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Antimicrobial Chemotherapy Flashcards

1
Q

Define bactericidal

A

An antimicrobial that kills bacteria

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2
Q

Define Bacteriostatic

A

Antimicrobial that inhibits growth of bacteria

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3
Q

Define Sensitive

A

Organism that is inhibited or killed by the antimicrobial, that is available at the site of infection

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4
Q

Define Resistant

A

Organism that is not killed or inhibited by the antimicrobial that is available at the site of infection

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5
Q

What does MBC stand for?

A

Minimal bactericidal concentration

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6
Q

What is MBC?

A

The minimum concentration of antimicrobial required to kill a given organism

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7
Q

What does MIC mean?

A

Minimal inhibitory concentration

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8
Q

What is MIC?

A

The minimum concentration of antimicrobial required to inhibit growth of a given organism.

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9
Q

What is topical administration and what is an example?

A

This treatment is applied to a surface (e.g. the skin or a mucous membrane), for example eczema creams)

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10
Q

What is systemic administration?

A

A treatment/ medication that is taken internally, either orally or parentally. (e.g. tablets)

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11
Q

What is parental administration?

A

This is medication that is taken intra-venously or intra-muscularly or occasionally subcutaneously. ( e.g. injections)

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12
Q

What is an additive effect?

A

When 2 or more drugs are taken in combination and they have no effect on each other. Both of their normal effects occur,

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13
Q

What is an antagonistic effect?

A

2 or more drugs that are taken together have a combined effect that is less than the sum of their individual contributions.

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14
Q

What is a synergistic effect?

A

When the combined effect of 2 or more drugs is greater than the sum of their individual contributions.

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15
Q

What groups of antibiotics inhibit cell wall synthesis?

A 
Beta lactams (Penicillins and Cephalosporins)
Glycopeptides
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16
Q

What groups of antibiotics inhibit protein synthesis?

A 
Aminoglycosides
Macrolides
Tetracyclines
Oxazolidinones
Cyclic Lipopeptide
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17
Q

What types of antibiotics inhibit nucleic acid synthesis?

A

Fluoroquinolones
When Bacteriostatic and Bactericidal antibiotics are used in combination ( e.g. Trimethoprim + Sulphamethoxazole = Co-trimoxazole )

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18
Q

Describe the mechanism of how beta lactams work

A

These are bactericidal antibiotics. Beta lactams bind to the penicillin binding proteins and deactivates them
prevents cross linking (with amino acids) of sugar strands (carb polymers).
so peptidoglycan can not be produced
the cell wall not synthesised.

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19
Q

Describe the mechanism of glycopeptides

A

These are bactericidal antibiotics, which bind to the amino acid chains and prevent penicillin binding proteins from binding, so peptidoglycan an not be synthesised.
(they inhibit the assembly of peptidoglycan precursor)

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20
Q

What are Beta lactams effective against?

A

Gram positive bacteria (mostly)

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21
Q

What are glycopeptides effective against?

A

They only act of gram positive bacteria

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22
Q

Briefly describe the mechanism of aminoglycosides

A

These bind in the ribosome and causes the messenger RNA to be misread or premature termination of the protein synthesis (or both).
This leads to inaccuracy in the protein produced, so this protein will then be destroyed.

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23
Q

What is an aminoglycoside and what is an example of one?

A

It is a concentration-dependant bactericidal antibiotic, so the concentration determines whether the aminoglycoside is bactericidal or not.

Example: gentamicin

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24
Q

What are aminoglycosides effective against?

A

A serious gram-negative infection (e.g. coliform)

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25
What are important examples of glycopeptides?
Vancomycin and Teiplanin
26
What advantage does Teicoplanin have over Vancomycin?
Teicoplanin is a less toxic than Vancomycin and can be taken as a single dose a day.
27
Describe the mechanism of macrolides
They prevent a peptide bond from forming between the growing amino acid chain to the next amino acid (being transported by tRNA molecule.
28
What is an example of macrolides?
Erythroycin
29
Describe the mechanism of tetracyclines
They block the attachment of (aminoacyl) tRNA to the A site on the ribosome, this prevents the addition of amino acids to the peptide chain.
30
What are tetracyclines used to treat?
Gram-positive bacteria
31
Describe the mechanism of oxazolidinones
These prevent the 2 subunits of the ribosome from linking, so that synthesis can not occur.
32
What is an example of an oxazolidinones?
Linezoild (only used in the treatment of serious infection)
33
What type of bacteria are oxazolidinones used to treat?
Gram- positive bacteria
34
How do cyclic lipopeptides work? (roughly)
They cause the cell to depolarise (by creating holes in the membrane that ions leak out of), which inhibits the synthesis of DNA, RNA and protein.
35
What is an example of a cyclic lipopeptide?
Daptomycin
36
What mechanism is co-trimoxazole an example of?
Inhibition of nucleic acid synthesis by combining the use of a Bacteriostatic and a Bactericidal antibiotic. This either directly effects DNA synthesis or interrupts the supply of the precursors of DNA synthesis.
37
What is co-trimoxazole a combination of?
Trimethoprim and sulphamethoxazole.
38
How do fluoroquinolones work?
They directly inhibit DNA synthesis
39
What are fluoroquinolones and what are they used to treat?
They are bactericidal antibiotics. Effective against: Gram-negative organisms including Pseudomonas Levofloxacin may work against Gram positive bacteria
40
What are two examples of fluoroquinolones?
Ciprofloxacin and Levofloaxcin
41
Name the four different types of anti-fungal drugs
Polyenes Azoles Allylamines Echinocandins
42
How do polyenes work?
Bind to ergosterol, increases fungal cell wall permeability.
43
What is a disadvantage of the use of polyenes?
They will bind to other sterols (e.g. cholesterol) in the mammalian cell membranes, so are toxic.
44
Give two examples of polyenes and how they are administered
Amphotericin B is used intravenously but only for serious systemic fungal infections as it is extremely toxic with a wide range of side effects. Nystatin is used topically for fungal skin infections or in pessaries for vaginal candida infections, or can be used orally for oral and oesophageal candidiasis.
45
How do azoles work?
Inhibit ergosterol synthesis
46
Give 3 example of recent azoles (triazoles)
Fluconazole, Itraconazole and Voriconazole
47
Give 2 examples of older azoles
Miconazole and ketoconazole (are both imidazoles)
48
Give an example of an allylamine and what it is used for.
Terbinafine is used against dermatophyte infections of the skin and nails. Mild infections are treated topically and more serious infections are treated orally.
49
What has to be monitored when Terbinafine is used?
Liver function has to be monitored every 2 weeks as terbinafine can damage the liver.
50
Name the different 7 anti-herpes drugs
``` Aciclovir Valaciclovir Flamciclovir Valganciclovir Ganciclovir Foscarnet Cidofovir ```
51
What is used to treat HIV?
(now) Usually a combination of 3 drugs is used to treat HIV. This includes 2 analogue reverse transcriptase inhibitors and either a non-nucleoside reverse transcriptase inhibitor or a viral protease inhibitor. This usually includes nevirapine and saquinavir
52
Name the drugs used to treat chronic Hepatitis B and C
Interferon- alpha Ribavirin (used in conjunction with PEGylated interferon- alpha) Adefovir dipivoxil Lamivudine (last 2 can also be used for HIV treatment)
53
What is used to treat Influenza A or B (viral respiratory infections)?
Zanamivir or Oseltamivir
54
Explain the mechanism of Beta- lactase resistance
The bacteria produce Beta-lactamases which are bacterial enzymes that cleave the Beta-lactam ring, which makes it inactive.
55
What bacteria are resistant to Beta-lactases?
Most hospital strains of staphylococcus aureus | Majority of Gram-negative bacilli
56
How can you combat Beta lactase resistance?
Either modify the antibiotic side chain to produce a new antibiotic that is resistant to the actions of Beta- lactamase (e.g. Flucloxacillin) Or use a Beta-lactase in conjunction with a Beta-lactamase inhibitor (which will attach the Beta-lactamase itself). An example of this is co-amoxiclav, amoxicillin + clavulanic acid)
57
What are the current issues faced in antibiotic resistance?
Beta-lactamase production Extended spectrum B-lactamases (ESBLs) Carbapenemase Producing Enterobacteriaceae (CPE)/ Carbapenem Resistant Enterobacteriasciae (CRE) Penicillin Binding Protein (PBP) target site alteration Glycopeptide resistance
58
In which organisms do CPE and CRE occur?
Gram negative organisms
59
What has to be done in the presence of CPE/CRE?
The patient must be isolated to prevent spread. In some cases there are no antimicrobial options for therapy.
60
Explain Penicillin Binding Protein (PBP) alteration
The target site on the Penicillin Binding protein, on to which the antibiotics bind, changes shape, so Beta-lactams can no longer bind to it and prevent cell wall synthesis.
61
Given an example of PBP alteration
S. aureus display this, including Methicillin resistant Staphylococcus Aureus (MRSA)
62
What can organisms with PBP alteration be treated with?
Flucloxacillin Vancomycin- a glycopeptide (can be used for MRSA) Linezolid- a oxazolidinone (can be used for MRSA)
63
Explain glycopeptide (vancomycin) resistance and what it is displayed by
Recently vancomycin resistant enterococci (VRE) e.g. Enterococcus faecalis and Enterococcus faecium, have emerged. VRE- the peptidoglycan precursor has altered shape so vancomycin can no longer bind to it.
64
What are ESBL's and what produces them?
Extended spectrum Beta Lactamases are enzymes that prevent Beta lactasms from killing the microorgansims. They are produced by Gram-negative organisms. Patients with ESBL's must be isolated so it does not spread to other pateints.
65
What are the factors that should be considered in choosing an antimicrobial for a patient?
Patient considerations: * age * renal function * liver function * pregnancy Drug Related considerations: * The antimicrobial chosen should normally be effective against the known or likely causative organism/s * monotherapy vs combination
66
Name the main types of side effects encountered with use of antimicrobials
``` Allergic reactions Immediate Hypersensitivity Delayed Hypersensitivity Gastrointestinal Side effects Thrush Liver Toxicity Renal Toxicity Neurological Toxicity Haematological toxicity ```
67
Name the 4 different types of neurological toxicity and what they are caused by.
Ototoxicity- (most often seen after) use of aminoglycoside or vancomycin Optic neuropathy- ethambutol (an anti-tuberculous drug) Peripheral neuropathy- metronidazole and nitrofurantoin (their effect is reversible), isoniazid may cause this side effect Encephalopathy(degenerative disease of the brain) and convulsions- high dose penicillin and cephalosporin
68
What type of drug are allergic reactions commonly associated with?
Beta- lactams, but can occur with any antimicrobials.
69
Explain what delayed hypersensitivity is
Develops hours or days after antimicrobial is administered. It is an immune or cell mediated mechanism, that can cause rash, fever, serum sickness (hypersensitive reaction to administration of foreign serum, includes rash, fever and lymph node enlargement) ect
70
What are gastrointestinal side effect?
Nausea and vomiting , pseudomembranous colitis
71
What drugs cause thrush as a side effect?
Penicillins or cephalosporins
72
What antimicrobials cause liver toxicity (hepatotoxicity) and which patients are more susceptible to it?
Tetracycline, isoniazid and rifampicin. | Pre-existing liver disease and pregnancy make a patient more susceptible to hepatotoxicity.
73
What drugs can cause renal toxicity?
Aminoglycosides (e.g. gentamicin) and Vancomycin
74
What is haematological toxicity and which drugs cause it?
It is the selective or unselective depression of bone marrow. It can be caused by Co-trimoxazole. (sulphonamide and trimethoprim)
75
What is the role of the laboratory?
They advice on what antimicrobial should be used when the infecting organism is not yet known, They will then identify the infecting organism from a sample. They would then help to monitor serum levels to ensure they are in the therapeutic range.
76
Name 5 examples of commonly used Beta-lactams: penicillins
``` Benzyl penicillin (Penicillin G) Amoxicillin Ampicillin Co-amoxiclav Flucloxacillin ```
77
Name 4 commonly used Beta-lactams: Cephalosporins
Cephradine Cefuroxime Ceftriaxone Ceftazidime
78
Give examples of commonly used macrolides
Clarithromycin, Erythromycin and Azithromycin
79
Describe the method of Echinocandins and what they are used to treat
Inhibit glucan polysaccharide synthesis | Treats Candida and Aspergillus, (only used after special advice given.)
80
Give 3 examples of Echinocandins
Caspofungin Micafungin Anidulafungin

Principles of Disease (12 decks)

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