this lecture was presented at the school for Enrolled Nurses and Midwives- The Gambia.

1. MR. ABDOU MARAM
PANNEH
(RM ,FWACN,NT,

2. INTRODUCTION
 ANTIMICROBAIL AGENTS are several groups of drugs
that are able to inhibit the growth and multiplication or
provoke the destruction of micro-organisms. They are all
referred to as ANTIBIOTICS.
 This term involved substances produced by various species
of microorganisms (e.g. bacteria, fungi, actinomycetes, etc)
that suppress the growth of other microorganism.
 Nowadays this term include synthetic antimicrobial agents
such as Sulfonamides, Quinolones, and Chloramphenicol
(the first antibiotic obtained synthetically).

3. ANTIMICROBAIL AGENTS
CLASSIFICATION.
 By their mode of action: BACTERIOSTATIC (when they
inhibit only the bacterial growth or their multiplication)
and BACTERICIDAL (when they provoke the lysis or
destruction of bacteria)
 By their chemical structure: -lactams, aminoglicosides.
 By their mechanism of action: Cell wall synthesis
inhibitors, protein synthesis inhibitors, antifolates, etc
 By their activity against particular types of organisms:
Antibacterias, antifungal, Antiviruses, Antimycobacterias,
etc.

4. ANTIBIOTICS
 Antibiotics are a very diverse class of compounds. They
can be classified according to their mode of action of
antimicrobial activity. These are:-
1. Penicillins 2. Cephalosphorins
3. Aminoglycosides 4. Quinolones
5. Tetracyclines 6. Macrolides
7. Chloramphenicols 8. Sulphonamides
9. Lincosamides 10. Glycopeptides

5. 1. THE PENICILLINS
 THE PENICILLINS are first antibiotics to be used in
therapeutics. They are obtained from a mixture of penicillin F,
G, X and K. penicillins are derived fro the mould of Penicillium
Notatum.
 BASIC CHEMICAL STRUCTURE: 6-aminopenicillanic acid.
Structural integrity of this acid nucleus is essential for
antimicrobial activity.
 This acid can be destroyed and lacks antibacterial activity by
metabolic pharmacokinetics processes and enzymatically by
bacterial (ß-lactamase or penicillinase).
 MECHANISM OF ACTION: They inhibit the transpeptidation
reaction of peptidoglycan (cross-linked polymer which provide
microorganism a rigid outer layer), therefore peptidoglycan
synthesis is blocked and the cell in isosmotic medium dies.
 Inside they are hyperosmotic, for that reason they are
considered bactericidal and their activity occurs only if cells are
actively growing and synthesizing cell wall.

6. 1. THE PENICILLINS Cont’d..
 GENERAL CHARACTERISTICS OF PENICILLINS:
 When the Penicillins are in dry crystalline form, they are
stable for longer periods of up to 5 years.
 When they dissolved, they can be stable for only 12 – 24hrs
if kept in a refrigerator.
 They solution of all Penicillins must be prepared and given
fresh.
 All type of penicillin display similar type of action.(ie. They
inhibit bacterial cell synthesis)
 All Penicillins to be given orally must be administered at
least one hour before food or two hours after food because
and gastric juice interfere with the absorption.

7. THE PENICILLINS Cont’d..
 CLASSIFICATION OF PENICILLINS
1. NATURAL PENICILLINS:
 Penicillin G- (Benzyl penicillin sodium or potassium
crystalline salts)-(Crystapen or X-pen.) Inj. 1-5mu 6 hourly.
 Penicillin G Procaine injection. 1mu, 4mu daily
 Penicilin G Benzathine injection. 1mu, 2.4mu stat, repeated
weekly for 3 weeks..
Characteristics:
 Has great activity against Gramm+ microorganism, Gramm-
cocci, non-ß-lactamase producing anaerobes.
 Susceptible to hydrolysis by ß-lactamase or penicillinase.
 Unstable at acidic pH (gastrointestinal specifically).

8. THE PENICILLINS Cont’d..
2. ANTI-STAPHYLOCOCCAL PENICILLINS:
 These include:- Methicillin, Nafcillin, Isoxazolyl
penicillins (Oxacillin, Cloxacillin, Dicloxacillin,
Flucloxacillin, Aspoxicillin, Oxicillin, ,). Given 6 hrly.
 Characteristics:
 Active agains staphylococci and streptococci.
 Stable at acidic pH.

9. 1. THE PENICILLINS Cont’d..
 3. EXTENDED OR BROAD- SPECTRUM PENICILLINS:
 Aminopenicillins: Ampicillin, Amoxicillin, Clavulanic
acid, Temocillic, etc
 Antipseudomonics: . Carboxypenicillins (Carbonicillin,
Ticarcillin).
 Ureidopenicillins (Piperacillin, Mezlocillin).
 Anti Gramm- bacteria: Mecillinams (PIU-Mecillinam)
 CHARACTERISTICS:
 They are particular antimicrobial spectrum
 Susceptible to hydrolisis by ß-lactamase or penicillinase.
 Stable at both acidic and alkaline pH.

10. 1. THE PENICILLINS Cont’d..
ADR OF PENICILLINS(Remarkably non toxic but):
 Hypersensivity (most of the serious adverse effects)-
ANAPHYLAXIS. Alergic reactions include: Urticaria, fever, joint
swelling, angioneurotic oedema, pruritus, respiratory disturbances,
oral lesions, hematologic disturbances, vasculitis.
 Seizures in patients with renal failure which receiving high doses or
intrathecal administration.
 Hematologic reactions: Hemolytic anemia and platelel dysfunction.
 Renal failure
 Hepatotoxicity
 Crystalline salts in IM injection produce severe pain.
DRUG INTERACTIONS
 Aminoglycoside inactivation: Penicillins should not be mixed in the
same IV fluid with Aminoglycosides.

11. 2. THE CEPHALOSPHORINS & BETALACTAMS
CEPHALOSPHORINS & BETALACTAMS are similar to
penicillins:
 Chemically
 In mechanism of action
 Toxicity
 More stable than penicillins to many bacterial beta-
lactamases
 Usually have a broader spectrum of activity
 Relatively stable to pH
 Allergic patients to penicillins may tolerate cephalosporins
but if the patient has anaphylaxis history to penicillins
should not receive cephalosporins.
 CLINICAL USES:-
 UTIs caused by E. coli
 Reduce the incidence of surgical wound infections
 Treat multiple resistance gram- infections, abd. and pelvic
infections.

12. 2. THE CEPHALOSPHORINS & BETALACTAMS
 CLASSIFICATION
 They are classified into four major groups or generations
depending mainly on the spectrum of antimicrobial activity.
 FIRST GENERATION (Narrow spectrum- better activity
against Gramm+ microorganisms):
 - Oral: Cefadroxil, Cephalotin, Cephalexin, etc.
 - IV: Cefazolin
 SECOND GENERATION (Intermediate spectrum- Have an
extended Gramm- coverage, less active against Gramm+
bacteria than the first generation.)
 - Cefaclor, Cefamandole, Cefonicid, Cefuroxime, Cefprozil,
Loracarbef, Ceforanide, Cephamicins (Cefoxitin, Cefmetazole,
Cefotetan).

13. 2. THE CEPHALOSPHORINS & BETALACTAMS
 THIRD GENERATION (Broad antimicrobial spectrum-
Ability to cross blood brain barrier)
 - Ceftriaxone, Cefixime, Cefoperazone, Cefotaxime,
Ceftazidime, Ceftizoxime, Cefpodoxime proxetil, Ceftibuten,
Moxalactam.
 FOURTH GENERATION (Broad antimicrobial spectrum-
More resistant to beta-lactamases and against anaerobic
microorganism, active agains P. aeruginosa)
 Cefepime
OTHER BETALACTAM DRUGS
 Monobactams: Aztreonam
 Beta-lactamase inhibitors: Clavulanic acid, Sulbactam,
Tazobactam (They have very weak antibacterial drugs, Are
available only in fixed combinations with specific penicillins).
 Carbapenems: Imipenem, Meropenem

14. 2. THE CEPHALOSPHORINS & BETALACTAMS
 ADR OF CEPHALOSPHORINS
 Skin rash
 Anaphylactic shock
 Renal toxicity
 Pain after an injection
 Bleeding disorders
 Thromboflebitis after an IV injection.
 INTERACTIONS
 When using Cephalosphorins, avoid the following:-
 Alcohol:- may lead to severe dizziness, nausea, vomiting
 Probenicid:- it inhibits the excretion of Cephalosphorins
 Chloramphenicol:- it antagonizes the effect of
Cephalosphorins.

15. 3. THE AMINOGLYCOSIDES:
 THE AMINOGLYCOSIDES are closely related group of
bactericidal antibiotics specifically derieved from two genuses:-
Streptomyces and Micromonospora.
 They include the following:-
 Gentamicin, Tobramycin, Amikacin, Netilmicin, Kanamycin,
Streptomycin, Neomycin, Sisomicin, Astromycin,
micronomycin.
 GENERAL CHARACTERISTICS
 Second therapeutic agent against gram-negative bacteria.
 Serious toxicities.
 Narrow therapeutic window.
 Bactericidal antibiotics
 Does not penetrate into the CNS.
 Must be given parenterally and topical application because is
poorly absorbed orally.
 Unchanged drug appears in the urine.

16. 3. THE AMINOGLYCOSIDES:
 MECHANISM OF ACTION
 Diffuses through porin channels in outer membrane.
 Once inside the cell, Aminoglycosides bind to polisomes and
interfere with protein synthesis by causing misreading and
premature termination of translation of mRNA.
 Alters bacterial cell membrane causing leakage of the outer
gram-negative membrane and disruption of the cell wall.
 Bactericidal activity appears to be multifactoral.
 THERAPEUTIC USES
 Streptomycin: Bacterial endocarditis, Tularemia, Plague,
Tuberculosis
 Gentamicin: Bacteremia, Infected burns, Osteomyelitis,
Peritonitis, Otitis, Pyelonephritis, Pneumonia (Hospital
acquired pneumonia), Meningitis (Pseudomonas,
Acinetobacter), Neutropenic patients.

17. 3. THE AMINOGLYCOSIDES:
 ADR OF AMINOGYCOSIDES:
 Otoxicity, Nephrotoxicity, Neuromuscular paralysis,
Allergic reactions
 INTERACTION:
 Aminoglycosides should not be combined with the
following:
 Antiemetic:- can produce ototoxicity
 Diuretics:- can increase the ototoxicity

18. 4. THE QUINOLONES:
 THE QUINOLONES are broad spectrum antibiotics and are active
against Gram+ and gram- bacteria.
 They have a similar mechanism of action and that they block bacterial
DNA synthesis.
 They have cross resistance and that can cross the placenta and
through breast milk.
 Rarely that micro-organism develop resistance against them. They all
display similar pharmacokinetic profiles.
 TYPES OF QUINOLONES:
 FIRST GENERATION: Used in the treatment of uncomplicated UTI.
 Nalidixic acid.
 SECOND GENERATION:
 Ciprofloxacin (Bactiflox)250mg, 500mg, 1gm.
 Norfloxacin (Uroctal)200mg, 400mg.
 Ofloxacin.

19. 4. THE QUINOLONES:
 THIRD GENERATION:
 Gatifloxacin.
 Levofloxacin.
 Moxifloxacin.
 Sparfloxacin.
 FOURTH GENERATION:
 Trovafloxacin.
 MECHANISM OF ACTION: Inhibit the replication of bacterial
DNA by interfering with the action of DNA gyrase
(topoisomerase II) and topoisomerase IV during bacterial
growth and reproduction. Binding of the Quinolone to both the
enzyme and the DNA forms a ternary complex that inhibits the
resealing step, and can caused cell death inducing cleavage of
the DNA.

20. 4. THE QUINOLONES:
 CLINICAL USES: Anthrax, Gonorrhea, UTI, Gastrointestinal
infections (Enterobacter, Shigella), drug of choice in traveler’s
diarrhea caused by E.coli, Resistant respiratory infections
(Haemophilus i, Legionella p, P. aeruginosa associated with
cystic fibrosis)
 ADR: Gastrointestinal: Nausea, vomiting and diarrhea. Central
nervous system problems: Headache and dizziness.
Phototoxicity. Liver toxicity (trovafloxacin). Connective tissue
problems: Arthropathy (erosion of growing articular cartilage
under 18 years of age), arthralgias and joint swelling, rupture of
tendon in adults.
 CONTRAINDICATIONS: Pregnant women, nursing mother,
and prepubertal children. Arrhythmias (Sparfloxacin and
Moxifloxacin prolong the QT interval).

21. 4. THE QUINOLONES:
INTERACTIONS:
 Antacids and cautions affect the absorption.
 Ciprofloxacin and Ofloxacin inhibit the metabolism of
Theophylline.
 Cimetidine interferes with the elimination of
Fluoroquinolones

22. 5. THE TETRACYCLINES:
 THE TETRACYCLINES are also a large group of antibiotics
with a similar base of structure.
 They are broad spectrum and effective against Gram+ and
Gram- bacteria, Chlamydia, Rickettsias, Mycoplasmas,
Spirochetes, some mycobacterium and protozoa.
 They are Bacteriostatic and display different pharmacokinetic
profile and ADR.
 When given orally, a part of the drug does remain in the gut
lumen to modify micro flora which may cause SUPER-
INFECTION.
 They can cross the placenta and be excreted in breast milk.
 Tetracyclines are now not generally of choice in treatment due
to their increase resistance rate.

23. 5. THE TETRACYCLINES:
MECHANISM OF ACTION: The drugs bind reversibly to the 30
subunit of the bacterial ribosome, thereby blocking access of
the amino acyl-tRNA to the mRNA-ribosome complex at the
acceptor site.
 By this mechanism, bacterial protein synthesis is inhibited.
CLINICAL USES:
 Treatment of chlamydia, mycoplasma, brucella, vibrio,
helicobacter, rickettsia, borrelia, ehrlichia (anaplasma)
infections.
 Mycobacterium marinum infections.
 Acne.
 Rarely the first drug of choice.

24. 5. THE TETRACYCLINES:
ADR:
 Gastrointestinal symptoms.
 Brown discoloration of the teeth (deposition of the drug in the
teeth and bones due to chelating property and the formation of
a tetracycline-calcium orthophosphate complex.
 Depression of the bone growth.
 Photosensitivity.
 Hepatotoxicity.
 Superinfections.
 Contraindications
 Pregnant or breast-feeding women.
 Children under eight years of age.
 In renal impaired (except Doxycycline)

25. 5. THE TETRACYCLINES:
INTERACTIONS:
 - With food containing milk or milk derivates- these
products have high calcium ions and their combination
makes tetracycline unabsorbed.
 Antacids impair their absorption
 Penicillins:- can interfere Penicillins bactericidal action.
 F/P Pills:- decreases F/P drugs effectiveness.

26. 5. THE TETRACYCLINES:
EXAMPLES TETRACYCLINES ARE:-
 Demeclocycline(ledermycin) 150mg tabs/caps
 Doxycycline (vibramycin) 50mg,100mg tabs/caps,
 Minocycline (minocin) 100mg tabs/caps
 Tetracycline (deteclo, achromycin)250mg, 500mg,
tabs/caps
 Lymecycline 300mg, 408mg caps/tabs
 Oxytetracycline (minocin) 100mg caps
 Meclocycline, Metacycline, Rolitetracycline,
Chlortetracycline, etc.

27. 6. THE MACROLIDES/KETOLIDES:
 These are of broad spectrum antibiotics derived from
Streptomyces.
 They are Bacteriostatic and Bactericidal in higher doses.
 They interfere with bacterial protein synthesis and have
similar mode of action.
 ORIGINAL AGENT: - Erythromycin (erymax, erythrocin,
erythroped) 250mg, 500mg tabs/syr
 Azalides: Azithromycin (zithromax) 500mg tabs
 Clarithromycin (klaricid) 250mg, 500mg tabs/syrup,
 Telithromycin, Fosfomycin, Kitamycin, Josamycin,
Flurithromycin, Roxithromycin, Pristinamycin,
Dirithromycin, etc.

28. 6. THE MACROLIDES/KETOLIDES:
MECHANISM OF ACTION: Bind irreversibly to a site on
the 50S subunit of the bacterial ribosome, thus inhibiting
the translocation steps of protein synthesis.
 They may also interfere at other steps, such as
transpeptidation.
PHARMACOKINETICS:
 Does not penetrate into the CSF, except with inflamation.
 Diffuses into prostatic fluid.
 Accumulating in macrophages.
 Azithromycin longest half-life (>40h)
 Erythromycin, Clarithromycin and Telithromycin inhibit
the cytochrome P450 system.

29. 6. THE MACROLIDES/KETOLIDES:
 THERAPEUTIC USES:
 Mycoplasma pneumoniae infections (community
acquired pneumonia), Legionnaires’ disease, Chlamydia
infections, Diphtheria, Pertrussis, Streptococcal
infections (Pharyngitis, scarlet fever, erysipelas, and
cellulitis), Staphylococcal infections, Gastroenteritis
caused by Campilobacter jejuni, Helicobacter pylori
infection, Tetanus, Syphilis, Mycobacterial infections,
Toxoplasmosis encephalitis.

30. 6. THE MACROLIDES/KETOLIDES:
 Prophylactic uses: Recurrences of rheumatic fever
(alternative) and Prevention of Bacterial endocarditis
following dental or respiratory-tract procedures
(alternative)
 ADR: Gastrointestinal symptoms (cramps, diarrhea),
Cholestatic jaundice, Ototoxicity
 Contraindications:
 - Patient with hepatic dysfunction should be treated
with caution.
 - Patient who is really compromised should be given
Telithromycin with caution.
 - Telithromycin may worsen myasthenia gravis.

31. 7. THE CHLORAMPHENICOLS
 They are also broad spectrum antibiotic isolated from cultures
of Streptomyces Venezuela in 1947.
 They are actually the first broad spectrum antibiotics to be
isolated or discovered.
 They include the following:
 - Chloramphenicol 250mg, 500mg, 1gm caps/syrup,
 - Florfenicol, Thiamphenicol, Azidamphenicol,
 General Characteristics:
 Active against gram-positive and gram-negative organisms.
 High toxicity.
 Its use is restricted to life-threatening infections for which no
alternatives exist.
 Drug crosses blood-brain barrier.
 Inhibit cythochrome P450 system.
 Metabolites appear in the urine.

32. 7. THE CHLORAMPHENICOLS Cont’d..
 MECHANISM OF ACTION: Binds to the bacterial 50S ribosomal
subunit and inhibits protein synthesis at the peptide transferase
reaction.
 CLINICAL USES: Not the drug of choice for any infection.
 Typhoid fever (s. typhi)
 Bacterial meningitis (H. influenza, N. meningitidis, S. pneumoniae)
 Anaerobic infections (Bacteroides, intrabdominal infections, brain
abscesses)
 Rickettsias diseases (Rocky Mountain Fever) and Brucellosis.
 ADR OF CHLORAMPHENICOLS
 Anemias
 Hemolytic anemia (low levels of glucose 6-phosphate dehydrogenase.
 Reversible anemia (dose-relate)
 Aplastic anemia (idiosyncratic and usually fatal)
 Gray baby syndrome.

33. 8. THE SULPHONAMIDES and TRIMETOPRIMS
 These are Folic acid antagonists.
 They are Bacteriostatic broad spectrum antibiotics,
although they have increased rate of resistance.
 THE SULFONAMIDES (sulfa drugs) are a family of
antibiotics that inhibit the synthesis of folic
acid.(Examples:- Sulphadimidine 250mg,500mg tabs,
Sulphamoxole, Sulphadiazine 500mg tabs, etc)
 TRIMETHOPRIM is a second type of folic acid
antagonist prevents the conversion of folic acid to its
active, coenzyme form (tetrahydrofolic acid). Examples:-
trimetoprim, Ormetoprim.
 Thus, both compounds interfere with the ability of an
infecting bacterium to divide.

34. 8. THE SULPHONAMIDES and TRIMETOPRIMS
 Co-trimoxazole 400mg/80mg
 This product has both sulphonamide 400mg and
Trimetoprim 80mg.
 Sulfonamide (sulfamethoxazole) with trimethoprim
provides a synergistic combination (co-trimoxazole) that
shows greater antimicrobial activity than equivalent
quantities of the either drug used alone.
 Has a broader spectrum than the sulfa drugs.
 It is effective in treating UTIs and respiratory tract
infections, as well as Pneumocystis jeroveci pneumonia
and ampicillin- or Chloramphenicol-resistant systemic
salmonella infections.

35. 8. THE SULPHONAMIDES and TRIMETOPRIMS
 ADROF THE SULPHONAMIDES and TRIMETOPRIMS:
 Dermatologic: Skin rash.
 GI: Nausea, vomiting, glossitis and stomatitis.
 Hematologic: Megaloblastic anemia, leukopenia,
thrombocytopenia.
 HIV patients with P. jeroveci show drug-induced fever, rashes,
diarrhea and pancytopenia.

 Urinary tract antiseptics.
 Methenamine.
 Nitrofurantoin.
 Nalidixic acid (quinolone)
 These drugs do not achieve antibacterial levels in the
circulation, they are concentrated in the urine and the
microorganisms at that site can be eradicated.

36. 9. LINCOSAMIDES and 10. GLYCOPEPTIDES:
 These are broad spectrum antibiotics produced by a strain of
Streptomyces lincolnensis and described in 1962.
 Although they are structurally not related to Macrolides but they have
similar antimicrobial activity. They are active against Gram+ bacteria and
Protozoa. They can used as alternate to Penicillins.
 Examples are:-Lincomycins:- Clindamycin (dalacin)150 caps , Lincomycin,
Pirlimycin, etc….
 Glycopeptides:- Vancomycin(vancocin)125mg,250mg caps, Ramaplanin,
Avoparcin, etc.
 ADR:
 Gastro-intestinal disorders:- diarrhea, nausea, vomiting
 Hypersensivity reactions:- skin rash, urticaria, etc
 Cardiac Arrest in elderly after rapid administration.
 Ototoxicity
 Nephrotoxicity.
 INTERACTIONS
 They should not be mixed with any other drugs as their reaction can cause
neuromuscular blockage.

37. REFERENCES
Basic and Clinical Pharmacology. Bertram G. Katzung.
 Pharmacology. H. P Rang, M. M. Dale, J. M. Ritter, P. K.
Moore.
 Pharmacology. 2005. Lippincott Willians and Wilkins.
 Basic Clinical Pharmacokinetics. Fourth Edition. Lippincott
Willians and Wilkins.
 British National Formulary 2009, London WC1H 9JP, UK
 Goodman and Gilman`s. The pharmacological basis
therapeutics.
 Morton J.R(BSN,PH.d.), Dorothy W.S.- Pharmacology and
drug therapy in nursing. J.B Lippicott company. Toronto, USA.
 Hall.J.W.: Drug therapy in infectious diseases. Am.J. Nursing,
61:56. 1961
 The Gambia Standard Drug Treatment Manual, MOHSW,
Banjul. July 2005,

38. ,
CLARIFICATIONS
&
CONSTRUCTIVE
CRITICISMS????
?