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445 Cards in this Set
- Front
- Back
|
Techoic acid
|
Found in cell wall of gram +'s
Induces TNF and IL-1 |
|
|
Lipid A
|
Found in gram negatives - endotoxin (LPS)
induces TNF and IL-1 |
|
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Periplasm
|
space between the cytoplasmic membrane and the peptidoglycan wall in gram-megative bacteria
site of many B-lactamases |
|
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Gram + cocci
|
staph
strep |
|
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Gram - cocci
|
Neisseria (menigitides and gonorrhea)
|
|
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Branching filamentous bacteria
|
Actinomyces
Nocardia (both gram +) |
|
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Pleomorphic bacteria
|
Rickettsiae
Chlamydiae (both gram -) |
|
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Spiral bacteria
|
Leptospira
Berrelia Treponema (all gram -) |
|
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Mycobacteria cell wall
|
contains mycolic acid, high lipid content (hence need for acid fast stain)
|
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Mycoplasma cell membrane/wall
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Contain sterols and have no cell wall!
|
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Bacteria that don't gram stain well
|
Treponema
Rickettsia Mycobacteria Mycoplasma Legionella Chlamydia |
|
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Giemsa Stain
|
Borrelia, Plasmodium, trypanosomes, chlamydia
|
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PAS stain
|
diagnose Whipple's disease (Tropheryma whippelii)
|
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Ziehl-Neelsen stain
|
Acid-fast organisms
|
|
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Chocolate agar w/ factors V (NAD+) and X (hematin)
|
H. influenzae
|
|
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Thayer-Martin (VPN)
|
N. gonorrhoeae
|
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Potato agar
|
Bordetella pertussis
|
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Lowenstein-Jensen agar
|
M. tuberculosis
|
|
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Eaton's agar
|
M. pneumoniae
|
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MacConkey's agar
|
pink colonies; lactose-fermenting enterics (gram-negative rods) (E. coli, Klebsiella)
|
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Charcoal yeast agar
|
Legionella
|
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Sabouraud's agar
|
Fungi
|
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Obligate aerobes
|
Nocardia
Pseudomonas aeruginosa M. tuberculosis Bacillus |
|
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Obligate anaerobes
|
Clostridium
Bacteroides Actinomyces |
|
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Obligate intracellular
|
Rickettsia
Chlamydia |
|
|
Encapsulated bacteria
|
Strep pneumo
Kebsiella HiB N. meningitidis Salmonella Group B Strep |
|
|
Capsule immunogenicity
|
bacterial anti-phagocytic virulence factor
|
|
|
Quellung reaction
|
if encapsulated bug is present, capsule swells when specific anticapsular antisera are added
|
|
|
Bacterial vaccines
|
Pneumovax
HiB Meningococcal *all are conjugated |
|
|
Urease-positive bugs
|
Proteus
Klebsiella H. pylori Ureaplasm |
|
|
Actinomyces israelii color
|
yellow "sulfur" granules composed of a mass of filaments and formed in pus
|
|
|
S. aureus color
|
yellow pigment (think of pus)
|
|
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Pseudomonas aeruginosa color
|
blue-green pigment
|
|
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Serratia marcescens
|
red pigment
|
|
|
Protein A virulence factor
|
produced by S. aureus:
binds Fc region of Ig. Prevents opsonization and phagocytosis |
|
|
IgA protease
|
Found in: S. pneumo, HiB, Neisseria (SHiN)
enzyme cleaves IgA in order to colonize respiratory mucosa |
|
|
M protein
|
Found in group A streptococcus.
Helps prevent phagocytosis |
|
|
S. aureus exotoxin
|
TSST-1 superantigen
Enterotoxins (food poisoning) Exfoliatin - SSS |
|
|
S. pyogenes exotoxin
|
Scarlet fever - erythrogenic toxin causes toxic shock-like syndrome
|
|
|
ADP ribosylating A-B toxins
|
Diptheria
Cholera E. coli pertussis |
|
|
Corynebacterium diptheriae toxin
|
inactivated EF-2
causes pseudomembrane |
|
|
Vibrio cholerae toxin
|
ADP ribosylation of Gs stimulates adenylyl cyclase ==> inc. cAMP ==> inc. pumping of Cl- into gut and dec. Na+ absorption so H20 moves into gut lumen causing rice water diarrhea
|
|
|
E. coli exotoxin
|
Stimulates adenylate cyclase (labile) or guanylate cyclase (stabile) causing watery diarrhea
ETEC |
|
|
Bordetella pertussis toxin
|
Inhibits Gi ==> inc. cAMP
whooping cough inhibits chemokine receptor causing lymphocytosis |
|
|
Clostridium perfringens toxin
|
alpha-toxin; lecithinase acts as a phospholipase to cleave cell membranes and causes gas gangrene
|
|
|
C. tetani toxin
|
blocks the release of GABA and glycine
causes "lockjaw" |
|
|
C. botulinum toxin
|
blocks the release of Ach
causes CNA paralysis, floppy baby syndrome (spores in honey) |
|
|
Bacillus anthracis toxin
|
edema factor, activates adenylate cyclase ==> inc. cAMP
|
|
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Shigella toxin
|
inactivated 60S ribosome
enhances cytokine release ==> HUS also found in E. coli 0157:H7 |
|
|
S. pyogenes toxin
|
streptolysin O is a hemolysin.
ASO antibody is used in the diagnosis of rheumatic fever |
|
|
Toxins encoded by phages
|
Shiga-like toxin
Botulinum toxin Cholera toxin Diptheria toxin Erythrogenic toxin of Strep. pyogenes |
|
|
Novobiocin test
|
for staph:
S. epidermidis is sensitive S. saprophyticus is resistant |
|
|
Optochin test
|
for alpha-hemolytic Strep:
S. viridans is resistant S. pneumo is sensitive |
|
|
Bacitracin test
|
for Beta-hemolytic Strep:
group B (S. agalactiae) are resistant group A (S. pyogenes) are sensitive |
|
|
Alpha-hemolytic bacteria
|
strep pneumo
viridans family *tell them apart with optochin test |
|
|
Beta-hemolytic bacteria
|
1) staph aureus
2) strep pyogenes 3) strep agalactiae 4) Listeria monocytogenes |
|
|
Staph aureus causes:
|
skin infections
organ abcesses pneumonia TSS Scalded skin syndrome Rapid onset food poisoning (mayo) MRSA Acute bacterial endocarditis Acute bacterial osteomyelitis |
|
|
Staph epidermidis causes:
|
infects prosthetic devices and IV caths
creates biofilm normal skin flora |
|
|
Strep pneumo causes:
|
Meningitis (<6 or >60 yrs old)
Otitis media (in kids) Pneumonia (in adults) - rusty sputum Sinusitis |
|
|
Viridan group strep causes:
|
dental carries (S. mutans)
subacute bacterial endocarditis (S. sanguis) |
|
|
Strep pyogenes cuases:
|
pharyngitis (strep throat)
cellulitis impetigo scarlet fever rheumatic fever acute glomerulonephritis |
|
|
Rheumatic fever findings:
|
Subcutaneous plaques
Polyarthritis Erythema marginatum Chorea Carditis |
|
|
Strep agalactiae causes:
|
colonizes vagina ==> pneumonia, meningitis, and sepsis in babies
|
|
|
Enterococci causes:
|
normal colonic flora
UTI subactue endocarditis |
|
|
Strep bovis causes
|
coloonizes the gut
bacteremia and subactue endocarditis in colon cancer patients |
|
|
Corynebacterium dyptheria causes:
|
Diptheria: pseudomembranous pharyngitis (grayish white membrane) with lymphadenopathy
|
|
|
Spore-forming bacteria
|
bacillus anthracis
clostridium perfringens C. tetani B. cereus C. botulinum |
|
|
C. perfringens
|
myonecrosis (gas gangrene)
hemolysis (alpha toxin) |
|
|
C. dificile toxins
|
Toxin A = enterotoxin - binds to the brush border of gut
Toxin B = cytotoxin - destroys the cytoskeletal structure of the enterocytes causing psuedomembranous colitis |
|
|
Bacillus anthracis causes:
|
Cutaneous anthrax - black eschar (painless) ==> bacteremia and death
Pulmonary anthrax - flulike sx ==> fever, pulmonary hemorrhage, mediastinitis and shock |
|
|
Listeria monocytogenes causes:
|
Amnionitis, septicemia and spontaneous abortion
granulomatous infantiseptica neonatal meningitis mild gastroenteritis |
|
|
Which bacteria exhibits "tumbling" motility?
|
Listeria monocytogenes
|
|
|
Actinomyces israelii causes and treatment:
|
Oral/facial abscesses that may drain through sinus tracts in skin
(normal oral flora) Tx = penicillin |
|
|
Nocardia asteroides causes and treatment:
|
pulmonary infection in immune-compromised patients
Tx=sulfa |
|
|
Ghon complex
|
Primary TB
Ghon focus (lower lobes) + hilar nodes |
|
|
Pott's disease
|
TB in the vertebral body
|
|
|
Reactivation TB
|
Fibrocaseous cavitary lesion in the upper lobes
|
|
|
Which organisms are acid fast?
|
Mycobateria:
tuberculosis kansaii avium-intracellulare leprae |
|
|
Mycobacteria leprae causes:
|
lepromatous leprosy: communicable, diffusely spread over skin and superficial nerves (can be lethal)
tuberculoid leprosy: few hypoesthetic skin nodules |
|
|
Leprosy tx
|
long-term oral dapsone
OR rifampin + clofazimine/dapsone |
|
|
Lactose-fermenters
|
macConKEES agar
Citrobacter Klebsiella E. coli Enterobacter Serratia |
|
|
N. gonorrhoeae causes:
|
gonorrhea
septic arthritis neonatal conjunctivitis PID Fitz-Hugh-Curtis syndrome |
|
|
N. meningitidis causes:
|
meningitis/meningococcemia
Waterhouse-Friderichsen syndrome |
|
|
N. gonorrhoeae immunogenicity
|
rapid antigenic variation of pilus proteins allows for multiple reinfections
|
|
|
Haemophilus influenzae causes:
|
haEMOPhilus:
Epiglottitis ("cherry red") in kids Meningitis Otitis media Pneumonia |
|
|
Legionella pneumophila causes:
|
Legionnairs' disease = severe pnuemonia and fever
Pontiac fever = mild flulike syndrome |
|
|
Meningococco prophylaxis
|
rifampin in close contacts
|
|
|
HiB prophylaxis
|
rifampin in close contacts
|
|
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H. influenzae tx
|
Ceftriaxone
|
|
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Legionella tx
|
erythromycin
|
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Pseudomonas aeruginosa
|
PSEUDOmonas:
Pneumonia (CF patients) Sepsis (black lesions on skin) External otitis UTI Diabetic Osteomyelitis hot tub follicultis associated with wound and burn infections |
|
|
Pseudomonas toxins
|
exotoxin A (inactivated EF-2 - same as cholera)
endotoxin (fever, shock) |
|
|
Pseudomonas tx
|
aminoglycoside puls extended-spectrum penicillin (piperacillin, ticarcillin)
|
|
|
E. coli virulence factors (all strains)
|
Fimbriae - cystitis
K capsule - pneumonia, neonatal meningitis LPS endotoxin - septic shock |
|
|
EIEC causes and toxins:
|
shiga-like toxin causes necrosis and inflammation of intestinal mucosa.
Invasive - causes dysentery |
|
|
ETEC causes and toxins:
|
Labile toxin/stabile toxin: no inflammation or invasion
Causes traveler's diarrhea (watery) |
|
|
EPEC causes and toxins:
|
No toxin. Adheres to apical surface, flattens villi, prevents absortion
Causes diarrhea in children P=pediatric |
|
|
EHEC causes and toxins:
|
Shiga-like toxin
endothelium swells and narrows lumen leading to mechanical hemolysis ==> HUS Causes dysentery |
|
|
Klebsiella causes
|
lobar pneumonia (aspiration in in alcoholics and diabetics)
Nosocomial UTI's |
|
|
Salmonella causes
|
bloody diarrhea
typhoid fever (rose spots) gallbladder chronic infection |
|
|
Salmonella tx
|
no antibiotics! makes it worse
|
|
|
Campylobacter jejuni causes
|
bloody diarrhea (esp. in kids)
may precede Guillain-Barre syn. |
|
|
Vibrio cholerae causes:
|
Profuse rice-water diarrhea
|
|
|
Yersinia enterocolitica
|
diarrheal outbreaks (day care centers)
bloody or watery mesenteric adenitis (mimics Crohn's or appendicitis) |
|
|
H. pylori tx
|
1) metro + pepto + tertacycline OR amoxicillin
2) Metro + omeprazole + clarithromycin |
|
|
Leptospirosis sx:
|
flulike sx such as fever, headache, abdominal pain, jaundice and photophobia + conjunctivitis
|
|
|
Leptospira interrogans spread
|
water contaminated with animal urine. most common among surfers and in the tropics
|
|
|
Weil's disease
|
icterohemorrhagic leptospirosis:
jaundice, azotemia, fever, hemorrhage, anemia |
|
|
Lyme disease: stage 1
|
erythem chronicam migrans
flulike symptoms |
|
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Lyme disease: stage 2
|
Bell's palsy
AV nodal block |
|
|
Lyme disease: stage 3
|
chronic monoarthritis
migratory polyarthritis |
|
|
Lyme disease vector
|
Ixodes tick
|
|
|
Borrelia burgdorferi causes:
|
Lyme Disease
|
|
|
Treponema pallidum causes:
|
Syphilis
|
|
|
Primary syphilis
|
painless chancre
|
|
|
Secondary syphilis
|
Maculopapular rash (palms and soles)
Condylomata lata |
|
|
Tertiary syphilis
|
Gummas
aortitis tabes dorsalis Argyll Robertson pupil |
|
|
Argyll Robertson pupil
|
Accomodates but does not react
|
|
|
neurosyphilis signs
|
broad-based ataxia
Romberg + Charcot joint Stroke w/out HTN |
|
|
Congenital syphilis
|
Saber shins
Saddle nose CN VIII deafness Hutchinson's teeth mulberry molars |
|
|
Syphilis tests
|
Screen with VDRL
confirm with FTA-ABS |
|
|
Bartonella causes
|
cat-scratch fever
bacillary angiomatosis in immunocompromised (ddx Kaposi's) |
|
|
Brucella transmission
|
dairy products
contact w/animals |
|
|
Brucellosis is
|
undulant fever??
|
|
|
Francisella tularensis transmission
|
tick bite
rabbits deer |
|
|
Clue cells
|
vaginal epithelial cells covered with bacteria
dx gardnerella (bacterial vaginitis) |
|
|
Rickettsia rickettsii causes:
|
Rocky mountain Spotted Fever (rash starts on hands and feet)
|
|
|
Rickettsia typhi
|
endemic typhus (rash starts centrally and moves out)
|
|
|
Coxiella burnetti causes:
|
Q fever (no rash, pneumonia sx)
|
|
|
Q fever transmission
|
livestock placenta
tick feces |
|
|
Weil-Felix rxn
|
anti-rickettsial antibodies cross-react with Proteus's O antigen and agglutinate
(not positive in Coxiella) |
|
|
Chlamydia trachomatis causes:
|
reactive arthritis
non-gonoccocal urethritis conjunctivitis PID |
|
|
Why is the chlamydial cell wall weird?
|
It lack muramic acid
|
|
|
Chlamydia trachomatis Types A-C
|
blindness due to follicular conjunctivitis in Africa
|
|
|
Chlamydia trachomatis Types D-K
|
urethritis/PID
neontal pneumonia and conjunctivitis |
|
|
Chlamydia trachomatis Types L1-L3
|
lymphogranuloma venereum
|
|
|
Mycoplasma pneumoniae causes
|
atypical pneumonia
(common in <30 age group) |
|
|
What's weird about mycoplasma pneumoniae cell membrane?
|
It's the only bacterial cell membrane that contains cholesterol
|
|
|
Cold agglutinins
|
IgM antibodies to M. pneumoniae (and others??)
|
|
|
Histoplasmosis region/transmission
|
Mississippi and Ohio river valleys
Bird/bat droppings |
|
|
Blastomycosis morphology
|
Broad-based buidding
|
|
|
Blastomycosis region
|
States east of the mississippi river and central america
|
|
|
Coccidioidomycosis morphology
|
spherule with endospores
|
|
|
Paracoccidioidomycosis morphology
|
Budding yeast with "captain's wheel" formation
|
|
|
Malassezia furfur morphology
|
spaghetti and meatballs on KOH prep
|
|
|
Systemic mycoses tx
|
local = fluconazole or ketoconazole
systemic = amphotericin B |
|
|
Candida tx
|
superficial - nystatin
systemic - ampho B |
|
|
Candida moprhology
|
pseudohyphae when in yeast form
germ tube formation at body temp (diagnostic) |
|
|
Aspergillus morphology
|
septate hyphae that branch at acute angles
|
|
|
Aspergillus causes:
|
allergic bronchopulmonary aspergillosis
lung cavity aspergilloma (fungus ball) invasive aspergillosis (esp. in transplant pts.) |
|
|
Cryptococcus neoformans morphology
|
heavily encapsulated yeast (not dimorphic) with wide capsular halo
narrow-based unequal budding |
|
|
Cryptococcus causes:
|
meningitis
|
|
|
Mucor causes
|
rhinocerebral, frontal lobe abscesses
black necrotic eschar on face penetrates cribiform plate |
|
|
Mucor morphology
|
nonseptate hyphae branching at wide angles
|
|
|
pneumocystis jiroveci morphology
|
yeast, saucer-shaped
|
|
|
PCP causes:
|
diffuse intersititial pneumonia
|
|
|
Sporothrix schenckii morphology
|
dimorphic fungus
cigar-shaped yeast forms, unequal budding |
|
|
Sporothrix schenckii causes:
|
"rose gardener's" disease
local pustuale/ulcer ascending lymphangitis |
|
|
sporothrix tx
|
potassium iodide
itraconazole |
|
|
Giardia tx
|
Metronidazole
|
|
|
Entamoeba hystolytica cuases:
|
bloody diarrhea
liver abscess (reddish brown "ancovy paste") submucosal abscess of colon |
|
|
Entamoeba tx
|
Metronidazole + iodoquinol
|
|
|
Toxoplasmas gondi causes:
|
brain abscess in HIV (ring enhancing leasion on CT)
|
|
|
Congentical toxoplasmosis
|
chorioretinitis + hydrocephalus + intracranial calcifications
|
|
|
Toxo tx
|
Sulfadiazine + pyrimethamine
|
|
|
Naegleria fowleri causes
|
Rapidly fatal meningoencephalitis (goes up cribiform plate)
|
|
|
Trypanosoma brucei causes
|
African sleeping sickness:
lymphadenopthy recurring fevers somnolence coma |
|
|
Trypanosoma brucei transmission
|
tsetse fly
|
|
|
Trypanosoma brucei tx
|
blood born: suramin
CNS: melarsoprol |
|
|
Trypanosoma cruzi causes:
|
Chagas' disease:
dilated cardiomyopathy megacolon megaesophagus |
|
|
T. cruzi tx
|
Nifurtimox
|
|
|
Leishmania donovani causes:
|
viscerl leishmaniasis:
spiking fevers hepatosplenomegaly pancytopenia |
|
|
Leishmania donovani tx
|
Sodium stibogluconate
|
|
|
P. vivax/ovale tx
|
Primaquine (dormant forms in liver, hypnozoites)
|
|
|
Babesia diagnosis
|
"maltese cross" in RBC
|
|
|
Babesia transmission
|
Ixodes tick
|
|
|
Babesia causes:
|
Babesiosis (malaria of the US):
fever hemolytic anemia |
|
|
Babesia Tx
|
quinine
clindamycin |
|
|
Enterobius vermicularis causes:
|
pinworm itchy butt
|
|
|
Enterobius vernicular tx
|
#NAME?
|
|
|
Ascaris lumbricoides causes:
|
giant round worm visible in feces (and coming out of other orifices too!)
|
|
|
Ascaris lumbricoides
|
#NAME?
|
|
|
Trichinella spiralis causes:
|
pork tapeworm:
inflammation of muscle (larvae encyst) periorbital edema systemic sx (fever, GI upset etc) |
|
|
Strongyloides stercoralis causes:
|
vomiting
diarrhea anemia |
|
|
Trichinella spiralis tx
|
#NAME?
|
|
|
Strongyloides stercoralis tx
|
#NAME?
|
|
|
Ancylostoma duodenale trasmission
|
larvae penetrate the skin of feet
|
|
|
Ancylostoma duodenale causes:
|
hookworm
anemia |
|
|
Necator americanus transmission
|
larvae penetrate the skin of feet
|
|
|
Necator americanus causes:
|
hookworm
anemia |
|
|
Necator americanus tx
|
-bendazoles or pyrantelpamoate
|
|
|
Ancylostoma duodenale tx
|
-bendazoles or pyrantelpamoate
|
|
|
Dracunculus medinensis causes:
|
guinea worm:
skin inflammation and ulceration (match-stick) |
|
|
Dracunculus medinensis tx:
|
niridazole
|
|
|
Onchocerca volvulus causes:
|
hyperpigmented skin nodules
river blindness |
|
|
Onchocerca volvulus tx:
|
Ivermectin
|
|
|
Onchocerca volvulus transmission:
|
female blackflies
|
|
|
Loa loa transmission
|
deer fly, horse fly, mango fly
|
|
|
Loa Loa causes
|
swelling of skin (can see worm crawling in conjunctiva)
|
|
|
Loa Loa tx
|
diethylcarbamazine
|
|
|
Wuchereria bancrofti trasmission
|
female mosquito
|
|
|
Wuchereria bancrofti causes
|
elephantitis (blockage of lympahtic vessels)
|
|
|
Wuchereria bancrofti tx
|
diethylcarbamazine
|
|
|
Toxocara canis causes:
|
granulomas (if in retina ==> blindness)
visceral larva migrans |
|
|
Toxocara canis tx
|
diethylcarbamazine
|
|
|
Taenia solium causes:
|
larvae in pork ==> tapeworm
eggs ==> cysticercosis |
|
|
Taenia solium tx
|
praziquantel
(-bendezoles for neurocystercercosis) |
|
|
Diphyllobothrium latum causes:
|
fish tapeworm:
Vitamin B12 deficiency ==> macrocytic anemia |
|
|
Diphyllobothrium latum tx
|
praziquantel
|
|
|
Echinococcus granulosus causes:
|
(hyatid) cysts in liver
anaphylaxis if ruptured during surgery |
|
|
Echinococcus granulosus tx
|
-bendazoles
|
|
|
Schistosoma causes:
|
swimmer's itch
granulmoas, fibrosis and inflammation of spleen and liver S. haematobium ==> squamos cell carcinoma of bladder S. mansoni ==> portal HTN |
|
|
Schistosoma tx
|
praziquantel
|
|
|
Clonorchis sinensis causes:
|
inflammation of the biliary tract ==> pigmented gallstones
cholangiocarcinoma |
|
|
Clonorchis sinensis tx
|
praziquantel
|
|
|
Paragonimus westermani causes
|
inflammation and secondary bacterial infection of lung ==> hemoptysis
|
|
|
Paragonimus westermani tx
|
praziquantel
|
|
|
Intestinal nematodes routes of infection:
|
Ingestion: enterobius, ascaris, trichinella
Cutaneous: strongyloides, ancylostoma, necator |
|
|
Typhus is caused by:
|
Rickettsia
prowazekii - epidemic typhi - endemic tsutsugamushi - scrub |
|
|
Live attenuated vaccines
|
smallpox
yellow fever chickenpox polio (Sabin) MMR |
|
|
Killed vaccines
|
Rabies
Influenza Polio (Salk) HAV |
|
|
Recombinant vaccines
|
HBV
HPV |
|
|
Positive-stranded RNA viruses
|
Retro
Toga Flavi Corona Hepe Calici Pico |
|
|
Naked (non-enveloped) viruses
|
Calici
Picorna Reo Parvo Adeno Papilloma Polyoma |
|
|
EBV causes:
|
Mono
Burkitt's nasopharyngeal carcinoma |
|
|
HHV-6 causes:
|
Roseola:
high fevers for several days that an cause seizures, followed by a diffuse macular rash |
|
|
Tzanck smear
|
used to detect HSV-1/2 and VZV
look for intranuclear Cowdry A inclusions |
|
|
Mono symptoms
|
fever
hepatosplenomegaly pharyngitis lymphadenopathy (esp. post. cervical) "atypical lymphocytes" |
|
|
Picornavirus family members
|
PERCH:
polio echo rhino coxsackie HAV |
|
|
Hepevirus family members
|
HEV
|
|
|
Calicivirus family members
|
Norwalk
|
|
|
Flavivirus family members
|
HCV
Yellow fever Dengue st. Louis encephalitis West Nile virus |
|
|
Togavirus family members:
|
Rubella
Eastern equine encephalitis Wester equine encephalitis |
|
|
Paramyxovirus family:
|
Parainfluenza
RSV Rubeola (measles) Mumps |
|
|
Filovirus family:
|
Ebola/Marburg
|
|
|
Arenavirus family:
|
Lymphocytic choriomeningitis virus
Lassa fever encephalitis |
|
|
Bunyavirus family:
|
california encephalitis
sandfly/rift valley fevers crimean-congo hemorrhagic fever hantavirus |
|
|
Adenovirus causes:
|
Febrile pharyngitis
Pneumonia Conjunctivitis |
|
|
Parvovirus causes:
|
B19 virus - slapped cheek" - 5th disease
hydrops fetalis aplastic crises in sickle cell disease |
|
|
Polyomavirus causes
|
JC virus - progressive multifocal leukoencephalopathy in HIV
|
|
|
Negative stranded viruses:
|
Always Bring Polymerase Or Fail Replication
Arenaviruses Bunyaviruses Paramyxoviruses Orthomyxoviruses Filoviruses Rhabdoviruses |
|
|
Segmented viruses:
|
All are RNA viruses "BOAR"
Bunyaviruses Orthomyxoviruses Arenviruses Reoviruses |
|
|
Asceptic meningitis caused by:
|
Poliovirus
Echovirus Coxsackievirus (B) |
|
|
Coxsackie A causes:
|
Herpangina
|
|
|
Yellow fever sx:
|
high fever
black vomitus jaundice |
|
|
Yellow fever transmission
|
Aedes mosquitos
|
|
|
Influenza virus virulence factors
|
Hemagglutinin - viral entry
Neuraminidase - progeny virion release |
|
|
Rubella virus causes:
|
German measles:
fever postauricular tenderness lymphadenopathy arthralgias fine truncal rash *mild in kids but serious congenital |
|
|
Paramyxoviruses virulence factor (all strains)
|
surface F (fusion) protein causes respiratory epithelial cells to fuse and form mulinucleated cells
|
|
|
RSV tx:
|
Palivizumab
neutralizes F protein |
|
|
Rubeola virus causes:
|
Measles:
Cough Coryza Conjunctivitis Koplik spots (buccal mucosa) Rash (presents last and spreads from head to feet - includes hands and feet) |
|
|
Measles sequelae
|
Subacute sclerosing panencephalitis
encephalitis giant cell pneumonia |
|
|
Mumps sx
|
"POM-poms"
Parotitis Orchitis asceptic Meningitis |
|
|
Rabies virus histology/microscopy
|
Negri bodies - cytoplasmic inclusions in Purkinje cells
Bullet-shaped capsid |
|
|
Progression of Rabies disease
|
fever, malaise ==> agitation, photophobia, hydrophobia ==> paralysis, coma ==> death
|
|
|
rabies vectors
|
bat
raccoon skunk dogs |
|
|
HBV replication
|
1) cellular RNA polymerase transcribes RNA from DNA template
2) DNA dependent DNA polymerase in virion reverse transcribe DNA genome from RNA intermediate |
|
|
HEV disease
|
transmitted enterically
water-borne epidemics resembles HAV in its course High mortality rate in pregnant women |
|
|
HDV disease
|
requires HBsAg as its envelope
superinfection is worse than coinfection |
|
|
To which family does each hepatitis virus belong?
|
A - picorna
B - hepadna C - flavi D - delta E - hepe |
|
|
What marker best to detect active hepatitis A?
|
IgM antibody to HAV
|
|
|
What marker indicate current HBV infection?
|
HBsAg
Anti-HbcAg IgM |
|
|
What marker indicates you have been vaccinated (or are immune) to HBV?
|
Anti-HbsAg
|
|
|
What marker is positive during the window period in HBV?
|
Anti-HBcAg
|
|
|
Which marker indicates active HBV replications and high transmissibility?
|
HBeAg
|
|
|
Which marker indicates low HBV transmissibility?
|
Anti-HbeAg
|
|
|
What does env gene in HIV code for?
|
gp120 and gp41 envelope proteins
|
|
|
gp 120 protein in HIV is responsible for:
|
attachment to host T cell
|
|
|
gp41protein in HIV is responsible for:
|
fusion and entry
|
|
|
what does gag code for?
|
p24
|
|
|
what is p24?
|
HIV capsid protein (what is measured when doing viral load assay)
|
|
|
what does HIV bind to on T cells?
|
CD4 and CXCR4
|
|
|
What does HIV bind to on macrophages?
|
CD4 and CCR5
|
|
|
What is ELISA testing for in HIV?
|
anti-gp120 and anti-gp41 antibodies
|
|
|
CD4 <400, increased risk for:
|
oral thrush
tinea pedia shingles reactivation TB H. flu/S. pneumo/Salmonella |
|
|
CD4 <200, increased risk for:
|
Reactivation HSV
Cryptosporidosis (GI) Isospora Coccidio (disseminated) PCP |
|
|
CD4 <100, increased risk for:
|
Candidal esphagitis
toxo histo |
|
|
CD4 <50, increased risk for:
|
CMV retinitis/esophagitis
M. avium-intracellulare (disseminated) Cryptococcal meningoencephalitis |
|
|
Prion diseae
|
PrPc ==> PrPsc (beta-pleated)
spongiform encephalopathy dementia ataxia death |
|
|
Acquired prion disease
|
Kuru
|
|
|
sporadic prion disease
|
Creutzfeldt-Jakob (mad cow)
|
|
|
inherited prion disease
|
Gerst-mann-Straussler-Scheinker syndrome
|
|
|
Bugs causing food poisoning
|
Vibrio
B. cereus S. aeureus C. perfringens C. botulinum E. coli (O157:H7) Salmonella |
|
|
Bugs causing blood diarrhea
|
Salmonella
Shigella Campylobacter EHEC/EIEC Yersinia enterocolitica Entamoeba histolytica C. dificile |
|
|
Bugs causing watery diarrhea:
|
ETEC
Vibrio cholera C. perfringens Giardia Cyptosporidium (immune-deficient) Rotavirus Adenovirus Norovirus |
|
|
Neonatal pneumonia
|
Group B strep
E. coli |
|
|
Pneumonia in kids
|
"Runts May Cough Sputum"
RSV M. pneumo S. pneumo C. pneumo |
|
|
Pneumonia in young adults
|
M. pneumo
S. pneumo C. pneumo |
|
|
Pneumonia in adults (40-65)
|
M. pneumo
S. pneumo H. flu Viruses Anaerobes |
|
|
Pneumonia in elderly (>65)
|
S. pneumo
H. flu Influenza virus Anaerobes Gram-negative rods |
|
|
Nosocomial pneumonia
|
Staph
enteric gram-negative rods |
|
|
Alcoholic/IV drug user pneumonia
|
S. pneumo
Klebsiella Staph |
|
|
Post viral pneumonia
|
Staph
H. flu |
|
|
Atypical pneumonia
|
M. pneumo
C. pneumo Legionella |
|
|
Meningitis in newborns (<6mos)
|
Group B strep
E. coli Listeria |
|
|
Meningitis in kids
|
S. pneumo
N. meningitidis HiB Enterovirus |
|
|
Meningitis in adults
|
N. menigitidis
Enterovirus S. pneumo HSV |
|
|
Meningitis in elderly
|
S. pneumo
Gram - rods Listeria |
|
|
Viral causes of meningitis
|
enteroviruses (esp. coxsackie)
HSV HIV WNV VZV |
|
|
Osteomyelitis in most people is caused by:
|
S. aureus
|
|
|
Osteomyelitis in diabetics and drug addicts
|
Pseudomonas
|
|
|
Osteomyelitis in sickle cell
|
Salmonella
|
|
|
Osteomyelitis in prosthetic replacements
|
S. aureus
S. epidermidis |
|
|
UTI caused by
|
E. coli
Staph. saprophyticus Klebsiella |
|
|
Nosocomial UTI's
|
Serratia
Enterobacter cloacae Proteus mirabilis Psuedomonas |
|
|
ToRCHeS infections
|
Toxo
Rubella CMV HIV HSV Syphilis |
|
|
Congenital rubella
|
PDA
cataracts deafness "blueberry muffin" baby |
|
|
Congenital CMV
|
Hearing loss
Seizures Petechial rash |
|
|
Congenital HSV
|
temporal encephalitis
herpetic (vesicular) lesions |
|
|
What causes chancroid?
|
Haemophilus ducreyi
|
|
|
What is Reiter's syndrome
|
reactive arthritis of chlamydia
|
|
|
Condylomata acuminata
|
genital warts
|
|
|
Fitz-Hugh-Curtis syndrome
|
infection of the liver capsule and "violin string" adhesions of parietal peritoneum to liver. secondary to PID
|
|
|
Which antibiotic(s) block peptidoglycan synthesis?
|
bacitracin
vancomycin |
|
|
Which antibiotics work by disrupting bacterial cell membranes?
|
Polymyxins
|
|
|
Which antibiotics work by disrupting 50s ribosomal subunit?
|
Chloramphenicol
macrolides clindamycin stregptogramins linezolid |
|
|
Which antibiotics work by disrupting 30s ribosomal subunit?
|
aminoglycosides
tetracyclines |
|
|
Methicillin hypersensitivity rxn
|
interstitial nephritis
|
|
|
Ampicillin/Amoxicillin coverage
|
HELPS kill enterococci:
H. influenza E. coli Listeria monocytogenes Proteus mirabilis Salmonella enterococci |
|
|
Ticarcillin, Carbenicillin, Piperacillin are used for what?
|
TCP: Takes Care of Pseudomonas (and gram- rods)
|
|
|
Which drugs can prevent antibiotic destruction by Beta-lactamases?
|
CAST:
Clauvulanic Acid (add to ampicillin/amoxicillin) Sulbactam Tazobactam |
|
|
1st generation cephalosporins include:
|
cefazolin
cephalexin |
|
|
1st generation cephalosporins coverage:
|
gram+ cocci plus:
Proteus mirabilis E. coli Klebsiella |
|
|
2nd generation cephalosporins include:
|
cefoxitin
cefaclor cefuroxime |
|
|
2nd generation cephalosporins coverage:
|
same as 2st generation, plus:
H. flu enterobacter aerogenes Neisseria spp. |
|
|
3rd generation cephalosporins include:
|
ceftriaxone
cefotaxime ceftazidime |
|
|
3rd generation cephalosporins coverage:
|
serious gram - infections resistant to other B-lactams
ceftriaxone - N. meningitis, N. gono Ceftazidime - pseudomonas |
|
|
4th generation cephalosporins include:
|
cefepine
|
|
|
4th generation cephalosporins coverage:
|
pseudomonas
extended gram+ coverage |
|
|
Cephalosporin toxicity
|
hypersentivity rxns
vitamin k deficiency inc. the nephrotoxicity of aminoglycosides disulfiram-like rxn (cefamandole) |
|
|
Aztreonam MOA
|
monobactam resistant to Beta-lactamases
inhibits cell wall synthesis by binding PBP3 synergistic with aminoglycosides |
|
|
Aztreonam coverage
|
gram-negative rods ONLY
(give to penicillin-allergic patients and those with renal failure who can't take aminoglycosides) |
|
|
Imipenem/cilastatin
Meropenem coverage |
Gram + cocci
gram - rods anaerobs |
|
|
Imipenem/cilastatin
Meropenem toxicities |
significant GI distress
skin rash CNS toxicity (seizures) life threatening, limit use to when others have failed |
|
|
Vancomycin MOA
|
inhibits cell wall mucopeptide formation by binding D-ala D-ala
*resistance occurs in bacteria that have D-ala D-lac |
|
|
Vancomycin coverage
|
Gram + ONLY
good for MRSA, C. dificile, enterococci |
|
|
Vancomycin toxicity
|
Nephrotoxicity
Ototoxicity Thrombophlebitis, diffuse flushing - "red man syndrome" |
|
|
Aminoglycides include:
|
Gentamicin
Neomycin Amikacin Tobramycin Stretomycin |
|
|
Aminoglycoside MOA
|
blocks A site tRNA binding on 30s ==> inhibition of initiation complex formation, misreading of mRNA
*require O2 for uptake so not useful for anaerobes |
|
|
Aminoglycoside MOA coverage:
|
severe gram - rod infections
synergistic with B-lactams neomycin for bowel surgery |
|
|
Aminoglycoside MOA toxicity:
|
Nephrotoxicity (esp. when used with cephs)
Ototoxicity (esp. when in utero or with loop diuretics) |
|
|
tetracyclines MOA
|
similar to aminoglycosides, block the tRNA from binding to the A site of the 30s ribosomal subunit
|
|
|
tetracyclines coverage
|
Borrelia burgdorferi
M. pneumo Chlamydia Rickettsia H. pylori |
|
|
Tetracycline toxicity:
|
GI distress
discoloration of teeth inhibition of bone growth in kids photosensitivity |
|
|
Demeclocycline
|
a tetracycline that acts as an ADH antagonist and is used as a diuretic in SIADH
|
|
|
Macrolides include:
|
erythromycin
azithromycin clarithromycin |
|
|
Macrolides MOA
|
block translocation at the 50S ribosomal subunit
|
|
|
Macrolides toxicity
|
prolonged QT interval
GI discomfort acute cholestatic hepatitis eosinophilia Skin rashes Inc. serum conc. of theophyllines and oral anticoagulants |
|
|
Macrolides coverage
|
atypical pneumonias
URI's STD's gram + cocci (use if penicillin allergy) Neisseria |
|
|
Chloramphenicol MOA
|
similar to macrolides - inhbits 50S peptidyltransferase activity
|
|
|
Chloramphenicol coverage
|
Menigitis (H. flu, N. meningitidis, S. pneumo)
|
|
|
Chloramphenicol toxicity
|
Anemia (aplastic)
Gray baby syndrome in premies who lack UDP-glucuronyl transferase |
|
|
Clindamycin MOA
|
Blocks peptide formation at 50S ribosomal subunit
|
|
|
Clindamycin toxicity
|
Pseudomembranous colitis (c. Dificile)
Fever Diarrhea |
|
|
Sulfonamides MOA
|
PABA metabolizes block dihydropteroate synthetase upstream in DNA synthesis
|
|
|
Sulfonamides coverage
|
Gram + and gram -
Nocardia Chlamydia SMX for simple UTI |
|
|
Sulfonamides toxicity
|
Hypersensitivity
Hemolysis in g6PD def Tubulointerstitial nephritis Photosensitivity Kernicterus in infants Displaces warfarin etc from albumin |
|
|
Trimethoprim MOA
|
Inhibits bacterial dihydrofolate reductase.
Used with SMX to cause sequential block of folate synthesis |
|
|
Trimethoprim coverage
|
Recurrent UTIs
Shigella Salmonella PCP |
|
|
Trimethoprim toxicity
|
Megaloblastic anemia
Leukopenia Granulocytopenia *leucovorin rescue - suppl folinic acid |
|
|
Sulfa drug allergies
|
Besides the obvious:
Thiazides Acetazolamide Furosemide Celecoxib Probenecid |
|
|
Fluoroquinolones MOA
|
Inhibit DNA gyrase (topoisomerase II)
|
|
|
Fluoroquinolones coverage
|
Gram - rods of urinary and GI tracts
Pseudomonas Neisseria Some gram + |
|
|
Fluoroquinolones Toxicity
|
GI upset
Superinfections Skin rash Headache Dizziness Damage to cartilage (contra in preggers and kids) Tendinitis and tendon rupture in adults, myalgias in kids |
|
|
Metronidazole MOA
|
Forms free radical toxic metabolites that damage dna
|
|
|
Metronidazole coverage
|
Giardia
Entamoeba Gardnerella vaginalis Anaerobes (Bacteriodes and clostridium) Part of triple therapy for h. Pylori |
|
|
Metronidazole toxicity
|
Disulfiram like rxn with etOH
Headache Metallic taste |
|
|
Polymyxins MOA
|
Bind to cell membranes of bacteria and disrupt their osmotic properties. Cationic, basic proteins that act like detergents
|
|
|
Polymyxins coverage
|
Resistant gram - infections
|
|
|
Polymyxins toxicity
|
Neurotoxicity
Acute renal tubular necrosis |
|
|
Tuberculosis tx
|
Isoniazid
Rifampin Pyrazinamide Ethambutol |
|
|
M. Avium-intercellulare tx
|
Azithromycin, rifampin, ethambutol, streptomycin
|
|
|
Pyrazinamide MOA
|
Effective in acidic environment of phagolysosomes where TB engulfed by macros is found
|
|
|
Ethambutol MOA
|
Dec. carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase
|
|
|
Isoniazid MOA
|
Dec. synthesis of mycolic acid
Needs to be converted to active metabolite by bacterial catalase-peroxidase |
|
|
Isoniazid toxicity
|
Neurotoxicity
Hepatotoxic Lupus B6 helps prevent liver damage and lupus |
|
|
Ethambutol toxicity
|
Optic neuropathy
Red-green color blindness |
|
|
Rifampin MOA
|
Inhibits DNa dependent RNA polymerase
|
|
|
Rifampin coverage
|
Used in combo with Dapsone for leprosy tx (less resistance)
HiB prophylaxis in unimmunized kids |
|
|
Rifampin toxicity
|
Hepatotoxic
Revs up P-450 Orange body fluids |
|
|
Amphotericin B MOA
|
Binds ergosterol to form membrane pores
|
|
|
Amphotericin B clinical use
|
Serious, systemic mycoses (crypto, blasto, histo, candida, mucor)
Doesn't cross bbb |
|
|
Amphotericin B toxicity
|
Fever/chills
Hypotension Nephrotoxiocity Arrhythmias Anemia |
|
|
Nystatin MOA
|
Same as ampho B
|
|
|
Nystatin clinical us
|
Oral candida
Diaper rash Vaginal candidiasis |
|
|
Azoles MOA
|
Inhibits fungal ergosterol synthesis
|
|
|
Fluconazole clinical use
|
Cryptococcal meningitis for AIDS because crosses bbb
Candida's infections of all types |
|
|
Ketaconazole MOA
|
Blasto, coccidiosis, histo, candida
Hypercortisolism |
|
|
Topical azoles
|
Clotrimazole
Miconazole |
|
|
Azole toxicities
|
Gynecomastia
Liver dysfunction (inhibits p-450) Fever Chills |
|
|
Flucytosine MOA
|
Converts to 5-FU and inhibits DNA synthesis
|
|
|
Flucytosine clinical use
|
In combo with ampho B tx for systemic fungal infections like crypto and candida
|
|
|
Flucytosine toxicity
|
Nausea
Vomiting Diarrhea Bone marrow suppression |
|
|
Caspofungin MOA
|
Inhibits cell wall synthesis by inhibiting synthesis of beta-glucan
|
|
|
Caspofungin clinical use
|
Invasive aspergillosis
|
|
|
Caspofungin toxicity
|
GI upset
Flushing |
|
|
Terbinafine MOA
|
Inhibits squalene oxidase so no ergosterol synthesis
|
|
|
Terbinafine clinical use
|
Dermatophytes (esp onchomycoses)
|
|
|
Griseofulvin MOA
|
Interferes with microtubules so no mitosis.
Concentrates in keratin containing tissues |
|
|
Griseofulvin clinical use
|
Oral tx for dermatophytes
Tinea, ringworm |
|
|
Griseofulvin toxicity
|
Teratogenic
Carcinogenic Confusion Headaches Inc. P-450 so inc. warfarin metabolism |
|
|
Pyrimethamine MOA
|
Selectively inhibits plasmodial dihydrofolate reductase
|
|
|
Suramin MOA
|
Inhibits enzymes involved in protozoan metabolism
No CNS involvement |
|
|
Melarsoprol
|
Inhibits sulfhydryl groups in parasite enzymes. cNS involvement
Used in combo with suramin for tx of sleeping sickness (T. Brucei) |
|
|
Nifurtimox
|
Forms intracellular oxygen radicals which are toxic to the parasite
Used in tx of chagas |
|
|
Sodium stibogluconate
|
Inhibits glycolysis at PFK rxn.
Used to tx leishmania |
|
|
Chloroquine MOA
|
Blocks plasmodium heme polymerase leading to accumulation of toxic hb products
|
|
|
Mebendazole MOA/use
|
Inhibits glucose uptake and microtubule synthesis
Used for nematodes |
|
|
Pyrantel pamoate MOA/use
|
Depolarization-induced paralysis via nicotinic receptors
Use for nematodes, no effect on flukes or tapeworms |
|
|
Ivermectin MOA/use
|
Intensifies GABA causing immobilization but doesn't cross bbb so no efx on humans
Used for river blindness (onchocerciasis) |
|
|
Praziquantel MOA/use
|
Inc. membrane permeability to calcium causing contraction and paralysis
Tapeworms and flukes |
|
|
Zanamivir clinical use
|
Both influenza A and B
|
|
|
Zanamivir MOA
|
neuraminidase inhibitor. prevents release of progeny virions
|
|
|
Ribavirin MOA
|
Inhibits guanine nucleotide synthesis by competitively inhibiting IMP dehydrogenase
|
|
|
Ribavirin clinical use
|
RSV
chronic hep c |
|
|
Ribavirin toxicity
|
hemolytic anemia
sever teratogen |
|
|
Acyclovir MOA
|
Guanosine analog - preferentially inhibits viral DNA polymerase by chain termination
Must be phosphorylated to be active by viral thymidine kinase and cellular enzymes |
|
|
Acyclovir clinical use
|
HSV
VZV EBV (for zoster use famciclovir) |
|
|
Ganciclovir MOA
|
Same as Acyclovir:
Guanosine analog - preferentially inhibits viral DNA polymerase by chain termination Must be phosphorylated to be active by viral kinase and cellular enzymes |
|
|
Ganciclovir clinical use
|
CMV (esp. in immunocompromised)
|
|
|
Ganciclovir toxicity
|
Leukopenia
Neutropenia Thrombocytopenia renal toxicity |
|
|
Foscarnet MOA
|
Pyrophosphate analog:
viral DNA polymease inhibitor that binds to the pyrophosphate-binding site of the enzyme. Does NOT require activation by viral kinase |
|
|
Foscarnet clinical use
|
second line therapy for CMV when ganciclovir fails
or for acyclovir resistant HSV |
|
|
Foscarnet toxicity
|
nephrotoxicity (severe, so not used as first line)
|
|
|
HAART
|
2 NRTI's + 1 protease inhibitor
OR 2 NRTI's + 1 NNRTI |
|
|
Protease inhibitors include:
|
-avir
|
|
|
Protease inhibitor MOA
|
inhibits the enzyme that cleaves HIV mRNA into functional units --> prevents maturation of new viruses
|
|
|
Protease inhibitors toxicity
|
hyperglycemia
GI intolerance lipodystrophy thrombocytopenia (indinavir only) |
|
|
NRTI's include
|
Zidovudine (ZDV aka AZT)
Didanosine (ddI) Zalcitabine (ddC) Stavudine (d4T) |
|
|
NRTI's MOA
|
competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3' OH)
must be phosphorylated by thymidine inase to be activated |
|
|
NRTI's toxicity
|
bone marrow suppression (can be reversed with G-CSF and epo)
peripheral neuropathy lactic acidosis rash (NNRTI's only) Megaloblastic anemia (ZDV) |
|
|
NNRTI's include
|
Nevirapine
Efavirenz Declaviridine |
|
|
NNRTI's MOA
|
bind to reverse transcriptase at a site different from NRTI's
Do not require phosphorylation to be active or compete with nucleotides |
|
|
NNRTI's toxicity
|
Same as NRTI's:
bone marrow suppression peripheral neuropathy lactic acidosis rash megalobalstic anemia (ZDV only) |
|
|
Enfuvirtide MOA
|
fusion inhibitor:
binds viral gp41 subunit inhibiting the conformational change needed for fusion with CD4 cells |
|
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Enfuvirtide toxicity
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hypersensitivity rxn
inc. risk of bacteria pneumonia |
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Interferons MOA
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blocks replication of both RNA and DNA viruses
is a glycoprotein synthesized by virally infected cells normally |
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INF-alpha use
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Chronic hep B and C
Kaposi's sarcoma |
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INF-beta use
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MS
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IFN-gamma use
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NADPH oxidase deficiency syndrome
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Interferon toxicity
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Neutropenia
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Antimicrobials to avoid in pregnancy
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"SAFE Moms Take Really Good Care"
Sulfonamides - kernicterus Aminoglycosides - ototoxicity Fluoroguinolones - cartilage damage Erythromycin - acute cholestatisis Metronidazole - mutagenesis Tetracyclines - inhibitor of bone growth (yellow teeth) Ribavirin - teratogenic Griseofulvin - teratogenic Chloramphenicol - "gray baby" |
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Amantidone toxicity
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Ataxia
Dizziness Slurred speech |
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Amantidine clinical use
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Prophylaxis and tx of influenza A (90% are resistant)
Parkinson's |
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Amantidine MOA
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Blocks viral penetration/uncoating (M2) proteins
Crosses bbb and causes release of dopamine Rimantidine is a derivative with fewer CNS efx |
