Chemotherapeutic Agents, chapter 3439

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Chemotherapeutic Agents, chapter 34-39

• Antibacterial compounds (procaryotes)
• Antifungal compounds (eucarytotes)
• Antiparasitic agents (eucarytotes)
• Antiviral compounds
• Anticancer compounds

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Different living organisms
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Antibacterial compounds, chapter 34 (-
antimycobacterials)

• Synthitic antibacterials (chemotherapeutica)
• Antibiotics

• Antibiotics
• Product from metabolism (natural product)
• (also applies if compd is prepared synthetically,
• or is a synthetic analog of a naturally occuring
  antibiotic/ semisynthetic compd)
• Inhibit growth (bacteriostatic) or kill
  (bacteriocide) microorg.
• Effective in low conc.

Antimicrobial chemotherapeutics Antimicrobial
comp ? Antibiotics
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G and G- bacteria
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Synthetic antibacterials (chemotherapeutica)
Antibacterial sulfonamides
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Nøytral sulfonilamid dårlig vannløselig. Urine
pH ca 6 Crystallization neutral form, kidney
damage Modern sulfa drugs pKa 5 7 better
solubility
Sulfametoxazol Bactrim, Trimetoprim-Sulfa -
Urine infections Combi. with trimethoprime
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Trimetoprim
Inhib. of folate reductase
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Quinolones
Inhib DNA-synthesis DNA-gyrase (prokaryoter)
uwounding DNA before replic.. DNA-topoisomerase
(humans), anticancer compds. ex.
doxorubicin Unique mecanism, no cross
resistance Broad spectrum G and G- also
mycobactria, clamydia
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Ciprofloksacin Ciprox, Ciprofloxacin Cilox
Ofloksacin Tarivid
()
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Oxazolidones
Linesolid Zyvoxid

• Reg. Norge 2002,
• 1. antibact. drug with new mechaanism of action
  in 35 years
• Inhib. protein synthesis early
• No cross resist.. G and some G-.
• Resistant strains

New drugs?
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Other antibiotics
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Antibiotics
b-Lactam-antibiotics
Penicillines
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G
G-
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Semi synthesis
Stability
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Nat. occuring P.
Semisynthetic, increased acid stability
Piperacillin Tazocin
Ampicillin Pentrexyl,
Amoxicillin Amoxicillin,
Pivampicillin Pondocillin,
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Kloksacillin Ekvacillin
Dikloksacillin Diclocil
Meticillin
Acid labile, last resort drug resist. strains
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Semisynthetic, Broad spectrum, Imines
Meticillinam Selexid
Pivmeticillinam Selexid
No nucleophilic cabronyl
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b-Lactamase Inhibitors
Combination with penicillines
Tazobaktam
Clavulanic acid

• Mechanism based irreversible enzyme inactivators

Suicide substrate - kcat inhibitors - Trojan
horse inhib. - latent alkylating agent
Pro-drug, must be activated by the enzyme
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Carbapenems / Carbapenins
Meropenem Meronem
Imipenem cilastan Tienam
2. Gen. Not cleaved by DHP-1
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Cephalosporins
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1. generation Relatively broad spectrum (G,
some G-) Cleaved by b-Lactamase
Cephalexin Cefalex Keflex
Cefalotin Cefalotin Keflin
2. generation More broad spectrum Not cleaved
by b-Lactamase
Cefoxitin Mefoxitin
Cefuroxim Cefuroxim Zinacef
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3. generation Very broad spectrum, also
Pseudomonas sp Not cleaved by
b-Lactamase Acid labile
Cefotaxim Cefotaxime Claforan
Ceftazidim Fortum
Oral 3. gen (not in N)
Ceftriaxon Rohephalin
R -H, -CHCH2, -CH2OCH3
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Monobactams
Aztreonam Azactam
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Aminoglycosides
Bind to mRNA read wrong Transloc. blocked
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Lincomycines
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Tetrasyclines
Chelate
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Stability acid / base
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Makrolides
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Polypeptides
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Others