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* The History of Chemotherapy

Fleming discovered penicillin, produced by Penicillium

Prontosil red dye used for streptococcal infections

First clinical trials of penicillin

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Today there is a growing problem of antibiotic resistance. RSA, MRSA) Jl : A

* spectrum of Antimicrobial Activity

Narrow spectrum of
Broad-spectrum antibiotics Extended-spectrum antibiotics
microbial activity

Effective against
affect a broad range of
drugs that affect a gram-negatives as
gram-positive or gram-
narrow range of well as gram-
microbial types. negative bacteria. positives.

*The Action of Antimicrobial Drugs

Bactericidal Bacteriostatic

Kill microbes directly Prevent microbes from growing

List-a HIEI
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Major Action Modes of Antibacterial Drugs

* ‫*اغلب هاي االمثلة مذكورة لقدام‬

 Prevent the cross-linking of
peptidoglycans, interfering with cell wall
""" Penicillin

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construction (especially gram-positives) structures

a β-lactam ring chemical side chains attached to the ring

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Types ofpencillinare
differentiated by them

Natural penicillins Semisynthetic penicillins

from Penicillium fungi cultures. Synthesized.

spectrum of activity Narrow spectrum of activity narrow (Oxacillin ) Extended(Ampicillin

Susceptible to penicillinases Susceptible to penicillinases (β- resistant to penicillinases

.li#gI-o . lactamases) because: they contain chemically added
side chains .

Examples *Penicillin G (injected) . Oxacillin : narrow spectrum only

*Penicillin V (oral). gram positives.

Ampicillin: Extended spectrum,

Affect gram-negatives

Penicillinase-resistant penicillins 8M£ Penicillinase Was .ws.W↳ñk£H8Jb&④

Methicillin and oxacillin JI
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Augmentin ‫من مكونات ال‬ 3 Aminopenicillins 2 Extended-spectrum penicillins 1861 amoxicillinIn -

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Extended-spectrum
]→ Aminopenicillins .

Extended-spectrum

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Substitute a C for an S and add a double bond to the penicillin nucleus
doripenem Broad spectrum
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*Synthetic; single ring instead of the β-lactam double ring

*Low toxicity; works against only certain gram- negatives

Work similar to penicillins

*β-lactam ring differs from penicillin.
* Grouped according to their generation of development →
* *→ *

Topical application; works against gram-positives

Glycopeptide, Last line against antibiotic-resistant MRSA
Teixobactin A new class of antibiotics; works against gram-positives

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mycobacteria Nice
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 Nitrofurantoin *Converted to intermediates that attack bacterial ribosomal proteins
*Synthesized chemically
*Treatment for urinary bladder infections

*Inhibits peptide bond formation

Chloramphenicol (Binds to the 50S subunit of the ribosome)
*Synthesized chemically; broad spectrum
*Can suppress bone marrow and affect blood cell formation
Amino sugars linked by glycoside bonds

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*Change the shape of the 30S subunit of the ribosome
examples .

*Can cause auditory damage

Produced by Streptomyces spp.

Tetracyclines
*Interfere with the tRNA attachment to the ribosome obligate intracellular
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*Broad spectrum; penetrate tissues, making them valuable against rickettsias and chlamydias
*Can suppress normal intestinal microbiota

Broad spectrum; bacteriostatic

Glycylcyclines
*Bind to the 30S ribosomal subunit 15.46-a
antibody @is
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*Inhibits rapid efflux; administered intravenously
*Useful against MRSA

Macrolides
Contain a macrocyclic lactone ring
Erythromycin *Narrow spectrum against gram-positives

Streptogramins
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Oxazolidinones Bind to the 50S/30S subunit interface
*Synthetic; combat MRSA (linezolid) , MRSA JIG *

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Pleuromutilins Retapamulin: topical and effective against gram- positives
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suppress bone marrow and affect blood cell formation Chloramphenicol s.SN#.k-u1Ii-W-W- 4

Can cause auditory damage Aminoglycosides

suppress normal intestinal microbiota Tetracyclines

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Inhibitors of Cell Wall Synthesis

Last line against antibiotic-resistant MRSA Vancomycin

Useful against MRSA Inhibitors of Protein Synthesis Glycylcyclines

Synthetic; combat MRSA (linezolid) Inhibitors of Protein Synthesis Oxazolidinones

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gentamicin 3 2 19 Aminoglycosides e. JIA -Ag
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neomycin Streptomycin

7-
Erythromycin 9 Macrolides 81 I-III g-
 *used for skin infections
Daptomycin
* Attacks the bacterial cell membrane

‫ من اسمها‬lipopeptides ‫تحت عائلة ال‬ Esau

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Polymyxin B ‫ في‬lipid‫ يعني بتأثر على ال‬lipo *Topical; bacteriocidal; effective against gram- negatives
plasma membrane‫ال‬
*Combined with bacitracin and neomycin in nonprescription
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ointments *Inhibitors of Cell wall. inhibitor of Protein Synthesis
*works against gram-positives

Polymyxin E (colistin) Effective against gram-negatives

*Inhibits mRNA synthesis

*Penetrates tissues; antitubercular activity → M@ tuberculosis
• first-line drugs JI

Quinolone and Fluoroquinolones

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Synthetic; inhibits DNA gyrase
Nalidixic acid -

Norfloxacin and ciprofloxacin

Broad spectrum; relatively nontoxic

penetrates tissues @ 1%2 drugs ↳ ↳ 8 ④

inhibitor of Protein Synthesis Tetracyclines I

Nucleic Acid Synthesis Inhibitor Rifamycin 2

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Competitively bind to the enzyme for para- aminobenzoic
PABA J1÷qjÑ*A acid (PABA), a folic acid precursor
Sulfamethoxazole 4. ¥5 .

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(Sulfamethoxazole is a structural analog of PABA)
Sulfamethoxazole and Trimethoprim
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acid and protein synthesis
 Competitive Inhibition of Essential Metabolites

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Combination of trimethoprim and sulfamethoxazole (TMP-SMZ) is an example of drug synergism

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☒Antifungul drugs

Interrupt the synthesis of ergosterol,making the membrane excessively permeable

most commonly used

produced by Streptomyces; toxic to the kidneys

*
Imidazoles topical; treat cutaneous mycoses
Triazole
treat systemic fungal infections Coral
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, injection ) .

Allylsmines
Allylamines For azole-resistant infections

Echinocandins Inhibit the synthesis of β-glucan→

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Cytosine analog interferes with RNA synthesis

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*Produced by Penicillium
Griseofulvin *Inhibits microtubule formation
*Active against superficial dermatophytes

Tolnaftate For athlete's foot

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Pentamidine Anti-Pneumocystis; may bind to DNA

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Amphotericin B 2 Tetracyclines 18 Streptomyces JI
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Antifungal Drugs Inhibitors of Protein Synthesis

-Agents affecting fungal sterols
-polyenes.

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Griseofulvin 2 Natural penicillins I

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 Antiviral Drugs
① d d
Entry and fusion inhibitors ③ Assembly inhibitors ⑨Exit inhibitors
Block Block

the receptors on fusion of the Protease inhibitors

the host cell virus and cell Block
that bind to the
the cleavage of protein precursors
virus
Inhibit neuraminidase,
an enzyme required for
② Uncoating, genome integration, and nucleic acid synthesis inhibitors
some viruses to bud

d.
from the host cell
Prevent viral uncoating KANZAKI *
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Inhibit viral DNA integration into the host genome

Nucleoside analogs inhibit RNA or DNA synthesis.

Non-nucleoside inhibitors of RNA synthesis .

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DNA JI @

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8 Antiviral drugs I w ⑥, ⑤ ↳ A

Produced by viral-infected
5 Imiquimod Promotes production of :
Interferons cells to inhibit further
spread of the infection

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6 Antiretrovirals for Treating HIV/AIDS

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Antiprotozoan Drugs

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Antiprotozoan Drugs Treat Notes

' Quinine and chloroquine Treat malaria

2 Artemisinin Treat malaria Kills Plasmodium → *

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3 Metronidazole Treats Trichomonas, giardiasis, and interferes with anaerobic bacteria

amebic dysentery

Treats amebic encephalitis, and Inhibits cytochrome oxidase in

4 Miltefosine
mitochondria
leishmaniasis
 Antihelminthic Drugs

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Antihelminthic Drugs Treat Notes

Niclosamide Treats tapeworms Prevents ATP production

Praziquantel Treats tapeworms and flukes Alters membrane permeability

3 Mebendazole and Treat intestinal helminths Interfere with nutrient absorption

albendazole

Treats roundworms and mites Paralysis of helminths

4 Ivermectin
 Resistance to Antimicrobial Drugs
I

Persister cells Superbugs

*Resistance genes are often spread horizontally among bacteria

on plasmids or
: transposons via conjugation or transduction

Mechanisms of Resistance

Prevention of penetration to the target site within the microbe

Or destruction

Of the drug

• rapid j€ -
(ejection)

5. Variations of mechanisms of resistance:

Microbe affecting by trimethoprim

synthesizing very large amounts of enzyme (against which the drug is targeted.)

The Microbe could become resistant to trimethoprim

Antibiotic Misuse “Misuse of antibiotics selected for resistance mutants”

Using outdated or weakened antibiotics

Using antibiotics for the common cold and other inappropriate conditions

Using antibiotics in animal feed

Failing to complete the prescribed regimen

Using someone else’s leftover prescription

Antibiotic Safety

l
Therapeutic index: risk versus benefit

Reactions of antibiotics with other drugs

Damage to organs

Risk to the fetus

Future of Chemotherapeutic Agents

Target virulence factors

Sequester iron, which feeds pathogens

Antimicrobial peptides produced by various organisms

Bacteriocins: antimicrobial peptides produced by bacteria

I Phage therapy

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‫كل ما اضطريت ازيد الجرعة يعني البكتيريا‬
highly sensitive
Selective toxicity selectively finding and destroying pathogens without damaging the host

Chemotherapy the use of chemicals to treat a disease

Antibiotic a substance produced by a microbe that, in small amounts, inhibits

another microbe ‫طبيعي‬

Antimicrobial drugs synthetic substances that interfere with the growth of microbes ‫صناعي‬

Antibiosis is the mechanism of inhibition reaction between colonies on solid

media.
From this word comes the term antibiotic

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Persister cells microbes with genetic characteristics allowing for their survival when
exposed to an antibiotic

Superbugs bacteria that are resistant to large numbers of antibiotics

bug‫احيانا ا&يكروب بحكوله‬

Synergism the effect of two drugs together is greater than the effect of
either alone

Antagonism the effect of two drugs together is less than the effect of
either alone

‫ج‬
"‫سبَُلن َا‬ َِّ ‫"َوَما َلن َآ أ ََّال َنت ََوَّكَل َعَلى ٱ‬
ُ ‫هلل َوَقْد َهَدٰىن َا‬

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