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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
TMP-SMX
 Spectrum of Activity
good gram + including S. aureus and good gram - including Stenotrophomonas maltophilia No ANAEROBE activity
26
TMP-SMX
 absorption
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
TMP-SMX distribution
Good distribution – lungs, urine, prostate, etc Penetrates the CSF – TMP (30-50%), SMX (20%) SMX is 70% protein bound
28
TMP-SMX
 elimination
Both are eliminated by the liver and kidney require dose adjustment if creatine clearence is less than 30ml/min - and follow renal function
29
TMP-SMX 
Clinical Uses
** Acute, chronic, or recurrent infections of the urinary tract ** Acute or chronic bacterial prostatitis ** Skin infections due to CA-MRSA Bacterial Sinusitis Nocardia
30
the treatment of choice for nocardia is
TMP-SMX
31
some common uses for TMP-SMX
Pneumocystis carinii pneumonia Stenotrophomonas Toxoplasmosis Listeria monocytogenes Nocardia
32
TMP-SMX 
Adverse Effects - hematologic and GI
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
TMX-SMX hypersensivity
*Rash, urticaria, epidermal necrolysis, Stevens-Johnson, drug fever
34
TMP-SMX 
Adverse Effects - CNS, Renal and other
• CNS Headache, aseptic meningitis, seizures • Renal toxicity Tubular necrosis Interstitial nephritis * Drug-induced lupus * Serum sickness-like syndrome * Other - crystalluria**
35
Chloramphenicol
 - general information
``` 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
Chlorampenicol
 Mechanism of action
Binds to 50s subunit of 70s ribosome Prevents peptide bond formation Static activity except for: Haemophilus influenza Streptococcus pneumoniae Neisseria meningitidis
37
Chloramphenicol 
Resistance mechanism(s)
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
Chloramphenicol absorption
Well absorbed by the GI tract | IV administration – peak level approximately 70% of peak following oral administration
39
Chloramphenicol distribution
Distribution Lipid soluble Not highly protein bound (25-50%) CSF levels 30-50% of serum levels
40
Chloramphenicol
 elimination
Elimination Metabolized by the liver Enterohepatic circulation Excreted by the kidneys Decrease dose in liver failure Does adjustment not required in renal failure
41
Chloramphenicol 
Antimcrobial spectrum
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
specific types of bacteria chloramphenicol is used for in other countries
Rickettsiae sp. Spirochetes Chlamydia Mycoplasma
43
clinical uses of chloramphenicol
Pneumonia Bacterial meningitis Typhoid fever Rocky mountain spotted fever
44
Chloramphenicol
 adverse effects
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
grey baby syndrome
due to use of chloramphenicol during pregnancy or given to a baby ``` Abdominal distention Vomiting Flaccidity Cyanosis Circulatory collapse/Death ```
46
Urinary Tract Agents
Nitrofurantoin and Methenamine
47
Nitrofurantoin mechanism of action
Poorly understood Binds to ribosomal proteins Inhibits translation Inhibits bacterial respiration and pyruvate metabolism
48
Methenamine mechanism of action
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
Nitrofurantoin mechanisms of resistnace
Poorly understood Development of resistance while on treatment rare E. coli – Chromosomal or plasmid-mediated production of nitrofuran reductase
50
methenamine mechanisms of resistance
Alkaline urine | No bacterial resistance to formaldehyde described
51
both nitrofurantoin and methenamine are given
orally
52
nitrofurantoin absorption
40-50% absorption following oral administration Occurs in small intestine Enhanced with food
53
Methenamine absorption
Rapid absorption after oral administration | May be partially degraded by gastric acid
54
Nitrofurantoin distribution
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
methenamine distribution
Rapid absorption following oral dose | Broad distribution in tissue
56
Nitrofurantoin elimination
``` Eliminated in the urine Glomerular filtration Tubular secretion Tubular reabsorption Biliary excretion: minor Serum half life ```
57
methenamine elimination
Renal excretion | Half-life 3-4 hours with normal renal function
58
clinical uses of Nitrofurantoin
Acute, uncomplicated UTIs (commonly used for E. coli among many others) Do not use for: Pyelonephritis Complicated UTi
59
clinical uses of Methenamine
Suppression or prophylaxis against recurrent UTIs Do not use for: Established infections Prophylaxis against catheter-associated UTI
60
Nitrofurantoin
 Adverse reactions
• 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
Methenamine 
Adverse reactions
``` 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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