Flashcards in Microbiology--Pharmacology Deck (104):
Penicillin G ,V use
G+ organisms: S pneumoniae, S pyogenes, Actinomyces, Also used for N meningitidis, T pallidum
Ampicillin, amoxicillin use
H flu, E coli, Listeria, Proteus, Salmonella, Shigella
Oxacillin, nafcillin, dicloxacillin
S aureus--has bulky R group to prevent penicillinase breakdown
antibiotic that can cause pseudomembranous colitis
antipseudomonals--use with B lactamase inhibitors like tazobactam
what are organisms typically not covered by cephalosporins?
LAME: listeria, atypicals (chlamydia, mycoplasma), MRSA, Enterococci
1st generation cephalosporin
cefazolin, cephalexin--gram+ and PEcK: proteus, e coli, Klebsiella
2nd generation cephalosporin
cefoxitin, cefaclor, cefuroxime--gram +, and HEN PEcKS: h flu, enterobacter, Neisseria spp, Proteus, E coli, Klebsiella, Serratia
3rd generation cephalosporin
ceftriaxone, cefotaxime, ceftazidime; use ceftriaxone in meningitis and gonorrhea; use ceftazidime in pseudomonas
4th generation cephalosporin
cefepime--increased activity against pseudomonas and G+ organisms
5th generation cephalosporin
ceftaroline--broad gram+ and - coverage including MRSA, but does NOT cover pseudomonas
toxicities of cephalosporins?
vit K deficiency; low cross reactivity with penicillis; greater nephrotoxicity than aminoglycosides
what is a monobactam?
aztreonam--prevents peptidoglycan cross linking by binding to PBP3. Synergistic w/ aminoglycosides; no cross reactivity with penicillin
gram - only; no activity against g+ or anaerobes; use in penicillin allergics or renal failure patients who can't tolerate aminoglycosides
What is imipenem always administered with?
cilastatin--inhibitor of renal dehydropeptidase I
Which carbapenem is stable to dehydropeptidase I
GI distress, skin rash, CNS toxicity (seizures)--last resort bug
inhibits cell wall peptidoglycan formation by binding D-ala Dala portion of cell wall precursors; resistance forms when AA modified to DalaDlac
only for G+, MRSA, enterococci, C diff
NOT; nephrotoxicity, ototoxicity, thrombophlebitis, diffuse flusing (red man syndrome)--prevent with antihistamines and slow infusion rate
Which antibacterial protein synthesis inhibitors target which ribosome?
buy AT 30; CCEL at 50: 30S: aminoglycosides, tetracyclines; 50S: chloramphenicol, clindamycin, erythromycin (macrolides), linezolid
What are some aminoglycosides?
Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin
30S: inhibit formation of initiation complex and cause misreading of mRNA; also blocks translocation; requires O2 for uptake so ineffective against anaerobes
severe gram negative rod infections; synergistic with B lactam anbx; neomycin for bowel surgery;
transferase enzymes inactive the drug by acetylation, phophorylation or adenylation
bind to 30S and prevent attachment of aminoacyl tRNA; limited CNS penetration; doxycycline eliminated by gut and can use in renal failure patients; do not take with milk, antacids, or iron containing preps because divalent cations inhibit gut absorption
borrelia, mycoplasma, rickettsia, Chlamydia--drug can accumulate intracellularly
decreased uptake or increased efflux out of bacterial cells by plasmid encoded transport pumps
Inhibit protein synthesis by blocking translocation; binds to 23S rRNA of 50S ribosomal subunit
MACRO: GI motility issues, arrhythmia (prolonged QT), acute cholestatic hepatitis, rash, eosinophilia; increases serum concetrations of theophylines, oral anticoagulants
methylation of 23S rRNA-binding site prevents drug binding
blocks peptidyltransferase at 50S ribosomal subunit
anemia, aplastic anemia, gray baby syndrome (lack liver UDP-glucuronyl transferase)
plasmid encoded acetyltransferase inactivates the drug
blocks peptide transfer (translocation) at 50S ribosomal subunit,
inhibit folate synthesis, PABA antimetabolites inhibit DHF synthase
Sulfonamides, trimethoprim, pyrimethamine affect the THF pathway at which enzymes?
Sulfonamides: Dihydropterate synthase; Trimethoprim/pyramethamine: dihydrofolate reductase
hemolysis if G6PD deficient; tubulointerstitial nephritis; photosensitivity; kernicterus in infants; displaces other drugs from albumin (like warfarin)
inhibits DHF reductase
TMP: treats marrow poorly: megaloblastic anemia, leukopenia, granulocytopenia (can alleviate with folinic acid (leucovorin))
inhibit DNA gyrase (topoisomerase II) and topoisomerase IV; do NOT take with antacids
tendonitis/tendon rupture/leg cramps/myalgias, contraindicated in pregnant women, nursing mothers, children < 18 over concerns for cartilage damage, can cause prolonged QT,
chromosome encoded mutation in DNA gyrase, plasmid mediated, efflux pumps
Metronidazole MoA? Tox?
forms free radical toxic metabolites in the bacterial cell that damage DNA; disulfiram like reaction with alcohol; headache; metallic taste
decreases synthesis of mycolic acids, bacterial catalase peroxidase (KatG) needed to convert INH to active metabolite
Neurotoxicity; hepatotoxicity; B6 can prevent neurotoxicity and lupus
Rifampin, rifabutin MoA
inhibits DNA dependent RNA polymerase
Rifabutin is favored in patients w/ HIV over Rifampin why?
Rifampin ramps up CYP450; rifabutin does not
decreases carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase
optic neuropathy--can cause red green color blindness
Prophylaxis: endocarditis with surgical or dental procedures
Prophylaxis history of recurrent UTIs
Prophylaxis meningococcal infx
Ciprofloxacin (rifampin for child)
Prophylaxis Pregnant women carrying group B strep
Prophylaxis Prevention of gonococcal or chlamydial conjunctivitis in newborn
Prevention of postsurgical infection due to S aureus
Prophylaxis strep pharyngitis in child with prior rheumatic fever
prophylaxis in HIV patients with CD4 counts < 200, <50
<50 azithromycin for MAC; use pentamidine if TMPSMX cannot be tolerated
serotonin syndrome anbx
Amphotericin B MOA?
binds ergosterol and forms membrane pores that allow electrolyte leakage
what supplements must be given with amphotericin B?
supplement K and Mg because of altered renal tubule permeability
fevers/chills, hypotension, nephrotoxicity, arrhythmias, anemia, IV phelbitis, hydration decreases renal damage; liposomal forms can decrease toxicity
binds ergosterol--pores; only topical because so toxic
inhibit fungal sterol (ergosterol) synthesis by inhibiting CYP450 enymes that convers lanosterol to ergosterol
chronic supression of cryptococcal meningitis in AIDS and candida infx of all types
blastomyces, coccidiodes, histoplasma
topical fungal infx
clotrimazole and miconazole
testosterone synthesis inhibitor (esp ketoconazole), liver (inhibits CYP450)
Flucytosine moA? tox
converted to 5-FU via cytosine deaminase to inhibit DNA and RNA biosynthesis; bone marrow supression
Caspofungin, micafungin, anidulafungin MoA? Tox?
inhibits cell wall synthesis by inhibiting synthesis of B glucan; GI upset/flushing via histamine release
Terbinafine MoA? tox?
inhibits funal enzyme squalene epoxidase (squalen to squalene epoxide); use for skin funal infections esp finger/toe nails; GI upset/HA/liver tox/taste disturbance
Griseofulvin moA? Tox?
interferes with microtubule function to disrupt mitosis; teratogenic/carcinogenic/confusion/H/A; increases p450 and warfarin metabolism
block detoxification of heme into hemazoin; heme accumulates and kills plasmodia; do not use for falciparum
Zanamivir, oseltamivir moa?
neuraminidase inhibitor, prevent release of progeny virus; used for flu A/B
ribavirin moa? tox?
inhibits synthesis of guanine nucelotides by competitively inhibiting IMP dehydrogenase; RSV/chronic hep C; hemolytic anemia, severe teratogen
acyclovir, famciclovir, valacyclovir moa? Tox?
guanosine analog that requires phosphorylation by thymidine kinase; used for HSV/VZV; crystalline nephropathy and ARF if not adequately hydrated
Ganciclovir moa? Tox?
5' monophosphate formed by CMV viral kinase. Guanosine analog; use for CMV; leukopenia/neutropenia/thrombocytopenia/renal toxicity
Foscarnet moa? Tox?
viral DNA Polymerase inhibitor that binds to pyrophosphate binding side of enzyme; does not need activation by viral kinase; nephrotoxicity
used in CMV retinitis when gancyclovir fails, used in acycolvir resistant HSV
cidofovir moa, tox?
preferentially inhibits viral DNA polymerase; no need for kinase activation; nephrotoxicity, administer with probenecid and IV saline to decrease toxicity
when to initiate HAART?
aids defining illness, CD4 < 500; high viral load: 2NRTIs and 1 NNRTI/1 protease inhibitor/1 integrase inhibitor
-navir HIV drug MoA?
protease inhibitors; prevent maturation of new virus;
whats special about ritonavir?
can boost other drug concentrations by inhibiting P450
hyperglycemia, GI intolerance, lipodystrophy, thrombocytopenia
tox of indinavir?
competitively inhibit nucleotide binding to reverse transcriptase and terminate DNA synthesis (lack 3' OH group)
nucleotide; all others are nucleosides that need to be phosphorylated to be active
bone marrow supression (give GCSF and EPO); peripheral neuropathy; lactic acidosis (nucleosides)
NRTI that can cause anemia
zidovudine; used in general phrophylaxis and during pregnancy
NRTI that causes pancreatitis
NNRTI that causes vivid dreams/CNS symptoms
rash and heptotoxicity--do not use delavirdine or efavirenz in pregnancy
integrase inhibitor; reversibly inhibits HIV integrase; hypercholesterolemia
fusion inhibit; binds gp41; inhibits viral entry
binds CCR-5 on surface of T cells/monocytes inhibiting interaction with gp120 on HIV
chronic hep B/C, kaposi, hairy cell leukemia, condyloma acuminatum, renal cell carcinoma, malignant melanoma
chronic granulomatous disease