Antibiotics II Flashcards

1
Q

Antifolate drugs are bacteriostatic but become bacteriocidal when?

A

Sulfonamethoxazole (SMX) + Trimethoprim (TMP)

combined = (Bactrim) = Synergism

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2
Q

What does Sulfonamethoxazole inhibit?

A
  • Inhibits dihydropteroate synthase (DS)
  • Mimics PABA (Para-aminobenzoic acid)
    Folate Competitive inhibitor
  • Prevents Dihydrofolic Acid formation
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3
Q

What does Trimethoprim inhibit?

A
  • Inhibits Dihydrofolate reductase (DHFR)

- Preventing Tetahydrfolic Acid formation

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4
Q

Bactrim uses synergistic effects which means?

A
  • In combination

Additive effects = Greater effect

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5
Q

True or False

Trimethoprim (TMP) is a folate analog that binds to the bacterial DHFR 1000x more effectively than human DHFR ?

A
  • True
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6
Q

What does Sulfamethoxazole mimic ?

A
  • PABA (Para AminoBenzoic Acid)
  • Absolute selective toxic
    (Only in bacteria)
  • Humans depend on dietary folate
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7
Q

What does Trimethoprim mimic?

A
  • Dihydrofolate reductase (DHFR)

- Relative selective toxic
Both in Humans and Bacteria

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8
Q

What does SMX + TMP treat?

A
  • Topical MRSA

- AntiMycoplasma activity

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9
Q

Trimethoprim can block sodium channels in the kidney collecting tube leading to hyperkalemia and thus should be avoided in patients taking?

A
  • Potassium-elevating agents
  • ACE inhibitors
  • Angiotensin receptor blockers
  • Spironolactone
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10
Q

What are the three major side effects of bactrim?

A
  • Hemolysis in G6PD deficiency
  • Hypersensitivity to Sulfa (Do not prescribe to sulfa allergic pt’s)
  • Stevens Johnson Syndrome Delayed IV reaction (Must Monitor)
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11
Q

Stevens Johnson Syndrome Delayed IV reaction is caused by what medications?

A
  • Sulfa drugs
  • Penicillins
  • Mouth and Mucus membranes always affected
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12
Q

What does Ciprofloxain do ? MOA

A
  • DNA gyrase inhibitor
  • Blocks transcription
  • Blocks DNA replication
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13
Q

DNA gyrase / Fluoroquinoloes are synthetic analogs of what?

A
  • Nalidixic Acid
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14
Q

Ciprofloxain is NOT used first line, why?

A
  • Because of all the adverse effects
  • GI irritation
  • Photosensitivity
  • Risk of tendon rupture (x100)
  • Aortic aneurysm
  • Teratogen (Not in Prego)
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15
Q

T of F

Divalent/trivalent cations and acids impair Ciprofloxacin absorption?

A
  • True
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16
Q

What does Ciprofloxacin treat?

A
  • DOC for Anthrax
  • Chlamydia
  • Some antifungal activity
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17
Q

T of F

Ciprofloxacin has a post antibiotic effect?

A
  • True

- Kills bacteria after treatment stops

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18
Q

Nitrofurantoin (Macrobid) treats what type of infection?

A
  • Lower urinary tract infections
  • Bladder and Urethra ONLY
  • Urinary tract antiseptic
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19
Q

Nitrofurantoin (Macrobid) is safe in pregnancy?

T or F

A
  • True
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20
Q

Nitrofurantoin (Macrobid) is contraindicated in pt’s with?

A
  • Renal failure

- Drug can’t be cleared and builds up in body

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21
Q

What are the 5 questions to ask before prescribing an antibiotic?

A

1) Patient (Host)
2) Syndrome
3) Pathogen
4) Drugs
5) Cost

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22
Q

Two major mycobacterial infections in humans? that are difficult to treat?

A
  • Tuberculosis

- Leprosy

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23
Q

What are the two strategies in fight mycobacterial infections?

A
  • Multi drug therapy

- Long treatment course (6 to 12 months)

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24
Q

Two factors that my Mycobacteria hard to treat?

A
  • Intrinsic Factors

- Environmental factors

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25
Q

What are the Mycobacteria environmental factors?

A
  • Goes Dormant (Non-dividing)
  • Cell Division (Long dividing time 1200mins)
  • Physical barriers (Granuloma formation protects microb)
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26
Q

Intrinsic factors of Mycobacteria?

A
  • Mycolic Acid (Sugar / Waxy fatty acid coating)
  • Peptidoglycan (Unusual L - D linkage)
    Insensitive to Vancomycin
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27
Q

Active TB disease treatment?

A
  • Get RIPE
  • Rifampin
  • Isoniazid
  • Pyrazinamide
  • Ethambutol

For 2 months

Then

  • Rifampin
  • Isoniazid

For 6 months

28
Q

Latent TB Disease treatment?

A
  • Isoniazid (9 months)
29
Q

T or F

Latent TB disease is always treated?

A
  • False

Only Tx when

  • High risk of active TB
  • HIV
  • Immuno Comp
  • CXR with TB changes
  • IV drug users
  • High risk settings
    (Correction facilities & Nursing homes)
30
Q

What does multi drug therapy provide in mycobacteria diseases?

A
  • Suppresses development of drug resistance

- Attacks fast and Attacks hard

31
Q

MOA of Rifampin?

A
  • Inhibitor of bacterial RNA polymerase from binding DNA
  • Jams up active site
  • Prevents elongation of RNA
32
Q

T or F

Rifampin can penetrate the CNS but only when the Meninges are inflamed?

A
  • True
33
Q

T or F

Pt with liver disease can take Rifampin?

A
  • False

- Extensive enterohepatic recirculation = hepatotoxicity

34
Q

T or F

Bright orange bodily fluids is a good sign that Rifampin is working in a pt?

A
  • True

- Orange Tears, Sweat, Urine

35
Q

What does Extensive enterohepatic recirculation mean?

A
  • Drug secreted inot duodenum via the bile after liver metabolism
  • Reabsorbed downstream in the ilium
  • Take back to the liver
  • Taken back to the liver many times
  • Prolonged lifetime of the drug in the body
36
Q

Isoniazid (INH) MOA ?

A
  • Vitamin B6 (pyridoxine) analog
  • Prevents the synthesis of Mycolic acid
  • By Inhibiting InhA reductase enzyme
37
Q

Isoniazid inhibits what in the mycobacteria?

A
  • Inhibits the growing fatty acid chain necessary for the completion of Mycolic acid Syn
38
Q

What dose Isoniazid (INH) + NAD (Suicide Complex) prevent in Mycobactria?

A
  • Prevents key reduction step necessary for Mycolic acid syn
  • Inhibits INhA that prevents the saturation (Reduction) of Acyl chains
  • No Acyl chains = No Mycolic acid syn
39
Q

What are the two adverse side effects of INH (Isoniazid) ?

A
  • INH Induced hepatitis

- INH Induced Neuropathy

40
Q

What happens when a pt develops INH Induced hepatitis ?

A
  • Stop taking Isoniazid ASAP
41
Q

What happens when a pt develops INH Induced Neuropathy?

A
  • Treat them with B6 Pyridoxine to reverse the symptoms
42
Q

B6 Deficiency classically presents with?

A
  • Seborrhoeic
    Dermatitis
  • Craddle cap in Newborns
  • Sore tongue
  • Neurological effects
  • Sideroblastic Anemia (Heme syn impaired)
43
Q

What is Pyridoxine ?

A
  • Dietary form of B6
  • Serves as a cofactor for enzyme reactions
  • AA metabolism
  • Glucose metabolism
  • Lipid metabolism
44
Q

What medication is an analog of Vitamin B3 ?

A
  • Pyrazinamide (PZA)
45
Q

MOA of Pyrazinamide (PZA)?

A
  • Enters mycobacteria via passive diffusion
  • activated by pncA enzyme
  • Accumulates in non-dividing cells and ultimately damages cell membranes to cause death
46
Q

How does PZA enter the Mycobacteria?

A
  • Via passive diffusion
47
Q

What converts Pyrazinamide (PZA)

prodrug into its active metabolite Pyrazinoic Acid (POA) ?

A
  • Mycobacteria Pyrazinamdase (pncA)
48
Q

T or F

The Mycobacteria pumps POA out of the intracellular into the extracellular but then POA gets protonated and becomes uncharged and diffuses back into the cell.

A
  • True
  • Pumping only occurs in active TB
  • Drug accumulates when the TB metabolism shuts down
  • Driving Toxic acidification of the cytosol
49
Q

What is the major resistance of Pyrazinamide (PZA) ?

A
  • Mutations in the pncA Enzyme
50
Q

T or F

PZA is highly effective against intracellular pathogens?

A
  • True
  • Sterilizing agent
  • Diffuses through cell membranes @ Physiological ph
  • Taken up by Macrophages
51
Q

T or F

PZA only becomes POA - Protonated in the Low pH of the Lysosome but NOT neutral pH?

A
  • True

- Prodrug into active Drug metabolite

52
Q

Major side effect of Pyrazinamide (PZA) ?

A
  • Hyperuricemia

- Gouty arthritis due to decreased renal excretion or urate

53
Q

What medication blocks mycobacteria cell wall syn by Inhibiting Arabinosyltransferases?

A
  • Ethambutol (Myambutol)
54
Q

What does arabinosyltransferases do in the mycobactria?

A
  • Catalyzes the attachment of Arabinose to Galactose to create Arabinogalactan
55
Q

Why is Arabinogalactan important in mycobacteria?

A
  • Needed for the hub attachment of Mycolic Acids
56
Q

What layer does Ethambutol act on?

A
  • Acts on the Arabinogalactan layer

- Acts on the layer upstream from the Isoniazid target, above the peptidoglycan layer

57
Q

How is Ethambutol excreted?

A
  • Renal 50%
  • Liver 30%
  • Feces 20%
58
Q

Adverse effects of Ethambutol?

A
  • Retrobulbar (optic) neuritis
  • Damages optic nerve (Myelin Sheath)
  • Causes red and green color blindness
59
Q

Contraindication of Ethambutol ?

A
  • Kids too young for an eye test
60
Q

Only Aminoglycoside approved for treatment of TB?

A
  • Streptomycin
61
Q

MOA of Streptomycin?

A
  • Multi modal activity all through ribosome 30S
    1) Blocks ribosome initiation complex
    2) Promotes translation errors
    3) Blocks ribosomal translocation
62
Q

When is Ethambutol used to treat TB?

A
  • When Antimycobacterial agents are resistant
  • Resistance mutations of Ribisomal subunits rpsl or rrs
  • Or when injectable drug is needed
63
Q

True of False

Ethambutol is very pain when given IM?

A
  • True
64
Q

What are the two major toxicity’s associated with Ethambutol?

A
  • Ototoxicity Hearing lose
  • Nephrotoxicity
    Kidney damage
65
Q

T or F

Ethambutol is contraindicated in pregnancy?

A
  • True

- Risk of deafness in infant

66
Q

What does Isoniazid (INH) treat?

A
  • Mycobacterial infections

- Nosocomial CAP (Pneumonia)