Antibiotics Flashcards
Describe Penicillins (Strucutre, MOA, Resistance)
Thiazolidine ring attached to a Beta-lactam ring
Bind to PBP to inhibit peptidoglycan synthesis and activate autolytic enzymes in cell wall
Bactericidal
Resistance via beta-lactamase secretion, Lack or altered PBP, efflux of drug out of the cell, and failure to synthesize peptidoglycans (mycoplasmas or metabolically inactive bacteria
Oral Availability varies
Most excreted through kidneys
Wide tissue distribution including the CNS
Generally short half-lives
Concentration independent pharmacodynamics
Describe Penicillin G and its uses
Natural Penicillin
Highly active against Gram Positive bacteria and spirochetes
acid liable (not oral)
IM or IV
DOC for streptococci, pneumococci, meningococci, spirochetes, clostridia, anaerobic gram psotive rods, and actinomyces. Also used for enterococci
Describe Penicillin V and its uses
Natural Penicillin
Highly active against Gram Positive bacteria and spirochetes
Oral Formulation
more acid stable than Penicillin G but, needs to be taken on an empty stomach
DOC for streptococci, pneumococci, meningococci, spirochetes, clostridia, anaerobic gram psotive rods, and actinomyces. Also used for enterococci
Describe Isoazolyl Penicillins (name them all) and there uses
Mthicillin (cloxacillin, flucloxacillin, and dicoloxacillin)
Relative resistnace to beta-lactmases
IV and Oral
Less gram positive activity
Used for staphylococcal infections, specfically Staph aureus that is MSSA
NOT USED for MRSA
Describe Aminopenicillins (name both) and there uses
Activity agaisnt both gram postive and gram negative bacteria but negative spectrum is fairly limited
destroyed by beta-lactamases
Ampicillin: IV, more acid stable than natural penicillins but,poor bioavailabilty
Amoxicillin: Oral, better absorption and more acid stable, commonly combined with clavulanic acid
Amoxicillin is the only penicillin acid stable enough to take with food
Used for: Streptococci, enterococci, Neiserria sp., non-beta-lactamase producing H. influenzae, E. coli, P. mirabilis, Salmonella, and more.
Describe Ureidopenicillins and there uses
Piperacillin
Increased activity against gram negative rods
active against Pseudomonas aeruginosa
Parenteral only
Can be combined with tazobactam
Name some Adverse Effects of Penicillins
Diarrhea, upset GI, fever, nephritis, eosinophilia, serum sickness, skin rashes, anaphylactic shock
allergic reaction, seizures, electrolyte imbalances, newutropenia, thrombocytopenia
Describe Cephalosporins
7-aminocephalosporanic acid, contain beta-lactam ring
Bind to PBP to inhibit peptidoglycan synthesis and activate autolytic enzymes in cell wall
Bactericidal
Resistance: lack of PBP or altered PBP, beta-lactamase production; resistant to beta-lactamases produced by staph aureus and common gram negative bacilli, efflux, inability of drug to penetrate
Cephamycin = an O where the S is
Describe First Generation Cephalosporins
Cephalexin and Cefadroxil are Oral agents
Cefazolin is IV/IM agent
Active agianst gram postive cocci but not active agaisnt enterococci or MRSA
Active agianst some gram negative bacilli such as E. coli, Proteus, and Klebsiella
Do not penetrate CNS
Cefazolin used for surgical prophylaxis
Describe Second Generation Cephalosporins
Cefuroxime axetil and Cefprozil are oral agents
Cefuroxime is IV/IM
Cephamycin drug is cefoxitin
Active agianst gram postive cocci but not active agaisnt enterococci or MRSA
Active agianst some gram negative bacilli such as E. coli, Proteus, and Klebsiella
Greater gram negative bacilli coverage but not Pseudomonas aeruginosa
cephamycin is used in mixed aerobic/anaerobic infections
Describe Third Generation Cephalosporins
Cefotaxime, Ceftriaxone, Ceftazidime
Cefixime is the oral agent
Have decreased activity against gram postive cocci except Streptococcus pneumoniae
Enhanced activity against gram negative bacilli
ability to penetrate the CNS
Ceftazidime is reserved for Pseudeomonas aeruginosa infections
Ceftriaxone uses the biliary system for excretion
Describe Fourth Generation Cephalosporins
Cefepime has enhanced activity against entrobacter and Citrobacter; active against Pseudomonas aeruginosa
Ceftaroline and Ceftobiprole have activity against MRSA, ampicillin sensitive E. faecalis, and penicillin resistant Streptococcus pneumoniae
Used almost always in hospital with a disease consultant as it is so broad spectrum
List adverse effects of Cephalosporins
Hypersensitivity
Diarrhea
Skin rash
Fever
Granulocytopenia
Hemolytic anemia
Biliary pseudolithiasis - ceftriaxone
Describe Carbapenems
Structure is related to beta-lactams
Imipenem given with cilastatin, meropenem
active agaisnt gram postive, gram negative, including Pseudomonas aeruginosa, and anaerobic organisms
Ertapenem has a long half life (OD) but poor activity against enterococcus sp. and Pseudomonas aeruginosa
Why is Imipenem always given with cilastatin?
Imipenem is inactivated by dihydropeptidases so, a peptidase inhibitor (cilastatin) is given with it.
Describe Monobactams
Monocyclic beta-lactam ring
Resistant to beta-lactamases
Aztreonam -s not available in Canada
active against gram negative bacilli including Pseudomonas aeruginosa
not active agaisnt ESBL or AmpC producers
What is MRSA?
MRSA stands for Methicillin resistant staphylococcus aureus;
resistant to the whole methicillin class as well as all penicillins
contains mecA gene and a low affinity PBP 2a
What agent is used in Canada for MSSA?
Cloxacillin, in the US nafcillin is used
What is ESBL? NDM-like?
ESBL is extended psectrum beta-lactamases that are found in E. coli and Klebsiella pneumoniae, resistance to even more drugs
NDM-like is New Dehli metallo-beta-lactamase ACinobacter baumannii; destroys even more drugs compared to ESBLs
Both have high resistnace to antibiotics, scary infections
What is a Concentration Independant Drug?
Threshold where no increase in effectiveness with increase of drug; want to keep at threshold level
What are the Macrolide Drugs?
Eryhtromycin
Clarithromycin
Azithromycin
Describe Macrolides (MOA, Resistance, Bacteria efficacy, etc.)
Attach to the 23S rRNA on the 50S subunit of bacterial ribosome resulting in inhibition of protein synthesis.
Bacteriostatic; time dependant killing
REsistance through methylation of the rRNA receptor, Inactivating enzymes, Active efflux
Covers gram positive organisms
Why is Erythromycin not seen much anymore?
Adverse effects; poor GI tolerability main reason it is not seen.
QT prolongation/ cardiac arrhythmias particularily when combined with CYP 3A inhibitors
What Activity dose Clarithromycin and Azithromycin have/ is used for? Why is it more used than Eryhtromycin
Active against Strep and Staph
Useful for some MRSA
less frequent dosing than erythromycin
Have less GI adverse effects than erythromycin
True or False, If an organism is resistant to erythromycin it is resistant to Clarithromycin and Arithromycin as well.
True
What are some unique characteristics of azithromycin
Long half-life
5 days azithromycin = 10 day therapy
Long intracellular concentrations
What are some main uses of macrolides?
URTI’s
STI’s
Acne
Beta-lactam allergy patients
What are Drug interactions of macrolides?
Antiarryhthmics
antidepressants
benzodiazepines
anticonvlsants
statins
CYP 3A4 substrates and inhibitors (for E and C)
Describe the MOA of Clindamycin and its spectrum of activtiy
Attach to the 23S rRNA on the 50S subunit of bacterial ribosome resulting in inhibition of protein synthesis.
Bacteriostatic; time dependant killing
Used for anaerobes, S. aureus including some MRSA as wellas streptococci.
Nota DOC for any infection
Used in penicillin allergies or resistant organisms
What are adverse effects of Clindamycin?
Nausea
vomiting
Diarrhea
Rash
C DIFF association
Elevated LFTs
Always be taken with water or liquid and sit upright for some time after taking to avoid esophageal irritation
what are the Tetracycline drugs?
Tetracycline
Monocycline
Doxycycline
What is the MOA of Tetracycline? How is there resistance?
Inhibit binding of aminoacyl-tRNA to the 30S unit of ribosome thereby inhbiting protein synthess
Bacteriostatic
High levels of resistance, methylation, change of 30S unit of ribosome, more
What is the spectrum of Tetracyclines?
Gram positive and Gram Negative but, high rates of resistance
DOC for rickettsiae, bartonella, chlamydiae, and M. pneumoniae
Nocardia
P. acnes
What are adverse effects of Tetracyclines?
Upset GI
Skin rashes
Photosensitivity
Yeast Overgrowth
Deposited in bones and teeth - do not use in < 8 years of age
hepatitis
Minocycline associated with hypersenstivity reactions as well as dizziness, vertigo, and ataxia
What are drug interactions of Tetracyclines?
Divalent and Trivalent actions redice absorption
Increased INR and bleeding with warfarin
Some anticonvulsants can reduce tetracycline levels
What is glyclcycline?
Syntehtic analogue of tetracycline
What is the spectrum of glycylcycline?
Has activity against gram negative and gram positive organisms
MRSA
S. pneumoniae
enterococci
Salmonella
Shigella
Acinetobacter
anaerobes
Explain how glycycline can be taken, how it is eliminated, and when it is used.
taken IV or IM
eliminated through the biliary tract and feces
Reserved for resistant organisms
What is the glycopeptide drug?
Vancomycin
What is the MOA of Vancomycin?
inhibits cell wall peptidoglycan synthesis
Bactericidal
What is the resistance seen in Vancomycin?
VRE, VISA (Staph aureus super infection)
What is the spectrum of activtiy of Vancomycin?
gram positive cocci
enterococci
PRSP
MRSA
Clostridia
Clostrioides
SOme bacilli
NO grame negative activity
How is Vancomycin adminsitered?
IV only for serious infections
Orally for C. difficile as it is not orally absorbed
Long infusion rates with drug monitoring
What are adverse effects of Vancomycin?
Nephrotoxicity
Ototoxicity
Red-man syndrome
Granulocytopenia
What are some similar drugs to Vancomycin?
Teicoplann has similar structure
Daptomycin is a lipopeptide adminstration is OD but has a major adverse effect of myopathy
What are the aminoglycoside drugs?
Streptomycin
gentamicin
tobramycin
amikacin
What is the MOA of aminoglycosides? How is there resistance?
inhibit protein synthesis by inhibiting 30S subunit of bacterial ribosome
Resistance through methylation of 16S rRNA-binding site, enzymatic destruction of teh drug, lack of permeability to the drug
active efflux
When do you use tobramycin instead of gentamicin?
Only when there is resistance to gentamicin
Gentamicin is the workhorse aminoglycoside
What is the spectrum for aminoglycosides?
aerobic gram negative bacilli
Synergistic with penicillins for enterococci and streptococci
Streptomycin for TB
How is aminoglycoside administered? How is it excreted?
IV or IM only
Renal elimination
Does not penetrate the CNS
Therapeutic drig monitoring is often preformed
What are the adverse effects of aminoglycosides?
nephrotoxicity
ototoxicity
neuromuscular blockade
What are drug interactions Aminoglycoside
Other nephrotoxic drugs
otehr ototoxic drugs
neuromuscular blocking agents
What are the Fluoroquinolone drugs?
Ciprofloxacin
Levofloxacin
Moxifloxacin
What is the MOA of Fluoroquinolones and how is there resistnace?
inhibit DNA gyrase or topoisomerase II and IV
Bacteriocidal: concentration dependant killing
Resistance:
alteration of the A or B subunit of DNA gyrase
Mutation of ParC or ParE of topoisomerase IV
change in outer membrane permeability
efflux pumps
What is the spectrum of fluoroquinolones?
high activity agaisnt gram negative bacilli, Haemophilus sp, neisseriae, chlamydiae, etc.
What is ciprofloxacin most active against?
Pseudomonas aeruginosa
What organism is Levofloxacin active against?
S. pneumoniae
What organisms is Moxifloxacin active against?
Anaerobes
What are fluoroquinolones used for?
UTI’s
lower RTI’s
enteritis
drug resistant mycobacterial infections
How are the fluoroquinolones eliminated?
Cipro and Levo renal elimination
Moxi is biliary elimination
What are adverse effects of fluoroquinolones?
Nausea
Vomiting
diarrhea
insomnia
headache
dizziness
CNS effects
skin rashes
C DIFF
PNS pain
tendon rupture
Can be very toxic; drugs in this category have been added and removed due to mortality such as hepatic failure causing and fatal skin affects
Why are fluoroquinolones not used in the elderly?
Tendon rupture risk side efect
How are fluoroquinolones taken?
Orally
Very bioavailable, not often seen IV/IM
What are the drug interactions of fluoroquinolones?
divalent and trivalen cations
QTc prolongation
CYP 1A2 inhibtion result in increased levels of many drugs
increased INR with warfarin
Why are fluoroquinolones not used often?
Many toxicities
reserved for resistant organisms and situations where DOC cannot be used
Not used in children < 18 years old
what is the MOA of SMX and TMP?
SMX is a structural analogue of PABA; comeptitively inhibits dihydrofolic acid synthesis
TMP binds to dihydrofolte reductase therefore inhbiting the reduction of dihydrofolic acid to tetrahydrofolic acid
BActeriostatic alone but bacteriocidal together
Can you use TMP alone?
Yes, is seen when there is sulfa allergies
What is SMX/TMP spectrum?
wide spectrum of gram negaive and gram positive, chlamydiae, nocardiae, and protozoa
MRSA included
No anaerobe activity or group A strep
What are SMX/TMP main uses?
UTI’s
Skin and sof tissue infection such as MRSA
PJP
What are adverse effects of SMX/TMP?
Skin rashes; can be sever (SJS)
hypersensitivity
headache
GI symptoms
bone marrow suppression
hyperkalemia and hyponatremia
photosensitivity
What are drug interactions of SMX/TMP?
2C9 inhibitor; 3A4 substrate
increased INR and bleeding with warfarin
hypoglycemic agents
increasing Potassium level drugs
caution in renal dysfuncting
and in first and 3rd trimester
What is the spectrum of activity of Metronidazole?
Anaerobes such as C. diff
protozoa
propionibacrium are resistant
How is metronidazole taken?
IV and Oral, very bioavailable
What are adverse effects of Metronidazole?
Drug Interactions?
GI
metalic taste
headache
dark urine
peripheral neuropathy
insomnia
stomatitis
Reaction with alcohol causing sweating, naseau, flushed, feeling very ill.
Increased INR and bleeding with warfarin
What is the MOA of Linezolid?
inhibits protein synthesis
bacteriostatic but, bactericidal against streptococci
What is the spectrum of activity of Linezolid?
streptococci, enterococci (includes VRE), staphylococci including MRSA
What is the main use of Linezolid? Why is it not commonly used?
REserved for mulit-drug resistant organisms, an alternative to vancomycin
Not commonly used as it is the most expensive antibiotic available.
Is both IV and oral dosage forms
What are adverse effects of Linezolid?
headache
nausea, vomitting, diarrhea
rash
increased LFTs
Myelosppression
optic neuropathy
peripheral neuropathy
lactic acidosis
decreased seizure threshold
What are drug interaction of Linezolid?
Increased serotonin syndrom risk with SSRI’s and MAOI’s
rifampin decreases linezolid levels
