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56 Cards in this Set

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Name the sub groups of bacterial protein synthesis inhibitors
*Streptogramins and Oxazolidinones
*Macrolides
*Lincosamides
*Aminoglycosides
*Tetracyclines
*Chloramphenicol
Bacterial Protein Synthesis Inhibitors: Streptogramins and Oxazolidinones
Streptogramin-Quinupristin and Dalfopristin- Formulated and used in combination, Q/D (Synercid).
Linezolid (Zyvox) is an oxazoladinone derivative
MOA of bacterial protein synthesis inhibitors
Inhibit bacterial protein synthesis. Bind to the 23S RNA of 50S ribosomal subunit of bacte
MOA of Quinupristin / Dalfopristin
inhibits peptidyl transferase, thereby blocking the elongation of the peptide chain. Dalfopristin acts at the early phase of protein synthesis, quinupristin acts at the late phase.
MOA of Linezolid
binds to the 23S RNA on the 50S subunit and inhibits the formation of ribosome complex and initiation of protein synthesis.
Antimicrobial activity of bacterial protein synthesis inhibitors
Narrow-spectrum: active against gram-(+), some gram-(-) bacteria, anaerobes, and chlamydiae
Q/D: also active against Vancomycin-resistant Enterococcus (VRE) faecium, Methicillin-resistant Staphylococcus Aureus (MRSA), Penicillin-resistant Streptococcus Pneumoniae (PRSP), & S Pyogenes
Bactericidal: when Linezolid & Q/D are combined.
Bacteriostatic: Q/D
Antimicrobial activity of linezolid
Linezolid represents a new class of antimicrobials, highly active
against susceptible and resistant gram-(+) bacteria, including: VRE, MRSA,
Penicillin-Resistant Streptococcus Pneumoniae (PRSP), & Streptococcus Pyogenes.
Primarily bacteriostatic agent except for streptococci, for which is bactericidal
Not useful against gram-(-) species.
Pharmokinetics and adverse effects of linezolid and D/Q
D/Q present poor oral absorption; mostly metabolized in the liver and
eliminated in feces. Causes pain and frequent thrombophlebitis at injection site; may produce arthralgia and myalgia. Linezolid: good oral absorption, also used IV, oxidized (metabolized by non-P450 enzymes), excreted in urine and feces.
GI distress: diarrhea, nausea, vomiting, thrombocytopenia (chronic use), inhibits monoamine oxidase activity
Drug interactions with linezolid and D/Q
Q/D increases the levels of warfarin, diazepam, non-nucleoside. reverse transcriptase inhibitors, and cyclosporine. Linezolid augments the action of SSRI, other antidepressants, as well as increases action of pseudoephedrine &
phenylpropanolamine
CNS psychotic effects at higher doses
Name the Bacterial Protein Synthesis Inhibitors: Macrolides
Erythromycin
Clarithromycin
Azithromycin
Also the KETOLIDES
MOA of macrolides (bacterial protein synthesis inhibitors)
MA: Bind to the 50S ribosomal subunit and block the aminoacyl translocation and formation of translation complex.
Antimicrobial activity of macrolides
Bacteriostatic, but bactericidal at high doses; Limited
coverage for gram-(+) and (-) bacteria, & anaerobes.
Also: Chlamydia, Mycoplasma pneumoniae, Mycobacterium


Hospital / community-acquired pneumonia.
Mycobacterium avium complex (MAC) pneumonia
Legionnaire’s disease
Alternative to penicillins (patients allergic to penicillin)
PK of macrolides
Good oral absorption (except erythromycin-acid sensitive).

Extensive distribution (except the brain)
Erythromycin, clarithromycin: liver metabolized
Azithromycin is eliminated unchanged via kidney & feces

GI distress: particularly by erythromycin
Cholestatic hepatitis with erythromycin estolate (causing failure of bile flow)
Drug interactions with macrolides
Erythromycin and clarithromycin increase serum levels of:
Theophylline (bronchodilator)
Warfarin (oral anticoagulant)
Cyclosporine (immunosuppressive agent)
Statins (cholesterol synthesis inhibitors)
Astemizole (histamine H1 receptor inhibitor)
Various anticonvulsants

Methylation or mutation of binding site leads to Macrolide-Lincosamide-Streptogramin B resistance
Reduced access to cells
Hydrolyzed by esterases
Telithromycin
Telithromycin. Effective against many traditional
macrolide-resistant strains. Structural modification makes
them poor substrates for efflux pump-mediated resistance.
Bind to ribosomes of some bacterial species with higher
affinity than macrolides
Taken orally, good tissue and intracellular penetration

Use for respiratory tract infection, including community-
acquired bacterial pneumonia and S pharyngitis
Reversible inhibits CYP3A4 enzyme system, may slightly
prolong QTc interval. Rare cases of hepatitis reported
Name Bacterial Protein Synthesis Inhibitors: Lincosamides
clindamyacin
MOA of clinda
Bind to the 23S RNA of 50S ribosomal subunit and inhibit the aminoacyl translocation and formation of initiation complex (similar to streptogramins/oxazolidenones and macrolides)
Clinical uses of clinda
Narrow spectrum: active against some gram-(+), most anaerobes, and some chlamydia, but not gram-(-) bacteria. Bacteriostatic. Treatment of penicillin-resistant gram-(+) infections and in patients allergic to penicillins.
Streptococci, staphylococci, and pneumococci are inhibited by clindamycin
Anaerobic infections. Polymicrobial peritoneal infections.

Hospital-acquired pneumonia (combined with G3 or G4 cephalosporins).
PK, adverse reactions, and drug interactions with clinda
Methylation or mutation of the binding site causes MLS-type B resistance. Reduced drug access to bacteria. Good oral absorption.
Extensive distribution (except into the brain).
Metabolized in the liver, eliminated in feces and bv kidneys. GI distress, Rash, Superinfections, Hepatotoxicity, Neutropenia

Respiratory paralysis could be induced with use of muscle relaxants: baclofen, diazepam, atracurium
MOA of aminoglycosides
Aminoglycosides have two (or more) aminosugars linked to an hexose ring (or aminocyclitol) via glycosidic links. Bind 16S RNA of the 30S ribosomal subunit and inhibit protein synthesis
Name aminoglycosides
Streptomycin: the 1st to be isolated, derived from
Streptomyces griseus, Neomycin, Gentamicin, Tobramycin, Kanamycin, Amikacin
Clinical uses of aminoglycosides
Narrow-spectrum, mostly Bactericidal
Active against gram-(-) and limited gram-(+); Some
are effective against Pseudomonas aeruginosa.
Not effective against anaerobes

Infective bacterial endocarditis
Septicemia, Hospital-acquired pneumonia
Chronic urinary tract infections
Resistance and PK of aminoglycosides
Mutation at the ribosome binding site. Enzymatic Inactivation: by acetylation, adenylation or Poor oral absorption.
Variable distribution in body; do not enter the brain
Reduced activity in low pH, hyperosmolarity, & anaerobiosis. Unmetabolized and eliminated by the kidneys.
Adverse reactions and drug interactions with aminoglycosides
Ototoxicity, Nephrotoxicity, Neuromuscular blockade
Increased ototoxicity with loop diuretics, vancomycin
Increased nephrotoxicity with vancomycin, cyclosporin,
NSAIDs, radiographic contrast (iodine-based) agents. Respiratory depression with neuromuscular blockers. In vitro mixing with penicillins reduces the activity of both
Name some tetracyclines
Tetracycline, Doxycycline, Minocycline
Tigecycline (Glycycycline)

Some isolated from certain species of Streptomyces. Others are semisynthetic.
MOA of tetracyclines
Bind 16S to the 30S ribosomal subunit and block the docking of tRNA on the ribosomes (similar to aminoglycosides)
Clinical uses of tetracyclines
Broad-spectrum, Bacteriostatic
Effective against many gram-(+) and -(-) bacteria, including,
anaerobes, chlamydia, mycoplasmas, some protozoa

Use doxycycline unless otherwise noted: Chlamydial
infections with gonorrhea, Mycoplasma pneumoniae

Alternatives for (partial list):
Hospital-acquired pneumonia
Ulcers, Bronchitis, Syphilis, Cholera, Tularemia, Plague & anthrax.
Tigecycline
Tetracycline derivative, the first glycylcycline

New IV broad spectrum antibiotic with activity against many drug-resistant organisms.

Approved for treatment of complicated skin/skin-structure infections and intra-abdominal infections with resistant organisms (but not Pseudomonas), particularly in patients who cannot tolerate other drugs
Resistance and PK of tetracyclines
Enzymatic inactivation by phosphorylation, adenylation or acetylation. Reduced permeability into the cells. Ribosome protecting proteins mutation. Efflux pumping

Variable oral absorption, reduced by food, dairy, aluminum hydroxide gels, cations, and alkaline medium
Extensive distribution in the body except the brain
Metabolized in the liver
Eliminated by the kidneys (doxy~ is eliminated in feces).
Tetracyclines
Incorporates into teeth and bones (not given to children ≤8)-yellowish color
Phototoxicity, GI distress, oto-, hepato-, and nephrotoxicity. Superinfections. Serum levels of doxycycline is reduced by some anticonvulsants and barbiturates.
May cause increase digoxin toxicity

Contraindications: Pregnancy, renal or liver impairment or failure, children under 8 years of age
Chloramphenicol MOA
Binds to the 50S ribosomal subunit A site (similar to macrolides and clindamycin), preventing the docking of aminoacyl tRNA.
Binds to mitochondrial ribosomes inhibing the activity of peptidyl transferase, causing side-effects
Clinical uses of Chloramphenico
Broad-spectrum: Bacteriostatic: aerobic and anaerobic
gram-(+) and -(-) bacteria. Bactericidal for some gram-(-)
bacteria, etc
Rarely used: potential toxicity, bacterial resistance,
availability of effective alternatives; may be
considered e.g., typhus and Rocky Mountain spotted fever
Alternative to a B-lactam antibiotic in patients showing a
major hypersensitivity reaction to penicillin. Topical for eye
infections-penetration of ocular tissues and aqueous humor
Name two classes of Folic Acid Metabolism Inhibitors
Sulfonamides, Trimethoprim
MOA and chemical structure of sulfonamides
Sulfadiazine, Sulfamethoxazole, Sulfasalazine. The “Sulfa drugs” are structurally related
to para-aminobenzoic acid (PABA). Competitively inhibit folic acid production by suppressing the activity of dehydropteroate synthase

Inhibition of tetrahydrofolate synthesis interrupts various metabolic reactions.
Antimicrobial activity and PK of sulfonamides
Broad-spectrum, Bacteriostatic
Gram-(+) streptococci and pneumococci, Gram-(-)
meningococci and gonococci, Gram-(-) bacilli (E. coli and
shigellae) and more
Active against chlamydia and some protozoa. Stimulate
Rickettsiae. Largely replaced by less toxic, more effective agents. However,
Trimethroprim/sulfamethoxazole combo has increased their use for the prophylaxis and treatment of specific microbial infections. Good oral absorption, extensive distribution (body and brain), inactivated by acetylation in the liver, eliminated by the kidneys, except sulfasalazine
Clinical uses and resistance to sulfonamides
Enterocolitis: sulfasalazine
Burns: silver sulfadiazine
Ocular infections
Toxoplasmosis: sulfadiazine and pyrimethamine.
Sulfamethoxazole can be formulated with phenazopyridine , an analgesic, to treat urinary distress in UTIs

Overproduction of PABA (to compete with sulfonamides)
Reduced affinity of dehydropteroate synthase for the sulfa drugs.
Natural resistance if organisms import folic acid.
Adverse reactions and drug interactions with sulfonamides
Crystalluria, Hematopoeitic toxicities, Photosensitivity, Skin
Rashes, Exfoliative dermatitis, GI distress
Stevens-Johnson syndrome (skin and mucous membrane eruption), Kernicterus.
Increase serum levels of oral anticoagulants sulfonylureas, and hydantoin anticonvulsants. Avoid use with methenamine (UTI) since it forms formaldehyde that condenses with sulfonamides
MOA of Trimethoprim / Sulfamethoxazole
Trimethoprim is used in combination with sulfamethoxazole
because the two drugs markedly potentiate each other.

Trimethoprim inhibits dihydrofolate reductase, while sulfamethoxazole inhibits dehydropteroate synthases, leading to an enhanced inhibition in THF synthesis.
Antimicrobial activity of Trimethoprim
Broad spectrum, Synergism with a sulfonamide
(bactericidal), but bacteriostatic if used alone.
Active against gram-(+), gram-(-), but not anaerobes. Also active to chlamydia. Prevent recurrent UTI urinary track infections, treat
upper respiratory infections, bronchitis. Mutations of dihydrofolate reductase.Natural resistance if organism imports folic acid. Metabolic bypass
Clinical uses of Trimethoprim
Good oral absorption.
Extensive distribution, including the brain.
Inactivated by oxidation and conjugation. Excreted mostly by the kidney, some in feces. Prevent recurrent UTI urinary track infections, treat
upper respiratory infections, bronchitis. Mutations of dihydrofolate reductase. Natural resistance if organism imports folic acid, Metabolic bypass
DNA Replication and Transcription Inhibitors: Fluoroquinolones. Name some
Fluoride derivatives of nalidixic acid. Large number, including
Ciprofloxacin
LevofloxaciN All have fluorinated R6 (-F)
MOA of fluoroquinolones
Block bacterial DNA synthesis (transcription & replication) by inhibiting α-subunit of DNA gyrase (topoisomerase II) and topoisomerase IV (separating DNA strands). The two strands of double-helical DNA must be separated to permit DNA duplication or transcription
Antimicrobial activity of fluoroquinolones
BROAD-SPECTRUM. BACTERICIDAL
EFFECTIVE AGAINST GRAM-(+) AND (-), LIMITED
ACTIVITY AGAINST ANAEROBES
ONLY CIPROFLOXACIN AND LEVOFLUOXACIN ARE
ACTIVE AGAINST PSEUDOMONA AEUROGINOSA.
Also effective against CHLAMYDIAE MYCOPLASMA
Clinical uses and resistance of fluoroquinolones
Genital (acute and chronic UTIs; Gonorrhea), GI, bone,
joint and complicated skin infections.
Conjunctivitis: ciprofloxacin ophthalmic solution
Anthrax: ciprofloxacin is FDA approved to treat and
protect people who have been exposed to anthrax spores
Different fluoroquinolones show specific pharmacological
profile (antibacterial effects)
Mutation at quinolone binding site. Reduced access-reduced porin number. Drug efflux
DNA Replication and Transcription Inhibitors: Fluoroquinolones. Name some
Fluoride derivatives of nalidixic acid. Large number, including
Ciprofloxacin
LevofloxaciN All have fluorinated R6 (-F)
MOA of fluoroquinolones
Block bacterial DNA synthesis (transcription & replication) by inhibiting α-subunit of DNA gyrase (topoisomerase II) and topoisomerase IV (separating DNA strands). The two strands of double-helical DNA must be separated to permit DNA duplication or transcription
Antimicrobial activity of fluoroquinolones
BROAD-SPECTRUM. BACTERICIDAL
EFFECTIVE AGAINST GRAM-(+) AND (-), LIMITED
ACTIVITY AGAINST ANAEROBES
ONLY CIPROFLOXACIN AND LEVOFLUOXACIN ARE
ACTIVE AGAINST PSEUDOMONA AEUROGINOSA.
Also effective against CHLAMYDIAE MYCOPLASMA
Clinical uses and resistance of fluoroquinolones
Genital (acute and chronic UTIs; Gonorrhea), GI, bone,
joint and complicated skin infections.
Conjunctivitis: ciprofloxacin ophthalmic solution
Anthrax: ciprofloxacin is FDA approved to treat and
protect people who have been exposed to anthrax spores
Different fluoroquinolones show specific pharmacological
profile (antibacterial effects)
Mutation at quinolone binding site. Reduced access-reduced porin number. Drug efflux
Adverse reactions of fluoroquinolones
Generally well tolerated. May cause GI distress, headache,
dizziness, insomnia, skin rush; damage growing cartilage. They are not usually suggested for children younger than
18-yr-old (cartilage damage) & contraindicated during
pregnancy or patients allergic to other quinolones.

and cause arthralgia
PK and drug interacations with fluoroquinolones
Generally good oral absorption and extensive body
distribution (except the brain), but enoxacin penetrates into
the CNS. Mostly partially metabolized and eliminated via the kidneys (some exceptions).
Cause cardiac arrhythmias when used with some anti-
arrhythmic agents. Generally, there is an increased chance of seizures when
used with NSAIDS. Decreased absorption with sucralfate, cations, antacids, dairy and citric acid
Name UTI bacteriostatics and other antibiotics
1. Nitrofurantoin
Acute (and chronic) urinary tract infection

2. Methenamine
UTIs prophylaxis but not as a primary agent for treatment

3. Metronidazole: vaginitis and other bacterial infections

4. Mupirocin: Used topically for staphylococci-caused impetigo. May cause local itching, rash contact dermatitis……..

5. Polymyxins: Because of toxicity use restricted to topical therapy of resistant gram-negative infections
MOA of Nitrofuranton
Mechanism of Action and Antimicrobial Activity
Bacteria reduce Nitrofurantoin more easily than mammalian
cells and reduced drug products damage bacterial DNA

Bacteriostatic, active against E.coli and enterococci, but
not proteus, Pseudomonas and Enterobacters.
Nitrofuranton pharm phacts
Clinical Uses: primarily to treat UTIs, also prophylaxis for recurrent UTIs.
Pharmacokinetics: good oral absorption; partially eliminated by the kidneys.
Adverse Reactions: GI distress, anorexia, hemolytic anemia, neuropathies, renal failure. Resistance: Inability to reduce the drug nitrogen in
the presence of oxygen. Susceptible bacteria rarely
become resistant.
MOA and clinical use of Methenamine
Mechanism of Action and Antimicrobial Activity
Antiseptic converted to formaldehyde in water and low urinary pH; nearly all bacteria are sensitive.

Clinical Uses: prophylactic treatment for recurrent UTI, formulated with mandelate or hippurate to increase effectiveness.
Methenamine pharm phun phacts
Pharmacokinetics
Good oral absorption, concentrated in acidic compartments (e.g., in the urinary tract, bladder, and gastric juices).
Adverse Reactions: GI distress; frequency of micturition, albuminuria, hematuria and rashes
Drug Interactions:
Form insoluble compound with sulfa drugs
Resistance: Proteus that raise pH in urine are resistant
Contraindications: Hepatic disease since ammonia is produced
Flagyl MOA and clinical uses
MA and Antimicrobial Activity:
Anti-protozoal drug, with potent activity against
anaerobes (e.g., trichomonas). Inhibits DNA synthesis

Clinical Uses: vaginitis (trichomonas and bacterial vaginosis),
amebiasis (intestinal, amebic dysentery; hepatic,
abscesses), & giardiasis (giardia, diarrhea).