Lecture 3: Use of Antibiotics Flashcards
What is the normal oral temperature?
37 degrees
What is the normal axillary (armpit) temperature?
36.3 degrees
What is the normal rectal temperature?
37.7 degrees
What is the normal (ear) temperature?
37.7 degrees
What is temperature regulated by?
The hypothalamus
What does a fever trigger?
Release of prostaglandin E2 (PGE2)
This acts on the hypothalamus
What are internal pyrogens?
Cytokines
IL-1
IL-6
TNF
Can cross the blood brain barrier
What are external pyrogens?
Gram negative bacterial lipopolysaccharides
Superantigens, some bacterial toxins are super pyrogens
What is the normal respiration rate for an adult at rest?
Range from 15-20 breaths per minute
When is a respiration rate considered abnormal?
Over 25 breaths or under 12 breaths per minute
What areas within the brain are control points to respiration rate?
Medulla
Pons
Cerebral cortex
What are the chemical influences on respiration rate?
Chemoreceptors in blood and CSF, O2, CO2, pH
Drugs, medication, hormones
What is the normal heart rate?
Normal pulse is 60 to 100 beats per minute
What numbers are recorded when measuring blood pressure?
Systolic pressure - arterial contraction
Diastolic pressure - arterial relaxation
What unit is blood pressure measured in?
mm Hg
Millimetres of mercury
What is considered a normal blood pressure?
<120/<80
What values are considered pre-hypertension?
120-139/80-89
What values are considered high blood pressure (hypertension)?
140/90
What are the common features of a gram-positive bacteria?
Cell wall mostly peptidoglycan
Peptide cross links for stability of the cell wall
Cross links formed by penicillin binding proteins
What does Beta-lactams inhibit?
Inhibits formation of cross-links by penicillin binding proteins
What are common gram-positive bacteria in the bowel?
Enterococci
Alpha-haemolytic streptococci
Beta-haemolytic streptococci
What are common gram-negative rods?
Escherichia coli
Klebsiella pneumoniae
Pseudomonas aeruginosa
What are the common features of gram-negative cell wall?
External layer cross-linked peptidoglycan with a lipid bilayer
Porin channels allow small hydrated molecules to pass across
Outer membrane
What are the anaerobes of the bowel?
Clostridium spp
Anaerobic streptococci
Bacteroides spp
What is metronidazole active against?
Only active against obligate anaerobes
What is the mode of action of Metronidazole?
Activated by reducing environment
Damage and destroy DNA and chromosome
Negative oxidation-reduction potential of obligate anaerobic bacteria acts as an electron sink, capturing electrons that would be transferred to hydrogen ions
What does reduction of metronidazole create?
A concentration gradients that drives uptake of more drug
Promotes formation of intermediate compounds and free radicals that are toxic to the cell - shearing DNA
Why are coliforms grown under anaerobic conditions physiologically resistant?
The oxidation-reduction potential is not sufficiently negative to convert the antibiotic to its active form in facultative bacteria
What new compound have promising activity against mycobacterium tuberculosis?
PA 824
What is the mode of action of Gentamicin?
Enters the gram-negative cell by an active transport system based on oxidative metabolism
Needs active uptake and proton motive force
Inhibits protein synthesis
What is Gentamicin active against?
No activity against anaerobes, streptococci and enterococci
What are teichoic acids? And where are they found?
Polymers of glycerol or ribitol linked via phosphodiester bonds
Found in the cell wall of gram-positive bacteria
Extend to the surface of peptidoglycan layer
What type of bacteria are teichoic acids found in?
Gram-negative bacteria
What are teichoic acids linked to?
Either covalently bonded to N-acetylmuramic acid of the peptidoglycan layer or linked to the plasma membrane lipids found in the cytoplasmic membrane
What contribution do teichoic acids make?
Structural support for the cell wall
Negatively charged so contribute to the negative charge of the gram-positive cell wall
Scaffold against turgor pressure
Anchoring point
Immunogenic inflammatory compounds
What is the rough process of cell wall biosynthesis?
Synthesis starts in the cytoplasm
Amino acids are added
Appended to lipid carrier 1
Lipid II is a precursor for peptidoglycan biosynthesis
Polymerizes via enzymes to stich sugars
What does Beta lactam antibiotic interfere with?
Synthesis of peptidoglycan of bacterial cell wall
Bind covalently to the active site of penicillin binding proteins
Preventing peptide cross lining by penicillin binding protein enzymes
What does bacterial cell wall biosynthesis UDP pentapeptide bind with?
Lipid II precursor
How are penicillin binding proteins inhibited?
Shared spatial structure of the terminal D-Ala-D-Ala terminus of the peptidoglycan pentapeptide and beta-lactams
What bacteria is Benzylpenicillin active against? Why?
Only activity against gram positives
(not MSSA & MRSA)
Cannot cross the protein channels
Bacteria produce Beta-lactamase that cuts the bond of the 4-membered beta-lactam ring
How does ampicillin differ from benzylpenicillin?
Ampicillin differs only by the addition of an amino residue
Why does benzylpenicillin have no activity against b-lactamase negative coliforms?
Not sufficiently polar to cross the outer lipid bilayer
What are ampicillin able to do?
They are polar enough to go through the porin channel in the outer lipid bilayer of the gram-negative cell wall
What kinds of bacteria are amoxicillin active against?
Active against coliforms
(those that are Beta-lactamase negative)
What is an example of a Beta-lactamase inhibitor?
Co-amoxiclav
(combination of amoxicillin and clavulanic acid)
What is clavulanic acid?
Beta-lactam like agent
Has no useful antibacterial activity
Binds avidly to the active site of Beta-lactamase enzymes
What is the mechanism of action of clavulanic acid?
3 amoxicillin molecules are inactivated by the Beta-lactamase enzyme, inactivating it
Leaves amoxicillin unaltered to perform its function
What has the activity of co-amoxiclav been enhanced by?
Addition of clavulanic acid
What is the general activity of piperacillin-tazobactam similar to?
Similar to co-amoxiclav but has anti-pseudomonal activity
What are cephalosporins?
Large class of antibiotics
Not inactivated by standard Beta-lactamase
1st generation: better gram-positive activity
2nd-3rd generation: better gram-negative activity
What are some common carbapenems?
Imipenem
Meropenem
Ertapenem
What activity do imipenem and meropenem have?
Anti-pseudomonal activity
What agents are imipenem and meropenem resistant to?
Resistant to the activity of standard Beta-lactamase of MSSA, E.Coli, Klebsiella pneumoniae and Bacteroides spp
How can resistance to carbapenems be acquired with pesudomonas?
Mutation in gene coding for the protein prevents antibiotic using this channel
Permeability changes are another mechanism
What are 2 examples of glycopeptides?
Vancomycin and teicoplanin
What is the activity of glycopeptides restricted to?
Gram-positive bacteria
Due to large size preventing them crossing the outer lipid membrane of gram-negative bacteria
What is glycopeptides mode of action?
Acts on peptidoglycan synthesis
Sits across 2 terminal alanine residues of peptidoglycan building block - preventing its incorporation
What do vancomycin and teicoplanin have activity against?
Specific activity against gram-positive bacteria
