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Antibacterials Flashcards

1
Q

Antibiotics general

A

Exploits differences between human cells and bacteria

Ideally, causative organisms are identified before antibiotics

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2
Q

Invaders

A

Prokaryotes - cell without nucleus. Bacteria causes most infectious diseases

Eukaryotes - cells with nuclei

  • Fungi
  • Protozoa
  • Helminths

Viruses

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3
Q

Infection vs. Colonization

A

Infections: invasion and multiplication of organisms. Prevalent in immunocompromised patients

Colonization: happens in the body by normal flora. Can help in controlling growth of potentially pathogenic organisms

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4
Q

Micro Review

A

Shape

  • Cocci (circular)
  • Bacilli (rod like)
  • Staphlococci (cocci in clumps)
  • Streptococci (cocci in chains)

Aerobes and anaerobes

Gram positive and Gram negative

  • Whether or not wall stains with Gram stain
  • Implications for action of antibacterials
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5
Q

Gram positive cell wall

A
  • Thick peptidoglycan layer, up to 40 layers, 50% of wall.

- Gram stain (crystal violet) turns it purple

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6
Q

Gram negative cell wall

A
  • Cell wall has a thin peptidoglycan (5%) of wall
  • Has an outer membrane
  • Less gram stain is trapped
  • LPS barrier to some antibiotics to penetrate
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7
Q

Bactericidal

A

Drugs are directly lethal to bacteria at clinically achievable concentrations

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8
Q

Bacteriostatic

A

Drugs can slow bacterial growth but do not cause cell death

Host defences especially important for these antibiotics

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9
Q

Superinfection

A

New microbes take over when antibiotics kill normal floral

Microbe resistant to drug action = difficult to treat

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10
Q

Resistance to Antibiotics

A

Selection of mutant bacteria enhanced by
Improper choice of antibiotic
- Dose of antibiotic is too low
- Dosing not continued for long enough
- Improper use of antibiotics, e.g. to treat a viral infection
- Prophylactic use of antibiotics, e.g. in animal feed

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11
Q

Antibiotic Therapy

A

Host factors - age, allergies, organ health, pregnancy, site of infection, and general health

Allergic reactions

  • Immune response
  • GI upset is not an allergic reaction
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12
Q

Mechanisms of Action

A
  1. Disruption of critical metabolic reaction
    - Sulfamethoxazole
    - Trimethoprim
  2. Interference with cell wall synthesis
    - Penicillins
    - Vancomycin
    - Amino-glycosides
  3. Interference with protein synthesis
    - Macrolides
    - Tetracyclines
    - Aminoglycosides
  4. Interference with DNA replication
    - Fluoroquinolones
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13
Q

Sulfonamides

A

One of the first groups of antibiotics. First industrial scale antibiotics. Use is a lot narrower than it once was

  • Broad spectrum
  • Sulfa-drug

eg. Sulfamethoxazole

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14
Q

Indication - Sulfonamides

A

Combined with trimethoprim
- co-trimoxazole

Reaches effective concentrations in the kidney

  • Used for UTI and otitis media
  • Upper respiratory tract infections
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15
Q

Contraindicated Condition - Sulfonamides

A

Known allergy: applies to other derivatives of the sulfa-like drugs

Pregnant women

  • linked to birth defects in 1st trimester
  • can increase fetal bilirubin in end of pregnancy
  • not advised during breastfeeding or for infants less than 2 months of age
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16
Q

Adverse Effects - Sulfonamides

A

Skin allergies (hypesensitivity)

  • Stevens-Johnsons syndrome. Swelling of mouth and tongue
  • Photosensitivity

Blood (bone marrow suppression)
- Agranulocytosis, thrombocytopenia, aplastic anemia

GI
- Nausea and vomiting (not allergic reactions)

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17
Q

Interactions with Sulfonamides

A
  • May enhance the hypoglycemic effects in diabetes
  • Increase toxic effects of phenytoin (anti seizure drug)
  • Increase anticoagulant effects of warfarin (coumadin)
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18
Q

B-Lactam Antibiotics

A

Alexander Fleming

  • Inhibits cell wall enzyme responsible for peptidoglycan synthesis - bactericidal
  • Characterized by the B-lactam ring in structures

4 groups

  • Penicillins
  • Cephalosporins
  • Monobactams (very rare in Canada, not covered)
  • Carbapenems
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19
Q

Penicillins

A

B-Lactam group

Naturally occurring substance
- Sensitive to B-lactamase

Semi-synthetic - changed slightly

  • B-lactamase-resistant
  • Broad-spectrum or aminopenicillins
  • Extended-spectrum or antipseudomonal penicillins

Aminopenicillins (broad-spectrum)
- Amoxicillin (more acid-stable), ampicillin

Antipseudomonal penicillins

  • Ticarcillin, piperacillin
  • Includes Pseudomonas aeruginosa: affects mostly ill people (immunocompromised, cystic fibrosis)
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20
Q

Pseudomonas aeruginoas

A

Opportunistic infections

respiratory tract
ears
eyes
CNS
UTI
endocarditis
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21
Q

Penicillins - Mechanism of Action

A

Enter the bacteria and bind to penicillin-binding proteins, normal cell wall synthesis is disrupted and bacteria cells rupture.

Only targets bacteria cells

22
Q

Penicillins Indication

A

Bactericidal - depends on type used

  • Active against most Gram-positive bacteria
  • Broad/extended-spectrum kills gram negative

Administration

  • PO, IM, IV
  • Pen G is IV or IM
  • Pen V is PO
23
Q

Drug Resistance to Penicillins

A

Can produce enzymes capable of destroying penicillins
Bacteria make B-lactamases that split the B-lactam ring

B-lactamases inhibitors

  • Clavulanic acid used to avoid drug resistance
  • Tazocatam
24
Q

Penicillins: Adverse effects

A

Generally well tolerated

GI problems - disturb normal gut flora

Allergic reactions

  • skin rashes
  • subcutaneous edema (lips)
25
Cephalosporins
Most widely used B-lactam antibiotics Bactericidal action Generations 1-5. Gens names based on when they were introduced into clinical settings. Each gen has better gram-negative coverage and better B-lactamase resistance
26
Gen 1 Cephalosporins
Cefazolin (Ancef) - Good gram-positive coverage. The best generation for these bacteria - Poor gram-negative coverage - Used for surgical prophylaxis, UTI's otitis media - Very commonly used - IV admin
27
Gen 2 Cephalosporins
Cefuroxime (Ceftin/Zinacef) - Good gram-positive coverage - Better gram-negative coverage than first gen - Taken PO for surgical prophylaxis
28
Gen 3 Cephalosporins
Cefotaxime - More broad spectrum - Most potent group against gram-negative - IV and IM - Easily passes meninges and diffused into CSF to treat CNS infections like meningitis
29
Gen 4 Cephalosporins
Cefepime (Maxipime) Broader spectrum of antibacterial activity than gen 3, especially gram +
30
Gen 5
Ceftaroline - MRSA infections
31
Adverse Effects - Cephalosporns
Generally well tolerated GI problems - disturb normal gut flora Allergic reactions - skin rashes - subcutaneous edema (lips) Cross hypersensitivity with penicillin, but does not exclude its use
32
Carbapenems
Imipenem Broad-spectrum antibacterial action Gram positive, negative and anaerobic - Effective for mixed infections, not for MRSA - All parentally given, not orally Reserved fro severe, complciated body cavity and connective tissue infections - Last resort antibiotics - Cannot be treated by more narrow drug Imipenem-cilastatin - Combination drug - Cilastatin inhibits breakdown of imipenem in kidney
33
Resistance - Carbapenems
Carbapenem-resistant Enterobacteriaceae (CRE) KPC (Klebsiella pneumoniae carbapenemase) and NDM (New Delhi Metallo-beta-lactamase) - Enzymes that break down carbapenems Resistant to most antibacterial drugs - You can buy carbapenem without a prescription, increases resistance
34
Macrolides Function
Erythromycin Inhibits protein synthesis - binds to ribosomes Mostly affects gram positive, some gram negative Highly protein bound - competes for hepatic metabolism Bacteriostatic* and bactericidal - Depending on concentration and bacterial susceptibility
35
Macrolides Indication
Respiratory, skin and soft tissue infections - Strep infections - Streptococcus pyogenes Syphilis and other STI's and lyme disease
36
Macrolides Adverse Effects
GI disturbances - Primarily with erythromycin - Nausea, vomiting, diarrhea, hepatotoxicity, anorexia Azithromycin and clarithromycin have fewer side effects and better tissue penetration
37
Tetracyclines
Tetracycline* Broad spectrum antibiotics - inhibit protein synthesis Bacteriostatic
38
Tetracyclines: Indications
Gram negative and gram positive Demeclocycline used to treat SIADH (syndrome of inappropriate ADH)
39
Tetracycline: Adverse Effects
- Bind to metal ions (Ca, Mg, iron, aluminum and forms insoluble complexes (chelation) - If taken with dairy products, antacids, and iron salts it reduces the absorption. Do not use in - Children < 8 years old - During pregnancy/breast feeding Strong affinity for calcium - causes discoloration of permanent teeth and tooth enamel - may retard fetal skeletal development is taken during pregnancy GI disturbances - direct irritation - alteration in gut flora can result in superinfection, diarrhea, and clostridium difficile Warafin effect (oral anticoagulant) Photosensitivity Antagonistic to bactericidal antibiotics - timing needed for both drugs
40
Aminoglycosides
Gentamicin Natural and semisynthetic * Bactericidal - Prevents or causes abnormal protein synthesis - Affective mostly aginstly Gram-negative and some gram-positive
41
Aminoglycosides - Indications
Used to kill gram negative bacteria | Often used in combination for synergistic effect
42
Aminoglycosides - Function
Poorly absorbed through GI tract - given IV or IM Given orally to decontaminate GI tract before procedures
43
Aminoglycosides - Toxicities
Ototoxicity (ear) - Irreversible - Auditory impairment (tinnitus) deafness - Vestibular balance problems, dizziness, vertigo Made worse if other ototoxic drugs are given (like loop diuretics) Nephrotoxicity (kidney) - Reversible - Extreme in neonates and pre-existing renal conditions - Measure proteinuria, serum creatinine levels, BUN - Must monitor plasma drug levels to prevent toxicities
44
Aminoglycosides - Interactions
Increased risk for nephrotoxicity (additive effect) if used with - Vancomycin (anti infective)- - Cyclosporine (immunosuppressant) - Amphotericin B (antifungal)
45
Quinolones
Ciprofloxacin Very effective and most commonly used Oral admin
46
Quinolones - Mechanism of Action
Bactericidal Gram negative organisms and some gram-positive - Broad spectrum Alteres DNA of bacteria - does not affect human DNA
47
Quinolones - Indications
* Urinary tract infections - Lower resp tract infections - Bone and joint infections - infectious diarrhea - Skin infections - STI * Anthrax
48
Quinolones - Adverse Effects
GI - nausea, vomiting, diarrhea Skin - rashes CNS - headache, dizziness
49
Quinolones - Interactions
- Theophylline (asthma drug) - Warfarin (anticoagulant) Oral absorption reduced by: - Antacids - Iron, zince, calcium containing preparations - Drugs given 1-2 hours before
50
Vancomycin
Inhibits cell wall synthesis Bactericidal Different protein target than B-lactams IV admin - Treatment of choice for MRSA and other Gram-positive infections Oral admn for pseudomembranous colitis (C diff)
51
Vancomycin - Adverse Effects
Infusion rate related - infuse over 1 hours - Red man or red neck syndrome possible Fever, chills, and phlebitis (inflamed vein at injection) Ototoxicity Nephrotoxicity Therapeutic drug monitoring (serum concentration)

Pharmacology (29 decks)

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