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Pharm test #3 > Miscellaneous Antibiotics lecture > Flashcards

Miscellaneous Antibiotics lecture Flashcards

1
Q

Tetracyclines first and second generation

A

First Generation
Tetracycline

Second Generation
Doxycycline, Minocycline

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2
Q

Glycylcycline

A

Tigecycline

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3
Q

Tetracyclines/Glycylcyclines Mechanism of action

A

Reversibly binds to the 30S ribosomal subunit
Inhibit the binding of aminoacyl transfer-RNA to the acceptor (A) site on the mRNA-ribosomal complex, which prevents addition of amino acid residues on elongating peptide chain

Bacteriostatic
Bactericidal when present at high concentrations against very susceptible organisms

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4
Q

Tetracyclines/Glycylcyclines mechanism of resistance

A

• Efflux Pumps
decreased accumulation of tetracycline within bacteria
• Ribosomal protection proteins
Cytoplasmic proteins that protects ribosomes from 1st and 2nd generation tetracyclines
• Enzymatic inactivation

Cross-resistance observed between tetracyclines, except for minocycline

Tigecycline resistant to these mechanisms

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5
Q

which drug is not susceptable to the resistance mechanisms against tetracyclines/glycocyclins

A

Tigecycline

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6
Q

tigecyline spectrum of activity

A

very broad, gram + and gram - aerobes plus some anaerobes

not active against: Proteus spp or Pseudomonas aeruginosa

not for bacteremias or UTIs bc you cannot maintain good levels in the blood/urine

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7
Q

which Tetracyclines/Glycylcyclines
 is available po and IV

A

doxycycline is available PO and IV

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8
Q

What affects Tetracyclines/Glycylcyclines absorption?

A

Absorbed best on an empty stomach

Absorption impaired by di- and trivalent cations (dietary supplements, Ca2+)

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9
Q

Tetracyclines/Glycylcyclines
 distribution

A

Widely distributed with good penetration into synovial fluid, prostate, seminal fluid (prevents high concentrations in the blood)
Minimal CSF penetration
poor distribution to the bladder- no UTI use

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10
Q

Demeclocycline/tetracycline
 elimination

A

excreted unchanged in the urine
**dosage adjustment required in renal insufficiency

Tetracycline half-life = 6 to 12 hours; demeclocycline half-life = 16 hours

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11
Q

Doxycycline, minocycline elimination

A

metabolized (excreted mainly by non-renal routes)

Half-lives = 16-18 hours (doxy, mino) but dosed every 12 hrs

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12
Q

tigecycline elimination

A

biliary - does not need adjustment for renal insufficiency but does for liver disease

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13
Q

The Clinical Uses of Tetracyclines/Glycylcyclines

A

Respiratory infections
Community-acquired pneumonia (doxy)
Acute exacerbation of chronic bronchitis
Pertussis

STDs –Chlamydia, Syphilis, gonorrhea

Treatment or prophylaxis of malaria

The Others:
**Rocky Mountain Spotted Fever, Q Fever, Lyme
Brucellosis, Bartonellosis, plague, Tularemia, chancroid, anthrax, H. pylori

Polymicrobial infections (Tigecycline)
Complicated skin and soft tissue infections
Intraabdominal infections

Acne

SIADH (demeclocycline)

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14
Q

Pertussis treatment with tetracyclines/glycylcyclines

A

decreased colonization and therefore spread but does not significantly reduce symptoms

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15
Q

Tetracycline/Tigecycline 
Adverse Effects

A

Gastrointestinal
Nausea, vomiting – high incidence with tigecycline (29%)
Diarrhea, pseudomembranous colitis

Hypersensitivity
Rash, pruritus, urticaria, angioedema, anaphylaxis

**Photosensitivity
Exaggerated sunburn (hands and face)

Renal
Fanconi-like syndrome with outdated tetracycline
Reversible dose-related diabetes insipidus (demeclocycline)

Other
Hepatic enzyme elevation

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16
Q

why is tigecycline not well tolerated

A

many pts have severe nausea and vomiting

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17
Q

why is it important to check tetracyclines expiration dates

A

expired tetracycline causes Fanconi-like syndrome (renal disease)

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18
Q

can you give Tetracycline/Tigecycline
 to a pregnant woman?

A

NO - Pregnancy Category D

Discoloration of permanent teeth and decreased bone growth in children

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19
Q

Sulfonamides mechanism of action

A

** Inhibits dihydropteroate synthetase –
Inhibits incorporation of p-aminobenzoic acid (PABA) into tetrahydropteroic acid

Bacteriostatic

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20
Q

long acting sulfonamides

A

Sulfadoxine

Combined with pyrimethamine (Fansidar)

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21
Q

Trimethoprim mechanism of action

A

Bacteriostatic

Inhibits dihydrofolate reductase
Interferes with conversion of dihydrofolate to tetrahydrofolate

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22
Q

Trimethoprim-Sulfamethoxazole 
(TMP-SMX, Bactrim®) advantages

A

Bactericidal in combination with synergistic activity

Broader spectrum of activity

Decreased emergence of resistance

work at 2 different placed on the same pathway to prevent the production purines

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23
Q

Sulfonamide resistance

A

• Resistance widespread
(Streptococci, Staphylococci, Enterobacteriacae, Neisseria sp., Pseudomonas sp., Shigella, Salmonella)
• PABA overproduction
• Structural change of Dihydropteroate synthetase
• Plasmid mediated production of drug resistant DHPS or decreased bacterial cell wall permeability to sulfonamides

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24
Q

Trimethoprim resistance

A

Chromosomal or plasmid mediated

Plasmid-mediated production of dihydrofolate reductase resistant to trimethoprim

Changes in cell permeability

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25
Q

TMP-SMX
 Spectrum of Activity

A

good gram + including S. aureus and good gram - including Stenotrophomonas maltophilia

No ANAEROBE activity

26
Q

TMP-SMX
 absorption

A

Absorption – available IV and PO
Rapidly and completely absorbed (F > 90%)
Peaks are higher and more predictable with IV administration

use oral unless a pt cannot take it

27
Q

TMP-SMX distribution

A

Good distribution – lungs, urine, prostate, etc
Penetrates the CSF – TMP (30-50%), SMX (20%)
SMX is 70% protein bound

28
Q

TMP-SMX
 elimination

A

Both are eliminated by the liver and kidney

require dose adjustment if creatine clearence is less than 30ml/min - and follow renal function

29
Q

TMP-SMX 
Clinical Uses

A

** Acute, chronic, or recurrent infections of the urinary tract

** Acute or chronic bacterial prostatitis

** Skin infections due to CA-MRSA

Bacterial Sinusitis

Nocardia

30
Q

the treatment of choice for nocardia is

A

TMP-SMX

31
Q

some common uses for TMP-SMX

A

Pneumocystis carinii pneumonia

Stenotrophomonas

Toxoplasmosis

Listeria monocytogenes

Nocardia

32
Q

TMP-SMX 
Adverse Effects - hematologic and GI

A

Gastrointestinal
• Nausea, vomiting, diarrhea, glossitis
• Jaundice
• Hepatic necrosis

Hematologic
• **Leukopenia, **thrombocytopenia, eosinophilia
• Acute hemolytic anemia, aplastic anemia, agranulocytosis
• Megaloblastic anemia (impaired folate usage with prolonged administration)

33
Q

TMX-SMX hypersensivity

A

*Rash, urticaria, epidermal necrolysis, Stevens-Johnson, drug fever

34
Q

TMP-SMX 
Adverse Effects - CNS, Renal and other

A

• CNS
Headache, aseptic meningitis, seizures

• Renal toxicity
Tubular necrosis
Interstitial nephritis

  • Drug-induced lupus
  • Serum sickness-like syndrome
  • Other - crystalluria**
35
Q

Chloramphenicol
 - general information

A 
Isolated from mulched field and compost
Streptomyces venezuelae
Introduced into use in U.S. in 1949
Due to significant adverse events, this agent is not used in the U.S.
Use is common in the developing world
36
Q

Chlorampenicol
 Mechanism of action

A

Binds to 50s subunit of 70s ribosome
Prevents peptide bond formation

Static activity except for:
Haemophilus influenza
Streptococcus pneumoniae
Neisseria meningitidis

37
Q

Chloramphenicol 
Resistance mechanism(s)

A
  1. Reduced permeability or uptake
  2. Ribosomal mutation
  3. Acetyltransferase inactivation
    Responsible for widespread outbreaks of typhoid fever and Shigella dysentery in Central and South America, Vietnam, India
38
Q

Chloramphenicol absorption

A

Well absorbed by the GI tract

IV administration – peak level approximately 70% of peak following oral administration

39
Q

Chloramphenicol distribution

A

Distribution
Lipid soluble
Not highly protein bound (25-50%)
CSF levels 30-50% of serum levels

40
Q

Chloramphenicol
 elimination

A

Elimination
Metabolized by the liver
Enterohepatic circulation
Excreted by the kidneys

Decrease dose in liver failure
Does adjustment not required in renal failure

41
Q

Chloramphenicol 
Antimcrobial spectrum

A

Gram Positives
Unreliable against Staph aureus and not active against enterococci

Gram Negatives
Not active against P. aeruginosa

Anaerobes (Gram negative and Gram positive)

42
Q

specific types of bacteria chloramphenicol is used for in other countries

A

Rickettsiae sp.
Spirochetes
Chlamydia
Mycoplasma

43
Q

clinical uses of chloramphenicol

A

Pneumonia
Bacterial meningitis
Typhoid fever

Rocky mountain spotted fever

44
Q

Chloramphenicol
 adverse effects

A

Hematologic
Reversible bone marrow suppression
Aplastic anemia (1 in 24,500 – 40,800)

Gray baby syndrome (neonates)
Optic neuritis
Hypersensitivity reaction
Anaphylaxis
GI intolerance (vomiting, diarrhea)
Stomatitis
porphyria
45
Q

grey baby syndrome

A

due to use of chloramphenicol during pregnancy or given to a baby

Abdominal distention
Vomiting
Flaccidity
Cyanosis
Circulatory collapse/Death
46
Q

Urinary Tract Agents

A

Nitrofurantoin and Methenamine

47
Q

Nitrofurantoin mechanism of action

A

Poorly understood
Binds to ribosomal proteins
Inhibits translation
Inhibits bacterial respiration and pyruvate metabolism

48
Q

Methenamine mechanism of action

A

Converted in acid pH to ammonia and formaldehyde

Formaldehyde – non-specific denaturant of proteins and nucleic acids

not really an antibiotic more of a denaturant

49
Q

Nitrofurantoin mechanisms of resistnace

A

Poorly understood
Development of resistance while on treatment rare
E. coli – Chromosomal or plasmid-mediated production of nitrofuran reductase

50
Q

methenamine mechanisms of resistance

A

Alkaline urine

No bacterial resistance to formaldehyde described

51
Q

both nitrofurantoin and methenamine are given

A

orally

52
Q

nitrofurantoin absorption

A

40-50% absorption following oral administration
Occurs in small intestine
Enhanced with food

53
Q

Methenamine absorption

A

Rapid absorption after oral administration

May be partially degraded by gastric acid

54
Q

Nitrofurantoin distribution

A

Large urine concentrations
Low/undetectable serum concentration
Therapeutic concentrations not attained in prostate

(bc it doesn’t accumulate anywhere else it is only useful for UTIs)

55
Q

methenamine distribution

A

Rapid absorption following oral dose

Broad distribution in tissue

56
Q

Nitrofurantoin elimination

A 
Eliminated in the urine
Glomerular filtration
Tubular secretion
Tubular reabsorption
Biliary excretion: minor
Serum half life
57
Q

methenamine elimination

A

Renal excretion

Half-life 3-4 hours with normal renal function

58
Q

clinical uses of Nitrofurantoin

A

Acute, uncomplicated UTIs (commonly used for E. coli among many others)

Do not use for:
Pyelonephritis
Complicated UTi

59
Q

clinical uses of Methenamine

A

Suppression or prophylaxis against recurrent UTIs

Do not use for:
Established infections
Prophylaxis against catheter-associated UTI

60
Q

Nitrofurantoin
 Adverse reactions

A

• GI intolerance
• Rashes
• Acute pulmonary symptoms – reversible hypersensitivity phenomenon
- Weeks to months after drug exposure
- Rapid onset of fever, cough, dyspnea, myalgia
- Peripheral blood eosinophilia and lower lobe pulmonary infiltrates
• Subacute and chronic pulmonary reaction
- Gradual onset of progressive, non-productive cough and dyspnea
- Interstitial infiltrate on CXR
- Reversible but may lead to pulmonary fibrosis
- May have + antinuclear antibodies
- Bronchiolitis obliterans and organizing pneumonia reported

61
Q

Methenamine 
Adverse reactions

A 
Generally well-tolerated
GI (nausea, vomiting)
Rash
Pruritis
Bladder irritation
Hemorrhagic cystitis (higher doses)
Peripheral sensory neuropathy
Hepatitis
Hemolytic anemia
Leukopenia
Aplastic anemia
Megaloblastic anemia (folic acid responsive)
Eosinophilia

Pharm test #3 (17 decks)

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