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General Pharmacology Test 4 > Antibiotics and Antibiotic Resistance > Flashcards

Antibiotics and Antibiotic Resistance Flashcards

1
Q

Inhibit bacterial ribosomes (inhibit protein synthesis)

A

Tetracyclines and Chloramphenicol block tRNA binding
Erythromycin and clindamycin block translocation
Erythromycin and chloramphenicol block peptide bonds.

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2
Q

Tetracycline types

A

Tetracycline
Doxycycline
Oxytetracycline
Minocycline

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3
Q

Properties of Tetracyclines

A

Naturally occurring, broad spectrum, blocks protein synthesis (30S), bacteriostatic.
Forms complexes with divalent metals (e.g. calcium, magnesium, and iron) harms teeth and bones. Absorbs UV causing sunlight sensitivity and formation of free radicals to cause inflammatory response.

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4
Q

Advantage of Tetracyclines

A

Orally effective, favorable therapeutic index, broad spectrum, penetrates well in most tissues, penetration of human cells to target intracellular parasitic bacteria.

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5
Q

Disadvantages of tetracyclines

A

Emerging resistance

Side effects/toxicity.

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6
Q

Side Effects of Tetracyclines

A

Binding to bone and teeth: serious in pregnancy by discoloring teeth and blunting skeletal growth.
Photosensitivity to the sun
GI upsets
Vertigo
Hepatic and renal toxicity (rare with long course of therapy)

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7
Q

Emerging Resistance to Tetracyclines

A

Tet-induced transporter protein

Active Efflux.

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8
Q

Clinical Use of Tetracyclines

A

Safe alternative for beta-lacatam allergies.
Drug of choice for chlamydia/mycoplasma, rickettsial diseases (typhus, rocky mtn spotted fever, Q fever), lyme disease and relapsing Borrelia fevers.

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9
Q

Alternate clinical use of tetracyclines

A

Syphilis, mycoplasma, ligonella

Treat acne, bronchitis

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10
Q

Commonly used tetracyclines

A

Doxycycline

Minocycline

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11
Q

Chloramphenicol General Properties

A

Blocks protein synthesis (50s)
Extremely broad spectrum (aerobic/anaerobic gram (+ and -)
Bacteriostatic (few cidal)
Oral, IV; well absorbed, distributed

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12
Q

Chloramphenicol Side Effects

A

Bone marrow toxicity (fatal)
“Gray baby” syndrome (elimination)
Multiple Drug Interactions

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13
Q

Chloramphenicol Clinical Uses

A

Rarely used in US (previous wide use); common in developing countries.
Alternative to B-lactams for CNS
Many safer replacements.

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14
Q

Macrolides and Ketolides

A

Erythromycin - prototype
Azithromycin - Current usage
Clarithromycin - current usage
Ketolides (semi-synthetic derivatives of erythromycin)
Telithromycin (Ketek) newly approved 2004

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15
Q

Properties of Macrolides/ketolides

A

Spectrum: Gram + bacteria with Gram -
Blocks protein synthesis (50S ribosome)
Bacteriostatic
Old (erythromycin, E) acid sensitive
New (azithromycin, az) not acid sensitive
Distributes well in tissues (except CNS)
Resistance: Ribosomal methylation and efflux

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16
Q

Side Effects of Macrolides/Ketolides

A

Few; all relatively safe
Mild G.I. Upset
Erythromycin (E) and Telithromycin (T) interact w/ P450s. Interact w/ theophylline, warfarin, digoxin
Infrequent hepatotoxicity

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17
Q

Clinical Uses of Macrolides

A

Few advantages over B-lactams
Used often as alternative to penicillin allergic or uncertain allergic
Safe for children

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18
Q

Macrolides Use

A

Drug of Choice: mycoplasma infections, ligonella, bordetella pertussis, campylobacter jejuni, respiratory strep infections.
Syndromes: Bacterial bronchitis, otitis media, acne
Phrophylaxis: endocarditis, large bowel surgery, oral surgery

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19
Q

Ketolide Use

A

Developed for special uses: limited resistance, used for resistant gram + stains

20
Q

Clindamycin (cleocin)

A

Spectrum: mostly gram + and limited gram -.
Action: blocks protein synthesis (50S binding)
Bacteriostatic
Oral (90% absorbed), IV, and IM

21
Q

Clindamycin Side Effects

A

Risk of severe diarrhea, fatal colitis (rare)

22
Q

Clindamycin Clinical Uses

A

Limited due to side effects
Topical treatments, acne
Substitute for macrolides (azrithromycin)

23
Q

Peptide Antibioitics

A

Polymyxin B (aeorsporin)
Polymyxin E (colistin)
Bacitracin (generic)
Vancomycin (vancocin)

24
Q

Polymyxin general properties

A

Charged decapeptides, cation detergents
Gram - bacteria
Act on membrane lipid PE causing membrane lysis
Batericidal

25
Q

Polymyxin Side Effects

A

Serious nephrotoxicity, neurotoxicity

26
Q

Polymyxins Clinical Use

A

Limited to topical application only (usually in combo with gram + topical)
Cutaneous pseudomonal infections of mucous membranes, eyes, ears.

27
Q

Bacitracin General Properties

A 
Mixture of polypeptides
Block cell wall synthesis (different from B-lactams)
Gram + bacteria
Bactericidal
NOT absorbed by GI tract
28
Q

Bacitracin Side Effects

A

Serious Nephrotoxicity

29
Q

Bacitracin Clinical Uses

A

Limited to topical application
Used often in combination with polymyxins to offer broad spectrum
Polymyxins = gram -
Bacitracin = gram +

30
Q

Vancomycin General Properties

A 
Glycopeptide
Blocks cell wall synthesis
Gram + bacteria
Bactericidal
IV and oral
31
Q

Vancomycin Side Effects

A

Ototoxicity

Nephrotoxicity w/ aminoglycosides

32
Q

Vancomycin Clinical Uses

A

Important alternative for resistant gram + strains
Drug of choice for methicillin-resistant S. Aureus (MRSA) and other (MR) strains
Limited but growing resistance

33
Q

Most prevalent bacterial infection in the world

A

Mycobacterium tuberculosis exists in 1/3 of the world’s popultion
MTB is a subclass of gram - bugs with high fat outer membrane - not detected by gram stain.
Cell wall distinct from gram +/gram - and high in mycolic acid fatty lipids.

34
Q

Characteristics of Mycobacteria

A 
Slow growth (24 hr vs 20 minutes double time)
Susceptible to develop drug resistance
Chronic disease (many years)
35
Q

Drug Treatment of Mycobacterium Tuberculosis

A

Isoniazid: blocks fatty acid synthase required for mycolic acid synthesis
Rifampicin: Directly inhibits bacterial RNA polymerase to block mRNA synthesis
Ethambutol: Blocks arabinosyl transferase (required for mycolic acid coupling)
Pyrazinamide: Blocks pyrazinamidase to cause acid build-up and cell death

36
Q

Treatment of Mycobacterium Tuberculosis

A

Chronic combination multi-drug therapy is required to overcome resistance.
2 months: isoniazid + rifampicin, ethambutol and pyrazinamide
4 months: Isoniazid + rifampicin

37
Q

Barriers to Successful treatment of Mycobacterium Tuberculosis

A

Complexicity (5 drugs/6 months)
Lack of compliance
Cost and Availability
Multiple Side effects (deters compliance)
Results: Emergence of drug-resistant strains

38
Q

Example Drug-Resistant Bacteria

A

Methicillin-resistant Staphylococus aureus (MRSA)
Vancomycin-resistant enteroccous (VRE)
Fluoroquinolone-resistant Pseudomonas (FQRP)
Drug-resistant Tuberculosis (DRTB)
Cabapenem-resistant Bacteriaacae (CRE) - NEW!!

39
Q

Common Mechanisms of Drug Resistance

A

Spontaneous mutation in target proteins.
Modification of antibiotic binding site on target
Natural enzymes that inactivate agents
Spontaneous changes in membrane permeability (cell wall thickening, upregulation of transporters)

40
Q

Man-made contributions to resistance

A 
Over-prescription
Close quarters health care facilities
Day Care
Agriculture feedlots (environment)
Foreign Exposure
41
Q

New Techniques

A

Drugs bind ribosomes to fight resistant bacterial strains

Tigecycline, Quinupristin/Dalfopristin, and Linezolid

42
Q

Trigecycline

A

Modified form of minocycline
Blocks protein synthesis at tRNA binding on 30S ribosome.
Bacteritstatic
Good for MRSA and vancomycin resistant strains.

43
Q

Quinupristin/Dalfopristin

A

Semisynthetic Derivatives
Blocks protein synthesis at tRNA binding sites on 30S ribosomes (similar to macrolides)
Acts on gram + cocci
Good for MRSA and vancomycin resistant strains.

44
Q

Linezolid

A 
Oxazolidone
Blocks protein synthesis at tRNA formation
Bactericidal
Minimal side effects
Good for resistant strains
45
Q

Daptomycin (cidectin, cubecin)

A

Natural cyclic lipopeptide
Membrane ionophore-depolarization
Broadly acting against gram +
Good for MRSA and VRE on the skin.

General Pharmacology Test 4 (13 decks)

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