This document discusses antimalarial drugs. It begins by introducing malaria and its causative parasites. It then describes the life cycle of the malaria parasite, involving stages in both the human host and mosquito vector. The objectives and classifications of antimalarial drugs are outlined. Key drugs like chloroquine, primaquine, quinine, and artemisinins are then described in detail, including their mechanisms of action, uses, and adverse effects. Combination therapies using artemisinins are emphasized as the most effective strategy to prevent drug resistance from emerging.
These are antibiotics having a macrocyclic
lactone ring with attached sugars. Erythromycin
is the first member discovered in the 1950s,
Roxithromycin, Clarithromycin and Azithromycin
are the later additions. Antimicrobial spectrum is narrow,
includes mostly gram-positive and a few gramnegative
bacteria, and overlaps considerably with
that of penicillin G. Erythromycin is highly active
against Str. pyogenes and Str. pneumoniae, N.
gonorrhoeae, Clostridia, C. diphtheriae and
Listeria, but penicillin-resistant Staphylococci
and Streptococci are now resistant to erythromycin
also.
All cocci readily develop resistance
to erythromycin, mostly by acquiring the
capacity to pump it out. Resistant Enterobacteriaceae
have been found to produce an erythromycin
esterase. Alteration in the ribosomal binding
site for erythromycin by a plasmid encoded
methylase enzyme is an important mechanism of
resistance in gram-positive bacteria. All the above
types of resistance are plasmid mediated. Change
in the 50S ribosome by chromosomal mutation
reducing macrolide binding a
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.
Anthelmintics | B.Pharm 3rd year 2nd Sem | Medicinal Chemistry-III | History, Classification, Structures & Synthesis of anthelmintics, Synthesis of Diethylcarbamazine citrate, Synthesis of Mebendazole
These are antibiotics having a macrocyclic
lactone ring with attached sugars. Erythromycin
is the first member discovered in the 1950s,
Roxithromycin, Clarithromycin and Azithromycin
are the later additions. Antimicrobial spectrum is narrow,
includes mostly gram-positive and a few gramnegative
bacteria, and overlaps considerably with
that of penicillin G. Erythromycin is highly active
against Str. pyogenes and Str. pneumoniae, N.
gonorrhoeae, Clostridia, C. diphtheriae and
Listeria, but penicillin-resistant Staphylococci
and Streptococci are now resistant to erythromycin
also.
All cocci readily develop resistance
to erythromycin, mostly by acquiring the
capacity to pump it out. Resistant Enterobacteriaceae
have been found to produce an erythromycin
esterase. Alteration in the ribosomal binding
site for erythromycin by a plasmid encoded
methylase enzyme is an important mechanism of
resistance in gram-positive bacteria. All the above
types of resistance are plasmid mediated. Change
in the 50S ribosome by chromosomal mutation
reducing macrolide binding a
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.
Anthelmintics | B.Pharm 3rd year 2nd Sem | Medicinal Chemistry-III | History, Classification, Structures & Synthesis of anthelmintics, Synthesis of Diethylcarbamazine citrate, Synthesis of Mebendazole
sulfonamides are the antimicrobial agents.It's act by folic acid synthesis inhibitors.It is PABA analogue competitive antagonist. first synthesised drug is prontosil.
In this slide contents history, mechanism of action, SAR, classification of drugs, some structure of important drugs, choice of drugs in different purpose, side effect, adverse effect.
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
Pharmacology of antimalarial drugs with treatment of malaria. mechanism of action, uses, adverse effects of antimalarial drugs like chloroquine, quinine, artemisinin compounds.
Sulphonamides Pharmacology For Pharmacy studentsMalay Pandya
This is the PowerPoint presentation of the Antimicrobial drug - SULPHOANMIDE.
Sulphonamide is the first antimicrobial agent
It Can be employed for suppressive therapy of chronic urinary tract infection, streptococcal pharyngitis and gum infection.
Combined with trimethoprim (cotrimoxazole) sulfamethoxazole is used for many bacterial infections.
This will be useful to all Pharmacy Student ...
Anti Malarial Drugs of medicinal chemistryPranjal Saxena
This slide contain information about Anti Malarial Drugs and their description with the synthesis of Chloroquine and pamaquine
SAR of quinolines
Miscellaneous agents of anti Malarial
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
sulfonamides are the antimicrobial agents.It's act by folic acid synthesis inhibitors.It is PABA analogue competitive antagonist. first synthesised drug is prontosil.
In this slide contents history, mechanism of action, SAR, classification of drugs, some structure of important drugs, choice of drugs in different purpose, side effect, adverse effect.
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
Pharmacology of antimalarial drugs with treatment of malaria. mechanism of action, uses, adverse effects of antimalarial drugs like chloroquine, quinine, artemisinin compounds.
Sulphonamides Pharmacology For Pharmacy studentsMalay Pandya
This is the PowerPoint presentation of the Antimicrobial drug - SULPHOANMIDE.
Sulphonamide is the first antimicrobial agent
It Can be employed for suppressive therapy of chronic urinary tract infection, streptococcal pharyngitis and gum infection.
Combined with trimethoprim (cotrimoxazole) sulfamethoxazole is used for many bacterial infections.
This will be useful to all Pharmacy Student ...
Anti Malarial Drugs of medicinal chemistryPranjal Saxena
This slide contain information about Anti Malarial Drugs and their description with the synthesis of Chloroquine and pamaquine
SAR of quinolines
Miscellaneous agents of anti Malarial
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.
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Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
3. Introduction
• Malaria is major health problem in India & tropics.
• Malaria caused by 4 species of plasmodium parasite :-
-> Plasmodium vivax (tertian)
-> Plasmodium ovale (tertian)
-> Plasmodium falciparum (tertian)(severe malaria)
-> Plasmodium malariae (quartan)
Sir Ronald Ross
4.
5. Life cycle of the malarial parasite
Sporogeny
(sexual)
Schizogony
(asexual)
Man : Intermediate host
Mosquito : Definitive host
6. Life cycle (brief)
• Causative organism - Plasmodium vivax
• Vector/definitive host - female anopheles mosquito,
intermediate host - man.
• Life cycle occurs partly inside the mosquito (sexual sporogony )
& man (asexual schizogony)
• Mosquito bites man, it transmits sporozoites to his blood.
• Sporozoites travel to liver where it reproduces asexually (tissue
schizogony) producing merozoites. Merozoites infect new RBCs
and initiate asexual multiplication in RBC (blood schizogony)
leading to production of more merozoites. The RBC bursts and
starts the infective cycle. Some merozoites develop into male
and female gametes. Some merozoites remain dormant in the
liver (hypnozoites) which can cause a relapse of infection later
(p. vivax & ovale)
7. • When mosquito bites infected person, gametes are taken
up with the blood.
• The gametocytes mature in the mosquito gut and fuse to
form an ookinate which develops into sporozoites.(Sexual
sporogony)
• Sporozoites migrate to salivary glands and infect a new
host when mosquito bites the person.
Recurrent malaria : Can be relapse(hypnozoites) or
recrudescence (parasites surviving in blood due to
incomplete treatment)
9. Objectives of use of antimalarial
drugs/THERAPEUTIC CLASSIFICATION
1. To prevent clinical attack of malaria (prophylactic)
- Causal prophylactics attack the pre-erythrocytic phase in
liver which is the cause of malarial infection.(TISSUE
SCHIZONTOCIDE) E.g. Primaquine, proguanil
- Suppressive prophylactics suppress the erythrocytic
phase & prevents attack of malarial fever. E.g.
Chloroquine, proguanil, mefloquine
Prophylaxis adviced in:-
- Non immune travellers to endemic areas
- Non immune persons living in endemic areas for fixed
time (e.g.army units)
- Infants, children, pregnant women in endemic areas
10. 2. To treat clinical attack of malaria (clinical curatives)
- Attack the erythrocyte schizonts & terminates episode
of malarial fever.(ERYTHROCYTIC SCHIZONTOCIDE)
There are Fast acting high efficacy ones
(E.g.Chloroquine, quinine, artemisinin ) & Slow acting
low efficacy drugs (E.g.Proguanil, pyrimethamine,
sulfonamides)
3. To completeley eradicate the parasite from the body
(radical cure)
- Indicated only in P.vivax & P. ovale because they
produce relapsing malaria due to persistence of
hypnozoites. E.g. Primaquine
11. 4. Gametocidal drugs
- Helps in decreasing the transmission of malaria from
infected person to another.
- No use to the infected person
Eg. Primaquine, proguanil, pyrimethamine.
15. Chloroquine
- Rapid action Erythrocytic schizontocide of all species
of Plasmodium.
- Controls clinical attacks in 1-2 days.
16. Mechanism of action
• Plasmodia digest hemoglobin to heme & globin in their
acidic vacuole. Globin is used by plasmodia for
nutrition. Heme being toxic to plasmodium is
converted to non toxic pigment hemazoin by heme
polymerase enzyme of the parasite.
• Chloroquine concentrates inside the acidic vacuole of
parasite & raises the pH of vacuole. Interferes with
conversion of toxic heme to non toxic hemazoin by
inhibiting heme polymerase.
CQ-Heme complex formed damages plasmodial
membranes.
17. Hemoglobin Globin utilized by
malarial parasite
Heme (highly toxic for malaria parasite)
Chloroquine
Quinine, (+) Heme Polymerase
mefloquine (-)
Hemozoin (Not toxic to plasmodium)
Mechanism of action
18. Chloroquine resistance
• Chloroquine resistance is fast developing in
P.falciparum & is a major problem because severe
cases of malaria are caused by this species.
• Resistance develops due to efflux mechanism
20. Pharmacokinetics
• Good oral absorption.
• Concentrated in liver , spleen, kidney, lungs ,skin,
leucocytes
• Selective accumulation in retina: ocular toxicity
on prolonged use.
• Metabolized in liver, excreted in urine.
• T1/2 = 3-10 days. Due to tissue binding, small
amounts persist in body with terminal t1/2 of 1-2
months.
21. Adverse drug reactions
Occuring at low dose/ short duration use
– Nausea, vomiting, anorexia, epigastric pain
– uneasiness
– Uncontrollable itching
– Headache, difficulty in accommodation
Occuring at high doses/prolonged use
- Loss of vision(retinal damage)/, corneal deposits
leading to diminished vision
- Loss of hearing
- Mental disturbances
- Graying of hair
- Rashes, photoallergy
22. Contraindication
• Liver damage
• Severe GIT, neurological, retinal , hematological
diseases.
• Should not be co-administered with mefloquine,
amiodarone, antiarrhythmics.
• CAN BE GIVEN IN PREGNANCY
• 250 mg oral tablet of chloroquine phosphate consists of 150
mg base
23. Therapeutic uses
1. Malaria : Used for clinical cure against P. ovale,
P.malariae, P.ovale & some P. falciparum that are
still sensitive.
2. Giardiasis
3. Extraintestinal amoebiasis
4. Rheumatoid arthritis
5. Discoid Lupus Erythematosus
6. Lepra reaction
7. Infectious mononucleosis
8. Photogenic reactions
24. Amodiaquine
– Identical properties to chloroquine
– Even Chloroquine resistant strains may be
effective.
Piperaquine
Appears effective in resistant cases
25. Mefloquine (Quinoline methanol)
• Developed to deal with chloroquine resistant P.falciparum
• Rapidly acting Erythrocytic schizonticide of chloroquine
sensitive & resistant plasmodia (clinical curative).
Also effective suppressive prophylactic for multidrug
resistant P.falciparum.
• Mechanism of action similar to Chloroquine.
• Adverse effects : Nausea, vomiting, diarrhoea, QT
prolongation, neuropsychiatric reactions (ataxia, anxiety,
hallucinations)
• Contraindicated in psychiatric disorders, cardiac conduction
defects, 1st trimester of pregnancy.
26. Quinine
• L-isomer alkaloid isolated from cinchona bark.
(Quinidine is d-isomer used as antiarrhythmic(mainly) &
as antimalarial)
• Erythrocyte schizontocide against all plasmodium
(including CQ &MDR P.falciparum) but more toxic than
CQ.
Also kills gametes of P.vivax
• Mechanism of action: Similar to chloroquine
27. Adverse drug reactions
Cinchonism ( large single dose/higher therapeutic doses
for longer period)
• Tinnitus, nausea & vomiting
• Headache, mental confusion, vertigo, difficulty in hearing &
visual disturbances
• Diarrhoea , flushing & marked perspiration
• Still higher doses : exaggerated symptoms with delirium ,
fever, tachypnoea, respiratory depression , pulmonary
edema, hypoglycemia.
- Idiosyncrasy in some individuals: cinchonism develops at
therapeutic doses itself
- Occasional hemolysis in pregnant women & patients with P.
falciparumhemoglobinuria (black water fever)&kidney
damage
28. Uses
• Malaria:
– uncomplicated resistant falciparum malaria – oral
quinine given.
– Complicated & severe malaria including cerebral
malarial – IV quinine used
• Nocturnal muscle cramps
29. Proguanil
– Not a popular drug for acute attack (slow action)
Pyrimethamine
- Used only in combination with sulfonamides for
malariaa treatment.
30. Sulfadoxine-pyrimethamine
• Long acting sulfonamides (Sulfadoxine) are not effective
antimalarial but combination with Pyrimethamine
causes sequential blockade of folic acid synthesis in
plasmodia.
• Effective against erythrocytic stage of P.falciparum.
• Combination acts faster &prevents development of
resistance.
• Risk of hypersensitivity reactions due to sulfonamide
component.
31. Primaquine
• Most active against Liver hypnozoites (pre-erythrocytic
phase).
• Weak action against erythrocytic stage of vivax. No
action against erythrocytic stage of falciparum
• Has gametocidal action against all species.
34. Use
• Primary use is radical cure of relapsing malaria in P.
vivax . ( 15 mg daily for 14 days with dose of
chloroquine)
• Gametocidal in Falciparum malaria(45 mg of single
dose with chloroquine ) & cut down transmission of
malaria.
36. Antibiotics
• Slow but potent action on erythrocytic stage of all
malarial parasites including multidrug resistant ones.
• Always used in combination with quinine or S-P for
treatment of chloroquine resistant malaria.
37. Halofantrine & Lumefantrine
• Amino alcohols
• Used in chloroquine resistant malaria since 1980
• Erratic bioavailabilty, lethal cardiotoxicity & cross
resistance to mefloquine limited its use
• Now a days used only when no other alternative
available
39. Artemisinin
• Artemisinin is the active principle of the plant
artimisia annua .
• Sesquiterpine lactone derivative.
• Most potent and rapid acting against blood
schizonticides of P.falciparum resistant to all other
drugs.
• Due to short duration of action high
recrudescence rate .
42. Mechanism of action
• These compounds have endoperoxide bridge.
• Heme iron cleaves this endoperoxide bridge to form
highly reactive free radicals which damage parasite
membrane by covalently binding to membrane proteins
43. Artesunate
• Water soluble ester
• Can be given oral, IM,IV, rectal
Artemether
• Lipid soluble ester.
• Oral & IM
Arteether
• Ethyl ester
• Available for IM use.
Arterolane
• Used in combination therapy only
• Oral use
44. Adverse effects
• Mild adverse effects like nausea, vomiting, abdominal
pain, drug fever, itching (common)
• Tinnitus, dizziness, bleeding, dark urine, ECG changes ,
QT prolongation, leucopenia are rare.
46. Artemisinin based combination therapy (ACT)
• Artemisinin compunds are shorter acting drugs.
• Monotherapy needs to be extended beyond
disappearance of parasite to prevent recrudescence.
This can be prevented by combining artemisin
compounds with one long acting drug like mefloquine
etc.
47. Why combination therapy ?
• Rapid clinical & parasitological cure.
• High cure rates and low relapse rates.
• Absence of resistance.
• Good tolerability profile.
51. • Chloroquine phosphate 250 mg
– Contains 150 mg of base
– Give 4 tablets stat , 2 tablets after 8 hours and , 1
tablet BD for 2 days
• Tab primaquine 15 mg OD for 14 days in Plasmodium
vivax, ovale
• Primaqine 45 mg single dose for falciparum after
chloroquine (gametocidal)
Acute attack of chloroquine sensitive malaria:
53. • Pts who cannot take orally
– Inj Quinine Hcl 20 mg/kg in 500 ml dextrose saline
over 4 hrs then
– 10 mg/kg in dextrose saline over 2 hrs every 8 hrly
till patient is able to swallow
– Then quinine 600 mg TDS for 7 days &
tetracycline/ doxycycline
Or
– artemether / arteether injection
54. Treatment of severe and complicated
falciparum malaria
• Artesunate 2.4 mg/kg IV/IM, BD on day1 then 2.4
mg/kg daily for 7 days OR
• Artemether 3.2 mg/kg IM on day 1 then 1.6
mg/kg daily for 7 days OR
• Arteether 3.2 mg/kg IM on day1, followed by 1.6
mg/kg daily for next 4 days
55. OR
• Quinine: 20 mg quinine salt/kg on admission (i.v.
infusion in 5% dextrose/dextrose saline over a period
of 4 hours) followed by maintenance dose of 10
mg/kg body weight 8 hourly.
– When ever patient can swallow orally switch over
to oral quinine 10 mg/kg 8 hrly and complete 7
days course
Malaria is one of the most devastating parasitic infections all over the world all over the world 1-3 million deaths occur world wide and in india about 8 lac deaths per year due to malaria
Causative organism of malaria is Plasmodium vivax
Vector/definitive host is female anopheles mosquito & intermediate host is man.
Life cycle occurs partly inside the mosquito(sexual sporogony ) and man(asexual schizogony)
When a mosquito bites man, it transmits sporozoites to blood.
Sporozoites travel to liver where it reproduces aswxually (tissue schizogony) producing merozoites. Merozoites infect new RBCs and initiate asexual multiplication in RBC (blood schizogony) leading to production of more merozoites. The RBC bursts and starts the infective cycle. Some merozoites develop into male and female gametes. Some merozoites remain dormant in the liver (hypnozoites) which can cause a relapse of infection later (p. vivax & ovale)
When mosquito bites infected person, gametes are taken up with the blood. The gametocytes mature in the mosquito gut and fuse to form an ookinate which develops into sporozoites.(sexual sporogony)
Sporozoites migrate to salivary glands and infects a new host when mosquito bites the person.
Recurrent malaria
Can be relapse(hypnozoites) or recrudescence (parasites surviving in blood due to incomplete treatment)
Synthesized as a part of extensive cooperative programme of antimalarial research in US during world war2 . Proved most promising and was released for field trials .
It was discovered that the compound had been synthesized by germans as early as 1934 under name of resochin at bayer laboratories in germany but had been rejected due to toxicity in avian models
Chlorine atom attached to position 7 of quinoline ring confers most potent antimalarial activity.
Short chain derivative and piperaquine new compunds SAR : demonstrate activity against chloroquine resistant malaria
Hydroxychloroquine: N-ethyl substituent of chloroquine is hydroxylated same as chlorpquine. But preferred over chloroquine in treatment of rheumatoid arthritis and lupus erythematosus because in the high doses required it may cause less ocular toxicity.
Oxidative damage to the membranes , digestive proteases & other critical biomolecules of malarial parasite
Heme polymerase present inside lysosomes of the malarial parasite which convert toxic heme to non toxic hemozoin
Now chloroquine concentrates in the acidic lysosomes binds to liberated heme to form heme quinoline complex which interupts the heme polymerisation by inhibiting enzyme heme polymerase
Chloroquine also inhibits RNA & DNA synthesis at higher conc but these effects are unlikely to be involved in MOA
MECHANISM OF QUININE & MEFLOQUINE ARE SIMILAR
Partly metabolized by liver and slowly excreted in urine. The early plasma half life varies from 3-10 days, because of tighttissue binding small amounts persist in body with terminal half life of 1-2 months
Mefloquine resistance among plasmodium falciparum has become common in Thailand cambodia and myanmar, as it has not been used extensively in india mefloquine resistance is not a problem over here. But due to its long half life chances of selection of resistant strains are high; mefloquine resistant isolates have been reported from gujrat and andhra pradesh.
Resistance to mefloquine confers resistance to quinine and halofantrine
A large single dose or higher therapeutic
Myotonia congenita: heriditory myopathy characterized by tonic spasm of skeletal
Slow acting erythrocytic schizonticide which also inhibits the preerythrocytic stage of p.falciparum.
Resistance develops rapidly due to mutationsal changes in plasmodial DHFRase enzyme
Compliance is good
India 5 day therapy
Fixed dose combination of atovaquone available with proguanil atovaquone 250 mg + proguanil 100 mg 4 tablets daily single dose for 3 days in resistant malaria
Artimisia annua is used in chinese traditional medicine as quinghauso as
Elicit quicker defervescence and clearing of parasitemia in 48 hours
Artemisinin is poorly soluble in water and oil several derivatives have been produced of which 3 are marketed in India
Do not kill hypnozoites but have some action on gametocytes of falciparum
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.
Artemisinin is not very soluble either in water or oil.
This and its short elimination half life led to the search for the derivatives that had improved pharmacological properties as well as better antimalarial activity
Converted to dihydroartemisinin, which is a potent antimalarial compound
Available for oral and rectal use in several countries in Asia, especially in Vietnam
Dihydroartemisinin
Intraparasitic ferrous protoporphyrinIV catalyses breakdown of endoperoxide bridge
Chloroquine antagonizes the antimalarial activity
Iron chelators antagonize antiparasitic effect of artemisinin
Trade name : falcigo
Oral: artesunate & artemether , IM: ALL 3, IV & rectal artesunate
Duration of action 3 to 4 hrs
No serious adverse events
Artemisinin compounds rapidly kill more than > 95 % of the plasmodia and only leave small biomass of the parasites to be killed by long t1/2 drugs
Supportive measures:
ICU administration
Good nursing care, Tepid sponging, sodium bicarbonate
Hypoglycemia, anemia, BP , Increase ICT
GC, urea, mannitol not used now a days
; infusion rate should not exceed 5 mg/kg body weight per hour.
If parenteral quinine therapy needs to be continued beyond 48 hours, dose should be reduced to 7 mg/kg body weight 8 hourly.
If possible oral quinine should be replaced by 3 daY ACT TREATMENT