Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

year 2 > Antibiotics--exam 1 > Flashcards

Antibiotics--exam 1 Flashcards

1
Q

Penicillin (prototype)

A
  • β lactam ring forms irreversible covalent acyl-bond w/ transpeptidase enzyme (PBP)
  • Prevent x-linking (transpeptidation)
  • -cell continues to degrade wall (remodel)→ osmotic lysis
  • time dependent killing
  • most rapidly excreted drug by normal kidney
  • -can be partially blocked → probenecid
  • -can exacerbate gout
  • one of the most NON-TOXIC and SAFEST drugs
  • can produce all 4 types of hypersensitivities
  • -**most allergenic of Abx, then Sulfa then cephalosporins
  • -all are cross-allergic & sensitizing
  • -procaine-penicillin combo is worst

Toxicities (mostly dose dependent)

1) tissue irritation
2) excess Na, K+ from large doses → cardiac & renal toxicity
3) Soft frothy stools & diarrhea → broader spectrum is worse
- overgrowth of staph, pseudomonas, proteus or yeast
4) Superinfection
5) Jarisch-Herxheimer Rxn → severe febrile reaction
- -occurs in syphilis or leptospirosis due to massive killing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Penicillin G potassium (IV, IM)
Penicillin G benzathine (IM depot)
Penicillin G procaine (IM)
Penicillin V (acid resistant → oral)

A

Natural penicillin

  • Penicillin G benzathine → longest acting preparation
  • -Treat → Syphilis (DOC) & Rheumatic fever
  • -mild/mod infections
  • -prophylaxis
  • activity against gram positives→ **HIGHEST
  • spectrum→ some G-
  • activity against anaerobes→ some
  • activity against pseudomonas aeruginosa→ none
  • penicillinase resistance→ readily inactivated
  • acid resistance→ only penicillin V
  • main route of elimination→ active transport in kidney
  • -no metabolism → no drug interactions
  • CNS penetration→ poor penetration (↑ w/ inflammation)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Nafcillin (parenteral)

  • Oxacillin (oral)
  • Dicloxacillin (oral)
  • Methicillin
A

Penicillinase resistant penicillins*
(Anti-staphylococcal penicillins)

  • -**DOC for penicillinase producing staph. auerus
  • Methicillin was most common cause of interstitial nephritis
  • activity against gram positives→ lower against certain
  • spectrum→ some
  • activity against anaerobes→ some
  • activity against pseudomonas aeruginosa→
  • penicillinase resistance→ resistant
  • acid resistance→ some & **highly protein bound
  • -loading dose → 2x usual dose
  • main route of elimination→ **hepatic & renal excretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Amoxicillin

–Ampicillin

A

Extended spectrum penicillins* (amino penicillins)

  • activity against gram positives→ lower
  • spectrum→ extended G- (PeSSkEy, H. influ)
  • activity against anaerobes→ yes; w/ penicillinase inhibitors
  • activity against pseudomonas aeruginosa→ none
  • penicillinase resistance→ susceptible
  • acid resistance→ resistant
  • main route of elimination→ urinary excretion
  • Ampicillin rash → not allergic or itchy
  • -can occur w/ EBV
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Piperacillin

–Ticarcillin

A

Antipseudomonal Penicillin

  • activity against gram positives→ lower
  • spectrum→ same as amoxicillin + some G- enteric bacilli
  • activity against anaerobes→ yes; w/ penicillinase inhibitors
  • activity against pseudomonas aeruginosa→ YES
  • penicillinase resistance→ susceptible
  • acid resistance→ sensitive
  • main route of elimination→ renal excretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Aztreonam

A

Monobactam (same mxn as penicillin)

  • relatively resistant to β-lactamases
  • Targets → Gram negative rods (including Pseudomonas & Serrate)
  • NO ACTIVITY → Gram+ or anaerobes
  • Safe in pts w/ Penicillin allergy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Imipenem, Cilastatin

  • -meropenem
  • -ertapenem
  • -doripenem
A

Carbapenems (same mxn as penicillin)

  • broad spectrum → anaerobes, G+, G- rods
  • -Pseudomonas may develop res. → add amino glycoside
  • Imipenem → inactivated by renal dehydropeptivdases
  • -must be given w/ Cilastatin
  • -can cause seizures
  • Meropenem → resistant to dehydropeptidases
  • less likely to cause seizures
  • Ertapenem → highly stable against β-lactamases
  • particularly effective against Enterobacteriaceae

-Doripenem → good activity against pseudomonas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Clavulanic acid

  • -sulbactam
  • -tazobactam
A

Beta-lactamase inhibitors

  • resemble beta-lactam molecule
  • weak antibacterial action
  • inhibit many, but not all BETA LACTAMASES
  • -most active against → plasmid encoded lactamases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Vancomycin

–teicoplanin

A

Inhibitor of cell wall synthesis (glycopeptides)

  • binds terminal D-alanine D-alanine of nascent PG pentapeptide
  • → inhibits transglycosylase → no chain elongation
  • -**inhibits transpeptidation (cross linking)
  • ONLY effective for Gram+
  • staph aureus & epidermidis
  • strep & enterococci, corynebacterium & clostridium
  • penicillin and methicillin resistant staphylococcal (DOC)
  • -patient w/ penicillin allergy
  • parenteral
  • -sometimes oral → GI infections (pseudomem. colitis)
  • poor CNS penetration → don’t use for meningitis

Resistance → D-Ala-D-Ala → D-Ala-D-LACTATE

  • excreted unchanged in kidney → marked accumulation
  • nephrotoxicity in presence of renal insufficiency
  • -uremia after high dose may be FATAL
  • ototoxic
  • red man syndrome → histamine release
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Telavancin

A

Inhibitor of cell wall synthesis (lipoglycopeptide)

  • binds terminal D-alanine D-alanine of nascent PG pentapeptide (no elongation or x-linking like vancomycin)
  • ↑ membrane permeability (like daptomycin)
  • bactericidal → select Gram+, MRSA
  • complicated skin & skin structure infections
  • take 1x day
  • CI → pregnancy & renal insufficiency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Fosfomycin

A

Inhibitor of cell wall synthesis

  • inhibits one of the key 1st steps of peptidoglycan synthesis
  • -irreversibly inactivates enolpyruvyl transferase
  • -nucleotide precursors accumulate → death & lysis
  • active against Gram+ & Gram-
  • -uncomplicated lower UTI in women

-taken orally → excreted by kidney

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Bacitracin

A

Inhibitor of cell wall synthesis

  • inhibits activation (dephosporylation) of the lipid carrier
  • -no transport of peptidoglycan subunits (water soluble) through cell membrane
  • accumulate in cytoplasm→ not added to growing PG chain

-mainly target Gram+
-topical or parenteral
–serious nephrotoxicity w/ PE admin
–most commonly use in combo w/ polymyxin B & Neomycin
topically→ prevent superficial skin and eye infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Cycloserine

A

Inhibitor of cell wall synthesis

  • analog of D-alanine
  • competes w/ D-alanine for 2 enzymes (incorporate alanine)
  • -inhibits both enzymes & peptidoglycan synthesis
  • → weak cell wall & eventual cell lysis
  • 2nd line against active pulmonary & extra-pulm TB
  • severe CNS toxicity (anxiety, confusion, memory loss, seizures, etc.)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Cephalosporins

A
  • β lactam ring forms irreversible covalent acyl-bond w/ transpeptidase enzyme (PBP)
  • Prevent x-linking (transpeptidation)
  • -cell continues to degrade wall (remodel)→ osmotic lysis
  • has a 7-methyl group → ↑ resistance to β-lactamase
  • resistance mxn → same as w/ penicillin
  • most have some plasma protein binding
  • penetrate most tissues → not eye & CNS
  • most excreted unchanged by kidney
  • -Probenecid → ↓ excretion & ↑ 1/2 life
  • -adjust dosage w/ renal insufficiency

Adverse

  • pseudomembranous colitis → ↑ specturm ↑ chance
  • dose dependent renal tubular necrosis
  • synergistic nephrotoxicity w/ aminoglycosides (esp in elderly)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Properties of ICWS

A
  • activity against gram positives→
  • spectrum→
  • activity against anaerobes→
  • activity against pseudomonas aeruginosa→
  • penicillinase resistance→
  • acid resistance→
  • main route of elimination→
  • CNS penetration→
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Mechanisms of Bacterial Resistance

A
  • Inactivation by penicillinase (may be inducible)
  • ↓ permeability of outer membrane (only G-) → prevents reaching PBP
  • Alteration of PBP (mxn if resistant to Methicillin)
  • Autolytic enzymes not activated (Listeria & Staph)
  • Lack cell wall (Mycoplasma)
  • Non-peptidoglycan cell wall (Chlamydia)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Daptomycin

A

Inhibitor of cell wall synthesis (lipopeptide)

  • binds to bacterial membranes → rapid depolarization
  • → inhibits protein, DNA, and RNA synthesis → death
  • bactericidal → Gram+
  • NO MXN OF RESISTANCE

-IV → excreted unchanged by kidneys

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Cefazolin (IV)

  • Cefadroxil Monohydrate (oral)
  • Cephalexin (oral)
A

First Gen. Cephalosporin (narrow spectrum)

  • good activity → Gram + (EXCEPT enterococci)
  • -most G+ cocci except → enterocci, MRSA, MRSEpi
  • -NO β-lactam is effective against MRSA
  • moderate activity → Gram -
  • good activity → E. coli, Klebsiella pneum., Proteus marbles
  • -1st & 2nd gen. → DOC for E. coli

Cefazolin → surgical prophylaxis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Cefoxitin (IM, IV)

  • Cefaclor (Oral)
  • Cefotetan (IM, IV)
  • Loracarbef (Oral)
A

Second Gen. Cephalosporin (intermediate spectrum)

  • good activity → Gram +
  • increased activity → Gram -
  • good activity → E. coli, Klebsiella pneum., Proteus marbles
  • -1st & 2nd gen. → DOC for E. coli

Cefaclor → serum sickness like SE
Cefotetan & Loracarbef → disulfiram like effect
–inhibits acetyladehyde deydrogenase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Cefotaxime Sodium

  • Ceftizoxime
  • Ceftazidime
  • Ceftriaxone
  • Cefixime
A

Third Gen. Cephalosporin (broad-spectrum)

→ diff from 1st & 2nd gen

  • pretty good G+ and G- coverage
  • -↓ G+ cocci but ↑ enterobacteriaceae coverage
  • even more resistant to B-lactamase
  • some will get into CNS → Cefotaxime & Ceftriaxone
  • effective against → Pseudomonas
  • first line choice → Salmonella
  • mostly/half metabolized → liver
  • -if it is lipid soluble wont be excreted in kidney and must be conjugated in liver
Ceftriaxone → ↑ hepatic elimination
--DOC gonnorhea
--penicillin resistant strep. pneumoniae
Cefixime → ORAL
Ceftizoxime & Ceftazidime → antipseudomonal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Cefepime

A

Fourth Gen. Cephalosporin

  • good G+ and G- (similar to 3rd gen)
  • more resistant to some β-lactamases
  • anti-pseudomonal (similar to Ceftazidime)
  • better activity → Enterobacter & Citrobacter
  • reserved for ICU and severe systemic infections
  • ↑ penetrvity → Enterobacter & Citrobacter
  • reserved for ICU and severe systemic infections

-penetrates CSF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Ceftarolime fosamil

A

Unnamed gen. Cephalosporin

effective against MSSA, MRSA, & VRSA

  • high affinity to → PBP 2A (responsible for resistance)
  • -encded by mega
  • no antipseudomonal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Organisms not reliably covered by cephalosporins

A
  • Enterococci → Penicillin
  • List. Monocytogenes → Penicillin
  • MRSA
  • Atypicals → Chlamydia & Mycoplasma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Cephalosporins are 1st choice for infections with:

A
  • Moraxella catarrhalis → 2nd or 3rd gen
  • Neisseria gonorrhoeae → ceftriaxone, cefixime (oral)
  • E. coli, Klebsiella, Proteus → 1st or 2nd gen.
  • Salmonella → 3rd gen
  • Penicillin resistant Strep. pneumonia → ceftriaxone

MAY be used:

  • Gram + infections in penicillin-sensitve patiens
  • mixed infections → cellulitis or skin ulcers in diabetic
  • surgical prophylaxis → cefazolin
  • UTI → excreted & concentrated in urine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Sulfonamide mechanism & uses

A

Sulfonamide (bacteriostatic)

-competes w/ PABA at dihydropteroate synthase
→ blocks formation of DHF
–folic acid necessary for Purine & DNA synthesis
–susceptible bacteria can’t multiply, grow, or survive
–mammals do not synthesize folic acid like bacteria

-inhibit both Gram+ and Gram-

RESISTANCE

  • -↓ sensitivity of target enzyme
  • -↑ formation of PABA
  • -use of exogenous folate

USES

  • DOC→ UTI infections (1st attack & prophylaxis)
  • DOC→ Nocardiosis
  • Toxoplasmosis & Trachoma
  • Pneumocytstis carinii → children and AIDS patients
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Sulfonamide distribution, metabolism/excretion, interactions and Toxicity

A
  • good distribution
  • -cross placenta and BBB
  • Good degree of plasma protein binding → no neg. effect
  • ***urine conc. → 10-20x plasma can be reached for UTI
  • -at high concentrations → bactericidal
  • Metabolized in liver → acetylated products
  • Excreted through kidney
  • -insoluble (esp. *acidic urine) → crystalluria & renal dmg
  • –drink more water or alkalize urine

TOXICITIES

  • every organ systems may be adversely affected
  • Kernicterus in nursing infant → displaces bound bilirubin →CI infants <2 months
  • Drug sensitivy (allergy 6%, 2nd to penicillin)
  • Blod dyscrasia, leukopenia, granulocytopenia,
  • -thrombocytopenia, agranulocytosis
  • Kidney & Liver damage
  • Stevens-Johnson syndrom (dermal toxic lysis → lose epi)
  • Microscopic hematuria→ crystals damage
  • PHOTOSENSITIVITY
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Sulfasalazine

A

Sulfonamide (bacteriostatic)

  • competes w/ PABA→ blocks formation of DHF
  • -prodrug cleaved GI bacteria→ sulfapyridine + mesalamine
  • -local actions of melamine → effectiveness of sulfasalazine
  • used to treat Ulcerative Colitis
  • oral
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Silver Sulfadiazine

A

Sulfonamide (bacteriostatic)

  • exact mechanism is unknown→ dent inhibit FA synthesis
  • -damages cell membrane and cell wall
  • Topical → prevent & treat infections → 2nd/3rdº burns
  • Activity against → Bacteria AND yeast
  • does not inhibit CA (Mafenide does)
  • doesn’t stain dressing or tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Trimethoprimp

A

Folate Antagonist

  • inhibits DHF reductase → blocs formation of THF
  • -THF needed for carbon transfer → NA, protein synthesis
  • -therapeutic does → no human enzyme inhibition
  • activity against Gram+ and Gram-
  • commonly used systemically for treatment & prophylaxis:
  • -uncomplicated UTI
  • –alone may be as effective → recurrent UTI
  • -traveler’s diarrhea
      • SMX or dapsone → pneumocystis carinii
  • can be used w/ impaired renal function or if sulfa drugs can’t be tolerated
  • may be TERATOGENIC → don’t take during pregnancy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Co-trimoxazole (Bactrim)

Sulfamethoxazole + Trimethoprim (TMP-SMX)

A

Sulfonamide Combo

  • Sulfamethxazole blocks PABA incorporation to DHF
  • Trimethoprim prevents reduction of DHF to THF
  • -selective for DHF reductase of lower organisms
  • fixed 1:5 ratio (TMP-SMX) → 1:20 serum concentrations
  • DOC for uncomplicated UTI (except for enterococci)
  • -Prostatitis (along w/ doxycycline & fluoroquinolones)
  • DOC for Moraxella catarrhalis
  • P. jiroveci pneumonia (also TMP + dapsone)
  • -respiratory tract pathogens → pneumococcus
  • –Haemophilus, Moraxella catarrhalis, Klebsiella pneumonia
  • Shigellosis & systemic salmonella infections
  • some non TB myco infections
  • MSSA & MRSA
  • otitis media
  • 2nd line for Listeria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Sulfadoxine + Pyrimethamine

A

Sulfonamide Combo

pyrimethamine → inhibits parasitic DHF reductase
sulfadoxine → antagonizes PABA
–synergistic activity on FA production

  • used in combo → malaria treatment
  • -not prophylaxis → fatal toxic epidermal necrolysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Sulfadiazine

A

Sulfonamide (bacteriostatic)

-competes w/ PABA→ blocks formation of DHF

  • oral, intermediate duration
  • used w/ Pyrimethamine → toxoplasmosis
  • POORLY SOLUBLE in urine → CRYSTALLURIA (most likely)
  • -limited use for serious infection
33
Q

Macrolide Group

A

Protein Synthesis Inhibitor

  • bacteriostatic??
  • effective alternative to penicillin → allergy or kidney failure
  • among the SAFEST antibiotics
  • Clarithromycin & Azithromycin → respiratory, skin & skin structure infections
34
Q

Eryhthromycin mechanism, uses, resistances

A

Macrolide

  • reversibly binds 50s subunit → blocks translocation (A→P)
  • -near binding site for Chloramphenicol → antagonistic
  • spectrum similiar to Penicillin G
  • most active against → G+ cocci
  • active against → G+ bacilli (clostridium
  • effective against → Mycoplasma pneumonia
  • majority of gram negative → resistant

USE

  • most commonly → mixed infections of skin, soft tissue, body cavities caused by Gram-positive organisms
  • alternative to penicillin
  • Group A strep pyogenes → cellulites, scarlet fever, pharyngitis, erysipelas
  • Acute diphtheria
  • 1ry pneumonia → M. pneumoniae & chlamydia
  • DOC → Legionnaire’s disease (legionella pneumophila)
  • -atypical pneumonia ??

RESISTANCE (mostly plasmid encoded)

1) Drug efflux by active pump
2) **Methylase enzymes→ modify ribosomal target; ↓binding
- -cross resistance w/ all members of group
3) Hydrolysis by esterases from enterobacteriaceae
4) Chromosomal mutations → alter a 50s ribosomal proein

35
Q

Eryhthromycin metabolism, toxicity, adverse reactions, and drug interactions

A
  • Gastric acid → rapidly destroy erythromycin base
  • crosses placenta, penetrates prostatic fluid
  • no CNS penetration
  • Primarily fecal excretions (large amounts lost)
  • -some in bile → reabsorbed
  • Intravenous → E. Gluceptate & E. Lactobionate when large doses needed

ADVERSE

  • GI disturbances
  • DIARRHEA → stimulates motilin
  • -may help constipation
  • QT prolongation, torsades de pointes
  • -worst in group, but all do it
  • transient hearing loss → ototoxicity

INTERACTIONS

  • inhibits CYP3A4 → ↑ serum [ ] of other drugs
  • -→ serious QT prolongation and cardiac arrhythmias w/
  • -Cispride, Pimozide, Sparfloxacin or Grepafloxacin
  • changes GI flora → ↓ estrogen enterohepatic circulation
  • ICWS are made ineffective → they need growth to work
  • statins -> rhabdomyolysis
36
Q

Clarithromycin

A

Macrolide
-binds to 50s subunit → protein synthesis inhibition

  • most common use → infections of respiratory tract
  • penetrates lung tissue & macrophage > Erythromycin
  • -**effective against MAC
  • H. pylori-associated duodenal ulcer
  • community-acquired pneumonia in children
  • inhibition of CYP3A4 → ↑ serum [ ] of other drugs
  • less QT elongation than Erythromycin
  • well tolerated → no disabling nausea & vomiting
  • other adverse reactions similar to erythromycin
  • best oral of macrolides
37
Q

Azithromycin

A

Macrolide
-binds to 50s subunit → protein synthesis inhibition

  • not metabolized by liver & excreted into bile
  • → less interactions & inhibition of P450
  • can be dosed → 1 daily
  • less GI intolerance than Erythromycin
  • reaches higher intracellular concentrations
  • -↑ efficacy & duration of action

USES

  • active against same organisms as erythromycin
  • STD → Chlamydia & gonorrhea combine w/ Ceftriaxone
  • pediatric otitis media, pharyngitis, MAC prophylaxis
  • IV for initial treatment of CA pneumonia & PID
38
Q

Telithromycin

A

Ketolide
-binds 50s subunit → inhibits protein synthesis

  • greater antibacterial killing than macrolides
  • good against respiratory pathogens
  • -**erythromycin & penicillin resistant pneumococci
  • activity → intracellular and atypical bacteria
  • metabolized by CYP3A4
  • diarrhea, nausea, vomiting → most common SE
  • serious hepatoxicity
39
Q

Clindamycin

A

Inhibitor of Protein synthesis
-binds 50s subunit → inhibits protein synthesis

  • **effective anti-aerobic antibiotic
  • -MOST anaerobes → G+ & G-
  • w/ pyrimethamine → toxoplasmic encephalitis in AIDS
  • strep (not enterococci) & staph → very susceptible
  • topically for acne → inhibits lipase-producing organism
  • -↓ FFA in sebum → inflammatory lesion w/ acne
  • well absorbed orally → high [ ] **BONE, bile, and urine
  • -poor CSF concentrations
  • well know cause → pseudomembranous colitis (c. dificile)
40
Q

Dalfopristin; Quinupristin (Synercid)

A

Streptogramin

  • irreversible block ribosome functioning
  • -Dalfopristin → 70s or 50s → inhibits early phase
  • -Quinupristin → 50s → inhibits late phase
  • combo has up to 16x activity of each agent alone

USE (IV infusion)

  • **Vancomycin resistant enterococcus faecium bacteremia
  • Complicated skin and skin structure due to staph aureus
  • nausea, vomiting, pain, puritis, rash
  • inhibits CYP 3A4 (↓ cyclosporin, midazolam, nifedipine)

CI → pregnancy, children, breast feeding, hepatic disease

41
Q

Linezolid

A

Oxazolidinones

-binds 50s → prevents formation of functional 70s initiation complex → blocks translation

**-reversible, non-selective inhibition → MAO!!

  • predominant activity → aerobic gram positive
  • -bacterial pneumonia
  • -skin & skin structure infections
  • -Vanco resistant enterococcal infections
  • -MRSA

-CI → pheochromocytoma or hypersensitivity

42
Q

Isoniazid

A

Primary Antimycobacterial agent

  • inhibits biosynthesis of Mycolic acid
  • can reach intracellular bacteria (streptomycin can’t)
  • prodrug activated by Mtb protein (KatG → resistance)
  • -develops quickly when given alone
  • ALWAYS combo w/ rifampin, streptomycin or ethambutol for ACTIVE TB
  • given SOLO for LATENT TB
  • bactericidal → actively growing bacilli
  • bacteriostatic → latent or dormant infection
  • combo w/ Rifampin → bacteriocidal
  • most atypical mycobacteria → resistant to INH

TOXICITY:

  • CNS stimulation (convulsions
  • peripheral neuritis → slow acetylators (↓ by Pyridoxine)
  • liver damage → fast acetylators (MUST test liver enzymes)
  • Hemolysis → G6PD
  • Lupus like syndrome
43
Q

Rifampin

A

Primary Antimycobacterial agent

  • inhibits DNA-dependent RNA polymerase
  • -resistance → mutation rpoB gene
  • primarily used for TB in combo w/ other anti-TB drugs
  • effective against TB & some atypical in very low [ ]
  • inhibits growth → G+ cocci and some G-
  • **bactericidal → active, latent, intra-/extra-cellular bacilli
  • -can be used alone for latent TB
  • prophylaxis for TB → HIV pts (Rifabutin if taking protease inhibitors)
  • Asymtomatic carriers of N. meningitidis (not for usual infxn)
  • ***strong bactericidal activity → Leprosy
  • excreted primarily through Bile
  • induces CYP3A4
  • ↓↓ effectiveness of oral contraceptives
  • ↑ requirement of methadone
  • make tears, urine, and sweat harmless ORANGE
44
Q

Rifabutin

A

Primary Antimycobacterial agent

-inhibits DNA-dependent RNA polymerase

  • very lipophilic → wide dist. (5-10x [ ] in lungs than serum)
  • → substantial intracellular accumulation
  • Alternative to Rifampin
  • -LESS potent inducer of CYP → HIV pts on HAART
  • alternative to Clarithromycin or Azithromycin for 1ry MAC prophylaxis in HIV pts.
  • alternative to Rifampin for TB/TB prophylaxis in HIV pts if resistant to isoniazid
  • discoloration → URINE, tears, sweat, feces, saliva, sputum
  • thrombocytopenia (not significant)
45
Q

Pyrazinamide

A

Primary Antimycobacterial agent

  • requires conversion to active form
  • -resistance → mutation pncA
  • Mechanism not well understood
  • bacteriostatic/bacteriocidal
  • HIGH risk of hepatic injury
  • hyperuricemia
  • -CI if any degree of hepatic dysfunction
46
Q

Ethambutol

A

Primary Antimycobacterial agent

  • inhibits arabinosyl transferases → cell wall synthesis
  • -inhibits arabinogalactan synthesis
  • -resistance → mutation in embCAB
  • bacteriostatic

-about 1/2 excreted in urine unchanged

  • ↓ visual acuity
  • loss of green-red perception → retrobulbar neuritis
  • -not recommended for children < 13 yrs.
47
Q

Streptomycin

A

Aminoglycoside (Primary Antimycobacterial agent)

-Protein synthesis inhibitor → 30s (bactericidal)

48
Q

(para-)Aminosalocylic acid

A

Secondary Antimycobacterial agent

-ORAL→ absorbed from GI and dist. widely (not CSF)

  • Anorexia, nausea, diarrhea
  • peptic ulcer, hemorrhage
  • kidney & liver damage
  • Thyroid injury → goiter w/o myxedema
  • Drug fever, joint pain, rashes, granulocytopenia
49
Q

Ethionamide

A

Secondary Antimycobacterial agent

-ORAL

  • GI irritation, neurological complications
  • resistance rapidly develops (give in combo)
50
Q

Rifapentine

A

Secondary Antimycobacterial agent

  • inhibits DNA-dependent RNA polymerase
  • has longer 1/2 life than rifampin and rifabutin
  • once weekly dosing
  • intermediate induction of CYP
51
Q

Capreomycin

A

Secondary Antimycobacterial agent

  • IM injection
  • Kidney damage (most serious)
  • nitrogen retention
  • 8th nerve deafness & vestibular disturbances
52
Q

Clofazimine (off market in USA)

A

Secondary Antimycobacterial agent

-binds preferentially to mycobacterial DNA (high GC)
→ ↓ reproduction & growth

  • bactericidal → TB, M. marinum
  • slowly bactericidal → leprosy
  • bacteriostatic → MAC
53
Q

Thalidomide

A

Anti-leprosy agent

  • ↑ degradation of TNF-α mRNA encoding protein
  • → ↓ TNF-α
  • treatment of choice → Erythema nodosum leprosum
  • TERATOGENESIS (most regulated Rx in US)
  • -CI in pregnancy and breastfeeding
54
Q

Dapsone

A

Anti-leprosy (similar to sulfonamide)

  • PABA antagonist → bactericidal
  • part of MDT for leprosy
  • -given alone Leprosy always develops drug resistance
  • bacteria disappear very slowly
  • -after 5 yrs of treat → 1/2 pts have positive smears
55
Q

Treatment for MAC

A

1) include either Clarithromycin or Azithromycin
2) include Ethambutol
3) add third oral drug (rifabutin, rifampin, clofazimine, cipro)
4) Include IV amikacin in certain cases (resis. clarithromycin)

56
Q

Amino glycoside group

  • -Gentamicin
  • -Tobramycin
  • -Amikacin
  • -Streptomycin
  • -Neomycin
  • -Kanamycin
  • -Paromomycin
A
  • inhibit protein synthesis → inhibts 30s subunit
  • -block initiation of protein synthesis
  • -block further translation → premature termination
  • -promote usage of incorrect AA → bactericidal
  • transport into cell req. O2 → no effect anaerobic
  • Polarity responsible for properties
  • NONE is absorbed adequately orally
  • NONE penetrate CSF
  • kidney rapidly excretes ALL
  • -accumulate w/ renal failure → ↓ dose
  • more active at ALKALINE pH
  • used almost exlusively for:
  • -***Gram- enteric bacteria (enterobacteriaceae)
  • -suspicion of sepsis or endocarditis (combine w/ penicilin)
  • Ototoxicity → auditory and vestibular (8th CN)
  • Nephrotoxicity
  • neuromuscular weakness
  • resistance is plasmid mediated (R-factor derived)
  • -enzymes that adenylate, phosphorylate, or acetylate
  • killing → concentration dependent
  • adverse effects → time dependent
57
Q

Streptomycin

A

Aminoglycoside

  • Tularemia
  • Bubonic plague
  • Only TB drug that is injected
  • endocarditis
  • inhibit protein synthesis → inhibts 30s subunit
  • -block initiation of protein synthesis
  • -block further translation → premature termination
  • -promote usage of incorrect AA → bactericidal
58
Q

Kanamycin
Neomycin
Paromomycin
Gentamicin

A

Aminoglycoside (30s)

-Kanamycin & Neomycin → pre-op suppression of enteric aerobic flora

  • Neomycin → hepatic encephalopathy
  • -kills GI bacteria that make ammonia

-Paramomycin → intestinal amebiasis

Neomycin & Gentamicin → topical application

59
Q 
Streptomycin → 
Gentamicin → 
Tobramycin → 
Amikacin → 
Spectinomycin →

Neomycin →
Kanamycin →
Paromoycin →

A 
Streptomycin → tuberculosis (enterococcal endocarditis)
*Gentamicin → gram neg, combination
*Tobramycin → gram neg, combination
*Amikacin → gram neg, combination
Spectinomycin → gonorrhea

*effective against p. aeruginosa

Neomycin → oral, topical
Kanamycin → rarely used
Paromoycin → cryptosporidium parvum, amebiasis, tapeworm

60
Q

Chloramphenicol

mxn, resistance, distribution, metabolism, toxicity

A

Broad Spectrum (protein synthesis inhibitor)

  • binds 50s → inhibits peptide bond formation
  • -usually bacteriostatic
  • -bactericidal → common meningeal pathogens

resistance → acetyl transferase → acetylate & inactivates

  • orally → ALL tissues, (including eyes and CNS)
  • conjugated w/ glucuronic acid (90%)
  • -toxic levels w/ hepatic insufficiency
  • 10% active drug excreted by glomerular filtration
  • reversible BM depression & hematopoietic problems
  • can inhibit mitochondrial protein synthesis
  • -*FATAL APLASTIC ANEMIA
  • Gray baby syndrome → unable to conjugate and excrete
  • -glucuronyl transferase deficiency
61
Q

Chloramphenicol

uses, interactions

A
  • NOT used as DOC for any bacterial infection
  • DO NOT use for minor infection, viral, URT, or w/o careful follow up
  • Typhoid fever
  • Meningitis
  • Eye infections
  • infections from Gram-negative organisms
  • Rickettsia, Brucellosis, RMSF
  • not effective → Entamoeba histolytic or pseudomonas
  • inhibits metabolism→ Tolbutamide & Chlorpromaide
  • may interfere w/ Warfarin metabolism
  • -→ ↑ hypoprothrombinemic effect
  • inhibits P-450 (phenobarbital & phenytoin)
  • ↓ plasma [ ] by use w/ phenobarbital, phenytoin, rifampin
  • can displace erythromycin from binding site
62
Q

Tetracycline (group)

A

Tetracycline

  • bind 30s → prevent access of aminoacyl tRNA to receptor site → prevents addition of AA to growing chain
  • bacteriostatic
  • resistant mutants → transport drug out of cell
  • poor solubility→ unabsorbed modifies intestinal flora
  • -overgrowth → yeast, enterococci, proteus, pseudomonas
  • chelates Ca++, Fe++ and Al++ → ↓ solubility
  • wide list. → except CNS and JOINTS
  • -deposited in bone and teeth
  • should not be given to pregnant women or children <8
  • may impair hepatic function → liver necrosis
  • may cause renal tubular acidosis
  • photosensitization
63
Q

Tetracycline uses

A

Drug of Choice:

  • mycoplasma pneumonia
  • chlamydia (DOC → azithromycin)
  • rickettsiae
  • some spirochetes
  • H. pylori → combo w/ metronidazole & bismuth
  • alternative for gonococcal infection
  • plauge, tularemia, brucellosis → combo w/ aminoglycoside
  • Entamoeba histolytica, plasmodium falciparum
64
Q

Doxycycline

A

Long acting Tetracycline

  • more active than tetracycline HCl
  • absorption not sig. affected by food
  • slowly excreted → mostly in bile
  • good tissue penetration → esp. prostate
65
Q

Minocycline

A

Long acting Tetracycline

  • hich concentration in saliva and tears
  • meningococcal carrier state (DOC rifampin)
  • absorption not sig. affected by food
  • slowly excreted → mostly in bile

-viestibular ototoxicity

66
Q

Demeclocycline

A

Tetracycline

  • Blocks ADH receptor function in collecting tubules
  • used for SIADH
67
Q

Tigecycline

A

Glycylcycline

  • binds 30s → bacteriostatic
  • developed to circumvent resistance mxns
  • -bad substrate to pump
  • similar activity to tetracyclines → active against resistant
  • MRSA, MRSE, PRSP, and VRE
  • IV → complicated skin/structure, intra abdominal infxn
68
Q

Nitrofurantoin

A

UTI drugs

  • interferes w/ bacterial enzymes
  • activity higher in ACIDIC urine → keep < 5.5
  • used for UTI (often used in elderly)
  • wide spectrum against G+ and G-
  • -most Proteus and Pseudomonas are resistant

-highly protein bound → no effect in blood

ADVERSE (mainly long term or renal impairment)

  • colors urine BROWN
  • Interstitial pulmonary fibrosis
  • neurological disorders

-CI → pregnancy & impaired renal function and allergy

69
Q

Methenamine Mandelate

A

UTI drug

  • Decomposes in urine → formaldehyde & ammonia
  • Formald. → binds amino groups → inactivates proteins
  • -CHEMICAL rxn → no receptor → NO RESISTANCE

-CHRONIC suppressive treatment of UTI (esp e. coli)

  • essentially NON-TOXIC
  • CI → renal and hepatic insufficiency
70
Q

Ciprofloxacin

  • -Levofloxacin
  • -Ofloxacin
A

2nd gen fluoroquinolone

  • inhibition of DNA gyrase → alter DNA’s structure & function
  • -bactericidal
  • resistance → mutation of topoisomerase enzyme
  • -plasmid mediated → Qnr proteins protect gyrase
  • -acetyltrasferase → modify fluoroquinolones
  • CROSS RESISTANCE
  • UTI (pseudomonas)
  • travelers diarrhea (trimethoprim)
  • soft tissue infections
  • prophylaxis of inhalational anthrax
  • Mg++ (antacids) → interfere w/ absorptions
  • poorly penetrates CSF

ADVERSE

  • GI disturbances
  • Seizures
  • ↑ QT interval (macrolides–Azithromycin)
  • transient ↑ serum transaminase, LDH, alk phos
  • cartilage erosion → tendon rupture
  • CI → pregnant women & children <18
71
Q

Shortcomings of Ciprofloxacin

A
  • limited activity against S. pneumonia
  • poor CNS penetration
  • not effective against anaerobes
72
Q

Moxifloxacin

  • -Gatifloxacin → only TOPICAL
  • -Gemifloxacin → approved for CAP
A

3rd gen fluoroquinolone
-inhibits DNA gyrase → alters DNA structure & function

  • oral ONCE a day
  • ↑ activity penicillin-susceptible/resistant PNEUMOcocci
  • ↓ activity → pseudoonal & enterobacteriaceae
  • ↑ activity anaerobes
  • treatment of acute exacerbations of:
  • chronic bronchitis, acute sinusitis, and pneumonia
  • good penetration → respiratory tissue & CNS
  • metabolized → glucuronide & sulfate conjucation
  • -CI w/ hepatic insufficiency
73
Q

Norfloxacin→

Ciprofloxacin→
Olfloxacin→
Levofloxacin→

Moxifloxacin→
Gatifloxacin→
Gemifloxacin→

A

Norfloxacin→ UTI and prostatitis

Ciprofloxacin→ systemic infections, UTI
Olfloxacin→ prostatitis, STD (not syph), some systemic, TB
Levofloxacin→ CAP

Moxifloxacin→ penicillin resistant S. pneumoniae
Gatifloxacin→ Ocular application only
Gemifloxacin→ penicillin resistant S. pneumoniae, CAP

74
Q

Metronidazole

A
  • reduced metronidazole disrupts DNA helical structure
  • -inhibts NA synthesis → bactericidal
  • selective for ANAEROBES
  • DOC → c. dificie
  • metallic taste
  • disulfiram-like effect → don’t use alcohol
75
Q

Fidaxomicin

A

-inhibits protein synthesis → binds RNA pol

  • active → G+ aerobe and anaerobe
  • -NO gram neg activity (vancomycin)
  • negligible systemic absorption → high [ ] in feces
  • 3rd line treatment for C. difficile colitis
    1) metronidazole 2) vancomycin 3) fidaxomicin
76
Q

Mupirocin

A
  • inhibits protein & RNA synthesis
  • → reversible binds isoleucyl-tRNA synthetase
  • bacteriostatic → low [ ]
  • bactericidal → high [ ]
  • little potential for cross-resistance
  • TOPICAL administation to skin or nares
  • imetigo → staph aureus, β hemolytic strep (pyogenes)
77
Q

Polymyxin B; Polymyxin E

A

Poypeptide antibiotic

  • disturbs cell membrane → ↑ permeability → loss of metabolites essential to bacteria existence
  • -bactericidal
  • mostly for Gram-neg infections
  • -very effective against G- bacilli (pseudomonas and coliform organisms)
  • topically → wounds, burns (pseudomonas)
  • UTI, septicemia, bacteremia
  • used when other Abx are INEFFECTIVE of CI
  • no GI absorption → no oral use
  • poor dist after parenteral
  • bind very well to plasma proteins
  • Nephrotoxiciy → CI kidney disease
  • Paresthesia (respiratory arrest), ataxia, dizziness
78
Q

Polymyxin drug interactions

A

Aminoglycosides → ↑ risk of renal dysfunction & respiratory paralysis

Cephalothin → ↑ risk nephrotoxicity

Non-depolarizing muscle relaxant → enhance blockade

year 2 (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions