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246 Cards in this Set
- Front
- Back
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Amantadine
1. Clinical uses 2. MOA 3. Side effects 4. Interactions/cautions |
1. Used as prophylaxis and treatment (within 48 hours of symptoms) of Influenza A
2. Blocks viral uncoating by inhibiting M2 proton pump; Also stimulates dopamine release in the CNS 3. Anorexia, nausea, peripheral edema, nervousness, anxiety 4. Excreted into the urine completely unchanged and need to adjust for renal clearance; CNS side effects more serious when taken with anticholinergics |
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Rimantadine
1. Clinical uses 2. MOA 3. Side effects 4. Interactions/cautions |
1. Prophylaxis and treatment (within 48 hours of symptoms) of Influenza A
2. Blocks viral uncoating by inhibiting M2 proton pump 3. Less CNS side effects tan amantadine 4. Extensively metabolized before excretion, do nothave to adjust for renal clearance |
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Oseltamivir (Tamiflu)
1. Uses 2. MOA 3. Side effects 4. Metabolism and excretion |
1. Influenza A and B prophylaxis and treatment (decreases time to improvement by 1-3 days and prevents influenza complications); also treatment and prophylaxis of bird flu
2. Neuraminidase inhibitor that increases viral aggregation in cells, thus decreasing viral release and dissemination 3. Nausea, vomiting, and headache 4. Prodrug that increases its bioavailability; active drug excreted unchanged by the kidney |
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Zanamivir (Relenza)
1. Uses 2. MOA 3. Side effects 4. Metabolism and excretion |
1. Influenza A and B prophylaxis and treatment (decreases time to improvement by 1-3 days and prevents influenza complications)
2. Neuraminidase inhibitor that increases viral aggregation in cells, thus decreasing viral release and dissemination 3. Nausea, vomiting, and headache 4. Poor bioavailability; comes as powder that is administered by inahlation or nasally; excreted unchanged by the kidney |
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Acyclovir (Zovirax) [Valacyclovir, Famciclovir, and Penciclovir]
1. Clinical Uses 2. MOA 3. Side effects 4. Metabolism and excretion |
1. -Antiviral against Herpes Simplex 1 and 2
-Treatment of Herpes encephalitis -Mucocutaneous and Genital herpes lesions (topical administration) -Prophylaxis against herpes recurrence for up to one year (oral adminstration) -Also antiviral against Varicella Zoster 2. Phophorylated by viral thymidine kinase; acyclovir triphosphate inhibits DNA polymerase and causes chain termination 3. 1% experience nauseau, CNS toxicity, delirium, tremor; IV doses can cause renal insufficiency 4. Only 1/3 of drug available when taken orally; Metabolized very little and excreted by the kidney; distributes widely |
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Trifluridine (Viroptic)
1. Uses 2. MOA 3. Side effects 4. Interactions/caution |
1. HSV ocular infections (herpes keratitis)
2. Nuceloside analogue, phophorylated form inhibits DNA polymerase 3. Local irritation 4. Effective against acyclovir resistant strains, but too toxic for systemic use; must put directly in eye only |
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Fomivirsen
1. Uses 2. MOA 3. Side effects 4. Interactions/caution |
1. Cytomegalovirus retinitis (second line)
2. Anti-sense oligonucleotide against mRNA that encodes a CMV regulatory protein 3. Local irritation 4. Used intravitreally only |
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Ganciclovir
(Valgnciclovir=prodrug) 1. Clinical uses 2. MOA 3. Side effects 4. Interactions/cautions 5. Administration |
1. -Severe CMV retinitis
-CMV colitis -CMV esophagitis -CMV prophylaxis in HIV patients -Used with anti-CMV antibodies to prevent CMV pneumonia in kidney transplants 2. Phophorylated by viral kinase and inhibits DNA polymerase 3. Bone marrow suppression/neutropenia; CNS side effects 4. More toxic than acyclovir becaue less selective for viral DNA polymerase 5. Poor oral bioavailability; given IV or as an ocular implant |
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Foscarnet
1. Clinical uses 2. MOA 3. Side effects 4. Interactions/Cautions |
1. -CMV retinitis resistant to ganciclovir
-HSV and VZV resistant to acyclovir 2. Not a nucleoside analogue; inhibits DNA polymerase by binding to pyrophosphate site; also inhibits reverse transcriptase 3. Nephrotoxicity 4. Given IV only, less tolerated than ganciclovir because requires large volumes of infused liquid |
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Cidofovir
1. Clinical uses 2. MOA 3. Side effects 4. Administration |
1. CMV retinitis (no cross resistance with ganciclovir) and HSV resistant to Acyclovir
2. Nuleotide analogue that doesnt require viral kinase to be active; inhibitis DNA polymerase 3. Nephrotoxicity and neutropenia 4. Given IV only; must be given with probenicid to inhibit its secretion and excretion from kidney |
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Ribavarin
1. Clinical uses 2. MOA 3. Side effects 4. Interactions/caution |
1. -Given aerosol for respiratory syncitial virus in children
-Given orally in combination with interferon for Hepatitis B and C -Aerosol used for influenza A and B -Given IV for Lassa Fever 2. Inhibits Inosine monophosphate dehydrogenase, which depletes virus of GTP; Inhibits viral RNA poylmerase; Inhibits capping of viral mRNA 3. Oral form causes myelosuppression; also causes hemolytic anemia 4. Contraindicated in pregnancy; carefully monitory respiratory function if given as aerosol |
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Interferon
1. Clinical use 2. MOA 3. Side effects 4. Administration |
1. -Chronic hepatitis B and C with Ribavarin
-Hairy cell leukemia -Genital warts -Kapolsi's Sarcoma 2. Glycoproteins that inhibit viral replication 3. Neutropenia and flu like symptoms 4. Given subcutaneously or intramuscularly |
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Sulfonamides
-Mechanism of action |
PABA analogues that inhibit dihydropteroate synthase, which converts PABA to folic acid; inhibition of folic acid synthesis inhibits DNA syntehsis
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Sulfonamides
-Antimicrobial spectrum and resistance |
-Bacteriostatic only
-Active against Gram positive, Gram negative bacteria; chlamydia; and nocardia -Resistance is wide spread, due to microbial overproduction of PABA, structural changes in dihydropteroate synthase, and/or decreased permeability |
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Sulfonamides
-Pharmacokinetics |
-High oral bioavailability
-Distributed to most tissues, including to CSF -Acetylated by the liver, with the metabolites still able to produce toxicity -Metabolites excreted in the urine by kidney |
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Sulfonamides
-Adverse effects |
-If used topically, can get irritation, stinging, or burning
-Hypersensitivity, such as rashes, fever, urticaria; can occur as cross-sensitivity to other sulfa drugs -Nausea and vomiting, diarrhea -Urinary tract disturabances, crystalluria, and allergic nephritis -Hematopoietic disturbances (rare) -Hemolytic anemia in patients with G6P Dehydrogenase deficiency -Kernicterus in the newborn |
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Dapsone
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Sulfonamide used for leprosy
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Silver Sulfadiazine
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Sulfonamide used for burns, most of its antibiotic effects due to silver; caues local irritation
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Sulfacetamide
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Sulfonamide used for conjunctivitis and corneal ulcers; can cause local irritation
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Triple sulfa
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Sulfonamide used for Vaginitis caused by Haemophilus; can cause local irration
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Sulfasoxazole, Sulfamethoxazole
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Sulfonamides used for uncomplicated urinary tract infection; can be given with phenazopyridine (urinary analgesic)
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Sulfadoxine
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Long lasting sulfonamide used for malaria
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Sulfadiazine (without silver)
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Sulfonamide used to treat toxoplasmosis
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Sulfasalazine
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Sulfonamide used to treat inflammatory bowel disease
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Trimethoprim
1. Clinical uses 2. MOA 3. Side effects 4. ADME |
1. Alone, used for unomplicated urinary tract infections
2. Bacteriostatic only, inhibits dihydrofolate reductase 3. Same as sulfonamides(Hypersensitivity, nephrotoxicity, GI, hemolysi in G6PD patients) plus megablastic anemia, leukopenia, and granulocytopenia 4. High availability; readily distributed, including to CNS; Mostly excreted unchanged by the kidney |
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Sulfamethoxazole/Trimethoprim combination
1. Clinical uses 2. MOA 3. Side effects 4. Interactions |
1. Used for urinary tract infections; Pneumocyscarinii, Shigella, Salmonell, Nocardia, Haemophilus influenza, and Strep Pneumoniae IV
2. Sequentially blocks folate synthesis 3. Side effects=Hypersensitivity, nephrotoxicity, GI disturbances, hemolysis in G6PD deficiency, megablastic anemia, leukopenia, granulocytopenia 4. Cross sensitivity with other sulfa drugs |
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Quinolones
-MOA |
-Inhibit DNA synthesis by inhibting DNA gyrase and topoisomerase IV
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Quinolones
-Antimicrobial spectrum |
-Ciprofloxacin=activity against Gram negative some activity against Haemophilus influenzae
-Levofloxacin, gatifloxacin, and moxifloxacin=more activity against Gram positive, especialy Strep pneumoniae |
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Quinolones
-ADME |
-Well absorbred, but taking with food or antacids limits availability
-Widely distributed to most tissues -Protein binding is low -Only small amount transformed in liver; Mostly eliminated by kidney secretion unchanged |
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Quinolones
-Adverse effects |
-Local effects: Irritation, stinging, burning
-Nausea and vomiting, diarrhea -Photosensitivity -Dizziness, confusion, hallucinations -May damage growing cartilage and should not be used for pregnant women or children -Tendinitous -Some drugs prolong the QT interval; avoid use if patients taking antiarrhythmics or any drugs that prolong QT interval |
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Ciprofloxacin (and any other quinolone ending with -oxacin)
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-Used for infections from Gram negative bacteria
-Resistant Urinary tract infection -Bone and skin infections -STDs, such as gonorrhea -Infectious diarrhea -Anthrax -Typhoid fever -Pseudomonas |
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Levofloxacin, Gemifloxacin, Moxifloxacin
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-More gram positive activity than ciprofloxacin; used to treat community acquired pneumonia cause by S. pneumoniae; also used for atypical pneumonia
-Used for same things as ciprofloxacin |
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Classes of antibiotics that inhibit cell wall synthesis
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-Beta lactams
-Glycopeptides -Bacitracin -Fosfomycin |
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What are necessary properties of antibiotics targeting Gram positive bacteria?
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-Gram positive=thicker peptidoglycan layer on membrane; drug must be able to diffuse through the Proteoglycans
-Peptidoglycan synthesis targeted by Beta lactams |
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What are necessary properties of antibiotics targeting Gram negative bacteria?
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-Drug has to be able to get through porin channels on the outer membrane
-Mechanism of resistance is the alteration of porin channels |
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What are the 5 classes of penicillins?
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1. Natural
2. Anti-staphylococcal 3. Aminopenicillins 4. Antipseduomonal 5. Penicillin/beta lactamase inhibitor combos |
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What are the 4 classes of Beta lactams?
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1. Penicillin
2. Cephalosporins 3. Carbapenems 4. Monobactams |
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What is the MOA of Beta lactams?
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-Have 4 membered ring that irreversibly binds to and inhibits transpeptidases that cross link peptidoglycans (Penicillin Binding Proteins)
-This inhibits peptidoglycan crosslinking, which then reduces the strength of the membrane -Cells swell because of weak points in the membrane and explode |
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General characteristics of Beta Lactams:
-Tissue penetration |
-Genrally good tissue penetration
-Variable to CNS -Poor to prostate |
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General characteristics of Beta Lactams:
-Activity |
-Bactericidal activity (some exceptions)
-Time dependent: Give in relatively constant dose via small, frequent doses (have to do anyway because have short t1/2) |
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General characteristics of Beta Lactams:
-Elimination |
-Renal elimination for most, not all
-Should adjust dose for renal dysfunction |
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General characteristics of Beta Lactams:
-Adverse effects |
-Hypersenstivity (type I): Penicillin is #1 cause of drug induced anaphylaxis
-N/V/D -Seizures (at high doses) -Thrombocytopenia |
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If you're allergic to Penicillin, then theres a ___% chance you're allergic to Cephalosporins
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3-5%
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If you're allergic to Penicillin, there's a ___% chance you're allergic to carbapenems
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50% or less
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If you're allergic to Penicillin, carbapenems, or cephalasporins, there's a ___% chance you're allergic to aztreonam.
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0%
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______ is a good alternative to use if you have a Penicillin allergy, unless you're also allergic to ______
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Aztreonam, Ceftazidime
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If you have no choice but to use a penicillin to treat someone who is allergic to penicillin, what can you do?
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-Can perform desensitization: Slowly give small doses to deplete patient's IgE; Give repeated, progressively larger doses until reach desired dose
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What are the natural penicillins?
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-Penicillin G (benzylpenicillin)
-Penicillin V (phenoxymethyl penicillin) |
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What is the administration route of Penicillin G and Penicillin V?
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PCN G=IV/IM only
PCN V=PO -The oral dose of V is in smaller concentrations than the IV/IM dose of G; can't substitute V for G if have severe infections (i.e. meningitis) |
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Natural penicillins:
-Elimination -Dosing |
-Eliminated renally
-Have very short half lives, so give doses frequently (can do as continual infusion) |
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Natural Penicillins:
-Uses |
-Most bacteria are resistant
-Used for susceptible strep infections (Group A strep pharyngitis) -Used for syphilis (Treponema pallidum); IM injection comes as oil immersion form that sticks around in muslce and lasts longer (can't give oil immersions IV because can cause a fat embolism) |
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What are four antistaphylococcal penicillins?
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-Methicillin
-Dicloxacillin -Oxacillin -Nafcillin |
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1. How are Nafcillin and oxacillin administered?
2. How is Dicloxacillin adminstered? |
1. Given IV
2. Given PO |
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How do antistaphylococcal penicillins differ from natural penicillins?
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-They are not broken down by most of the beta lactamases produced by resistant bacteria(but now methicillin resistant Staph (MRSA) are resistant)
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How are nafcillin and oxacillin eliminated?
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-Nafcillin=hepatic elimination
-Oxacillin=dual elimination -Do not have to adjust doses for renal patients |
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What is an extra side effect of Nafcillin?
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-Causes phlebitis; better tolerated as a central line than peripheral line
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-Why was methicillin removed from the market?
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-It had too high of an incidence of acute interstitial nephritis
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What are the uses of the antistaph PCNs?
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-Methicillin susceptible staph infections (MSSA), such as cellulitis and endocarditis
-also as Streptococci activity |
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What are 2 aminopenicillins?
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-Ampicillin
-Amoxicillin |
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1. Administration of ampicillin
2. Administration of amoxicillin |
1. Ampicillin=PO, IV
2. Amoxacillin=PO |
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Why do aminopenicillins have improved Gram negative activity?
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-Have an amino group that makes them more lipophillic and can get through porins better
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Who has better bioavailability, amoxicillin or ampicillin, and why is that important?
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-Amoxicillin has better bioavailability than ampicllin, so is less likely to kill the GI flora and cause diarrhea
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Why aren't the aminopenicllins active against staph?
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-Because they are susceptible to beta lactamases
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What is the spectrum of aminopenicillins?
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-Strep
-Enterococci -Some non-beta lactamase producing gram negative rods (susceptible e. coli, susceptible Protues, suceptible Klebsiella) -Listeria monocytogenes -H. pylori |
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What are the main uses of aminopenicillins?
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1. Upper respiratory infections
2. UTIs, especially in pregnant women 3. Peptic ulcer disease 4. Drug of choice for enterococcal infections |
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What are 2 antipseudamonal penicilloins?
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-Piperacillin
-Ticarcillin |
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How are piperacillin and ticarcillin administered?
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-Given IV
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You should not give _______ in the same central line as antipseudamonal penicillins
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aminoglycosides (because piperacillin or ticarcillin can inactivate aminoglycosides)
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1. How is ticarcillin eliminated?
2. How is piperacillin eliminated? |
1. Renally
2. Both renal and biliary elimination, saturatable |
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What is an addition adverse effect of antipseudamonal PCNs?
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Causes more severe thrombocytopenia than others
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What is the spectrum of piperacillin and ticarcillin?
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-Active against P. Aeruginosa
-Same activity as aminopenicillins, but more GNR coverage -Suceptible to beta lactamases (not used against staph) |
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What are the main uses of piperacillin and ticarcillin?
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-Hospital acquired pneumonia
-Nosocomial infections (because active against p. aeruginosa and better GNR coverage than ampicillin/amoxicillin) |
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What are the most common Beta lactam/Beta lactamase inhibitor combos?
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1. Piperacillin/Tazobactam (Zosyn)
2. Ticarcillin/Clavulanate (Timentin) 3. Ampicillin/Sublactam (Unasyn) 4. Amoxicillin/Clavulanate (Augmentin) |
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How are BL/BLIs administered?
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All IV, except amox/clav (Augmentin) is oral
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What are the spectrums of combo drugs?
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-Same as parent + bacteria that would be susceptible without beta lactamases
All active against: -Strep -Enterococcus -MSSA -Have better GNR coverage than parent alone -Anaerobes (BLI adds little anti-pseudamonal activity of piperacillin or ticarcillin because pseudamonal resistance is via different mechanism) (Less potential to produce resistance than cephalosporins) |
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Main uses of BL/BLI combos
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-GI infections, including abscess and peritonitis
-abscesses -hospital acquired pneumonia -serious nosocomial infections -diabetic would infections |
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Cephalosporins
-MOA -General characteristics |
-Beta lactams with six member ring making them less susceptible to beta lactamase
-None are active against enterococcus -as you increase in generation number, you get better Gram negative rod activity |
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Two first generation cephalosporins
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-Cefazolin
-Cephalexin |
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Administration of first generation cephalosporings
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-Cefazolin=IV
-Cephalexin=PO |
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Elimination and distribution of 1st generation cephalosporins
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-Renal elimination
-No CNS penetration |
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Useful spectrum of cefazolin and cephalexin
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-Good gram + activity plus some GNR
-MSSA, Streptococci |
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Uses of cefazolin and cephalexin
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-Surgical prophylaxis
-cellulitis -UTIs |
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Four second generation cephalosporins
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-Cefuroxime
-Cefaclor -Cefoxitin (cephamycin) -Cefotetan (cephamycin) |
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Administration of Cefuroxime, Cefaclor, Cefoxitin, Cefotetan
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Cefuroxime=PO and IV
Cefaclor=PO Cefoxitin=IV Cefotetan=IV |
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-Activity of second generation cephalosporins
-Activity of cephamycins |
-Worse Gram + activity and better Gram - activity than first generation
-Especially active against Neisseria (gonorrhea) -Cephamycins (Cefoxitin, cefotetan) active against gut anaerobes |
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Uses of 2nd generation cephalosporins
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-Gonorrhea
-URTI and LRTI -Surgical prophylaxis (cefoxitin, cefotetan) |
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Four third generation cephalosporins
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-Ceftriaxone
-Cefotaxime -Ceftazidime -Cefpodoxime |
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Administration of third generation cephalosporins:
-ceftriaxone -cefotaxime -ceftazidime -cefpodoxime |
-ceftriaxone=IV
-cefotaxime=IV -ceftazidime=IV -cefpodoxime=PO |
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Spectrum of Ceftriaxone, cefotaxime, cefpodoxime
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Decreased anti-staph activity and increased anti-strep activity
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Spectrum of Ceftazidime
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-No useful Gram positive coverage; better Gram negative coverage
-active against Pseudomonas |
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Elimination of 3rd generation cephalosporins
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-Renally
-Except ceftriaxone is eliminated both renally and via biliary system: Can cause biliary sludging in neonates and jaundice |
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Main uses of third generation cephalosporins
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-meningitis
-CAP and HAP -lyme disease (Cefazidime DOC) -skin and soft tissue infections -UTIs, including severe pyelonephritis -febrile neutropenia (ceftazidime) |
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Fourth generation cephalasporin
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-Cefepime
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Cefepime
-Admiistration -Elimination |
-IV only
-Renal |
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Cefepime spectrum
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-broadest of the cephalosporins, both Gram + and Gram -
-MSSA and Strep -GNRs -Pseudomonas aeruigonsa |
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Name a monobactam
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Aztreonam
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Aztreonam
-Administration -Elimination |
-IV only
-renal |
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Spectrum of Aztreonam
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-Only active against Gram negative rods
-Active against pseudamonas (similar to ceftazidime because have same side chain) |
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Main uses of aztreonam
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-Gram negative infections in patients with allergies to other beta lactams, except if have allergies to ceftazidime
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Name four carbapenems
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-Imipenem/Cilastatin
-Meropenem -Doripenem -Ertapenem |
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Carbapenems
-Administration -Elimination |
-IV only
-Renal |
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Addition adverse effects of carbapenems
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-Higher incidence of seizures, especially imipenem
-nausea |
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Why is imipenem always given with cilastatin?
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Imipenem is broken down by a renal dihydropeptidase, and cilastatin inhibits it
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Useful spectrum of Imipenem, Meropenem, Doripenem
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-Have very broad spectrum and should not be first line agent for most indications; stable to most beta lactamases
-MSSA and Strep (not if PCN resistant) -Enterococci -Many GNRs -Pseudamonas -anaerobes |
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Useful spectrum of Ertapenem
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-Not active against enterococci
-Not active against pseudamonas -not active against acinetobacter species -Otherwise active against MSSA, strep, and other GNRs |
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Carbapenems are the drugs of choice for....
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Extended Spectrum beta lactamase (ESBL) producing Gram negative rods; i.e. GNRs that are resistant to beta lactams except carbapenems
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Main uses of carbapenems
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-Nosocomial infections
-Mixed aerobic/anaerobic infections -febrile neutropenia |
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Bactitracin
-MOA |
-Peptide antibiotic
-interferes with dephosphorylation of bacoprenol pyrophosphate, disrupting peptidoglycan translocation |
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Bactitracin
-adverse reactions |
-Highly nephrotoxic
-therefore only used topically |
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Bactitracin
-uses |
-minor skin infections; active against Gram positive cocci and bacilli
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Fosfomycin
-MOA -uses |
-inhibits peptidoglycan monomer synthesis
-used for simple UTIs; can give just once but has lower cure rates |
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Cycloserine
-MOA -uses |
-Inhibits enzyme that links D-ala molecules
-used as 2nd or 3rd line TB med |
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Name a Glycopeptide
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-Vancomycin
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MOA of glycopeptides (vancomycin)
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-Bind to terminal D-ala-Dala chain of peptidoglycan, inhibiting cell wall synthesis
-slowly bacteriacidal |
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Glycopeptides (Vancomycin)
-Administration -kinetics |
-Given IV for systemic infections; given orally only for GI infections and C dif colitis
-time-dependent: give at relatively constant dose |
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Vancomycin
-Adverse effects |
-Red man syndrome (when infused too quickly, not an allergy)
-Nephrotoxicity (increased risk if using other nephrotoxic agents) -Ototoxicity |
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Useful spectrum of vancomyin
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-Gram positive
-anaerobes -DOC for MRSA infections -active against C. difficile |
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Main uses of vancomycin
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-MRSA infections
-Gram positive infections in patients with severe beta lactam allergies |
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Daptomycin
-MOA |
-Inserts into cell membrane of Gram positive organisms; causes cations to leak in, depolarize cell, and clean cell death
-rapidly bacteriacidal |
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Daptomycin
-kinetics -administration -distribution -excretion |
-Concentration dependent
-Poor bioavailibility, given IV only -Distributes well to lungs, but inactivated by surfactant and can't use for pneumonia -excreted renally |
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Daptomycin
-useful spectrum |
-Gram positives
-Anaerobes -MRSA and VRE |
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Daptomycin uses
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-Skin and skin structure infections
-staph bacteremia -endocarditis -MRSA and VRE |
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Adverse effects of Daptomycin
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-Elevations of Creatinine kinase, possibly from rhabdomyolisis
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Name two polymyxins
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-Colisin
-Polymyxin B |
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MOA of polymyxins (colisin, polymyxin B)
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-Bind to cell membrane of Gram negative organisms, disrupting permeability and causing leakage of cellular components
-rapdily bacteriacidal |
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Polymyxins (colisin, polymyxin B)
-kinetics -administration -excretion |
-concentration dependent
-Poor bioavailability; given via inhalation, IV, or topically -renal excretion |
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Spectrum of polymyxins
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-Many Gram negatives
-Multi-drug resistant strains of pseudamonas -MDR Klebsiella -MDR Acinetobacter -Inactive against Serratia and Providentia |
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Adverse effects of Colisin and polymyxin B
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-Nephrotoxicity
-Neurotoxicity |
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Uses of polymyxins
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-Treatment of MDR GNR infections (especially pneumonia and bacteremia)
-Eliminate colonization in CF pations |
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What are the seven classes of protein synthesis inhibitors?
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-Aminoglycosides
-Oxazolidinones -Tetracyclines -Chloramphenicol -Lincosamides -Macrolides -Streptogramins |
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Name five aminoglycosides
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-Gentamicin
-Tobramycin -Amikacin -Neomycin -Streptomycin |
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MOA of aminoglycosides
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-Bind to 16S rRNA of 30S ribosomal subunit, causing misreading and incorporation of incorrect tRNAs into A site
-Leads to cell death; bacteriacidal |
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Aminoglycosides
-Administration -kinetics -Distribution -Elimination |
-Very low bioavailability; given IV (Neomycin also topical)
-Concentration dependent; highly reliant on Peak:MIC ratio for efficacy -Sub optimal penetration of lung, bone, CNS; inactivated by the acidic environment of stomach and abcesses -Eliminated renally; nephrotoxicity can worsen elimination |
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Spectrum of aminoglycosides
|
-Excellent activity against Gram negative rods, including Enterobacteraciae, Acinetobacter, and Pseudamonas aeurginosa
-When used in synergy with cell-wall active agents (make membrane more permeable), has good activity against Gram positive cocci -Streptomycin and amikacin are active against Mycobacterium |
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|
Pseudamonas has develped resistance to which aminoglycosides?
|
Gentimicin>Tobramycin>Amikacin
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Adverse effects of aminoglycosides
|
-Neuromuscular blockade; or can prolong the action of NM blockers
-Ototoxicity; can be auditory of vestibular, irreversible -Nephrotoxicity: More suceptible if elderly, hypovolemic, renal dysfunction, or taking other nephrotoxic agents; dependent on time exposed, not concentration |
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What are the benefits of extended interval dosing of aminoglycosides (once daily)?
|
-Higher peak
-Lower trough (doesn't affect efficacy because AGs have good post-antibiotic effect) -Less monitoring -NOT for Gram-positive synergy with cell wall Abxs |
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General dosing guidelines for aminoglycosides
|
-Can give q8h or q24h
-Do not use extended interval dosing for Gram positive synergy -Based on ideal body weight or adjusted BW if obese -Dosing can be variable depending on indication and renal function -Amikacin requires 3-4x higher levels than gentamicin and tobramycin; NOT USED IN GRAM POSITIVE INFECTION |
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Main uses of Aminoglycosides
|
-Gram negative nosocomial infections
-Pseudomonal infections -Mycobacterial infections (Streptomycin, Amikacin) -Gram positive synergy in endocarditis |
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Name a Lincosamide
|
-Clindamycin
|
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|
MOA of Lincosamides (Clindamycin)
|
-Binds to 50S subunit of bacterial ribosomes and inhibits translation
-Bacteriastatic |
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|
Lincosamides (Clindamycin)
ADME |
-90% bioavailable, given orally
-Concentration independent (efficacy does not rely on peak:MIC ratio) -Metabolized by the liver (do not need to adjust for renal function) -Minimal CNS penetration |
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Adverse effects of Lincosamides (Clindamycin)
|
-Pseudomembranous colitis; associated with increased rate of C. difficile infections
-severe nausea, ab pain, diarrhea -skin rash |
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Activity of Lincosamides
|
-Staphylococci and Streptococci
-Active against some MRSA, but NOT used for MRSA pneumonia -Active against anaerobes, but NOT C. difficile -NOT active against Gram negatives -NOT active againstg atypicals |
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Uses of Lincosamides
|
-community penumonia
-Aspiration pneumonia -Skin and soft tissue infections -anaerobic infections -acne |
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Lincosamides (Clindamycin) is often cross resistant with _____ and _______
|
macrolides and streptogramins
-can do a D test to see if staph that is resistant to erythromycin (macrolides) is cross resistant with lincosamides; positive D test=cross resistant |
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Name 3 Macrolides
|
-Erythromycin
-Clarithromycin -Azithromycin |
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|
MOA of macrolides (erythromycin, clarithromycin, azithromycin)
|
-Bind to 23S rRNA of 50S subunit and block exit tunnel
-Bacteriostatic |
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|
Macrolides
-Administration -Distribution -Kinetics -Elimination |
-Highly bioavailable, given orally
-Excellent lung penetration and achieves high intracellular concentrations (good for intracellular infections); poor CNS concentrations -Concentration independent (Efficacy not affected by peak:MIC ratio) -Eliminationm=hepatic metabolism or biliary; don't need to adjust for renal function |
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What is special about Azithromycin clearance?
|
-Is biphasic, with rapid initial elimination followed by a long terminal half life; probably because leeches out slowly from intracellular macrophage location
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Activity of macrolides
|
-Strep pneumoniae
-Atypicals (Legionella, chlamydia, mycoplasma, etc.) -Some Gram negative rods, including H. influenza and M. catarrhalis -Clarithromycin has activity against H. pylori |
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Clarithromycin and azithromycin have _____ resistance issues than erythromycin
|
less
|
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Clarithromycin and azithromycin are taken ____ per day, whereas erythromycin is taken _______ per day
|
once, few times
|
|
|
Adverse effects of macrolides
|
-GI disturbances: N/V/D, especially erythromycin because it directly stimulates gut motility
-Rash |
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Drug interactions of macroclides
|
-Erythromycin and Clarithromycin inhibit CYP450 1A2, 3A3/4
-Cause increased levels of astemizole, cisapride, terfenadine, and fluoroquinolones, which can all increase the QT interval and lead to torsades -Many other interactions as well (Pimozide, statins, verapamil, cyclosporine, benzos) -Azythromycin as lower interaction potential |
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Main uses of macrolides
|
-Community acquired pneumonia
-URTIs -STDs -MAC infections -peptic ulcer disease (Clarithromycin) -promotility (Erythromycin) |
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Name a ketolide
|
Telithromycin (Ketek)
|
|
|
MOA of ketolides (Telithromycin)
|
-macrolide analog; binds to 23S rRNA of 50S subunit and blocks exit tunnel
|
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|
Spectrum and uses of ketolides (telithromycin)
|
-Same spectrum as macrolides (some GNRs, atypicals, etc.) but is more active against strep pneumonia
-Used for outpatient Community acquired pneumonia |
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|
Adverse reactions of ketolides
|
-N/V/D
-Rash -Hepatotoxicity (has black box warning) |
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|
Name 3 tetracyclines
|
-Minocycline
-Tetracycline -Doxycycline (also Demeclocycline) |
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|
MOA of tetracyclines (Minocycline, tetracycline, doxycycline)
|
-Binds reversibly to 16S rRNA of 30S subunit, inhibiting tRNA binding and formation of the initiation complex
-Bacteriostatic |
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|
Tetracyclines
-Administration -Distribution -Kinetics -Excretion |
-Hihgly bioavailable, can be given orally
-Poor CNS penetration -Concentration-independent -Minocycline and doxycycline are hepatically eliminated; tetracycline is renally eliminated |
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|
Spectrum of tetracyclines
|
-Atypicals
-Some GNRs (limited by resistance, esp. tetracycline) -Gram positive cocci (limited by resistance, esp. tetracycline) -Minocycline has some MRSA activity -Bacillus antracis, Burgdorferi, Y. pestis, T. pallidum, H. pylori |
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|
Adverse effects of tetracyclines
|
-Tooth discoloration
-N/V, borborygmous (stomach growling) -Photosensitivity |
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|
Drug interactions with tetracyclines
|
-Multivalent cations (Mg, Ca, Al) chelates tetracyclines and decreases their absorption; avoid taking with milk and supplements [cations can also chelate with FQs and decrease their absorption]
-Decreases the bacteriacidal activity of cell wall synthesis inhibitors |
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|
Main uses of tetracyclines
|
-Acne
-community acquired pneumonia (doxycycline) -tick borne disease -peptic ulcer disease -STDs |
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|
Use of demeclocycline (member of tetracyclines)
|
-used in treatment of syndrome of inappropriate antidiuretic hormone (SIADH)
|
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|
Name a Glycylcycline
|
Tigecycline (Tagacil)
|
|
|
MOA of Glycylcyclines (Tigecycline)
|
-Modified tetracycline that expands it spectrum because there is less efflux pump resistance
|
|
|
Spectrum of Tigecycline
|
-Many GNRs and GPCs, including MRSA and VRE
-Good anaerobe coverage -Does NOT cover pseduamonas, Proteus, or C. difficile |
|
|
Adverse effects of Tigecycline
|
-High incidence of nausea and vomiting
|
|
|
Uses of Tigecycline
|
-Skin and soft tissue infections
-Intra-abdominal infections -not adequate enough coverage for hospial acquired pneumonia because doesn't cover pseudamonas |
|
|
Chloramphenicol MOA
|
-Binds to 23S rRNA of 50S subunit, inhibiting synthesis by blocking tRNA peptidyl transferase activity
-Bacteriastatic |
|
|
Chloramphenicol
-Administration -Distribution -Elimination |
-High bioavailability (IV dose=PO dose)
-Good CNS penetration -Metabolized hepatically via conjugation |
|
|
Spectrum of chloramphenicol
|
-Streptococci
-Staphylococi (not MRSA) -Enterococci, including VRE -Anaerobes -Some GNRs |
|
|
Drug interactions with chloramphenical
|
-Increases levels of phenytoin, phenobarbital, and warfarin
|
|
|
Adverse effects of chloramphenicol
|
-Gray baby syndrome, due to inability of new borns to conjugate chloramphenicol: vomiting, flaccidity, gray coloration, respiratory distress, metabolic acidosis
-Bone marrow suppressiohn; reversible, dose-related suppression is fairly common, whereas idiopathic, irreversible suppression is less common |
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|
Main uses of choramphenicol
|
rarely in US-VRE
|
|
|
Name 2 Streptogramins
|
-Quinupristin and Dalfopristin; marketed together as Synercid
|
|
|
MOA of Streptogramins (Quinipristin/Dalfopristin)
|
-Bind to different parts of 23S rRNA of 50S ribosome, halting protein synthesis
|
|
|
Spectrum of Streptogramins
|
-Bacteriacidal against Penicillin-resistant Strep and MRSA when used in combo
-Bacteriastatic against Enterococcus Faecium, NOT active against E. faecalis -also has activity against atypicals |
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|
Adverse effects of Streptogramins
|
-Phlebitis; should be infused via a central line
-Severe myalgia and/or arthralgia -Hepatotoxicity -Line crystallization when mixed with saline |
|
|
Drug interactions with Quipristin/Dalfopristin
|
-Inhibits CYP3A4; increases levels of cyclosporine, nefidipine, midazolam, tacrilomus, etc.
|
|
|
Maine uses of Streptogramins
|
Vancomycin resistant E. faecium infections and MRSA infections in patients who cannot take other agents
|
|
|
Name an Oxazolidinone
|
Linezolid
|
|
|
MOA of Oxazolidinones (Linezolid)
|
-Binds to 23S rRNA of 50S subunit, blocks formation of 70S complex
-Binding site is ditinct from other protein synthesis inhibitors |
|
|
Spectrum of Linezolid
|
-Bacteriostatic against staph (including MRSA)
-Bacteriastatic against Enterococcus (including VRE -Bacteriacidal against Streptococci (including PCN resistant) |
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|
Linezolid
-Administration -Elimination |
-Highly bioavailable: PO=IV dose
-Elimination: Dual hepatic (not via CYP450) and renal elimination |
|
|
Drug interactions with Linezolid and adverse effects
|
-Weak reversible inhibitor of MAO; avoid tyramine, MAOIs, careful with SSRIs, TCAs, neosynephrine nose sprays
-potential for increased BP and seratonin syndrome: muscle rigidity, high fever, change in mental status -Myelosuppresion, particularly thrombocytopenia |
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|
Main uses of Linezolid
|
-MRSA or VRE infections
|
|
|
Name six major dimorphic fungi
|
1. Histoplasma
2. Coccidioides 3. Blastomyces 4. Paracoccidiodes 5. Penicillium 6. Sporothrix |
|
|
Name three major yeast fungi
|
1. Trichosporon
2. Cryptococcus 3. Candida |
|
|
Name four major mold fungi
|
1. Aspergillus
2. Fusarium 3. Scedosprium 4. Zygomycetes (Mucor) |
|
|
MOA of polyenes
|
-Bind ergosterol in fungal cell membrane, leading to leakage of cell membrane and death
|
|
|
2 common polyenes
|
1. Amphotericin B
2. Nystatin |
|
|
Adverse effects of polyenes
|
1. Nephrotoxicity
2. Electrolyte wasting 3. Infusion-related reactions: fever, chills rigors; can ameliorate by giving Tylenol or hydrocortisone before infusion |
|
|
Pharmacokinetics of polyenese
|
1. Poorly absorbed (not oral)
2. Well distributed, but not detectable in CNS 3. Metabolism and elimination unknown 4. Are concentration dependent |
|
|
Uses of Nystatin B
|
-Used topically for superficial infections
-Swish and swallow for thrush -Nephrotoxic |
|
|
Spectrum of Amphotericin B (polyene)
|
1. Candida species EXCEPT C. Lusitaniae
2. Drug of choice for Cryptococcus neoformans (meningitis) 3. Active against dimorphic fungi 4. Active against many molds -Broad spectrum |
|
|
Adverse effects of amphotericin B
|
-Toxicity is considerable: nephrotoxicity, electrolyte wasting, infusion reactions
|
|
|
What is the difference between amphotericin B deoxycholate and the lipid formulations?
|
-Deoxycholate is soap-like and helps AmB into solution
-The lipid formulations are all less nephrotoxic and have less infusion reactions than the conventional AmBDd -But the lipid formulations are less efficacious and require higher doses -Liposomal formulation is the least nephrotoxic and causes the least infusion reactions -But the |
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|
MOA of the Echinocandins
|
-Inibit 1,3 glucan synthase, which decreases 1,3 glucan production (component of cell wall)
|
|
|
Pharmacokinetics of Echinocandins
|
-Poor bioavailibility, IV only
-Well distributed -NOT eliminated renally -Concentration dependent |
|
|
General spectrum of Echinocandins
|
-Strong activity against all Candida species, but has weaker activity against C. parapsilosis
-Pseudo-static against Aspergillus species, but inactive against many molds -Fungicidal against yeasts, EXCEPT ineffective for Cryptococcus |
|
|
Adverse effects of Echinocandins
|
-Hepatotoxicity
-Infusion related reactions -Phlebitis (expensive too) |
|
|
Name 3 Echinocandin drugs
|
-Caspofungin
-Micafungin -Anidulafungin |
|
|
Caspofungin (Echinocandin)
-approved uses |
-Salvage therapy of Invasive Aspergillosis
-Esophageal candidiasis -Candidemia -Febrile neutropenia |
|
|
Caspofungin
-Metabolism -Drug interactions |
-Metabolized in liver, but not by CYP450
-Drug interactions with cyclosporin (added hepatotoxicity) -Drug interactions with Rifampin (decreased casopfungin AUC) |
|
|
Micafungin (Echinocandin)
-approved uses |
-Esophageal Candidiasis
-Invasive Candidiasis -Prophylaxis of Candida infecytions in HSCT patients |
|
|
Micafungin
-Metabolism -Drug interactions |
-Metabolized by liver, not CYP450
-Increases AUC of Sirolimus and Nifedepine |
|
|
Anidulafungin
-approved uses |
-Invasive candidiasis
-esophageal candidiasis |
|
|
Anidulafungin
-metabolism -interactions |
-Not metabolized, degrades slowly in the plasma
-Anidulafungin comes in a solubilizer ethanol solution, which has potential for Antabuse-like reactions when taken with metronidazole |
|
|
Azoles
-MOA |
-Inhibit fungal cytochrome p450, decreasing ergosterol formation
-Are not antagonistic with polyenes |
|
|
Azoles
-Adverse reactions |
-Hepatoxicity
-Rash |
|
|
Azoles
-pharmacokinetics |
-Absorption variable between different azoles (some can be given orally)
-Widely distributed, EXCEPT Itraconazole does not reach CNS -All have some hepatic metabolism -Time-dependent -Are fungicidal against modles and fungistatic against yeasts |
|
|
Name 4 common Azoles
|
1. Fluconazole
2. Itraconazole 3. Voriconazole 4. Posaconazole |
|
|
Fluconazole (azole)
-Administration -Elimination -Adverse effects |
-IV, tablets, oral suspension
-Eliminated hepatically and renally; need to adjust for renal function -Hepatoxicity, rash, and drug interactions |
|
|
Fluconazole
-Activity |
-Active against yeasts, including Cryptococcus and Candida
-BUT not active against C. Kruseii and C. Glabrata -Active against some dimorphic fungi -NO anti-mold activity |
|
|
Fluconazole
-Uses |
-Treatment of many forms of candidiasis (except C. Kruseii and C. glabrata)
-Prophylaxis of Candidiasis -Treatment of some dimorphic fungal infections |
|
|
Itraconazole (azole)
-Administration -Adverse effects |
-Available IV, capsules, and oral solution
-Absorption from oral solutions not so great, and does not get into CNS -Hepatotoxic, rash, plus diarrhea -Black box warning: can cause CHF -Drug interactions |
|
|
Itraconazole
-Activity |
-Active against dimorphic fungi
-Active against Aspergillus and many other molds, including Dematiaceous molds -Active against yeasts, including Cryptococcus and Candida -BUT not active against C. Glabrata and C. Kruseii |
|
|
Itraconizole
-Uses |
-Not used for cryptococcus because doesn't get into CNS
-Drug of choice for dimorphic fungal infections -Main use is for Onychomycosis -Some mold and yeast infections |
|
|
Volriconazole
-Administration -Pharmacokinetics |
-IV, capsule, oral solution
-Metabolized hepatically -Non-linear Pharmacokinetics (doubling dose greatly increases plasma concentrations by way more than 2x) -SBECD IV formulation is renally eliminated |
|
|
Voriconazole
-Adverse effects |
-Drug interactions, esp. with immunosuppressives
-Visual disturbances -Hepatotoxicity -Visual hallucinations |
|
|
Voriconazole
-Activity |
-Yeasts, including Cryptococcus and all Candida species
-Drug of choice for molds, including Aspergillus, Fusarium, Scedosporium, demateaceous molds, and endemic fungi -BUT not active against zygomycetes |
|
|
Voriconazole
-uses |
-Invasive aspergillosis and other mold infections (NOT zygomycetes)
-Invasive Candidiasis -Esophageal Candidiasis -Febrile Neutropenia? |
|
|
Posaconazole
-Administration -Adverse effects |
-Only available orally, absorbed better with higher fat meals
-Rash, hepatotoxicity, and drug interactions |
|
|
Posaconazole
-Activity |
-Yeasts, including Candida and Cryptococcus
-Molds, including Aspergillus and Zygomycetes |
|
|
Posaconazole
-Utility |
-Prophylaxis of fungal infections
-Mold infections, especially Zygomycetes |
|
|
Ketaconazole
-drug class -uses |
-azole
-Used topically in anti-dandruff shampoo, sometimes orally |
|
|
Clotrimazole, Econazole, Miconazole, Oxiconazole, Sulconazole, Terconazole, Tioconazole
|
-Azoles used topically on skin or vagina
-Have dermatologic side effects |
|
|
5-Flucytosine
-MOA |
-Antimetabolite; the fungal version of 5-FU
-Deaminated within fungal cells to 5-Fluoro-uracil, which inhibits RNA production and DNA synthesis |
|
|
5-Flucytosine
-Pharmacokinetics |
-Highly bioavailable
-Widely distributed, including CNS -Excreted renally; adjust dose for renal dysfunction |
|
|
5-Flucytosine
-activity |
-Active against Cryptococcus neoformans
-Active against Candida species, BUT less active against C. Kruseii -Some activity against Aspergillus and other molds |
|
|
5-Flucytosine
-Clinical uses |
-Combo therapy for cryptococcal meningitis
-Rarely used for Candidiasis because resistance develops quickly |
|
|
5-Flucytosine
-Adverse effects |
-Bone marrow suppression, dose related
-GI intolerance -Rash -Hepatotoxicity |
|
|
Terbinafine
-MOA |
-Allyamine antifungal
-Inhibits squalene epoxidase, preventing synthesis of ergosterol |
|
|
Terbinafine
-Administration -Pharmacokinetics |
-Orally or topically
-40% bioavailable, high first pass effect -Concentrates in nails, fat, and skin -Metabolized in liver -Non-linear elimination: stayes in body for a long time |
|
|
Terbinafine
-Adverse effects |
-Hepatotoxicity
-Neutropenia -Stevens-Johnson Syndrome (epidermis separates from dermis) |
|
|
Terbinafine
-Activity and uses |
-Clinical activity mostly against dermatophytes
-Used for onychomycosis |
|
|
Griseofulvin
-MOA |
-Inibits fungal mitosis by interacting with microtubules
|
|
|
Griseofulvin
-Administration -adverse effects |
-Given orally
-Has prolonged half life -Causes headaches, other CNS effects |
|
|
Griseofulvin
-Activity and uses |
-Active against dermatophytes
-Used for onychomycosis, but not preferred |
|
|
Uses of 3rd generation cephalosporins
|
1. Skin and soft tissue infections
2. UTIs (including severe pyelonephritis) 3. Meningitis 4. Community acquired pneumonia 5. Hospital acquired pneumonia 6. Ceftazidime=DOC for Lyme Disease 7. Ceftazidime=febrile neutropenia |
|
|
Uses of Cefepime
|
-Febrile neutropenia
-Hospital acquired pneumonia -Nosocomial infections |
