Antimicrobials Flashcards by M B

Beta-lactams

Mechanism

Block cell wall synthesis

Inhibit peptidoglycan cross-linking

(penicillin, methicillin, ampicillin, piperacillin, cephalosporins, aztreonam, imipenem)

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Bacitracin, vancomycin

Mechanism

Block peptidoglycan synthesis

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TMP, sulfonamides

Mechanism

Block nucleotide synthesis-

Inhibit folic acid synthesis

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Fluoroquinolones

Mechanism

Block DNA topoisomerases

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Rifampin

Mechanism

Block mRNA synthesis

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Metronidazole

Mechanism

Damage DNA

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Chloramphenicol, macrolides, clindamycin, streptogramins, linezolid

Mechanism

50S ribosomal subunit inhibitor

Chloramphenicol, macrolides, clindamycin, streptogramins (quinupristin, dalfopristin), linezolid

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Aminoglycosides, tetracyclines

Mechanism

30S ribosomal subunit inhibitor

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Bind transpeptidases

Gram-positives, gram-neg cocci, spirochetes

Hypersensitivity, hemolytic anemia

Beta-lactamases for resistance

Penicillin G (IV,IM)

Penicillin V (oral)

Penicillinase susceptible

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Penicillinase resistant

S. aureus

Hypersensitivity, interstitial nephritis

Oxacillin, nafcillin, dicloxacillin

(naf for staph)

bulky -R group

blocks beta-lactamase access to b-lactam ring

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MRSA

Mechanism of resistance

Altered penicillin-binding protein target site

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HELPSS kill enterococci

Hypersensitivity, rash, pseudomembranous colitis

Combined with clavulanic acid

Aminopenicillins

Ampicillin, amoxiciliin

amoxi > bioavailability

penicillinase susceptible (add clavulate)

HELPSS:

Haemophilus, E. coli, Listeria, Proteus, Salmonella, Shigella

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Gram-neg rods, Pseudomonas

Combined with clavulanate

Hypersensitivity

Antipseudomonals

Ticarcillin, piperacillin

Susceptible to penicillinase

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Beta-lactamase inhibitors

CAST

Clavulanic acid, sulbactam, tazobactam

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Covers everything but LAME

(Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, Enterococci)

Cephalosporins

except ceftaroline covers MRSA

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Can cause

Hypersensitivity, Vit K deficiency, increased nephrotoxicity of aminoglycosides

Cephalosporins

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Gram-pos cocci

PEcK

(Proteus, E. coli, Klebsiella)

1st gen cephalosporins

Cefazolin, Cephalexin

Cefazolin - prior to surgery to prevent

S. aureus wound infections

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Gram-pos cocci

HEN PEcKS

(Haemophilus, Enterobacter aerogenes, Neisseria, Proteus, E. coli, Klebsiella, Serratia marcescens)

2nd gen cephalosporins

Cefoxitin, Cefaclor, Cefuroxime

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Serious gram-neg infections

(meningitis, gonorrhea)

resistant to other beta-lactams

3rd gen cephalosporins

Ceftriaxone- meningitis, gonorrhea

Ceftazidime- Pseudomonas

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Gram-neg rods only

monobactam (resistant to beta-lactamases)

No penicillin cross-allergenicity

Binds PBP3

Aztreonam

Binding to PBP3 prevents peptidoglycan cross-linking

Syngeristic with aminoglycosides

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Beta-lactamase resistant

Inactivation in renal tubules prevented by cilastatin

Wide spectrum- serious infections

GI distress, seizures, rash

Imipenem/cilastatin

meropenem

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Binds D-ala portion of cell wall precursors

Gram-pos only

Red man syndrome

Vancomycin

Red man syndrome:

Nephrotoxicity, ototoxicity, thrombophlebitis,

diffuse flushing

(pretreat w/ antihistamine, do slow infusion)

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Result of

D-ala D-ala

change to

D-ala D-lac

in cell wall precursor

Vancomycin resistance

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Inhibits intiation complex formation

Ineffective against anaerobes

Nephrotoxic, ototoxic, teratogen, neuromuscular block

Inactivated by acetylation, phosphorylation, adenylation

Aminoglycosides

(gentamicin, neomycin, amikacin, tobramycin, streptomycin)

Cause misreading of mRNA

Requires O2 for uptake

Resistance: transferase enzymes

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Prevents aminoacyl-tRNA attachment to 30S Divalent cations inhibit absorption in gut GI distress, discoloration of teeth, inhibits bone growth in children, photosensitivity. Contraindication: pregnancy Resistance: plasmid-encoded transport pumps

Tetracyclines (tetracycline, doxycycline, demeclocycline, minocycline) Intracellular accumulation- effective against: B. burgdorferi, M.pneumoniae, Rickettsia, Chlamydia Divalent cations in milk, antacids, iron-preps Demeclocycline- ADH antagonist. SIADH- first line

Blocks translocation by binding 23S subunit (of 50S) Atypical pneumonias, Chlamydia, gram-pos cocci Motility issues, long QT arrythmia, acute cholestatic hepatitis, rash, eosinophilia Resistance: methylation of 23S binding site

Macrolides Azithromycin, clarithromycin, erythromycin

Blocks peptidyltransferase at 50S Meningitis (3rd world) Anemia, gray baby syndrome

Chloramphenicol

Blocks peptide transfer at 50S Anaerobic infections- aspiration pneumonia, oral infections Pseudomembranous colitis, fever, diarrhea

Clindamycin Clindamycin- anaerobes above diaphragm Metronidazole- anaerobes below diaphragm

Inhibit dihydropteroate synthase Nocardia, Chlamydia, UTIs Hypersensitivity, hemolysis, nephrotoxicity, kernicterus

Sulfonamides Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine PABA antimetabolites inhibit enzyme Hemolysis in G6PD deficiency

Inhibit dihydrofolate reductase UTI, Shigella, Salmonella, Pneumocystis jirovecii Megaloblastic anemia, leukopenia, granulocytopenia

Trimethoprim Leucovorin reverses folate deficiency due to TMP

Reverses side-effects of Trimethoprim

Leucovorin | (Supplemental folinic acid)

Inhibit DNA gyrase (topo II) and topo IV Gram-neg rods in urinary, GI. Neisseria, Pseudomonas. Rarely tendon rupture, leg cramps, myalgias. Contra: pregnant, children (cartilage damage)

Fluoroquinolones (ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, sprafloxacin, moxifloxacin, gatifloxacin, enoxacin, nalidixic acid) No antacids

Free radical metabolites damage DNA Anaerobes, protozoa (Giardia, Entamoeba, Trichomonas, Gardernella) Reacts with EtOH, metallic taste

Metronidazole Treats anerobes below the diaphragm

Mycobacterium tuberculosis

_RIPE_ Rifampin, isoniazid, pyrazinamide, ethambutol Prophylaxis: Isoniazid

Mycobacterium avium-intracellulare

_ARES_ Azithromycin, rifampin, ethambutol, streptomycin Prophylaxis: Azithromycin

Mycobacterium leprae

Tuberculoid- dapsone, rifampin Lepromatous- dapsone, rifampin, clofazimine No prophylaxis

Active metabolite decreases sythesis of _mycolic acids_ Bacterial catalase-peroxidase (KatG) creates metabolite Solo prophylaxis against TB Neurotoxicity, hepatotoxicity, lupus.

Isoniazid INH- Injures Neurons and Hepatocytes pyridoxine (B6) can prevent neurotoxicity

Inhibits DNA-dependent RNA Pol TB, leprosy, meningococcal prophylaxis Activates P450, orange body fluids

Rifampin Meningococcal prophylaxis in contacts of children with Haemophilus influenzae B Delays resistance to dapsone in leprosy.

Uncertain mechanism Active in pH of phagolysosome TB Hyperuricemia, hepatotoxicity

Pyrazinamide

Blocks arabinosyltransferase Decreased carbohydrate polymerization in cell wall TB Optic neuropathy (red-green colorblindness)

Ethambutol

HIV prophylaxis CD4 \< 200 CD4 \< 100 CD4 \< 50

TMP-SMX (Pneumocystis) TMP-SMX (Pneumocystis and toxoplasmosis) Azithromycin (M. avium complex)

Vancomycin resistant enterococcus (VRE)

Linezolid Streptogramins (quinupristin, dalfopristin)

Binds ergosterol Forms membrane pores (2)

Amphotericin B Nystatin

Inhibits fungal ergosterol synthesis

-azoles Fluconazole, itraconazole, voriconazole

Inhibits synthesis of beta-glucan Inhibits fungal cell wall synthesis

Caspofungin

Inhibits squalene epoxidase Disrupts lanosterol synthesis

Terbinafine, Naftifine

Inhibits fungal DNA and RNA biosynthesis

5-Flucytosine By conversion to 5-fluorouracil by cytosine deaminase

Bind ergosterol Systemic mycoses: Cryptococcus, Blastomyces, Coccidioides, Histoplasma, Candida, Mucor, meningitis Fever/chills, nephrotoxic, arrhytmias, IV phlebitis, anemia

Amphotericin B Supplement K+ and Mg2+ (altered renal tubule permeability) Hydration reduces nephrotoxicity Liposomal reduces toxicity

Binds ergosterol Topical Oral candidiasis, diaper rash, vaginal candidiasis

Nystatin

Blocks conversion of lanosterol to ergosterol (inhibits P450) AIDS- cryptococcal meningitis suppression, candida Blastomyces, Coccidioides, Histoplasma Testosterone synth inhibition, liver dysfunction

Fluconazole Itraconazole Gynecomastia- ketoconazole

Inhibits DNA, RNA biosynthesis Systemic infections, Cyptoccal meningitis Bone marrow suppression

Flucytosine Active metabolite: 5-fluorouracil by cytosine deaminase

Inhibits fungal cell wall synthesis (beta-glucan) Invasive aspergillosis, candida GI upset, flushing (histamine)

Caspofungin, micafungin

Inhibits squalene epoxidase Dermtophytoses (i.e. onychomycosis) Abnormal liver function tests, visual disturbances

Terbinafine

Disrupts microtubule formation, mitosis Deposits in keratin-containing tissues (nails) Oral Tx of superficial infections (tinea, ringworm) Teratogen, carcinogen, increases P450

Griseofulvin

Blocks detox of heme to hemozoin Plasmodium (other than falciparum) Retinopathy Resistance: membrane pump

Chloroquine Heme accumulates, is toxic to Plasmodia. Life-threatening malaria in US: _quinidine_

Flukes- such as Schistosoma

Praziquantel

Pyrimethamine Suramin and melarsoprol Nifurtimox Sodium stibogluconate

_Antiprotozoans_ Pyrimethamine- toxoplasmosis Suramin and melarsoprol- Trypanosoma brucei Nifurtimox- Trypanosoma cruzi Sodium stibogluconate- Leishmaniasis

Mebendazole Pyrantel pamoate Ivermectin Diethylcarbamazepine Praziquantel

Antihelminthic

Inhibits neuraminidase Influenza A and B

Oseltamivir, Zanamivir

Inhibits synthesis of guanine nucleotides (competitive IMP dehydrogenase inhibition) Respiratory synctial virus, chronic HCV Hemolytic anemia, severe teratogen

Ribavirin

Guanosine analog Monophosphorylation by viral thymidine kinase DNA Pol chain termination Herpes simplex virus, Varicella zoster virus

Acyclovir Prophylaxis in immunocompromised Valacyclovir (prodrug) better bioavailability For herpes zoster- famiciclovir

Guanosine analog Converted to monophosphate by viral kinase Inhibits viral DNA Pol Cytomegalovirus Leukopenia, neutropenia, thrombocytopenia, renal toxicity

Ganciclovir Valganciclovir (prodrug)- better oral bioavailability

Inhibits viral DNA Pol by binding pyrophosphate binding site No activation by viral kinase CMV retinitis in immunocompromised (when ganciclovir fails) Acyclovir-resistant HSV Nephrotoxicity

Foscarnet Pyrophosphate analog

Inhibits viral DNA Pol No activation by viral kinase CMV retinitis in immunocompromised Acyclovir-resistant HSV Long half-life Nephrotoxicity

Cidofovir Codminister with _probenecid and IV saline_ to reduce toxicity

HIV therapy

2 nucleoside reverse transcriptase inhibitors (NRTIs) + 1 non-NRTI or 1 protease inhibitor or 1 integrase inhibitor

Prevent cleavage of HIV proteins into functional parts Hyperglycemia, GI intolerance, lipodystrophy

Protease inhibitors Lopinavir, atazanavir, darunavir, fosamprenavir, saquinavir, ritonavir, indinavir -navir tease a protease

Protease inhibitor Nephropathy, hematuria

Indinavir

Competitive inhibition of nucleotide binding to RT DNA chain termination (lack 3' OH group) Most need to be phosphorylated Bone marrow suppression, peripheral neuropathy, lactic acidosis, rash, anemia

Nucleoside reverse transcriptase inhibitors Tenofovir, emtricitabine, abacavir, lamivudine, zidovudine, didanosine, stavudine Tenofovir- doesnt need phosphylation (a nucleo_tide)_ Zidovudine- prophylaxis during pregnancy

Competitive inhibition of nucleotide binding to RT No phosphorylation Bone marrow suppression, peripheral neuropathy, lactic acidosis, rash, anemia

Non-nucleoside reverse transcriptase inhibitors Nevirapine, efavirenz, delavirdine

Inhibits HIV genome integration into host cell Reversible inhibition Hypercholesterolemia

Integrase inhibitors Raltegravir Reversible inhibition of HIV integrase

Block both DNA, RNA viral replication Glycoproteins synthesized by infected cells Chronic HBV, HCV, Kaposi's sarcoma Multiple sclerosis NADPH oxidase deficiency Neutropenia, myopathy

_Interferons_ IFN-alpha IFN-beta IFN-gamma