Antimicrobials Flashcards

1
Q

What is an Antimicrobial?

A
  • Drugs/chemicals that kill micro-organisms or inhibit their growth
  • can be used to treat microbial infections
  • most selective of all pharm agents because of selective toxicity
    Most overused and misused therapeutic agents - leads to antimicrobial resistance
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2
Q

What are the different types of antimicrobials?

A

Antibiotics = against bacteria
Antifungals = against fungi
Antivirals = against viruses

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3
Q

What is selective toxicity?

A

Target microbial cells over mammalian cells (thru structural and metabolic toxicity) and cause greater harm to the micro-organisms than the host.

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4
Q

What are the antimicrobial actions?

A

Microbicidal KILL - decrease (immunocompromised preferred)
Microbiostatic PREVENT - remain constant

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5
Q

What are the antimicrobial spectrums of activity?

A

Narrow-spectrum - kills/inhibits narrow range (ex. Penicillin gram +)

Broad-spectrum - kills/inhibits a wide range (ex. Tetracyclines gram +/-, anaerobes, and aerobes)

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6
Q

What are examples of inappropriate antimicrobial use?

A

-antibiotics for viral infections
-inadequate dose/duration
-Rx w/out culture or data
-overuse of unnecessary broad spectrum

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7
Q

What should you consider in optimal antimicrobial therapy?

A

Efficacy, safety, decreasing microbial resistance

  • Organism ID (culture, gram staining, morphology) and susceptibility testing
  • Use of antimicrobial with the narrowest spectrum of activity, at adequate dose and appropriate duration
  • Use of agents in combo if needed (synergistic effect)
  • Consideration of client factors (immune status, age, pregnancy, renal function)
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8
Q

What are antibiotics?

A

Treat infections caused by bacteria that aren’t part of normal flora

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9
Q

What’s the diff b/w mammalian and bacterial cells?

A
  • Bacteria has cell wall
  • Essential metabolic pathways (i.e. synthesizes folic acid)
  • Different macromolecule anabolism (protein synthesis and nucleic acid synthesis) [no nucleus - non-eukaryotic]

(Antibiotics target these!)

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10
Q

What are the mechanisms of action of antibiotics?

A

Inhibition of:

1) Cell wall synthesis
2) Protein synthesis
3) Nucleic acid metabolism
Essential metabolites (folic acid)

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11
Q

Describe the mechanism of cell wall inhibition?

A

Made of peptidoglycan and prevents cell from bursting. If cell wall is fucked with - osmotic pressure = cell lysis.

Interferes with cross linking of peptidoglycan
· Inhibited by glycopeptides (transglycosoylation and transpeptidation)
Inhibited by Beta-lactams (transpeptidation catalysed by penicillin binding proteins)

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12
Q

Describe the mechanism of Beta Lactams

A

Cell wall inhibition - Covalently binds to the active site of penicillin-binding proteins (penicillins and cephalosporins)
BACTERIACIDAL

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13
Q

Describe the mechanism of glycopeptides?

A

Binds to the d-alanyl-D-alinine resides to prevent cell wall synthesis. (Vancomycin)
BACTERIACIDAL

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14
Q

What is gram +?

A

Thick peptidoglycan layer

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15
Q

What is gram -?

A

Thin peptidoglycan layer. Outer layer contains phospholipids and lipopolysaccharides

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16
Q

What’s the deal with penicillin?

A

Cell wall inhibition VIA Beta Lactam
Primarily effective against Gram +
- R side chain determines the class of penicillin (determines: spectrum, susceptibility to acid (route), susceptibility to inactivation (resistance to resistance lol)
- Ends with -cillin
Beta-lactamase enzymes (penicillinase) destroy antibacterial activity causes resistance to penicillin.
Safe in pregnancy, unless anaphylaxis, allergy

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17
Q

What are the classes of penicillin?

A

Class 1: Narrow spectrum, Class 2 : Penicillinase Resistant, Class 3: Extended spectrum

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18
Q

What’s the deal with Narrow Spectrum penicillin?

A

Injected
Active against non-penicilinase producing Gram + an some Gram -
Penicillin G p used in group B strep, effective against streptococci

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19
Q

What’s the deal with Penicillinase Resistant penicillin?

A

Cell wall inhibition

Not as effective against other infections as pen G or pen V
cloxacillin, dicloxacillin (ORALLY ADMIN restricted for use against staphylococci) - MASTITIS

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20
Q

What’s the deal with extended spectrum penicillin?

A

NOT penicillinase-resistant
**Ampicillin (usually parenteral - non GI); **amoxicillin (oral)
Combined with clavulanic acid (irreversible inhibitor of penicillinase)
Active against gram+, but major use gram -
Many strains resistant due to overuse

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21
Q

What’s the deal with cephalosporins?

A

Cef-
Cell wall inhibition VIA beta lactam
Structural relatives of pen (so if someone anaphylactic against pen shouldn’t be prescribed ceph 5%)
Two R groups so more can be made
Classified by 5 generations Narrow —-> Broad *effectiveness against Beta lactamases and against Gram (-)
**Gen 1 = **Cefazolin, **Cephalexin (gram +, ok gram -)
** Gen 3 = ** Cefixime (gram -)

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22
Q

Describe the mechanism of glycopeptides?

A

Cell wall inhibition.
Bind to D-alanyl-D-alanine residues (binds to amino acid)
Bactericidal
(Vancomycin)

23
Q

What’s the deal with Vancomycin?

A

Cell wall inhibition via glycopeptides
Injected
Gram +
Last line treatment of prophylaxis of Group B strep and serious life threating infections not responsive to other antibiotics
Side effects: turn red

24
Q

Describe the mechanism of protein synthesis inhibition?

A

Fuck with 30s or 50 s subunits (not in mammalian cells), messing with ribosomal activity

(Aminoglycosides, Tetracyclines = 30 s) ( Macrolides, Clindamycin = 50 s)

25
Q

What’s the deal with Aminoglycosides?

A

Protein synthesis inhibitor
Injected
Irreversibly binds to 30s - misreads mRNA codes
Aerobic gram -
Bactericidal

26
Q

What are the adverse effects of aminoglycoside?

A

Ototoxicity (damage to inner ear) - irreversible partial or total hearing loss
Avoid in pregnancy

And damage to kidneys

27
Q

What’s the deal with Tetracyclines?

A

Protein synthesis inhibitor
Reversibly bind to 30s - prevents binding of rTNA to mRNA
Bacteriostatic
Broad spectrum - many gram + and - strains, but many have developed resistance
Reserve for specific indications: Lyme, chlamydia

28
Q

What are the adverse effects of Tetracyclines?

A

GI discomfort
Effects on calcified tissue - bone deposits/teeth
**Avoid in pregnancy, lactating ppl, and children under 8 yo - permanent teeth discolouration an temporary inhibition bone growth

29
Q

What’ the deal with macrolides?

A

Protein synthesis inhibitor
Reversibly bind to 50s subunit - inhibit translocation
Bacteriostatic
Many Gram + and some Gram -
**ERYTHROMYCIN
Can be used in pregnancy - alternative to penicillin, safe w limited toxicity
**AVOID ERYTHROMYCIN ESTOLATE in preg - hepatotoxicity

Adverse effect: GI discomfort

30
Q

What’s the deal with Clindamycin**?

A

Protein synthesis inhibitor
Reversibly binds to 50s subunit - inhibits translocation
Bacteriostatic
Gram+ and some Anerobic gram - strains
Alternative to pen
Bacterial Vaginosis

Adverse effect - inflammation of colon

31
Q

Describe the mechanism of Nucleic Acid Metabolism Inhibition?

A

Target enzymes of bacterial DNA replication - DNA gyrase (topoisomerase II) and topoisomerase IV - not in mammalian cells
IV - facilitates DNA replication
II and IV - reduce tension of DNA coil

(Fluoroquinolones, Metronidazole, Nitrofurantoin)

32
Q

What’s the deal with Fluoroquinolones?

A

Ciprofloxacin most widely used
Usually not first defence
Many gram - and some gram +
UTIS, respiratory and intestinal tract, lungs, skin, bones
Interfere with DNA gyrase (topoisomerase II) and topoisomerase IV
Bactericidal
Well tolerated

33
Q

Adverse effects of Fluoroquinolones?

A

GI discomfort
Tendon rupture
**Arthropathy - avoid in 1st trimester and use caution under 18 yo

34
Q

What’s the deal with **Metronidazole?

A

Anaerobic bacteria
Bactericidal
Converted to reactive metabolite by proteins in anaerobic bacteria
Good for treatment of BV

35
Q

What’s the deal with **Nitrofurantoin?

A

Converted to a reactive metabolite causing damage to DNA
Good for UTIs
Can cause hemolytic anemia in neonates
Avoid in late pregnancy, neonates, and lactating ppl

36
Q

Describe the mechanism of Essential Metabolite Inhibition

A

Fuck w/ synthesis of folic acid
Bacteria must make folic acid (mammalian cells obtain from diet)
Bacteriostatic
Inhibits enzyme needed to make folic acid
(Sulfonamides and Trimethoprim)
Broad spectrum Gram + / -, resistance
S and T usually administer together - co-trimoxazole
UTI an resp infections

37
Q

What’s the deal with Sulfonamides?

A

Essential metabolite inhibition VIA enzyme inhibition
Enzyme = dihydropteroate synthase (DHPS) - 1st step of folic acid
Adverse effects -
Hypersensitivity
Kernicterus in neonates - bilirubin induced brain damage
Avoid late preg, neonates, lactating ppl

38
Q

What’s the deal with Trimethoprim?

A

Essential metabolite inhibition VIA enzyme inhibition
Enzyme = dihydrofolate reductase - 2nd step folic acid
50,000 x more active against the bacterial version
Adverse effects-
Megaloblastic anemia
Avoid first trimester of pregnancy = increase in neural tube defects

39
Q

Common indications for antibiotics in midwifery?

A

UTIs, Intrapartum prophylaxis group B streptococcus, Mastitis, Prophylaxis of ophthalmia neonatorum, BV

40
Q

UTIs treatments?

A

Amoxicillin (most common), cephalexin, Nitrofurantoin (avoid late preg), Cefizime (once a day)

41
Q

Group B Strep Proph?

A

Order of Preference:

Penicillin G
Ampicillin
Cefazolin
Clindamycin
Vancomycin

42
Q

Mastitis treatment?

A

Cephalexin
Cloxacillin or Dicloxacillin
Co-amoxiclav
Clindamycin

43
Q

Ophthalmia Neonatorum proph?

A

Erythromycin ointment 1 hour after birth

44
Q

BV treatment?

A

Metronidazole
Clindamycin

45
Q

What’s the difference b/w mammalian and fungal cells?

A

Fungal - cell membrane (ergosterol instead of CHO) and Cell wall (made from chitin and beta-glucan)

46
Q

Method of Action for Cell membrane disruption in antifugals?

A

Interferes w/ ergosterol or ergosterol synthesis

(Polyenes and Azoles)

47
Q

What’s the deal with Polyenes?

A

Includes **nystatin (topical, systemically toxic)
Treats candida in mouth (thrush), esophagus, skin, vagina
Disrupt cell membrane of fungal cells

48
Q

What’s the deal with Azoles?

A

Disrupt cell membrane of fungal cells (fungal enzyme 14 - alpha - demethylase (P450) )
Most widely used antifungal
2 Groups (1) Imidazoles (**Miconazole, **clotrimazole) (2) Triazoles
Topical or systemically
Treat candida infections, athletes foot, ringworm, systemic fungal infections

AVOID SYSTEMIC AZOLES IN PREGNANCY

49
Q

What’s Candidiasis?

A

Aka Yeast infection - yeasts from genus Candida

50
Q

Treatment for Candidiasis?

A

(TOPICAL)
Clotrimazole
Miconazole

51
Q

Treatment for thrush?

A

Nystatin

52
Q

Nipple infection treatment

A

Miconazole or Clotrimazole
All purpose nipple ointment (antifungal and anti-inflammatory)
Nystastin cream

53
Q

Treatment of Herpes

A

HSV -1 cold sores
HSV 2 - genital herpes

Suppressive proph with history of recurrent genital herpes 36 weeks till delivery

Acyclovir
Valaciclovir (less doses)

54
Q

Drug risk classification?

A

A and B considered safe in preg

X - never use!