Term
| tetracycline family includes which drugs? |
|
Definition
| tetracycline, doxycycline, minocycline, tigecycline |
|
|
Term
| tetracyclines are used against which classes of microbes? |
|
Definition
| gram+ and gram- (wide range); although used more frequently against gram- bacteria (fewer problems with resistance) |
|
|
Term
| which 2 tetracyclines are especially good for intracellular microbes? |
|
Definition
| doxycycline, minocycline - bc they can pass directly through the lipid bilayer |
|
|
Term
| are tetracyclines bacteriostatic or bacteriocidal? |
|
Definition
|
|
Term
| what are the best ways to administer tetracyclines? |
|
Definition
| orally (poor absorption, but achieves adequate therapeutic levels; absorption decreased by dairy products) or parenterally |
|
|
Term
| what limits the use of tetracyclines? |
|
Definition
|
|
Term
| how does resistance against tetracyclines happen? (mechanism) |
|
Definition
| decreased influx or increased efflux of the antibiotic (rarely d/t changes in the ribosome) |
|
|
Term
| what are the adverse reactions of tetracyclines? |
|
Definition
| effects on calcified tissues (binds to newly formed bone and teeth; can cause tooth discoloration in children); hepatotoxicity (high doses, pregnancy); renal toxicity |
|
|
Term
| what is tigecycline used for? |
|
Definition
| hugely broad spectrum, activity against variety of multi-drug resistant microbes. for skin and soft tissue infections, does not achieve high urinary concentrations bc it is excreted thru the bile |
|
|
Term
| what drug(s) are in the class oxazolidinones? |
|
Definition
|
|
Term
| what microbes does linezolid protect against? |
|
Definition
| broad spectrum tx of multi-drug resistant gram+ microbes |
|
|
Term
|
Definition
| orally, 100% bioavailability |
|
|
Term
| mechanism of resistance against linezolid? |
|
Definition
|
|
Term
| adverse side effects of linezolid? |
|
Definition
|
|
Term
| what are the aminoglycoside antibiotics? |
|
Definition
| streptomycin, gentamicin, tobramycin, amikacin |
|
|
Term
| are aminoglycosides bacteriostatic or bacteriocidal? |
|
Definition
|
|
Term
| what blocks the active transport of aminoglycosides into cells? |
|
Definition
| acidic pH or anaerobic conditions |
|
|
Term
| how is transport of aminoglycosides enhanced? |
|
Definition
| by agents that disrupt cell walls (synergistic action with B-lactams and vancomycin) |
|
|
Term
| use of aminoglycosides limited by what? |
|
Definition
| resistance and adverse side effects |
|
|
Term
| aminoglycosides are useful against which microbes? |
|
Definition
| susceptible, aerobic, gram- bacteria |
|
|
Term
| how are aminoglycosides administered? |
|
Definition
| IV or IM, poor oral bioavailability |
|
|
Term
| mechanism of resistance to aminoglycosides? |
|
Definition
| drug adenylation, phosphorylation, acetylation (less commonly, alterations of rRNA or ribosomal proteins) |
|
|
Term
| adverse effects of aminoglycosides? |
|
Definition
| ototoxicity and nephrotoxicity |
|
|
Term
| what is spectinomycin used for? |
|
Definition
| (related to aminoglycosides) used against a variety of gram+ and gram- organisms; confined to tx of drug-resistant gonorrhea or gonorrhea in pcn-allergic pts |
|
|
Term
| what is chloramphenicol use limited by? |
|
Definition
| adverse effects, resistance, other effective drugs |
|
|
Term
| mechanism of resistance to chloramphenicol? |
|
Definition
|
|
Term
| adverse effects of chloramphenicol? |
|
Definition
| 1. aplastic anemia (non-dose related, 50% fatality rate) 2. dose-related thrombocytopenia, recticulocytopenia, and leukopenia 3. gray baby syndrome (fatality 40%) |
|
|
Term
| what drugs are under streptogramins? |
|
Definition
| quinupristin-dalfopristin (30:70 ratio) |
|
|
Term
| use streptogramins against which microbes? |
|
Definition
| multi-drug resistant gram+ microbes |
|
|
Term
| how are streptogramins administered? |
|
Definition
|
|
Term
| adverse effects of streptogramins? |
|
Definition
| increases total and conjugated bilirubin, reverses with end tx |
|
|
Term
|
Definition
| class of rRNA mutations --> resistance to macrolide, lincosamide (clindamycin), and streptogramin B |
|
|
Term
| mechanism of resistance against streptogramins? |
|
Definition
| MLSb resistance (of quinupristin); and more uncommonly: enzymatic inactivation (of dalfopristin), increased efflux |
|
|
Term
| what drugs are macrolides? |
|
Definition
| erythromycin, azithromycin, clarithomycin (telithromycin) |
|
|
Term
| are macrolides bacteriocidal or bacteriostatic? |
|
Definition
| either depending on organism, drug concentration, and bac growth rate |
|
|
Term
| mechanism of resistance against macrolides? |
|
Definition
| reduced permeability or increased efflux, drug inactivation by estereases (enterobac), MLSb resistance |
|
|
Term
| adverse reactions for macrolides? |
|
Definition
|
|
Term
| telithromycin adverse side effects? |
|
Definition
| severe hepatotoxicity and liver failure (black box warning) |
|
|
Term
|
Definition
|
|
Term
| is clindamycin bacteriocidal or bacteriostatic? |
|
Definition
|
|
Term
| use of clindamycin limited by? |
|
Definition
|
|
Term
| mechanism of resistance against clindamycin? |
|
Definition
|
|
Term
| which drugs show concentration dependent killing? |
|
Definition
| aminoglycosides and quinolones (microbe can bind high concentrations of drug) |
|
|
Term
| which drugs demonstrate time-dependent killing? |
|
Definition
| beta-lactams, vancomycin, clindamycin, macrolides, linezolid (bc remain bound to microbe for a prolonged period of time) |
|
|
Term
| bacteria are considered sensitive to a drug if? |
|
Definition
| an achievable peak serum concentration is 2-4x the MIC |
|
|
Term
| what is the mechanism of action for SMX? |
|
Definition
| competes with PABA, competitive inhibitor of dihydropteroate synthase (in folic acid synthetic path)and folic acid used for synthesis of thymine, purines and methionine |
|
|
Term
| are sulfa drugs bacteriostatic or cidal? |
|
Definition
|
|
Term
| mechanisms of resistance to sulfa? |
|
Definition
| synthesis of altered dihydropteroate synthase, increased PABA synthesis, decreased sulfa uptake |
|
|
Term
| what are the main adverse effects of sulfa? |
|
Definition
| allergy, toxicity, hematuria (from microcrystals or sensitization, can be prevented with fluid intake, serum sickness, displaces albumin bound drugs and bilirubin (elevated bilirubin may damage the basal ganglia of the brain) |
|
|
Term
| trimethoprim is used to treat? |
|
Definition
| UTI (combination with smx), respiratory tract infections (pneumococcus, haemophilus, klebsiella), prostatitis, PCP |
|
|
Term
| trimethoprim mode of action |
|
Definition
| inhibits dihydrofolate reductase |
|
|
Term
| when smx-tmp is given orally, what is the ratio of one to the other given and the ratio in plasma? why so different? |
|
Definition
| administer tmp:smx in a 1:5 ratio --> 1:20 in plasma b/c TMP has a larger Vd due to its lipid solubility |
|
|
Term
| adverse effects of trimethoprim? what causes it? |
|
Definition
| megaloblastic anemia, leukopenia, granulocytopenia d/t inhibition of human dihydrofolate reductase (usually inhibits bacterial reductase a LOT more) |
|
|
Term
| resistance to trimethoprim d/t? |
|
Definition
| reduced permeability, overproduction of dihydrofolate reductase or altered production |
|
|
Term
| fluoroquinolones used against which microbes? |
|
Definition
| gram negative - enterobac, pseudomonas, neisseria, haemophilus, campylobacter. early ones (cipro, oflo, levo) have good gram neg activity; later ones (gati, gemi, moxi) have improved activity against gram positives at some cost to gram neg activity; some resistant strains of pseudomonas and enterobacter, legionellosis (alt to erythro); effective against intracellular microbes |
|
|
Term
| which drugs are in the fluoroquinolone family? |
|
Definition
| ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, gemifloxacin, moxifloxacin |
|
|
Term
| what types of infections do fluoroquinolones treat? |
|
Definition
| UTI (alternative to tmp-smx); community acquired respiratory infections, 2nd line of drugs to tx TB |
|
|
Term
| are fluoroquinolones static or cidal? |
|
Definition
|
|
Term
| how do fluoroquinolones work? |
|
Definition
| inhibits bacterial topoisomerase II (dna gyrase) and topoisomerase IV --> stops dna synthesis, high affinity for bacterial enzymes |
|
|
Term
| mechanisms of resistance to fluoroquinolones |
|
Definition
| altered topoisomerase, decreased permeability |
|
|
Term
| how are fluoroquinolones administered? |
|
Definition
|
|
Term
| what decreases the absorption of fluoroquinolones? |
|
Definition
| divalent cations in antacids |
|
|
Term
| are fluoroquinolones contraindicated in any patients? |
|
Definition
| not for pregnant or nursing mothers (secreted in breast milk); not recommended for children under 18 |
|
|
Term
| what's different about moxifloxacin from the rest of the quinolones? |
|
Definition
|
|
Term
| adverse effects of fluoroquinolones |
|
Definition
| reversibly inhibit cartilage synthesis (arthropathies), drug interactions (inhibits p450) |
|
|
Term
| what microbes is metro useful against? |
|
Definition
| anaerobes, c. difficile, trich |
|
|
Term
|
Definition
| reduction of nitro group in anaerobic cell --> reactive species that form adducts on DNA |
|
|
Term
| how is metro administered? |
|
Definition
| parenterally, orally, rectally, topically (vaginal), readily absorbed from GI |
|
|
Term
| is metro contraindicated in any patients? |
|
Definition
| no, but its excreted mostly via urine, so we'd probably decrease dosage in liver or kidney insufficient patients |
|
|
Term
|
Definition
| nausea, headache, metallic taste, antabuse reaction with alcohol |
|
|
Term
| what are the 3 agents used for HSV and VZV? |
|
Definition
| acyclovir, valacyclovir, famciclovir |
|
|
Term
| mechanism of action for acyclovir, valacyclovir and famciclovir |
|
Definition
| phosphorylation to monophosphorylated state by virally encoded thymidine kinase --> cellular coded enzymes convert monophosphorylated to triphosphorylated drug --> inhibits DNA synthesis by competition with dGTP for the viral DNA polymerase (acyc and valacyc also act as chain terminators, and triphos famcyc does not act as one) |
|
|
Term
| mechanisms of resistance against acyc, valacyc and famcyc? |
|
Definition
| mutations of viral thymidine kinase, mutations in viral dna pol (less common). resistance occurs more often in immunoompromised who receive chronic or multiple rounds of tx (cross resistance among all 3) |
|
|
Term
| mechanisms of resistance against acyc, valacyc and famcyc? |
|
Definition
| mutations of viral thymidine kinase, mutations in viral dna pol (less common). resistance occurs more often in immunoompromised who receive chronic or multiple rounds of tx (cross resistance among all 3) |
|
|
Term
| acyc/valacyc/famcyc how are they administered and where do they distribute? |
|
Definition
| orally, well distributed in plasma (CSF and aqueous humor concentrations are 1/3 of serum) |
|
|
Term
| what is unique about valacyclovir? |
|
Definition
| valacyclovir is an L-valyl ester of acyclovir -> after oral administration valacyclovir is rapidly converted to acyc with serum levels 3-5x higher than acyc |
|
|
Term
| what happens to famciclovir after ingestion? |
|
Definition
| converted by first pass metabolism to penciclovir and penciclovir achieves higher IC concentrations than acyc |
|
|
Term
| what are the 2 main adverse reactions of acyc/valacyc/famcic/pencic |
|
Definition
| (generally safe) but nephrotoxicity (d/t crystallization of acyclovir in the urine, more common in pt with renal dysfunc); can exacerbate preexisting seizure disorder or neurologic disease |
|
|
Term
| what are some topical agents for HSV? |
|
Definition
| penciclovir (active metabolite of famciclovir); docosanol, trifluridine |
|
|
Term
|
Definition
| (topical HSV) blocks HSV-cytoplasmic membrane fusion for viral entry into cells |
|
|
Term
| how does trifluridine work? |
|
Definition
| (topical HSV) phosphorylated form competes with dTTP for incorporation into DNA |
|
|
Term
| what is ganciclovir use indicated for? |
|
Definition
| CMV infection (retinitis and CMV prophylaxis in AIDS and transplant pts) |
|
|
Term
| ganciclovir mechanism of action |
|
Definition
| similar to anti-hsv drugs. phosphorylated by CMV-encoded kinase (UL97) to monophosphate form --> cellular kinases phosphorylate monophosphorylated ganciclovir to triphosphorylated form --> directly inhibits DNA polymerase and acts as chain terminator |
|
|
Term
| mechanisms of resistance to ganciclovir |
|
Definition
| mutations in UL97 or CMV DNA pol (DNA pol mutations remain susceptible to foscarnet) |
|
|
Term
| how is ganciclovir administered? |
|
Definition
| orally, poor oral bioavailability |
|
|
Term
| adverse effects of ganciclovir |
|
Definition
| hematopoietic effects (common - granulocytopenia, thrombocytopenia); CNS toxcitiy (rare - seizures), hepatotoxicity (rare), mutagenic, potentially carcinogenic and teratogenic |
|
|
Term
| is ganciclovir contraindicated in any patients? |
|
Definition
| pregnant women bc its potentially teratogenic |
|
|
Term
|
Definition
| ganciclovir prodrug with better oral bioavailability |
|
|
Term
| what drug is ganciclovir used in combination with sometimes? |
|
Definition
| foscarnet, synergistic effect |
|
|
Term
| what infections/viruses is it useful against? |
|
Definition
| broad spectrum. antiviral, hsv, vzv, ebv, hsv6, cmv, hiv, hepB, cmv retinitis and disseminated cmv infections, acyclovir-resistant mucocutaneous hsv inf |
|
|
Term
| mechanism of action of foscarnet |
|
Definition
| inhibits viral-specific DNA pol @ pyrophosphate-binding-site (no enzymatic activation required), prevents pyrophosphate cleavage from deoxynucleoside triphosphates (blocking elongation of viral DNA), cellular DNA pol not affected |
|
|
Term
| how is foscarnet usually administered? |
|
Definition
| IV (poor oral bioavailability) |
|
|
Term
| adverse reactions to foscarnet? |
|
Definition
| foscarnet accumulates in bone & cartilage d/t structural similarity to phosphate --> increase in skeletal abnormalities. anemia, renal toxicity (avoid co-admin with nephrotoxic drugs), hyper/hypo calacemia d/t chelation of calcium by foscarnet (can exacerbate sezirues or cardiac disorders) |
|
|
Term
| what is cidofovir used for? |
|
Definition
| broad spectrum - for CMV retinitis |
|
|
Term
| mechanism of action for cidofovir |
|
Definition
| cytosine analog, viral DNA polymerase inhibitor and chain terminator |
|
|
Term
| how is cidofovir administered? |
|
Definition
| parenteral administration only (poor csf penetration, long half life, infreq dosing) |
|
|
Term
| mechanism of resistance against cidofovir? |
|
Definition
| primarily in dna polymerase (frequent cross-resistance with ganciclovir but not foscarnet) |
|
|
Term
| adverse effects of cidofovir? |
|
Definition
| nephrotoxicity (need slow admin and concurrent probenecid to decrease active tubular excretion) |
|
|
Term
|
Definition
| CMV retinitis in pts that cannot be treated with other anti-CMV drugs |
|
|
Term
| how is fomivirsen administered? |
|
Definition
| injected into vitreous of the eye |
|
|
Term
| how is fomivirsen administered? |
|
Definition
| injected into vitreous of the eye |
|
|
Term
| formivirsen mechanism of action |
|
Definition
| formivirsin is an antisense DNA oligonucleotide --> formivirsen complementary to IE2 region of CMV genome (encodes necessary proteins for CMV replication) --> mRNA transcribed from IE2 binds formivirsen --> forms formivirsen-RNA heteroduplex --> formivirsen-RNA heteroduplex digested by RNAase --> IE2 proteins not synthesized --> CMV replication inhibited |
|
|
Term
| mechanism of resistance to formivirsen? |
|
Definition
| resistance not observed clinically. no known cross resistance. |
|
|
Term
| what are the uses for amantadine? |
|
Definition
| tx and prophylaxis of influenza A (in adults and children >1yr) |
|
|
Term
|
Definition
| tx and prophylaxis of influenza A virus in adults |
|
|
Term
| rimantadine and amantadine mechanism of action |
|
Definition
| blocks viral entry/uncoating by binding to M2 ion channel protein of influenza A virus (most effective when administered before inf, but remains effective 24-48 hrs after onset of sx) |
|
|
Term
| how are amantidine and rimantidine given? |
|
Definition
| orally, well absorbed from GI tract, long half-life increased in elderly and renal dysfunc pts. (rimantadine reaches higher concentrations in resp secretions after oral admin and has fewer CNS effects) |
|
|
Term
| resistance to amantadine and rimantadine? |
|
Definition
| due to mutations in the M2 gene |
|
|
Term
| adverse effects of amantadine and rimantadine? |
|
Definition
| CNS toxicity (hallucinations, seizures, coma) due to effects on dopamine metabolism; minor CNS problems (insomnia, difficulty concentrating) |
|
|
Term
| are amantadine/rimantadine contraindicated in any patients? |
|
Definition
| contraindicated in pregnant or nursing mothers, patients with psych disorders, epilepsy, or cerebral atherosclerosis |
|
|
Term
| what are zanamivir and oseltamivir used for? |
|
Definition
| prophylaxis and tx of influenza A and B (most effective when tx started within 48 hours of onset of sx) |
|
|
Term
| mechanism of action of zanamivir and oseltamivir? |
|
Definition
| inhibit influenza A and B neuraminidase (NA removes the terminal sialic acid of glycoproteins, required for efficient release of virus, may play a role in viral entry); decrease virus release, inhibit virus entry into respiratory epithelial cells, promote viral aggregation |
|
|
Term
| how is zanamivir administered? |
|
Definition
| oral inhalation, IV, intranasally (only 4-17% of inhaled dose systemically absorbed. poor oral bioavailability. inhalation provides high concentration at inf site --> greater anti-viral efficacy and reduced viral resistance. rapidly eliminated with IV use |
|
|
Term
| how is oseltamivir administered? |
|
Definition
| orally as an inactive prodrug. 75% converted to oseltamivir carboxylate by hepatic estrases |
|
|
Term
| resistance to zanamivir/oseltamivir? |
|
Definition
| mutations in influenza neuraminidase |
|
|
Term
| adverse effects of zanamivir? |
|
Definition
| bronchospasm in pt with mil or moderate asthma following inhalation |
|
|
Term
| adverse effects of oseltamivir? |
|
Definition
| nausea/vomiting early in tx |
|
|
Term
| what is ribavirin used for? |
|
Definition
| broad antiviral activity. tx of infants and children w/respiratory syncytial virus; tx of adults with severe influenza A and B, parainfluenza, lassa fever, various other inf |
|
|
Term
| what is ribavirin combined with sometimes? for what? |
|
Definition
| with interferon alpha for hepC tx |
|
|
Term
| ribavirin mechanism of action? |
|
Definition
| not fully understood, multiple sites of antiviral action. mimics guanine and adenosine. phosphorylated to monophosphate form by host adenosine kinase --> monophosphate form inhibits guanine synthesis by inhibiting inosine monophosphate dehydrogenase; ribavirin also lowers GTP --> inhibition of viral RNA and protein synthesis |
|
|
Term
| how is ribavirin administered? |
|
Definition
| aerosol for RSV; IV for serious systemic infections (lassa fever); half life 9 hrs after aerosol delivery, but low systemic bioavailability by that route |
|
|
Term
| adverse effects of ribavirin? |
|
Definition
| respiratory depression in infants; cardiac arrest, hypotension, may be dose-related. rash and conjunctivitis (more severe in contact lens wearers) |
|
|
Term
| is anyone contraindicated in using ribavirin? |
|
Definition
| pregnant women. teratogenesis or fetal death --> effect can be delayed bc blood levels can remain up for 4 weeks d/t sequestration in RBC |
|
|
Term
| what is palivizumab used for? |
|
Definition
| prevention of RSV in high-risk infants |
|
|
Term
| mechanism of action for palivizumab? |
|
Definition
| monoclonal antibody against F surface protein, inhibits adsorption and/or entry |
|
|
Term
| how is palivizumab administered? |
|
Definition
|
|
