Exam 8 Flashcards
Fxn of Penicillins
B lactam abx: inhibit transpeptidase and formation of PG cell wall
acute otitis media species
- s. pneumo
- hib
- moraxella catarrhalis
side chains added to what part of penicillin?
6 aminopenicillanic acid
other fxns of penicillin binding proteins
cell shape and septum formation during division of cell
penicillins activate what in bacteria
autolysins (murein hydrolases)
penicillins used often in combo with:
aminoglycoside (gentamycin)
Penicillin G’s downfall
cant pass through porin channels
P. aeruginosa resistance mechanisms
lack of porins, active efflux
P. aeruginosa, E. coli, N gonorrhoeae
active efflux of PCNs
PCN not affected by food
Amoxicillin
Highly protein bound penicillins
Nafcillin, Oxacillin, Dicloxacillin
PCN poor penetration
CNS, eye, prostate
What blocks tubular secretion of PCN
Probenecid
major antigenic determinant for PCN
Benzypenicilloyl
Oral administration PCN
least sensitizing
topical administration PCN
most sensitizing
Most common reaction to PCN
Type I HSN rxn
Methicillin
most common cause of acute interstitial nephritis
Ampicillin and Amoxicillin
cause skin rashes that are not allergic
Large doses of PCH=excess Na and K=…
cardiac and renal toxicity
PCN intrathecally into CSF
Seizures
Natural PCNS
PCN G, PCN V Potassium, PCN G Procaine, PCN G Benzathine
Penicillinase Resistant Penicillins (anti-Staph PCNS)
Methicillin, Nafcillin, Oxacillin
Extended Spectrum PCNS
Ampicillin, Amoxicillin. Greater GN activity
Antipseudomonal PCNS
Ticarcillin+Clavulanate Potassium, Piperacillin+Tazobactam
B lactamase inhibitors
clavulanic acid, tazobactam
PCN G
NATURAL PCN
- pH of gastric juice destroys, food interferes with absorption
- Parenteral use
- Probenicid increases plasma and CNS levels of CSF
- ACTIVE AGAINST MANY GP AND GN COCCI, spirochetes
- INACTIVE AGAINST GN BACILLI
- USE FOR NON RESISTANT STAPH and STREP
- C. PERFRINGENS AND TETANI
- SYPHILIS
- ACTINOMYCES ISRALEII
- NOT EFFECTIVE AGAINST ENTEROCOCCAL
N. Gonorrhoea
3rd Gen Cephalosporin
Anthrax
Cipro is good initial drug
PCN V Potassium
NATURAL PCN
- MORE STABLE THAN PCN G IN ACID (can be absorbed in GIT
- LESS ACTIVE THAN PCN G
- only use for minor infections
PCN G Procaine, PCN G Benzathine
NATURAL PCN
- Slow release from injected area
- injections into gluteus maximus/thigh
- avoid nerves–permanent neuro damage
- Resistance to Strep pneumo pneumonia and gonorrhea
PCN G Procaine
NATURAL PCN
Last several days
1. S. PYOGENES (GABHS)
PCN G Benzathine
NATURAL PCN 26 days 1. Strep pharyngitis 2. RF prophylaxis (GAS) 3. Syphilis
Nafcillin
Penicillinase resistant penicillins-anti staph penicillin
- IV administration is preferred (acid inactivation)
- SERIOUS STAPH INFECTIONS
- doses don’t need to be adjusted in renal failure
- bulkier side chain-resistant to destruction by b lactamase
- MOST RESISTANT TO BREAKDOWN
- drug of choice for PCNase + S. aureus
- PENETRATES CNS AND CAN BE USED FOR STAPH MENINGITIS
- Not used for GN aerobes
Oxacillin
Penicillinase resistant penicillins-anti staph penicillin
- IV administration is preferred (acid inactivation)
- SERIOUS STAPH INFECTIONS
- doses don’t need to be adjusted in renal failure
- bulkier side chain-resistant to destruction by b lactamase
- drug of choice for PCNase + S. aureus
- not used for GN aerobes
MRSA
VANCOMYCIN
Ampicilin
EXTENDED SPECTRUM PCNS
- can be given IV
- need to be adjusted for renal failure
- susceptible to b lactamase
- SE: DIARRHEA, RASH, decreased effectiveness with OCPS
- Better than PCN G for GN bacteria
- EXTENDED SPECTRUM: HELPSS ME
- H. flu
- E. coli
- L. monocyt
- P. mirab
- Salmonella
- S. pyogenes/S. pneumo
- M. catarrhalis
- E. faecalis
Amoxicillin
EXTENDED SPECTRUM PCNS
- can use lower dose b/c better absorbed in GI
- need to be adjusted for renal failure
- susceptible to b lactamase
- SE: DIARRHEA, RASH, decreased effectiveness with OCPS
- Better than PCN G for GN bacteria
- EXTENDED SPECTRUM: HELPSS ME
- H. flu
- E. coli
- L. monocyt
- P. mirab
- Salmonella
- S. pyogenes/S. pneumo
- M. catarrhalis
- E. faecalis
Ticarcillin + Clavulanate Potassium
ANTIPSEUDOMONAL PCN
- semisynthetic
- adjust for renal fxn
- TX GN aerobic bacilli and mixed anaerobic infections
- Excess Na problematic for CHF or renal failure
- can prolong bleeding time
- CAN USE WITH AMINOGLYCOSIDE (DONT MIX)
- must monitor for resistance
Tiementin
mixed aerobic-anaerobic infections-intrabdominal with B. fragilis (preferred being metronidazole)
Piperacillin + Tazobacam
ANTIPSEUDOMONAL PCN
- if CREATININE clearance is <40: dosage must be adjusted
- tx of GN aerobic bacilli/ mixed aerobic/anaerobic infxns
- MORE USEFUL FOR PTS WITH CHF OR RENAL FAILURE
- less prolonged bleeding time
- tx CAP (H. flu, P aeru)
- Septiciemia by GN bacteria, UTI, PID, Intraabdominal infxn, skin infections (s. aureus)
HAP
- Empiric: aminoglycoside
- P. aeruginosa: Piperacillin plus fluoroquinolone
- Higher dose required
Aztreonam
MONOBACTAM
- monocyclic B lactam ring
- resistant to enzymatic inactivation by B lactamases
- MUST BE IV
- adjust for renal impiarment
- Less HSN RXNS
- ONLY ACTIVE AGAINST GNR (similar to aminoglycosides)
- many tx including empiric tx for febrile neutropenic pt
- E. coli, K. pneumo, multi-drug resistant p. aeruginosa, s. marcescens, H. flu, Enterobacter
Imipenem + Cilastatin
CARBAPENEM
- B lactam ring. B lactam ab.
- Imipenem Not absorbed orally
- Broken down by dehydropeptdiases in renal tubule-Cilastin inhibits this enzyme. increases Imipenem concentration
- Disrupt cell wall synthesis
- Metallo B lactamases will inactivate carbapenems. otherwise resistant to b lactamases
- SE: induce B lactamase production. May cause resistance to other drugs. Nausea, vomiting. Allergic rxns to PCN, Seizures
- Activity against GP and GN aerobes, and B fragilis (anaerobe)
- Should be reserved for serious nosocomial infection (resistant microbes or mixed infections)
- DONT USE FOR SURGICAL PROPHYLAXIS, MRSA, C. DIFF, E. FAECIUM
Clavulanic Acid
B lactamase inhibitor
1. weak antibacterial activity
2. inactivates b-lactamase
3. most active against AMBER class A B lactamases (plasmid)
4. only included with PCNS
NOT GOOD WITH CLASS C B-LACTAMASES (chromosomal and inducible b lactamases of GNB)
Tazobactam
B lactamase inhibitor
1. weak antibacterial activity
2. inactivates b-lactamase
3. most active against AMBER class A B lactamases (plasmid)
4. only included with PCNS
NOT GOOD WITH CLASS C B-LACTAMASES (chromosomal and inducible b lactamases of GNB)
Amoxicillin + Clavulanic Acid
AUGMENTIN
- Oral
- penetrates peritoneal and pleural fluids
- high levels of drug in urine
- doesnt penetrate CNS
- must adjust for renal impairment
- Clavulanic Acid: “suicide inhibitor of b lactamase”
- Severe respiratory infections: double dose of Amox
- DRUG OF CHOICE FOR ACUTE OM, SINUSITIS, HUMAN/ANIMAL BITES, ALTERNATIVE FOR STREP PHARYNGITIS
- UTI
- CA NOT ACTIVE AGAINST ENTEROBACTER, PSEUDOMONAS, SERRATIA
P. aeruginosa
Aminoglycoside
Cephalosporins
- Derivative of 7 amino cephalosporanic acid
- Interfere with bacterial cell wall synthesis
- Bactericidal
- Antacid decrease absorption, H2 antagonists can decrease oral absorption
- 1st/2nd gen: not for CNS
- 3rd/4th: use for meningitis
- Avoid alcohol. inhibit aldehyde dehydrogenase–accumulation of acetaldehyde (usually methylthiotetrazole group)–dont use for 24-72hrs
- kill of VitK bacteria-coagulation issues
- seizures with renal impairment
Cefdoxime, cefuroxime,
decreased oral absorption with H2 antagonists
Cefdinir, Cefpodoxime, Cefaclor ER
Antacids decrease oral absorption
Longest half life of cephalosporins
Ceftriaxone
cephalosporin highly protein bound
cefonicid
cephalosporin and serum sickness
Cefaclor
Coagulation abnormalities, Cephalosporins
Cefazolin, cefmetazole, cefamandole, cefotetan, cefoperazone (dt methyltriotetrazole group)
cephalosporin plus aminoglycoside or loop diuretic
renal tubular necrosis
inactivation by b lactamase, cephalosporins
1st gen and 2nd gen cefaclor
1st gen cephalosporins
Cefazolin, cephalexin
2nd gen cephalosporins
cefaclor, cefoxitin, cefuroxime, cefprozil
3rd gen cephalosporins
ceftriaxone, cefixime, cefotaxime, ceftazidime
4th gen cephalosporin
cefepime
5th gen cephalosporin
ceftaroline
Cefazolin
1st gen cephalosporin
1. alcohol interolerance, bleeding disorders (vit K)
2. GOOD FOR GP BACTERIA (not Enterococci, MRSA)
3. GOOD FOR ORAL CAVITY ANAEROBES (NOT B. Fragilis)
4. GN enterics: PECK (proteus, E coli, Kleb)
5. DRUG OF CHOICE FOR SURGICAL PROPHYLAXIS
DONT USE FOR SYSTEMIC REACTIONS
Cephalexin
1st gen cephalosporin
1. alcohol interolerance, bleeding disorders (vit K)
2. GOOD FOR GP BACTERIA (not Enterococci, MRSA)
3. GOOD FOR ORAL CAVITY ANAEROBES (NOT B. Fragilis)
4. GN enterics: PECK (proteus, E coli, Kleb)
DONT USE FOR SYSTEMIC REACTIONS
Cefaclor
2nd gen cephalosporin
- Antacids decrease oral absorption with ER tablets
- LESS GP ACTIVITY THAN 1st
- MORE GN ACTIVITY
- Good against Sinusitis and OM
- Not effective against P. aeruginosa, enterobacter
Cefoxitin
ACTIVITY AGAINST B. FRAGILIS NOT GOOD AGAINST SINUSITIS AND OM 2nd gen cephalosporin 2. LESS GP ACTIVITY THAN 1st 3. MORE GN ACTIVITY 5. Not effective against P. aeruginosa, enterobacter
cefuroxime axetil
COVERAGE AGAINST S. PNEUMO, H FLUE, K PNEUMO
GOOD FOR CAP
H2 antagonists decrease oral absorption.
HYDROLYZED INVIVO by esterases to active drug
2nd gen cephalosporin
2. LESS GP ACTIVITY THAN 1st
3. MORE GN ACTIVITY
4. Good against Sinusitis and OM
5. Not effective against P. aeruginosa, enterobacter
cefprozil
2nd gen cephalosporin
- LESS GP ACTIVITY THAN 1st
- MORE GN ACTIVITY
- Good against Sinusitis and OM
- Not effective against P. aeruginosa, enterobacter
Ceftriaxone
3rd Generation cepahlosporin LONGEST HALF LIFE BILE EXCRETION-dont need to adjust for renal failure MORE GN ACTIVITY THAN 2nd RESISTANT TO B lactamases LESS GP CANT USE FOR L. Monocytogenes Meningitis FIRST LINE FOR GONORRHEA CAN PENETRATE CNS and TX GNR LYME DISEASE EMPIRICAL TX of SEPSIS
Cefixime
FIRST LINE FOR GONORRHEA 3rd Generation cepahlosporin MORE GN ACTIVITY THAN 2nd RESISTANT TO B lactamases LESS GP CANT USE FOR L. Monocytogenes Meningitis EMPIRICAL TX of SEPSIS
Cefotaxime
CAN PENETRATE CNS AND TX GNR 3rd Generation cepahlosporin MORE GN ACTIVITY THAN 2nd RESISTANT TO B lactamases LESS GP CANT USE FOR L. Monocytogenes Meningitis EMPIRICAL TX of SEPSIS
Ceftazidime
EFFECTIVE AGAINST P AERUGINOSA CAN PENETRATE CNS AND TX GNR (use in combo with Aminoglycoside) 3rd Generation cepahlosporin MORE GN ACTIVITY THAN 2nd RESISTANT TO B lactamases LESS GP CANT USE FOR L. Monocytogenes Meningitis EMPIRICAL TX of SEPSIS
Cefepime
4th generation cephalosporin
1. extended spectrum
resistant to plasmid and chromosomal B lactamases
2. GOOD FOR P. aeruginosa and enterobacteriaceae
ENTEROBACTER INFECTIONS LIKE UTI
can penetrate CSF
Ceftaroline fosamil
5th generation cephalosporin
- increase PBP binding
- activity against enterococci
- CAP
- Acute skin infections including MRSA
Highly PCN resistant strep meningitis
VANCO
Chloramphenicol
- chloramphenicol palmitate bd to active drug in duodenum
- IV use
- USE IN MENINGITIS
- BD in liver to glucorinide conjugate
- adjust for hepatic failure
- Binds 50s ribosomal subunit of 70s ribosome. prevents binding of aa tRNA. NO INTERACTION WTH PEPTIDYLTRANSFERASE
- SE: can inhibit mitochondrial protein synth in mammals
- CIDAL FOR H. flu, N men, S pneumo
- GOOD FOR GP GN and anaerobes
- MRSA and Pseudomonas are resistant
- CAN TREAT ROCKY MOUNTAIN SPOTTED FEVER, Q FEVER, TYPHUS
- Alternative tx for meningitis when allergy to PCN
- empiric tx for brain abscess
- Resistance dt production of acetyltransferase.
- SE: bone marrow suppresion, aplastic anemia (def. RBC production)
GREY BABY SYNDROME: babies dont have enough glucoronl transferase. vomiting tachypnea, abdominal distantion, cyanosis
PHENOBARBITAL AND RIFAMPIN DECREASE LEVELS
INDUCES CYP450
Tetracycline
PREFERRED FOR RICKETSIAL IFX
SHORT ACTING Tetra
found in breast milk and placenta
taking standing up with water. RISK OF ESOPHAGUS ULCERATION
antacids decrease absorption. no dairy
IV can cause thromboembolism
topical: used for blepharitis, conjunctivitis
NO CSF
bacteriostatic. INHIBIT PROTEIN SYNTH BY BINDING 30S. aa cant be added to peptide chain.
NOT DRUG OF CHOICE FOR GP
WILL TREAT GN aerobes. NOT PSEUdOMONAs OR ENTEROBAC
RICKETSIA, MYCOPLASMA, CHLAMYDIA, LYME
duodenal ulcers
RESISTANCE: Tet(AE) efflux pump of GN bacteria. DOXY AN DMINO NOT SUBSTRATES
-resistance encouraged by giving to animals for growth
SE: GI, superinfection, Dental discooration, flourescence, deformity (dont give during pregnancy), renal damage (FANCONI SYNDROME)–>ingestion of outdated drug, increased sens. to sun
Doxycicline
LONG ACTING tetra
PREFERRED PARENTERAL
DOES NOT ACCUMULATE WITH RENAL FAILURE
DOC for LYME DISEASE
taking standing up with water. RISK OF ESOPHAGUS ULCERATION
antacids decrease absorption. no dairy
IV can cause thromboembolism
topical: used for blepharitis, conjunctivitis
NO CSF
bacteriostatic. INHIBIT PROTEIN SYNTH BY BINDING 30S. aa cant be added to peptide chain.
NOT DRUG OF CHOICE FOR GP
WILL TREAT GN aerobes. NOT PSEUdOMONAs OR ENTEROBAC
RICKETSIA, MYCOPLASMA, CHLAMYDIA, LYME
duodenal ulcers
RESISTANCE: Tet(AE) efflux pump of GN bacteria. DOXY AN DMINO NOT SUBSTRATES
-resistance encouraged by giving to animals for growth
SE: GI, superinfection, Dental discooration, flourescence, deformity (dont give during pregnancy), renal damage (FANCONI SYNDROME)–>ingestion of outdated drug, increased sens. to sun
Minocycline
LONG ACTING tetra
LIPID SOLUBLE. secreted in tears and saliva. eliminate meningococcal carrier state
IMPORTANT FOR PERIODONTITIS. DECREASE POCKET DEPTH
taking standing up with water. RISK OF ESOPHAGUS ULCERATION
antacids decrease absorption. no dairy
IV can cause thromboembolism
topical: used for blepharitis, conjunctivitis
NO CSF
bacteriostatic. INHIBIT PROTEIN SYNTH BY BINDING 30S. aa cant be added to peptide chain.
NOT DRUG OF CHOICE FOR GP
WILL TREAT GN aerobes. NOT PSEUdOMONAs OR ENTEROBAC
RICKETSIA, MYCOPLASMA, CHLAMYDIA, LYME
duodenal ulcers
RESISTANCE: Tet(AE) efflux pump of GN bacteria. DOXY AN DMINO NOT SUBSTRATES
-resistance encouraged by giving to animals for growth
SE: GI, superinfection, Dental discooration, flourescence, deformity (dont give during pregnancy), renal damage (FANCONI SYNDROME)–>ingestion of outdated drug, increased sens. to sun
Tigecycline
Tetracycline
1. derivative of monocycline
2. IV
3. eliminated non renally
4. inhibit protein synth by binding 30s ribosomal. prevent protein growth.
5. cant be pumped by Tet(Ae) or Tet(K) or Tet(M)
EFFLUX PUMPS FROM PROTEUS AND PSEUDO PREVENT IT
WORKS AGAINST MRSA< ACINETOBACTER, B lactamase GN
-skin infections, abdominal infxn
Erythromycine base film coated
MACROLIDE
1. poor oral absorption
2. food decreases absorption
3. esters increase absorption (stearate, estolate, ethysuccinate)
4. IV if necessary
5. not in brain or CSF
6. crosses placenta
Bacteriostatic. reversible binding to 50s ribosomal subunit. inhibit movement of polypep chain and transpeptidation
7. CHLORAMPHENICOL AND MACROLIDES ANTAGONISTIC DT BINDING
8. H flu and Enterbac are resistant
GP and GN good
B fragilis is resistant
Mycoplasma, chlamydia, spirochetes good
CLINCAL USE: mycoplasma DOC, legionella pnemonia, COP, nonstrep hpahryngitis (cornebac), chlamydia. DOC in preg for UG infxn
9. PCN resistant S pneumo resistant to ery
Tx Campy infections
Methylase main cause of resistance
SE: can be used to increase gastric emptying, liver tox (cholestatic hepatitis), QT prolongation ,v tach, arrythmia
INHIBITS CYP450 (increase theophylline, anticoags, antihistamines)
Erythromycine estolate
MACROLIDE
1. poor oral absorption
2. food decreases absorption
3. esters increase absorption (stearate, estolate, ethysuccinate)
4. IV if necessary
5. not in brain or CSF
6. crosses placenta
Bacteriostatic. reversible binding to 50s ribosomal subunit. inhibit movement of polypep chain and transpeptidation
7. CHLORAMPHENICOL AND MACROLIDES ANTAGONISTIC DT BINDING
8. H flu and Enterbac are resistant
GP and GN good
B fragilis is resistant
Mycoplasma, chlamydia, spirochetes good
CLINCAL USE: mycoplasma DOC, legionella pnemonia, COP, nonstrep hpahryngitis (cornebac), chlamydia. DOC in preg for UG infxn
9. PCN resistant S pneumo resistant to ery
Tx Campy infections
Methylase main cause of resistance
SE: can be used to increase gastric emptying, liver tox (cholestatic hepatitis), QT prolongation ,v tach, arrythmia
INHIBITS CYP450 (increase theophylline, anticoags, antihistamines)
Erythromycine sterate
MACROLIDE
1. poor oral absorption
2. food decreases absorption
3. esters increase absorption (stearate, estolate, ethysuccinate)
4. IV if necessary
5. not in brain or CSF
6. crosses placenta
Bacteriostatic. reversible binding to 50s ribosomal subunit. inhibit movement of polypep chain and transpeptidation
7. CHLORAMPHENICOL AND MACROLIDES ANTAGONISTIC DT BINDING
8. H flu and Enterbac are resistant
GP and GN good
B fragilis is resistant
Mycoplasma, chlamydia, spirochetes good
CLINCAL USE: mycoplasma DOC, legionella pnemonia, COP, nonstrep hpahryngitis (cornebac), chlamydia. DOC in preg for UG infxn
9. PCN resistant S pneumo resistant to ery
Tx Campy infections
Methylase main cause of resistance
SE: can be used to increase gastric emptying, liver tox (cholestatic hepatitis), QT prolongation ,v tach, arrythmia
INHIBITS CYP450 (increase theophylline, anticoags, antihistamines)
Erythromycin ethysuccinate
MACROLIDE
1. poor oral absorption
2. food decreases absorption
3. esters increase absorption (stearate, estolate, ethysuccinate)
4. IV if necessary
5. not in brain or CSF
6. crosses placenta
Bacteriostatic. reversible binding to 50s ribosomal subunit. inhibit movement of polypep chain and transpeptidation
7. CHLORAMPHENICOL AND MACROLIDES ANTAGONISTIC DT BINDING
8. H flu and Enterbac are resistant
GP and GN good
B fragilis is resistant
Mycoplasma, chlamydia, spirochetes good
CLINCAL USE: mycoplasma DOC, legionella pnemonia, COP, nonstrep hpahryngitis (cornebac), chlamydia. DOC in preg for UG infxn
9. PCN resistant S pneumo resistant to ery
Tx Campy infections
Methylase main cause of resistance
SE: can be used to increase gastric emptying, liver tox (cholestatic hepatitis), QT prolongation ,v tach, arrythmia
INHIBITS CYP450 (increase theophylline, anticoags, antihistamines)
Erthyromycin lactobionate
MACROLIDE
1. poor oral absorption
2. food decreases absorption
3. esters increase absorption (stearate, estolate, ethysuccinate)
4. IV if necessary
5. not in brain or CSF
6. crosses placenta
Bacteriostatic. reversible binding to 50s ribosomal subunit. inhibit movement of polypep chain and transpeptidation
7. CHLORAMPHENICOL AND MACROLIDES ANTAGONISTIC DT BINDING
8. H flu and Enterbac are resistant
GP and GN good
B fragilis is resistant
Mycoplasma, chlamydia, spirochetes good
CLINCAL USE: mycoplasma DOC, legionella pnemonia, COP, nonstrep hpahryngitis (cornebac), chlamydia. DOC in preg for UG infxn
9. PCN resistant S pneumo resistant to ery
Tx Campy infections
Methylase main cause of resistance
SE: can be used to increase gastric emptying, liver tox (cholestatic hepatitis), QT prolongation ,v tach, arrythmia
INHIBITS CYP450 (increase theophylline, anticoags, antihistamines)
Clarithromycin
MACROLIDE More acid stable than ery better oral absorption penetrates macrophages and PMNS active metabolite in liver: 14 hydroxyclariothromycin adjust doses for renal clearance binds 50s ribosomal subunit USES: pharyngitis (s. pyogenes (PCN is DOC), acute maxillary sinusitis, CAP dt mycoplasma, s pneumo, skindi infections. TX and PX of MAC LESS GI UPSET THAN ERY inhibits CYP
Azithromycin
Macrolide
more acid stable. better orally than ery
penetrates all but cns
dont use to treat sepsis
slowly release, long duration of action (3d 1/2)
binds 50s ribosomal subunit
SINGLE DOSE TO TX GENITAL AND CHLAMYDIAL INFXN (as effective as 7d doxy)
MORE EFFECTIVE AGAINST H FLU
LESS ACTIVE AGAINST STAPH/STREP
doesNT inactivate CYP450. no drug interactions
Telithromycin
Macrolide
oral
TX RESPIRATORY INFXN
MACROLIDE RESISTANT BACTERIA MAY BE SUSCEPTIBLE
binds to 50s ribosomal subunit but differently. can avoid methylase.
inhibits CYP3A4. increase statins. LIVER TOX
First safe drug for infectious diseases
sulfonamides
Sulfa and TMX
inhibit DNA synthesis by inhibiting folic acid pathway (need for purine bases)
separate: static
together: cidal
Sulfasalazine
Sulfonamide
1. remains in bowel. use in UC and IBD
2. bd to 5 aminosalycilic acid. topical anti inflammatory and immune modulating
3. INHIBITS BACTERIAL DIHYDROPTEROATE SYNTHAse (converts PABA to dihydropteroic acid…precursor of folic acid)
4. ENTEROCOCCUS FAECALIS IS RESSITANT. AUXOTROPHIC FOR FOLIC ACID
–
SE: Crystaluria at acid pH
pts should increase fluids.
hemolytic anemia
bone marrow suppression-blood dyscrasia
anemia
HSN (more common in HIV). SJS
HyperK (blocks Na import in distal nephron)
malnourished pts: folate decrease
KERNICTERUS-BABIES: BILIRUBIN CROSSES BBB.
SULFA dipslaces drugs that bind albumin. increase serum? (warfarin, phenytoin, sulfonylurea hypglycemics)
Sulfacetamide, Mafenide, Silver sulfadiazine
Sulfonamide
Topical agents for burns, opthalmological ointments for conjunctivitis and trachoma. Silver sulf is statndard for prevention of burn infection (negligable absorption is less toxicity)
3. INHIBITS BACTERIAL DIHYDROPTEROATE SYNTHAse (converts PABA to dihydropteroic acid…precursor of folic acid)
4. ENTEROCOCCUS FAECALIS IS RESSITANT. AUXOTROPHIC FOR FOLIC ACID
–
SE: Crystaluria at acid pH
pts should increase fluids.
hemolytic anemia
bone marrow suppression-blood dyscrasia
anemia
HSN (more common in HIV). SJS
HyperK (blocks Na import in distal nephron)
malnourished pts: folate decrease
KERNICTERUS-BABIES: BILIRUBIN CROSSES BBB.
SULFA dipslaces drugs that bind albumin. increase serum? (warfarin, phenytoin, sulfonylurea hypglycemics)
Sufadoxine
Sulfonamide
ROLE IN MALARIA PROPHYLAXIS
3. INHIBITS BACTERIAL DIHYDROPTEROATE SYNTHAse (converts PABA to dihydropteroic acid…precursor of folic acid)
4. ENTEROCOCCUS FAECALIS IS RESSITANT. AUXOTROPHIC FOR FOLIC ACID
–
SE: Crystaluria at acid pH
pts should increase fluids.
hemolytic anemia
bone marrow suppression-blood dyscrasia
anemia
HSN (more common in HIV). SJS
HyperK (blocks Na import in distal nephron)
malnourished pts: folate decrease
KERNICTERUS-BABIES: BILIRUBIN CROSSES BBB.
SULFA dipslaces drugs that bind albumin. increase serum? (warfarin, phenytoin, sulfonylurea hypglycemics)
Trimethoprim
inhibis dihydrofolate reductase (converts dihydrofolic acid to tetrhydrofolic acid)
1. more sensitive to bacteria than humans
MORE POTENT THAN SULFONAMIDES
1:5 ratio of trimeth: sulf (1:20 ratio in serum)
2. kidney excretion
3. Trimeth distributes more widely than sulfa
4. penetrates CSF
USES: UTI Prostatitis (in combo)
UT pathogens, RT pathogens, GI pathogens (E. coli, salmonella, vibrio)
5. L monocytogenes, yersinia, nocardia, toxoplasma, pneumocystis
6. high metabolites of bacteria=resistance
7. resistant to TMX-sulf: P aeruginosa, b fragilis, treponema, campy, rickets
E faecalis is auxotrophic!!
–
SE: Crystaluria at acid pH
pts should increase fluids.
hemolytic anemia
bone marrow suppression-blood dyscrasia
anemia
HSN (more common in HIV). SJS
HyperK (blocks Na import in distal nephron)
malnourished pts: folate decrease
KERNICTERUS-BABIES: BILIRUBIN CROSSES BBB.
SULFA dipslaces drugs that bind albumin. increase serum? (warfarin, phenytoin, sulfonylurea hypoglycemics)
Aminoglycosides
- more active at alkaline pH
- forms complexes with b lactams. dont mix
- poor oral absorption
- polar. does not enter cells or CNS or eye
- can be intrathecal for meningitis (3rd gen ceph preferred)
- NEPHROTOXICITY AND OTOTOX
- uses O2 dependent active transport (not effective against anaerobes)
- cleared from kidney in direct proportion to creatinine
- irreversibly binds to 30s ribosomal subunit. cidal.
- block ribosome movement. mutant proteins. still works after MIC
- must determine trough concentration 30 min prior to next dose >2 is toxicity
- resistance: bacterial enzymes phosphorylate drug
- best against GN bacteria. NOT ANAEROBES
- endocarditis, severe systemic infxn
Aminoglycoside ototoxicity
Streptomycin is worst
(SK, AG, TN)
worse if with loop diuretic
accumulate endolypm and perilymph in inner ear. destruction of vestbular and cochlear hair cells
Auditory toxicity aminoglycoside
amikacin, kanaycine, netilmicin, neomycin
vestibular toxicity aminoglycoside
gentamycin, streptomycine, tobramycin
nephrotoxicity aminoglycosides
gent, tobra, neomyin
treat neuromuscular block of aminoglycoside
IV ca slat, AChesterase inhibitor, mechanically ventilate
NEOMYCIN AND NETILMICIN
aminoglycosides most resistant to inactivating enzymes
amikacin and netilmicin
Gentamycin and tobramycin
good against S. aureus and S epdiermidis
enterococci adn viridians group strep:
tx with gent/strep plus PCN G or AMP
Bacterial endocarditis
PCN plus aminoglycoside
