Exam 2 Flashcards

Question

What are the mechanisms of action of erythromycin, clindamycin, and lincomycin?

Answer 1

* Inhibits the 50 S ribosome * Inhibits protein synthesis

Answer 2

* Inhibits binding of aminoacyl tRNA to ribosomes * Targets the 30 S ribosome * Inhibits protein synthesis

Answer 3

* Targets 23 S ribosomes * Inhibits protein synthesis

Answer 4

* Interferes with the cell membrane function by using cationic detergent

Answer 5

* Inhibits DNA-dependent RNA polymerase * Overall, interferes with nucleic acid synthesis

Answer 6

* Interferes with supercoiling of DNA by action on DNA gyrase (topoisomerase II)

Answer 7

* Inhibits lipid synthesis

Answer 8

* Prevents synthesis of folic acid

Answer 9

* Oral * Mild to moderate infections * IV * Moderate to severe infections * Patient is unable to take oral agents * If afebrile for 2-3 days, consider switching to oral * IM * IV access isn't obtainable * This is only a short term solution

Answer 10

* Want an antibiotic that is renally excreted * Want an antibiotic where a high concentration of the drug is eliminated unchanged

Answer 11

* Used to estimated creatinine clearance rate to determine kidney function * [ (140-age) x (weight) ] / [ serum creatinine x 72 ] * If female, multiple equation by 0.85 * Can be used for majority of renally excreted drugs

Answer 12

* B-lactamase production * Staphylococcus, Haemophilus influenza * PBP (penicillin binding protein) changes * Pneumococcus (strep pneumo), MRSA, Enterococcus * Porin channel changes * Gram negative organisms

Answer 13

Methyltransferases that alter drug binding sites on 50S ribosomal subunits

Answer 14

Transport systems that pump drugs out of the cell

Answer 15

* Increased PABA formation * Target enzyme sensitivity

Answer 16

* The target enzyme changes * Drug efflux

Answer 17

* Alterations in normal flora results in the removal of inhibitory influences in the body, which can lead to superinfections * Usually due to broad spectrum antibiotics * Enterobacteriaceae (PEK, SE) * Candida spp. * C. diff

Answer 18

* Aztreonam - used in cases with anaphlaxis allergic reactions * Last resort is Colistin (kitchen sink) * Only choose 1 from each row

Answer 19

* Renal elimination - most important route of elimination for most PCNs * Optimize dose for varying renal function levels * Adjustment for renal insufficiency is a must * Allows for high concentrations in the urine * Minimizes side effects from accumulation * Infants excrete PCNs at slower rate due to immature transport system

Answer 20

* Majority of PCNs yield peak levels 1-2 hours after ingestion * Food delays and decreases absorption * EXCEPTIONS: Amoxicillin, Pen V, Carbenicillin

Answer 21

* Penicillin VK * Oxacillin * Cloxacillin * Dicloxacillin * Nafcillin * Ampicillin * Amoxicillin

Answer 22

* Penicillin G * Methicillin * Carbenacillin * Ticarcillin * Mezlocillin * Piperacillin

Answer 23

* Well distributed to: * Lung, liver, muscle, kidney, bone, placenta * Levels are sufficient to inhibit bacteria in: * Abscesses * Middle ear * Pleural * Peritoneal * Synovial fluids * Insoluble in lipid * Unless inflammation is present, there is poor distribution to the brain, CSF, and prostate

Answer 24

**Hypersensitivity reactions** * Hypersensitivity to one PCN means probable hypersensitivity to all PCNs * All PCNs have equal potential for inducing allergic reaction * May occur on the first exposure or upon unknown re-exposure * Types * Immediate (anaphylaxis) - IgE mediated (E for emergency) * Delayed (rash) - IgM or IgG. Maculopapular rash is most common

Answer 25

* Hypersensitivity reaction (most common) * Eosinophilia * Interstitial Nephritis * Pseudomembranous Colitis

Answer 26

* Penicillin G is a natural penicillin * Not very soluble, makes it harder to absorb * Four variants: * Benzathine Penicillin (IM) * Sustained release * Prophylaxis in rheumatic fever * Procaine Penicillin G (IM) * Penicillin G with sodium salt * Has sodium salt to help with solubility * Pencillin G VK (v potassium) * Has potassium salt to help with solubility * Pen VK must be used for oral administration - others are acid labile

Answer 27

Some gram positive organisms * Staph produce B-lactamases: 99% resistant * Streptococcus pneumoniae resistant * PBP changes * Gonorrhea resistance occuring

Answer 28

* Penicillinase resistance * They are resistant to B-lactamase enzymes produced by bacteria * IV * Methicillin * Oxacillin * Nafcillin (hepatic elimination) * PO * Cloxacillin * Dicloxacillin

Answer 29

* Penicillins with an amino group that allows for penetration into gram negative cell wall * Ampicillin - QID * Amoxicillin - TID * Adverse effects: * Hypersensitivity * Diarrhea * Take with food to decrease sx * When taken with food: * Amoxicillin - absorption not impaired

Answer 30

* Streptococcus * Enterococcus * Haemophilus (non B-lactamase producing) * Salmonella/Shigella (non B-lactamase producing) * Proteus mirabilis, E. coli, +/- Klebsiella

Answer 31

* Carboxypenicillins have increased permeability to cell wall * **Carbenicillin** * Indanyl salt - stable oral form (Geocillin) * High urine concentrations * Body normally cannot tolerate high dosages necessary for concentrations to treat systemic infections * **Ticarcillin** * 2-4x more active than Carbenicillin against Pseudomonas * Can be significant (so restrict use) * Adverse effects: * Hypersensitivity * Platelet dyfunction (dose dependent side effect caused by carboxy group) * Na+ overload

Answer 32

* Streptococcus * Piddly/PEK * SPACE bugs * Pseudomonas aeruginosa (high concentration necessary)

Answer 33

* Bacteroides fragilis (non B-lactamase producing strain) * Streptococcus, enterococcus * PEK bugs * SPACE bugs

Answer 34

* Mezlocillin * Piperacillin * Azlocillin

Answer 35

**Combo drugs** * Augmentin - amoxicillin + clavulanic acid * Unasyn - ampicillin + sulbactam * Timentin - ticarcillin + clavulanic acid * Zosyn - piperacillin + tazobactam Advantages: * Adds staphylococcus coverage * Adds anaerobic coverage

Answer 36

* R1 - Spectrum of activity, PBP affinity, B-lactamase susceptibility * R2 - Stability, metabolism, adverse effects, drug interactions, protein binding, t_1/2

Answer 37

* Oral agents * Rapidly and completely absorbed * Available as prodrug esters and nonesterified compounds * **Prodrug esters** * Cefuroxime axetil (Ceftin - 2nd gen) * Cefpodoxime proxetil (Vantin PO - 3rd gen) * Hydrolyzed in intestines to the active drug * Food _enhances_ absorption

Answer 38

* Binds to PBPs * Inhibits crosslinking of peptidoglycan strands * Efficacy of each is related to affinity to PBPs * Can be susceptible to some B-lactamases * Similar in MOA to PCNs

Answer 39

* Well distributed to a variety of body tissues and fluids * CSF penetration especially with inflamed meninges * 3rd gen cephalosporins (Ceftriaxone) are great choice for various meningitis bacterial infections * Requires high dose

Answer 40

* Renal excretion * All agents except 2 below * Dosage adjustments in patients with renal insufficiency * Hepatic elimination * Ceftriaxone, Cefoperazone

Answer 41

* **Hypersensitivity reaction** * Rash, drug fever * 5-15% cross reactivity with PCNS * Do not use in patients who had anaphylaxis (or other severe reaction) to PCNs * **Bleeding** * NMTT side chain * Cefamandole, cefoperazone * Disturbance in vitamin K dependent clotting factors * ** Alcohol, disulfiram-like intolerance** * Agents with NMTT side chain (Cefamandole, Cefaperazone) * **GI symptoms** * Diarrhea * C. diff (also called Pseudomembranous colitis) * **Interstitial nephritis** * Rare * Cephalosporins are "close cousins" PCNs * Remember - Methicillin PCN taken off market for this SE * **Serum sickness in children** * Cefaclor (Ceclor - 2nd gen)

Answer 42

* Cefamandole, Cefaperazone * Can cause unique adverse effects such as: * Alcohol intolerance * Bleeding

Answer 43

* **Warfarin** * Potentiation of anticoagulant effects * **Alcohol** * Disulfiram-like reaction * Agents with NMTT side chain only * **Probenecid** * Prolongs excretion in cephalosporins that have tubular secretion

Answer 44

Oral: * Cephalexin (Keflex) << * Cefadroxil Parenteral: * Cefazolin << Spectrum: * Staph, Strep * Piddly, Ecoli

Answer 45

Oral: * Cefuroxime << * Cefprozil * Cefaclor Parenteral: * Cefuroxime << Spectrum: * Staph, Strep * PEK, Piddy

Answer 46

Parenteral: * Cefoxitin << * Cefotetan << Spectrum: * Staph, Strep * PEK, Piddly * Anaerobes (Bacteroides) <<

Answer 47

Oral: * Cefixime * Cefdinir * Cefopodoxilme Parenteral: * Ceftriaxone << * Cefotaxime Spectrum: * Strep * SACE (+ PEK, Piddly)

Answer 48

Parenteral: * Ceftazidime << * Cefoperazone Spectrum: * Poor Gram + * SPACE (+ PEK, Piddly)

Answer 49

Parenteral: * Cefepime << * Ceftaroline << * Ceftaz-avibactam << * Ceftolozane/tazobactam << 4th gen spectrum: * Staph, Strep * SPACE (PEK, Piddly) 5th gen spectrum: * Staph, Strep * SCE

Answer 50

* **Enterococcus** * Exception: Ceftaroline (4th/5th gen) * **MRSA** * Exception: Ceftaroline (4th/5th gen) * **Chlamydia, Mycoplasma, Legionella** (CML - atypicals) * **Listeria monocytogenes** * **Anaerobes (Bacteroides)** * Exception: Tan Fox (2nd gen cephamycins - Ce _fox_ itin, Cefote _tan_ )

Answer 51

* 4th/5th gen cephalosporin with B-lactamase inhibitor * Approved for complicated UTIs * Very expensive * **Decrease efficacy observed in patients with moderate renal function** * CrCL 30<50 mL/min, not bad renal function, not great

Answer 52

* 4th gen cephalosporin with B-lactamase inhibitor * Can be used for very resistant bacteria and complicated cases * Save for only more resistant bacteria * Very expensive * **Clinical cure rates were low in subgroups with decreased renal function** * CrCl < 31-50 mL/min (Not terrible, not great)

Answer 53

* CAP * 3rd gen - recommended in CAP guidelines * These do not cover atypical pathogens * Nosocomial Pneumonia * Ceftaz, Cefepime * Consider double coverage for SPACE bugs * Meningitis * Ceftriaxone * 3rd gen - use higher doses * Skin or soft tissue infections * 1st gen for Staph/Strep (simple cellulitis, non-DM) * 2nd gen cephamycins or 3rd/4th gens for severe cases OR diabetic patients

Answer 54

Surgical prophylaxis * Cefazolin * Long t_1/2 * Covers Staph * Convenient dosing for Osteomyelitis/MSSA Sepsis * 2nd gen cephamycins * Abdominal/GI surgeries Febrile neutropenia * Ceftazidime or Cefepime, +/- Vancomycin Endocarditis * Depends on organisms

Answer 55

**DIME** * Doripenem * Imipenem * Meropenem * Ertapenem

Answer 56

* Carbacephem (carbapenem) B-lactam agent * Extensive renal metabolism by the brush border enzyme *dehydropeptidase-1* * Cilastatin added to prevent renal metabolism (Doesn't add coverage, just enhances pharmacokinetic principles) Spectrum: * Staph, Strep, Enterococcus * SPACE * Anaerobes * ESBL organisms (PEK resistant bugs)

Answer 57

* A combo drug: carbapenem + cyclic boronic acid B-lactamase inhibitor * Very expensive * Reserved for very resistant bugs (particularly resistant to Box-and-one) * Precaution: * B-lactam allergery * Hx of seizures

Answer 58

* Etrapenem - longest half life * Allows once daily administration

Answer 59

* Seizures * Particularly for imipenem * Watch for history of epilepsy, seizures, etc. * Cross Allergenicity with PCNs * Hematologic * Anemia, leukopenia, thrombocytopenia

Answer 60

* **Broad spectrum** * Staph, Strep, Enterococcus * SPACE * Anaerobes * ESBL organisms - PEK resistant bugs

Answer 61

* **Broad spectrum** * Staph, Strep, Enterococcus * SPACE * Anaerobes * ESBL organisms - PEK resistant bugs

Answer 62

* **Broad spectrum** * Staph, Strep, Enterococcus * SPACE * Anaerobes * ESBL organisms - PEK resistant bugs

Answer 63

* Broad spectrum coverage * However, should save to use only in resistant cases * Covers ESBL organisms - not many drugs cover this * Use imipenem and meropenem over doripenem (IM statistically work better than D) * Watch for seizures

Answer 64

* Carbapenem antibiotic * Spectrum: * Staph/Strep ( _no_ Enterococcus coverage) * Anaerobes * ESBL organisms (PEK) * _No_ SPACE bugs * Not quite as big of gram neg coverage * Reserve for: * Serious, life threatening illnesses * Multi-organism infections * Acute necrotizing pancreatitis * ESBL organisms <<

Answer 65

* "Ace in the Hole" * Monobactam antibiotic * Used when a patient has an anaphylaxis reaction to PCN, use this instead * Not quite as good as PCNs, but safer * Covers serious gram negative infections

Answer 66

* Aminoglycoside binds to outer membrane of cell * Results in rearrangement of LPS (Lipopolysaccharide) * Uptake is energy dependent * Source of energy is an electrochemical gradient * Gradient is decreased in an anaerobic environment * Once across the membrane, the drug is irreversibly trapped into the bacteria cytoplasm * AGs bind to the 30S and 50S ribosomal subunit leading to decreased protein synthesis and misreading of mRNA * Very high intracellular concentrations

Answer 67

* Bacteri _cidal_ * Mechanism appears static, but its action is cidal. Not fully understood * Concentration depenent killing with PAE * After exposure to AGs, continued killing occurs

Answer 68

* **Absorption** * Poorly absorbed from GI tract * **Distribution** * Distributed freely into vascular space * Concentration in lungs are 25-50% of those achieved in serum * Distribution to CSF is only 20%, even with inflammation * HOWEVER, distribution to CSF is much better in neonates * **Excretion** * 99% unchanged via glomerular filtration

Answer 69

* Local reactions * Thrombophlebitis * Nephrotoxicity * Usually associated with high troughs * Ototoxicity - Impairment of 8th cranial nerve * Usually associated with high peaks * Neuromuscular blockade (rare)

Answer 70

**Gram negative** * Piddly, PEK, SPACE * Kanamycin does not cover PACE **Gram positive** * Staph, sometimes - usually use in a combo to cover this * Enterococcus * Use combo drug for synergy * Common combo: Ampillicin + Gent

Answer 71

* Mainly used for serious gram negative infections * Can be used in combo drugs

Answer 72

* TB (Streptomycin - used as a second line) * Brucellosis (Gentamycin + TCN or Chloramphenicol)

Answer 73

* Neomycin * Used for: * Suppression of intestinal bacterial flora for elective colorectal surgical prophylaxis * Hepatic coma - decreases the number of ammonia forming bacteria * Hyperlipidemia - reduces cholesterol absorption

Answer 74

* Monitor peak and trough values * Keep trough > 2 mcg/mL * Peak concentrations depend on location * Consider the Hartford Nomogram, but assess level frequently * Large daily doses may be equally as effective as smaller multi-daily doses, but with lower toxicity (b/c peaks and troughs) * Rely on PAE * Narrow therapeutic index

Answer 75

* Glycopeptide antibiotic derived from streptomyces orientalis **Mechanism of action** * Inhibits biosynthesis of peptidoglycan during cell wall formation * Complexes with D-alanyl-D-alanine precursor * Bacteri _cidal_ , for multiplying organisms * Exhibits PAE

Answer 76

**Absorption** * Poorly absorbed from GI tract * IV only for systemic infections * Oral route for C.dif **Distribution** * Distributed freely into most body fluids and tissues (if IV) * Distribution to CSF _only_ with inflammation **Excretion** * Excreted almost entirely unchanged via glomerular filtration **Half life** * 6-12 hours * Dosing interval Q8, 12, 24, 48 hours

Answer 77

* Local reactions * Thrombophlebitis * Red-Man Syndrome (Vancomycin Infusion Reaction) << * Histamine-like reaction * Hematologic reactions * Neutropenia * Eosinophilia * Thrombocytopenia * Hypersensitivity * Maculopapular rash * Nephrotoxicity * More common with concomitant AGs or other nephrotoxic agents * Oral vancomycins do not have nephrotoxicity risk due to breakdown in intestines * Ototoxicity * Correlates with high peak

Answer 78

* **Gram Positive** * Staphylococcus aureus (including _MRSA_ ) * Staphylococcus epidermidis (including _MRSE_ ) * Streptococcus spp. * Enterococcus spp. * Clostridium spp. * Bacillus anthracis * Corynebacteria **Does not work for VRE**

Answer 79

* Serious B-lactam resistant gram positive infections * C. diff infection * Prophylaxis for major surgical procedures involving implantation of prosthetic materials * Surgical prophylaxis * Prophylaxis for endocarditis in patients at high risk for endocarditis

Answer 80

* Routine surgical prophylaxis * Empiric therapy in febrile neutropenic patients * Unless: evidence of possible gram positive infection in hospital setting * Eradication of MRSA colonization * Continued empiric use in patients whose cultures are negative * Gram negative infections * Treatment of B-lactam-sensitive gram positive infections in patients with renal failure

Answer 81

* Both have risk of nephrotoxicity/ototoxicity * In both, monitor peaks and troughs * Vancomycin - gram positive * Aminoglycosides - gram negative

Answer 82

**Mechanism of action** * Irreversibly binds to the 50S bacterial ribosomal subunit * Quinupristin - inhibits chain formation, resulting in early termination * Dalfopristin - inhibits peptide elongation by interfering with peptidyl transferase * Individually - static, combo - cidal **Used for:** * MRSA * PCN resistant strep pneumo * VRE * Covers E. faecium, but not great * Anaerobes * Some gram negative **IV only**

Answer 83

Mechanism: * Oxazolidinone class * Binds to 23S rRNA of 50S subunit Used for: * MRSA, VISA, VRE, PCN-resistance strep pneumo * Can be IV or PO (both 100% bioavailability) Adverse effects: * Myelosuppression - thrombocytopenia * Superinfection (Yeast) * Mitochondrial toxicity - long course Interactions: * MAOI * Watch with co-administration of SSRIs for serotonin syndrome

Answer 84

Mechanism: * Oxazolidinone class * Binds to 23S rRNA of 50S subunit * Reversible MAOI Used for: * Most resistant gram positives - MRSA, VISA, VRE, PCN-resistant strep pneumo * IV = PO (100% bioavailability) Adverse effects: * Thrombocytopenia, neutropenia, paresthesias, blurred vision Interactions: * MAOI, watch for co-administration with SSRIs Pearl: * Breast cancer resistance protein (BCRP) inhibitor in intestine

Answer 85

* Glycolipopeptide Spectrum: * Gram positive - Staph (MRSA), Strep, Enterococcus Adverse effects: * Contraindication with concomitant IV unfractionated heparin infections << * May falsely elevate INR * Nephrotoxicity * Red man syndrome with infusion * Increased mortality for patients with renal dysfunction * Risk of fetal development toxicity Cons: * Semi-synthetic derivative of Vancomycin * May have cross sensitivity with vanco * Same side effects * REMS program watch list Pros: * No need to monitor peaks/troughs

Answer 86

* Glycolipopeptide * Single dose per week - but costs $1500-2000 per dose Interactions: * Weak inhibitor of 2C9 and 2C19, and weak inducer of 3A4 and 2D6 * May increase bleed risk with warfarin Adverse effects: * Infusion related reaction (red-man syndrome) * Monitor LFTs and SCr Coverage: * Gram positive - Staph (MRSA), Strep, Enterococcus * Approved for skin and soft tissue infections

Answer 87

* Glycolipoptide * Single or double dose per week * May use with CrCl < 30mL/min, but not dialysis Coverage: * Gram positive (including MRSA) * Approved for skin and soft tissue infections Interaction: * CAN use with warfarin

Answer 88

* Polymyxin E antibiotic - bacteriocidal * Polymyxin B - OTC triple antibiotic ointment Coverage: * SPACE bug coverage (+ Piddly, PEK) Administration: * Prodrug * Mainly IV, some inhaled or intrathecal (but rare) * Dose based on colistin base activity (CBA) Adverse effects: * Nephrotoxicity * Neurotoxicity "Kitchen Sink: * Reserved for last ditch effort, when Box-and-One doesn't work * Used especially for PA in SPACE bugs, resistant PEK, Pan-resistant gram negative organisms

Answer 89

* Phosphoric acid derivative, bacteriocidal * Covers only UTIs (low serum concentration) - also called cystitis * Gram positive and gram negative organisms * MRSA/VRE * ESBL * Dose - 1 packet dose, PO * Adverse effects: mostly GI

Answer 90

* Glycylcycline agent - bacteriorstaic * Very expensive Coverage: * MRSA/VRE * Gram negative * Acinetobacter (not pseudomonas) * Anaerobes (GI infections) * Approved for complicated skin infection, intra-abdominal infections, community acquired pneumonia * **Does not** cover bacteremia, does not attain high serum concentrations

Answer 91

* Lipopeptide (bacteriocidal) Covers: * Gram positive - very well * MRSA, VRE * Complicated skin and soft tissue infections * Bacteremia, right sided endocarditis * **Does not** cover pneumonia * Inactivated by pulmonary surfactant Adverse effects: * Rhabomyolysis * Monitor CPK baseline and weekly * Eosinophilic pneumonia (rare)

Answer 92

* Topical treatment (cream/ointment 2%) * MRSA colonization eradication from Nares * Controversial regarding long term efficacy of eradication * Other uses: Impetigo, infected wounds

Answer 93

* Bacteria require tetrahydrofolic acid (derivative folic acid), which is a cofactor in the synthesis of thymidine, purine, DNA * Bacterial cell walls are impermeable to folic acid, so they must synthesize it from PABA * Sulfonamides compete with PABA for the enzyme dihydropteroate synthetase * Sulfonamides may have an increased affinity for the enzyme, compared to PABA * Host cells are not affected b/c they require pre-formed folic acid (cannot synthesize it). * Sulfonamides = bacteriostatic

Answer 94

* Anaphylaxis * Cutaneous reactions * Morbilliform rash * SJS * Erythema Multiforme * Photosensitivity reaction * Hematological rash * Hypersensitivity reaction * Drug fever, rash * Nephrotoxicity * Crystalluria w/less soluble compounds (Sulfadiazine, Sulfathiazole) * Administer with fluids, check hydration status of patients prior to use * Kernicterus * Pregnancy - competes for bilirubin binding sites on plasma albumin * Results in increased fetal blood levels of unconjugated bilirubin

Answer 95

* Excreted via glomerular filtration * Extent of glomerular filtration varies with each agent

Answer 96

* Gram Positive * Staph (MRS), Strep * Bacillus anthracis * Gram Negative * Piddly, PEK, CE of SPACE * Other * Chlamydia trachomatis * Toxoplasma gondii (protozoa) * Plasmodium falciparum (protozoa-malaria) * Nocardia

Answer 97

* Overproduction of PABA * Neusseria, Staph * Structural change in dihydropteroate synthetase * E. coli * Decreased permeability of bacteria to drug

Answer 98

* Uncomplicated UTIs * Pneumocystis carinii (tx and prophylaxis) * Nocardosis * Toxoplasmosis * Malaria (Chloroquine-resistant) * Rheumatic fever prophylaxis (PCN allergy)

Answer 99

* Combo drug: Sulfonamide (sulfamethoxazole) + Trimethoprim * Sulfonamide - targets dihydropteroate enzyme (PABA --> Folic acid) * Trimethoprim - targets dihydrofolate reductase (Folic acid -> Tetrahydrofolic acid)

Answer 100

* Inhibits dihydrofolate reductase, which prevents the formation of tetrahydrofolic acid * 50,000x more active against bacterial DHFR than the human enzyme * Can be bacteriostatic or bacteriocidal

Answer 101

Excretion: * Excreted 80% unchanged via glomerular filtration and tubular secretion Adverse effects: * Cutaneous Reactions * Pruitis * Rash * GI Reactions * Nausea, vomiting, diarrhea * Elevated serum transaminases, bilirubin * Hematologic Reactions * **Caution** in patients with possible folate deficiency * Alcoholics, pregnant women, debilitated patients, malabsorptive syndromes

Answer 102

**Spectrum:** * Gram positive * Staph spp., Strep spp., Bacillus anthracis * Gram negative * Piddly, PEK, CE of SPACE * Other * Pneumocystis carinii - used in conjunction with dapsone **Indications** * Acute uncomplicated UTI * Recurrent UTI prophylaxis * Traveler's diarrhea

Answer 103

Gram positive: * Staph, strep * Bacillus anthracis Gram negative: * Piddly, PEK, CE from SPACE Other: * Nocardia asteroides * Chlamydia trachomatis * Toxoplasma gondii (protozoa) * Plasmodium falciparum (protozoa - malaria) * Pneumocystic carinii (fungus)

Answer 104

* UTI * Uncomplicated UTI * Prophylaxis of UTI * Acute and chronic prostatitis * RTI * COPD exacerbations * Pneumonia * Acute otitis media * Acute sinusitis * PCP (Px and Tx) * GI Infections * Salmonella/Shigella * Traveler's Diarrhea * Cholera * STDs * Uncomplicated gonococcal infections * Chancroid * Bacterial vaginosis * Other Infections * Stenotrophomonas maltophilia (DOC)

Answer 105

* Warfarin * Highly likely to potentiate anticoagulant effects * Methotrexate * Can displace methotrexate from protein binding sites * Increases free methotrexate

Answer 106

* Unclear mechanism * Possibly interferes with early stages of bacterial carbohydrate metabolism by inhibiting acetyl CoA * Possibly due to production of reactive 5-nitro anion, free radicals

Answer 107

* Distribution * Serum/tissue concentrations are insignificant * Urine concentrations are very high * Excretion * Rate of excretion is linear, related to CrCl * Patients with impaired GFR - decrease in efficacy, increase in systemic toxicity * Do not use if CrCl < 40-60

Answer 108

* Hypersensitivity reactions * Rash * Hematologic reactions * Hemolytic anemia * Hepatotoxicity * Peripheral neuropathy * Esp. in renal insufficiency * GI reactions * Nausea, vomiting, diarrhea * Less with macrocrystalline preparation, compared to microcrystaline suspension form * Pulmonary reactions * Acute - hypersensitivity (fever, cough, dyspnea, eosinophilia, infiltrate) * Subacute - after 1 month therapy (cough, dyspnea, interstitial infiltrate) * Chronic - after 6 months therapy (cough, dyspnea, interstitual infiltrate) Subacute, chronic reactions are often reversible after drug is stopped

Answer 109

Gram positive: * Staph aureus * Staph saprophyticus * Enterococcus faecalis * Enterococcus faecium Gram negative: * E. coli * Klebsiealla pneumonia * Citrobacter spp. * Enterobacter aerogenes Indications: * Acute uncomplicated UTI treatment * UTI prophylaxis

Answer 110

* No antibacterial effect alone * At adequate urine pH (< 5.5), hydrolyzed to formaldehyde, which kills bacteria by denaturing proteins * Urine must sit long enough for this to work. Does not work for catherized patients

Answer 111

* Hypersensitivity reactions * Rash/Pruritis * Hippurate form contains the dye tartrazine - may lead to allergic reactions in asthma patients * Hemorrhagic Cystitis * GI reactions (nausea, vomiting, diarrhea) * **Avoid** in hepatic insufficiency - ammonia byproduct * Renal failure - acid forms could potential lead to systemic acidosis

Answer 112

Absorption * Rapidly absorbed from GI tract * Excellent bioavailability * 10-30% of dose can be hydrolyzed to formaldehyde by gastric acid - enteric coated formulation avoids this Excretion * t_1/2 = 3-4 hours * Renal clearance is 95% total clearance

Answer 113

Spectrum: * Virtually all bacteria and fungi are susceptible to formaldehyde * Certain urease positive bacteria (Proteus) can alkalinize the urine, which stops conversion to formaldehyde Indications: * UTI prophylaxis only * NOT recommended for treatment of acute UTIs

Answer 114

* Rate of hydrolysis of methenamine to formaldehyde * Rate of urine loss from bladder by voiding or drainage

Answer 115

Mech of Action: * Reversibly binds to 50S-ribosomal subunit of bacteria (decreases protein synthesis) * Bacteriostatic Mech of Resistance: * Decreased permeability of the cell envelope * Alteration in 50S ribosomal receptor site * Enzymatic inactivation of erythromycin by esterases

Answer 116

* Erythromycin base * Rapidly inactivated by gastric acid * Enteric coated and film coated forms decrease this inactivation * Base, stearate, and ethylsuccinate * Absorbed better in fasting state * Emycin Estolate * Not affected by food

Answer 117

* Distributes in tissues longer than in blood * Very high concentration in alveolar macrophages and leukocytes compared to extracellular fluids * Azithromycin tissue concentration * 10-100x serum concentrations * Usually 3-5 day course of therapy, stays in body much longer

Answer 118

**Erythromycin** * Primarily biliary excretion * Small percentage in urine * Large proportion of absorbed drug may be inactivated in liver by demethylation **Clarithromycin** * Metabolized in the liver by oxidation and hydrolysis * 20-30% of drug excreted into the urine unchanged **Azithromycin** * Small proportion is metabolized * Mainly biliary excretion * t_1/2 = 68 houts (after multiple doses)

Answer 119

* GI - abdominal cramps, NVD * Thrombophelbitis - IV admin * Allergic reactions * Cholestatis hepatitis (rare) * Avoid estolate form in pregnancy * Large IV doses - ototoxicity, QT prolongation (rare)

Answer 120

* GI symptoms - not as severe as erythromycin * HA * Dizziness * Allergic reactions

Answer 121

* Metabolites form inactive complexes with p450 enzymes * Decreased metabolism of: Theophylline, Warfarin, Carbamazepine, Cyclosporine **Azithromycin** - does not inactivate p450 enzymes

Answer 122

**All** * Gram positive (Staph, Strep) * Atypicals **Clarithromycin & Azithromycin** * Piddly gram negatives * MAC (Mycobacterium avian complex) **Clarithromycin only** * Helicobacter pylori

Answer 123

* Penicillin allergic patients * Community acquired pathogens (Clarithro and azithromycin) * Mycoplasma pneumoniae * Legionnaire's disease * Chlamydia trachomatis nongonococcal urethritis and cervicitis * Chlamydia trachomatis - during pregancy (don't use estolate form)

Answer 124

Mechanism of action: * Binds to 50S ribosome, leading to inhibition of protein synthesis * Derived from lincomycin Pharmacokinetics * Bioavailability = 90% * Food delays absorption * Good tissue penetration * Good for skin and soft tissue infections * Metabolized by liver

Answer 125

* Strep * Staph * Limited bactericidal rate compared to B-lactams * Anaerobes * Bacteroids * Clostridium * Peptostreptococcus, peptococcus * Toxoplasmosis * Sulfonamide allergy

Answer 126

* Allergic reactions * Diarrhea << * 20% of patients * More common with oral form * C. diff infection * Hepatotoxicity (mild and severe)

Answer 127

Mech of action: * Reversibly binds to large 50S subunit of the 70S ribosome Spectrum: * Gram positive * Gram negative * Aerobic and anaerobic organisms * Rickettsia * Chlamydia * Large coverage range

Answer 128

* Suspension * Must be hydrolyzed in the intestines for active chloramphenicol * IV form has incomplete hydrolysis * Serum concentrations after IV therapy are only about 70% of those after oral administration * Excellent CSF concentrations * 30-50% without inflammed meninges * Metabolism via glucuronidation in liver * Wide variations in metabolism and excretion in children - must monitor serum levels

Answer 129

* Bacterial meningitis * H. influenza, Strep pneumo, Neisseria meningitidis * Penicillin/Cephalosporin allergy * Oral alternative if IV cannot be used * Rickettsial infections

Answer 130

Hematologic * Reversible bone marrow depression due to direct pharmacologic effect on inhibition of mitochondrial protein synthesis * Anemia, leukopenia, thrombocytopenia Idiosyncratic Aplastic Anemia * Majority of cases occur weeks-months after completion of therapy, and is not necessarily dose related Gray Baby Syndrome * Abdominal distension, vomiting, cyanosis, circulatory collapse * Drug accumulates -> toxicity -> vomiting, flaccidity, hypothermia, respiratory collapse, gray color * Newborns lack effective glucuronic acid conjugation mechanism to degrade/detoxify system

Answer 131

* Adverse effect of chloramphenicol * Sx: abdominal distension, vomiting, cyanosis, circulatory collapse * Fundamental mechanism of toxicity: inhibition of mitochondrial protein synthesis * Newborns lack effective glucuronic acid conjugation mechanism that degrades/detoxifies the system

Answer 132

Rifampin, Tetracyclines, Ampicillin

Answer 133

* Inhibits bacterial DNA gyrase (topoisomerase II) and topoisomerase IV * DNA gyrase is essential for supercoiling of cellular DNA by a nicking, passing through, and resealing process * Bactericidal * PAE * PAE averages 1-2 hours * Tends to increase with increasing concentrations and length of exposure

Answer 134

* Tendonitis, tendon rupture * Peripheral neuropathies * Psychiatric disturbances * Severe hypoglycemia, coma * Risk for aortic dissection and/or rupture

Answer 135

* No longer recommended as first line treatment options for: * Uncomplicated UTIs * Acute exacerbation of COPD * Sinusitis * May justify use based on: * Allergies * Recent antibiotics * Cultures (new or recent) * Do not use in patients under 18 y/o

Answer 136

* Hypersensitivity reactions * Photosensitivity * Hematologic reactions * Neutropenia * Eosinophilia * Cardiac * QT prolongation * GI * Diarrhea, nausea, vomiting * Nephrotoxicity (rare) * CNS * Headache, dizziness, mental status change * MSK * Arthropathy * Tendon rupture

Answer 137

* Theophylline * Cipro can double Theophylline levels * Levofloxacin - little to no effect * Antacids, iron, sucralfate, multivitamins * Do not give within 2-4 hours of quinolone dose * Warfarin * Increased anticoagulant effect possibly due to metabolism or protein binding changes * Levofloxacin - possibly no effect, but still monitor

Answer 138

Gram positive: * Older agents (Cipro, oflox) - not good coverafe * Newer agents (Levo, moxi, gemi) - better staph/strep coverage Gram negative: * Cipro, levo - SPACE * Moxi - SACE Anaerobics: * Moxifloxacin only * Has indication for complicated abdominal infections Atypicals: * Levo, moxi, cipro - cover CML * Watch for Cipro resistance with Chlamydia

Answer 139

* Type of quinolone * Generally very good coverage, with wide range of FDA approved indications * Not great gram positive coverage, use with another agent * Very potent against gram negative organisms, including pseudomonas * Excellent bioavailability * Use oral form if possible

Answer 140

Gram positive * All three are good for Staph and Strep * Excellent for PCN resistant Strep Pneumo Gram negative * Levofloxacin (SPACE) potency is less than cipro * SACE (no P) for gemifloxacin or moxifloxacin Atypicals * All three cover CML and mycoplasma (walking pneumonia) Anaerobics * Moxifloxacin only

Answer 141

* Newest fluoroquinolone (approved 2017) Coverage: * Staph, Strep, MRSA * E. coli, Enterobacter, Klebsiella, Pseudomonas * Approved for acute bacterial skin and skin structure infections Pearls: * No QT prolongation * No phototoxicity * No markers of ADRs to liver, kidneys or glucose control * Retained FDA warning for tendon ruptures, neuropathy, CNS symptoms

Answer 142

* Altered target enzyme (altered DNA gyrase) * Reduction of Quinolone concentrations intracellularly * Altered drug permeability across cell membrane due to changes in porin channels * Efflux of drug from bacterial cells

Answer 143

* Doxycycline * Minocycline * Demeclocycline * Oxytetracycline * Chlortetracycline * Tetracycline

Answer 144

* Reversibly binds to 30S ribosomal subunit * Decreases protein synthesis * Bacteriostatic

Answer 145

* Bioavailability depends on products * Doxy, Mino: 90-100% * Tetra, Demeclo, Oxy: 58-75% * Absorption decreases with food * Renal elimination: * Tetra, Oxy, Demeclo * Hepatobiliary elimination: * Doxy, Mino

Answer 146

* Photosensitivity * Discoloration of developing teeth * Bones and teeth developing during pregnancy and in children through ~8 y/o * Reversible diabetes insipidus - Demeclocycline * Vestibular effects - Minocycline * Dizziness, ataxia, vertigo * Fanconi-like Syndrome * Associated with outdated citric acid formulation of tetracycline * Nausea, vomiting, lethargy, polydipsia, polyuria, proteinuria, acidosis, hypokalemia

Answer 147

* Decreased absorption of tetracycline agents when co-administered with: * Di- and trivalent cations (Ca, Mag, Zinc, Alum, Iron) * Antacids * Dairy products * Potential antagonism effect with bacteriocidal agents * Tetracyclines are bacteriostatic. Bacteriocidal agents require active growth * Enhances anticoagulation of Warfarin

Answer 148

* Rickettsia infections (parasites) * Rocky Mountain spotted fever * Mycoplasma pneumonia * Chlamydia infections * Urogenital 7 days of doxycycline * Acne * H. pylori in combo with other agents

Answer 149

* In humans, can cause flu-like symptoms (fever, sweats, headaches, back pain, physical weakness) * Contracted by coming in contact with infected animals or animal products (cheese, milk) * Severe infections of CNS or lining of the heart may occur * May cause long-lasting or chronic symptoms such as fever, joint pain, fatigue Treatment: * Tetracycline + Gentamicin

Answer 150

* Acute diarrheal disease, mainly in India and Southeast Asia * Causative agent is Vibrio cholerae * Condition can lead to severe dehydration in a matter of hours * Can cause disease in those who eat contaminated seafood, or have an open wound that is exposed to seawater Treatment: tetracyclines

Answer 151

* Better known as Lyme disease * Bull's eye rash, fever, headache, muscle/joint pain, flu-like symptoms Treatment: tetracyclines

Answer 152

* Syndrome of Inappropriate Antidiuretic Hormone * Treatment: Demeclocycline * Only thing Demeclo is used for

Answer 153

* Viral encephalopathy * Herpes Simplex Virus 1 (oropharyngeal) & 2 (genital) * Herpes simplex labialis (cold sores) * Varicella Zoster Virus * Chickenpox * Zoster (shingles)

Answer 154

1. Attachment - mediated by proteins 2. Entry - cross host membrane 3. Uncoating - virus loses capsid proteins 4. Transcription - exposed nucleic acid transcribed to mRNA 5. Translation 6. Genome replication * RNA virus requires ribonucleic triphosphates * DNA virus requires deoxyribonucleoside triphosphates 7. Assembly 8. Exiting - via cell lysis or budding * Retroviruses have extra steps and occur in a different order

Answer 155

* Acyclovir * Glanciclovir * Zidovudine * Efavirenz * Nucleoside and nucleotide analogues * Inhibits polymerase

Answer 156

* Amantadine * Rimantidine * Blocks M2 (pH gated proton channel) that opens in response to acidification

Answer 157

* Oseltamivir * Zanamivir

Answer 158

* Herpes Family * Varicella (chickenpox), Zoster (shingles), Encephalitis * Cytomegalovirus (CMV) * Common in transplant patients (retinitis and pneumonia) * Influenza * Types A and B * Hepatitis * Types A, B, and C * Respiratory Syncytial Virus (RSV) * Pneumonia in children * HIV * Systemic destruction of helper T-cells

Answer 159

* Active drug (Prodrug is Valacyclovir) * Acyclovir phosphorylated to monphosphate form via HZV or VZV thymidine kinase * Monophosphate to triphosphate via cellular enzymes --> Chain termination

Answer 160

* Bioavailability: 10-30% (IV, PO, topical) * Good CSF penetration for treatment of viral meningitis * Renally eliminated, requires dose reduction Adverse effects: * Reversible nephrotoxicity d/t crystalline nephropathy, more likely with high dose bolus and IV formulations * CNS (HA, hallucinations, seizures) * Nausea, vomiting, diarrhea - dose and age dependent * Hepatic (hyperbilirubinemia)

Answer 161

* Prodrug (Active form is acyclovir) * Bioavailability: 70% * PO form only * Rapidly converted to acyclovir via intestinal and hepatic metabolism

Answer 162

* Best outcome if used within 48-72 hours of appearance of lesion/rash * IV Acyclovir is drug of choise (DOC) for Encephalitis * Valacyclovir - Zoster and Herpes Simplex (less frequent dosing) * Genital Herpes Simplex * 1st episode: 10 day treatment * Recurrent: 5 day treatment

Answer 163

* One of the most commonly identified causes of viral encephalitis * Occurs in all age groups * Symptoms: * Fever * Focal neurologic symptoms, altered mental status * Other invasive herpes infections (immunocompromised patients) * HSV Esophagitis * HSV Pneumonitis * Treatment of choice: * IV Acyclovir 10 mg/kg for 14-21 days

Answer 164

* Reactivation of Varicella Zoster (chicken pox) * Risk increases with age, immune statue * Unilateral dermatome * Painful lesions * Complication: * Post-herpetic neuralgia * Blindness

Answer 165

* Steroids * Neuropathic pain medicine (Gabapentin, pregabalin, TCAs, NSAIDs) * Treatment for painful herpetic lesions * Antiviral treatments Prevention: Shingles vaccine (Zostavax) * Approved for patients > 50 y/o * Recommended for patients > 60 y/o

Answer 166

* Docosanol - oral herpes simplex * Imiquimod - gential/perianal warts * Podofilox - gential/perianal warts * Podophyllin - 25% liquid administered in clinic directly to wart

Answer 167

* DNA double stranded virus within the Herpes Virus Family * Commonly infects advanced immunosuppressed patients and transplant patients * Impacts specific organ symptoms: * Retinitis * Colitis * Esophagitis

Answer 168

* Active drug (pro drug - Valganciclovir) * MOA - similar to Acyclovir * 10x more potent than Acyclovir for treating CMV * Bioavailability = 6-9% (IV, intravitreal, PO) * Use for: * CMV retinitis prophylaxis + treatment * Adverse effects: * CNS with behavior changes and headache * Nausea, vomiting * Neutropenia (15-40%) * Thrombocytopenia (5-20%)

Answer 169

* Prodrug (active form is Ganciclovir) * MOA - Similar to Acyclovir * Bioavailability = 60% (PO only) * Used for: * CMV Retinitis prophylaxis and treatment * Can do intravitreal treatment - surgically implanted to treat CMV retinits in AIDS patients

Answer 170

* Active drug (prodrug form is Famciclovir) * MOA - similar to Acyclovir * Available in US as topical cream * Used to treat herpes simplex cold sore treatment * Adverse effect: application site irritation

Answer 171

* Prodrug (active form is Penciclovir) * MOA - similar to acyclovir * Bioavailability: 65-77% * Renally excreted * Adverse effects: Headache, GI symptoms * Used to treat herpes simplex, herpes zoster * Best result if started within 72 hours

Answer 172

* Used to treat CMV * Must be administered with Probenecid * Second line treatment - reserved for CMV retinitis if other treatments fail * Administer with normal saline to decrease chances of nephrotoxicity (hydration is key!) * MOA - Interacts with DNA polymerase either as an alternative substrate or a competitive inhibitor * Adverse effects: * Highly nephrotoxic * Neutropenia (15%)

Answer 173

* Inorganic phosphate that doesn't require phosphorylation by thymidine kinase * MOA - competes for pyrophosphate in viral DNA polymerases * Adverse effects: * Nausea, vomiting, diarrhea (25-50%) * Nephrotoxic, severe electrolyte imbalances * Seizures, anemia (33-50%), neutropenia * EKG changes (1st degree AV block, hyper/hypotension) * Used for: * CMV in AIDS patients, in combo with Ganciclovir for recurrence

Answer 174

* Topical treatment of Condylomata acuminate (warts) * Induces local immuno-response (interferon alpha, beta, gamma, TNF) to decrease viral load * Apply 3x weekly for 16 weeks (~50% complete clearance) * Keep in mind: recurrence is common

Answer 175

* Herpes family virus * Mono (mononucleosis - infectious EBV) * Most people are infected at some point * Transmitted through body fluids (Saliva, sharing drinks, kissing, etc) * Symptoms: * Extreme fatigue * Sore throat * Spleenomegaly * Lymph node enlargement * Treatment: * Rest, avoid straining if splenomegaly is present * Typically resolves in 2-6 weeks * No drug treatment to shorten symptoms

Answer 176

* MOA - prevents virus from entering host cell * Renally excreted, adjustment to dose required * Adverse effects: CNS (confusion, insomnia) * Used for: * Was once used to treat and prevent influenza A * Must be started within 48 hours of symptoms * May play a small role in treating Parkinson's Disease, but reserved for advancing symptoms

Answer 177

* MOA - prevents virus from entering host cell * Renally excreted, no dose adjustment needed * Adverse effects: CNS (confusion, insomnia) - more pronounced with Amantadine * Used for: * Was once used to treat and prevent influenza A * Must be started within 48 hours of symptoms

Answer 178

* Tamiflu * MOA - inhibits neuroaminidase which is required for the release of the virus from the infected cell * Taken PO, causes GI side effects, take with food * Used for: * Prophylaxis and treatment of Influenza type A and B * Usually only lessons symptoms by 1 day if taken within 48 hours of start of symptoms

Answer 179

* MOA - inhibits neuroaminidase which is required for the release of the virus from the infected cell * Taken as a dry powder delievered by inhalation * May cause wheezing and bronchospasm * Avoid in patients with COPD/Asthma * Used for: * Prophylaxis and treatment of Influenza type A and B * Usually only lessons symptoms by 1 day if taken within 48 hours of start of symptoms

Answer 180

**Anti-herpetic** * Acyclovir * Valacyclovir * Famciclovir * Penciclovir (topical) **Anti-CMV** * Ganciclovir * Valganciclovir * Cidofovir * Foscarnet **Anti-influenza** * Amantadine * Rimantadine * Ostelmavir * Zanamivir