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Pharmacology > Antimicrobial drugs > Flashcards

Antimicrobial drugs Flashcards

1
Q

Penicillin

A

Class: beta-lactam
Bacteriocidal, beta lactamase sensitive

Penicillin G (IV, IM) Penicillin V (oral)

Uses: Gram (+), gram(-) cocci and spirochetes

Mechanism: binds PBP (penicillin binding protein) to disrupt cell wall, blocks transpeptidase -> inhibits formation of peptidoglycan cross linking in cell wall-> abnormal cell wall structure –> cell death; activates autolytic enzymes –> cell death

Side effects: Hypersensitivity rxns- rashes, itchy eyes, swollen tongue or face, some can have anaphylaxis; High penicillin doses -> autoimmune hemolytic anemia (Abs against complex of penicillin attached to RBC -> complement activation-> removal by spleen)

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2
Q

Antipseudomonal penicillins (carboxypenicillins)

A

Beta lactam antibiotic, Bacteriocidal, beta lactamase sensitive

Ex: Ticarcillin, Carbenicillin, Piperacillin

Uses: extended spectrum - cover gram (-) bacteria: pseudomonas and proteus

Same mechanism as penicillin- bind PBP, blocks transpeptidase, activates autolytic enzymes

Use w clavulanic acid (beta lactamase inhibitor)

Hypersensitivity reactions - same as penicillin

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3
Q

Ticarcillin

A

Antipseudomonal penicillin, used with clavulanic acid= Timentin
injectable

Used for pseudomonal infections

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4
Q

Carbenicillin

A

beta lactam, used for pseudomonal infections, limited gram + coverage

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5
Q

Piperacillin

A

beta lactam used for pseudomonal infections - combined with beta lactamase inhibitor-> piperacillin tazobactam combo
Cannot be given orally -> give as IV or IM injection

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6
Q

Aminopenicillin uses

A

beta lactam antibiotics, same mechanism as penicillin

Combine with clavulanic acid (beta lactamase inhibitor)

Hypersensitivity rxn like with penicillin

Ex: Ampicillin, Amoxicillin

Treat most gram (+) infections and some gram (-) infectsion such as: H. influenzae, E. coli, Enterococci, Listeria, Proteus, Salmonella, Shigella

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7
Q

Ampicillin

A

aminopenicillin, gram (+) and limited gram (-)

can cause rash if mistakenly used with patients with mononucleosis

associated with pseudomembranous colitis precipitation from C. diff after ampicillin

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8
Q

Amoxicillin

A

aminopenicillin, used for otitis media, skin infections, strep throat

usually combined with bet lactamase inhibitor (clavulanic acid) and given orally

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9
Q

Clavulanic acid

A

beta lactamase inhibitor - binds to active site,

added to penicillin antibiotics:
Augmentin= amoxicillin + clavulanic acid
Timentin= ticarcillin + clavulanic acid

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10
Q

Sulbactam

A

beta lactamase inhibitor, commonly used with cefoperazone or ampicillin

Administered via injection

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11
Q

Tazobactam

A

beta lactamase inhibitor,
usually combined with extended spectrum antipseudomonal antibiotics:
piperacillin + tazobactam = Tazocin

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12
Q

Cephalosporin - general characteristics

A

beta lactam drug, inhibits cell wall synthesis

higher resistance to beta lactamases –> more effective and cover more infections

Bactericidal

Side effects:

  • Hypersensitivity rxn (penicillin hypersensitivity cross reacts w cephalosporins)
  • Vitamin K deficiency with long term use
  • Increased nephrotoxicity when used with aminoglycosides
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13
Q

1st gen cephalosporins

A

beta lactam drug

Ex: cefazolin (given IM or IV for gram+ skin infections, frequently used pre-op prevent s. aureus), cephalexin (given orally, commonly used to treat gram + infections in middle ear, bone, lungs, skin and endocarditis prophylaxis)

Treats: Gram+ cocci, Proteus, E. coli, Klebsiella,

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14
Q

2nd gen cephalosporins

A

beta lactam drug, slightly more extensive than 1st gen

Ex: cefoxitin, cefuroxime, cefaclor

Uses: Gram+ cocci, Proteus, E.coli, Klebsiella, H. influenzae, Neisseria, Serratia, Enterobacter

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15
Q

Cefoxitin

A

2nd generation cephalosporin
Strong beta-lactamase inhibitor
Used for gram-, gram+ and anaerobes

Not effective against pseudomonas and enterococci

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16
Q

Cefaclor

A

2nd gen cephalosporin

Used for gram + and - bacteria

Treats septicemia, pneumonia peritonitis, UTI and biliary tract infections

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17
Q

Cefuroxime

A

2nd gen cephalosporin

can cross BBB

Active against H. influenzae, N. gonorrhea, lyme disease (borrelia)

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18
Q

Cefotaxime

A

3rd gen cephalosporin, Can cross BBB

Treat respiratory tract, connective tissue, UTI, genital, meninges, blood infections

Covers most gram(-) EXCEPT psuedomonas
gram(+) EXCEPT enterococcus

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19
Q

Ceftriaxone

A

3rd gen cephalosporin, Can cross BBB

Used for community acquired pneumonia, H. influenzae, bacterial meningitis, disseminated lyme disease

*IM injection can be given for gonorrhea

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20
Q

Ceftazidime

A

3rd gen cephalosporin

treats gram+ and gram- AND psuedomonas! (unlike other 3rd gen drugs)

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21
Q

3rd generation cephalosporins

A

used to combat serious gram (-) infections that are resistant to other beta lactams

Cefotaxime, ceftriaxone, ceftazidime

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22
Q

4th generation cephalosporins

A

beta lactam antibiotic

most extensive coverage for gram (+) and (-) AND PSEUDOMONAS, and Staph aureus

Ex: cefepime

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23
Q

Cefepime

A

4th gen cephalosporin

used for moderate-severe hospital acquired infections by pseudomonas and can cover resistant Strep. pneumonia and enterobacteriaceae

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24
Q

5th generation cephalosporins

A

beta lactam
broad spectrum gram (+) and (-), target resistant organisms like MRSA, does NOT cover pseudomonas

Ex: ceftobiprole, ceftaroline

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25
Q

Ceftobiprole

A

5th gen cephalosporin

strong antipseudomonal activity and activity against MRSA, strep pneumonia, enterococci

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26
Q

Ceftaroline

A

5th gen cephalosporin

broad spectrum against gram (+) MRSA, MRSE, VRE

Does NOT have good coverage of gram (-) bacteria like bacteroides (gram - anaerobes)

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27
Q

Vancomycin - mechanism and use

A

glycopeptide antibiotic, bactericidal

Used to treat serious infections by gram (+) ONLY susceptible organisms:
MRSA, C. diff (given orally when unresponsive to metronidazole), Enterococci resistant to penicillin derivatives

Mechanism: forms H-bonds w D-Ala-D-Ala moities of cell wall -> prevents synthesis of polymers N-acetylmuramic acid and N-acetylclucosamine (forms backbone strands of cell wall), also prevents polymer cross linking

Resistance mechanism: D-Ala-D-Ala changes to D-Ala-D-Lac

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28
Q

Vancomycin - toxicity

A

Thrombophlebitis - swelling and inflammation of veins caused by blood clot, complication of IV vancomycin

Nephrotoxicity, Ototoxicity

Diffuse flushing - “red man syndrome” w/in 10 minutes of infusion - erythematous rash of face, neck and torso due to mast cell degranulation; can be prevented with slow infusion and antihistamines

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29
Q

Imipenem

A

Carbapenem, beta lactamase resistant antibiotic, inhibits cell wall synthesis

Uses: broad spectrum gram+, gram-, aerobes and anaerobes

  • *Susceptible to degradation by renal dehydropeptidase I in renal tubules
  • -> Must be co-administered with cilastatin (inhibits renal dehydropeptidase I)

**seizure risk!

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30
Q

Meropenem

A

Carbapenem, beta lactamase resistant antibiotic, inhibits cell wall synthesis

Uses: broad spectrum gram+, gram-, aerobes and anaerobes

  • reduced seizure risk, less CNS toxicity risk
  • NOT degredated by dehydropeptidase I
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31
Q

Carbapenem toxicities

A

GI distress (nausea, diarrhea), skin rash, seizures (imipenem>meropenem),

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32
Q

Aztreonam

A

monobactam, more resistant to beta lactamases (may be inactivated by some extended spectrum)

mechanism: binds PBP3 (low affinity to PBP of gram (+) and anaerobes) and inhibits bacterial cell wall synthesis -> bactericidal

Uses: For patients w penicillin allergy and those w renal insufficiency who cant tolerate aminoglycosides. Works against gram (-) aerobes, especially bacilli: Pseudomonas, Enterobacter, E. coli, Haemophilus, Klebsiella, Proteus

Doesn’t work against gram (+) or anaerobic bacteria

Can be used synergistically with aminoglycosides, especially for psuedomonas

*Does NOT cause penicillin allergy

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33
Q

Which drugs are 30S protein synthesis inhibitors?

A

Aminoglycosides and tetracyclines

34
Q

Which drugs are 50S protein synthesis inhibitors?

A

Chloramphenicol, clindamycin, erythromycin, lincomycin, linezolid

35
Q

Aminoglycosides

A

Protein synthesis inhibitors - bind to 30S subunit to inhibit formation of initiation complex -> misreading mRNA -> bacteriacidal

Ex: Gentamicin, Neomycin, Amikacin, Tobramycin

Use: severe gram (-) rod infections, synergistic with beta-lactam antibiotics, *Neomycin for bowel surgery

Require O2 for uptake-> ineffective against anaerobes

Toxicities: Nephrotoxicity, Neuromuscular blockade, Ototoxicity (especially w loop diuretics), Teratogen

Resistance mechanism: inactivation of drug by bacterial transferase enzymes

36
Q

Tetracyclines

A

Protein synthesis inhibitors - bind to 30S subunit and prevent attachment of aminoacyl-tRNA, *bacteriostatic
*tetracycline chelates divalent cations (Ca2, Mg2, Fe2) and inhibit its absorption -> do NOT take with milk, antacids or iron!

Examples: doxycyline, demeclocycline, minocycline

Clinical use: Lyme disease (borrelia), H. pylori, M. pneumonia, Rickettsia and Chlamydia

Toxicities: GI distress, photosensitivity, contraindicated in pregnancy- teratogen, discoloration of teeth and inhibition of bone growth in children.

37
Q

Chloramphenicol

A

Protein synthesis inhibitors - inhibits 50S peptidyltransferase (can’t form peptide bonds btwn adjacent AAs), bacteriostatic

Associated with bone marrow toxicity: anemia (dose dependent), aplastic anemia (dose independent), gray baby syndrome –> used conservatively in US for meningitis

More widely used in developing countries bc cheap

38
Q

Clindamycin

A

Protein synthesis inhibitors - binds 50S subunit and inhibits ribosomal translocation (prevents elongation of polypeptide chain) similar mechanism to macrolides.

Bacteriostatic

Used for anaerobic infections- bacteroides fragilis and C. perfringens (above diaphragm vs metronidazole below diaphragm)- aspiration pneumonia, lung abscess,

Toxicity: pseudomembranous colitis (C.diff), fever, diarrhea

39
Q

Erythromycin

A

Macrolide, inhibits protein synthesis by binding 23S rRNA of 50S subunit -> blocks translocation

Uses: atypical pneumonia by Mycoplasma, Chlamydia and Legionella, URIs and STDs

Toxicity:
*motilin agonist -> GI disturbances

*P450 inhibitor -> avoid use with statins (causes myopathy) and can increase serum concentrations of anticoagulants and theophyllines (respiratory disease med)

40
Q

Lincomycin

A

Similar in structure to macrolide, protein synthesis inhibitor- inhibits 50S

*high toxicity -> rarely used unless patient with penicillin allergy and bacteria highly resistant

41
Q

Linezolid

A

Drug class: oxazolidinones
Mech: protein synthesis inhibitor- inhibits 50S from forming initiation complex

Uses: gram (+) infections resistant to other antibiotics- MRSA, VRE, Strep

Indications: infection of skin, soft tissues, and hospital acquired pneumonia

Toxicity: bone marrow suppression-> thrombocytopenia, peripheral neuropathy, serotonin syndrome

42
Q

Dicloxacillin, nacillin, oxacillin

A

penicillinase-resistant penicillins

same mechanism as penicillin -> large R group blocks access of beta lactamase

*use nafcillin for staph aureus (except MRSA)

Toxicity: hypersensitivity rxn, interstitial nephritis

43
Q

Doxycycline

A

Tetracycline drug

Used in prophylaxis for malaria

*unique: fecally eliminated! –> can use in patients with renal failure

44
Q

Demeclocyline

A

tetracycline used in treatment of SIADH, since it is an ADH antagonist

*In patients without SIADH, it can induce nephrogenic diabetes insipidus

45
Q

Minocycline

A

tetracycline with broader spectrum than rest of group

  • long acting- t1/2 2-4x longer
  • highest action in brain and prostate
  • > greatest CNS side effects like vertigo
46
Q

Macrolides

A

Protein synthesis inhibitor

Examples: Azithromycin, clarithromycin (also used in H. pylori triple therapy), erythromycin

Mechanism: Blocks translocation “macroslides”, binds to 23S rRNA of 50S, bacteriostatic

Use: Gram(+) cocci (strep infections w penicillin allergies), Atypical pneumonias, STIs (Chlamydia), B. pertussis,

Toxicity: GI Motility issues (diarrhea), Arrhythmia caused by prolonged QT, Cholestatic hepatitis, Rash, Eosinophilia

*Clarithromycin and erthromycin inhibit cytochrome p450 -> increase serum concentration of anticoagulants and theophyllines, *Avoid using with statins -> myopathy

Resistance: methylation of 23S rRNA binding site

47
Q

Trimethoprim

A

Mech: Bacterial dihydrofolate reductase inhibitor-> cant make THF, Bacteriostatic

Clinical use: used in combo with sulfonamides (trimethoprim-sulfamethoxazole, TMP-SMX) -> sequential block of folate synthesis –> UTIs, Shigella, Salmonella, Pneumocystis jirovecii pneumonia treatment and prophylaxis, toxoplasmosis prophylaxis

Toxicity: “TMP Treats Marrow Poorly” Megaloblastic anemia, leukopenia, granulocytopenia - supplement with folinic acid (aka Leucovorin)

48
Q

Sulfonamides

A

Ex: Sulfamethoxazole (SMX, used with trimethoprim against staph, strep, e.coli and oral anaerobes), sulfisoxazole, sulfadiazine (used in combo with pyrimethamine to treat toxoplasmosis)

Mech: PABA competitive antagonist, inhibits dihydropteroate synthase -> inhibits folate synthesis

Bacteriostatic, but bactericidal when combined with TMP

Clinical use: gram (+) and (-), Nocardia, Chlamydia

Toxicity: ~3% will have adverse rxns -> hypersensitivity rxn, hemolysis if G6PD deficient, nephrotoxicity (acetylated drug is insoluble in acidic urine and precipitates into crystals, prevent by hydration and alkalinization of urine), photosensitivity, displace drugs from albumin (warfrin), Kernicterus in infants (bilirubin accumulates in gray matter bc sulfonamides displaces from albumin)

49
Q

Fluoroquinolones - examples, mechanism and clinical use

A

“-floxacin” Ex: Ciprofloxacin, norfloxacin, levofloxacin,
moxifloxacin (use limited to serious life threatening infections when other drugs cant be used)

Mechanism: Inhibits prokaryotic topoisomerase II (DNA gyrase) and topoisomerase IV

Bactericidal

Uses: gram (-) rods or urinary and GI tracts- incl psuedomonas and neisseria, some gram (+)

50
Q

Ciprofloxacin

A

Fluoroquinolone

Uses: Strong activity against gram (-) rods like E. coli, 1st line for UTIs

P450 inhibitor

51
Q

Fluoroquinolone toxicity

A

GI upset, superinfections, skin rashes, headache, dizziness

Less common: leg cramps and myalgias (especially in kids)

Contraindicated in pregnancy- Teratogen, nursing women and children cartilage damage

Tendonitis or achilles tendon rupture in elderly and patients taking prednisone

52
Q

Daptomycin

A

Lipopeptide disrupts cell membrane of gram (+) cocci

Clinical use: MRSA, bacteremia, endocarditis, VRE *NOT used for pneumonia

Toxicity: myopathy rhabdomyolysis

53
Q

Metronidazole

A

Mechanism: forms toxic free radical metabolites in cell -> Bactericidal and antiprotozoal

Clinical use: Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (bacteroides, c. diff) BELOW diaphragm (contrast w clindamycin), Used with PPI and clarithromycin for triple therapy for H. pylori

Toxicity: disulfram-like rxn w/ alcohol (flushing, tachycardia, hypotension), HA, metallic taste

54
Q

What drugs are used for M. tuberculosis prophylaxis and treatment?

A

Prophylaxis: Isoniazid

Treatment: Rifampin, Isoniazid, Pyrazinamide, Ethambutol

55
Q

What drugs are used for M. avium-intracellulare prophylaxis and treatment?

A

Prophylaxis: Azithromycin, rifabutin

Treatment: Azithromycin or clarithromycin + ethambutol. Can add rifabutin or cipro

56
Q

What drugs are used to treat M. leprae?

A

Tuberculoid form: dapsone and rifampin

Lepromatous form: dapson, rifampin and clofazimine

57
Q

Rifamycins

A

Rifampin, rifabutin

Mechanism: Inhibit DNA-dependent RNA polymerase -> blocks RNA polymerization

Clinical use: M. tuberculosis; delay resistance to dapsone for leprosy. Prophylaxis for meningococcal infection and prophylaxis in contacts of kids w H. influenzae type B

Toxicity: Orange body fluids (nontoxic), hepatotoxicity and drug interactions (induce P450)

Rifabutin favored over rifamin in HIV patients, less P450 stimulation

Resistance: monotherapy rapidly leads to resistance, mutations reduce drug binding to RNA polymerase

58
Q

Isoniazid

A

Mechamism: decrease synthesis of mycolic acid, Note: bacterial catalase-peroxidase (KatG) needed to convert INH to active metabolite

Clinical use: TB, prophylaxis against TB
*Different INH half lifes in slow/fast acetylators

Toxicity: Can cause B6 deficiency, Neurotoxicity (can be prevented by B6), hepatotoxicity, drug induced lupus.

Resistance: mutations in KatG (decreased bacterial catalase-peroxidase)

59
Q

Which drugs are associated with drug-induced SLE?

A

Isoniazid (TB treatment), hydralazine (vasodilator for HTN), procainamide (anti arrhythmic)

60
Q

Pyrazinamide

A

Used to treat TB

Toxicity: hyperuricemia (gout), hepatotoxicity

61
Q

Ethambutol

A

mechanism: Blocks arabinosyl transferase-> decreases carbohydrate polymerization of mycobacterium cell wall

Use: TB treatment

Toxicity: Optic neuropathy (red-green color blindness)

62
Q

High risk for endocarditis and undergoing surgical/dental procedure - what drug to use?

A

Amoxicillin

63
Q

Exposure to gonorrhea - what drug to use?

A

Ceftriaxone

64
Q

Hx of recurrent UTIs - what drug to use?

A

TMP-SMX

65
Q

Exposure to meningococcal infection - what drug to use?

A

Ceftriaxone, ciprofloxacin, or rifampin

66
Q

Pregnant woman carrying group B strep - what drug to use?

A

Penicillin G

67
Q

Prevention of gonococcal conjunctivitis in newborn - what drug to use?

A

Erythromycin ointment

68
Q

Prevent postsurgical infection from S. aureus

A

Cefazolin

69
Q

Prophylaxis of strep pharyngitis in child with prior rheumatic fever - what drug?

A

benzathine penicillin G or oral penicillin V

70
Q

exposure to syphilis - what drug to give?

A

Benzathine penicillin G

71
Q

Prophylaxis in HIV patient CD4

A

TMP-SMX, prevent pneumocystis pneumonia

72
Q

Prophylaxis in HIV patient CD4

A

TMP-SMX, prevent pneumocystis pneumonia and toxoplasmosis

73
Q

Prophylaxis in HIV patient CD4

A

azithromycin or clarithromycin, prevent mycobacterium avium complex

74
Q

Treatment of MRSA

A

Vancomycin, daptomycin, linezolid, tigecycline, ceftaroline (5th gen cephalosporin)

75
Q

Treatment of VRE

A

linezolid and streptogramins (quinupristin, dalfopristin)

76
Q

Treatment of multi-drug resistant pseudomonas and acinetobacter baumannii

A

polymyxins B and E

77
Q

Polymyxins

A

Cationic- bind to cell membranes by interacting w phospholipids, alter structure -> permeable to water -> cell death

Uses: resistant gram (-) infections: multidrug resistant psuedomonas or highly resistant enterobacteriaceae, last resort!

Toxicity: Neurotoxicity and Renal Tubular Necrosis

78
Q

Treatment of C. diff

A

Oral metronidazole (mild to moderate), oral vancomycin (severe), Fidaxomycin for recurrent C.diff (bacteriacidal with less effect on normal flora than metronidazole or vancomycin)

79
Q

What drugs are commonly used to treat MRSA? What are the common side effects of each?

A

Vancomycin - red man syndrome
Daptomycin - myopathy, rhabdomyolysis (increased CPK)
Linezolid - bone marrow suppression, peripheral neuropathy, serotonin syndrome

80
Q

Antibiotics effective against Psuedomonas

A

Class/ Drugs
Anti-pseudomonal penicillins: Ticarcillin, Piperacillin

Cephalosoprins: Ceftazidime (3rd gen), Cefepime (4th gen)

Aminoglycosides: Amikacin, Gentamicin, Tobramycin

Fluoroquinolones: Cipro, Levofloxacin

Monobactams: aztreonam

Carbapenems: imipenem, meropenem

Pharmacology (19 decks)

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