Exam 1: Antibiotics Flashcards
1st Generation Penicillins
Penicillin G (IV), Penicillin VK (PO)
structural analog of D-Ala D-Ala is ____
B-lactam drugs
Penicillin pharmacokinetics
inactivated by gastric acid
small Vd, short half life
wide distribution but poor CNS penetration
renal secretion
beta lactam mechanisms of resistance
1 - physical barrier 2 - mutant porin 3 - efflux pump 4 - beta-lactamases 5 - mutant peptidoglycan transpeptidase (PBP- 2a present in MRSA, resistant to essentially all B-lactams)
Penicillin adverse effects
low direct toxicity
kills GI bugs –>Cdiff
CNS tremors or convulsion
hypersensitivity
2nd Generation Beta Lactams
Nafcillin (IV), Dicloxacillin (PO QID), Methicillin.
Penicillinase resistant
Nafcillin pharmacokinetics
erratic oral absorption so give IV
biliary excretion
Nafcillin and Dicloxacillin are used for ____
gram + only
common for skin infections
MSSA
Amoxicillin and Ampicillin are used for
gram + and some gram -
but penicillinase sensitive
Amoxacillin kinetics
well absorbed, acid stable
can be taken with food (PO TID)
first line for syphilis
Penicillin
first line for GAS
Penicillin
tx for MSSA
Vancomycin, Nafcillin (IV) or Dicloxacillin (PO)
tx for otitis media
amoxicillin
IV/IM tx for pseudomonas
Pipericillin
tx for bite wounds
ampicillin/sulbactam or amoxicillin/clavulanate
tx for Lyme dz (bergdorferi)
ampicillin or amoxicillin
tx for H. flu
amp/sulbactam or amoxi/clavulanate
tx for MRSA
linezolid, tigecycline, daptomycin
glucosyltransferase (peptidoglycan synthetase) is blocked by ____
vancomycin
external phase of cell wall synthesis, step 1
peptidoglycan transpeptidase (penicillin binding protein) is blocked by _____
Beta lactase (external phase of cell wall synthesis, step 2)
4 classes of beta lactams
penicillins
cephalosporins
carbapenems
monobactams
which penicillins are penicillinase resistant?
nafcillin (IV)
dicloxacillin (PO)
Which penicillin is better absorbed orally? Pen G or Pen VK?
Pen VK
used PO QID
why would one give probenecid with penicillin?
it inhibits renal tubular secretion of the drug, keeping it in the system longer (longer t1/2)
which drugs have a post antibiotic effect?
penicillins
Nafcillin (IV) is excreted via _____
bile
PBP-2a
mutant peptidoglycan transpeptidase (penicillin binding protein)
makes it resistant to all beta lactams
MRSA has it
1st gen cephalosporins are___
Cefazolin (IV)
Cephalexin (PO)
Cefazolin and Cephalexin are resistant to_______ and used for _____ bacteria.
penicillinases
gram positive
cephalosporins are excreted via
kidney (secreted)
________ is often given prior to surgery to prevent wound infections.
Cefazolin (IV)
_______ is the drug of choice for gonorrhea, severe Lyme dz, and meningitis.
Ceftriaxone (IV)
_______ is useful for treatment of pseudomonas.
Ceftazidime (IV)
“makes pseudomonas turn on a dime”
3rd generation cephalosporins are resistant to _______ and have good penetration of ______.
ESBL (extended spectrum beta lactams)
CNS
the broadest spectrum beta lactic class is
carbapenems
Cilastin is given with Imipenem to inhibit ______ in the kidney, increasing it’s half life.
dehydropeptidase I, which rapidly hydrolyzes imipenem for excretion
Adverse effect of high dose imipenem is ______
seizures
esp. be careful with renal failure
Cilastin is not needed with _______ (carbapenem).
Meropenem
2nd line drug for pseudomonas (after aminoglycosides)
Aztreonam
Aztreonam is useful for treatment of __________.
gram negative aerobic rods
enterobacteriae
Which beta lactic has the least cross-allergenicity with penicillins or cephalosporins?
Monobactams (Aztreonam)
Which beta-lactam drug should be reserved for “last resort” use?
Carbapenems
Vancomycin is only useful for gram ______ bacteria.
positive
Vancomycin resistant bacteria have converted D-Ala to _________.
D-Lactate
Vancomycin should be reserved for treatment of _________ and _________.
MRSA
C. diff
True or False: Vancomycin is absorbed in the gut.
False.
Give orally to treat Cdiff to concentrate effect in the GI.
Adverse effects of Vancomycin (name 4)
Ototoxicity
Flushing (Red man syndrome)
Nephrotoxicity
Thrombophlebitis
List drugs that are nephrotoxic.
Vancomycin
What can se use for vancomycin resistant enterococci (VRE) or MRSA?
Linezolid
Daptomycin
2nd or 3rd line drug for resistant gram positives or when vancomycin use is contraindicated?
Linezolid
If your patient is taking Linezolid, they must not be eating foods high in ________ because the drug inhibits ___________.
Tyramine
monoamine oxidase
Linezolid MOA
blocks initiation of protein synthesis
binds to 23S RNA to prevent formation of 70S functional initiation complex
Which drug’s MOA is so unique that there is no cross-drug resistance?
Linezolid
resistant bacteria have mutated 23S RNA
Linezolid is metabolized in the ________
liver
no problem for patients with renal failure
Myelosuppression is an adverse effect of __________.
Linezolid
Drugs that inhibit protein synthesis
Rarely, Linezolid can cause _______ (adverse effect).
optic neuropathy
peripheral neuropathy
3rd/4th line for drug resistant gram +
Daptomycin
or when vancomycin & linezolid are contraindicated
This drug is a lipopeptide that uniquely forms pores in cell membranes to allow passive K+ efflux (—>depolarization–>death).
Daptomycin
Daptomycin is not very selective, its lipid tail can also embed in ________, causing _________.
muscle
weakness, discomfort, rhabdomyolysis
Daptomycin is excreted via ________.
urine (kidney)
Macrolides bind to _________ to block translocation (stall protein synthesis).
50S RNA
The ___________ are good for the funny bugs and gram positive organisms.
macrolides
Bacteria develop cross drug resistance to macrolides, _______, and _________, by __________.
lincosamides, streptogramins (MLS)
methylation of the 50S ribosome (“MLS site”)
_________ synergistically decrease bioavailability of several drugs, and is inhibited by ________.
P-gp/CYP34A
erythromycin & clarithromycin
(not inhibited by azithromycin)
Erythromycin & clarithromycin can cause toxicity to ______ and _______.
liver
reversible hearing loss
____________ and _________ can cause QT prolongation
Erythromycin
Fluoroquinolones
Ototoxic drugs include:
erythromycin
clarithromycin
Clarithromycin is “better tolerated” than erythromycin, in reference to _______ side effects.
GI
Clindamycin is good for treating _______
mixed anaerobes (oral > bowel)
gram positive aerobes
MRSA
Anti-anaerobes are ________ and ________.
L incosamide (clindamycin) nitroimadazole (metronidazole)
treatment for Cdiff
oral metronidazole
oral vancomycin
Clindamycin is metabolized by ________ so should be dosage adjusted in _______ failure
liver
Metronidazole is only useful for _________ infections.
anaerobic
What “gut sterilizer” is often given prior to bowel surgery?
metronidazole
dark brown urine
metallic taste
disulfiram-like reaction
inhibits p450 enyzmes
metronidazole
Paraquat (herbicide) causes _______ toxicity.
lung
The antidote for parathione (pesticides) is ________.
atropine sulfate
compete w/ Ach for muscarinic receptor
Nitrates exposure results in production of _________.
Methemoglobin (Hb(F+++))
The antidote for methemoglobinemia is __________
methylene blue
reduces Fe+++ to Fe++
Cyanide inhibits ___________ which is required in the electron transport chain
cytochrome oxidase (results in switch to anaerobic metabolism)
The three antidotes for cyanide is __________.
Nitrates. (cyanide binds Fe+++ in methemoglobin)
Hydroxycobalamin (forms complex)
Sodium thiosulfate (forms complex)
The antidote for metal poisoning (lead, mercury) is ___________.
succimer/DMSA
Buy AT 30, Cell at 50.
Aminoglycosides
Tetracyclines
inhibit 30S ribosomal subunit
Chloremphenical and Clindamycin Erythromycin Lincomycin Linezolid inhibit 50S ribosomal subunit
Doxycycline is a _________.
Tetracycline
Tetracyclines MOA
anti-protein synthesis
bacteriostatic
reversibly bind 30S subunit
selective to prokaryotes
Cross-resistance usually does not extend to _________, which should be reserved for MDR organisms and is only given ______.
Tigecycline
IV
Doxycycline is primarily _______ soluble with a ______ half life.
lipid
long
given PO BID
What are the “funny bugs” that Doxycycline can treat?
Chlamydia
Rickettsii (Rocky Mt Spotted Fever)
Bergdorferi
Mycoplasma
You should not take _________ with a tetracycline. Absorption is impaired by taking with food.
antacids
milk
Tetracyclines is widely distributed and can accumulate in _______ (what tissue?).
bone, teeth
can cause discoloration
Tetracyclines are contraindicated in _________, ___________, and __________.
renal failure
pregnancy
children < 8
If a patient takes expired tetracycline, she/he can develop__________.
renal tubular acidosis
“Mean” GNATS can NOT kill anaerobes. What is GNATS (hint: bacteria)?
Gentamycin Neomycin Amikacin Tobramycin Streptomycin
“Mean” GNATS can NOT kill anaerobes. What is NOT (hint: toxicities)?
Nephrotoxic
Ototoxic
Teratogenic
inhibits protein synthesis
impairs proof reading
irreversible binding to 30 S subunit – bacteriocidal, with postantibiotic effect
concentration-dependent killing
Aminoglycosides
Aminoglycosides are highly _________ soluble, making them good for treatment of _______.
water
sepsis
Why can’t aminoglycosides kill anaerobes?
needs an oxygen-dependent pump to cross inner cell membrane (pump is inhibited by low pH)
Bacteria develop resistance to aminoglycosides is by _________.
enzymatic modification of the drug so that it cannot bind to the ribosome
Effective against aerobic gram negative enteric bacteria (including pseudomonas), but not effective against anaerobes.
Aminoglycosides
Aminoglycosides are typically given with a __________ to compensate for it’s inability to cross cell walls.
cell-wall inhibitor
mixed gram + and -: penicillin or vancomycin;
Just gram+: ceftazidime for pseudomonas
Aminoglycosides are not given _______ (route of administration).
orally
Tobramycin can be nebulized.
Why do we not like Chloramphenicol?
inhibits CYPs
Gray baby syndrome
bone marrow suppression (aplastic anemia)
DNA synthesis inhibitors include which classes of drugs?
Antifolates/Sulfonamides
Fluoroquinolone
Nitroimidazole. (metronidazole)
Which drug blocks production of dihydrofolate in bacteria?
SMX (sulfamethoxazole)
Which drug blocks reduction of dihydrofolate to tetrahydrofolate?
TMP (trimethoprim)
Bacteria can become resistant to sulfonamides by increasing synthesis of _______.
PABA (folate precursor)
Cotrimoxazole (TMP/SMX) is used for:
uncomplicated UTI/prostatits
otitis and sinusitis
If you prescribe a sulfonamide, you must instruct the patient to __________.
Drink plenty of water.
Drug can crystallize in urine
Sulfonamides are contraindicated in _________ because they can cause _______.
newborns
kernicteris
Which drug class inhibits topoisomerase II (in gram negatives) and IV (in gram positives) to prevent DNA synthesis?
Fluoroquinolones
Fluoroquinolone are indicated for treatment of:
complicated UTI traveler's diarrhea drug resistant gram negative rods anthrax lung infections (levo & moxi)
The respiratory fluoroquinolones are:
levofloxacin and moxifloxacin
Fluoroquinolone absorption is impaired by:
divalent cations (milk, antacids)
Fluoroquinolone toxicity/adverse effects
growing cartilage tendon rupture acute psychosis (esp with NSAIDS) drug interactions - inhibits p450
Fluoroquinolone are contraindicated in
pregnancy
children <18
urinary tract antiseptic
nitrofurantoin
Uncomplicated pyelonephritis can be treated with:
ciprofloxacin
levofloxacin
TMP/SMX
Nitrofurantoin MOA
free radical damage (nonspecific, so rare resistance)
Nitrofurantoin contraindications
pregnancy
newborns
renal impairment
Nitrofurantoin side effect
turns urine brown
accumulates in the bladder
methanamine
Uncomplicated bladder infection can be treated with:
TMP/SMX
Nitrofurantoin
Methanamine
