Exam 3 Pharmacology: Antibiotics

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Basically took Javi's list and placed it into flashcards. Please let me know of any edits

Penicillin G

Action: PBP block IV
(D-ala-D-ala analog → covalent binding → ↓transpeptidation → ↓cell wall synthesis - cross-linking)

Pharm: CIDAL, t1/2 = 0.5 hrs; Crosses BBB ;RENAL ELIM → Organic acid transporter secretion (blocked by probenicid = OAT blocker); β-lactamase susceptible

Uses: Strep (NO enterococcus), Grp A Strep, prevent Rheumatic fever, neisseria meningitidis, syphillis, listeria, pasteurella, clostridium

Se/Tox: Allergy, seizure, hemolytic anemia (Coombs +)

Penicillin V

Action: PBP block ORAL
(D-ala-D-ala analog → covalent binding → ↓transpeptidation → ↓cell wall synthesis - cross-linking)

Pharm: CIDAL, t1/2 = 0.5 hrs; Crosses BBB;
RENAL ELIM → Organic acid transporter secretion (blocked by probenicid = OAT blocker)
β-lactamase susceptible

Uses: Strep (NO enterococcus), Grp A Strep (DOC!!), prevent Rheumatic fever, neisseria meningitidis, syphillis, listeria, pasteurella, clostridium

Se/tox: Allergy, seizure, hemolytic anemia (Coombs +)

Procaine Penicillin

Action: PBP block IM
(D-ala-D-ala analog → covalent binding → ↓transpeptidation → ↓cell wall synthesis - cross-linking)

Pharm: CIDAL, (↑t1/2); Crosses BBB
RENAL ELIM → Organic acid transporter secretion (blocked by probenicid = OAT blocker)
β-lactamase susceptible

Uses: Strep (NO enterococcus), Grp A Strep, prevent Rheumatic fever, neisseria meningitidis, syphillis (DOC!!, listeria, pasteurella, clostridium

Se/tox: Allergy, seizure, hemolytic anemia (Coombs +)

Ampicillin

Action: PBP block

Pharm: CIDAL, Renal elim.; Crosses BBB; β-lactamase susceptible

Uses: LIKE PENICILLIN G PLUS H. flu, enterococci, shigella, E. coli, proteus, salmonella, (more gram neg), otitis media, bronchitis, UTI

Se/tox: RASH (mononucleosis), diarrhea, CLL; allergy, seizure, hemolytic anemia

Amoxicillin

Action: PBP block

Pharm: CIDAL, Renal elim.; Crosses BBB; β-lactamase susceptible

Uses: LIKE PENICILLIN G PLUS H. flu, enterococci, shigella, E. coli, proteus, salmonella, (more gram neg), OTITIS MEDIA (DOC!!!!), bronchitis, UTI

Se/tox: RASH (mononucleosis), less diarrhea & GI s/e; CLL; allergy, seizure, hemolytic anemia

Piperacillin

Action: PBP block

Pharm: CIDAL, Renal elimination; β-lactamase susceptible

Uses: LIKE AMPICILLIN PLUS PSEUDOMONAS, klebsiella (synergy: aminoglycosides)

Se/tox: Mod Na+ load (1.85 mEq), HYPOKALEMIA (arrhythmia), platelet defect (ADP block)

Nafcillin

Action: PBP block

Pharm: CIDAL, crosses BBB, Renal (70%) & Liver (30%) elim; β-lactamase RESISTANT
Resistance: altered PBP, MecA transposon (MRSA)

Uses: strep (NO enterococcus), "anti-staph"

Se/tox: Interstitial nephritis, leukopenia

Oxacillin

Action: PBP block

Pharm: CIDAL, crosses BBB, Renal (70%) & Liver (30%) elim; β-lactamase RESISTANT
Resistance: altered PBP, MecA transposon (MRSA)

Uses: strep (NO enterococcus), "anti-staph"

Se/tox: Hepatitis, leukopenia

Cefazolin

1st Gen Cephalasporin
Action: PBP block

Pharm: CIDAL; Does NOT cross BBB; IV

Uses: LIKE AMPICILLIN & OXACILLIN PLUS klebsiella (NO enterococcus); Not active w/Pseudomonas or Bacteroides

Se/tox: Allergy, seizure, hemolysis
METHYLTHIOTETRAZOLE→ vit k epoxide reductase block

Cephalexin

1st Gen Cephalasporin
Action: PBP block

Pharm: CIDAL; Does NOT cross BBB; ORAL

Uses: LIKE AMPICILLIN & OXACILLIN PLUS klebsiella (NO enterococcus); Not active w/Pseudomonas or Bacteroides

Se/tox: Allergy, seizure, hemolysis
METHYLTHIOTETRAZOLE→ vit k epoxide reductase block

Cefuroxime

2nd Gen Cephalosporin
Action: PBP block

Pharm: CIDAL; CROSSES BBB

Uses: H. influenzae (CA-Pnemonia); Not active vs. Pseudomonas; sinusitis, otitis, and lower respiratory tract infections.

Se/tox: Allergy, seizure, hemolytic anemia, antabuse

Cefoxitin

2nd Gen Cephalosporin
Action: PBP block

Pharm: CIDAL; CROSSES BBB

Uses: B. FRAGILIS (abd or pelvic sepsis, mixed bacterial infections); Not active vs. Pseudomonas; sinusitis, otitis, and lower respiratory tract infections.

Se/tox: Allergy, seizure, hemolytic anemia, antabuse

Ceftazidime

3rd Gen Cephalasporin

Action: PBP block; IV

Pharm: CIDAL

Uses: Wide aerobic Gram negatives; PSEUDOMONAS, meningitis (resistant to others), gonorrhea, strep pneumoniae, Lyme

Se/tox: Immediate hypersensitivity, rash, seizures

Ceftriaxone

3rd Gen Cephalasporin

Action: PBP block; IV

Pharm: CIDAL, t1/2 = 8 hrs; BILE ELIM (renal safe)

Uses: Very widely used; MENINGITIS, GONORRHEA, pseudomonas, strep pneumoniae, Lyme

Se/tox: BILIARY CONCENTRATION, diarrhea

*CONTRAINDICATIONS: Ca2+ IV solutions, hyperbilirubin neonates (kernicterus)

Cefepime

4th Gen Cephalasporin

Action: PBP block

Pharm: CIDAL, crosses BBB; RENAL ELIM; more resistance to chromosomal β-lactamases (Enterobacter)

Uses: BROAD SPECTRUM GRAM +/-, Staph, strep, Pseudomonas, H. influenza, Neisseria

Se/tox: BILIARY CONCENTRATION, diarrhea

*CONTRAINDICATIONS: Ca2+ IV solutions, hyperbilirubin neonates (kernicterus)

Ceftaroline

MRSA-susceptible Cephalosporin
Action: Increased binding to PBP 2A, which medaites MRSA

Pharm: CIDAL; IV

Use: CA-Pneumonia and complicated skin and skin stricture infections (MRSA). (Comparable to vancomycin)

Se/tox: Known serious hypersensitivity reaction, diarrhea, nausea, rash

Aztreonam

Monobactams
Action: PBP 3 block (G-negative only)

Pharm: CIDAL, t1/2 = 1.5-2 hrs; RENAL ELIM (RF t1/2 = 6 hrs): β-lactamase RESISTANT; Cross BBB

Uses: PSEUDOMONAS, aerobic gram negatives; Not active against gram positives or anaerobes

Se/tox: Minimal cross-immunogenicity w/ other β-lactams; CONCERN with ceftazidime because side chains are identical

Primaxin (Imipenem + Cilastatin)

Carbapenems
Action: PBP BLOCK (inactived by RENAL DIPEPTIDASE; prevent w/ CILASTATIN)

Pharm: CIDAL, t1/2 = 1 hr; IV; RENAL ELIMINATION;
β-lactamase RESISTANT

Uses: PSEUDOMONAS, H.A. GRAM NEGATIVES, gram positives, anaerobes

Se/tox: SEIZURE (esp in renal failure or high doses), resistance to Pseudomonas

Meropenem

Carbapenems
Action: PBP BLOCK (STABLE TO RENAL DEHYDROPEPTIDASE) MORE ACTIVITY AGAINST G-NEGATIVES, LESS WITH G-POSITIVE

Pharm: CIDAL, t1/2 = 1 hr; IV; RENAL ELIMINATION;
β-lactamase RESISTANT

Uses: PSEUDOMONAS, H.A. GRAM NEGATIVES, gram positives, anaerobes

Se/tox: LOWER incidence of seizures

Ertapenem

less active
Carbapenems
Action: PBP BLOCK (inactived by RENAL DIPEPTIDASE; prevent w/ CILASTATIN)

Pharm: CIDAL, t1/2 = longer to allow for once daily dosing; IV; RENAL ELIMINATION;
β-lactamase RESISTANT

Uses: H.A. GRAM NEGATIVES, gram positives, anaerobes; LACKS ACTIVITY to pseudomonas and acinetobacter

Se/tox: SEIZURE (esp in renal failure or high doses), resistance to Pseudomonas

Augmentin

Penicillin Combo Drug: Amoxicillin + Clavulanic Acid

Action: PBP BLOCK, extend spectrum of amoxicillin vs Otitis Med.

Pharm: CIDAL; β-lactamase RESISTANT

Uses: STAPH, strep, moraxella, B. FRAGILIS, N. GONORRHOEAE, OM

Se/tox: DIARRHEA

Clavulanic acid

Suicide Inhibitors
Action: min antimicrobe fxn; suicide substrate→ inactivate β-lactamases

Added to penicillin to ↑duration of action

Vancomycin

Glycopeptides
Action: D-ala-D-ala BLOCK
(↓peptidoglycan elongation and crosslinking → ↓cell wall synthesis)

Pharm: CIDAL, t1/2 = 6 hrs; Parenteral (IV);
RENAL ELIM (RF t1/2 = 240 h)

Resistance: D-ala → D-lac (VRE/Enterococci)

Uses: Staph (MRSA), strep, enterococci, C. DIFFICILE (pseudomembrane colitis), diphtheria

Se/tox: Ototoxicity, nephrotoxicity, leukopenia, "red neck syndrome" (rapid infusion w/ HISTAMINE RELEASE & flushing)

Daptomycin

Cyclic Lipopeptide
Action: PLASMA MEMBRANE DEPOLARIZATION (Ca2+-dependent pore formation → ion loss → cell depol → cell death)

Pharm: RAPID CIDAL, t1/2 = 9 hrs; RENAL ELIM (t1/2 unchanged); Poor lung penetration
CONCENTRATION DEPENDENT

Uses: Skin and wound infections; S. pyogenes, MRSA, MRSE, VISA, VRSA, *VRE (NO PNEUMONIA → inactivated by surfactant); NO CLOSTRIDIUM SPP

Resistance: Rare

Se/tox: Muscle toxicity (no IM admin), ↑CPK

*=important

Isoniazid (INH)

Tuberculosis Therapy
Action: MYCOLIC ACID SYNTHESIS BLOCK (prodrug)

Pharm: CIDAL, t1/2 = 2 hrs (acetylation); Crosses BBB
Oral or parenteral (IM); RENAL ELIM (RF t1/2 = 10 h)
Resistance: 1:10^6 mutate

Uses: Mycobacterium tuberculosis (MTB)
Support: pyridoxine (prevents neuropathy)

Se/tox: PERIPHERAL NEUROPATHY, HEAPATITIS (pregnancy, liver disease, alcoholics), LIVER TOXICITY (age-dependant), ↑phenytoin

Rifampin

Tuberculosis Therapy
Action: DNA dep RNA pol block (intracellular & extracellular)

Pharm: CIDAL, t1/2 = 1.5-5 hrs; Crosses BBB
Oral & parenteral (IV); HEPATIC ELIMINATION
Resistance: 1:10^7 mutate

Uses: BROAD SPECTRUM; MTB, leprosy, MRSA, legionella, FOREIGN BODY (biofilm)
PROPHYLAXIS: meningococcal & H. flu

Se/tox: ORANGE-RED BODY FLUIDS, LIVER TOXICITY, flu-like (fever, ATN, hemolytic anemia, shock), P450 INDUCTION (methadone, birth control)

Ethambutol

Tuberculosis Therapy
Action: Arabinoglycan synthesis block (myco cell wall)

Pharm: STATIC, t1/2 = 3-4 hrs; Oral, RBC depot
RENAL EILM (RF t1/2 = 8 hrs)

Uses: Mycobacterium tuberculosis (MTB)

Se/Tox: OPTIC NEURITIS, ↓visual, red-green COLORBLIND (rev); CONTRAINDICATION: young children

Gentamicin

Aminoglycosides:
Action: 16S RNA of 30S ribosome block (which blocks 50S)
(abnormal initiation, mRNA misreading, ribosomal detachment)

Pharm: CIDAL, t1/2 = 2 hrs
Does NOT cross BBB; Parenteral (IM, IV)
RENAL ELIM (RF t1/2 = 72 h)

Resistance: enzyme inactivation, impermeability, aerobic conditions; CYP450 INHIB

Uses: Aerobic gram negatives, pseudomonas, SERIOUS INFECTIONS
*CONCENTRATION DEPENDENT KILLING (1x/day at higher doses)

Se/tox: OTOTOXICITY(irreversible), nephrotoxicity, ataxia (CN 8 loss), neuromuscular paralysis (reversed w Ca-gluconate or neostigmine), ↓protein synthesis, kidney damage (proximal tubule)

Tobramycin

Aminoglycosides:
Action: 16S RNA of 30S ribosome block (which blocks 50S)
(abnormal initiation, mRNA misreading, ribosomal detachment)

Pharm: CIDAL, t1/2 = 2 hrs
Does NOT cross BBB; Parenteral (IV)
RENAL ELIM (RF t1/2 = 72 h)

Resistance: enzyme inactivation, impermeability, aerobic conditions; CYP450 INHIB

Uses: Aerobic gram negatives, pseudomonas (MORE ACTIVE than gentamicin), SERIOUS INFECTIONS
*CONCENTRATION DEPENDENT KILLING (1x/day at higher doses)

Se/tox: OTOTOXICITY(irreversible), LESS nephrotoxicity, ataxia (CN 8 loss), neuromuscular paralysis (reversed w Ca-gluconate or neostigmine), ↓protein synthesis, kidney damage (proximal tubule)

Amikacin

Aminoglycosides:
Action: 16S RNA of 30S ribosome block (which blocks 50S)
(abnormal initiation, mRNA misreading, ribosomal detachment)

Pharm: CIDAL, t1/2 = 2 hrs
Does NOT cross BBB; Parenteral (IV)
RENAL ELIM (RF t1/2 = 72 h)

Uses: Aerobic gram negatives, pseudomonas, SERIOUS INFECTIONS; ACTIVE AGAINST gentamicin, tobramycin-resistant strains.

*CONCENTRATION DEPENDENT KILLING (1x/day at higher doses)

Se/tox: OTOTOXICITY(irreversible), nephrotoxicity, ataxia (CN 8 loss), neuromuscular paralysis (reversed w Ca-gluconate or neostigmine), ↓protein synthesis, kidney damage (proximal tubule)

Erythromycin

Macrolide:
Action: 50S block (abn initiation & translocation)

Pharm: STATIC, t1/2 = 1.4 hrs; Oral & parenteral (IV)
Resistance: alt ribosome, ↓perm, active efflux pumps

Uses: Staph, strep; T. pallidum; ATYPICAL PNEUMONIA (chlamydia, mycoplasma, legionella)

Se/tox: GI SYMPTOMS, cholestatic jaundice, OTOTOXICITY (rare, reversible); P450 INHIBITION (theophylline, CBZ, warfarin)

Clarithromycin

Macrolide:
Action: 50S block

Pharm: STATIC; Oral; t1/2 = 4-6 hrs (Dose twice daily); RENAL ELIM

Uses: ATYPICAL PNEUMONIA, H. flu, moraxella, H. pylori; increased activity for MAC, toxoplasma and M lepare

Se/tox: Fewer GI symptoms; P450 INHIBITION

Azithromycin

Macrolide:
Action: 50S block

Pharm: STATIC; Oral, IV; t1/2 > 11 hrs (tissue t1/2 = 55-76 hrs)

Uses: ATYPICAL PNEUMOIA, H. flu, moraxella, Mycobacterium avium complex (use with ceftriaxone as INITIAL THERAPY), chlamydia; Less active vs Gram positive cocci than eryhtromycin

Se/tox: Fewer GI symptoms; NO P450 INHIBITION

Telithromycin

Macrolide:
Action: 50S block (at 2 sites)

Pharm: STATIC; Oral; t1/2 > 10 hrs (more acid stable) Resistance: less vs Erythro bc ↑ribos bind & ↓export susc

Uses: CA PNEUMONIA (RESISTANT PNEUMOCOCCUS PNEUMO), acute exacerbation of chronic bronchitis, sinusitis

Se/tox: P450 34A (Inhibition), vision problems (accommodate), hepatotoxicity (rare), WORSEN MYASTHENIA GRAVIS, GI prob

Tetracycline

Tetracyclines
Action: 30S block (↓aminoacyl-tRNA binding)

Pharm: BACTERIOSTATIC; Oral & parenteral (IV); SMALL BOWEL ELIM

Resistance: alt perm or active efflux pumps; Divalent cations impair oral absorption

Uses: ATYPICAL PNEUMONIA (chlamydia, morax, legion), rickettsia, ehrlichia, spirochetes, syphilis, LYME (prophylaxis), PROSTATITIS

Se/tox:GI upset, hepatotoxicity, photosensitivity, deposition in bone and teeth
CONTRAINDICATION: pregnancy, < 8 yrs

Doxycycline

Tetracyclines
Action: 30S block (↓aminoacyl-tRNA binding)

Pharm: BACTERIOSTATIC; Oral & parenteral (IV); LONGER half-life (t1/2=18h) SMALL BOWEL ELIM

Resistance: alt perm or active efflux pumps

Uses: CA-Pneumonia; Exacerbation of bronchitis

Se/tox: GI upset, hepatotoxicity, photosensitivity, deposition in bone and teeth
CONTRAINDICATION: pregnancy, < 8 yrs

Tigecycline

Tetracyclines
Action: 30S block (tetracycline analog)

Pharm: STATIC; Parenteral (IV); VERY BROAD SPECTRUM

Resistance: Unaffected byb common tetracycline resistance mechanisms

Uses: MRSA, VRE, bacteroides, aerobic gram negatives

Se/tox: Nausea, vomitting

Synercid (Quinupristin-Dalfopristin)

Streptogramins
Action: 50S block

Pharm: STATIC/CIDAL, t1/2 < 1 hr; FECAL ELIM
Resistance: alt ribosome

Uses: Strep, staph (MRSA), enterococci (VRE), mycoplasma, legionella, chlamydia pneumoniae

Se/tox: GI symptoms, pain at infusion site, myalgia, P450 3A4 INHIBITION

Linezolid

Oxazolidinones
Action: 23S/50S block (prevents 30S & 50S complex formation)

Pharm: STATIC (except strep) t1/2 = 5 hrs; Oral & parenteral (IV)
Resistance: 23S point mut

Uses: Enterococci (VRE), staph (MRSA), strep, listeria, corynebacteria, atypical myco, nocardia

Se/tox: GI symptoms, lactic acidosis, thrombocytopenia, periph neuropathy, MAO INHIBITION

Clindamycin

Lincosamides:
Action: 50S block (abn initiation & translocation)

Pharm: STATIC, t1/2 = 2-4 hrs; Does NOT cross BBB; Oral & parenteral (IM, IV); RENAL & HEPATIC ELIM
Resistance: alt ribosome

Uses: Staph, strep (NO enterococcus), anaerobes (intraabdominal infection), toxoplasmosis

Se/tox: PSEUDOMEMBRANE COLITIS, allergy (eosinophilia, rash), hepatotoxicity (reversible), neuromusclar paralysis (rare)

Chloramphenicol

Action: 50S block (transpeptidation)

Pharm: STATIC, PO/IV; HEPATIC ELIM; crosses BBB
Resistance: acetylation by plasmid → ↓ribos binding; DOSE-DEPENDENT TOXICITY

Uses: BROAD-SPECTRUM; Rickettsia (pts cant take tetracycline), meningitis, Rocky Mount SF, anaerobic inf, brain abscess

Se/tox: BONE MARROW SUPPRESSION (anemia, thrombocytopenia, leukopenia), aplastic marrow aplasia, GRAY BABY SYNDROME, INHIBITS P450, antagonize cell wall inhibs

Sulfonamide

Sulfa
Action: Dihydropteroate synthetase block; (competitive w/ PABA, ↓folate synthesis)

Pharm: STATIC; Crosses BBB; Resistance: ↑PABA, ↓enzyme affinity

Uses: Nocardiosis, toxoplasmosis (w/ pyrimethamine)

Se/tox: Crystalluria, G-6PD def (hemolysis), ↓WBC, hepatitis, KERNICTERUS, potentiates coumadin

TMP-SMX (Trimethoprim-Sulfamethoxazole)

Sulfa
Action: Dihydrofolate reductase (DHFR) block; (↓folate synthesis)

Pharm: STATIC, t1/2 = 9-11 hrs; Oral & parenteral (IV); RENAL ELIM
Resistance: ↓enzyme affinity & cell permeability

Uses: BROAD SPECTRUM; UTI, bronchitis, shigella, otitis media, PCP, TOXO, gram neg, PROSTATITIS (NO syphilis, pseudomonas or myco)

Se/tox: MINIMAL; bone marrow depression, renal injury

Ciprofloxacin

Quinolones
Action: DNA gyrase (topo II/IV) block; (↓neg superhelical twists, DNA damange)

Pharm: CIDAL, t1/2 = 4 hrs; Oral and parenteral (IV), mixed clearance; RENAL ELIM (RF t1/2 = 10 h)
Resistance: "a-subunit" alt, ↓drug perm; divalent and trivalent cations impair oral absorption

Uses: ATYPICAL PNEUMONIA, shigella, E. coli (UTI), neisseria, H. flu, anthrax (prophylaxis), PSEUDOMONAS, MRSA, strep, PROSTATITIS
*CONCENTRATION DEPENDENT KILLING

Se/tox: GI symptoms, neurotoxicity, TENDONITIS

CONTRAINDICATION: pregnancy and young children due to cartilage erosion, theophylline (toxicity), HF

Ofloxacin

Quinolones
Action: DNA gyrase (topo II/IV) block; (↓neg superhelical twists, DNA damange)

Pharm:CIDAL; Oral; Improved pharmacokinetics and pharmodynamics

Use: Limited to UTIs and nongonnococcal urethritis and cervicitis

Levofloxacin

Quinolones
Action: DNA gyrase (topo II/IV) block; (↓neg superhelical twists, DNA damange)

Pharm: CIDAL; Oral, IV; L‐isomer of ofloxacin; Improved RENAL CLEARANCE

Uses: "Respiratory Fluoroquinolone" Improved activity vs pneomococcus
*CONCENTRATION DEPENDENT KILLING

Se/tox: GI symptoms, headache, lightheadedness, seizure (rare), CARTILAGE EROSION, TENDONITIS, dysglycemia
CONTRAINDICATION: pregnancy, young children, theophylline (toxicity), HF

Moxifloxacin

Quinolones
Action: DNA gyrase (topo II/IV) block; (↓neg superhelical twists, DNA damange)

Pharm: CIDAL, t1/2 = 4 hrs; Oral and parenteral (IV); RENAL ELIM (RF t1/2 = 10 h)
Resistance: "a-subunit" alt, ↓drug perm

Uses: Improved activity vs anaerobes and MTB; Do NOT USE IN UTI (lowers urinary levels)

Se/tox: GI symptoms, headache, lightheadedness, seizure (rare), CARTILAGE EROSION, TENDONITIS, dysglycemia
CONTRAINDICATION: pregnancy, young children, theophylline (toxicity), HF

Metronidazole

Nitroimidazole
Action: DNA disruption; (prodrug, nitro group reduction by electron transport w/ low redox)

Pharm: CIDAL, t1/2 = 6-14 hrs; Crosses BBB; Oral (TISSUE amebicide) & parenteral (IV); RENAL ELIM (RF unchanged)

Uses: Trichomonas, ENTAMOEBA HISTOLYTICA (non-cyst), giardia, H. pylori, C. diff
*CONCENTRATION DEPENDENT KILLING

Se/tox: NAUSEA, metallic taste, vertigo, ataxia, NEUROPATHY, brown urine, leukopenia, antabuse CONTRAINDICATION: pregnancy, alcohol

Tinidazole

Nitroimidazole
Action: DNA disruption (prodrug)

Pharm: CIDAL, t1/2 = 12-14 hrs; HEPATIC ELIM (CYP3A4)

Uses: Trichomonas (met-resistant), entamoeba, GIARDIA, H. pylori, B. fragilis

Se/tox: Nausea, metallic taste, vomit, seizure, neuropathy CONTRAINDICATION: pregnancy, metronidazole allergy

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