This document summarizes information about antimalarial drugs. It describes the different species of Plasmodium that cause malaria in humans and classifies malaria as either uncomplicated or severe. It then discusses the malaria life cycle within the human host and mosquito vector. The document proceeds to classify antimalarial drugs based on the stage of the parasite they affect and their chemical structure. Specific antimalarial drugs are then described in more detail, including their mechanisms of action, pharmacokinetics, uses, and adverse effects. These drugs include quinine, chloroquine, mefloquine, proguanil, primaquine, and tetracyclines.
Broad spectrum antibiotics chloramphenicol, anaerobic,soil bacteria. Description includes Physicochemical Properties,Mechanism of action-50S ribosome ,Inhibits Bacterial protein synthesis,Resistance,Interactions,Indications of chloramphenicol-Pyogenic meningitis.
Anaerobic infections.
Intraocular infections.
Enteric fever
Drug of choice in some conditions.
Urinary tract infections
Topically In conjunctivitis & external ear Infections. Snehal chakorkar
Sulfonamide (also called sulphonamide, sulfa drugs or sulpha drugs) is the basis of several groups of drugs. The original antibacterial sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group.
classification of antiviral agents,replication of HIV virus and replication of virus.targets of virus,classification of antiviral agents with structure and mechanism action of antiviral agents
Broad spectrum antibiotics chloramphenicol, anaerobic,soil bacteria. Description includes Physicochemical Properties,Mechanism of action-50S ribosome ,Inhibits Bacterial protein synthesis,Resistance,Interactions,Indications of chloramphenicol-Pyogenic meningitis.
Anaerobic infections.
Intraocular infections.
Enteric fever
Drug of choice in some conditions.
Urinary tract infections
Topically In conjunctivitis & external ear Infections. Snehal chakorkar
Sulfonamide (also called sulphonamide, sulfa drugs or sulpha drugs) is the basis of several groups of drugs. The original antibacterial sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group.
classification of antiviral agents,replication of HIV virus and replication of virus.targets of virus,classification of antiviral agents with structure and mechanism action of antiviral agents
Antiviral Agents,Medicinal Chemistry
•Introduction to Viruses
•Structure of Virus
•Types of Viruses.
•The viral Life cycle.
•Classification of Antiviral Agents
Anthelmintics | B.Pharm 3rd year 2nd Sem | Medicinal Chemistry-III | History, Classification, Structures & Synthesis of anthelmintics, Synthesis of Diethylcarbamazine citrate, Synthesis of Mebendazole
Natural compounds from the bark of the cinchona tree, most notably quinine was observed to exhibit antimalarial activity.
Until the development of synthetic derivatives (ie. 4-aminoquinoline antimalarials), quinine continued to be the first choice to treat malaria.
Quinine is associated with side effects such as diarrhœa.
4-aminoquinoline antimalarials such as amodiaquine and chloroquine largely replaced quinine because of reduced unpleasant side effects.
The life cycle of the parasite and the immunological defence mechanisms against the parasite are complex.
Part of the parasite’s life cycle involves invasion of red blood cells (erythrocytes).
The haemoglobin within the red blood cell is broken down by the parasite and is used as a source of amino acids.
The 4-aminoquinolines act at the erythrocytic stage of the parasite.
Doxycycline is a compound used in prophylaxis against plasmodial parasites.
Other compounds associated with treating malaria include halofantrine and lumefantrine, often used in combination with other drugs.
synthetic antimicrobials having a quinolone structure that are active primarily against gram-negative bacteria, though newer fluorinated compounds also inhibit gram-positive ones.
Aminoglycosides(medicinal chemistry by p.ravisankar)Dr. Ravi Sankar
Aminoglycosides,Aminocyclitols,Source,Structures of streptomycin,Dihydrostreptomycin,A mention of other aminoglycoside antibiotics,Acid hydrolysis,Mechanism of action,SAR,Dihydrostreptomycin and its importance,therapeutic uses, toxicity.
The current slide include the pharmacology og cephalosporins.
Contents
Introduction to Cephalosporins
Classification of Cephalosporins
Cefazolin
Cephalexin
Cefuroxime
Cefuroxime axetil
Cefotaxime
Cefixime
Cefpodoxime proxetil
Cefepime
Adverse effects of Cephalosporins
Uses of Cephalosporins
Antiviral Agents,Medicinal Chemistry
•Introduction to Viruses
•Structure of Virus
•Types of Viruses.
•The viral Life cycle.
•Classification of Antiviral Agents
Anthelmintics | B.Pharm 3rd year 2nd Sem | Medicinal Chemistry-III | History, Classification, Structures & Synthesis of anthelmintics, Synthesis of Diethylcarbamazine citrate, Synthesis of Mebendazole
Natural compounds from the bark of the cinchona tree, most notably quinine was observed to exhibit antimalarial activity.
Until the development of synthetic derivatives (ie. 4-aminoquinoline antimalarials), quinine continued to be the first choice to treat malaria.
Quinine is associated with side effects such as diarrhœa.
4-aminoquinoline antimalarials such as amodiaquine and chloroquine largely replaced quinine because of reduced unpleasant side effects.
The life cycle of the parasite and the immunological defence mechanisms against the parasite are complex.
Part of the parasite’s life cycle involves invasion of red blood cells (erythrocytes).
The haemoglobin within the red blood cell is broken down by the parasite and is used as a source of amino acids.
The 4-aminoquinolines act at the erythrocytic stage of the parasite.
Doxycycline is a compound used in prophylaxis against plasmodial parasites.
Other compounds associated with treating malaria include halofantrine and lumefantrine, often used in combination with other drugs.
synthetic antimicrobials having a quinolone structure that are active primarily against gram-negative bacteria, though newer fluorinated compounds also inhibit gram-positive ones.
Aminoglycosides(medicinal chemistry by p.ravisankar)Dr. Ravi Sankar
Aminoglycosides,Aminocyclitols,Source,Structures of streptomycin,Dihydrostreptomycin,A mention of other aminoglycoside antibiotics,Acid hydrolysis,Mechanism of action,SAR,Dihydrostreptomycin and its importance,therapeutic uses, toxicity.
The current slide include the pharmacology og cephalosporins.
Contents
Introduction to Cephalosporins
Classification of Cephalosporins
Cefazolin
Cephalexin
Cefuroxime
Cefuroxime axetil
Cefotaxime
Cefixime
Cefpodoxime proxetil
Cefepime
Adverse effects of Cephalosporins
Uses of Cephalosporins
Artemisinin(qinghaosu), is a drug used for treatment of malaria. It is extracted from the Chinese herb Artemisia annua.
It has three major derivatives— Artemether, Artesunate and Dihydroartemisinin
Entropy in physics, biology and in thermodynamicsjoshiblog
Entropy is a measure of probability and the "disorder" of a system.
Disorder refers to is really the number of different microscopic states a system can be in, given that the system has a particular fixed composition, volume, energy, pressure, and temperature.
the exact definition is
Entropy = (Boltzmann's constant k) x logarithm of number of possible states
= k log(N).
The first law of thermodynamics defines the relationship between the various forms of energy present in a system (kinetic and potential), the work which the system performs and the transfer of heat.
We can imagine thermodynamic processes which conserve energy but which never occur in nature.
For example, if we bring a hot object into contact with a cold object, we observe that the hot object cools down and the cold object heats up until an equilibrium is reached. The transfer of heat goes from the hot object to the cold object.
According to the second law of thermodynamics, in any process that involves a cycle, the entropy of the system will either stay the same or increase. When the cyclic process is reversible then the entropy will not change. When the process is irreversible, then entropy will increases.
The second law states that there exists a useful state variable called entropy S. The change in entropy delta S is equal to the heat transfer delta Q divided by the temperature T.
delta S = delta Q / T
Order can be produced with an expenditure of energy, and the order associated with life on the earth is produced with the aid of energy from the sun.
For example, plants use energy from the sun in tiny energy factories called chloroplasts Using chlorophyll in the process called photosynthesis, they convert the sun's energy into storable form in ordered sugar molecules. In this way, carbon and water in a more disordered state are combined to form the more ordered sugar molecules.
In animal systems there are also small structures within the cells called mitochondria which use the energy stored in sugar molecules from food to form more highly ordered structures.
Anti-malarial drugs [Drugs used for Malaria].pptx slide share Imad Agarwal
Malaria is major health problem in Pakistan and tropics. Malaria is caused by 4 species of plasmodium parasite.
☆ Plasmodium Vivax
☆ Plasmodium Ovale
☆ Plasmodium Falciparum
☆ Plasmodium Malaria
Chemically Anti-malarial drugs are classified to two categories. 4 aminoquinolines and 8 aminoquinolines.
1• 4 Aminoquinolines
Chloroquine, Amodiaquine, Piperaquine, Mefloquine, Quinine, Proguanil, pyrimathamine, and Sulfadoxine .
3•8 Aminoquinolines
Primaquine, Tafenoquine, Atovaquone, pyronarodin, Halofantrene, Lumefantrene, Artesunate, Artemether, Arteether and Arterolane.
#pharmacology #Nursing #Nursingnotes #antimalarial
Hello friends. In this PPT I am talking about antiprotozoal drugs. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
At the end of this e-learning session you are able to…
A. Discuss malarial life cycle.
B. Explain pharmacology of anti-malarial drugs.
I am happy to share lecture series on different topics of Pharmacology experiments, Pharmacy practice, Clinical pharmacy and Pharmacology. Wish you all happy learning.
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able of ContentsIntroductionObjectives of Giemsa stainPrincipleReagents UsedProcedureStaining procedure 1: Thin Film stainingStaining Procedure 2: Thick Film StainingResultsInterpretation/ConclusionApplications Giemsa stainAdvantagesLimitationsReferencesFour Charged in Plot to Kidnap an Iranian Journalist in New YorkIntroductionGiemsa stain was a name adopted from a Germany Chemist scientist, for his application of a combination of reagents in demonstrating the presence of parasites in malaria.It belongs to a group of stains known as Romanowsky stains. These are neutral stains made up of a mixture of oxidized methylene blue, azure, and Eosin Y and they performed on an air-dried slide that is post-fixed with methanol. Romanowsky stains are applied in the differentiation of cells, pathological examinations of samples like blood and bone marrow films and demonstration of parasites e.g malaria. There are four types of Romanoswsky stains:Giemsa stainJenner StainWright stainMay-Grunwald StainLeishman stainObjectives of Giemsa stainTo accurately prepare the Giemsa stain stock solutionTo stain and identify blood cellsTo differentiate blood cells nuclei from the cytoplasmPrincipleGiemsa stain is a gold standard staining technique that is used for both thin and thick smears to examine blood for malaria parasites, a routine check-up for other blood parasites and to morphologically differentiate the nuclear and cytoplasm of Erythrocytes, leucocytes and Platelets and parasites.Like any type of Romanowsky stains, it composed of both the Acidic and Basic dyes, in relation to affinities of acidity and basicity for blood cells. Azure and methylene blue, a basic dye binds to the acid nucleus producing blue-purple color. Eosin is an acidic dye that is attracted to the cytoplasm and cytoplasmic granules which are alkaline-producing red coloration. The stain must be buffered with water to pH 6.8 or 7.2, to precipitate the dyes to bind simple materials.Classically, Giemsa stain is a differential stain which is made up of a combination of reagents (Azure, Methylene blue, and Eosin dye) used widely in cytogenetics and histopathology for the diagnosis of:Malaria, spirochetes and other blood parasitesChlamydia trachomatis inclusion bodiesBorrelia sppYersinia pestisHistoplasma sppPneumocystis jiroveci cystsReagents UsedMethanolGiemsa powderGlycerinWater (Buffer)ProcedurePreparation of the Giemsa Stain Stock solution (500ml)Into 250ml of methanol, add 3.8g of Giemsa powder and dissolve.Heat the solution up to ~60oCThen, add 250ml of glycerin to the solution, slowly.Filter the solution and leave it to stand for about 1-2 months before use.Preparation of Working solutionAdd 10ml of stock solution to 80ml of distilled water and 10ml of methanolStaining procedure 1: Thin Film stainingOn a clean dry microscopic glass slide, make a thin film of the specimen (blood) and leave to air dry.dip the smear (2-3 dips) into pure methanol for fixation of the
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
Honest Reviews of Tim Han LMA Course Program.pptxtimhan337
Personal development courses are widely available today, with each one promising life-changing outcomes. Tim Han’s Life Mastery Achievers (LMA) Course has drawn a lot of interest. In addition to offering my frank assessment of Success Insider’s LMA Course, this piece examines the course’s effects via a variety of Tim Han LMA course reviews and Success Insider comments.
Embracing GenAI - A Strategic ImperativePeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
A Strategic Approach: GenAI in EducationPeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Biological screening of herbal drugs: Introduction and Need for
Phyto-Pharmacological Screening, New Strategies for evaluating
Natural Products, In vitro evaluation techniques for Antioxidants, Antimicrobial and Anticancer drugs. In vivo evaluation techniques
for Anti-inflammatory, Antiulcer, Anticancer, Wound healing, Antidiabetic, Hepatoprotective, Cardio protective, Diuretics and
Antifertility, Toxicity studies as per OECD guidelines
Normal Labour/ Stages of Labour/ Mechanism of LabourWasim Ak
Normal labor is also termed spontaneous labor, defined as the natural physiological process through which the fetus, placenta, and membranes are expelled from the uterus through the birth canal at term (37 to 42 weeks
3. Classification of Malaria
• Uncomplicated Malaria
• Cold stage (sensation of cold, shivering)
• Hot stage (fever, headaches, vomiting; seizures
in young children)
• Sweating stage (sweats, return to normal
temperature, tiredness)
4. Classification of Malaria
• Severe Malaria
– Cerebral malaria (seizures, coma)
– Severe anemia
– Hemoglobinuria
– Abnormalities in blood coagulation
– Cardiovascular collapse and shock
5. Types of Infections
• Recrudescence
– exacerbation of persistent undetectable parasitemia, due to survival
of erythrocytic forms, no exo-erythrocytic cycle (P.f., P.m.)
• Relapse
– reactivation of hypnozoites forms of parasite in liver, separate from
previous infection with same species (P.v. and P.o.)
• Recurrence or reinfection
– exo-erythrocytic forms infect erythrocytes, separate from previous
infection (all species)
• Can not always differentiate recrudescence from reinfection
6. CLASSIFICATION OF ANTIMALARIALS
• Based on stage of parasite they affect:
– Causal prophylactics: Primaquine, Pyrimethamine,proguanil
– Supressives: Quinine, 4-aminoquinolines, mefloquine,artemisinin
– Radical curatives: Primaquine,pyrimethamine
– Gametocidal:
• Supressives – Pl Vivax ,
• Primaquine – against all,
• Proguanil ,pyrimethamine – prevent development also
prevent development of sporozoites
9. Malaria Life Cycle
Life Cycle
Sporogony
Oocyst
Sporozoites
Mosquito Salivary
Gland
Zygote
Exoerythrocytic
(hepatic) cycle
Gametocytes
Erythrocytic
Cycle
Schizogony
Hypnozoites
(for P. vivax
and P. ovale)
10. Malaria Transmission Cycle
Exo-erythrocytic (hepatic) Cycle:
Sporozoites infect liver cells and
develop into schizonts, which release
merozoites into the blood
Sporozoites injected
into human host during
blood meal
Parasites
mature in
mosquito
midgut and
migrate to
salivary
glands
MOSQUITO
Parasite undergoes
sexual reproduction in
the mosquito
HUMAN
Some merozoites
differentiate into male or
female gametocyctes
Dormant liver stages
(hypnozoites) of P.
vivax and P. ovale
Erythrocytic Cycle:
Merozoites infect red
blood cells to form
schizonts
11. Components of the Malaria Life Cycle
Sporogonic cycle
Infective Period
Mosquito bites
uninfected
person
Mosquito bites
gametocytemic
person
Mosquito Vector
Parasites visible
Prepatent Period
Human Host
Symptom onset
Recovery
Incubation Period
Clinical Illness
12. Exo-erythrocytic (tissue) phase
• Blood is infected with sporozoites about 30
minutes after the mosquito bite
• The sporozoites are eaten by macrophages or
enter the liver cells where they multiply –
pre-erythrocytic schizogeny
• P. vivax and P. ovale sporozoites form parasites
in the liver called hypnozoites
13. Exo-erythrocytic (tissue) phase
• P. malariae or P. falciparum sporozoites do not
form hypnozites, develop directly into preerythrocytic schizonts in the liver
• Pre-erythrocytic schizogeny takes 6-16 days post
infection
• Schizonts rupture, releasing merozoites which
invade red blood cells (RBC) in liver
14. Exo-erythrocytic (tissue) phase
• P. vivax and P. ovale hypnozoites remain
dormant for months
• They develop and undergo pre-erythrocytic
sporogeny
• The schizonts rupture, releasing merozoites
and producing clinical relapse
15. Erythrocytic phase
• Pre-patent period – interval between date
of infection and detection of parasites in
peripheral blood
• Incubation period – time between infection
and first appearance of clinical symptoms
• Merozoites from liver invade peripheral
(RBC) and develop causing changes in the
RBC
• There is variability in all 3 of these features
depending on species of malaria
16. Erythrocytic phase
stages of parasite in RBC
• Trophozoites are early stages with ring form the
youngest
• Tropohozoite nucleus and cytoplasm divide forming a
schizont
• Segmentation of schizont’s nucleus and cytoplasm
forms merozoites
• Schizogeny complete when schizont ruptures,
releasing merozoites into blood stream, causing fever
• These are asexual forms
17. Erythrocytic phase
stages of parasite in RBC
• Merozoites invade other RBCs and
schizogony is repeated
• Parasite density increases until host’s
immune response slows it down
• Merozoites may develop into gametocytes,
the sexual forms of the parasite
18. •
•
Quinine
Oldest antimalarial alkaloid isolated from barks of chinchona tree.
Present indication-cerebral malaria
-chloroquine resistant p. falcifarum
Pharmacological actions
1.Antimalarial :Suppressive agent
2.Local irritational action: General protoplasmic poison
-decrease cilliary actvity
-Inhibit phagocytosis & fibroblast growth
Local anesthetic action, At high conc. edema , pain at site of inj.
3.GI tract- bitter, nausea ,vomiting
4.CVS- myocardial depression, decrease excitability and conductivity
iv. dose- hypotension
5. Miscellaneous- analgesic, antipyretic, sk. muscle relaxant
P/K-well absorbed ,peak 1-3 hrs, cross placenta, metabolized in liver,
excreted in urine
19. Adverse effect
1.Cinchonism:
Mild - ringing in ears, nausea, vomiting, headache, visual impairment.
Large doses-Tinnitus, deafness, vertigo, blurring,photophobia, delirium,
confusion.
Poisoning progress- Skin pale, cold, resp. depress,BP falls, comma,
death.
2.Idiosyncrasy
3.CVS toxicity-cardiac arrest
4.Black Water Fever
-acute intravascular haemolysis,haemoglobinuria,fever, acute renal
failure,focal hepatic necrosis
5.Hypoglycemia
6.Acute renal Failure
20. Uses & Dose
1.Malaria:
• schizontocidal drug
• very active against erythrocytic phase.
• No effect against proerythrocytic, sexual gametocytes,
exoerythrocytic phase, relapse.
2.Myotonia Congenita
3.Nocturnal muscle cramps
4.Cerebral malaria
IV Quinine 600mg in 500ml of 5% dextrose slowly over 4 hrs
repeated every 8 hrs till patient is conscious followed by oral
treatment to complete 7 day coarse.
Dose:300-600mg orally
21. Chloroquine
• It is a 4-aminoquinolone
• It was produced in USA as a less toxic alternative to
mepacrine.
• It is rapidly acting erythrocytic schizontocide against
all species of plasmodia.it is highly efficacious drug.
• It controls most clinical attack in 1-2 days.
• It does not prevent relapses in vivax & ovale malaria.
22. Mechanism of action
• It is actively concentrated by sensitive intraerythrocytic
plasmodia
• It interfers with degradation of Hb by parasitic lysosomes
• Heme itself or its complex with chloroquine damages
plasmodial membrane
• Clumping of pigment & changes in parasite membrane
follows
• It has anti-inflamatory, local irritant, local anaesthetic, weak
smooth muscle relaxant, anti-histaminic & anti-arrhythmic
23. Resistance
• Chloroquine resistance among P. vivax has been slow
in developing.
• However P. falciparum has acquired significant
resistance
• Resistance in P. falciparum is associated with a
decreased ability of parasite to accumulate
chloroquine
24. Pharmacokinetics
• Oral absorption of chloroquine is excellent , about
50% gets bound in plasma
• It gets bound to melanin & nuclear chromatin and is
concentrated in liver, spleen, kidney, lungs, skin,
leucocyte
• Absorption after i.m. injection is also good
• Plasma concentration is 15-30ng/ml
• Chloroquine is partly metabolised by liver & slowly
excreted in urine
• Plasma t-1/2 varies from 3-10 days
25. Toxic effects
• Toxicity of chloroquine is low but side
effects are frequent & unpleasant:
• nausea
• vomiting
• anorexia
• uncontrollable itching
• epigastric pain
• uneasiness
• headache
26. …contd.
Parenteral administration can cause
• hypotension
• cardiac depression
• arrythmias
CNS toxicity including convulsions.
• Prolonged use of high doses can cause loss of
vision.
27. …contd.
• Loss of hearing , rashes, photo allergy, mental
disturbance, myopathy and graying of hairs
can occur as long term use.
• Attack of seizures, porphyria & psoriasis may
be precipitated.
28. Routes of administration & dosage
• Chloroquine phosphate is given orally
• As prophylaxis –
Dose: adults – 500mg once each week
children – 5mg/kg weekly
• For treatment –
Initial dose - 600mg
followed by 300mg after 6-8 hrs
then 300mg on 2 consecutive days
29. Indications
• Chloroquine is drug of choice for malaria
• It completely cures sensitive falciparum
disease, but relapses in vivax and ovale are
not prevented .
Other uses
• Extra intestinal amoebiasis
• Rheumatoid arthritis
31. Mefloquine
Introduction
It is a quinoline methanol derivative
It is a drug developed to deal with problem of
chloroquine resistant P.falciparum
It is rapidly acting erythrocytic schizontocide.
It is effective against chloroquine sensitive as
well as resistant plasmodia
It has not been extensively used in India.
32. Mechanism of action
Acts on erythrocytic stage
Highly effective in a single dose against
P.falciparum including chloroquine resistant
strains.
Appears to bind to heme and the complex
damages membrane of the parasite
No action on persistant tissue form.
33. Pharmacokinetics
Given orally
Rapidly and completely absorbed
Highly bound to plasma protein
Eliminated slowly with plasma half life of 20
days
34. Adverse effects
GIT
Dizziness, nausea, vomiting, diarrhoea, abdominal
pain
Neuropsychiatric disturbances
Anxiety, halloucination, sleep disturbances,
Single dose may cause light headedness and loss
of concentration
36. Uses
Effective drug for multiresistant P.falciparum
Treatment of uncomplicated falciparum
malaria in areas with multidrug resistance
Dose -25 mg per kg (maximum 1.5 g)
Prophylaxis of malaria among travellers to
areas with multidrug resistance
Dose -5 mg per kg (adult 150 mg)
37. Proguanil
Introduction
Commonly used salt of these drug is proguanil
hydrochloride
Has negligible antiplasmodial action in vitro
Slow acting erythrocytic schizonticide
Cyclized in body to triazine derivative
38. Actions
Effective schizonticide against P.vivax and
P.falciparum
Effective against primary pre-erythrocytic
forms of P.falciparum
Prevents development of gametes encysted in
gut wall of mosquito
No action against persistant tissue forms
P.vivax
41. Uses
Use dependent on sensitivity of strain
In multiresistant falciparum malaria
Combination of proguanil 100mg and
atovaqoune 250mg
Used prophylactically (in dose of 1 tablet
taken with food)
42. PRIMAQUINE
Poor erythrocytic schizontocide : has weak
action of P. vivax.
In contrast it is more active against preerythrocytic stage of P. falciparum than that
of P. vivax
Highly active against gametocytes &
hypnozoites.
43. PHARMACOKINETICS
Readily absorbed by oral ingestion.
Oxidized in liver with a plasma t1/2 of 3-6 hrs.
Excreted in urine within 24 hrs.
Not a cumulative drug.
44. Mechanism of action :• Mechanism of action of primaqunine is not known.
However it is difficult from that of chloroquine.
Uses :• Radical cure of relapsing malaria : 15 mg daily for 2
weeks is given with full curative dose of chloroquine.
• Falciparum malaria : single 45 mg dose of primaquine
is given with curative dose of chloroquine to kill
gametes & cut down transmission to mosquito.
45. Adverse effect
• Abdominal pain
• GI upset
• Weakness or uneasiness in chest
• CNS & cardiovascular symptoms are infrequent
leucopenia
• Haemolysis, methemoglobinemia, cyanosis
46. TETRACYCLINES
Introduction
• Broad spectrum antibiotic having a nucleus of four
cyclic ring.
• All are obtained from soil actinomycetes
• Slowly acting & weak erythrocytic schizontocidal
action against all plasmodial species
47. Mechanism of action
• Tetracyclines are primarily bacteriostatic, inhibit
protein synthesis by binding 30 s ribosomes in
susceptible organism. To such binding attachment of
aminoactyl – t- RNA to the m – RNA ribosomes
complex is interfered with. Thus peptide chain fails
to grow.
48. Adverse effects
• Irritative effects :- epigastric pain, N, V & D
• Dose related toxicity
Liver damage :- fatty infiltration of liver &
jaundice.
Kidney damage :- It is prominent only in the
presence of existing kidney disease.
Phototoxicity:- A sun like or other severe skin
reaction on exposed parts is seen
Teeth & bones:- Tetracyclines have chelating
property.
49. Cont…
Given between 3 months to 6 years of age affect
permanent anterior dentition.
Antianabolic effect:- Reduce protein synthesis & have
an overall catabolic effect
Increased intracranial pressure
Diabetes insipidus
Hypersensitivity
Super infection :- Tetracyclines are most common
antibiotics response for superinfections
50. Uses
• Used in combination with quinine or pyrimethamine
sulfadoxine for the treatment of chloroquine
resistant falciparum malaria.
• Doxycycline 100 mg /day in used as a 2nd line
prophylactic for travelers to chloroquine resistant p.
falciparum areas.
51. Precautions
• Should not given during pregnancy, lactation
& in children.
• Should be avoided in patients on diuretics
• Do not inject tetracycline intrathecally.
52. PYRIMETHAMINE
Mechanism of action
It is a directly acting inhibitor of plasmodial
DHFRase.
It gradually reduces the schizogony of malarial
parasite in blood.
It is slowly acting erythrocytic schizontocide.
53. Pharmacokinetics
Absorption from the gut is good but slow.
It is excreted in urine.
Half life time = 4 days.
Adverse Effects
Nausea & rashes,
Folate deficiency,
Megaloblastic anemia & granulocytopenia.
54. Uses
• Used only in combination with
sulfonamide/dapsone to treat P.falciparum
malaria.
S/P Combination
• Sulfonamide has some inhibitory action on
erythrocytic phase of P.falciparum like
pyrimethamine..
• It is a supra-additive synergistic combination
by sequential block.
56. Contraindications
• Infants
• Individuals allergic to sulfonamide
• Cautious use in pregnancy
Uses
• Chloroquine resistant falciparum malaria.
• Toxoplasmosis
Resistance
• Pyrimethamine develops resistance quickly & cross
resistance to biguanides is seen.
• It decreases due to sulfonamide & no cross
resistance seen
57. Cont…
• Resistance was first noted in 1980.
• It is more in south-east asia,s.america, southern
Africa.
• It is sporadic in India except for north-east
Some Combinations
• Sulfonamide(500mg)+pyrimethamin(25mg
• Sulfamethapyrasine+pyrimethamine
•
(500mg)
(25mg)
• Dapsone(100mg)+pyrimethamine(25mg)
• As clinical curative- sulfadoxine(1500mg)
+pyrimethamine(75mg)
58. Artemisia annua
• Also known as sweet wormwood
• Origin from northern parts of China
• Artemisinin present in leaves and flower of
the plant in 0.01-0.08% dry weight
59. Artemisia annua
• Used in Traditional Chinese Medicine for more
than 2000 years
• First antimalarial application described in “The
Handbook of Prescriptions for Emergencies”
in the 4th century by a Chinese chemist
60. Artemsia annua
“take a handful of sweet
wormwood, soak it in a
sheng (liter) of water, and
squeeze out the juice and
drink it all”
• Li Shizhen, a great
Chinese herbalist
• Use of wormwood is also
recorded in the “Great
Compendium of Herbs”
in 1596
61. Artemisinin
• One of the most novel discoveries in recent
medicinal plant research
• 1967- extracts of Artemisia was found to have
antimalarial activity
• 1972- artemisinin isolated from the plant
• 1979- structure of artemisinin determined by
X-ray analysis
62. Key Features
• Rapid onset of actions
•
Effective against severe malaria
• Rapid clearance rate
•
Slow development of artemisinin resistance
•
Frequent recurrence of infections
64. Mechanism of Action
• Killing of malaria parasite is mediated by
production free radicals
– Artemisinin derivatives lacking endoperoxide
bridge are devoid of antimalarial activity
– Addition of free radical generating compounds
enhances antimalarial activity
– Antioxidants block antimalarial activity
65. ARTEMISININ
• Oral formulation - 250mg capsule
• Dosage
Adults and children: 25mg/Kg on the first day followed by 12.5mg/Kg
on the second and third day in combination with mefloquine
(15mg/Kg) in a single dose on the second day. In some areas, a
higher dose (25mg/Kg) of mefloquine may be required for a cure to
be obtained.
67. ARTEMETHER
•
Methyl ether of dihydroartemisinin
• Superior to intravenous quinine with respect to
survival and parasite clearance
• Available as tablets, capsules and as IM injectable form
• In India, available as 40mg capsules and 80mg/ml
ampoule
68. ARTEETHER
• Ethyl
ether of dihydroartemisinin
• Therapeutically equivalent to quinine in cerebral malaria
• Available as β arteether and α/β arteether
• β arteether developed by WHO and The Special
Programme for Research and Training in Tropical
Diseases (TDR)
• α/β arteether developed by CDRI
69. ARTEETHER
• A longer t1/2 beta and more lipophilic properties than
artemether favouring accumulation in brain tissue and thus
the treatment of cerebral malaria were regarded as
advantages over the other compounds.
• Available as 150mg per 2ml ampoule
70. ARTESUNATE
• Water soluble hemisuccinate derivative
• Used for oral, rectal, intravenous and intramuscular
administration.
• Available as tablets and as powder with separate vial
containing 5% sodium bicarbonate
• In India, available as 50mg tablets and 60mg/ml injection
• In China also available as 100mg suppository and in
Switzerland available as 200mg rectocap
71. • Artemisinin based combination therapy:
• WHO has recommended that acute uncomplicated Pl
Falciparum be treated only by combining one
Artemisinin with other effective erythrocytic
schizonticide
• ACT Regimens in use:
– Artesunate – Sulfadoxine, pyrimethamine:
• Adopted as first line in India under NMP
• Not effective against MDR strains which are non responsive to S/P
• ARTESUNATE 100 mg BD for 3 days with S-P, 3 tablets
– Artesunate Mefloquine:
–
Highly effective, well tolerated, first line of treatment
for uncomplicated falciparum malaria
• By combining artesunate further spread of mefloquine resistance
can be prevented
• Artesunate 100 mg BD for 3 days, + mefloquine 750 mg on second
day & 500 mg on third day
72. • Artemether & lumefantrine:
– Lumefantrine is highly effective , long acting oral
erythrocytic schizonticide related to mefloquine
– Same mechanism of action
– Highly lipophilic onset delayed , peak 6 hrs
– Slower acting than chloroquine, 99 % bound ,
metabolized by CYP3A4, T1/2= 2-3 days
– Available as fixed dose combination
– Adverse events: headache, dizziness, sleep disturbances,
abdominal pain, arthralgia, pruritis & rash
– 80 mg artemether BD with 480 mg lumefantrine BD for 3
days
• DHA – Piperaquine, Artesunate- pyronaridine
73. Resistance
• Currently no evidence for clinically relevant
artemisinin resistance
• Reasons for delay of artemisinin resistance:
– Short half-life
– Reduces transmission potential
– Used in combination with other antimalarial drugs
74. PHARMACOKINETICS
• Absorption of orally administered artemisinin or its derivatives seems to
be rapid but incomplete
• Substantial hydrolysis of artesunate (probable complete) and artemether
into dihydroartemisinin probably occurs even before absorption
• Elimination is mainly by hepatic metabolism
• Arteether has much slower elimination
• Artesunate, artemether, arteether and probably also artemisinin itself are
transformed into dihydro-artemisinin, which is subsequently
converted into inactive metabolites
75. ARTEMISININ DERIVATIVES
IN PREGNANCY
• Very limited data on the use of artemisinin group in pregnant women.
• Artemisinin and derivatives should be avoided during first
trimester of pregnancy, but in case of severe malaria the risks have to
be balanced against the benefits.
• No congenital malformations were detected in six children born to
mothers who received intramuscular artemisinin or artemether at 17 to
27 weeks of gestation.
Editor's Notes
I am giving the old names for these malarias in parentheses to give some historical perspective in case you see these terms again. I will also explain how these old terms relate to the pathogenesis of these respective diseases and the associated fever patterns.
Recrudescence:
A fresh outbreak of a disorder in apt after a period during which its sign and symptoms had died down and recovery seemed 2 be taking place
The life cycle of all species that infect humans is basically the same. There is an exogenous asexual phase in the mosquito called sporogony during which the parasite multiplies. There is also an endogenous asexual phase that takes place in the vertebrate or human host that is called schizogeny. This phase includes the parasite development that takes place in the red blood cell, called the erythrocytic cycle and the phase tthat takes place in the parencymal cells in the liver, called the exo-erythrocytic phase. The exo-erthrocytic phase is also called the tissue phase. The schizogeny that takes place here can occur without delay during the primary infection or can be delayed in the case of relapses of malaria. I will focus on the development of the parasite in the human host.