Lecture 3: Use of Antibiotics Flashcards

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1
Q

What is the normal oral temperature?

A

37 degrees

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2
Q

What is the normal axillary (armpit) temperature?

A

36.3 degrees

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3
Q

What is the normal rectal temperature?

A

37.7 degrees

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4
Q

What is the normal (ear) temperature?

A

37.7 degrees

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5
Q

What is temperature regulated by?

A

The hypothalamus

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6
Q

What does a fever trigger?

A

Release of prostaglandin E2 (PGE2)

This acts on the hypothalamus

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7
Q

What are internal pyrogens?

A

Cytokines
IL-1
IL-6
TNF

Can cross the blood brain barrier

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8
Q

What are external pyrogens?

A

Gram negative bacterial lipopolysaccharides

Superantigens, some bacterial toxins are super pyrogens

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9
Q

What is the normal respiration rate for an adult at rest?

A

Range from 15-20 breaths per minute

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10
Q

When is a respiration rate considered abnormal?

A

Over 25 breaths or under 12 breaths per minute

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11
Q

What areas within the brain are control points to respiration rate?

A

Medulla
Pons
Cerebral cortex

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12
Q

What are the chemical influences on respiration rate?

A

Chemoreceptors in blood and CSF, O2, CO2, pH

Drugs, medication, hormones

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13
Q

What is the normal heart rate?

A

Normal pulse is 60 to 100 beats per minute

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14
Q

What numbers are recorded when measuring blood pressure?

A

Systolic pressure - arterial contraction

Diastolic pressure - arterial relaxation

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15
Q

What unit is blood pressure measured in?

A

mm Hg

Millimetres of mercury

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16
Q

What is considered a normal blood pressure?

A

<120/<80

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17
Q

What values are considered pre-hypertension?

A

120-139/80-89

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18
Q

What values are considered high blood pressure (hypertension)?

A

140/90

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19
Q

What are the common features of a gram-positive bacteria?

A

Cell wall mostly peptidoglycan

Peptide cross links for stability of the cell wall

Cross links formed by penicillin binding proteins

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20
Q

What does Beta-lactams inhibit?

A

Inhibits formation of cross-links by penicillin binding proteins

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21
Q

What are common gram-positive bacteria in the bowel?

A

Enterococci
Alpha-haemolytic streptococci
Beta-haemolytic streptococci

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22
Q

What are common gram-negative rods?

A

Escherichia coli

Klebsiella pneumoniae

Pseudomonas aeruginosa

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23
Q

What are the common features of gram-negative cell wall?

A

External layer cross-linked peptidoglycan with a lipid bilayer

Porin channels allow small hydrated molecules to pass across

Outer membrane

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24
Q

What are the anaerobes of the bowel?

A

Clostridium spp

Anaerobic streptococci

Bacteroides spp

25
Q

What is metronidazole active against?

A

Only active against obligate anaerobes

26
Q

What is the mode of action of Metronidazole?

A

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

27
Q

What does reduction of metronidazole create?

A

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

28
Q

Why are coliforms grown under anaerobic conditions physiologically resistant?

A

The oxidation-reduction potential is not sufficiently negative to convert the antibiotic to its active form in facultative bacteria

29
Q

What new compound have promising activity against mycobacterium tuberculosis?

A

PA 824

30
Q

What is the mode of action of Gentamicin?

A

Enters the gram-negative cell by an active transport system based on oxidative metabolism

Needs active uptake and proton motive force

Inhibits protein synthesis

31
Q

What is Gentamicin active against?

A

No activity against anaerobes, streptococci and enterococci

32
Q

What are teichoic acids? And where are they found?

A

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

33
Q

What type of bacteria are teichoic acids found in?

A

Gram-negative bacteria

34
Q

What are teichoic acids linked to?

A

Either covalently bonded to N-acetylmuramic acid of the peptidoglycan layer or linked to the plasma membrane lipids found in the cytoplasmic membrane

35
Q

What contribution do teichoic acids make?

A

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

35
Q

What is the rough process of cell wall biosynthesis?

A

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

36
Q

What does Beta lactam antibiotic interfere with?

A

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

37
Q

What does bacterial cell wall biosynthesis UDP pentapeptide bind with?

A

Lipid II precursor

38
Q

How are penicillin binding proteins inhibited?

A

Shared spatial structure of the terminal D-Ala-D-Ala terminus of the peptidoglycan pentapeptide and beta-lactams

39
Q

What bacteria is Benzylpenicillin active against? Why?

A

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

40
Q

How does ampicillin differ from benzylpenicillin?

A

Ampicillin differs only by the addition of an amino residue

41
Q

Why does benzylpenicillin have no activity against b-lactamase negative coliforms?

A

Not sufficiently polar to cross the outer lipid bilayer

42
Q

What are ampicillin able to do?

A

They are polar enough to go through the porin channel in the outer lipid bilayer of the gram-negative cell wall

43
Q

What kinds of bacteria are amoxicillin active against?

A

Active against coliforms

(those that are Beta-lactamase negative)

44
Q

What is an example of a Beta-lactamase inhibitor?

A

Co-amoxiclav
(combination of amoxicillin and clavulanic acid)

45
Q

What is clavulanic acid?

A

Beta-lactam like agent

Has no useful antibacterial activity
Binds avidly to the active site of Beta-lactamase enzymes

46
Q

What is the mechanism of action of clavulanic acid?

A

3 amoxicillin molecules are inactivated by the Beta-lactamase enzyme, inactivating it

Leaves amoxicillin unaltered to perform its function

47
Q

What has the activity of co-amoxiclav been enhanced by?

A

Addition of clavulanic acid

48
Q

What is the general activity of piperacillin-tazobactam similar to?

A

Similar to co-amoxiclav but has anti-pseudomonal activity

49
Q

What are cephalosporins?

A

Large class of antibiotics

Not inactivated by standard Beta-lactamase

1st generation: better gram-positive activity

2nd-3rd generation: better gram-negative activity

50
Q

What are some common carbapenems?

A

Imipenem
Meropenem
Ertapenem

51
Q

What activity do imipenem and meropenem have?

A

Anti-pseudomonal activity

52
Q

What agents are imipenem and meropenem resistant to?

A

Resistant to the activity of standard Beta-lactamase of MSSA, E.Coli, Klebsiella pneumoniae and Bacteroides spp

53
Q

How can resistance to carbapenems be acquired with pesudomonas?

A

Mutation in gene coding for the protein prevents antibiotic using this channel

Permeability changes are another mechanism

54
Q

What are 2 examples of glycopeptides?

A

Vancomycin and teicoplanin

55
Q

What is the activity of glycopeptides restricted to?

A

Gram-positive bacteria

Due to large size preventing them crossing the outer lipid membrane of gram-negative bacteria

56
Q

What is glycopeptides mode of action?

A

Acts on peptidoglycan synthesis

Sits across 2 terminal alanine residues of peptidoglycan building block - preventing its incorporation

57
Q

What do vancomycin and teicoplanin have activity against?

A

Specific activity against gram-positive bacteria

58
Q
A