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Medicine 2 - 03 Pneumonia > 4 Pharmacology of Antibiotics > Flashcards

4 Pharmacology of Antibiotics Flashcards

1
Q

Describe features of gram Positive bacteria

A
  • Lack outer membrane
  • Thick cell wall - 15-50nm thick
  • Made of peptidoglycan (50%) and acid polymer (40-45%)
  • Highly charged (streptococci, staphylococci)
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2
Q

Describe features of gram Negative bacteria

A
  • They have a complex liposaccharide outer membrane
  • Complex outer layer makes it more resistant to antibiotics (pseudomonas aeruginosa)
  • And thinner cell wall (than gram +ve)
  • Peptidoglycan layer 2nm and 5% of cell mass
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3
Q

List some common gram-positive bacteria

A
  • Staph. aureus
  • Strept. pneumoniae
  • Clostridium botulinum
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4
Q

List some common gram-negative bacteria

A
  • Escherichia coli (E. coli)
  • pseudomonas aeruginosa
  • Acinetobacter baumanii
  • Haemophilus influenzae
  • Neisseria gonnorhoeae
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5
Q

Describe the principles of antibiotic chemotherapy

A

There are different ways of classifying antibiotics:

  • Bacteriostatic antibiotics (stop the growth of bacteria)
  • Bactericidal antibiotics (kill bacteria)
  • Broad-spectrum antibiotics (act against a wide range of bacteria - like on gram +ve and -ve; e.g. Amoxicillin)
  • Narrow-spectrum antibiotics (act against specific bacteria - are targeted e.g. Vancomycin)
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6
Q

List the categories of antibiotics

which target different aspects of a bacteria

A
  • Cell wall synthesis inhibitors
  • Cell membrane integrity disruptors
  • Protein synthesis and nucleic acid inhibitors
  • Metabolic pathway inhibitors
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7
Q

List the different types of cell wall synthesis inhibitors and cell membrane integrity disruptors

A
  • Beta-lactams

- Glycopeptides

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8
Q

Name the different types of Beta-lactam antibiotics

A
  • Penicillins
  • Cephalosporins
  • Carbapenems
  • Monobactams
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9
Q

Describe the principle by which bacterial cell walls are made up of

A

Bacterial cell walls are made up of alternating amino sugar units of:

  • N-acteylglucosamine (NAG)
  • N-acetylmuramic acid (NAMA)

The NAMA has a short peptide side chain that is cross-linked using an enzyme called TRANSPEPTIDASE to from a polymeric lattice

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10
Q

State the mechanism of action of Beta-lactams

A

Beta-lactams target bacterial cell wall synthesis:
- by binding irreversibly to a transpeptidase, thus preventing cross-links peptidoglycans in the bacterial cell wall being made

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11
Q

Describe penicillin

A

It is a type of Beta-lactam antibiotics

  • It is only effective against dividing organisms
  • Division requires cell wall synthesis - leads to lysis if cell wall is disrupted
  • So, penicillins are BACTERICIDAL (lysis of bacteria)
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12
Q

Give some examples of penicillin antibiotics

A
  • Amoxicillin
  • Benzylpenicillin
  • Flucloxacillin
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13
Q

Give the side effects of penicillin

A

Few side effects

  • Penicillin allergy (hypersensitivity reactions are like skin rashes, hives, itchy eyes, and swollen lips, tongue, or face)
  • Anaphylactic shock is very rare but can be fatal
  • Wide-spectrum antibiotics can cause GI disturbances and candida
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14
Q

Describe resistance to penicillin by some bacteria

A

Some penicillins are inactivated by B-lactamases (enzyme), which are secreted by bacteria, destroying the antibiotic - thus creating resistance
- e.g. Amoxicillin, flucloxacillin

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15
Q

Describe how penicillin resistance (by B-lactamases) are overcome

A

Clavulanic acid is included with some agents (e.g. amoxicillin) to inhibit the B-lactamase enzymes:

Co-amoxiclav = amoxicillin + clavulanic acid

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16
Q

Describe cephalosporins

A

It is a Beta-lactam antibiotic

  • with a similar MOA to penicillins (transpeptidase inhibitor - preventing cross-linking of peptidoglycans in the cell wall)
  • It is widely given parentally
  • About 10% of penicillin-sensitive patients will have an allergic reaction to cephalosporins
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17
Q

Give some examples of cephalosporin antibiotics

A
  • Cefaclor
  • Cefalexin
  • Cefotaxime
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18
Q

Describe the mechanism of action of glycopeptide antibiotics

A

They inhibit peptidoglycan biosynthesis:

  • by binding to D-Ala-A at the terminal of the growing peptide chain during cell wall synthesis
  • resulting in the inhibition of transpeptidase
  • further preventing elongation + cross-linking of the peptidoglycan chains (transpeptidation)
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19
Q

Give some examples of glycopeptide antibiotics

A
  • Vancomycin

- Teicoplanin

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20
Q

Describe the use of vancomycin

and give its side effects

A

Vancomycin is bactericidal

  • and given by I.V. for multi-resistant Staphylococcus aureus (MRSA) infections
  • and given orally for pseudomembranous colitis

Side effects:

  • ototoxicity
  • nephrotoxicity
21
Q

List the different types of protein synthesis + nucleic inhibitors and metabolic pathway inhibitors

A

Antibiotics inhibiting protein synthesis:

  • Tetracyclines
  • Macrolides
  • Aminoglycosides

Antibiotics inhibiting Bacterial DNA:

  • Quinolones
  • Sulphonamides
  • Trimethoprim
22
Q

Describe tetracyclines, and give it’s MOA

A

It is an antibiotic that inhibits protein synthesis:
MOA: tetracyclines inhibit protein synthesis, by binding to the 30s subunit of the bacterial ribosome and preventing tRNA from binding at the acceptor site (A)

Tetracyclines:

  • actively accumulate in bacterial cells
  • are BACTERIOSTATIC
  • are resistant to a wide range of bacteria - but doxycycline used in exacerbations of acne and bronchitis
23
Q

Give some examples of tetracyclines

A
  • Tetracyclines
  • Oxytetracyclines
  • Doxycycline
24
Q

Give some side effects of tetracyclines

A
  • Bone staining (avoid giving to under 12s)

- Phototoxicity

25
Describe macrolides, and give it's MOA
Antibiotic, that can be bacteriostatic or bactericidal - They have a similar antibiotic spectrum as penicillins - a good alternative if px has a penicillin allergy MOA: - Macrolides prevent the translocation of the 50s subunit of the bacterial ribosome along the mRNA and hence inhibit protein synthesis
26
Give some examples of macrolide antibiotics
- Azithromycin - Clarithromycin - Erythromycin
27
Give some side effects of macrolides
Macrolides are cytochrome P450 inhibitors and associated with a range of drug interactions (increasing conc. of interacting drugs) - theophylline, warfarin Side effects: - Nausea (especially erythromycin) - Cardiac - QT prolongation
28
Describe aminoglycosides, and give it's MOA
They are bactericidal antibiotics - used to manage infections caused by gram -ve bacteria - They have a synergy with penicillin - breakdown of the cell wall, leads to increased uptake of aminoglycosides MOA: - Aminoglycosides bind irreversibly to the 30s subunit of bacterial ribosomes, hence leading to the misreading of mRNA, and interferes with protein synthesis
29
Give some examples of aminoglycoside antibiotics
- Gentamicin - Amikacin - Neomycin - Tobramycin
30
Give the uses of gentamicin
Gentamicin is an aminoglycoside antibiotic - that is most widely used against gram -ve bacteria alongside penicillins - It is used in sepsis, infective endocarditis, and pseudomonas aerunginosa infections - Give via injections Caution! - Half-life is 2-3 hours - IT IS A DRUG OF NARROW TW: drug monitoring needed - Mainly excreted unchanged in urine - CAUTION in patients with lower renal function
31
State some side effects of aminoglycosides (gentamicin)
- Ototoxicity | - Nephrotoxicity
32
List some types of antibiotics that inhibit bacterial DNA
- Quinolones - Sulphonamides - Trimethoprim (metronidazole)
33
Describe quinolones
Antibiotics that are inhibitors of bacterial DNA gyrase and topoisomerase IV - Quinolones are bactericidal
34
Give the mechanism of action of quinolones
In gram +ve: - DNA gyrase is inhibited, hence supercoiling of bacterial DNA is inhibited (supercoiling is essential for DNA repair + replication) In gram -ve: - Topoisomerase IV is inhibited, which interferes with the separation of DNA strands on replication
35
Give some examples of quinolone antibiotics
- Ciprofloxacin | - Norfloxacin
36
Give some side effects of quinolones
- Disabling, long-lasting, potentially irreversibly adverse reactions affecting musculocutaneous + nervous systems have been reported very rarely seen with fluoroquinolone abx Fluoroquinolone treatment should be discontinued at 1st signs of serious adverse reaction: - tendon pain or inflammation - there is also an increased risk of tendon rupture/convulsions with steroids and NSAIDs - inhibition of P450 enzymes
37
Describe metronidazole
It is a pro-drug (inactive); it needs to be activated to exert antibacterial/antiprotozoal actions it has interaction with alcohol
38
Give the mechanism of action of metronidazole
It is activated by anaerobic bacteria to cytotoxic products, which damages the helical structures of DNA - fragmentation of DNA, protein, and the cell membrane
39
Give clinical uses of metronidazole
- It is used against anaerobic bacteria and protozoa | - Also used for surgical prophylaxis (high-risk procedure)
40
Describe sulphonamides
Bacteriostatic antibiotics, which work to inhibit the production of folate (DNA synthesis) - there is a high degree of bacterial resistance to sulphonamides
41
Give the principle upon which sulphonamides work as an antibiotic agent, hence give the MOA of sulphonamides
To make DNA, folate is needed - Bacteria make folate, by converting p-aminobenzoic acid (PABA) into folate using the enzyme dihydropteroate synthetase MOA: - Sulphonamides inhibit the growth of bacteria by competitively inhibiting the enzyme dihydropteroate synthetase, involved in the synthesis of folate from PABA - The availability of DNA and RNA precursors is therefore reduced In effect, sulphonamide is a PABA antagonist
42
Give an example of a sulphonamide antibiotic
Sulfasalazine (sulfapyridine-aminosalicylate) - which is widely used in inflammatory bowel disease - and rheumatoid arthritis and sulfamethoxazole
43
Give some side effects of sulphonamides
- Skin rash, nausea, headache, and very rarely Stevens-Johnson syndrome - Use silver sulfadiazine for infected burns
44
Describe trimethoprim
So, trimethoprim is a folate antagonist - trimethoprim is less potent against the human form of the enzyme (DHFR, which trimethoprim inhibits) - It is bacteriostatic - Bacteria have a high degree of resistance to them - They have a narrow antibiotic spectrum Uses: - Main use is to treat simple urinary tract infections like cystitis
45
Give the MOA of trimethoprim
In the pathway to make RNA, folate is converted to tetrahydrofolate. Trimethoprim is a folate antagonist: - It inhibits the bacterial enzyme dihydrofolate reductase, which converts folate to tetrahydrofolate
46
Give the side effects of trimethoprim
Side effects: | - Limited, but make sure to avoid first 3 months of pregnancy (folate is important)
47
Explain what co-trimoxazole is, and give its uses
Co-trimoxzole is a combination of antibiotics: - Co-trimoxozole = trimethoprim + sulfamethoxazole Uses: - limited uses in treatment, except for pneumonia causes by yeast-like fungus pneumocystis jiroveci in immunocompromised patients (AIDS or transplant px)
48
Give the principles upon which selection of antibiotics is based:
- Guided by Culture and Sensitivity testing - Be aware of patterns of resistance - Query about allergies! - Apply pharmacological knowledge: > IV for rapid effects > Oral route: depends on bioavailability (f) - Be aware of drug-drug interactions - Patient education; considering MDT approaches - Advise the patient to COMPLETE THE COURSE > there could be small pool of bacteria remaining

Medicine 2 - 03 Pneumonia (8 decks)

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