Chemotherapeutic Agents

A PRESENTATION ON CHEMOTHERAPEUTIC AGENTS, ITS

PROPERTIES, DRUG RESISTANCE, TRIMETHOPRIM,
QUINOLONE, ISONIAZID.

Group Members
BG13018. Fazle Rabbi

BG13029. Abdus Salam

BG13021. Subarna Sayed Ety

BG13053. Fatema Khan

BG13024. Nazneen Nahar

BG12003. Musabbir Hasan

BG13026. Shahriar Hasan

BG12042. Prianka Basak

BG13027. Md. Omar Faruque

Definition

Antimicrobial agents of synthetic origin.

Useful against microbial or viral disease.

What is
Chemotherapeutic
Agent.

Examples are sulfonilamide, isoniazid,

AZT, etc.

Selective Toxicity.

Properties

Antimicrobial Spectrum.
No Side Effects.
No Killing Effect on Normal Flora.

Properties of
therapeutic agents.

No Inactivation.
No Development of Drug Resistance.

Genetic Alterations.
Spontaneous Mutation of DNA.

Drug
Resistance

DNA of Drug Resistance.

Altered Expression of Proteins.

Causes of Drug
Resistance.

Modification of Target Sites.

Decreased accumulation.
Enzymatic inactivation.

Structurally similar to folic acid.

Trimethoprim

General Properties.

Weak base trapped in acidic

environments.
A fraction is excreted unchanged
through urine.
Half life is 10 to 12 hours.

Active form of folate is tetrahydro

derivatives.

Trimethoprim

Formed through reduction of

Dihydrofolic acid.
Catalyzed by Dihydrofolate Reductase.

Mode of Action.
Inhibited by Trimethoprim.

Usually given orally.

Trimethoprim

Or in combination with
Sulfomethoxazole.
Mainly excreted into urine.

Pharmacokinetics.
More activity in prostatic and vaginal
fluid.

Reduced cell permeability.

Trimethoprim
Trimethoprim
Resistance.

Overproduction of DHF reductase.

Altered affinity of reductase.

Against gram negative bacteria.

Acute urinary infection.

Trimethoprim

Pneumonia, Shigellosis, Systemic

Salmonella infection.
Against many respiratory pathogens.

Clinical Use.
Against gram negative species.

Megaloblastic Anemia.

Trimethoprim

Leukopenia, Granulocytopenia.

Can be prevented by folinic acid.

Adverse Effects.
AIDS patients have frequency of
unwanted reaction.

Synthetic antimicrobials.

Fluroquinolone

Bactericidal.

First member is Nalidixic Acid.

General Properties.
Primarily works against gram negative
bacteria.

Fluroquinolon
e

Classification.

First Generation.
Norfloxacin.
Ciprofloxacin.
Oflofloxacin.
Pefloxacin.

Second Generation.
Levofloxacin.
Lomefloxacin.
Moxifloxacin.
Prulifloxacin.

Fluroquinolon
e

Mode of Action.

Quinolone targets DNA Gyrase.

Relaxation of Supercoiled DNA.
Promoting DNA strand breakage.

Quinolone targets Topoisomerase IV.

Chromosomal stabilization during
cell division.
Separation of newly replicated
DNA.

Plasmid mediated resistance.

Fluroquinolone

Resistance via enzymatic degradation.

Due to altered target.

Drug Resistance.
Due to decreased accumulation.

Well absorbed after oral administration.

Fluroquinolone

Good distribution.

Divalent cations impair absorption.

Pharmacokinetics.
Excreted renally.

Urinary tract infection.

Fluroquinolone

Bacterial diarrhea.
Infections of soft tissues like bones,
and joints.

Clinical Use.

Intra-abdominal and respiratory tract

infection.
Chalmydial urethritis and cervicitis.

Nausea, Vomiting, and Diarrhea.

Fluroquinolone

Headache, Dizziness, Light Headache.

Acute Hepatitis and Hepatic Failure.

Adverse Effects.

Cause phototoxicity, pefloxacin,

lomefloxacin.
Hyperglycemia or Hypoglycemia.

Bacteriostatic at low concentration.

Isoniazid

Bactericidal at high concentration.

Inhibits synthesis of myolic acid.

General Properties.
Essential components of mycobacterial
cell wall.

Activated by mycobacterial catalaseperoxidase (katG).

Isoniazid

Active form bind to Acyl carrier protein

(acp M)

Mode of Action.

Also binds to kasA (beta-ketoacyl

carrier protein synthase) covalently.
Inhibit synthesis of mycolic acid.

Good absorption from GIT.

Isoniazid

Readily distributed to body fluids and

tissues.
Ratio in CFS 20 to 100 percent.

Pharmacokinetics.
Metabolised by N-Acetyltransferase.

Mutation or deletion of katG.

Isoniazid

Drug Resistance.

Overexpression of inhA.
Overexpression of ahpC, oxidative
stress protection.
Resistance mutants occur in 1 in 106.

Isoniazid

Single agent in latent tuberculosis.

In combination with second agent in
active form.

Clinical Use.

User pyrodoxin in conditions

predisposing to neuropathy.

Isoniazid

Adverse Effects.

Allergic Reactions:
Fever, Skin rashes.
Drug induced systemic lupus
erythematosus.
Direct Toxicity:
Hepatitis.
Neuropathy.
CNS effects.
Drug Interactions.