Learning Objectives
At the end of this lecture the learner should
be able to;
1. Classify antibiotics according to their chemical
structure
2. Give properties of an ideal antibiotic.
3. Give general properties of an antibiotic.
4. Discuss different basic structures of antibiotic
classes.
General Properties
1. Grouped in classes based on their chemical
structure.
2. Members of the class share characteristics
i.
ii.
iii.
iv.
Clearance
Mechanism of action
Absorption
Side effects
General properties
5. Selective in their effect on different
microorganisms (spectrum of activity).
6. Vary in chemical structure (simple to
complex).
7. Vary in their toxicity to patients.
8. Vary in mode of action upon organisms.
9. Some are rapidly destroyed by various
bacteria while others are highly resistant to
microbial action.
Penicillins
Basic structure;
Thiazolidine ring
Beta-lactam ring
Amino-group; substituents (R) are attached to the
amino group
Penicillins
Resistance; most significant- bacterial production
of beta-lactamase
Destroys the beta-lactam ring by means of hydrolysis
Alteration of binding sides for the penicillins (PBPs)
Penicillin groups
Group Work/Discussion
Group 1: Structure of Cephalosporins, monobactams and
carbapenems and beta-lactamase inhibitors. (3156 3161)
Group 2: Structure of Tetracyclines and macrolides. (31623167)
Group 3: Structure of Aminoglycosides (3168 3173)
Group 4: Structure of Sulphonamides and quinolones (3174
3179)
Group 5: Structure of Antimycobacterial (3180 3184)
Look at structural modifications and how they affect;
Water solubility.
Lipid solubility.
Kinetics properties of the drug.
Pharmacodynamic activity of a drug.
23 January 2014
Penicillins
Penicillin a group of antibiotics derived from
Penicillium fungi, Examples include; penicillin
G, procaine penicillin, benzathine penicillin,
and penicillin V.
-lactam antibiotics used in the treatment of
bacterial infections caused by susceptible,
usually Gram-positive, organisms.
6-aminopenicillanic acid
6-APA is the core of penicillins.
It is obtained from the fermentation brew of
the Penicillium mold.
Used as the main starting block for the
preparation of numerous semisynthetic
penicillins.
Preparation of 6-APA
6-APA can be prepared enzymatically or chemically
starting from penicillin G.
The first major development was ampicillin, which
offered a broader spectrum of activity than either of the
original penicillins.
Further development yielded -lactamase-resistant
penicillins, including flucloxacillin, dicloxacillin, and
methicillin.
Another development was the antipseudomonal
penicillins, such as carbenicillin, ticarcillin, and
piperacillin.
Preparation of 6-APA
Penicillin biosynthesis
Basic/core structure
Natural Penicillins
Benzyl penicillin destroyed by gastric acid
Phenoxymethylpenicillin resist acid
(improved oral absorption)
Benzylpenicillin
Commonly known as penicillin G.
Phenoxymethylpenicillin
Commonly known as Penicillin V
Antistaphylococcal penicilins
Are beta-lactamase resistant
-possess an acyl side-chain to resist the action
of staphylococcal beta-lactamase, by stearic
hindrance of access of the drug to the
enzymes active sites.
Cloxacillin resists degradation by gastric acid
(improved oral absorption)
Flucloxacillin better oral absorption than
cloxacillin.
Cloxacillin
Cloxacillin is a semisynthetic antibiotic in the
same class as penicillin. Cloxacillin is used
against staphylococci that produce betalactamase, due to its large R chain, which does
not allow the beta-lactamases to bind.
Cloxacillin
Dicloxacillin
The presence of the isoxazolyl group on the
side-chain of the penicillin nucleus facilitates
the -lactamase resistance, since they are
relatively intolerant of side-chain steric
hindrance.
able to bind to penicillin-binding proteins
(PBPs) and inhibit peptidoglycan crosslinking,
but not inactivated by -lactamases.
Dicloxacillin
Flucloxacillin
The presence of the isoxazolyl group on the
side-chain of the penicillin nucleus facilitates
the -lactamase resistance, since they are
relatively intolerant of side-chain steric
hindrance.
able to bind to penicillin-binding proteins
(PBPs) and inhibit peptidoglycan crosslinking,
but not inactivated by -lactamases.
Flucloxacillin
Amoxycillin
Ampicillin
Antipseudomonal Penicillins
Carboxypenicillins (same antibacterial
spectrum as Ampicillin and susceptible to
beta-lactamase)
Ticarcillin
Carbenicillin
Ureidopenicillins
Piperacillin -
Carboxypenicillins
TICARCILLIN
Carbenicillin
Ureidopenicillins
PIPERACILLIN
is an extended spectrum beta-lactam antibiotic of
the ureidopenicillin class.
It is normally used together with a beta-lactamase
inhibitor, notably in the combination
piperacillin/tazobactam.
Piperacillin