells and vascular endothelium • Extracted for pharmaceutical use from porcine intestinal mucosa,
bovine lung • Unfractionated heparins (UFH) are large 5-30 kDa • Low molecular weight heparins (LMWH) 1-5 kDa
produced in 1980’s • Inhibits coagulation in vitro and in vivo
- Enhance antithrombin III activity - ~ 1000-fold