Exam1Lec8/9/10Antimicrobials Flashcards
What are antibotics
Chemicals produced by microorganisms to inhibit the growth of, or, kill other microorganisms
NATURAL
We want antibiotics to have selective toxicity, why?
- Kill or damage a microbe without damage to the host
- Therefore, the ideal antibiotic would kill pathogenic microbes without side effects for the patient, e.g., penicillin G comes the closest
How do we obtain selectivity toxicity?
Antibiotics target cellular differences between the host & the pathogenic microbe, e.g., penicillin inhibits the cell wall which is not in the mammalian cells
Target differences
What is the therapetic ratio (index)
- Therapeutic ratio (index), Ratio of the toxic dose to the effective dose of the drug, e.g., TI = LD50/ED50 (want LD to be high and ED to be low so TI to be a big number)
- Differs for each antimicrobial agent, i.e., some more toxic than others
What are the human body defenses against infection?
(1) Barriers: e.g., skin & mucous membranes
(2) Responses: antibodies, complement system, etc.
When do we use antimicrobials?
- Human body naturally kills pathogenic microbes
- However antimicrobials used when those natural defenses, Overwhelmed or damaged
Antimicrobials can be either _ or _
Either bactericidal or bacteriostatic
What is bacteriostatic and what are examples?
- inhibit bacterial cell replication but do not kill the organism at clinically achieved concentrations (we need to be careful with doses)
- e.g. chloramphenicol, erythromycin, & tetracyclines (TEC)
What are bactericidal and examples?
- Bactericidal: causes microbial cell death & lysis at clinically achieved concentrations
- e.g. penicillins, cephalosporins, & aminoglycosides (PAC)
What is either cidal or static based on the composition of enviroment
sulfonamides
Label and give example for each
- Bacteriostatic-eg. erythromycin
- Bacteriocidial-eg. pencillin G
What drugs attack cell wall
- Penicillin
- Cephalosporins
- Monobactams
- Carbapenems
- Vancomyic
PEN hit a VAN, so her CErtification for her CAR was MONO
What is used to stop transcription
- Quinolones- DNA gyrase
- Rifampin-RNA polyerase
- Metronidazole-DNA
MET the Royal QUeen
What is used to stop protein synthesis
- Aminoglycosides
- Tetracyclines
- Macrolides
- Chloramphenicol
MAC and Tarte has an AMazing CHecking account
What is used for the cell membrane
- Polymyxins
- Daptomycin
POLY DAPed the membrane
What is used against folic acid
- Trimethoprime
- Sulfonamides
TRi SUrFing on ACID
What are the 4 reasons why a patient may not respond to therapy with antibacterials
- misdiagnosis (fungal/viral v bacterial)
- No infection (increase temp becasue of non microbial cause)
- Do not complete full length of therapy
- Patient self treatment of infection with antimicrobials that were not prescribed for them
What are the five factors to consider when treating an infection? (host determinants)
- Sensitivity of organism to drug (drug resistance)
- Appropiate dosage (adult v neonatal- might have immature enzymes)
- Route of administration (PO vs. IV)
- Duration of therapy (days, weeks, months)
- Special patent features (immune systam, age, renal fxn)
What might distrub the microflora and what might it cause?
- use of an antimicrobial agent might disturb the ecologically balance leading to the overgrowth of pathogenic microbes which are inherently resistant to the antimicrobial agent
- This phenomenon is known as superinfection
Empiric therapy?
clinician will start txt instead of waiting for results. They will take a history and get as much info to make a decision and sollow treatment guidelines
What microorganisms in burns would cause an acute infection
S. aureus, S. pyogenes, P. aeruginosa
What microorganism is most likely to cause an acute infection with skin infections
S. aureus, S. pyogenes, Herpes zoster
What microorganisms would most likely cause acute infections with decubitus wound infections (bed sore)
S. aureus, E. coli, Bacteroides fragilis
What microorganism will most likely cause acute infection in tranumatic and surgical wounds
S. aureus, S. pyogenes, P. aeruginosa
What should we do for optimal therapy (anitmicrobial susceptibility)
Obtain cultures in order to identify the pathogenic microbe(s) & then do drug sensitivity testing (e.g., Disk-diffusion test, Broth dilution susceptibility test, etc.) to determine the MIC (minimum inhibitory concentration) or MBC (minimum bactericidal concentration)
What is used for first choice of antibodic in treponema pallidum, syphilis
- Benezathine Penicillin G
- Given IM
What is used for first choice Antibiotic in TB
Rifampin + Isoniazid + Pyrazinamide + Ethambutol
RIPE
What is used for first choice antibodic in P. aeruginosa, Pneumonia
Piperacillin/Tazobactam+ Tobramycine
PIPER TAZed TOBY
Most antimicrobial drugs & their metabolites excreted primarily by the kidneys, might have to have their dosage modified with what type of patient
impaired renal function
In order to ensure the drug hits the site of infection, what should we do?
At least 3-5 times the MIC to ensure optimal therapeutic response
What are some areas of the body that are difficult to penetrate by some antimicrobial drugs?
Meninges, joint spaces or eye
What can serve as a guide to adjust the dose of drug in renal
Creatinine clearance rate, Surrogate measure of renal function, GFR
Where favorable penetration for drugs
sites with inflammation
If we have decrease in renal fxn, how is the AUC affect?
Area under curve (plasma cont): it will be higher due to a higher cont.
What two drugs should be careful with hepatic fxn impairment
- Chloramphenicol
- Clindamycin- becasue of increase in half life
What is used to measure heptatic function
Sound clinical judgment used to guide therapy, Child-Pugh score
What do neonates have low cont of?
Why do we need to be careful with drugs in neonates
- UDP-glucuronosyl transferase which conjugates chloramphenicol
- The transferase is not present to make drug more water solube so it can cause CV collapse, gray baby syndrome
What drug do we increase to infacts and young children? Why?
- Gentamicin becasue volume of distribution
- As we age, we increase lipid profile and younger pts are more aqueous
What does sulfonamides do and what population is contriaindicated?
- Displace bilrubin from alumin in the blood which can then deposit in the brain, kernicterus or toxic encephalopathy
- Contraindicated in neonates
What does tetracycline cause
- permanent discoloration of growing teeth of children
- casue intracranial hyertension infants and children
- Bind to calcium
What does isoniazid cause?
increase hepatitis
What drug do we need to be careful with in CHF patients? Why?
Ticarcillin disodium/Clavulanate potassium-> 2g of Na and 0.1 of K+ per day
Pts already has problem with cardiac output and the Na+K will cause more issues (ex. decrease HR)
What an example of synergy
- Cell wall synthesis inhibitor (penicillin) + protein synthesis inhibitor (aminoglycoside)
- Sequential pathway, B-lactamase inhibitor
For synergy, what do we not do?
Do not use two drugs of same class or have the same mechanism of action
What are five drugs that are issues in preganacy and nursing? explain why
- Metronidazole
* Mutagentic - Dulfonamides
* Breast milk
* Kernicterus: increase bilirubin, displaced from albumin - Antifolate drugs
* decrease of conts. of folic acid in pregnant women - Fluoroquinolones
* Affect cartilage growth
5.Tetracyclines
* inhibit bone growth, tooth enamel dysplasia
- additive (indifference)
- Synergism
- Antagonism
What is drug resistance
Condition in which there is insensitivity or decreased sensitivity to drugs that ordinarily cause inhibition of cell growth or cell dealth
What are mechanisms of antimicrobial resistance in pathogenic microbes:
- decrease drug uptake -> cannot get to site
- increase drug efflux -> bacteria can create a pumps and pump the drugs out
- Enzymatic inactivation -> B lactases
- decrease affinity for site of action
What are the gram postivity bacteria and what is used
Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, Listeria monocytogenes
Use Vanco
What are the gram negative bacteria and what do you use?
Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae
Aminoglycosides
What are the anaerobes
Clostridioides (Clostridium, Peptoclostridium) difficile, Bacteroides fragilis
Where are B lactamases located in gram neg and pos?
Neg: inside
Pos: outside
What are some key difference of gram - and +
-: porins, outer membrane and less peptidogylcan
+: thicker peptidoglycan layer
What is a target for vanco?
glucosyltransferese and peptidoglycan synthase
What are all the penicillins?
- Pen G
- Amoxicillin
- Dicloxacilin
- Ticarcillin
- Piperacillin
What is the mech of action and resistance of penicillins?
MOA:
* inhibit peptidoglycan transpeptidase (prevent corss linking)
* PBP
* Autolysins
Resist:
* Change in PMP
* tolerance, deficiency in autoytic enxymes
* change in porin
* b-lactamase
What is the pharmcokinetics of pen?
inflammation, treat meningitis, arthritis and endophtalmitis
Side effects of pen?
- Gastric distress
- IV pain
- C. Diff
- Pen allery
- Na+
- Neuroxitity because it inhibit GABA ⭐️
What is the MOA and resistance of cephaloporins
same as pen
What does the first gen of cephalosporins treat?
PECS
* Proteus miralilis
* E.coli
* Klebisella pneum
* Staph or strep
What does second gen cephalosporins treat
HEN PEK
* Haempphilius influ
* Enterobacter aerogenes
* Neisseria gon
What does 3rd gen of cephalosporins treat?
ACES
* acinetobacter cal.
* Citrobacter div.
* Enterobacter c.
* Serratia mar.
* serious G-
What does 4th gen of cephalosporins treat?
- Pseud. aeruginos
- Citrobacter freundii
- gram +
waht does 5th gen of cephalosporins treat
MRSA and not pseudomonas
What is the mechanisms of action and resistance in imipenem?
Same as pen
What is imipenem used for to treat?
G- rods, Pseudo artuinosa and listeria mono.
What is special about carbapenems and their pharmacokinetics?
formualted with dipeptidase inhibitor, cilastatin
What is the SE of carbapenems
Seizures and hypersensitivity rxns
What is the MOA and resistance of monobactam?
same as pen
What is aztrenonam used for to treat
Gr - rods
P.aerg
When do we use a monobactam
when pt has pen allergy
What is the MOA and resistance of vancomycin
MOA: inhibitor of pepidoglycan synthase, binds to D-ala-D-ala. Inhibitor of pentapeptide precursor and membrane carrier
Resistance: D-ala-D lactate
What is vanco used for?
G+, MRSA and C.diff
What is something unique about vanco’s Pharmacokin?
Can enter CSF with inglamed meninges
What is the SE of vanco
ototoxicity
nephrotoxicity
What the MOA and resistance of daptomycin?
Bind to cell membrane and fromas pores
increase MIC
What is daptomycin used for ? when can we not use it?
- G+, MRSA and VRE
- Cannot use for lung ingection because pulmonary surfactants inactivate it
What is the SE of cyclic lipopeptide
myppathy
rhabdomyolysis
What binds to the target A site?
Tectracycline and aminoglycosides
What is the MOA and resistance of tetracyclines
MOA: binds to 30s (STATIC)
resist: Ribosomal change
What is tetracycines used for?
Myco pneum
Cutibacterium acnes
What is imp with tetracylines pharmacokin
Chelation
Dox is fecally eliminated
What are the SE of tetracyclines?
- Contraindicated in preg
- Discoloar of teeth and inhibit bone
- photsensitivity
- superinfection: c.diff and c. albicans
What is the MOA for tigecyclines, used for what/
Bind to 30s and static
usef for MRSA, VRE and PRSP
What are macrolides MOA and MOR?
MOA: 50s (p site) STATIC
resist: meth of 23
What are macrolides used for?
- Chalmy pneum
- H. influ
- M. car
- URTI
- Pneumonia
- Otitis media
What is the SE of macrolides and the drug interactions?
SE: prolong the QTc interval
Inter: inhibit CYP3A4
What is the MOA and SE of chloramphenicol
MOA: 50s STATIC (cidal for meningitis)
MOR
SE: gray baby syndrome (premature infacnts, decr in UGT)
What is the MOA and MOR in Clindamycin
MOA: 50s STATIC
MOR: meth of 23
What are the uses and SE of lincosamides
Uses: CA-MRSA and BLA
Side: CDAD
What is the MOA AND MOR in streptogramins
- 50s and cidial
- ribosomal methylas and actyltransferase
What are streptogramins used for and their SE
USED; osteomyelitis and endocarditis
SE: arthralgias and myalgias
What is the MOA AND MOR in aminoglycosides
MOA: 30s (CIDIAL)
MOR:decr porin perm, decrease ribosomal binding
USED WITH B-LAC
WHat is teh MOA and the usage of fidaxomicin?
binds to RNA polymerase
C.DIFF and CDAD
vanco also for C.diff
What is teh MOA and MOR of sulfonamides
MOA: inhibit dihydropteroate synthase
MOR: do not biosysnthsize folic acid, increase PABA profuction, dihydropterote synthase. decrease sulfa permeability
Whart are sulfonamides used for and SE?
Broad spectrum and for UTIs
SE: RASH: SULFA ALLERGY, SJS,TEN, kernicterus (newborn encephalopathy)
What is something special about sulfonamides and their pharmocokin
inhibit CYP2C9 so increase warfarin
What is the useage of trimethoprim and sulfamethozaole
MRSA, E.coli, UTI and prostatitis
What is the SE of Trimethoprim/sulfamethozaole
hemolytic anemia
What is teh MOR of trimethoprim and sulf
Tri: decrease DHFR affinity, decrease cell pemeation and over production of DHFR
What is the MOA of quinolones
- Inhibit toposimerase II (DNA gyrase, Supercoli)
- Inhibit DNA REPLICATION
Under Fluroquinolone, what do we used to treat UTIs and inhalation anthrax
Cipofloxin for UTI and inhalation anthrax
Levofloxacin for UTI and UTRI
What is the SE for quinolones?
Tendonitis and Myasthenia gravis
What is the drug interaction and what does quinolones inhibit?
Chelation
Inhibt CYP1A2, increase caffeine
