ANTIMICROBIALS and

CYTOTOXIC DRUGS
DR CAROLINE TETTEYFIO KONEY
37 MILITARY HOSPITAL
ACCRA

Feb 2012
 OUTLINE

1. INTRODUCTION
2. ANTIMICROBIALS
 Antibiotics
 Antifungals
 Antiprotozoals
 Antivirals
3. CYTOTOXICS
 HISTORY

 Pasteur and Joubert discovered that one type of bacteria

could prevent the growth of another.
 Paul Ehrlich observed that certain dyes stain bacterial
cells and not animal cells
 1920 Alexander Fleming working on cultures of
staphylococcus noticed colonies growing near mold
looked odd. Found that mold was secreting substance
that was inhibiting the growth of bacteria
ANTIMICROBIALS
 DEFINITION

 Antimicrobial: A drug used to treat a microbial

infection.
 "Antimicrobial" is a general term that refers to a
group of drugs.
 Includes:
1. antibiotics
2. antifungals
3. antiprotozoals
4. antivirals
 ANTIBIOTICS

The term antibiotic originally described

only those formulations derived from living
organisms, but is now applied also to
synthetic antimicrobials
Mechanisms of action of Antibacterial
Drugs

1. Inhibit cell wall synthesis

2. Inhibit protein synthesis
3. Inhibit nucleic acid synthesis
4. Injury to plasma membrane
5. Inhibit synthesis of essential
metabolites
 Classification of antibiotics
Based on:
1. Origin
2. Mechanism of action
3. Spectrum of activity
4. Chemical structure
 CLASSIFICATION

Origin
1. Natural: found in nature, e.g. beta-lactams
penicillins, produced by fungi.
2. Semisynthetic: produced and isolated from living
organisms, such as aminoglycosides.
3. Synthetic: created through purely synthetic means:
sulfonamides, quinolones.
 CLASSIFICATION

Mode of action
1. Bactericidal: Antibiotics that target
 bacterial cell wall (penicillins, cephalosporins)
 cell membrane (polymixins)
 interfere with essential bacterial enzymes
(quinolones, sulfonamides)
2. Bacteriostatic: target protein synthesis, e.g.
aminoglycosides, macrolides, tetracyclines
 CLASSIFICATION

Spectrum of activity
 Narrow-spectrum antibiotics target particular types
of bacteria, e.g. gram-negative or gram-positive
bacteria
 Broad-spectrum antibiotics affect wide range of
bacteria.
Spectrum of antibiotic activity
 Classification

Chemical structure:
Penicillins
Cephalosporins
Quinolones
Tetracyclines
Macrolides
Aminoglycosides
 Classification

Chemical structure
Penicillins
 Oldest class of antibiotics.
 Penicillins have a common chemical structure which
they share with the cephalosporins.
 Penicillins are generally bactericidal, inhibiting
formation of bacterial cell wall.
 Used to treat skin, dental, ear, respiratory tract,
urinary tract infections.
 Penicillins side effects

 Most common side effect: diarrhea nausea, vomiting.

 In rare cases penicillins can cause immediate and
delayed allergic reactions
 Cephalosporins

 Cephalosporins have a mechanism of action identical to

that of the penicillins.
 Like the penicillins, cephalosporins have a beta-lactam ring
structure that interferes with synthesis of the bacterial cell
wall and so are bactericidal.
 Cephalosporins are grouped into four "generations" by
their antimicrobial properties. Each newer generation has a
broader spectrum of activity than the one before.
 Cephalosporins are used to treat respiratory tract, ear, skin
and urinary tract infections, for surgical prophylaxis.
first generation cephalosporins

provide good coverage against most gram-positive

pathogens and poor coverage against most gram
negative pathogens.
 include:
 cefalexin (Ceporex)
 cefadroxil
second generation cephalosporins

 In addition to the gram positive spectrum activity of

the first generation cephalosporins, these agents
have expanded gram negative spectrum activity.
 include:
 Cefuroxime (Zinacef/Zinnat)
third generation cephalosporins

Have much expanded gram negative activity. However,

some members of this group have decreased activity
against gram-positive organisms.
include:
 ceftriaxone
fourth generation cephalosporins

Extended-spectrum agents with similar activity against

gram-positive organisms as first-generation
cephalosporins.
They also have a greater resistance to beta-lactamases
than the third generation cephalosporins.
Many fourth generation cephalosporins can cross blood
brain barrier and are effective in meningitis.
 include:
 Cefepime
 Cephalosporins side effects

 Cephalosporins generally cause few side effects.

 Common side effects include: diarrhoea, nausea, mild
stomach cramps or upset.
 Approximately 5–10% of patients with allergic
hypersensitivity to penicillins will also have cross-
reactivity with cephalosporins.
 Fluoroquinolones

(Fluoro)quinolones

 Synthetic antibiotics

 Broad-spectrum

 Bacteriocidal: inhibit bacteria DNA synthesis.

 Used to treat urinary tract, skin and respiratory infections.

 Fluoroquinolones

Commonly used fluoroquinolones include

 ciprofloxacin
 levofloxacin
 norfloxacin
Fluoroquinolones side effects

 The most common side effects include nausea,

vomiting, diarrhea, abdominal pain.
 Other more serious but less common side effects are
central nervous system effects (headache, confusion
and dizziness), photosensitivity .
 All drugs in this class have been associated with
convulsions.
 Tetracyclines

 Broad-spectrum
 bacteriostatic agents
 Effective against a wide variety of microorganisms,
including rickettsia, amoebae, mycoplasma sp,
Chlamydia.
 Used in the treatment of infections of the respiratory
tract, sinuses, middle ear, urinary tract, skin,
intestines, Lyme disease, syphilis, anthrax and plague
 Tetracyclines

The most commonly prescribed are:

 tetracycline
 doxycycline
 oxytetracycline
 Tetracyclines side effects

 Toxic.
 Common side effects include cramps, diarrhea, sore mouth or
tongue.
 Skin photosensitivity
 Allergic reactions.
 Very rarely severe headache and vision problems.
 Tetracyclines should not be used in children under the age of 8,
and specifically during periods of tooth development (cause
browning, and slow bone growth).
 Use during pregnancy may cause alterations in bone
development.
 Macrolides

Bacteriostatic
Used to treat respiratory tract infections, genital,
gastrointestinal tract, and skin infections.
The most commonly prescribed macrolide antibiotics:
 Erythromycin
 Clarithromycin
 Azithromycin
 Macrolides side effects

 Nausea, vomiting, and diarrhea

 Temporary auditory impairment.
 Azithromycin has been associated with allergic reactions,
including angioedema, anaphylaxis and dermatologic
reactions.
 Oral erythromycin may be very irritating to the stomach
 IV injections may cause severe phlebitis.
 Macrolide antibiotics should be used with caution in
patients with liver dysfunction.
 Aminoglycosides

 Used to treat infections caused by gram-negative

bacteria.
 Bacteriocidal
 Poorly absorbed from the GIT
 Aminoglycosides

The most commonly-prescribed aminoglycosides:

 Gentamicin
 Neomycin
 Streptomycin
 Amikacin
 Tobramycin

 Side effects
 Ototoxic
 Nephrotoxic
 Newest Antibiotics

 When MRSA first started to cause hospital epidemics in the

1990s, the search for new antibiotics to treat these
resistant bacterial infections became intense.
 A new class of antibiotics, the oxazolidinones was
developed, of which there is currently only one available
drug, linezolid.
 Daptomycin, an antibiotic originally developed in the 1980s
and then put on hold because of its toxic side effects, has
been revived since the 1990s, again to treat MRSA.
 Selection and use of antibiotics

 Cultures and sensitivity testing are the best guide for

selecting an antibiotic.
 Often treatment begins before culture results are
available, necessitating selection according to the most
likely pathogens (empiric antibiotic selection).
 Certain bacterial infections (eg, large or extensive
abscesses, infections with foreign bodies)may require
surgical intervention in addition to antibiotic therapy
 Inappropriate use of antibiotics
- subject patients to drug complications without any benefit
- contributes to bacterial resistance.
Selection and use of antibiotics

1.Site of infection
2.Age of patient
3.Health condition of patient
4.Cost
 Antifungal agents

Systemic
 amphotericin B, fluconazole, ketoconazole,
itraconazole
Topical
 clotrimazole, miconazole, nystatin
 Classification

Based on their mechanisms of action

 Polyenes: amphotericin B and nystatin
 Pyrimidine : Flucytosine
 Imidazoles: ketoconazole, miconazole,
 clotrimazole, fluconazole
 Griseofulvin
 Allylmine: terbinafine
ANTIPROTOZOALS
 PROTOZOA

 1. Sarcodina (amoebae): Entamoeba histolytica

 2. Mastigophora (flagellates): Giardia,
trichomonas, trypanasoma, leishmania spp.
 3. Ciliata: Balantidium coli
 4. Sporozoa: Plasmodium, Toxoplasma,
Cryptosporidium, Microsporidium spp
 Antimalarials

• Quinine
• Camoquine
• Halofontrine
• Chloroquine
• Artemisin derivatives:
• Artesunate: for oral, rectal, intramuscular, or intravenous
use
• Artemether (gvither) : for oral, rectal or intramuscular use
 Quinine: Adverse Effects and Cautions
1. Cinchonism: tinnitus, headache, nausea, dizziness, flushing,
visual disturbances
2. Severe hypotension and arrhythmia can follow too-rapid
intravenous infusion.
3. Hypoglycemia through stimulation of insulin release
4. stimulate uterine contractions
5. Hypersensitivity reaction in malaria patients termed
blackwater fever that results in massive haemolysis,
haemoglobinuria and renal failure!
6. Idiosyncrasy: hemolysis with G6PD deficiency.
 Metronidazole

 Antibiotic/antiprotozoal
 Minor side effects include nausea, headaches, loss of
appetite, metallic taste in the mouth, and rarely a
rash.
 Serious side effects are rare: includes seizures ,
peripheral neuropathy, encephalopathy, and aseptic
meningitis.
ANTIVIRAL AGENTS
 Antivirals

 Anti-viral agents inhibit viral replication rather than

eliminating viral particles already present.
 Most of the antivirals now available are designed to
help deal with HIV, herpes, hepatitis B and C,
influenza A, and B viruses.
Classes of antiviral medications

1. Non-nucleoside reverse transcriptase inhibitors

2. Nucleoside reverse transcriptase inhibitors (nucleoside
analogs)
3. Protease inhibitors
4. Nucleotide analog reverse transcriptase inhibitors
(NtARTIs or NtRTIs)

 Each class of drug attacks a different phase in the life cycle

of the virus.
 Adverse effects of antimicrobial
drugs

 Allergic reactions
 Toxic effects on organs/systems
 Destruction of beneficial bowel flora:  vitamin
deficiencies, loss of minerals through diarrhea,
inflammation of the gut, malabsorption syndromes
 Overgrowth of candida albicans
 Development of resistant species of micro-organisms
 CYTOTOXIC DRUGS

Drugs that inhibit and combat the development of

neoplasms.
 CYTOTOXIC DRUGS

 Chemotherapy drugs acts by destroy cells that divide

rapidly, one of the main properties of cancer cells.
 This means that they also harms cells that divide
rapidly under normal circumstances: cells in the bone
marrow, digestive tract, hair follicles
 Results in the most common side effects of
chemotherapy—myelosuppression, inflammation of
the lining of the digestive tract and alopecia.
 Other uses of chemotherapy agents are the
treatment of autoimmune diseases and after organ
transplant
 Newer anticancer drugs act directly against abnormal
proteins in cancer cells - this is termed targeted
therapy
 CYTOTOXIC DRUGS

1. Alkylating agent e.g. cyclophosphamide,

chlorambucil, cisplatin
2. Anti-metabolites e.g. mercaptopurine, azothioprine
3. Plant alkaloids e.g. vincristine
4. Antitumour antibiotics e.g. doxorubicin, bleomycin
The anaesthetist and antimicrobials

 Theatre/ICU
 Prophylaxis of infections
 On-going treatment
 Adverse effects e.g. hypersensitivity
 Aminoglycosides/ neuromuscular blockers
Anaesthesia and Chemotherapy

 Bone marrow suppression

 Pneumonitis and pulmonary fibrosis may be induced
by many chemotherapy agents.
 Bleomycin induces sensitivity to oxygen toxicity.
Patients who had a bleomycin therapy should not
receive high inspired oxygen concentration.
 Hepatotoxicity may occur with the use of most of the
anticancer drugs.
 Busulfan, methotrexate, cisplatin and others may
cause nephrotoxicity.
Rehydration started the evening before surgery will
aid in maintaining optimal renal flow and glomerular
filtration. Potentially nephrotoxic drugs should be
avoided
 The effects of cyclophosphamide, a pseudo-
cholinesterase inhibitor, could last for 3–4 weeks
from the end of its use. The drug's interaction with
suxamethonium could lead to prolonged apnoea.
 Central and autonomic nervous system toxicity and
peripheral neuropathies occur with vincristine,
cisplatin.
 Cardiotoxicity may occur in-patients who have
received doxorubicin
 Diarrhoea is a side effect of many anti-cancer drugs.
Serum electrolyte and fluid abnormalities if present
should be corrected before surgery
 Patient with cancer often receive steroids as part of a
chemotherapy regimen
THANK YOU
 References

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Third Edition. Prentice Hall. Upper Saddle River, New Jersey.
pp. 356-387.
Tortora, G.J., Funke, B.R., Case, C.L. (1995). Microbiology. An
Introduction. Fifth Edition. The Benjamin/Cummings
Publishing, Co., Inc., Redwood City, CA, pp. 491-514.
Arain MR, Buggy DJ: Anaesthesia for cancer patients. Curr Opin
Anaesthesiol 2007; 20: 247-53.
Stephen P, Fischer P: Preoperative evaluation of the cancer
patient; Anesthesia Clinics of North America. 1998;16:533–546.