Antimicrobials and Antifungals Flashcards

Question

Imipenem

Answer 1

Carbapenem beta lactam antimicrobial nephrotoxic - drug degrades in renal tubule by kidney enzyme dehydropeptidase 1 Administer with Cilastatin to prevent degradation associated with seizures in humans

Answer 2

Carbapenem beta lactam antimicrobial not nephrotoxic

Answer 3

clavulanic acid sulbactam tazobactam bind irreversibly to beta lactamases so when administered with a beta lactam, the beta lactam can bind to bacterial PBP.

Answer 4

Toxicity to beta lactam group considered very low. Potential adverse reactions: Type 1 hypersensitivity from urticaria to anaphylaxis - frequency unknown in small animals (occurs in 0.7%-10% of people receiving penicillin Type 2 hypersensitivity can also occur -- hemolytic anemia, thrombocytopenia and neutropenia reported Type 4 reactions usually manifest as cutaneous disease Can rigger immune-mediated reactions such as IMHA Can kill neric flora which cause nausea, vomiting, diarrhea High doses can result in seizures and other neurologic diseases (more likely if brain diseases already present)

Answer 5

Antimicrobial used to treat gram negative infections Rely on aerobic bacterial metabolism parenteral administration only requires monitoring of renal function Exhibit synergistic bactericidal effects when administered in combination with beta lactams

Answer 6

Inhibit bacterial protein synthesis by binding to ribosome resulting in faulty protein. further synthesis increases aminoglycoside uptake by the cell which eventually leads to complete cessation of ribosomal activity. Stage 1: outer bacterial lipopolysaccharide membranes are negatively charged while aminoglycoside is positively charged. Ionic binding allows aminoglycoside entry into cell and increase cell wall permeability Stage 2: Energy dependent phase Faulty protein synthesis inserted into cytoplasmic membrane of bacteria allowing for more aminoglycoside entry (slow process and relies on ATP hydrolysis --> therefore reduced activity in anaerobic conditions). This stage can be blocked by inhibitors of oxidative phosphorylation or electron transport Stage 3: Aminoglycoside accumulate quickly after nonspecific membrane channels inserted --> increasing rate of mistranslation of protein synthesis

Answer 7

1. enzymatic mutation of aminoglycoside molecules 2. target modification in ribosomal 30s subunit structure 3. increase in aminoglycoside efflux 4. intrinsic resistance to anaerobes

Answer 8

Absorption: water soluble; poorly absorbed from GI tract therefore must be administered parenterally Distribution: primarily extravascular - can reach bone, synovial fluids, peritoneal fluid (especially if inflammation present). Distribution to bronchial secretions is good. Does not penetrate cell membranes well because of positive charge. Not recommended for CNS, eyes or prostate. Elimination: primarily through kidneys unchanged by glomerular filtration.

Answer 9

Aminoglycosides readily taken up by cells in proximal tubules and in ears 5-15% will suffer aminoglycoside induced nephrotoxicity (excreted through kidneys) Nephrotoxicity: dose dependent majority of aminoglycoside is excreted but small amount is absorbed by renal tubules Necrotic cells slough into tubular lumen which can result in obstruction Underlying renal dysfunction predisposes patient to aminoglycoside induced nephrotoxicity Often damage is reversible if caught early. Ototoxicity: hair cells update drug resulting in cell death and inflammation dose and duration dependent Ototoxicity is not reversible Neuromuscular blockade Rarely reported, but can be severe enough to cause respiratory depression @ high doses - calcium release impaired at level of neuromuscular junction --> hypocalcemia. Concurrent use of neuromuscular blockade medications or myorelaxants may augment effets.

Answer 10

Amikacin Gentamicin sulfate Tobramycin sulfate neomycin

Answer 11

aminoglycoside Monitor for casts in urine and increases in BUN/Creat dosage may need to be adjusted in critically ill patients can be administered IV, IM, SQ q 24 hrs

Answer 12

Aminoglycoside Monitor for casts in urine and increases in BUN/Creat Can be administered IV, IM, SQ, q 24 hours

Answer 13

Amino glycoside Monitor for casts in urine and increases in BUN/Creat Can be administered IV, IM, SQ q24 hours

Answer 14

Aminoglycoside Used to treat hepatic encephalopathy Minimal GI absorption administer PO q 6-12 hrs

Answer 15

synthetic antimicrobials Inhibit bacterial DNA gyrase which prevents bacterial DNA synthesis, replication and division, resulting in cell death Bactericidal Widest spectrum against gram-negative bacteria Incomplete effectiveness against gram-positive and anaerobic bacteria RESISTANCE TO FLUOROQUINOLONES CAN DEVELOP DURING THE COURSE OF THE TREATMENT

Answer 16

hepatic metabolism and excreted in bile +/- urine either unchanged or as metabolites Most are eliminated by the kidneys Half-life depends on renal elimination and dose

Answer 17

increasing rate of resistance attributed to widespread use of fluoroquinolones Use of fluoroquinolones can lead to development of resistance to other antimicrobial classes Fluoroquinolones should not be used as 1st line treatment. (exception - pyelonephritis, lower respiratory tract infections, bacterial prostatitis, hepatobiliary infections).

Answer 18

GI upset: V/D, nausea, abdominal cramping Neurologic: rapid administration risk CNS adverse effects including seizures It may lower the seizure threshold; therefore, do not use or use it with extreme caution in patients with seizure disorders. Juveniles: cartilage defects - not recommended in growing animals retinopathy: irreversible blindness in cats Rapid IV administration may result in histamine release in dogs Can chelate with positively charged ions - contains beta-keto acid group that can bind to and chelate with positively charged ions; most profoundly seen with aluminum and copper, but can also happen with magnesium and calcium Cardiovascular signs can result in hypotension, bradycardia, prolonged QT Rare reports of fluoroquinolones used in patients with necrotizing fasciitis resulted in activating bacteriophage, rapid bacterial cell lysis, and release of bacteriophage superantigen and the potential sequelae of toxic shock syndrome.

Answer 19

2nd fluoroquinolone only one available as injectable for dogs and cats generally safe, though adverse effects can be permanent Adverse effects can include: - blindness in cats - cartilage defects in juvenile animals Max dose in cats if 5mg/kg q24hrs primary metabolite of enrofloxacin is ciprofloxacin.

Answer 20

2nd gen fluroquinolone longest post-antibiotic effect and half-life No clinical trials support the translation of long half-life to superior antimicrobial efficacy.

Answer 21

3rd gen fluoroquinolone Labeled for use in cats 12 weeks +, off-label for dogs (use in dogs associated with bone marrow suppression) broad spectrum activity including many anaerobic bacteria High potency with lower MIC values when compared with other fluoroquinolones

Answer 22

2nd gen fluoroquinolone not labeled for veterinary use Significantly higher doses needed in dogs than in humans and even so does not always achieve desired serum levels

Answer 23

4th gen fluoroquinolones improved activity against gram-positive and gram-negative only used in human medicine

Answer 24

nitromidazole antimicrobial Indicated to treat most gram-positive anaerobic and all gram negative anaerobic organisms At higher dosages - effective against protoozoal diseases (giardia, amebiasis, trichomoniasis); however higher doses associated with CNS adverse effects Concentration dependent Within the bacteria: reduced and incorporates into bacterial DNA causing loss in helical structure inhibits nucleic acid synthesis results in cell death Bactericidal

Answer 25

Good oral bioavailability Excellent tissue distribution with good penetration to BBB and CSF Elimination is dose dependent with renal and biliary routes Hepatic metabolism --> dose reduction with liver dysfunction Use with caution in patients with neurologic disease

Answer 26

GI upset neurologic signs associated with higher doses and prolonged use Clinical signs: vertical nystagmus, ataxia, paraparesis, tetraparesis, hypermetria, head tilt, tremors Treatment: discontinue therapy and provide supportive care (IV fluids, antiemetics, sedatives PRN). Most patients improve within 3 days.

Answer 27

Phenicol Bacteriostatic Inhibit protein synthesis by binding to 50S ribosomal subunit In mammalian cells, can also inhibit mitochondrial protein synthesis (especially erythropoietic cells).

Answer 28

Gram-positive Gram-negative anaerobic intracellular organisms such as: Chlamydia, mycoplasma and rickettsia Not effective against pseudomonas aeruginosa

Answer 29

Good bioavailability through oral administration and tissue distribution Penetrates CNS Limited prostate Hepatic metabolism --> dose reduction with liver dysfunction Excreted in kidneys in mostly inactive form

Answer 30

Dose-dependent bone marrow suppression in humans, dogs and cats (cats more sensitive) **DO NOT SPLIT** **DO NOT PULVERIZE** Caretakers to wear gloves Dogs: hind end weakness and GI signs

Answer 31

Chloramphenicol is a potent inhibitor of CYP450. Drugs that require CYP450 may need dose adjust to prevent toxicity.

Answer 32

Competitive inhibitors of 50S ribosomal subunits Do not give chloramphenicols with lincosamides and macrolides Tetracyclines bind to 30S subunit Therefore Chloramphenicols may act synergistically with tetracyclines

Answer 33

Lincosamide Antimicrobial binds to 50S subunit of ribosome Bacteriostatic and time dependent

Answer 34

Effective against gram-positive aerobes and anaerobes Effective against mycoplasma and toxoplasmosis

Answer 35

Good bioavailability after oral administration. Can also be administered SQ and IV Good tissue distribution especially to skin and bone penetrates CNS penetrates blood prostate barrier --> good for gram-positive bacterial prostatitis penetrates biofilms --> use for gingivitis, and peridontal disease

Answer 36

Overall rare Humans: overgrowth of C. diff

Answer 37

Tetracycline inhibits protein synthesis by binding to 30S ribosomal subunit bacteriostatic Lipid soluble --> greater bacterial penetration

Answer 38

1st line therapy for tick borne rickettsial diseases felin upper airway canine respiratory Gram-positive, gram-negative, mycoplasma, chlamydia, rickettsial, spirochetes not considered effective against anaerobic infections

Answer 39

found in all bacteria secondary to presence of efflux pumps alterations to binding sites bacterial enzymatic destruction

Answer 40

high bioavailability drug is lipophilic so will also distribute into placenta and milk limited in prostate highly protein bound 30%-40% CSF elimination: mostly unknown with 16% in urine unchanged predominance for intestinal elimination and enterohepatic recirculation

Answer 41

Adverse effects more likely with decrease in rental function. Give with food to decrease GI upset Associated with ESOPHAGEAL EROSION - follow with 6ml water Incorporates into bone and enamel resulting in discoloration IV Doxycycline needs to be diluted and ideally given through central line to reduce risk of thrombophlebitis Give over 1 hour as anaphylactic shock has been reported Rarely hepatotoxic

Answer 42

should not be administered with antacids, aspirin or calcium containing fluids as it chelates with cations May bind to cholestyramine because of its lipophilic nature

Answer 43

individually - bacteriostatic used together = bactericidal and time dependent work on different stages of bacterial folic acid production Combo therapy 1:5 trimethoprim: sulfonamide

Answer 44

broad spectrum gram-positive, gram-negative and anaerobes Ineffective against mycoplasma and rickettsial disease

Answer 45

goo tissue distribution to include CNS for sulfadiazine and prostate for trimethoprim Both drugs undergo hepatic metabolism metabolites thought to be responsible for allergic and idiosyncratic reactions Both active drug and metabolites renally excreted TMS highly concentrated in urine therefore considered 1st line therapy for bacterial cystitis

Answer 46

allogenic, immunogenic and toxic metabolites (Dobermans, Samoyeds and Mini schnauzers more sensitive) hypersensitivity reactions: fever, polyarthritis, pancreatitis, hepatitis, glomerulonephritis, anemia, ITP, mucosal skin lesions. KCS most common because of direct cytotoxic effects of sulfonamides on lacrimal gland reversible with short treatments (<5 days), but may be irreversible with long term use. decrease in thyroid hormone in dogs --> reversible

Answer 47

drugs: Erythromycin, azithromycin, clarithromycin Mechanism of action: binds to 50S subunit inhibiting protein synthesis Bacteriostatis

Answer 48

Mainly effective against gram-positive bacteria and intracellular bacterial infections limited effectiveness against Gram-negative bacteria Not effective against anaerobic bacteria

Answer 49

Alternative drug option for patients that cannot take beta-lactams (allergies)

Answer 50

Macrolide enteral and parenteral administration rapid degradation by gastric acid when given orally DO NOT CRUSH TABLETS b/c coating helps prevent rapid degradation Drug of choice for Campylobacter jejuni

Answer 51

Macrolide Greater activity against gram-negative organisms More stable in acid --> higher bioavailability when taken orally

Answer 52

GI upset most commonly reported also highly effective as a prokinetic when administered at subantimicrobial doses

Answer 53

Prescription based on culture and susceptibility and lack of any other viable alternative treatment for multi drug resistant UTI inhibits cell wall synthesis, bacterial protein and DNA synthesis bactericidal Gram Positive and gram negative resistance is rare side effects: irreversible peripheral neuropathies use with caution in cats --> potential for hemolysis

Answer 54

Prescription based on culture and susceptibility and lack of any other viable alternative glycopeptide antibiotic Reserved only for serious life-threatening multi-drug resistant gram-positive bacterial infections that cannot be treated with other agents (ie MRSA) Mechanism of action: inhibits proper cell wall synthesis by binding to subunits preventing cross-link formation in peptidoglycan cell wall Adverse effects: nephrotoxicity, ototoxicity Rapid IV administration can be associated with histamine release Extravasation can result in severe soft tissue damage

Answer 55

Prescription based on culture and susceptibility and lack of any other viable alternative used to treat Methicillin-resistant staphylococcal pyodermas Mechanism of action: inhibits RNA synthesis Resistance develops in as short as 2 days when used as monotherapy Use in combo with other drugs to decrease emergence to resistance Rifampin + fluoroquinolone --> antagonistic Fair to good oral bioavailability when fasted Side effects: GI upset and hepatotoxicity Pretreatment and weekly biochem monitoring for hepatotoxicity

Answer 56

Prescription based on culture and susceptibility and lack of any other viable alternative Linezolid - synthetic antibiotic Treatment for multidrug resistant skin infections, pneumonia and bacteremia Mechanism of action: binds to p-site of 50S ribsomal subunit --> inhibit protein synthesis Bacteriostatic effective against gram-positive, including methicillin and vancomycin resistant staphylococci Anaerobic spectrum similar to clindamycin Good bioavailability with tissue distribution to lungs, CSF , bones well tolerated with dogs. No studies on cat pharmacokinetics

Answer 57

Prescription based on culture and susceptibility and lack of any other viable alternative Most recently discovered Drug: Daptomycin indicated for Gram-positive that are vancomycin resistant effective against gram-positive and anaerobic Mechanism of action: forms ion channels in cell membrane allowing it to depolarize and result in rapid cell death Gram-negative organisms inherently resistant Adverse effects: highly toxic, causes skeletal muscle damage

Answer 58

Polyene antibiotics Azole derivatives

Answer 59

1. amphotericin B 2. lipid-complexed emphotericin B