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3B : ANTI-BACTERIAL Flashcards

1
Q

Substance, produced by one microorganism, or produced partly or wholly through synthetic means, which at low concentrations can inhibit the growth of, or are lethal to other microorganisms

A

Antibiotic

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2
Q
  • first antibiotic
  • discovered in September 1928 by an English Bacteriologist, late Sir Alexander Fleming
  • accidentally obtained the antibiotic from a soil -inhabiting fungusPenicillium notatum
A

Penicillin

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3
Q

kill bacteria

A

Bactericidal

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4
Q

inhibit bacterial growth

A

Bacteriostatic

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5
Q

CHARACTERISTICS OF ANTIBIOTICS

A
  • Kill or inhibit the growth of pathogens
  • Cause no allergic reaction to host cell
  • Don’t cause damage to host cell
  • Should be stable when stored in liquid or solid form
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6
Q

HOW CLASSIFICATION OF ANTIBIOTICS BEING MADE

A

Classification according to
* Chemical or molecular structure
* Mechanism of action
* Spectrum of activity
* Absorbability from site of administration

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7
Q

Antibiotics within the same structural class will generally show similar pattern of

A
  • Effectiveness
  • Toxicity
  • Allergic potential side effects
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8
Q

CLASSIFICATIONS ACCORDING TO MECHANISM

A

INHIBITION OF CELL WALL SYNTHESIS
INHIBITION OF PROTEIN SYNTHESIS
INHIBITION OF BACTERIAL METABOLISM
INHIBITION OF NUCLEIC ACID SYNTHESIS
DISRUPTION OF PLASMA MEMBRANE

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9
Q

ANTIBIOTICS UNDER INHIBITORS OF CELL WALL SYNTHESIS

A
  • β-Lactams
  • Glycopeptide
  • Other Inhibitors of Cell Wall Synthesis
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10
Q

INHIBITION OF CELL WALL SYNTHESIS ANTIBIOTICS under β-Lactams

A
  • Penicillins
  • Cephalosporins
  • Carbapenems
  • Monobactams
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11
Q

INHIBITION OF CELL WALL SYNTHESIS ANTIBIOTICS under Glycopeptides

A

Vancomycin

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12
Q

INHIBITION OF CELL WALL SYNTHESIS ANTIBIOTICS under Other Inhibitors of Cell Wall Synthesis

A
  • Bacitracin
  • Cycloserine
  • Daptomycin
  • Fosfomycin
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13
Q

INHIBITION OF PROTEIN SYNTHESIS ANTIBIOTICS under 30S

A
  • Aminoglycosides
  • Tetracyclines
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14
Q

INHIBITION OF PROTEIN SYNTHESIS ANTIBIOTICS under 50S

A
  • Chloramphenicol
  • Macrolides
  • Lincosamides
  • Oxazolidinone
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15
Q

INHIBITION OF BACTERIAL METABOLISM ANTIBIOTICS under FOLIC ACID SYNTHESIS

A
  • Sulfonamides
  • Trimethoprim
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16
Q

INHIBITION OF BACTERIAL METABOLISM ANTIBIOTICS under MYCOLIC ACID SYNTHESIS

A

Isoniazid

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17
Q

INHIBITION OF NUCLEIC ACID SYNTHESIS under DNA Synthesis

A
  • Fluoroquinolones
  • Metronidazole
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18
Q

INHIBITION OF NUCLEIC ACID SYNTHESIS under RNA Synthesis

A
  • Rifamycins
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19
Q

Antibiotics with action of Disrupting the plasma membrane

A
  • Polymyxin
  • Mupirocin
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20
Q
  • Contain the beta-lactam ring
  • Inhibit bacterial cell wall biosynthesis- bactericidal
  • Modifications of the R- group side-chain (attached to the β-lactam ring) alter the pharmacologic properties and resistance to β- lactamase
A

BETA LACTAMS

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21
Q

Drug classes under beta lactams

A
  • PENICILLINS
  • CEPHALOSPORINS
  • MONOBACTAMS
  • CARBAPENEMS
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22
Q

Inactivate bacterial transpeptidases and prevent the cross-linking of peptidoglycan polymers which is essential for bacterial cell wall integrity. This results in a loss of rigidity and susceptibility to rupture.

A

PENICILLINS

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23
Q

bind to and inactivate penicillin-binding proteins (PBPs) involved in cell wall synthesis. The action of autolysinin the presence of penicillin further weakens the cell wall.

A

PENICILLINS

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24
Q

Gram-positive or gram negative bacteria with thick external cell walls are particularly susceptible to penicillin?

A

Gram-positive

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25
The major cause of resistance for penicillin is?
the production of the β- lactamases (penicillinases).
26
Common organisms capable of producing penicillinase
* Staphylococcus aureus, * Escherichia coli, * Pseudomonas aeruginosa, * Neisseria gonorrhoeae, and * Bacillus, * Proteus, and * Bacteroides species.
27
Resistance to penicillin may also occur because
* bacteria **lack receptors or other PBPs**, are **impermeable to penicillins, lack cell walls, or are metabolically inactive**.
28
Narrow-spectrum against gram-positive and a few gram-negative bacteria
Natural Penicillins
29
drugs under natural Penicillins
Penicillin G Penicillin V
30
Penicillinase Resistant. Narrow-spectrum against gram-positive bacteria only, including strains producing penicillinase
Semisynthetic Penicillins
31
drugs under semisynthetic penicillin
Methicillin Nafcillin, Oxacillin, Dicloxacillin
32
Narrow-spectrum against gram-positive bacteria but with an increased gram-negative spectrum
Extended Penicillin
33
what are the groups under extended penicillins
* Aminopenicillins * Anti-pseudomonal Penicillins
34
group under anti pseudomonal penicillins
* Ureidopenicillins * Carboxypenicillins
35
drugs under **Ureidopenicillins**
**Piperacillin** Mezlocillin Azlocillin
36
drugs under **carboxypenicillin**
**Carbenicillin** Ticarcillin Temocillin
37
Pharmacologic properties of penicillin
* Penicillins are absorbed **rapidly** **after enteral administration**, although erratically, and **parenteral administration** and are distributed throughout body fluids; * they **penetrate the cerebrospinal fluid (CSF)** and ocular fluid significantly **only during inflammation.** * **Gastrointestinal (GI) absorption** may be **decreased** in the **presence of food.**
38
drugs under pen G
Benzylpenicillin
39
PEN G IV or ORAL?
* Given by **injection** into a vein or muscle * **Long-acting form**s are given by **IM route:** Penicillin G Benzathine Penicillin G Procaine
40
Spectrum of activity of Pen G
* Aerobes * Gram-**positive cocci** * Gram-positive **rods**, e.g., Bacillus spp, Listeria spp, Clostridium * Gram-negative, e.g., Gonococci, Meningococci * Anaerobes Most, **except Bacillus fragilis** * Others: **Treponema** pallidum, **Leptospira** spp
41
Suspensions of penicillin G that **prolong its half-life ( 30 min)**, allowing a reduced frequency of injections A uricosuric agent that **blocks renal secretion of penicillin**, is used for this purpose, but only rarely.
Probenecid
42
An **oral form of Pen G** with **poor bioavailability**, has a narrower spectrum of activity
Penicillin V
43
used predominantly for penicillinase-producing staphylococcal infections
Penicillinase- Resistant Penicillins Used of these agents, which are **administered orally**, is **declining** due to the **increased incidence of methicillin-resistant S. aureus (MRSA)** that also confers resistance to cephalosporins.
44
inactivated by β- lactamases Have a broadened gram-negative coverage. Resistance has become a more common problem
Extended-Spectrum Penicillins
45
What are the drugs under Extended-Spectrum Penicillins
* Aminopenicillins * Ureidopenicillins * Carboxypenicillins
46
drugs under Aminopenicillins
Ampicillin Amoxicillin Bacampicillin
47
IV injections must be given slowly, as rapid IV injections can lead to convulsive seizures
Ampicillin
48
Useful in infections caused by **Haemophilus influenzae**, **Streptococcus pneumonia**, **Streptococcus pyrogenses**, **Neisseria meningitidis**, **Proteus mirabilis,** **Enterococcus faecalis, E. coli, Proteus mirabilis, Salmonella enterica, and Shigella**
Ampicillin
49
consideration on giving ampicillin
* Large doses of ampicillin can **increase the risk of bleeding** with concurrent use of **warfarin** and other oral anticoagulants, **possibly by inhibiting platelet aggregation** * When administered separately, a**minoglycosides and ampicillin can potentiate each other**
50
similar to ampicillin but has better oral absorption.
Amoxicillin
51
**Prodrug of ampicillin** with improved oral bioavailability
Bacampicillin
52
* **not absorbed orally**, and **must therefore be given by** **intravenous or intramuscular injection** * **Enhanced penetration into gram-negative bacteria** and reduced susceptibility to cleavage by gram-negative beta lactamase enzymes * These properties confer activity **against the important hospital pathogen Pseudomonas aeruginosa.** Sometimes referred to as an **"anti-pseudomonal penicillin“** * **When used alone,** **lacks strong activity against the gram-positive pathogens**
Piperacillin
53
* **Active against both Gram-negative** including Pseudomonas aeruginosa and some Gram-positive bacteria * Unlike most other extended spectrum penicillins, it is **excreted by the liver**, therefore it is **useful for biliary tract infections**
Mezlocillin
54
* Given orally, parenterally * Has Gram-negative coverage which includes Pseudomonas aeruginosa **but limited Gram-positive coverage** * At ***high doses*** can cause ***bleeding*** * ***Can cause hypokalemia*** by promoting **potassium loss at the distal convoluted tubule of the kidney**
Carbenicillin
55
* Not absorbed orally, so must be given by intravenous or intramuscular injection * Main clinical use is as an **injectable antibiotic for the treatment of Gram-negative bacteria, particularly Pseudomonas aeruginosa**
Ticarcillin
55
Adverse Effects of Penicillin
* hypersensitivity (All reactions, from a simple rash to anaphylaxis, can be observed within two minutes or up to 3 days following administration) * adverse effect results from direct irritation or **pain on injection,** **GI upset, or superinfection.**
56
* also have β- lactam ring. Substitutions at **R1 determine antibacterial** activity. **Substitution at R2** determines pharmacokinetics.
**Cephalosporins**
57
selected agents of Cephalosporins penetrate CSF.
* **cefuroxime**, 2nd generation * cefotaxime, and * ceftizoxime
58
* **newer generation** of cephalosporins is **increasingly resistant to penicillinases.** * **categorized by their antibacterial spectrum**, especially against Gram-negative organisms
cephalosporinss
59
First Generation Cephalosporins
Cefacetrile Cefadroxil **Cefalexin** Cefaloglycin Cefalonium Cefaloridine Cefalotin Cefapirin Cefatrizine Cefazaflur Cefazedone **Cefazolin** Cefradine Cefroxadine Ceftezole
60
1st generation cephalosporin have activity against
* some gram- positive organisms (streptococci) and * some gram- negative organisms * **Proteus mirabilis**, * **Escherichia coli** * **Klebsiella infections (PEcK),** and * **penicillin-and-sulfonamide-resistant urinary tract infections** **Prophylaxis** in various surgical procedures These agents **do not penetrate CSF**
61
Second Generation Cephalosporin
* **Cefaclor** * Cefonicid * Cefprozil * **Cefuroxime** * Cefuzonam
62
Antianaerobe activity of second generation
* Cefmetazole * Cefotetan * Cefoxitin
63
The following cephems are also sometimes grouped with second-generation cephalosporins
Carbacephems: * Loracarbef Cephamycins: * Cefbuperazone * Cefmetazole * Cefminox * Cefotetan * **Cefoxitin** * Cefotiam
64
second generation cephalosporins They are used in the treatment of
* **streptococcal** infections as well as infections caused by **E. coli, Klebsiella, and Proteus spp.** * **Most anaerobes** (**except Clostridium difficile)** * Used primarily in **managing urinary and respiratory tract, bone, and soft tissue infections** and prophylactically in various surgical procedures
65
Third Generation cephalosporins
Cefcapene Cefdaloxime Cefdinir Cefditoren Cefetamet **Cefixime** Cefmenoxime Cefodizime Cefotaxime Cefovecin Cefpimizole Cefpodoxime Cefteram Ceftamere Ceftibuten Ceftiofur Ceftiolene Ceftizoxime **Ceftriaxone**
66
Antipseudomonal activity of second generation cephalosporin:
* Cefoperazone * **Ceftazidime**
67
These cephems are also sometimes grouped with third-generation cephalosporins:
Oxacephems: **Latamoxef**
68
Uses for third generation cephalosporin
* enhanced activity against gram-negative organisms * against **H. influenzae, N. gonorrhoeae, N. meningitides, Enterobacter, Salmonella, indole-positive Proteus, Serratia spp., and E. coli and moderate activity against anaerobes.** * Serious hospital-acquired gram-negative infections, alone or in combination with an aminoglycoside * **Cefoperazone and ceftazidime**have excellent activity against **P. aeruginosa.**
69
is used for **sexually transmitted infections** caused by **gonorrhea**, as well as in **empiric** **therapy** for community-acquired **meningitis**.
Ceftriaxone
70
, ***third-generation- cephalosporins penetrate the CSF.*** except
for **cefoperazone**
71
third generation cephalosporin which are excreted through the biliary tract, thus enabling the use of these agents for infections of the biliary tree.
**cefoperazone** and **ceftriaxone**, also **Mezlocillin** (but not under cephalosporins)
72
Fourth Generation cephalosporins
Cefclidine **Cefepime** Cefluprenam Cefoselis Cefozopran Cefpirome These cephems are also sometimes grouped with fourth-generation cephalosporins: Oxacephems: * **Flomoxef**
73
4th generation cephalosporins that has **powerful coverage against Pseudomonas spp**., as well as **other gram-positive and gram-negative bacteria**
Cefepime
74
4th generation cephalosporins have
* a **greater resistance to β-lactamases** **than the third-generation cephalosporins** * Many **can cross the blood-brain barrier** and are effective in meningitis
75
5th-generation cephalosporins
* Ceftaroline, * Ceftobiprole, * Ceftolozane
76
Fifth-generation are Active against
* **Methicillin-resistant S. aureus (MRSA)** * **Penicillin-resistant streptococci** * **Ampicillin-susceptible and beta-lactamase–producing Enterococcus** faecalis
77
5th generation cephalosporins that Has powerful antipseudomonal characteristics and appears to be less susceptible to the development of resistance
Ceftobiprole
78
5th generation cephalosporins that * **Does not have the antipseudomonal coverage** * **Has MRSA** coverage
**Ceftaroline**
79
5th generation * New option for treatment of **Complicated Intra-abdominal Infections (cIAI), and Complicated Urinary Tract Infections (cUTI)** * Combined with the β-lactamase inhibitor tazobactam
Ceftolozane
80
adverse effects of cephalosporins
* **Hypersensitivity** reactions including urticaria, fever, joint pains, rashes, angioedema, anaphylaxis, serum sickness-like reaction * Penicillin/cephalosporin allergic **cross-reactivity** * **Rarely CNS toxicity**, including convulsions (especially with high doses or in severe renal impairment), interstitial nephritis, hemolytic anemia, leukopenia, thrombocytopenia, and coagulation disorders * **Alcohol intolerance (disulfiram-like)** is seen with ***cefamandole*** and ***ceftriaxone*** * Cephalosporins may cause **bleeding disorders**; **nephrotoxicity** when administered **with diuretics** * Also reported **diarrhea** (including antibiotic-associated colitis). * May cause **superinfection** with gram-positive organisms or fungi.
81
are the number one cause of hospital-acquired **C. difficile colitis**, a potentially life-threatening infection.
Cephalosporins
82
only commercially available monobactam antibiotic
AZTREONAM
83
* a naturally occurring monobactam lacking the thiazolidine ring that is highly resistant to β- lactamases * Poorly absorbed when given orally, so it must be administered as an intravenous or intramuscular injection * Has good activity against gram-negative organisms, but it lacks activity against anaerobes and gram-positive organisms. * Useful for various types of infections caused by **E. coli, Klebsiella pneumonia, H. influenzae, P. aeruginosa, Enterobacter spp., Citrobacter spp., and P. mirabilis.**
AZTREONAM
84
Demonstrates **no cross-reactivity with penicillins or cephalosporins** for hypersensitivity reactions
AZTREONAM
85
Generally, exhibit good activity against **anaerobes** such as **Bacteroides fragilis** This class of antibiotics is usually **reserved** for known or suspected **multidrug-resistant (MDR) bacterial infections** Useful for **infections caused by penicillinase-producing S. aureus, E. coli, Klebsiella spp., Enterobacter spp., and H. influenzae,** among others.
CARBAPENEMS
86
* are powerful agents used for Pseudomonas infections * Exhibit good activity against anaerobes such as Bacteroides fragilis
CARBAPENEMS
87
* are powerful agents used for Pseudomonas infections * Exhibit good activity against anaerobes such as Bacteroides fragilis
CARBAPENEMS
88
side effect of CARBAPENEMS
* Nausea, vomiting, diarrhea, skin rashes, and * **at higher doses**, **seizures** are their **most common adverse effects, particularly for imipenem.**
89
Hydrolyzed in the **mammalian kidney** by a **dehydropeptidase enzyme to a nephrotoxic intermediate**, and thus is co-formulated with the dehydropeptidase inhibitor cilastatin
Imipenem
90
* **Stable to mammalian dehydropeptidases** and **does not require co-administration of cilastatin** * Somewhat **less potent than imipenem against gram-positive** pathogens, and somewhat **more potent against gram-negative infections** * Unlike imipenem, which produced an unacceptable rate of seizures in a phase 2 trial, ____ is **effective for the treatment of bacterial meningitis**
Meropenem
91
**Lacks useful activity against the P. aeruginosa** and **Acinetobacter** species, both of which are important causes of hospital-acquired infections
Ertapenem
92
Occurs as a result of the expression of one of many genes for the production of β-lactamases, a class of enzymes that breaks open the β-lactam ring
BACTERIAL RESISTANCE TO BETA-LACTAM
93
Bacteria that can produce beta-lactamases include, but are not limited to:
Staphylococcus * MRSA (Methicillin-resistant Staphylococcus aureus) Enterobacteriaceae: * Klebsiella pneumoniae * Citrobacter * Proteus vulgaris * Morganella * Salmonella * Shigella * Escherichia coli Haemophilus influenzae Neisseria gonorrhoeae Pseudomonas aeruginosa Mycobacterium tuberculosis
94
To overcome this resistance, **β-lactam antibiotics are often given with β-lactamase inhibitors** such as
* Clavulanic acid or clavulanate * Sulbactam * Tazobactam
95
MOA of β-lactamase inhibitors
Act as **suicide substrates** which ultimately leads to the **degradation of the beta-lactamase**
96
durgs under Clavulanic acid or clavulanate
* Amoxicillin + Clavulanic acid (Co-amoxiclav) * Ticarcillin + Clavulanic acid (Co-ticarclav)
97
drugs under Sulbactam
Ampicillin + Sulbactam
98
drug under Tazobactam
Piperacillin + Tazobactam
99
* No antimicrobial property * **Irreversibly inhibits β- lactamase;** when administered with penicillins, * exposes penicillinase-producing organisms to therapeutic concentrations of penicillin.
Clavulanic acid
100
* Clavulanic acid Used in combination products **amoxicillin/clavulanic acid** and *ticarcillin/clavulanic acid* for administration **co-amoxiclav** *co-ticarclav*
**oral** and *parenteral*
101
DRUGS UNDER OTHER INHIBITORS OF CELL WALL SYNTHESIS
* VANCOMYCIN * BACITRACIN * CYCLOSERINE * DAPTOMYCIN * FOSFOMYCIN
102
MOA: Binds to the **terminal end of the peptidoglycan** to prevent further elongation and cross-linking due to ***inhibition of transglycosylase***; this results in **decreased cell membrane activity** and increased cell lysis.
VANCOMYCIN
103
THERAPEUTIC USE OF VANCOMYCIN
* **Active against gram-positive organisms**; resistant strains have been reported. * Used in **serious MRSA infections**, in patients **allergic to penicillins and cephalosporins**, and **to treat antibiotic-associated enterocolitis (C. difficile colitis).** * **Penetrates CSF** only during inflammation
104
Rapid infusion of vancomycin may cause
**anaphylactoid** reactions and **“redneck” syndrome** ***(flushing caused by the release of histamine).***
105
Rarely, high levels of vancomycin may cause
**ototoxicity** with permanent auditory impairment and **nephrotoxicity**
106
VANCOMYCIN INDICATION
* A variety of dosage forms (for example, oral, injections, etc.) exist for **treating serious or severe infections caused by susceptible strains of methicillin-resistant (beta-lactam-resistant) staphylococci. ** * Additionally, **a unique FDA-approved oral liquid treatment** is also available and indicated for the **treatment of Clostridium difficile-associated diarrhea and enterocolitis caused by Staphylococcus aureus, including methicillin-resistant strains**.
107
inhibits **dephosphorylation** and **reuse of the phospholipid required for acceptance of *N- acetylmuramic acid pentapeptide***, the building block of the peptidoglycan complex.
BACITRACIN
108
USES OF BACITRACIN
* Most active **against gram-positive bacteria.** * Used ***only topically*** in combination with neomycin or polymyxin for minor infections * **As a polypeptide, toxic, and difficult-to-use chemical, bacitracin doesn’t work well orally; however, it is very effective topically** * Used in **ointment form for topical treatment** of a variety of localized **skin and eye infections**, as well as for the prevention of wound infections
109
inhibits **alanine racemase and the incorporation of alanine** into the peptidoglycan pentapeptide.
Cycloserine * is active **against** **mycobacteria** and **gram-negative bacteria**.
110
agent is used only as a second-line drug for treating urinary tract infections and tuberculosis (TB)
CYCLOSERINE
111
At high doses, cycloserine may cause
**severe central nervous system (CNS) toxicity**, including **seizures and acute psychosis**
112
a bactericidal agent that binds to and **depolarizes the cell membrane,** **resulting in loss of membrane potential** and rapid cell death.
DAPTOMYCIN
113
* Has **antibacterial actions similar to that of vancomycin** * **Active in vancomycin-resistant strains** * May cause **myopathy**.
DAPTOMYCIN
114
inhibits the enzyme ***enolpyruvate transferase*** and thereby interferes downstream with the bacterial cell wall-specific N-acetylmuramic acid.
FOSFOMYCIN
115
This oral agent is active against both gram-negative organisms. It is used to treat simple lower urinary tract infections.
FOSFOMYCIN
115
drugs under AMINOGLYCOSIDES
Gentamicin Tobramycin Amikacin Kanamycin Neomycin Netilmicin Streptomycin
116
Mechanism of Action of aminoglycosides
* **inhibit bacterial protein synthesis**; they are **bactericidal** against **most gram-negative *aerobic* bacteria.** * Aminoglycosides passively diffuse via porin channels through the outer membrane of gram-negative aerobic bacteria. Transport across the inner membrane requires active uptake that is dependent on electron transport (gram-negative aerobes only), the so-called **energy-dependent phase I transport.** * Inside the cell, these agents interact with the **receptor proteins on the 30S ribosomal subunit**. This “**freezes” the initiation complex and leads to a buildup of monosomes; it also causes translation errors.**
117
how can resistance to aminoglycosides develop?
* Resistance generally results from bacterial enzymes that inactivate the drugs * It may occur through 3 separate mechanisms: 1. **DECREASED UPTAKE** - due to the **absence of oxygen-dependent permeases**; only in anaerobic bacteria (only aerobic bacteria have oxygen-dependent permeases) 2. **DECREASED AFFINITY** – **due to structural alterations of the 30S subunit** 3. **INCREASED INACTIVATION**– due to the **presence of aminoglycoside-inactivating enzymes** which modify the aminoglycosides, thus inactivating them – these enzymes include **acetyltransferases, nucleotidyltransferases, and phosphotransferases**
118
**Anaerobic** bacteria are generally **resistant to aminoglycosides** true or false and why?
true * Some bacteria use **an oxygen-dependent transport** system **to bring the amino-glycosides into the cell**. * The anaerobes (with non–oxygen-based metabolism) do not have this system. Therefore, they are generally resistant to the aminoglycosides
119
Aminoglycosides are **poorly absorbed from the GI tract.** Most aminoglycosides must be administered **parenterally** true or false
true
120
* Aminoglycosides agents do not penetrate the CSF. * They are **highly polar compounds** and are **relatively insoluble in fat**. * They do not readily penetrate most cells without help from penicillin or a transport system. what is the solution?
**Synergism** between **penicillins and aminoglycosides** - The penicillins cause cell wall abnormalities that allow the aminoglycosides to gain entry into the bacteria
121
* administered intramuscularly and/or IV * may cross the placental barrier * may not cross the blood-brain barrier
STREPTOMYCIN
122
treatment of **tularemia** due to **francisella infection**
STREPTOMYCIN
123
medical uses of streptomycin
* treatment of **pneumonia** due to **enterobacter**, **proteus**, **klebsiella** and/or **pseudomonas** infection * treatment of **cystitis** due to **escherichia**, **enterobacter**, **proteus** and/or **klebsiella** infection * treatment of **tularemia** due to francisella infection * treatment of **cholera gravis** due to **vibrio infection** * treatment of the ** bubonic plague due to yersinia infection** * treatment of **tuberculosis** due to **mycobacterium infection** (if resistant to first-choice antituberculotic drugs)
124
Side effects of streptomycin
* **vertigo** (due to **vestibular** nerve damage) * **deafness** (due to **cochlear** nerve damage) * **nephrotoxicity**
125
active against **Enterobacter**, ***Indole-positive Proteus***, **Pseudomonas**, **Klebsiella**, and **Serratia** spp., among other gram-negative organisms These agents are **often used synergistically in combination with β- lactam antibiotics or vancomycin** for serious infections that require broad coverage.
GENTAMICIN and TOBRAMYCIN
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Used in the treatment of **severe gram-negative infections**, especially to those **resistant to gentamicin or tobramycin**
AMIKACIN
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administered **topically** for **minor soft-tissue infections** (often in combination with bacitracin and polymyxin) or **orally (neomycin) for hepatic encephalopathy** (GI bacteria by-products result in large amounts of ammonia, which is normally cleared by the liver; use of ____ temporarily inactivates the normal flora).
NEOMYCIN and KANAMYCIN _____ neomycin
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**structurally related to aminoglycosides** and is administered **intramuscularly** as an alternative for **treating** **acute gonorrhea** or in patients **hypersensitive to penicillin** or for gonococci resistant to penicillin.
**SPECTINOMYCIN**
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ADVERSE EFFECTS of aminoglycosides
ototoxicity, nephrotoxicity, and neuromuscular toxicity The **margin of safety with these drugs is small.** This means that the toxic concentration is slightly higher than the therapeutic concentration.
130
The symptoms of ototoxicity include:
The ototoxicity can be both cochlear (auditory) and vestibular. **tinnitus** (ringing), **deafness**, **vertigo** or unsteadiness of gait, and ***high-frequency hearing loss***.
131
The cochlear toxicity results from
the selective destruction of the outer hair cells in the organ of Corti
132
drugs with Vestibular toxicity drugs with cochlear auditory toxicity
* Vestibular (**streptomycin, gentamycin, and tobramycin**) * Cochlear auditory (neomycin, kanamycin, amikacin, gentamicin, and tobramycin )
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____ , ____, ____ are **nephrotoxic**; they produce **acute tubular necrosis** that leads to a reduction in the glomerular filtration rate and a rise in serum creatinine and blood urea nitrogen. Damage is usually reversible
Gentamicin, neomycin, and tobramycin
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At high doses, these agents produce a **curare-like neuromuscular blockade** with **respiratory paralysis**
aminoglycosides
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antidote for curare-like neuromuscular blockade of aminoglycosides
* Calcium gluconate and * neostigmine
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Aminoglycosides rarely cause hypersensitivity reactions, except ____ and ____ , which, when applied topically, can cause contact dermatitis in as many as 8% of patients.
spectinomycin neomycin
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drugs under TETRACYCLINES
**Tetracycline** Oxytetracycline Demeclocycline **Doxycycline** Minocycline Tigecycline
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binds **reversibly to the 30S** subunit of bacterial ribosomes. This **prevents the binding of aminoacyl tRNA to the acceptor site on the mRNA- ribosome complex** and the addition of amino acid to the growing peptide, thus inhibiting bacterial protein synthesis; these agents are ***bacteriostatic***.
Tetracycline
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mechanism in which tetracycline is a bacteriostatic
Inhibition of protein synthesis would normally lead to the death of the bacteria, but due to the **inhibition occurring after assembly of the ribosome-mRNA complexes**, some bacterial proteins are still being randomly translated; thus, tetracyclines are bacteriostatic
140
how can resistance develops in tetracyclines?
Resistance is **plasmid- mediated** and r**esults primarily from a decreased activity to accumulate in the bacteria** and from the production of an inhibitor of the binding site for tetracyclines. **Resistance to one tetracycline confers resistance to some**, but not all congeners.
141
tetracycline absorption is impaired by
Absorption is impaired by **stomach contents, especially milk and antacids.**
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Tetracyclines are distributed throughout body fluids; therapeutic concentrations in the brain and CSF can be achieved with .____
minocycline
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The primary route of elimination for most tetracyclines is the **kidney**. ____ and ____ do not accumulate and hence are the **safest tetracyclines** to administer to individuals with impaired renal function
Doxycycline and Tigecycline
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Medical Uses of tetracycline
Treatment of * Rickettsial infection * Vibrio cholera * Chlamydia * Helicobacter pylori * Mycoplasma pneumoniae * Plasmodium * Inflammatory acne vulgaris * Treatment of syphilis due to treponema infection * **Tigercycine** has a broad spectrum of activity and has **activity against many tetracycline-resistant organisms**
145
used in refractory cases of SIADH because it interferes with the action of ADH at the renal collecting duct by impairing the generation and action of cyclic AMP
Demeclocycline
146
side effects of tetracycline
* phototoxicity * ***pseudotumor cerebri*** (benign intracranial hypertension) * diarrhea (due to gastrointestinal overgrowth by tetracycline-resistant bacteria) * gastric pain (due to irritation of the gastric mucosa) * **discoloration and hypoplasia of teeth** (due to deposition in teeth, primarily occurs in children) can complex with calcium resulting to deposition in bone and bone deformities (primarily occurs in children) * hepatic failure and death (if pregnant)
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* enters the **bacterial cytoplasm through permeases of the inner cell membrane**, where it binds to the **50S** subunit of **assembled ribosome-mRNA complexes** * Here it ***blocks the conjugation of the previously coded aminoacyl-tRNA*** with the presently coded aminoacyl-tRNA, thus leading to the inhibition of protein synthesis
CHLORAMPHENICOL
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Administered orally and/or IV May cross the blood-brain barrier **Inhibits cytochrome-450 isozymes (CYP)**
chloramphenicol
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medical uses of chloramphenicol
* Active **against most gram-negative organisms**, many anaerobes, Clostridia, Chlamydia, Mycoplasma, and Rickettsia * Treatment of **meningitis** due to Haemophilus infection * Treatment of **typhoid fever** due to Salmonella infection
150
Side effects of CHLORAMPHENICOL
* **Hypersensitivity** reactions leading to fever, skin rashes, and/or angioedema * **Diarrhea** (due to gastrointestinal overgrowth by chloramphenicol-resistant bacteria) * **Bone marrow depression** leading to ***pancytopenia*** and death * **Hemolytic anemia** (if glucose-6phosphate dehydrogenase deficiency) * ***Gray baby syndrome*** * Due to the **inadequacy of both cytochrome-450 glucuronic conjugation systems to detoxify the drug** * Due to the inhibition of mitochondrial protein synthesis and following decreased aerobe glycolysis in neonates This can result in **elevated and toxic levels of other drugs metabolized by CYP**
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DRUGS UNDER MACROLIDES
* Erythromycin * Clarithromycin * Azithromycin * Telithromycin
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enter the **bacterial cytoplasm** through **permeases** of the **inner cell membrane, where they bind to the 50S subunit of assembled ribosome-mRNA complexes**
Macrolides
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block the translocation of the ribosome along the mRNA to the next codon, thus leading to the inhibition of protein synthesis
Macrolides
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Inhibition of protein synthesis would normally lead to the death of the bacteria, but due to the inhibition occurring after assembly of the ribosome-mRNA complexes, some bacterial proteins are still being randomly synthesized; thus macrolides are bacteriostatic (but maybe bactericidal in some bacteria, and in high doses) true or false
true
155
resistance for macrolides
Resistance is **plasmid-encoded** and is **prevalent in most strains of staphylococci** and, to some extent, in streptococci. due primarily to **increased active efflux or ribosomal protection by increased methylase production**
156
* is inactivated by stomach acid and is therefore administered as an enteric-coated tablet. * distributes into all body fluids except the brain and CSF
Erythromycin
157
Therapeutic uses of erythromycin
* Erythromycin is **active against gram-positive organisms.** * Useful as a **penicillin substitute** in penicillin-hypersensitive patients. * Most effective drug for ***Legionnaires disease*** (Legionella pneumophila); it is also useful for the treatment of **syphilis**, **M. pneumoniae, corynebacterial infections** (e.g., diphtheria), and **Bordetella pertussis disease** (whooping cough).
158
commonly used for community-acquired “walking” pneumonia and sinusitis.
Azithromycin
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is effective in the **multidrug-regimen treatment of disseminated Mycobacterium avium**–intracellulare complex infections in **AIDS patients.**
Clarithromycin or azithromycin
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Adverse effects of macrolides
* Erythromycin and other macrolides cause **GI dysfunction** (clarithromycin less so) but rarely produce serious adverse effects; the oral form of erythromycin may cause **allergic cholestatic hepatitis,** which is **readily reversible by cessation of the drug.** * Erythromycin has a high incidence of ***thrombophlebitis*** when administered IV. * Erythromycin and clarithromycin inhibit hepatic cytochrome P-450–mediated metabolism of **warfarin, phenytoin, and others, possibly leading to toxic accumulation**. * Azithromycin is devoid of this action.

PHARMA (29 decks)

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