DRUG NAMES AND THEIR USE MG: INFECTIOUS DISEASES AND ONCOLOGY
Lecture 1: Introduction
No drugs named that are not explained in the other lectures.
Lecture 2: Antibiotics based on cell wall and membrane
Antibiotics that inhibit cell wall synthesis
Beta lactams: drugs with a lactam ring that resembles the D-alanyl-D-alanine and therefore occupy the
binding pocket of the transpeptidase enzyme, preventing crosslinking of sugars in the peptidoglycan and
weakening the cell wall.
Penicillin: core is 6-APA: a lactam ring and a thiazolidine ring, with a synthesized tail added to it.
examples are ampicillin, amoxicillin (both gram+ and gram-), flucloxacillin (only gram+), penicillin G
(only gram+) and penicillin V (only gram+).
Cephalosporins: core is 7-ACA: a lactam ring and a 6 membered ring
o First generation: Cefalexin acts on gram+ stable against beta lactamase.
o Second generation: Cefoxitin more stable against acids and beta lactamases, improved
gram- activity but worse gram+ activity.
o Third/fourth generation: Cefotaxime and Cefepime are more stable against beta lactamases
and against gram- bacteria.
o Fifth generation: Ceftobiprole is back-up antibiotic and used as anti-MSRA.
Monobactams: core group only contains the lactam ring.
Carbapenems: core group contains a lactam ring and a 5 membered ring without a sulfur atom.
Examples are Meropenem, Ertapenem and Imipenem.
Vancomycin: glycopeptide that binds to peptide chain of NAM to prevent cross linking, used against gram+
bacilli as backup antibiotic.
Bacitracin: inhibits export of building blocks, against gram+ bacilli in the form of cream.
Cycloserine: mimics alanine and inhibits D-alanine attachment to NAM (second choice tuberculosis).
Fosfomycin: mimics PEP and inhibits precursor of peptidoglycan, against gram+ and gram-.
*Lactamase inhibitors: drugs that prevent the ring opening of beta lactams by lactamase. Examples are
clavulanic acid, sulbactam or sultamicillin (ester of ampicillin and sulbactam). The lactamase inhibitors are
combined with beta lactams to have an effect.
Antibiotics that act on the cell wall, but not inhibit synthesis
Polymyxins: specific against gram-, bind and inactivate toxicity of LPS, used as backup antibiotic.
Daptomycin: cyclic peptide with tail that inserts in membrane and forms a pore, used in vancomycin
resistant S.aureus and Enterococci.
Malacidins: bind lipid II (cell wall precursor) leading to cell wall destruction.
Lecture 3: antimycotics
Antimycotics that act on the cell membrane
Polyene macrolides (amphotericin B): an antimycotic that targets ergosterol and probably forms pores,
acting on both single rounded cells and filamentous fungi.
Azoles: bind to CYP450 to prevent the C14 demethylation step in the biosynthesis of ergosterol. There can
be imidazoles (2 nitrogen atoms in 5 membered ring) or triazoles (3 nitrogen atoms in 5 membered ring).
Examples are itraconazole (dematophytosis and onychomycosis), voriconazole (aspergillosis) and
fluconazole (cryptococcal meningitis). However, resistance occurs often.
Allylamines: interact with the epoxidation step in ergosterol synthesis. Examples are terbinafine, or
amorolfine which inhibits both epoxidation and reduction (like morpholines do).
Antimycotics that act on the cell wall
Lecture 1: Introduction
No drugs named that are not explained in the other lectures.
Lecture 2: Antibiotics based on cell wall and membrane
Antibiotics that inhibit cell wall synthesis
Beta lactams: drugs with a lactam ring that resembles the D-alanyl-D-alanine and therefore occupy the
binding pocket of the transpeptidase enzyme, preventing crosslinking of sugars in the peptidoglycan and
weakening the cell wall.
Penicillin: core is 6-APA: a lactam ring and a thiazolidine ring, with a synthesized tail added to it.
examples are ampicillin, amoxicillin (both gram+ and gram-), flucloxacillin (only gram+), penicillin G
(only gram+) and penicillin V (only gram+).
Cephalosporins: core is 7-ACA: a lactam ring and a 6 membered ring
o First generation: Cefalexin acts on gram+ stable against beta lactamase.
o Second generation: Cefoxitin more stable against acids and beta lactamases, improved
gram- activity but worse gram+ activity.
o Third/fourth generation: Cefotaxime and Cefepime are more stable against beta lactamases
and against gram- bacteria.
o Fifth generation: Ceftobiprole is back-up antibiotic and used as anti-MSRA.
Monobactams: core group only contains the lactam ring.
Carbapenems: core group contains a lactam ring and a 5 membered ring without a sulfur atom.
Examples are Meropenem, Ertapenem and Imipenem.
Vancomycin: glycopeptide that binds to peptide chain of NAM to prevent cross linking, used against gram+
bacilli as backup antibiotic.
Bacitracin: inhibits export of building blocks, against gram+ bacilli in the form of cream.
Cycloserine: mimics alanine and inhibits D-alanine attachment to NAM (second choice tuberculosis).
Fosfomycin: mimics PEP and inhibits precursor of peptidoglycan, against gram+ and gram-.
*Lactamase inhibitors: drugs that prevent the ring opening of beta lactams by lactamase. Examples are
clavulanic acid, sulbactam or sultamicillin (ester of ampicillin and sulbactam). The lactamase inhibitors are
combined with beta lactams to have an effect.
Antibiotics that act on the cell wall, but not inhibit synthesis
Polymyxins: specific against gram-, bind and inactivate toxicity of LPS, used as backup antibiotic.
Daptomycin: cyclic peptide with tail that inserts in membrane and forms a pore, used in vancomycin
resistant S.aureus and Enterococci.
Malacidins: bind lipid II (cell wall precursor) leading to cell wall destruction.
Lecture 3: antimycotics
Antimycotics that act on the cell membrane
Polyene macrolides (amphotericin B): an antimycotic that targets ergosterol and probably forms pores,
acting on both single rounded cells and filamentous fungi.
Azoles: bind to CYP450 to prevent the C14 demethylation step in the biosynthesis of ergosterol. There can
be imidazoles (2 nitrogen atoms in 5 membered ring) or triazoles (3 nitrogen atoms in 5 membered ring).
Examples are itraconazole (dematophytosis and onychomycosis), voriconazole (aspergillosis) and
fluconazole (cryptococcal meningitis). However, resistance occurs often.
Allylamines: interact with the epoxidation step in ergosterol synthesis. Examples are terbinafine, or
amorolfine which inhibits both epoxidation and reduction (like morpholines do).
Antimycotics that act on the cell wall
