-inhibit transpeptidation enzymes involved in cell wall synthesis

-active against gram positive and gram negative

-B lactam ring structure inactivated by B-lactamases (penicillinases)

-cell wall synthesis inhibitors

-inhibit the transpeptidation enzymes involved in cell wall synthesis

-active against gram positive and gram negative

-have a B lactam ring structure that is inactivated by some B lactamases

-frequently used to treat patients allergic to penicillins

-inhibit transpeptidation enzymes involved in cell wall synthesis

-B-lactam ring fused to a 5 carbon ring 

-resistant to B lactamases

-aminoglycosides, macrolides, lincomycins, and tetracyclines

-known as broad-spectrum antibiotics

-require bacterial growth to be effective

-include streptomycin, neomycin, kanamycin, and gentamicin

-bactericidal for gram negative bacteria

-bind to 30S ribosomal subunit

-Require O₂ for uptake, not active against anaerobes or intracellular bacteria

-may irreversibily block initiation of translation or cause mRNA misreading

-narrow effective concentration range, Nephrotoxicity and 8th cranial nerve damage (hearing loss/ Ototoxicity especially wen used with loop diuretics).  Teratogen.

MAO: Inhibits 50S peptidyltransferase activity (peptide bond formation). Bacteriostatic

Use:  meningitis (H. influenzae, N. meningitidis, S. pneumoniae)  Conservative use due to toxicities. 

Toxicity:  anemia (dose dependent), aplastic anemia (dose independant), gray baby syndrome (in premature infants because they lack liver UDP-glucuronyl transferase).

Griseofulvin

MOA:  Interferes with microtubule function; disrupts mitosis.  Deposits in keratin-containing tissues (nails)

Use:  Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm)

Toxicity: teratogenic, carcinogenic, confusion, headaches, increases/induces P-450 and warfarin metabolism

-include erythromycin, azithromycin, clarithromycin

Macrolides

MOA

Use

MOA:  inhibit protein synthesis by blocking translocation, bind to 23S rRNA of the 50S ribosomal subunit

-Bacteriostatic

USE:  URI, pneumonias, STD (gram positive cocci), streptococcal infections in pts allergic to penicillin. Used to treat Mycoplasma, Legionella, Chlamydia, Neisseria.

Macrolides

Toxicity

Toxicity:  GI discomfort (most common cause of noncompliance), acute cholestatic hepatitis, eosinophilia, skin rashes.  

-Increase serum concentrations of theophyllines, oral anticoagulants

MAO:  Block peptide bond formation at 50S ribosomal subunit.  Bacteriostatic

USE:  Treat anaerobic infections above the diaphragm (Bacteroides fragilis, Clostridium perfringes)

Toxicity:  Pseudomembranous colitis (C. difficile overgrowth), fever, diarrhea

MOA:  Viral DNA polymerase inhibitor that binds to the pyrophosphate-binding site of the enzyme.  Does not require activation by viral kinase.

Use:  CMV retinitis in immunocompromised patients when Ganciclovir fails, Acyclovir-resistant HSV.

Toxicity:  Nephrotoxicity

Mech of Resistance:  Mutated DNA polymerase

Aminoglycosides and tetracyclines

Aminoglycosides (gentamicin, neomycin, amikacin, tobramycin, streptomycin  Mean GNATS canNOT kill anaerobes)

Tetracyclines (tetracycline, doxycycline, demeclocycline)

Polymyxins

MOA: bind to cell membranes of bacteria and disrupt their osmotic properties.  Are cationic, basic proteins that act like detergents

Use: Resistant gram-negative infections

Toxicity: Neurotoxicity, acute renal tubular necrosis

MOA: Inhibits DNA- dependent RNA polymerase

Use:  Mycobacterium tuberculosis; delays resistance to dapsone when used for leprosy.  Used for meningococcal prophylaxis and chemoprophylaxis in context of children with Haemophilus influenzae type B

Toxicity:  minor hepatotoxicity and drug interactions. Increase P-450.  Orange body fluids (nonhazardous)

Erythromycin, Clindamycin, Sulfamethoxazole, Trimethoprim, Tetracyclines, Chloramphenicol

Stop bacterial growth

ECSTaTiC about bacteriostatics

Vancomycin, Fluoroquinolones, Penicillin, Aminoglycosides, Cephalosporins, Metronidazole

Very Finely Proficient At Cell Murder

MOA:  Bind penicillin binding proteins, block transpeptidase cross-linking of cell wall, activate autolytic enzymes

Use:  Bactericidal for gram positive cocci, gram positive rods, gram negative cocci, and spirochetes.  Not penicillinase resistant

Toxicity:  Hypersensitivity reactions, hemolytic anemia

Methicillin, Nafcillin, Dicloxacillin 

(penicillinase-resistant penicillins)

MOA:  Bind penicillin binding proteins, block transpeptidase cross-linking of cell wall, activate autolytic enzymes.  Pencillinase resistant b/c of bulkier R group.

Use:  S. aureus (except MRSA which is resistant b/c of altered penicillin-binding protein target site)

Toxicity:  Hypersensitivity reactions, methicillin - interstitial nephritis

MOA:  Bind penicillin binding proteins, block transpeptidase cross-linking of cell wall, activate autolytic enzymes.  Wider spectrum than penicillin. Pencillinase sensitive.

Use:  Extended spectrum penicillin - certain gram positive bacteria and gram negative rods (H. influenzae, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, enterococci)

Toxicity: Hypersensitive reactions, ampicillin rash; pseudomembranous colitis.

(antipseudomonals)

MOA:  Bind penicillin binding proteins, block transpeptidase cross-linking of cell wall, activate autolytic enzymes.  Extended spectrum

USE:  Pseudomonas species and gram negative rods; penicillanse susceptible, use with clavulanic

Toxicity: Hypersensitivity reactions

Cefazolin and Cephalexin

MOA:  B lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.  Bactericidal

USE:  gram positive cocci, Proteus mirabilis, E.coli, Klebsiella pneumoniae

Toxicity:  Hypersensitivity reactions, cross hypersensitivity with penicillins in 5-10% people, nephrotoxicity of aminoglycosides, disulfiram like reaction with ethanol

CEPHALOSPORINS

2ND GENERATION

Cefoxitin, Cefaclor, Cefuroxime

MAO: B lactam drugs that inhibit cell wall synthesisi but are less susceptible to penicillinases.  Bactericidal

USE: Gram positive cocci, H. influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E.coli, Klebsiella pneumoniae, Serratia marcescens

TOXICITY:  Hypersensitivity reactions, cross hypersensitivity with penicillins in 5-10% people, nephrotoxicity of aminoglycosides, disulfiram like reaction with ethanol

Cephalosporins

3rd generation

Ceftriaxone, Cefotaxime, Ceftazidime

MOA: B lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases.  Bactericidal

USE: Serious gram-negative infections resistant to other B lactams, meningitis.  Ceftazidime for Pseudomonas. Ceftriaxone for gonorrhea

TOXICITY: Hypersensitivity reactions, cross hypersensitivity with penicillins in 5-10% people, nephrotoxicity of aminoglycosides, disulfiram like reaction with ethanol

MOA:  A monobactam resistant to B-lactamases.  Inhibits cell wall synthesis (binds to PBP3).  Synergistic with aminoglycosides

Use:  gram-negative rods:  Klebsiella species, Pseudomonas species, Serratia species.  No activity against gram positives or anaerobes

Toxicity:  occasional GI upset

MOA:  Imipenem is a broad-spectrum, B lactamase resistant carbapenem.  always given with cilastatin (inhibitor of renal dihydropeptidase I) to decrease inactivation in renal tubules

Use:  Gram positive cocci, gram negative rods, and anaerobes.  Drug of choice for Enterobacter. Limit use to life threatening infections b/c of significant side effects. Meropenem has reduced risk of seizures and is stable to dihydropeptidase I

Toxicity:  GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels.

Vancomycin

MOA: Inhibits cell wall mucopeptide formation by binding D-ala D-ala portion of cell wall precursors.  Bactericidal.  Resistance occurs with amino acid change of D-ala D-ala to D-ala  D-lac

Use:  serious gram positive multidrug resistant organisms including S. aureus, S. epidermidis, and Clostridium difficile.

Toxicity:   Nephrotoxicity, Ototoxicity, Thromboplebitis, diffuse flushing ("red man syndrome"  prevent by pretreatment with antihistamines and slow infusion rate)  Well-tolerated in general.

Isoniazid (INH)

MOA:  decreases synthesis of mycolic acids

Use: Mycobacterium tuberculosis.  Only agent used as solo prophylaxis against TB

Tox: Neurotoxicity, hepatotoxicity.  Pyridoxine (Vit 6) supplementation can prevent neurotoxicity.

Metronidazole- Bactericidal and antiprotozoal.

MOA: forms toxic metabolites in the bacterial cell that damage DNA.  

Use:  Treats Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (bacteroides, clostridium).  Used with bismuth and amoxicillin or tetracycline for "triple therapy" against H. Pylori.  GET GAP on the Metro

Used for Anaerobic infection below the diaphragm & Clindamycin for anaerobes above the diaphragm

Toxicity: Disulfiram like reaction with alcohol (also seen in Cephalosporins with methylthiotetraole group like cefamandole), headache, metallic taste

Sulfonamides- sulfamethoxazole (SMX), sulfisoxazole, and sulfadiazine

MOA:  PABA antimetabolites that inhibit dihydropteroate synthetase. Bacteriostatic

Use:  Gram positive, gram negative, Nocardia, Chlamydia, Triple sulfas or SMX for simple UTI

Toxicity: Hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin like warfarin.

MOA:  inhibits DNA synthesis by conversion to 5-fluorouracil blocking synthesis of pyrimidine precursors. 

Use:  systemic fungal infections (Candida, Cryptococcus) in combination with amphotericin B.

Tox: Nausea, vomiting, diarrhea, bone marrow suppression.

MOA:  Inhibits DNA-dependent RNA polymerase

Use:  TB.  Delays resistance to dapsone when used for leprosy.  used for meningococcal prophylaxis and chemoprophylaxis in contacts of children with H. influenzae type B.

Tox:  Minor hepatotoxicity and drug interactions (↑ P-450); orange body fluids (nonhazerous side effect)

MOA:  binds ergosterol; forms membrane pores that allow leakage of electrolytes

Use: systemic mycoses: cryptococcus, blastomyces, coccidiodes, aspergillus, histoplasma, candida, mucor.   does not cross blood-brain barrier

Toxicity: Fever/chills ("shake and bake"), hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis.  Hydration reduces nephrotoxicity.  Liposomal amphotericin reduces toxicity

MOA:  binds to ergosterol, disrupting fungal membranes.  Too toxic for systemic use.

Use:  "swish and swallow" for oral candidias (thrush); topical for diaper rash or vaginal candidias

fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole

MOA: inhibit fungal sterol (ergosterol) synthesis

Use:  systemic mycosis.  Fluconazole for cryptooccal meningitis in AIDS patients b/c can cross blood-brain barrier and candidial infections.  Clotrimazole and miconazole for topical fungal infections.

Tox:  hormone synthesis inhibition (gynecomastia).  Liver dysfunction b/c inhibits cytochrome P-450

MOA:  inhibits fungal enzyme squalene epoxidase

--> ultimately causing ↓ synthesis of ergosterol

Use:  used to treat dermatophytes (especially onychomycosis b/c accumulates in skin and nails)

MOA:  blocks viral penetration/uncoating (M2 protein), may buffer pH of endosomes.  Also causes release of dopamine from intact nerve terminal.  Blocks influenza A and rubellA and causes problems with the cerebellA.

Use:  Prophylaxis and treatment for influenza A; parkinson disease

Tox: Ataxia, dizziness, and slurred speech

Rimantidine is a derivative with fewer CNS side effects b/c does not cross blood brain barrier. 

Mech of resistance:  Mutated M2 protein. 90% of all influenza A strains are resistant to amantadine so not used.

MOA:  Inhibit influenza neuraminidase, decreasing the release of progeny virus

Use:  Both influenza A and influenza B

They are sialic acid analogue inhibitors of influenza A & B

MOA:  Inhibits synthesis of guanine nucleotides by competitively inhibiting IMP dehydrogenase.

Use:  RSV, chronic hepatitis C

Tox:  Hemolytic anemia and Severe teratogen

MOA:  Guanosine analog. Monophosphorylated by HSV/VZV thymidine kinase.  Triphosphate formed by host cellular enzymes.  Preferentially inhibits viral DNA polymerase by chain termination.  

Use:  HSV, VZV, EBV. Most effective for HSV and VZV then EBV and CMV.  Used for HSV induced mucocutaneous and genital lesions as well as encephalitis.  Prophylaxis in immunocompromised pts.  Herpes zoster use famciclovir.

Resistance:  lack of thymidine kinase 

MOA:  Guanosine analog. 5-monophosphate formed by a CMV viral kinase or HSV/VZV thymidine kinase. Triphosphate formed by cellular kinases.  Preferentially inhibits viral DNA polymerase

Use:  CMV, espicially in immunocompromised pts

Tox:  leukopenia, neutropenia, thrombocytopenia, renal toxicity. More toxic to host enzymes than acyclor.  bone marrow suppression and renal impairment.

Mech of resistance:  Mutated CMV DNA polymerase or lack of viral kinase

Foscarnet

MOA:  Viral DNA polymerase inhibitor that binds to the pyrophophate-binding site of the enzyme.  Does not require activation by viral kinase. 

Use:  CMV retinitis in immunocompromised pts, when ganciclovir fails, acyclovir-resistant HSV.

Tox: Nephrotoxicity

Mech of Resist:  Mutated DNA polymerase

All protease inhibitors end in -navir

MOA:  inhibit maturation of new virus by blocking protease in progeny virions

Tox: GI intolerance (nausea, diarrhea), hyperglycemia (insulin resistance), lipodystrophy, thrombocytopenia (indinavir)

Nucleoside Reverse transcriptase inhibitors. Must be converted to monophosphate form by cellular thymidine kinase before conversion to triphosphate

MOA:  Preferentially inhibit reverse transcriptase of HIV; prevent incorporation of DNA  copy of viral genome into host.

Tox:  bone marrow suppression in 40% (neutropenia, anemia), peripheral neuropathy, nucleosides cause lactic acidosis.  Non-nucleosides cause a rash.  Zidovudine causes megaloblastic anemia.  GM-CSF and erythropoietin can be used to reduce bone marrow suppression.  

Use:  in HAART (highly active antiretroviral therapy) which is combination of therapy with protease inhibitors and reverse transcriptase inhibitors.  Initiated when patients have low CD4 counts (less than 500 cells/mm³) or high viral load.

-Zidovudine (nucleoside reverse transcriptase inhibitor) used for general prophylaxis and during pregnancy to reduce risk of fetal transmission.

Never Ever Deliver nucleosides

MOA:  Preferentially inhibit reverse transcriptase of HIV; prevent incorporation of DNA  copy of viral genome into host.

Tox:  bone marrow suppression in 40% (neutropenia, anemia), peripheral neuropathy, nucleosides cause lactic acidosis.  Non-nucleosides cause a rash.  GM-CSF and erythropoietin can be used to reduce bone marrow suppression.  

MOA:  Fusion inhibitor.  Binds viral gp41 subunit; inhibit conformational change required for fusion with CD4 cells.  Therefore block entry and subsequent replication.

Use:  In patients with persistent viral replication in spite of antiretrovial therapy.  Used in combination with other drugs.

Tox:  Hypersensitivity reactions, reactions at subcutaneous injection site, increase risk of bacterial pneumonia.

Interferon therapy for what diseases and toxicities

IFN-α

IFN-β

IFN-γ 

IFN-α- chronic Hep B & C, Kaposi's sarcoma

IFN-β - Multiple Sclerosis

IFN-γ - NADPH oxidase deficiency

Toxicity:  neutropnenia

SAFE Moms Take Really Good Care

S-sulfonamides- kernicterus

A-aminoglycosides- ototoxicity

F-fluoroquinolones- cartilage damage

E-erythromycin- acute cholestatic hepatitis in mom and clarithromycin- embryotoxic

M-metronidazole- mutagenesis

T- tetracyclines- discolored teeth, inhibition of bone growth

R- ribavirin (antiviral) - teratogenic

G- griseofulvin (antifungal)- teratogenic

C-chloramphenicol- "gray baby"