MOA of Trimethoprim-sulfamethoxazole

-TMP/SMX or Co-trimoxazole

Inhibit DNA, RNA and protein production by blocking the folate pathway

Analog to PABA of bacteria

inhibits dihydrofolate reductase

G+ -Step pneumoniae and community acquired MRSA

G- H.flu, M.cat, E. coli, Klebsiella, serratia

Other: GI pathogens, listeria, nocardia, mycobacterium marinum, pneumocystis=fungus

1. Respiratory tract infections: DOC for pneumocystis pneumonia (AIDS)

2. Urinary tract infections: DOC for uncomplicated cystitis

3. GI -traveler diarrhea due to enterotoxigenic E. coli shigellosis

4.Other: B. cepacia, S. maltophelia, serratia, nocardia, Typhoid fever

1. TMP and SMX have same absorption

2. widely distributed including CSF

3. T1/2 8-10 hours (TMP), 10 hours (SMX)

4.Most excreted in urine - adjust for renal disease

Bactrim, Septra

Bactrim DS, Septra DS

15% sulfa allergy

rash, photosensitivity

renal toxicity

leukopenia, neutrapenia

Hyperkalemia-especially with ACEI, ARB, k+ sparing diuretic

Drug interactions with: CYP2C9 inhibitor-warfarin

Streptomycin

kanamycin

gentamicin

tobramycin

amikacin

netilmicin

Inhibit protein synthesis

-bind irreversibly to the 30S bacterial ribosome, interfere with the reading of  the genetic code

Bacteria:

-inactivate by acetylase, adenylase, and phosphorylase enzymes

-dec binding to 30S ribosimal subunit

-dec uptake via porin channels

Good against all gram (-) aerobes, including pseudomonas

especially Tobramycin

Serratia: Gentamicin

Parenteral administration only unless decontaminating the GO tract for surgery

Vd = similar to extracellular fluid

Does not penetrate into CSF

Renal elimination

Ototoxicity (vestibular and cochlear)

Nephrotoxicity (acute tubular necorosis)

Doxycycline

Tetracycline

Minocycline

Demeclocycline

MOA of

Tetracyclines

bacterial mechanism of resistance of

Tetracyclines:

Dec permeability via altered porin channels-prevent bacterial uptake of abx

widespread resistance to Tetracyclines

in animal feed

Spectrum of

Tetracyclines

Broad

Widespread G+ and G- resistance

Anaerobes: +/- B.fragilis; clostridium (non-difficile)

Other: Listeria, mycoplasma, chlamydia, rickettsiaae (rocky mountain), borrelia burgdoferi (lymes)

Pharmokinetics of

Tetracyclines

Absorption dec with milk, antacids, iron supplements, and other ca+2, aluminum or iron substances (DOX and MINO less effected)

All emiminated by renal- except mino and dox

Common uses of

Tetracyclines

1.Respiratory tract infections-

community acquired pneumonia

atypical pneumonia

2. Genital infections: chlamydia trachomatis, NGU, PID, siphylis

3. Systemic infections: rickettsiae, brucellosis, lymes disease, DOX DOC for early lymes, vibrio cholera, tularemia, ehrlichiosis

4. Other: Pasteurella multocida. H. pylori

Adverse effects of

Tetracyclines

Teeth and bones gray-brown to yellow permanent discoloration

GI upset

photosensitivity

diarrhea: tetracycline

Vertigo: mino only

rare hypersensitivity: lupus, hepatic, nephrotoxicity

GI

Erythromycin-derived from streptomyces erythreus

Clarithromycin-synthetic

Azithromycin-semi synthetic

MOA of

Macrolides

Inhibits RNA-dependent protein synthesis :

Bind to 50S ribosomal subunits of susceptible bacteria and induce dissociation of t-RNA from the ribosome during the elongation process

Bacterial mechanism of resistance for

Macrolides

Altered target

Drug efflux

Spectrum of Activity for

Macrolides

G+: moderate to poor

G-: H.flu, poor

Anaerobes: Clostridium (non-dificile)

Other: Mycoplasma pneumonia, legionella pneumonphilia, chlamydia species, bordetella pertussis, syphilis, jejuni, and some rickettsia, ureaplasma urealyticum

Pharmacokinetics of erythromycin (

Macrolide)

Absorption: 25% bioavailable, based destroyed by gastric acid (film-coated)--esters are more stable

food dec absorption

Distribution: Diffuses into most tissues, except CNS and CSF, Crosses placental barrier and breast milk

Metabolism: CYP3A3/4

Elimination: Excreted in bile upto 10x in plasma

t1/2 1.4 hours (serum levels maintained for 6hrs)

Common use of erythromycin

DOC for:

-mycoplasma pneumonia

-Diptheria

-Bordetella pertussis

safe abx

Adverse effects = GI

Rare: hearing loss, transient ventricular tachycardia, QT prolongation

CYP1A2 and 3A3/4 inhibitor

inhibits metabolism of:

theophylline, warfarin, triazolam, carbamazeoine, cyclosporine

Same as erythromycin except;

better H.flu activity

also: MAC, toxoplasma gondii, borrelia burgdorferi, Bebesia microti (Ixodes tick vector)

abs: 50% bioavailable

distribution: penetrates alveolar macrophages and PMNs

met: CYP3A3/4 substrate, metabolized to 14-hydroxy metabolite=active

Elmin: parent and metabolite excreted in urine. adjust dose when CrCl ,30 ml/min

G+, G- (improved H.flu vs. clar and eryth); Anaerobes(peptostreptococcis, non-deficile clostridium)

Other: Mycoplasma pneumonia and chlamydia, STI's, Treponema pallidum

Ab: 40% bioavailable

Dist: high intracellular uptake, high tissue levels

Metabolism: hepatic, t1/2 68hr

Elimination: 50% in feces; no dose modification for renal failure or class A or B cirrhosis

Pediatrics: Pharyngitis/Tonsillitis and Acute otitis medis

Adults: STIs, URI (sinusitis, pharyngitis), community acquired pneumonia

Well tolerated-better than erythromycin

GI problems more common

Drug interactions: none

G+: Staph Fair

Strep: Good

G-: H.flu Azithr>Clarithro>>erythro; bacteriologic failures with azithro for AOM; Neisseria, m. catarrhalis:good, other g- poor

Anaerobes: weak no B. fragilis

Erythro: M.Avium comlex, b.burgdoferi, cryptosporidium

Clarithro: Trep pallidum, Ureaplasma urealyticum, B.burgdoferi

Azithro: M. Avian complex. Entamoeba histolytica

Erythro: No prolonged tissue levels

Clarithro: No IV form, Fed state affects absorption, GI intolerance

Azithro: No Fed state affects absorption, GI intolerance, Drug-drug interactions

Inhibit protein synthesis

-Binds to 50S ribosomes and inhibits protein synthesis

Anaerobes and g(+)

G+= Staph, strep, Pen-rS.pneumoniae

Anaerones= B.frafilis, clostridia, peptostreptococcus, propionobacterium acnes, fusobacterium

Other= parasites, gardnerella, toxoplasmosis, PCP

Abs: 90 absorbed - undergoes first pass

Dis: widely distributed, except for CNS, accumulates in PMNs, abscesses

Met: hepatic metabolism

Elimination: in bile

Diarrhea in 20%

Pseudomembranous colitis

Hepatic toxicity-rare

hypersensitivity-rare

Anaerobes and parasites:

Anaerobes: G- anaerobes and some G+ anaerobes (clostridium)

Other: Various protoza (trichomonas, giardia, entamoeba) H.pylori

tx of serious anaerobic infections in peritineum,liver, skin, CNS, bone and joints, lower resp

Prophylaxis prior to abdominal, gyn, or colorectal surgery

C. Difficile colitis = DOC

Bacterial vaginosis

Hepatic encephalopathy

Recurrent Peptic ulcer disease

Abs: Well absorbed

Dis: Large VD penetrates all tissues, CSF levels = 50%

met: Extensively metabolized

Elimination: 20% excreted unchanged

May accumulate with renal and hepatic dysfunction

Neurological effects: seizures at high doses, peripheral neuropathy

Disulfiram-like effect in persons consuming alcohol

GI upset, metallic taste, dark urine

Flagyl

topical:

metrogel