miscellaneous antibacterials - urinary agents and others (test 3)

urinary agents

• fosfomycin (oral)

• nitrofurantoin (oral)

fosfomycin (oral)

inhibit peptidoglycan biosynthesis

nitrofurantoin (oral)

downregulate nucleic acids and protein synthesis

other miscellaneous

• polymyxins

  • colistimethate (IV, IM, inhaled)

  • polymyxin B (IV)

• mupirocin (nasal ointment)

• bacitracin

  • polymyxin B, bacitracin, neomycin (neosporin) {topical}

polymyxins

• colistimethate (IV, IM, inhaled)

• polymyxin B (IV)

cell membrane disruptors

mupirocin (nasal ointment)

inhibits protein synthesis

bacitracin

• polymyxin B, bacitracin, neomycin (neosporin) {topical}

cell wall synthesis inhibitor

fosfomycin tromethamine

charactistics

• static or cidal?

• used to treat lower _____

• not indicated for _____ infections

• occasionally used for _____ infections

• generally taken _____

• list of essential medicines — important for human medicine

• is it available as a generic?

• how is it made?

• salt prep with ___ or known during medical use as tromethamine, is an organic compund

• cidal

• UTI

• kidney

• prostate

• orally

• yes

• chemically

• tris

fosfomycin

MOA

• inhibits ______ _____, enzyme that catalyzes formation of diphosphate-N-acetylmuramic acid in peptidoglycan biosynthesis

  • inhibits what else?

• phosphoenolpyruvate transferase

  • 1st step in bacterial cell wall formation

fosfomycin

medical use

• _____ bacteria of UTI such as multidrug-resistant Escherichia coli (1^st line)

• _____ bacteria like Enterococcus faecalis (alternate treatment only)

• gram -

• gram +

fosfomycin

• name some side effects

• well tolerate, low incidence of harmful side effects

• D, N, headache, vaginitis

fosfomycin

• DDIs?

antacids and food can decrease absorption

fosfomycin

resistance

• resistance is common under therapy by _____ of enzymes that chemically modify the drug

overexpression

nitrofirantoin (macrobid)

characteristics

• static or cidal?

• not as effective for ____ infections

• how is it taken?

• list of essential medicines

• cidal

• kidney

• orally (tabs, caps)

nitrofirantoin (macrobid)

medical use

• ______ bacteria of UTI such as multidrug-resistant Escherichia coli (1^st line)

• ______ bacteria like Staphylococcus spp. (2^nd or 3^rd line)

• used in _____ ____ ___ to other commonly used agent , such as trimethoprim/sulfamethoxazole and fluoroquinolones

• gram -

• gram +

• bacterial antibiotic resistance

nitrofirantoin (macrobid)

MOA

• it is a _____

• bacterial flavoprotein enzyme “nitrofuran reductase” with (NAD) (nicotinamide adenine dinucleotide) coenzyme activity reduces what?

• prodrug

• nitrofurantoin to active derivatives

nitrofirantoin (macrobid)

MOA

• active derivatives generate superoxide anions (O₂^-) that will react with what?

  • what is the result?

• several bacterial targets ribosomal proteins, DNA, respiration, pyruvate metabolism and other macromolecules within the cell

• decreases synthesis of an damages proteins, DNA, RNA, and cell wall synthesis

nitrofirantoin (macrobid)

resistance

• multiple target sites or mechanism of superoxide anion make it what??

slow for bacteria to become resistant

nitrofirantoin (macrobid)

• name some side effects

• N, headache, flatulence (common)

• GI (D, abdominal pain, C), neurologic (dizziness, drowsiness), respiratory (acute pulmonary hypersensitivity reaction, pulmonary toxicity), others (allergic and dermatologic reactions, fever, chills, discomfort)

nitrofirantoin (macrobid)

• DDIs?

• activity of ntirofurantoin depends on acidic pH

• antacids and fluoroquinolones antagonized — can cause false urine glucose results

nitrofirantoin (macrobid)

• contraindications?

must be avoided by patients with renal failure

cell membrane disruptors (polymyxins)

• typical ionic detergents

forms micelles in water (hydrophobic tails cluster)

• polar outside dissolves micelle in water

polymyxin B

• what type of product is it?

• static or cidal?

• DAB ‘diaminobutyric acid‘ like protonated _____ with + charges at physiological pH

• natural

• cidal

• lysine

polymyxin B

MOA

• cationic detergent — binds to - charged _____ and disrupts what?

• what is it highly selective towards?

• phospholipids in gram - cell membranes; the membrane

• lipopolysaccharide (LPS) on gram - outer membrane

polymyxin B

medical use

• severe hospitalized/resistant ______ infections

• specific pseudomonas ____ infections (topical ophthalmic ointment)

• pseudomonas

• eye

polymyxin B

• name some side effects

neurotoxic and nephrotoxic effects

polymyxin B

• explain the metabolism

• not excreted by kidney

• not applied in kidney infections or UTI

cell membrane disruptors

• constitution of bacterial cell walls

• role of gram - lipopolysaccharides (LPS)

polymyxin B

MOA

• selectivity — binds to what?

• charged s groups in gram - lipopolysaccharides (LPS) on outer membrane

colistin (polymyxin E)

• static or cidal?

MOA

• comprised of what?

• the cationic regions interact with what?

• cidal

• hydrophilic and lipophilic moieties

• phosphate and lipopolysaccharides in the bacterial outer membranes

colistin (polymyxin E)

medical use

• multi drug resistant Klebsiella, Enterobacter, and Serratia (MDR-KES)

• _____/____ resistant (MDR) pseudomonas

• _______ resistant pseudomonas (including UTI)

• inhalation — ___ ___ (pseudomonas respiratory tract infections)

• topical — pseudomonas ____ infections

• penicillin/cephalosporin

• g -

• cystic fibrosis

• ear

colistin (polymyxin E)

• name some side effects

• nephrotoxicity (reversible dose dependent)

• neurotoxicity (dizziness, vertigo, blurred vision)

colistin (polymyxin E)

• DDIs?

• muscle relaxants (increase toxicity)

• amikacin (aminoglycoside) increase neuromuscular blockage

bacitracin

characterics

• ______ antibiotic

• mixture of peptides produced by Bacillus licheniformis bacteria

• static or cidal?

• polypeptide

• both, depending on concentration

bacitracin

MOA

• these peptides disrupt gram + bacteria by doing what?

interfering with cell wall and peptidoglycan synthesis

bacitracin

medical use

• used to treat ____ ____ ____ surface infections

• used in solutions for ______ of wounds

• used IM in highly ____ ____ infections

• mixed flora skin

• sterilization

• resistant gram +

bacitracin

MOA

• inhibits cell wall synthesis by blocking ____ ____ ____ required to trafficking (answer) to cell components

• this prevents ______ monomers from crossing the cytosol through he cytoplasmic membrane to form (answer) polymers and to connect the cell wall

• components manufactured on cytoplasmic membrane and trasported via _____ ____ ____ to gram + cell wall

• phospholipid carrier cycle

• peptidoglycan

• phospholipid carrier cycle

bacitracin

spectrum of activity

• ____ bacteria such as Staphylococcus aureus, Staph. epidermidis,

  Streptococcus pyogenes, and others Strep. pneumoniae (pneumococci),

  and tetanus bacilli (Clostridium tetani)

• OTC medicine can add ______ and _____

• gram +

• polymyxin B and neomycin

bacitracin

• available in generic?

• name some side effects

• yes — for parenteral use can lead to high nephrotoxic effects (when used internally)

• rare — hypersensitivity, allergic, or anaphylactic reactions (esp. in people allergic to neomycin)

mupirocin

characterics

• chemically a ____ ____ (pseudomonic acid)

• list of essential medicines

• available as generic?

• static or cidal?

• 2% ointment, cream, nasal ointment

• brand name = bactroban

• carboxylic acid

• yes

• cidal

mupirocin

• name some side effects

• skin cream — burning, stinging

• nasal ointment — headache, rhinitis, respiratory congestion

mupirocin

MOA

• containing region structurally similar to isoleucine (ILE), it inhibits protein synthesis by what?

binding selectively to the ILE tRNA ligase (responsible to incorporate ILE into proteins)

mupirocin

resistance

• what does plasmid encoding ILE tRNA ligase do?

decrease activity of mupirocin

mupirocin

spectrum and medical use

• _____ spectrum — name them

• isolated/minor ____ infections due to Staph. / Strep. Infections (i.e. impetigo)

• recurrent _____ (primarily Staph. in nasal hair follicles)

• ______ resistant Staph. aureus (MRSA) when present in the nose without symptoms

• narrow

  • gram + aerobes

  • gram - anaerobes

• skin

• furnunculosis

• methicillin