SYNOPSIS
PHARMACOLOGICAL EFFECT OF VARIOUS DRUG IN
TREATMENT OF MALARIA
BY
UJJWAL SHASHANK
(AKU REG:- 21109164051)
Batch Year (2021-2025)
GUIDED BY
Md Rustam Hussain
Asst Professor (M.Pharm)
Dept. of Pharmacy
GAUTAM INSTITUTE OF PHARMACY
VILL-SAIDBARHI,PO.-JAITPUR,PS.-CHANDI,DIST-NALANDA
CHANDI ROAD SAIYAD BAHRI, HILSA, BIHAR 801307
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TABLE OF CONTENTS
INTRODUCTION 3
AIMS AND OBJECTIVES 4
LITERATURE REVIEW 5
PROFILE OF ANTIMALARIAL 6-8
DRUGS
PLAN OF WORK 9
REFERENCES 10-11
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INTRODUCTION
Malaria is a parasitic disease caused by Plasmodium species transmitted by
the bite of infected Anopheles mosquitoes. Globally, malaria affects
hundreds of millions annually, causing significant morbidity and mortality,
particularly in sub-Saharan Africa and Southeast Asia. The pharmacological
management of malaria includes a range of antimalarial drugs targeting
different parasite stages and mechanisms.
This project focuses on exploring and analyzing the pharmacological
effects, mechanisms of action, therapeutic uses, adverse effects, and
resistance patterns of the major antimalarial agents currently used in
clinical practice.
Malaria remains one of the most significant parasitic diseases affecting
humankind, causing substantial morbidity and mortality worldwide. The
disease is caused by protozoan parasites of the genus Plasmodium, with P.
falciparum accounting for the majority of lethal infections. According to the
World Health Organization (2020), an estimated 241 million cases and
627,000 deaths occurred globally, underscoring the urgent need for effective
pharmacological interventions.
The treatment of malaria has evolved over centuries, progressing from
traditional herbal remedies to the development of synthetic and semi-
synthetic compounds. While historical breakthroughs such as quinine and
chloroquine revolutionized malaria therapy, the emergence of widespread
drug resistance has necessitated the continuous development of novel
pharmacological strategies.
Artemisinin-based combination therapies currently form the cornerstone of
treatment, demonstrating rapid parasite clearance and high efficacy.
However, resistance to artemisinin derivatives in Southeast Asia and parts
of Africa poses a grave threat to global malaria control.
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AIMS AND OBJECTIVES
AIMS:
To systematically study and document the pharmacological effects of
various drugs used in malaria treatment.
To analyze their mechanisms of action, pharmacokinetic properties,
therapeutic roles, and resistance issues.
OBJECTIVES:
• To review historical and current literature on antimalarial drugs.
• To prepare detailed pharmacological profiles of key drugs.
• To compare their efficacy, safety, and suitability in different malaria
types.
• To highlight current challenges in malaria pharmacotherapy.
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LITERATURE REVIEW
Malaria has afflicted humankind for millennia, with evidence of the disease
dating back to ancient Egyptian texts and Chinese medical writings. The
earliest pharmacological interventions emerged from traditional herbal
remedies, most notably the use of Cinchona bark by indigenous populations
of South America. The active compound, quinine, was isolated in the early
19th century and rapidly became the standard treatment. Early literature
describes quinine as a lifesaving therapy, though its narrow therapeutic
index and adverse reactions posed significant challenges.
By the mid-20th century, the synthesis of chloroquine during World War II
marked a milestone in antimalarial pharmacology. Chloroquine was
inexpensive, highly effective against Plasmodium falciparum, and widely
adopted as first-line therapy. However, as reported in numerous studies
from the 1950s onward (e.g., Edgcomb et al., 1950), the misuse and overuse
of chloroquine led to the emergence of resistance in Southeast Asia and
South America.
The limitations of chloroquine and quinine led to the exploration of
alternative compounds, including antifolate agents and antibiotics.
Sulfadoxine-pyrimethamine (SP) became another mainstay of therapy,
particularly in areas where chloroquine resistance was prevalent.
Unfortunately, as documented in extensive surveillance data (WHO, 1990s),
resistance to SP developed rapidly due to single-point mutations in the
Plasmodium dihydrofolate reductase gene.
In response to this escalating crisis, artemisinin derivatives emerged as a
transformative class of antimalarial agents. Artemisinin was derived from
Artemisia annua, an herb long used in traditional Chinese medicine. In the
1970s, Chinese scientists successfully extracted and characterized the
compound. Subsequent studies demonstrated artemisinin's remarkable
efficacy and rapid parasite clearance. The World Health Organization now
recommends Artemisinin-based Combination Therapy (ACT) as the first-line
treatment for P. falciparum malaria.
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PROFILE OF ANTIMALARIAL DRUGS
4.1 Chloroquine
Class: 4-Aminoquinoline
Mechanism of Action:
Inhibits heme polymerase in parasite food vacuole.
Accumulation of toxic heme leads to parasite death.
Pharmacokinetics:
Oral absorption, large volume of distribution.
Long elimination half-life (~1–2 months).
Therapeutic Uses:
Uncomplicated P. vivax, P. ovale, P. malariae infections.
Adverse Effects:
Retinopathy (prolonged use), pruritus, GI upset.
Resistance:
Widespread in P. falciparum.
4.2 Quinine
Class: Cinchona alkaloid
Mechanism:
Interferes with heme digestion.
Pharmacokinetics:
Rapid absorption, hepatic metabolism.
Uses:
Severe malaria.
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Adverse Effects:
Cinchonism, hypoglycemia, hypotension.
4.3 Artemisinin Derivatives
Artesunate, Artemether
Mechanism:
Generates free radicals damaging parasite proteins.
Uses:
First-line in severe falciparum malaria.
Safety:
Generally well tolerated.
4.4 Primaquine
Mechanism:
Active against hypnozoites.
Uses:
Radical cure of P. vivax and P. ovale.
Warning:
Hemolysis in G6PD deficiency.
4.5 Mefloquine
Uses:
Chloroquine-resistant malaria.
Adverse Effects:
Neuropsychiatric reactions.
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4.6 Atovaquone-Proguanil (Malarone)
Uses:
Prophylaxis and treatment.
Mechanism:
Inhibits mitochondrial electron transport.
4.7 Doxycycline and Clindamycin
Adjunctive therapy.
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PLAN OF WORK
1. Collection of Literature
Textbooks of Pharmacology, WHO guidelines, CDC reports.
2. Review of Pharmacological Data
Mechanisms, kinetics, clinical studies.
3. Compilation of Monographs
Individual drug profiles.
4. Analysis and Comparison
Efficacy, safety, resistance.
5. Preparation of Project Report
Drafting, editing, finalizing.
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REFERENCES
1. World Health Organization. (2021). Guidelines for the treatment of
malaria, 3rd edition. Geneva: WHO Press.
2. White, N. J. (2008). Qinghaosu (Artemisinin): The Price of Success.
Science, 320(5874), 330–334
3. Wellems, T. E., & Plowe, C. V. (2001). Chloroquine-resistant malaria.
Journal of Infectious Diseases, 184(6), 770–776.
4. Taylor, W. R. J., & White, N. J. (2004). Antimalarial drug toxicity: A review.
Drug Safety, 27(1), 25–61.
5. Ashley, E. A., Dhorda, M., Fairhurst, R. M., Amaratunga, C., Lim, P., Suon,
S., et al. (2014). Spread of Artemisinin Resistance in Plasmodium falciparum
Malaria. New England Journal of Medicine, 371(5), 411–423.
6. Edgcomb, J. H., Arnold, J., Yount, E. H., Alving, A. S., Eichelberger, L., &
Jeffery, G. M. (1950). Primaquine, SN 13272, a new curative agent in vivax
malaria; a preliminary report. Journal of the National Malaria Society, 9(3),
285–292.
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7. Nosten, F., van Vugt, M., Price, R., Luxemburger, C., Thway, K. L.,
Brockman, A., et al. (2000). Effects of artesunate–mefloquine combination
on incidence of Plasmodium falciparum malaria and mefloquine resistance
in western Thailand: a prospective study. The Lancet, 356(9226), 297–302.
8. Valecha, N., Srivastava, P., Mohanty, S. S., Mittra, P., Sharma, S. K., Tyagi,
P. K., et al. (2010). An open-label, randomized study of artesunate
sulphadoxine-pyrimethamine versus artesunate + mefloquine in Indian
patients with falciparum malaria. Malaria Journal, 9(1), 74.
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