1) Water solubility

2) Low protein binding (more lipophilic drugs tend to be protein-bound)

3) Organic anions (renal secretory clearance by active transport)

4) High doses are well tolerated--this provides favorable concentrations in tissues (though can cause seizure in very rare cases).

5) Though toxicity is low, propensity toward allergy is relatively high due to the foreign chemical structure.

Inhibition of transpeptidase which crosslinks third residue of N-acetylmuramic acid, L-Lysine to the terminal D-alanine residue of an opposite N-acetylmuramic acid.

Destabilizes cell wall which leads to osmotic pressure induced blebbing and eventual cell death.

Penicillin G

and

Penicillin V

ROUTE: G -- parenteral. V -- oral.

USE: 1) Streptococci. Except pneumococcus which should be treated with a 3rd Cephalosporin until sensitivity is established). 2) Neisseria meningitidis. 3) Syphilis. 4) Oral anaerobes. 5) Actinomyces. 6) Clostridial gas gangrene.

Methicillin

Oxacillin

Dicloxacillin

Nafcillin

GEN: Penicillinase-resistant beta-lactams produced in response to Staph. aureas penicillinase.

ROUTE: Oxa -- parenteral. Dicloxa -- oral.

USE: Penicillinase-resistant strains of Staph. aureas. Not a substitute for PenG where PenG can be used--not as effective (i.e. non-penicillinase producting Staph.).

TOX: Higher incidence of allergic interstitial nephritis.

Ampicillin

Amoxicillin

Amino-penicillins.

ROUTE: Amp -- parenteral. Amox -- oral.

USE: Originally added E. coli, Salmonella, Shigella to spectrum, however now many are resistant. 1) Strep. -- particularly enterococci. 2) Mouth anaerobes.

3) Haemophilus/moraxella (70% sensitive). 4. E. coli (however, 50% sensitive).

DISEASES: Good for upper resp. pathogens. Otitis media in children due to pneumococcus resistance to PenG.

Extended-spectrum penicillin (Anti-pseudomonals).

USE: 1) Strep. 2) Oral anaerobes. 3) Haemophilus/moraxella. 4) E. coli (50% resistant). 5) Proteus species. 6) Klebsiella. 7) Serratia. 8) Enterobacter. 9) Pseudomonas.

OTHER: Broadest spectrum of all penicillins when combined with a beta-lactamase inhibitor (i.e. Tazobactam). Zosyn is pip-taz.

Ampicillin/sulbactam

Piperacillin/tazobactam

Amoxicillin/clavulinate

Beta-lactamase inhibitors (suicide inhibitors)

USE: ONLY in combination with aminopenicillins or extended spectrum penicillins. Adds, Staph. aureas, gut anaerobes and all Haemophilus coverage to the above penicillins.

TOX: Immune-mediated thrombocytopenia.

Cefazolin

Cephalexin (keflex)

1st Generation Cephalosporins. Cefazolin -- parenteral; Cephalexin -- oral.

USE: Staph. aureas, Strep. (except enterococci), E. coli, Proteus, Klebsiella, mouth anaerobes. Good gram (+) coverage; modest gram (-) coverage.

NO CNS PENETRATION.

ALLERGY: If penicillin allergy is rash, OK to use cephalosporin. If urticarial/anaphylactic, then no.

2nd Generation Cephalosporin. Both oral and parenteral.

USE: Less Staph. aureas coverage than 1st gen. Same gram (-) coverage (E. coli, Proteus, Klebsiella, mouth anaerobes) but added Haemophilus including penicillinase producing strains. Anaerobes both above and below diaphragm.

Ceftazadime

3rd gen. Cephalosporin. Parenteral.

USE: Less Gram (+) activity than 2nd gen. (Loss of Staph. coverage). Same coverage on Haemophilus. Covers all anaerobes. Broader Gram (-) coverage. ANTI PSEUDOMONAS. EXCELLENT CNS PENETRATION.

3rd gen. Cephalosporin. Parenteral.

USE: Less Gram (+) activity than 2nd gen. Some Staph. coverage; retains pneumococcus activity because mutant PBP does not bind ceftriaxone. Same coverage on Haemophilus. Covers all anaerobes. Broader Gram (-) coverage. NON-ANTI PSEUDOMONAS. EXCELLENT CNS PENETRATION. Ceftriaxone and Vancomycin used for suspected bacterial meningitis (to cover possible pneumococcus resistance).

4th Generation Cephalosporin.

3rd gen. Cephalosporin. Parenteral.

USE: Less Gram (+) activity than 2nd gen. Same coverage on Haemophilus. Covers all anaerobes. Broader Gram (-) coverage. A little better coverage of Enterobacter, Citrobacter, Serratia than ceftazidime and piperacillin. EXCELLENT CNS PENETRATION.

Carbapenem. Parenteral.

USE: Broadest spectrum of all beta-lactams. Does NOT cover MRSA. For use in ICU patients or those with multiple resistant infections.

TOX: Do NOT use in patients with Seizure disorders. Can cause seizure if not renally dosed. Cross allergenic with penicillins maybe.

Monobactam. Parenteral.

USE: Gram (-) bacilli including Pseudomonas. No gram (+); no anaerobes.

TOX: Similar to penicillins. NOT CROSS-ALLERGENIC WITH PENICILLIN.

Glycopeptide.

USE: ONLY Gram (+) aerobes and Gram (+) anaerobes. Treatment of MRSA, coagulase negative Staph. infections and enterococcus infections resistant to aminopenicillins. Also useful orally against metronidazole-resistant C. diff. colitis.

TOX: Red-man syndrome (Flushing, Tachycardia, Hypotension--infuse IV slowly). Ototoxicity, nephrotoxicity, immune-mediated thrombocytopenia.

Phosphonic Acid derivative.

USE: Enterococcal UTIs.

Cyclic lipopeptide.

MECH: Binds to bacterial membranes causing depolarization, loss of membrane potential and cell death.

USE: Gram (+) cocci ONLY. For VRSA.

TOX: Rhabdomyolysis.

Ciprofloxacin

Levofloxacin

IV or oral. 100% bioavailability.

MECH: Inhibition of DNA Gyrase (low conc.) and Topoisomerase 4 (high conc.).

USE: Gram (-) enterobacteriaceae. For UTIs that are resistant to beta lactams and sulfonamides. Levofloxacin has added pneumococcal action but less gram (-) coverage as a result.

TOX: Dose-dependent CNS toxicity (confusion, agitation, dizziness). QTc widening - PVT.

Nitroimidazole. Prodrug.

MECH: Anaerobes use different electron-transport components that donate an electron to metronidazole creating a highly reactive nitro radical killing susceptible pathogens.

USE: Anaerobic and microaerophilic bacteria and parasites. All anaerobic bacteria. Protozoa including amoeba, giardia and trichomonas. Also used in combo for H. pylori.

TOX: Dose-dependent CNS stimulation. Neurotoxic to fetus; NOT good for PREGNANT. NO ALCOHOL --inhibits aldehyde dehydrogenase--builds up acetaldehyde.

Streptomycin

Gentamycin

Tobramycin

Amikacin

Aminoglycosides.

MECH: Binds to 30S subunit of ribosome interfering with initiation of translation. Requires Oxygen for transport into bacterium therefore no action on anaerobes. Work synergistically with beta lactams.

USE: Gram (-) powerhouse Except anaerobes. Effective in sepsis due to rapid bacteriocidal effect, long post-antibiotic effect, poor tissue and CNS penetration (except kidney).

KINETICS: Very water soluble. Short half-life. 100% renal excretion--concentrates in tubular cells so dose carefully according to GFR.

TOX: Dose dependent Ototoxicity and nephrotoxicity. Enhances neuromuscular blockade and apnea--contraindicated in Myesthenia Gravis patients, guillan-barre and ventilator patients OR concominant use with neuromuscular blocking meds.

Tetracycline.

MECH: Reversably binds to 30S ribosomal subunit inhibiting tRNA from binding to the A site.

USE: Intracellular organisms: Mycoplasma, chlamydia, rickettsia. 85-90% effective against pneumococcus. Also re-emerging as MRSA skin infection treatment (85% eff.).

TOX: Skin photosensitivity--may cause burns.

CONTRA: NO PREGNANCY or CHILDREN--deposits on bone and discolors permanent teeth (chelator of minerals).

Lincosamide.

MECH: Binds to 50S ribosomal subunit supressing protein synthesis.

USE: Staph. aureas (85% vs. MRSA; 100% vs. MSSA). Streptococci. Anaerobes (EXCEPT C. Diff). NO GRAM (-) action. Good in bowel perforations (anaerobic infections), aspiration pneumonia, Gram (+) infections where patient is allergic to penicillin.

TOX: Antibiotic related diarrhea and C. Diff pseudomembranous colitis.

Erythromycin

Clarithromycin

Azithromycin

Macrolides.

MECH: Binds to 50S ribosomal subunit inhibiting protein synthesis.

USE: Streptococci, Staph. aureas (85% MRSA), mycoplasma, (also Haemophilus and chlamydia--esp. azithromycin). Alternative for gram (+) coverage in penicillin allergic patients. Azithromycin also has wide tissue distribution and long half life.

TOX: GI distress, n + v. Metabolized in liver. Erythromycin and clarithromycin block certain Cytochromes increasing cyclosporin conc. etc...

Oxazolidinones.

MECH: Inhibition of 50S ribosomal subunit at peptidyl transferase site. Used (along with Daptomycin) against VRSA and Vanco resistant enterococcus.

USE: Marketed for MRSA but as effective as cheaper generics.

TOX: Bone marrow suppression with >2wk use.

Sulfonamide drugs (PABA analogs).

MECH: Inhibition of dihydropteroate synthase preventing the incorporation of dihydropteroic acid into PABA in order for microbes to synthesize Folic Acid. Bacteriostatic.

Trimethoprim = Dihydrofolate reductase inhibitor.

USE: For uncomplicated UTIs. Otitis media in children infected with sensitive Haemophilus or S. pneumonia.

Use 4 drugs for two months until sensitivities are discovered, then drop 2 drugs.

6 month treatment for initial, 18 months for recurrent.

For TB treatment. Prodrug.

MECH: Prodrug activated within bacillus by KatG leading to inhibition of mycolic acid synthesis and cell death.

TOX: Centrolobular hepatitis (jaundice with elevated aminotransferases); neurotoxicity (pyridoxine prevents).

Rifamycin.

MECH: Binds RNA polymerase preventing RNA synthesis.

USE: With Isoniazid for TB therapy.

TOX: Centrolobular hepatitis (high aminotransferases and jaundice); serious flu-like hypersensitivity reactions--especially if used intermittently).

Nicotinamide analog.

MECH: Activated by acidic environment (inside macrophage phagosomes or edges of necrotic granulomas where lactic acid is high); deaminated by mycobacterium nicotinamidase to pyrazinoic acid which is pumped out of the cell where it picks up a proton and diffuses back into cell then targets Fatty Acid Synthase I in mycolic acid synthesis.

USE: For TB therapy.

TOX: Centrolobular hepatitis; increased uric acid levels--->gout.

MECH: Inhibition of arabinosyl transferase involved in cell wall synthesis.

USE: TB infections--most active during growth phase so dropped (along with pyrazinamide) after 2 months.

TOX: Dose-dependent optic neuritis (inability to differentiate red and green); elevated uric acid---> gout.

Gatifloxacin

Temofloxacin

Fluoroquinolones.

USE: Active against resistant MTb for up to 24 months in comotherapy.

TOX: Well-tolerated. Resistance can occur.

Kanamycin

Streptomycin

Amikacin

Aminoglycosides.

USE: For resistant MTb.

TOX: Kanamycin: VERY TOXIC -- neuromuscular blockade, agranulocytosis. Streptomycin: ototoxic>>nephrotoxic. Amikacin: balanced ototoxicity=nephrotoxicity.

NEVER USE AMINOGLYCOSIDES IN COMBINATION!

MECH: Prodrug activated within bacillus by KatG leading to inhibition of enoyl-ACP reductase of fatty synthase II leading to inhibition of mycolic acid synthesis and cell death.

USE: Resistant MTb.

TOX: Neurotoxicity similar to INH---> B6 may help ameliorate.

MECH: Broad spectrum cell-wall synthesis inhibitor where alanine is used.

USE: Resistant MTb.

TOX: Severe CNS toxicity within 2 weeks--may disappear with discontinued use.

MECH: Specific inh. of MTb dihydropteroate sythase (sulfonamides can't act on MTb).

USE: Resistant MTb.

TOX: GI probs, Allergic phenomena, blood dyscrasias.

MECH: Unclear. Cross-resistance with aminoglycosides.

USE: Resistant MTb.

TOX: Significant--tinnitus, hearing loss, renal faliure, blood dyscrasia.

Acyclovir

Valacyclovir

Famcyclovir

Purine analogs. Valacyclovir is a prodrug of acyclovir.

MECH: DNA synth. inhibitors.

USE: HSV, VZV.

TOX: LOW. VZV requires higher dosage. CNS effects can occur if not renally dosed in presence of renal disease.

MECH: Pyramidine analog inhibitor of DNA synth.

USE: More active against VZV. Variable effects against HSV.

MECH: Non-nucleoside analogue, pyrophosphate congener. IV only due to high ionization--renal excr.

USE: Broad-spectrum: Broad spectrum. DNA viruses (HSV, VZV, CMV) and RNA viruses including HIV. Used in acyclovir failures.

TOX: Dose-dep. renal and CNS toxicity.

MECH: Guanine analogue

USE: CMV infections in immunocompromised (transplant and HIV--retinitis tmt. or prophylaxis).

TOX: Neutropenia, thrombocytopenia--dose dependent. Also, CNS effects.

MECH: Immunomodulator enhances interferon production.

USE: Topical treatment for HPV.

MECH: Cytosine analogue inhibits DNA production.

USE: HPV and other DNA viruses. There is a topical available.

Oseltamivir (Tamiflu)

Zanumavir

Peramivir

Oseltimavir is oral; zanumavir is inhalational; peramivir is IV. Use against RNA viruses.

MECH: Neuramidinase inhibition prevents release of viruses from host cells. Neuramidinase is on influenza A and B.

USE: Treatment of influenza A, B and H1N1. Prophylaxis in high risk populations. Treatment within 1-2 days reduces length of symptoms and decreases viral shedding (decr. transmission).

TOX: Neuropsychiatric toxicity.

Nevirapine (NVP)

Delavirdine (DLV)

Efavirenz (EFV)

Etravirine

Non-nucleoside Reverse Transcriptase Inhibitors

MECH: Binds allosterically to Reverse Transcriptase, inhibiting DNA synthesis.

USE: HIV-1 only. (if intolerant to protease inhibitors, these may take place).

TOX: Skin rashes. Affect Cytochrome P450 metabolism. Resistance is a concern.

Zidovudine (AZT)

Didanosine (DDI)

Stavudine (D4T)

Lamivudine (3TC)

Nucleoside Reverse Transcriptase inhibitors. Components of HAART therapy.

TOX: Zidovudine--granulocytopenia, n + v, anemia. Didanosine--Pancreatitis, peripheral neuritis. Stavudine--Periph. neuropathy, pancreatitis. Lamivudine--headache, n+v, rash, neutropenia, pancreatitis.

MECH: Protease inhibitors. HIV protease cleaves polyprotein into active components of HIV virion. Without it, the HIV virus is non-virulent.

USE: HIV--very active.

TOX: Poor oral bioavailability but well-tolerated. Lipodystrophy--atrophy of subcutaneous fat. Also hyperglycemia, hyperlipidemia and Cushing's-like fat redistribution.

MECH: Protease inhibitors. HIV protease cleaves polyprotein into active components of HIV virion. Without it, the HIV virus is non-virulent.

USE: HIV

TOX: More toxic than saquinavir--peripheral neuropathy, liver enzyme elevation. ALSO, potent cytochrome inhibitor boosts other protease inhibitors. Lipodystrophy--atrophy of subcutaneous fat. Also hyperglycemia, hyperlipidemia and Cushing's-like fat redistribution.

MECH: Protease inhibitors. HIV protease cleaves polyprotein into active components of HIV virion. Without it, the HIV virus is non-virulent.

USE: HIV.

TOX: Slow development of resistance but once this occurs, the strain is resistant to both saquinavir and ritonavir. Nephrolithiasis--hydrate patients! Lipodystrophy--atrophy of subcutaneous fat. Also hyperglycemia, hyperlipidemia and Cushing's-like fat redistribution.

MECH: incorporates into HIV gp41 causing a conformational change inhibiting the virus' ability to bind to the CD4+ T-cells.

USE: HIV-resistant strains only.

MECH: Binds T-cell CCR5 co-receptor prevents HIV gp120 binding and entry into lymphocyte.

TOX: Involves CD4+ membrane CCR5 receptor so may inhibit immunologic attack on microbes that are controlled by cell-mediated immunity (TB, fungi).

Interferon and Ribavirin (Purine nucleoside analog. Broad spectrum) together but non-selective.

Add Boceprevir or Teleprevir - these are HCV-specific protease inhibitors that act directly. Triple therapy.

USE: Life-threatening systemic mycoses. Occasionally used in combo (w/ flucytosine) for immunocompromised hosts with severe fungal infections.

TOX: Acute fever, chills, hypotension potential. Renal impairment almost always--and may be only partially reversable; Mg and K wasting; renal tubular acidosis. Normocytic anemia.

An imidazole.

USE: Topical for candidiasis and dermatophytes. Troche (losenge-like) dosage effective in thrush.

An imidazole.

USE: Topical for candidiasis and dermatophytes. Troche (losenge-like) dosage effective in thrush.

Triazole.

USE: Dermatophytes. Deep and superficial fungal infections. Oral administration when imidazoles fail.

TOX: Rarely hepatotoxicity. Inhibits Cytochromes.

Triazole.

USE: Dermatophytes. Onchymycosis. Oral administration when imidazoles fail.

TOX: Rarely hepatotoxicity. Inhibits Cytochromes.

Triazole.

USE: Dermatophytes. Oral administration when imidazoles fail.

TOX: Rarely hepatotoxicity. Inhibits Cytochromes.

Allylamine

USE: Topical dermatophytes that are refractory to imidazoles -- not so much candida. Also oral formulation for onchymycoses.

TOX: Hepatitis, rarely.

Allylamine

USE: Topical dermatophytes that are refractory to imidazoles -- not so much candida.

TOX: Hepatitis, rarely.

Allylamine

USE: Topical dermatophytes that are refractory to imidazoles -- not so much candida. Weak agent.

TOX: Hepatitis, rarely.

Echinocandin.

MECH: Inhibition of fungal wall synthesis--inhibits glucan synthase complex.

USE: Life-threatening fungal infections unresponsive to older agents--especially candida and aspergillus.

TOX: Less than amphoteracin B.