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314 Cards in this Set
- Front
- Back
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penicillins are inactive against...(4)
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organisms w/o a cell wall
1. mycobacteria 2. protozoa 3. fungi 4. viruses |
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mechanism of action of penicillins
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bactericidal
--> inhibits transpeptidation/crosslinking of bacterial cell wall |
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penicillin G
-> uses (3) |
natural penicillin
--> used for Tx. of pneumococcal pneumonia, syphillis and gonorrhea |
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penicillin V
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- more acid stable than penicillin G
- used for Tx. of strep. phargyngitis (group A) |
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what are the penicillinase-resistant penicllins? (4)
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methicilin
nafcilin oxacilin dicloxacillin |
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oral beta-lactamase resistant drugs (2)
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cloxacillin
dicloxacillin --> Tx. of gram (+) bacteria, esp. those that produce penicillinase (staph aureus) |
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DOC for staph-aureus infection
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penicillinase-resistant penicillins
i.e. nafcillin, oxacillin |
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DOC for gram (+) Listeria monocytogenes
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amoxicillin
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amoxicillin/ampicillin used frequently for which infections?
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upper respiratory tract infections (bronchitis, otitis media, sinusitis)
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gram (-) bacteria targeted by ampicillin/amoxicillin ? (4)
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1. E.coli*
2. H.influenza* 3. proteus mirabilis 4. salmonella typhi * increasing resistance |
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ampicillin is frequently formulated w/ (1); amoxicillin is frequently formulated w/ (2)
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1. sulbactam
2. clavulonic acid |
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what are the anti-pseudomonal penicillins? (3)
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1. Ticarcillin
2. Carbenicillin 3. Piperacillin |
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Ticarcicillin is formulated w/ ? (1)
Piperacillin is formulated w/ ? (2) |
1. clavulanic acid
2. tazobactam |
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bacterial coverage of anti-pseudomonal penicillins?
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1. extended gram (-) spectrum
2. pseudomonas 3. gram (+) 4. anaerobes -> B. fragilis |
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Disadvantages of Carbenicillin compared to other anti-psuedomonal penicillins (4)
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1. lower activity - high doses
2. high sodium level 3. platelet dysfunction 4. hypokalemia |
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antibacterial effects of all B-lactam antibiotics are synergistic with?
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aminoglycosides
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Major Adverse Reactions of Penicillins (6)
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1. hypersensitivity
- anaphylaxis or delayed rash 2. diarrhea 3. nephrotoxicity - esp. methicillin 4. neurotoxicity - may provoke seizures 5. decreased coagulation - w/ antipseudomonals, pen G 6. cation toxicity |
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cephalosporins are ineffective against ? (4)
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L - listeria monocytogenes
A - atypicals (Chlamydia, C. difficle, mycoplasma) M - MRSA E - enterococci |
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first generation cephalosporins
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"PH"
except: cefazolin, cefadroxil |
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cephalexin
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prototype first gen.cephalosporin
used for Tx. of pharyngitis |
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First generation cephalosporins have activity against...
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PEcK
proteus mirabilis E.coli klebsiella pneumonia |
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second generation cephalosporins - mnemonic
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FAM
FA FUR FOX TEA |
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ceflaxor
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2nd gen cephalosporin
-- associated w/ serum sickness |
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cefoxitin
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useful in pts. w/ intra-abdominal sepsis and gynecologic sepsis
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2nd generation cephalosporins have more activity against...
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gram (-) rods
H.influenza enterobacter aerogenes neisseria (HENPEcK) |
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which 2nd generation cephalosporins kill anaerobic organisms? (3)
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cefoxitin
cefmetazole cefotetan the fox met an anaerobic bug for tea |
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Cefuroxime is used to Tx.
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1. community acquired bronchitis and pneumonia (S. pneu, H.infl)
2. sinusitis/ otitis media (URI) |
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Third generation cephalosporins
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ceftriaxone
ceftazidime ceftaxime ceftizoxime ceftibuten -all follow T rule expcept: cefixime, cefoperozone, cefpodoxime |
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clinical uses of third generation cephalosporins (3)
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1. community acquired pneumonia
2. meningitis 3. pyelonephritis |
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first line drug for meningitis
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ceftriaxone
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main use of cefazolin
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- first gen ceph
- prophylactic dose before surgery to prevent infection from skin |
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the 3 cephalosporins that are active against pseudomonas ?
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ceftazidine
cefoperazone cefepime |
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aside from meningitis, ceftriaxone is effective against?
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genital, anal and pharyngeal penicillin-resistant neisseria gonorrhea
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adverse effects of cephalosporins
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10% of patients w/ penicillin allergies will also be allergic to cephalosporins
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what are the broadest spectrum B-lactam antibiotics?
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imipenem
meropenem |
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imipenem is usually compounded with (1) to prevent (2)
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1 - cilastin
2- metabolism by renal dehydropeptidase |
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adverse effects of imipenem (3)
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1. NVD
2. cross-reactivity w/ penicillin allergies (10%) 3. lower seizure threshold |
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imipenem should not be given to patients with (4)
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1. prior seizures
2. meningitis 3. prior strokes 4. brain masses |
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DOC for empiric coverage of severe diabetic foot ulcers...
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ertapenem
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unlike imipenem, ertapenem does not offer coverage for .. (2)
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1. pseudomonas
2. enterococcus |
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aztreonam
- which bacteria? |
gram negative AEROBIC bacteria
-- kills tough, hospital-acquired, multidrug resistant gram (-) bacteria, incl. pseudomonas |
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adverse effects of aztreonam
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relatively non toxic but may cause:
phlebitis skin rash abnormal liver function tests |
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which drug is a safe alternative for treating pts w/ penicillin allergies?
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aztreonam
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examples of B-lactamase inhibitors (3)
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1. clavulanic acid
2. sulbactam 3. tazobactam |
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bacitracin
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mixture of polypeptides that inhibit bacterial cell wall synthesis
--> topical use only |
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mechanism of action of tetracyclines
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broad-spectrum antibiotic
-- bind reversible to 30S subunit, blocking access to acceptor site |
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mechanism of resistance to tetracyclines
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Mg2+ dependent efflux pump
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Clinical uses of Doxycycline (4)
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1. venereal diseases - Chlamydia
2. mycoplasma pneumonia (alternative to erythromycin) 3. lyme disease - Brucella, Ricketssia 4 - acne |
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Adverse Effects of Tetracyclines (7)
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1. GI upset - NVD
2. phototoxicity - severe sunburn 3. hepatoxicity - esp. in pregnant women 4. deposition in bone and teeth in children - discoloration, hypoplasia 5. vestibular problems - w/ minocycline 6. superinfections 7. pseudotumor cerebri |
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C/I of tetracyclines
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1. renally impaired pts
2. pregnant/breast feeding women 3. children under age 8 |
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glycylcycline drug
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tigecycline
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indications of tigecycline
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1. complicated skin and soft tissue infections
2. empiric tx. of intra-abdominal infections 3. MRSA/VRE infections |
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tigecycline is not active against (3)
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1. proteus
2. providencia 3. pseudomonas |
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adverse effects of tigecycline (3)
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1. most common - GI (NV)
2. inhibits clearance of warfarin - monitor coagulation 3. decreases effectiveness of OCP |
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aminoglycosides used to treat infections caused by (1)
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aerobic gram (-) bacteria
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examples of aminoglycosides (5)
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1. gentamycin
2. amikacin 3. tobramycin 4. streptomycin 5. neomycin |
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mechanism of action of aminoglycosides
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diffuse through porins of gram (-) bacteria and an O2-dependent system transports it across cell mb
--> binds to 30S subunit and interferes w/ function --> interrupt polysome disaggregation and assembly |
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pharmacokinetics of aminoglycosides - 4 points
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1. parenteral admin only
2. bactericidal 3. once daily dosing (except in pregnancy, neonates, bacterial endocarditis) 4. excreted unchanged in urine |
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aminoglycoside is usually combined w/ (2)
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1. B-lactam antiobiotic
OR 2. vancomycin |
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which aminoglycoside is used to Tx. pseudomonas?
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Tobramycin
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adverse effects of aminoglycosides (4)
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1. 8th CN toxicity
- ototoxicity - vertigo and loss of balance 2. nephrotoxicity 3. neuromuscular paralysis - tx. w/ neostigmine or calcium gluconate 4. contact dermatitis - neomycin |
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ototoxicity of aminoglycosides is worsened if taking w/ (2)
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1. cisplatin
2. loop diuretics |
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what are the macrolide drugs? (4)
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1. erythromycin
2. clarithromycin 3. azithromycin 4. telithromycin |
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azithromycin
- clinical uses (3) |
1. respiratory infections due to H.influenza, moraxella catarrhalis
2. urethritis (chlamydia) 3. mycobacterium avium complex - in HIV pts |
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spectrum of activity of macrolides
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gram +, some gram - and atypicals such as Legionella, chlamydia pneumoniae, mycoplasma
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telithromycin
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ketolide
- used for macrolide resistant streptococcus pneumoniae |
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macrolides DOC for ... (1)
macrolides are 2nd line agents for (2) macrolides are frequently used for .. (3) |
1. community acquired pneumonia
2. skin and soft tissue infections 3. upper respiratory tract infections (sinusitis, otitis media, bronchitis) |
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macrolides concentrate in (1); azithromycin additionally conc. in (2)
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1. liver
2. neutrophils, macrophages and fibroblasts |
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clarithromycin interferes w/ metabolism of which 2 drugs?
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theophylline
carbamazepine |
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adverse effects of macrolides (4)
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1. epigastric distress - induces intestinal peristalsis
2. cholestatic jaundice/hepatitis 3. ototoxicity 4. prolonged QT syndrome |
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C/I of macrolides
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1. patients w/ hepatic dysfunction w/ caution
2. pts w/ proarrhythmic conditions 3. myasthenia gravis |
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chloramphenicol
- antimicrobial spectrum? |
kills most clinically important bacteria
- excellent anaerobic activity - DOES NOT affect pseudomonas or Chlamydia |
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mechanism of action of chloramphenicol
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inhibits peptidyl transferase
binds to 50S subunit |
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clinical uses of chloramphenicol (3)
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1. bacterial meningitis
- if organism is unknown and pt. is allergic to penicillins 2. rocky mountain fever in young children and pregnancy 3. used in under-developed countries ** bc of severe side effects, should only be used when no alternative exists |
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adverse effects of chloramphenicol (2)
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1. bone marrow depression
- dose-related = reversible anemia - aplastic anemia (rare) 2. Gray baby syndrome |
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gray baby syndrome
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caused by inability to conjugate chloramphenicol in the liver --> esp. in neonates due to decreased levels of glucoronyl transferase
results in : shock, cyanosis, abdominal distention |
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chloramphenicol blocks metabolism of which drugs ? (4)
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1. warfarin
2. phenytoin 3. tolbutaminde 4. chlorpropamide |
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antibacterial spectrum of clindamycin (3)
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1. anaerobic bacteria - B. fragilis
2. nonenterococcal gram + cocci 3 C. difficile is always resistant |
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Clinical uses of clindamycin
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1. penetrating wound infections to abdomen (+ aminoglycoside)
2. infections of female genital tract - septic abortions 3. acne vulgaris/rosacea - topically 4. toxic shock syndrome (+vanco, or b-lactam) 5. anaerobic aspiration pneumonia |
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most dangerous effect of clindamycin?
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pseudomembranous colitis caused by C. difficile
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Tx. of pseudomembranous colitis caused by C.difficle
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metronidazole
OR vancomycin |
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streptogramin drugs?
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quinupristin
dalfopristin |
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quinupristin/dalfopristin are active against ?
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1. VRE (faecium)
2. MRSA 3. group A strep skin infections |
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adverse effects of quinupristin/dalfopristin
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1. pain at infusion site (venous irritation)
2. arthralgia/myalgia 3. hyperbilirubinemia 4. inhibits CYP3A4 - digoxin toxicity |
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linezolid
- antibacterial spectrum |
broad spectrum antibiotic
- empiric coverage of hospital acquired pneumonia - MRSA - VRE - bactericidal against strep and clostridium perfringens |
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adverse effects of linezolid
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1. GI upset
2. rash 3. bone marrow suppression - low platelets 4. enhances pressor effects of pseudoephedrine |
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fluoroquinolone drugs
- mechanism of action |
inhibit DNA gyrase
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fluoroquinolones
- antibacterial spectrum |
- GRAM NEGATIVES
- poor against gram (+) - do NOT cover anaerobes |
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which gram (-) bacteria are fluoroquinolones effective against? (5)
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1. pseudomonas
- pts. w/ cystic fibrosis 2. enterobacteriacaea --> E.coli, salmonella, shigella and campylobacter 3. UTIs caused by resistant enterobacteria 4. facultative organisms --> legionella, brucella, salmonella, mycobacteria 5. gram (+) staph aureus |
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nalidixic acid
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first gen. fluoroquinolone
-> UTIs |
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second generation fluoroquinolones (6)
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1. norfloxacin
2. ciprofloxacin 3. enoxacin 4. lomefloxacin 5. ofloxacin 6. levofloxacin |
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third generation fluoroquinolones (1)
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gatifloxacin
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fourth generation fluoroquinolones (3)
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1. trovafloxacin
2. moxifloxacin 3. gemifloxacin |
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clinical uses of ciprofloxacin
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1. travelers diarrhea (E.coli)
2. prophylaxis/tx of anthrax 3. pseudomonal infections in cystic fibrosis 4. alternative to aminoglycosides 5. UTIs |
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clinical use of norfloxacin
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1. UTIs
2. prostatitis * not effective in systemic infection |
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clinical use of levofloxacin
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- expanded gram (+) coverage
Tx. of community acquired pneumonia and skin infections - prostatitis due to E.coli and STDs - alternative tx. for gonorrhea |
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fluoroquinolone drugs
- mechanism of action |
inhibit DNA gyrase
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fluoroquinolones
- antibacterial spectrum |
- GRAM NEGATIVES
- poor against gram (+) - do NOT cover anaerobes |
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which gram (-) bacteria are fluoroquinolones effective against? (5)
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1. pseudomonas
- pts. w/ cystic fibrosis 2. enterobacteriacaea --> E.coli, salmonella, shigella and campylobacter 3. UTIs caused by resistant enterobacteria 4. facultative organisms --> legionella, brucella, salmonella, mycobacteria 5. gram (+) staph aureus |
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nalidixic acid
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first gen. fluoroquinolone
-> UTIs |
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second generation fluoroquinolones (6)
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1. norfloxacin
2. ciprofloxacin 3. enoxacin 4. lomefloxacin 5. ofloxacin 6. levofloxacin |
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third generation fluoroquinolones (1)
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gatifloxacin
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fourth generation fluoroquinolones (3)
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1. trovafloxacin
2. moxifloxacin 3. gemifloxacin |
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clinical uses of ciprofloxacin
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1. travelers diarrhea (E.coli)
2. prophylaxis/tx of anthrax 3. pseudomonal infections in cystic fibrosis 4. alternative to aminoglycosides 5. UTIs |
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clinical use of norfloxacin
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1. UTIs
2. prostatitis * not effective in systemic infection |
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clinical use of levofloxacin
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- expanded gram (+) coverage
Tx. of community acquired pneumonia and skin infections - prostatitis due to E.coli and STDs - alternative tx. for gonorrhea |
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moxifloxacin - clinical use (2)
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"respiratory quinolone"
--> improved activity against strep. pneumonia empiric tx. of intraabdominal infections -> activity against anaerobes |
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absorption of fluoroquinolones is decreased w/ (3)
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1. sucralfate
2. antacids 3. dietary supplements |
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adverse effects of fluoroquinolones (7)
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1. GI - NVD
2. headache, restlessness, insomnia - rare 3. phototoxicity 4. articular cartilage erosion in immature animals - avoid in children/pregnancy - may cause tendon rupture 5. increase one's risk of C.difficle colitis 6. hypo/hyperglycemia - gatiflaxicin 7. decreases GABA - seizures (cipro only) |
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C/I of moxifloxacin
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avoid in pts w/ pro-arrhythmic conditions --> may prolong QT interval
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quinolones increase the serum levels of .. (4)
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1. theophylline
2. warfarin 3. caffeine 4. cyclosporin |
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antibacterial spectrum of VANCOMYCIN
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- ALL GRAM (+) bacteria
examples: MRSA enterococcus staph. epidermis strep/staph endocarditis C. difficile |
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Vancomycin - synergism
- aminoglycosides (1) - ceftriaxone (2) |
1 - enterococcal endocarditis
2. meningitis |
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mechanism of action of vancomycin
|
inhibits peptidoglycan production and polymerization
- given IV (not absorbed orally) |
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adverse effects of vancomycin (4)
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1. fever/chills
2. phlebitis at injection site 3. red man syndrome --> rapid infusion causes release of histamine i.e. red rash/itchy 4. dose related hearing loss in pts. w/ renal failure |
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mechanism of action of daptomycin
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induces rapid depolarization of membrane - inhibits intracellular synthesis of DNA, RNA and protein
--> bactericidal |
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moxifloxacin - clinical use (2)
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"respiratory quinolone"
--> improved activity against strep. pneumonia empiric tx. of intraabdominal infections -> activity against anaerobes |
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absorption of fluoroquinolones is decreased w/ (3)
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1. sucralfate
2. antacids 3. dietary supplements |
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adverse effects of fluoroquinolones (7)
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1. GI - NVD
2. headache, restlessness, insomnia - rare 3. phototoxicity 4. articular cartilage erosion in immature animals - avoid in children/pregnancy - may cause tendon rupture 5. increase one's risk of C.difficle colitis 6. hypo/hyperglycemia - gatiflaxicin 7. decreases GABA - seizures (cipro only) |
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C/I of moxifloxacin
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avoid in pts w/ pro-arrhythmic conditions --> may prolong QT interval
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quinolones increase the serum levels of .. (4)
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1. theophylline
2. warfarin 3. caffeine 4. cyclosporin |
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antibacterial spectrum of VANCOMYCIN
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- ALL GRAM (+) bacteria
examples: MRSA enterococcus staph. epidermis strep/staph endocarditis C. difficile |
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Vancomycin - synergism
- aminoglycosides (1) - ceftriaxone (2) |
1 - enterococcal endocarditis
2. meningitis |
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mechanism of action of vancomycin
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inhibits peptidoglycan production and polymerization
- given IV (not absorbed orally) |
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adverse effects of vancomycin (4)
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1. fever/chills
2. phlebitis at injection site 3. red man syndrome --> rapid infusion causes release of histamine i.e. red rash/itchy 4. dose related hearing loss in pts. w/ renal failure |
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mechanism of action of daptomycin
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induces rapid depolarization of membrane - inhibits intracellular synthesis of DNA, RNA and protein
--> bactericidal |
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clinical uses of daptomycin (3)
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1. complicated skin infections and bacteremia caused by staph. aureus
2. endocarditis 3. MRSA/ VRE infections |
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adverse effects of daptomycin (5)
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1. constipation, nausae
2. headache, insomnia 3. increased hepatic transaminases and elevated CPK - weekly monitoring 4. additive muscle toxicity w/ statins 5. myopathy |
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mechanism of action of sulfonamides
|
inhibit de novo synthesis of folate by acting as PABA analogues
--> bacteriostatic |
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what is the preferred treatment of toxoplasmosis and chloroquine-resistant malaria?
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sulfadiazine + pyrimethamine
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sulfonamides are active against... (2)
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1. enterobacteria in urinary tract
2. nocardia |
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which sulfonamide is used to treat inflammatory bowel disease?
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sulfasalazine
--> not absorbed orally or as suppository |
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adverse effects of sulfonamides (5)
|
1. crystalluria - nephrotoxicity
2. hypersensitivity - rashes, angioedema, Stevens'Johnson 3. hemolytic anemia 4. kernicterus in newborns 5. drug potentiation - hypoglycemic effect of tolbutamide - anticoagulant effect of warfarin |
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C/I of sulfonamides
|
1. newborns or infants < 2 mths
2. pregnant women close to term 3. pts. taking methanamine for UTIs |
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trimethoprim
- mechanism of action? |
inhibts dihydrofolate reductase
--> bacterial reductase has much stronger affinity than human enzyme |
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clinical use of trimethoprim (alone)
|
1. acute UTIs
2. bacterial prostatitis/vaginitis - weak base, therefore, it conc. in acidic prostatic and vaginal enviro |
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adverse effects of trimethoprim
|
folic acid deficiency
--> megaloblastic anemia --> thrombocytopenia --> agranulocytosis ** esp. in pregnant women reversed w/ admin of folinic acid |
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cotrimoxazole
|
sulfamethoxazole + trimethoprim
|
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clinical uses of cotrimoxazole (5)
|
1. URIs -> otitis media, sinusitis, bronchitis, pneumonia
2. GI infections --> E.coli, salmonella, shigella 3. genitourinary tract infections - prostatitis, urethritis 4. pneumocystic carinii pneumonia - in AIDs pts 5. protozoal infections - toxoplasma gondii - isospora belli |
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methenamine
|
urinary tract antiseptic
--> used to treat lower UTIs |
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side effects of methenamine (2)
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1. GI upset
2. high doses = albuminuria, hematuria, rashes |
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C/I of methenamine (3)
|
1. hepatic insufficiency
2. renal insufficiency 3. pts. taking sulfonamide drugs |
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mechanism of action of methenamine
|
at acidic pH (< 5.5), it produces formaldehyde which is toxic to most bacteria
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nitrofurantoin - mechanism of action
|
bacteria reduce the drug to an active agent that inhibits various enzymes and damages DNA
|
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nitrofurantoin is effective against...
|
1. E.coli
2. gram (+) cocci |
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adverse effects of nitrofurantoin
|
1. GI disturbances
2. acute pneumonitis 3. neurologic problems |
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therapeutic uses of metronidazole
|
1. entameoba histolytica
2. giardia lamblia 3. trichomonas vaginalis 4. anaerobic bacteria (b.fragilis, c, difficile) 5. gardnerella |
|
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metronidazole is not effective for (1) form of parasite, therefore usually given w/ (2) such as (3), (4) or (5)
|
1. luminal form
2. luminal amebicide 3. iodoquinol 4. paromomycin 5. diloxanide |
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adverse effects of metronidazole
|
1. metallic taste in mouth
2. disulfuram-like effect (severe hangover symptoms after alcohol) |
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metabolism of metronidazole in increased by (1) and decreased (2)
|
1. phenobarbital
2. cimetidine |
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tinidazole
|
alternative to metronidazole
esp. for trichomonas vaginalis |
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luminal amebicides (3)
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iodoquinol
diloxanide paromomycin |
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iodoquinol
- uses (1) - side effects (2) |
1. luminal trophozoites and cysts
2. rash, diarrhea, peripheral neuropathy (optic neuritis) |
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paromomycin
|
aminoglycoside antibiotic
--> effective against luminal E.histolytica and tapeworms --> alternative for cryptosporidiosis --> removes bacterial flora which the parasite feeds on |
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emetine/dihydroemetine
|
systemic amebicides
--> alternative agents - do not take for more than 5 days - inhibit protein synthesis by blocking chain elongation |
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mechanism of action of primaquine
|
kills liver schizonts of P.vivax and P.ovale
--> not effective against erythrocyte form of malaria |
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primaquine is used in combination w/ (1) for tx. of (2)
|
1. chloroquine
2. P.vivax/P.ovale malaria |
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adverse effects of primaquine (5)
|
1. acute hemolytic anemia (in G6PD deficiency)
2. do NOT use in pregnancy 3. abdominal discomfort 4. methemoglobinemia 5. granulocytopenia - in SLE/RA pts |
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mechanism of action of chloroquine
|
binds to heme and inhibits its polymerization leading to toxic build up of heme = oxidative damage and cell lysis
|
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chloroquine is effective in what form of malaria?
|
erythrocytic form of P. falciparum
used w/ primaquine for P.vivax/P.ovale |
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chloroquine alternatively can be used to treat ? (2)
|
SLE
RA |
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adverse effects of chloroquine (7)
|
1. color vision changes - retinal damage
2. GI disturbances 3. pruritis 4. acute hemolytic anemia - G6PD deficiency 5. safe in pregnancy BUT NOT in pts w/ psoriasis or porphyria 6. discoloration of nail beds 7. exacerbates dermatitis |
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chloroquine-resistant malaria is treated with ? (3)
|
1. quinine
2. pyramethamine 3. sulfadoxine |
|
|
mefloquine
- mechanism of action (1) - targets (2) - first line for (3) |
1. damages parasite membrane - only erythrocytic form
2. multi-drug resistant P.falciparum 3. prophylaxis w/ once weekly dosing |
|
|
adverse effects of mefloquine (4)
|
1. NV
2. dizziness/disorientation - psychosis 3. do NOT use in pregnancy 4. cardiac arrest if taken w/ quinidine or quinine |
|
|
mechanism of action of quinidine/quinine
|
inhibits heme polymerization = toxic buildup of heme
--> kills erythrocytic and gametocytic parasite forms |
|
|
clinical uses of quinidine
|
1. in combination w/ pyrimethamine+sulfadoxine for resistant P.falciparum
--> only severe infections 2. nocturnal leg cramping 3. local anesthesia |
|
|
adverse effects of quinidine (6)
|
1. cinchonism = NV, tinnitus, vertigo, headache
2. acute hemolytic anemia in G6PD def. 3. hypotension and heart block 4. blackwater fever 5. potentiation of NMJ-blockers/digoxin 6. absorption decreaes w/ alumimum and antacids |
|
|
Artemether/Artesunate
- mechanism of action - tx. of ? |
blocks P.falciparum encoded ER-ATPase
--> alternative for severe chloroquine-resistant malaria |
|
|
melarsoprol
|
- arsenical compound
- late stage infection |
|
|
melarsoprol
- treatment of ? |
1. African sleeping sickness w/ neurologic involvment
|
|
|
adverse effects of metarsoprol (3)
|
1. CNS toxicity - encephalopathy
2. hemolytic anemia 3. C/I in pts. w/ the flu |
|
|
pentamidine
- effective against? |
1. hematologic stage of African sleeping sickness - alternative
2. pneumocystis carinii - second line 3. alternative for Tx. of leishmaniasis |
|
|
adverse effects of pentamidine (4)
|
1. hypoglycemia
2. diabetes - Bcell toxicity 3. reversible renal failure 4. hypotension, dizziness, nausea |
|
|
what is the drug of choice for American sleeping sickness i.e. Chagas disease (T. cruzi)
|
nifurtimox
|
|
|
adverse effects of nifurtimox (5)
|
1. anaphylaxis
2. delayed hypersensitivity 3. GI problems - weight loss 4. peripheral neuropathy 5. suppresses cell mediated immune reactions |
|
|
suramin
- clinical uses (2) |
early treatment and prophylaxis of African sleeping sickness (w/o neuro involvement bc it does not penetrate CNS)
also used for: onchocerca volvulus |
|
|
adverse effects of suramin (6)
|
1. nausea/vomiting
2. shock - LOC 3. albuminuria 4. acute uriticaria 5. neurologic disorders 6. hyperesthesia of hands/feet |
|
|
benzinidazole
|
alternative Tx. for Chagas disease - w/ no benefit over nifurtimox
|
|
|
DOC for treatment of Leishmaniasis
|
sodium stibogluconate
|
|
|
treatment of choice for Toxoplasma Gondii
|
antifolate pyrimethamine
--> sulfadiazine+pyrimethamine is also effective |
|
|
what are the drugs of choice for intestinal nematodes?
|
mebendazole
albendazole thiabendazole |
|
|
mechanism of action of mebendazole
|
inhibits MT synthesis and MT-mediated glucose uptake in nematode
|
|
|
adverse effects of mebendazole
|
1. transient abdominal pain
2. C/I in pregnancy = teratogenic |
|
|
pyrantel pamoate
|
alternative to mebendazole for tx. of infections w/ roundworms, pinworms and hookworms
|
|
|
mechanism of action of pyrantel pamoate
|
depolarizing NMJ blocker in parasite -> paralyzed worm is expelled
|
|
|
thiobendazole
- effective against? (3) |
1. strongyloidiasis (threadworm)
2. cutaneous larva migrans 3. early stage trichonosis |
|
|
adverse effects of thiobendazole (4)
|
1. dizziness, anorexia, NV --> common
2. CNS symptoms 3. C/I in pregnancy 4. erythema multiforme/ Steven-Johnson = maybe fatal |
|
|
Ivermectin
- mechanism of action (3) |
1. opens Cl- sensitive channels
2. blocks GABA in peripheral neurons 3. kills microfilariae and impairs fertility |
|
|
Ivermectin
- DOC for ? (1) - primary choice for ? (2), (3) |
1. onchocerca volvulus (river blindness)
2. cutaneous larva migrans 3 strogyloides |
|
|
adverse effects for Ivermectin
|
due to host response to dying microfilariae in tissue
- pruritis - edema - rash - dizziness |
|
|
diethylcarbamazine
|
increases susceptibility of microfilariae to phagocytosis
|
|
|
diethylcarbamazine
- clinical uses? (3) |
1. Tx. of filiarisis
2. Wucheria bancroffti 3. Brugia malaya infections |
|
|
clinical uses of praziquantel
|
1. trematodes (flukeworms) - schistosomiasis
2. cestodes (tapeworms) 3. taenia solium |
|
|
mechanism of action of praziquantel
|
increases Ca2+ permeability - Ca2+ is lost, worm is paralyzed
|
|
|
adverse effects of praziquantel
|
1. abdominal pain, lethargy, diarrhea, and/or fever
2. C/I in pregnancy or nursing 3. C/I in tx. of ocular cystercicosis 4. increases metabolism of phenytoin, dexamethosone, carbamazepine |
|
|
niclosamide
|
DOC for tapeworms (cestodes)
also used to Tx: - taeniasis - diphyllobrothium latum |
|
|
first line drugs for treatment of tuberculosis (5)
|
1. isoniazid (INH)
2. rifampin 3. pyrazinamide 4. ethambutol 5. streptomycin |
|
|
mechanism of action of isoniazid
|
interferes w/ synthesis of mycolic acid in cell wall of mycobacterium
|
|
|
clinical uses of isoniazid
|
1. prophylaxis of tuberculosis (used alone)
2. active tuberculosis (used in combination w/ other drugs) |
|
|
adverse effects of isoniazid (6)
|
1. peripheral neuritis -> vit B6 deficiency
2. hepatotoxicity - risk increases w/ age and alcohol use 3. rash 4. anemia - vit B6 defiiciency 5. inhibits metabolism of phenytoin 6. convulsions in pts prone to seizures |
|
|
mechanism of action of Rifampin
|
inhibits DNA-dependent RNA polymerase
--> blocks transcription |
|
|
clinical uses of Rifampin (5)
|
1. tuberculosis
2. leprosy 3. prophylaxis in ppl exposed to pts ill w/ N. meningitidis 4. legionella pneumophilia 5. staph aurea endocarditis |
|
|
adverse effects of Rifampin (5)
|
1. asymptomatic jaundice - elevated liver enzymes, but hepatitis is rare
2. urine, sweat and tears = red orange 3. NV, rash 4. if dosed intermittently, flu-like syndrome 5. increases metabolism of drugs |
|
|
which drugs does Rifampin induce metabolism for ? (6)
|
1. coumadin
2. corticosteroids 3. OCP 4. oral hypoglycemics 5. digoxin 6. methadone |
|
|
rifabutin
|
derivative of rifampin commonly used to treat MAI
-> induces cyt P450 enzymes less than rifampin |
|
|
clinical use of rifabutin
|
treatment of tuberculosis in HIV patients
|
|
|
adverse effects of Rifabutin (5)
|
1. kidney/liver effects
2. bone marrow suppression 3. rash/fever 4. uveitis 5. orange discoloration |
|
|
Rifapentine
|
longer half life than rifampin or rifabutin which permits weekly dosing (twice weekly in intensive phase)
|
|
|
pyrazinamide
|
analogue of nictinamide
--> used for tx. of tuberculosis (in combo regimen) |
|
|
adverse effects of pyrazinamide (3)
|
1. hepatotoxicity
2. precipitates gout attacks - inhibits uric acid secretion 3. C/I in pregnancy |
|
|
ethambutol - mechanism of action (4)
|
1. bacteriostatic
2. inhibits arabinyl transferase which is necessary for synthesis of cell wall 3. penetrates CNS 4. metal chelator |
|
|
clinical use of ethambutol
|
used in combination w/ rifampin to treat tuberculosis
- adequate levels in CNS let it treat tuberculous meningitis |
|
|
adverse effects of ethambutol (2)
|
1. optic neuritis - bilateral, dose related
-> loss of visual acuity and color vision 2. precipitates gout attack |
|
|
streptomycin -mechanism of action
|
binds 30S ribosomal subunit and inhibits protein synthesis
--> aminoglycoside antibiotic can be used to Tx. tuberculosis |
|
|
capreomycin
|
aminoglycoside antibiotic for tx. of multi-drug resistant tuberculosis
|
|
|
cycloserine
|
bacteriostatic , 2nd line agent for Tx. of tuberculosis
|
|
|
adverse effects of cycloserine
|
1. CNS disturbances
2. epileptic seizure activity 3. peripheral neuropathy |
|
|
ethionamide
|
structural analog of isoniazid
2nd line agent in Tx. of tuberculosis |
|
|
what is the recommended treatment regiment for leprosy?
|
1. dapsone
2. clofazimine 3. rifampin triple drug regimen for 6-24 months |
|
|
Dapsone - mechanism of action
|
structurally related to sulfonamides --> inhibits folate synthesis
|
|
|
clinical uses of Dapsone
|
1. LEPROSY
2. tx. of pneumonia in pts w/ HIV |
|
|
adverse effects of Dapsone (6)
|
1. skin rash, drug fever
2. bone marrow suppression - agranulocytosis 3. hemolysis 4. methemoglobinemia 5. peripheral neuropathy 6. leprosy reactions --> erythema nodosum leprosum |
|
|
Clofazimine - mechanism of action (2)
|
1. phenazine dye that binds to DNA - prevents it from serving as a template
2. anti-inflammatory |
|
|
clinical uses of Clofazimine
|
1. leprosy
2. leprosy reaction |
|
|
adverse effects of Clofazimine
|
red and black skin discoloration
|
|
|
acyclovir -- is effective against?
|
HSV and VZV infections such as cold sores, varicella and zoster
|
|
|
clinical use of acyclovir
|
1. immunocompetent hosts
--> serious infections such as HSV encephalitis, HSV/VZV infections of eye as well as genital herpes infections 2. imunocompromised pts --> used to treat most herpes infections |
|
|
acyclovir is NOT use for tx of?
|
CMV
EBV |
|
|
adverse effects of acyclovir (2)
|
1. crystalluria - reversible renal toxicity
2. CNS side effects - confusion/seizures (1%) |
|
|
famciclovir and valacyclovir
|
similar to acyclovir but w/ increased drug levels after absorption
|
|
|
clinical uses of famciclovir and valacycovir?
|
herpes zoster and recurrent genital herpes in immunocompetent adults
|
|
|
adverse effects of famciclovir and valacyclovir
|
mild --> nausea, diarrhea, dizziness and headaches
|
|
|
ganciclovir
|
analogue of acyclovir but w/ broader coverage of herpesviridae
|
|
|
what is ganciclovir active against?
|
HSV
VZV CMV EBV HHV8 |
|
|
clinical use of ganciclovir (2)
|
used primarily for CMV infections in immunocompromised hosts
1. AIDS --> CMV retinitis, pneumonitis and esophagitis 2. bone marrow transplant pts --> CMV pneumonitis and prophylaxis against CMV |
|
|
adverse effects of ganciclovir? (5)
|
1. dose-limiting hematotoxicity
- thrombocytopenia, neutropenia 2. crystalluria 3. mucositis 4. fever/rash 5. seizures in overdose |
|
|
valganciclovir
|
L-valyl ester of ganciclovir w/ much better oral bioavailability
|
|
|
foscarnet
|
not a nucleoside analogue
-- inhibits DNA polymerase and reverse transcriptase |
|
|
anti-viral activity of foscarnet (3)
|
all herpes viridae
HIV - very minimal acyclovir-resistant HSV |
|
|
clinical use of foscarnet (2)
|
1. AIDS pts w/ CMV retinitis
2. AIDS pts w/ acyclovir-resistant HSV infection |
|
|
adverse effects of foscarnet
|
1. reversible nephrotoxicity
--> acute tubular necrosis --> HYPOCALCEMIA 2. increased seizure potential |
|
|
cidofovir - mechanism of action
|
phosphonate nucleoside analogue of cytosine
|
|
|
major use of cidofovir
|
CMV infections - primarily retinitis (if ganciclovir and foscarnet have failed)
|
|
|
anti-viral activity of cidofovir
|
all herpes viruses
DNA viruses --> small pox |
|
|
adverse effect of cidofovir
|
kidney damage
|
|
|
nucleoside reverse transcriptase inhibitors (7)
|
zidovudine
didanosine zalcatibine stavudine lamivudine emtricitabine abacavir |
|
|
nucleotide reverse transcriptase inhibitor
|
tenofovir
|
|
|
non-nucleoside reverse transcriptase inhibitors (3)
|
nevirapine
delaviradine efavirenz |
|
|
protease inhibitors (9)
|
saquinivir
indinavir ritonovir nelfinavir amprenavir fosamprenavir atazanavir tipranavir lopinavir |
|
|
entry inhibitor (1)
|
enfuvirtide
|
|
|
what is the first line anti-HIV medication?
|
zidovudine (AZT, ZDV)
|
|
|
side effects of zidovudine (5)
|
1. anemia/neutropenia --> bone marrow suppression
2. CNS --> headache, confusion, seizures, insomnia 3. myalgias 4. nausea 5. peripheral neuropathy |
|
|
lamivudine (3TC) and emtricitabine
|
newer generation w/ less side effects (well tolerated)
--> also suppress Hep B infection |
|
|
didanosine
|
ddI
--> synthetic purine nucleoside analogue (NRTI)` |
|
|
adverse effects of didanosine (5)
|
1. pancreatitis - life threatening
2. peripheral neuropathy 3. hyperuricemia 4. liver dysfunction 5. insomnia, headache |
|
|
zalcitabine (ddC)
|
NRTI
- no longer commonly used bc of other agents w/ superior efficacy |
|
|
adverse effects of zalcitabine (3)
|
1. peripheral neuropathy
2. pancreatitis - less than w/ ddI 3. severe oral ulcers - 3% |
|
|
adverse effects of stavudine (3)
|
1. mild increases in hepatic transmaminases
2. highest associated risk of lipoatrophy, hyperlipidemia and lactic acidosis 3. myelosuppression (< ZDV) |
|
|
stavudine
|
d4T
--> second line agent in treatment of HIV |
|
|
main finding w/ abacavir
|
hypersensitivity reactions w/in 5% of patients which usually appear w/in first 6 weeks of treat
--> if discontinued, should not be reintroduced in same pt |
|
|
what are common side effects of the NRTI drug class?
|
1. peripheral neuropathy
- more common w/ D class 2. lactic acidosis 3. fat redistribution |
|
|
main clinical use of nevirapine
|
given to pregnant women at time of delivery to decrease vertical transmission -- by 50%
|
|
|
adverse effects of nevirapine (3)
|
1. induction of CYP450 enzymes esp. CYP3A
2. rash -> may be severe w/ ulcerations or Stevens-Johnson 3. elevated liver function tests w/ occasional liver failure |
|
|
efavirenz
|
newest NNRTI --> preferred first line agent in this class bc of less extent of side effects
|
|
|
side effects of efavirenz (4)
|
1. dysmorphic dreams
2. insomnia, dizziness, impaired conc. 3. induction of CYP450 4. rash and induction of liver enzymes --> milder |
|
|
saquinavir
|
first protease inhibitor --> but has low oral bioavailability (should be taken w/ meals)
--> causes GI distress |
|
|
main side effect w/ indinavir (PI)
|
kidney stones
--> pt should drink 1.5 L of water daily to ensure adequate hydration |
|
|
ritonavir
|
commonly used to "boost" other PI's by slowing their metabolism
--> not used alone bc of GI side effects |
|
|
what is major side effect of ritonavir?
|
potent inhibitor of CYP450 system --> be cautious of drug interactions
|
|
|
lopinavir/rotanivir combo
|
preferred initial agents for patients who have not had prior anti-retroviral therapy
|
|
|
atazanavir - adverse effects (2)
|
1. consistent rise in indirect bilirubin but w/o clinical jaundice
2. C/I in pts taking proton pump inhibitors |
|
|
enfuviritide (T20)
|
fusion inhibitor
--> binds HIV along gp41 envelope proteins and prevents fusion of HIV w/ target cell membrane |
|
|
post-exposure (needle-stick) HIV prophylaxis
|
ZDV
or ZDV+ lamuvidine |
|
|
amantadine
|
antiviral agent against Influenza A
--> inhibits viral genome uncoating in host cell will decrease duration of flu symptoms |
|
|
oseltamivir
|
neuraminidase inhibitor for treatment and prophylaxis of Flu A and B
- take orally |
|
|
zanamivir
|
neuraminidase inhibitor used for treatment of Flu A and B
- intranasal spray - not recommended for pts w/ COPD or asthma |
|
|
clinical use of ribavirin (3)
|
1. severe respiratory syncitial virus (RSV) infections in infants
2. Lassa fever 3. hanta virus pulmonary syndrome |
|
|
interferon alpha can treat which viral infections?
|
Hep B and Hep C
- induces clinical remission |
|
|
what is the gold standard treatment for candidal and aspergillus infections?
|
amphotericin B
|
|
|
amphotericin is the first line agent for which infections (6)
|
1. systemic candida
2. cryptococcal meningitis 3. severe pneumonia - blastomycosis, histoplasmosis, coccidioidomycosis 4. aspergillosis 5. sporotichosis 6. mucomycosis |
|
|
mechanism of action of amphotericin B
|
forms a complex w/ ergosterol in plasma membrane, leading to leakage of cytoplasmic contents
|
|
|
amphotericin has a synergistic effect w/ ..(1) to treat (2)
|
flucytosine
tx. of cryptococcal meningitis |
|
|
amphotericin administration
|
IV - slow infusion
can be used topically |
|
|
adverse effects of amphotericin
|
1. renal toxicity - dose dependent azotemia --> must be monitored daily
2. acute febrile reaction 3. anemia 4. local thrombophlebitis 5. increased urinary excretion of K+, Mg2+ and HCO3- ** all are very COMMON |
|
|
purpose of adding amphotericin to lipid-complexed preparation or liposome capsule?
|
decreased nephrotoxicity and other side effects
|
|
|
flucytosine - mechanism of action
|
converted to 5-fluorouracil in fungal cells (not human cells) and inhibits thymidylate synthesis and thus, DNA synthesis
|
|
|
clinical use of flucytosine (2)
|
1. cryptococcal meningitis in conjunction w/ amphotericin B
2. candida infections |
|
|
adverse effects of flucytosine (3)
|
1. bone marrow depression
- leukopenia, thrombocytopenia - mild 2. NVD 3. rarely, hepatitis |
|
|
IMIDAZOLE drugs (3)
|
1. ketoconazole
2. miconazole 3. clotrimazole |
|
|
TRIAZOLE drugs (5)
|
1. fluconazole
2. itraconazole 3. voriconazole 4. posaconazole 5. ravuconazole |
|
|
mechanism of action of AZOLE anti-fungals?
|
inhibit CYP450 enzymes which are necessary for ergosterol synthesis --> depletion of ergosterol disrupts the permeability of fungal cell membrane
|
|
|
which azoles are used primarily as TOPICAL agents?
|
clotrimazole
miconazole |
|
|
ketoconazole
|
imidazole w/ broad spectrum anti-fungal activity
largely replaced by newer agents w/ less side effects |
|
|
adverse effects of ketoconazole (5)
|
1. GI - NV, anorexia
2. hepatotoxicity - follow enzymes 3. inhibition of testosterone synthesis 4. adrenal suppression 5. pruritis |
|
|
what is the most commonly prescribed antifungal ?
|
fluconazole
|
|
|
fluconazole - clinical uses (4)
|
1. candida infections!!
2. oral thrush in HIV pts 3. cryptococcal meningitis (usually after amphotericin B) 4. single oral dose for candidal vaginitis |
|
|
itraconazole is useful for treatment of (6) infections
|
1. chromoblastosis
2. histoplasmosis 3. coccidiodomycosis 4. blastomycosis 5. sporotrichosis 6. indolent cases of aspergillosis |
|
|
main problem w/ itraconazole?
|
poor oral absorption
-- should take w/ acidic drink such as orange juice or cola |
|
|
voriconazole has superior activity against....
|
invasive aspergillus
flucanazole-resistant candida species |
|
|
toxic effects of voriconazole (4)
|
1. transient visual changes (30%)
2. occasional hepatotoxicity 3. rash 4. should not be used in pts w/ creatinine clearance rates of < 50 |
|
|
echinocandins
|
caspofungin
micafungin |
|
|
mechanism of action of echinocandins
|
inhibit fungal cell wall synthesis by inhibiting 1,3 D -glucan synthase
|
|
|
therapeutic uses of echinocandins
|
1. all candida species
2. salvage for aspergillus infections |
|
|
nyastatin -mechanism of action
|
increases membrane permeability by binding ergosterol
|
|
|
therapeutic uses of nystatin (2)
|
1. oral, gastric and esophageal candidiasis (PO)
2. vaginal candiasis (topical) |
|
|
main side effect of nystatin
|
highly toxic if taken IV
|
|
|
griseofulvin - mechanism of action
|
inhibits mitosis of cells by disrupting spindle formation
|
|
|
therapeutic use of griseofulvin
|
dermatophytosis of skin, nails and hair --> works very slowly
|
|
|
adverse effects of griseofulvin (5)
|
1. headache
2. NV 3. photosensitivity 4. mental confusion 5. bone marrow suppression |
|
|
terbinafine - mechanism of action
|
blocks ergosterol synthesis by inhibiting squalene epoxide
|
|
|
therapeutic use of terbinafine
|
dermatophyte infections
-- largely replaced griseofulvin in tx. of onchomycosis (fungal nail infections) |
|
|
adverse effects of terbinafine
|
RARELY:
GI, rash and reverse agranulocytosis |
|
|
potassium iodide is used for Tx. of what fungal infections?
|
cutaneous sporotrichosis
|
