1. Malaria is a mosquito-borne infectious disease caused by Plasmodium parasites. It is transmitted via the bites of infected female Anopheles mosquitoes.
2. There are 5 Plasmodium species that cause malaria in humans: P. falciparum, P. vivax, P. malariae, P. ovale, and P. knowlesi. P. falciparum is the most dangerous species and a major cause of mortality.
3. Malaria is treated with antimalarial medications such as chloroquine, mefloquine, quinine, artemisinin derivatives, and primaquine. Treatment aims to cure the infection and reduce transmission.
Pharmacology of antimalarial drugs with treatment of malaria. mechanism of action, uses, adverse effects of antimalarial drugs like chloroquine, quinine, artemisinin compounds.
Acyclovir is in a class of antiviral medications called synthetic nucleoside analogues. It works by stopping the spread of the herpes virus in the body.
is used to decrease pain and speed the healing of sores or blisters in people who have varicella (chickenpox)), herpes zoster
Pharmacology of antimalarial drugs with treatment of malaria. mechanism of action, uses, adverse effects of antimalarial drugs like chloroquine, quinine, artemisinin compounds.
Acyclovir is in a class of antiviral medications called synthetic nucleoside analogues. It works by stopping the spread of the herpes virus in the body.
is used to decrease pain and speed the healing of sores or blisters in people who have varicella (chickenpox)), herpes zoster
Clinical situations when to use 2nd line agents
In case of resistance to first-line agents
In case of failure of clinical response to conventional therapy
In case of serious Rx-limiting adverse drug reactions
When expert guidance is available to deal with the toxic effects
Many of 2nd -line drugs , their dosage, emergence of resistance & long-term toxicity have not been fully established.
Ethionamide
Chemically related to isoniazid
Mechanism of action
Blocks synthesis of mycolic acids.
Anti-mycobacterial activity
M. tuberculosis & some other Spp of mycobacteria
It is heavy metal and bright silvery in appearance.It is liquid and is non poisonous if swallowed. However, it volatilizes at room temp and inhalation of vapors is toxic. It gets widely distributed throughout the body and causes toxic damage to brain, kidney, peripheral nervous system, mucous membranes etc
Clinical situations when to use 2nd line agents
In case of resistance to first-line agents
In case of failure of clinical response to conventional therapy
In case of serious Rx-limiting adverse drug reactions
When expert guidance is available to deal with the toxic effects
Many of 2nd -line drugs , their dosage, emergence of resistance & long-term toxicity have not been fully established.
Ethionamide
Chemically related to isoniazid
Mechanism of action
Blocks synthesis of mycolic acids.
Anti-mycobacterial activity
M. tuberculosis & some other Spp of mycobacteria
It is heavy metal and bright silvery in appearance.It is liquid and is non poisonous if swallowed. However, it volatilizes at room temp and inhalation of vapors is toxic. It gets widely distributed throughout the body and causes toxic damage to brain, kidney, peripheral nervous system, mucous membranes etc
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.
this lecture will help students from any medical field to learn more about the five species of Plasmodium Malaria, the clinical presentation of malaria, various strategies of malaria diagnosis, management of both complicated and non-complicated malaria, and management of malaria during pregnancy according to the recommendation of WHO.
https://www.youtube.com/watch?v=Tmk71zeydbw&t=12s
Presentation on malaria according to Pharmacotherapeutis-ll subject Pharm D 3rd year. It's helpful for Pharm D students, MBBS Students and other allied health care professionals.
In this slide we discussed everything about maria like definition, cause, risk factor, pathophysiology, sign and symptoms, diagnosis, treatment and prevention of malaria.
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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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
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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.
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.
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.
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
- 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
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
Title: Sense of Taste
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 structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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!
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Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
2. The oldest diseases known to mankind that has profound impact
on our history.
Malaria is a vector-borne infectious disease caused by single-celled
protozoan parasites of the genus Plasmodium.
Malaria is transmitted from person to person by the bite of
female mosquitoes.
2
3. INDIA:
NMEP started in 1958 caused malaria complete disappearance but
came back in 1970 and still now prevails a major disease
changed to NAMP then finally named it to NVBDCP
WHO :
2012 estimated 627 000 deaths (with an range of 473 000 to
789 000), mostly among African children.
Mortality rates ↓ 45% globally since 2000, by 49% in the African
Region.
3
4. Plasmodium falciparum : Falciparum malaria or Malignant Tertian
malaria
Plasmodium vivax : Benign Tertian, Tertian Malaria
Plasmodium malariae: Quartan malaria
Plasmodium ovale: Ovale tertian Malaria
Plasmodium knowlesi a species that causes malaria among
monkeys.
4
5. Transfusion of infected blood, congenitally, and by sharing
needles, but mainly by the bites of female Anopheles mosquitoes
Man develops disease after 10 to 14 days of being bitten by an
infective mosquito
Life cycle of malarian parasite:
1) Hepatic cycle/pre or exo Erythrocytic cycle
2) Erythrocytic cycle
3)Sexual forms
5
7. P. falciparum: Most dangerous invading
erythrocytes of any age, producing
endotoxin-like products, cause heavy
parasitemia, hypoglycemia, and shock with
multiorgan failure.
Delay in treatment may lead to death. If
treated early, the infection usually
responds within 48 hours.
7
8. P. vivax has low mortality rate - untreated adults relapses caused
by the reactivation of latent tissue forms.
(3) P. ovale affects periodicity and relapses similar to those of P.
vivax, but it is milder.
(4) P. malariae causes a generally indolent infection that is
common in localized areas of the tropics. Clinical attacks may
occur years or decades after infection.
8
12. 1.prevent & treat clinical attack of malaria (prophylactic)
2.completely eradicate the parasite from pt’s body (clinical
cure)
3.reduce the human reservoir of infection – cut down
transmission to mosquito (gametocidal)
12
16. Discovered in 1934 by Hans Andersag and coworker
Produced in U.S , introduced into clinical practice in 1947 for the
prophylactic treatment of malaria
Spectrum of activity
• Rapid acting Erythrocytic schizonticide against all species of
malaria
MOA :
• Accumulates in acidic vacuole of parasite it increases ph & inhibits
heme polymerisation.
• By formation CQ -heme complex it damages plasmodial membrane
complex inhibits formation of hemozoin
16
17. Resistance to chloroquine
PFCRT gene seen in chloroquine resistant p.falciparum it pumps out
the drug protecting heme
↓ ability of parasite to accumulate drug is the cause
NVBDCP : first line treatment against P.vivax & it slowly
developing resistance too within 1-2wks of treatment
P.vivax resistance to Chloroquine : Quinine with
Doxycycline/Clindamycin or ACT followed by Primaquine for
radical cure is treatment of choice
17
18. Absorbed orally, rapid absorption from IM, SC.
•Concentrated in various tissues like liver, spleen, kidney, lungs &
melanin.
•Distribution in brain & spinal cord with large apparent volume of
distribution -13000 liters in adult,
• loading dose – to attain therapeutic concentration in plasma & steady
state concentration
•t1/2 : 214 h, 60% plasma protein bound
•Metabolism- two active forms
18
19. • Desethylchloroquine & Bisdesethyl chloroquine by CYP-450 in
liver
• 50% eliminated by systemic and remaining eliminated renally
• On parentral administration entry is rapid & removal is slow
causes toxicity
• To prevent it slow IV & S.C/I.M is given in small divided doses
19
20. Therapeutic uses OF Chloroquine
1.Malaria prophylaxis :
300mg once a week for prevention
person visiting endemic area should receive one week before and four
week after
DDoossee ooff CChhlloorrooqquuiinnee
Uncomplicated vivax /ovale/ malaria:
600mg(10mg/kg)- 300mg(5mg/kg) after 8hrs,continue for next 2
days total 25mg/kg over 3 days + primaquine
15mg(0.25mg/kg)daily for 14 days
Chloroquine sensitive falciparum
Dose as above + primaquine 45mg(0.75mg/kg) single
dose(gametocidal)
20
21. Other uses of Chloroquine:
Extra intestinal amoebiasis/hepatic amaoebiasis :
500mg TDS for 2 Days/ 200mg BD for 2-3 wks
Giardiasis: Metronidazole is preferred
Clonorchis sinensis :250mg daily for 6wks
Rheumatoid arthritis:250mg 6-12 mths once a week
Lepra reaction –TYPE 2
SLE :250-500mg daily 1-4wks followed by maintenance
21
22. Common:
Nausea, vomiting, anorexia, itching, epigastric pain, difficult in
accommodation, headache are frequent & unpleasant
Toxic effects after prolonged use :
•Skin eruptions, headache, blurring of vision, diplopia, confusion &
convulsions.
•EKG changes : abnormal T waves, Wide QRS interval reversible
•Discoloration of nail beds, hairs & mucous membrane
•Haemolysis & blood dyscrasis
22
23. Adverse effects of chloroquine cont…
Retinopathy with reduced visual acuity - accumulation of drug in
melanin rich tissues (Bulls eye maculopathy) –reversible
Ototoxicity irreversible
Myopathy, cardiomyopathy, peripheral neuropathy, suicidal
tendency occurs
Periodic neurological and retinal check up should be done
23
24. >5g
Cardiovascular – hypotension due to vasodilatation, suppressed
myocardiac function, cardiac arrhythmias & cardiac arrest
CNS – mental confusion, convulsion & coma
24
25. with Mefloquine convulsion will occur
Digoxin level increases used along
With gold & phenylbutazone dermatitis will occur
Drug should be avoided in patients with ocular ,hepatic disease
,hemorrhage, hematological disease, peptic ulcer & neurological
disease
25
26. Epilepsy attacks will be precipitated in epileptic patients
Myasthenia gravis will worsen
Haemolysis occurs in G6PD deficient patients
Aggrevates exfoliative dermatitis & psoriasis
26
27. ↓ cost & safety in chloroquine resistance P.falciparum in certain
areas
Faster action & better tolerance than chloroquine
Prophylactically not used because of hepatotoxicity &
agranulocytosis in certain areas can be used in clinical attacks
Dosage :
25-35mg/kg for 3 days (10mg/kg is given immediately following
5mg/kg after 6hrs then 5mg/kg for next 2 days)
Mechanism, resistance, uses & ADR are similar to chloroquine
27
28. Chloroquine Congener with similar mechanism
High efficacy, erythrocytic schizonticide with prolonged action
& onset is slow
Activity:
Chloroquine sensitive & Chloroquine resistant P. falciparum
malaria
28
29. Mefloquine :
Tested during world war II, introduced in 1963
Its 4-quinoline methanol related chemically to quinine used in
chloroquine resistant P.falciparum malaria
Faster acting erythrocytic schizonticide slower than Chloroquine or
quinine.
Effective against Chloroquine sensitive organism also
Its suppressive prophylactic for multi resistant falciparum & other
types of malariae
29
30. Relapses - vivax , due to long t1/2 chances of resistant strains are
high
Cross resistance is seen with Quinine & Halofantrine
MOA of Mefloquine :
Similar to morphological changes in the intraerythrocytic
parasite of Chloroquine & Quinine
Act in cytosol of the parasite
Mechanism is unclear it can also inhibit heme polymerization
forming toxic complex with heme & damages membrane
30
31. Enhanced translation of Pfmdr1 gene
Pharmacokinetics of Mefloquine :
Well absorbed orally, enhanced in presence of food
High plasma protein bound 98% & concentrated in many organs
Metabolism in liver, 10 secreted in bile, undergoes enterohepatic
circulation, t1/2: 2-3wks
31
32. 1.Prophylaxis :
Reserved for prevalent Chloroquine resistant P.falciparum areas
Dose: 5mg/kg or 250mg/wk for adults 1-2wks before travel.
2.Treatment of malaria :
Reserve drug for multi drug resistance mainly Chloroquine resistant
vivax or falciparum
3.Current recommendation :
With Artesunate as ACT For uncomplicated falciparum malaria
32
33. 25mg/kg - 1.25gm single or 2 doses of 750 & 500mg 12hr apart
Children weight < 45kg :
First dose 15mg/kg → 10mg/kg after 12h after meals with plenty of
water since its irritant
Adverse drug reactions :
Common :
Dizziness, nausea, vomiting, diarrhoea ,abdominal pain, sinus
bradycardia & QT prolongation
33
34. Dose related effects :
Neuropsychiatric reactions present
Rare-hematological , hepatic & cutaneous toxicity
Safe during pregnancy but should be avoided in first trimester
Drug Interactions :
Halofantrine or Quinidine/Quinine or Chloroquine with this drug
causes QT lengthening & cardiac arrest reported.
Avoided : Epileptic patients, Neuropsychiatric disorders
34
35. Quinine
Isolated from bark of chinchona tree in 1820,due to military
importance many drugs were developed
Its levorotatory alkaloid
Spectrum Activity of Quinine :
Erythrocytic schizonticide for all species
Concentrated in food vacuole , less effective more toxic than
Chloroquine
Kills vivax & malariae gametes & also effective against
Chloroquine resistant & falciparum resistant strains
35
36. Terminates acute attack but does not completely eliminate the
parasite totally Doxycycline or Clindamycin are used
Its local irritant , anesthetic ,weak analgesic & antipyretic
MOA of Quinine
It forms heme – quinine complex ,
Inhibits polymerization of heme to hemozoin
Damages parasite membrane & kills it
Resistance:
Similar to Mefloquine
Have emerged in some parts of India
36
37. Rapidly absorbed orally, peaks -5hr
70% bound to alpha1 acid glycoprotein ↑ during malarial infection
Metabolized in liver by CYP3A4
Excreted in urine, crosses placental barrier
t1/2 9-18 hr, vol of distribution 100 L in adults
37
38. Uses of Quinine
1. Uncomplicated Chloroquine resistant malaria :
Its used orally alternative to S/P-ACT
NVBDCP : 7 day quinine 600mg 8hrly+ Doxycycline 100mg
daily/clindamycin 600mg 12hrly is second line treatment in
chloroquine resistance to falciparum & vivax malaria
38
39. Uses of quinine cont…
Complicated & severe malaria-cerebral malaria:
Dose : (7 days course)
Loading dose : 20mg/kg i.v over 4hrs diluted in 5% dextrose to
prevent hypoglycemia
Maintenance Dose: 10mg/kg over 4hr in adults or 2hr in children
every 8hr
Then switch over to oral 10mg/kg 8hrly
39
40. Parental Artemisinin are fast ,more effective, better tolerated and
now preferred over Quinine for severe malaria
2. Nocturnal muscle cramps & myotonia congenita –
Single tablet 300mg bed time
Adverse effects of Quinine
Higher doses : Affects hearing & vision Cardio depressant , anti
arrhythmic & hypotensive actions similar to Quinidine
On rapid i.v it causes hypoglycemia
40
41. Toxicity : 8-10g taken in single dose may be fatal
Cinchonism :reversible
Ringing in ears, nausea, vomiting, headache, mental confusion,
vertigo, difficulty in hearing & visual disturbance, diarrhoea
,flushing & marked perspiration
Poisoning higher doses:
QT prolongation during i.v
some develop idiosyncratic/hypersensitive reactions
41
42. Occasionally:
Haemolysis in pregnant women – falciparum malaria causing
hemoglobin urea & kidney damage
Caution : pregnant women only life threatening infection it
can be used
42
43. Slow acting erythrocytic schizontocide
Inhibits preerythrocytic stage of P.fal. gametocytes prevents
its development
It gets converted to active form cycloguanil, which inhibits
plasmodial DHFRase
MOA :
Inhibits DHFRase-thymidylate synthetase
43
44. partial cross resistance with pyrimethamine,
resistance develops due to mutation of DHFRase –thymidylate
Pharmacokinetics
Slow absorption
Except erythrocytes no accumulation in tissue
Peak plasma concentration : 5hr, t1/2:16-20h,
Noncumulative, well tolerated
Racial variations seen
Excreted : urine
44
45. Prophylaxis : ( P.falciparum & vivax )
Dose:
> 200mg daily in adults & children 4weeks after leaving endemic
area
Currently its either prophylaxis nor for clinical attack
Causal prophylaxis:
400mg proguanil + Atovaquine 1g for 3 days in multidrug
resistance
suppressive prophylactic :
With chloroquine in moderately CQ resistant P.falciparum areas.
45
46. Mild abdominal symptoms,
Occasional stomatitis, haematuria, rashes & transient loss of hair
Pyrimethamine
It direct inhibitor of DHFRase
Its slow acting blood schizonticide & More potent than Proguanil
Used with Sulfonamide or Dapsone to prevent resistance ,it may
be due to mutation in DHFRase .
resistance with falciparum is common than vivax
46
47. Pharmacokinetics:
Slow & good absorption
Attains good concentration in organs
Metabolized & excreted in urine
t1/2: 4 days,prophylactically stays in blood – 2wks
Uses:
Suppressive treatment chloroquine resistant falciparum
Toxoplasmosis -high doses given
47
48. Adverse drug reactions of pyrimethamine:
Nausea, rashes ,megaloblastic anemia & granulocytopenia with
higher doses.
Sulfonamide – pyrimethamine
Supra additive synergism - sequential block
Faster acting against chloroquine resistant p.falciparum
Has long half life
In India - with artesunate for all falciparum cases
48
49. Fixed dose Combinations :
Pyrimethamine 25mg + sulfadoxine 500mg
Pyrimethamine 25mg + sulphamethopyrazine 500mg
Pyrimethamine 25mg +dapsone 100mg :
given in 2nd & 3rd trimester of pregnancy with folic acid
In resistance quinine given with these combination
49
50. ADR :
Exfoliative dermatitis, stevens johnson syndrome
Precautions
Avoided in pregnancy due to antifolate & teratogenic effects,
avoid in children
50
51. Primaquine
8 – Aminoquinoline
Radical cure : given with chloroquine
only agent active against dormant hepatic forms of vivax & ovale
Gametocidal action against all four species of plasmodium
Mechanism of action Primaquine:
Not clear, its converted & produces active oxygen interfere with
plasmodial mitochondrial function
Resistance induced among p.vivax
51
52. Pharmacokinetics of primaquine:
Well absorbed oral,
wide distribution
Half life 3-8h,peak :1-2hrs
Generates 3 active metabolite ,excreted in urine
Uses of primaquine
1.Radical cure
a)P.vivax & ovale :
Given in acute attack or throughout incubation period
prevents relapse
52
53. Prophylactically: before & after leaving the endemic area to eradicate
hepatic forms
Effective vector control is possible or used in areas of low
transmission
b) Falciparum malaria:
45mg with chloroquine or ACT used like gametocidal & cut down
transmission or where effective control is needed
53
54. Primaquine cont..
2. AIDS:
15mg/day with clindamycin 600mg TDS alternatively used
Adverse drug reaction of Primaquine
Therapeutic doses:
Haemolysis & methaemoglobinaemia commonly seen in G6PD
deficiency
Causes nausea, headache, epigastric pain &abdominal cramps on
empty stomach
Rarely : leucopenia, leucocytosis & agranulocytosis
54
55. Precaution - Primaquine
G6-PD deficiency checked & blood counts repeated if >30mg of
Primaquine given
AVOID
In patient with haemolysis ,Rheumatoid arthritis & SLE
55
56. Tafenoquine
Newer 8-aminoquinolone single dose for vivax hypnozoites
Some activity was seen against asexual erythrocytic stage of
P.vivax,P.falciparum & chloroquine resistant state
Tafenoquine pharmacokinetics:
With long half life 16-19 days, acts lasting upto a week
Causes haemolysis in G6PD deficient patient, anaemia,
haemolysis & methaemoglobinaemia reported
Its undergoing phase-3 trial in India with 3 day chloroquine to
prevent relapse in vivax ,likely to be single dose radical cure
56
57. Tetracyclines & Doxycyclins
Erythrocytic schizonts are inhibited by all malarial parasite
Tetracycline used in combination with quinine in treatment of
chloroquine resistant as well vivax malaria
Avoid in children & pregnant women
Dose: 250mg QID or Doxycycline 100mg OD equally effective
57
58. Doxycycline cont..
Doxycycline used in places where high resistance present
200mg Doxycycline combined with artesunate to treat
mefloquine/chloroquine/s-p resistant malaria
100mg/day of Doxycycline used 2nd line prophylactic for short
travels to chloroquine resistant P.falciparum
Adverse effects:
Photosensitivity & suprainfection
58
59. Clindamycin:
Slow erythrocytic schizontocide, bacteriostatic
With Quinine used in treatment of resistant P.Falciparum
Its used where tetracyclines can not be used in pregnancy &
children less than 8 years old
59
60. Derived from plant Artemisia annua – (Chinese traditional
medicines)
Its sesquiterpine lactone endoperoxide, poorly soluble in oil &
water-used orally/rectally
Other compounds :
Dihydroartemisinin (oral)
Artemether(oral or i.m) & artesunate(oral/rectal/i.v/i.m)
Arteether –(i.m) produced in India in 1990
60
61. Arterolone - (oral) synthetic compound are developed
Spectrum Actions:
Rapidly acting erythrocytic schizonticides clears parasite in
<48hrs
Safe & 10-100 times potent compared to other antimalarials
Active against P.falciparum resistant to all other anti malarial
drugs as well sensitive strains
61
62. Artemisinin comp cont…
They are lethal to early gamete stage by reducing number of
gametes
MOA:
Endoperoxide moiety produces carbon centered radicals by
intramolecular rearrangement which modify & damages malarial
proteins
High reacted free radicals inhibit plasmodial sarcoplasmic
endoplasmic calcium ATPase –(pf ATP6)
Resistance ↓s response & combination of drug with different
mechanism & longer acting drugs given with these drugs in 3
days course will solve the problem
62
63. Artemisinin comp cont…
Pharmacokinetics
ORAL absorption of Artesunate -rapid peak of <60min, causes
auto induction by CYP2B6 & CYP3A4
Artemether absorption is delayed 2-4h, to increase absorption taken
with food,CYP3A4 metabolism extends ½ life to 3-10h
Both these drugs get converted to dihydroartemisinin
presystemically
63
64. Artemisinin comp cont…
Half life is 1-2h
Artemisinin and dihydroartemisinin extensively metabolised little
amount excreted in urine
Arteether long half life 24h can be used alone in 3days with very
low recrudescence
Dose:12mg of total oral dose for both children & adults in which
4mg/kg given on first day followed by 2mg/kg for 4 days(5
daystreatment)
64
65. Artemisinin comp cont…
Parenteral:
Artesunate-120mg i.v/i.m on first day followed by 60gm for next 4
days by same route
Artemether: 2mg/kg for 5 days
Arteether: for complicated malaria in adults i.m 150mg daily is
preferred since it has long t1/2 24h its used in 3 day course but
WHO recommends 5 day Course
Uses
For uncomplicated falciparum malaria,Chloroquine resistant &
sensitive strains:FDC of ACT used
65
66. in vivax where Chloroquine is resistant & Quinine +
Clindamycin cannot be used Artemisinin (ACT) is used
Single dose Primaquine used to kill circulating gametes after
ACT therapy
Severe complicated malaria:
Parentral artemisinin high effective &lower mortality
Quinine is used alternative when artemisinin cannot be used
During pregnancy quinine i.v given during 1st trimester of
pregnancy since safety of artemisinin compounds not yet
proved
66
67. Adverse effects:
Mild :nausea, vomiting, abdominal pain, itching &drug fever
Headache, tinnitus, dizziness, bleeding, dark urine, S-T segment
changes, Q-T prolongation, first degree A-V block, transient
reticulopenia & leucopenia are rare
Halofantrine (phenanthrene methanol)
Not preferred due to erratic bioavailability & cardiotoxicity &
extensive cross resistance with MEFLOQUINE
It was used in multidrug resistant strain of both falciparum &
vivax,it’s a blood schizonticide
67
68. Lumefantrine
Belongs to the arylaminoalcohol
has a similar mechanism of action it alters protein & nucleic
acid synthesis.
racemic fluorine derivative developed in China.
It is only available in an oral preparation coformulated with
artemether.
This ACT is highly effective against multidrug resistant P.
falciparum.
68
69. Lumefantrine cont…
orally active, long acting, highly effective blood schizonticide
Pharmacokinetics
Its lipophilic ,absorption starts after 2hrs peaks 6-8h
99%plasma protein bound
Metabolized by CYP3A4
½ Life 4-6 days
Taken with fatty diet to achieves adequate blood levels
Dose:
480mg BD - 3days,adult & chidren >35kg 4tab given with
artemether 80mg BD
Children 26-35 kg-3tab,16-25kg-2tab,5-15kg-1tab
69
70. Lumefantrine cont…
Uses:
In combination with artemether 20mg+lumefantrine 120mg in
one tab used as FDC
Both drugs prevent resistance
Decreases gametocyte number & prevents recrudescence
It achieves 99% cure rates
Adverse effects
Minor effects:
Gastrointestinal disturbances, headache, dizziness rashes &
pruritis
Little Q-T prolongation seen
Avoided in pregnant & lactating women
70
71. Pyronaridine
Newer drug from Mepacrine developed in china
Mechanism similar to chloroquine
High effective erythrocytic schizonticide,effective against
chloroquine sensitive & resistant vivax & falciparum malaria
Slow onset & long duration of action, concentrated in RBC
Water soluble, t1/2 : 7days
Orally & parenterally used , well tolerated
At high dose used analgesic/anti pyretic
71
72. Its used FDC with Artesunate in multi drug resistant falciparum
& vivax
Clinical trial proves >95% success rate in India
This ACT not approved for use in India
Adverse effects:
Abdominal pain, vomiting, headache, dizziness , loss of appetite,
palpitation
Dose:
Artesunate 100-200mg(2-4mg/kg)+pyronaridine 300-600mg(6-
12mg/kg)/day-3days
72
73. Atovaquone:
Hydroxy naphthoquinone antiparasitic drug active against all
Plasmodium species.
Rapid acting erythrocytic schizontocide & inhibits pre-erythrocytic
stage of falciparum.
Also active against pneumocystis jiroveci & Toxoplasma gondii
combined with proguanil Where its resistant, reduces relapse &
which is synergistic.
Collapses mitochondrial membrane interferes with cytochrome
electron transport.
73
74. Dosage
250 mg of atovaquone and 100 mg of proguanil hydrochloride for
adults. QID with food
Tablets containing 62.5 mg of atovaquone and 25 mg of
proguanil hydrochloride for paediatric use.
Given 3 days for uncomplicated chloroquine resistant falciparum
& vivax used in some countries but not in India
Uses:
Mild –mod malaria chloroquine & multi drug resistant
Can be used prophylactically by non immune travellers visiting
endemic areas,
74
75. In oppurtunistic infections, pneumonia, Toxoplasmosis & Babesiosis
Pharmacokinetics
poorly absorbed following oral administration can be improved by
taking the drug with fatty foods.
99% bound to plasma proteins and has plasma half-life of around
66–70 h due to enterohepatic recycling.
It is excreted in the faeces as unchanged drug
75
76. Adverse effects
Skin rashes, headache, fever, insomnia, nausea, diarrhoea,
vomiting, raised liver enzymes, hyponatraemia
Rarely: haematological disturbances.
Drug interactions
↓ plasma concentrations with Tetracycline and Acyclovir,
antidiarrhoeal drugs, Benzodiazepines, cephalosporins, laxatives,
Opioids and Paracetamol.
Atovaquone ↓ the metabolism of zidovudine and cotrimoxazole.
it displace other highly protein-bound drugs from plasma-protein
binding sites.
76
77. Antimalarial drugs alone – Resistance & fail to prevent malaria
WHO :Acute uncomplicated resistant P.F malaria should be treated
only by combining one of the artemisinin compounds with another
effective erythrocyte schizontocide.
Advantages of ACT over other antimalarials:
Rapid clinical & parasitological cure.
High cure rates, low relapse rate.
No resistance.
Good tolerability.
77
78. ACT regimens for uncomplicated falciparum malaria.
1.Artesunate – mefloquine (AS/MQ)
Artesunate 100 mg BD (4 mg / kg / day) 3 days + Mefloquine
750 mg (15 mg / kg) on 2 nd day and 500 mg (10 mg / kg) on 3
rd day (total 25 mg / kg).
2.Artimether – lumefantrine (1:6)
Artemether (80 mg BD) + lumefantrine (480 mg BD) 3 DAYS
78
79. Adult and child >35 kg :4 tab BD;
child 25 – 35 kg : 3 Tabs bid;
15 – 25 kg :2 tab BD;
5 – 15 kg 1 tab BD, All for 3 days
Act reg cont…….
3.Artesunate – sulfadoxine + pyrimethamine
Artesunate 100 mg BD (4 mg / kg / day ) 3 days +
sulfadoxine 1500 mg (25 mg / kg) and
pyrimethamine 75 mg (1.25 mg / kg) single dose
79
80. 4.Arterolane – Piperaquine.
Arterolane (as maleate)150mg+ Piperaquine750mg daily -3days
One capsule OD for 3 days
5. Dihydroartemisinin- Piperaquine(DHA/PPQ 1:8)
DHA120mg(2mg/kg)+piperaquine960mg(16mg/kg)daily for 3
days
6. Artesunate – Amodiaquine (AS/AQ)
Artesunate 200mg(4mg/kg)+Amodiaquine(10mg/kg)per day-3
days
80
81. ACT regimen cont…
Artesunate 25mg/50mg/100mg+Amodiaquine
67.5mg/135mg/270mg FDC approved in India
7.Artesunate -Pyronaridine(1:3)
Artesunate 100-200mg (2-4mg/kg) + pyronaridine 300-600mg(6-
12mg/kg)per day- 3 days.
TREATMENT OF UNCOMPLICATED MALARIA
a) Vivax (ovale,malariae) :
1. Chloroquine 600mg (10mg/kg base) followed by
300mg(5mg/kg)after 8hrs for next 2 days(total 25mg/kg over 3
days) + Primaquine 15mg(0.25mg/kg)daily -14days
81
82. ACT regimen cont…
In occasional case of chloroquine resistance:
Quinine 600mg(10mg/kg)8hrly – 7days + Doxycycline 100mg daily
-7 days
or
+ Clindamycin 600mg 12hrly -7days
+Primaquine (as above)
(or)
ACT based combination + primaquine (as above)
B) Chloroquine - sensitive falciparum malaria
Chloroquine(as above) + primaquine 45mg(0.75mg/kg)single dose
(gametocidal)
82
83. 1. Artesunate 100mg BD (4mg/kg/day) – 3 days + Sulfadoxine
1500mg(25mg/kg)+ Pyrimethamine 75mg (1.25mg/kg) single
dose
Or
2. Artesunate 100mg BD(4mg/kg/day)- 3 days + Mefloquine
750mg(15mg/kg) on 2nd day & 500mg(10mg/kg) on 3rd day
or
3. Artemether 80mg+ lumefantrine 480mg BD – 3 days(Child
25-35kg BW ¾ Dose;15-25 kg BW ½ dose;5-15 kg BW ¼ dose
83
84. (or)
4.Arterolane (as maleate) 150mg + Piperaquine 750mg OD – 3
days
Or
5. Quinine 600mg(10mg/kg)8hrly – 7 days + Doxycycline
100mg daily -7 days
Or
Clindamycin 600mg 12hrly -7 days
84
85. Artesunate 2.4 mg/kg IV or i.m as a first dose followed by
2.4mg/kg after 12 & 24h then OD -7days switch over to 3 day Oral
ACT in between whenever patient can take & tolerate oral
medication
(or)
2)Artemether 3.2 mg/kg IM on first day followed by 1.6 mg/kg
daily for seven days switchover to 3 days oral ACT inbetween
whenever patient can take & tolerate oral medication
(Or)
85
86. Arteether 3.2mg/kg i.M on the first day followed by 1.6mg/kg
daily for next 4 days switchover to 3 days oral act in between
whenever patient can take & tolerate oral medication
Or
Quinine di hcl 20mg/kg loading dose diluted in 10ml/kg
5%dextrose/dextrose –saline infused i.V -4hrs,followed
10mg/kg(maintenance dose)i.V. Infusion over 4hrs(in
adults)or 2h(in children)every 8hrs until patient can swallow
switchover to oral quinine 10mg/kg 8hrly to complete 7 day
course
86
87. Drugs Used in pregnancy:
Proguanil with folic acid 5mg/day
Chloroquine in usual doses
Quinine in low dose –chloroquine resistant malaria
high dose- induce labour
Pyrimethamine + Dapsone -2nd & 3rd trimester with
folinic acid
Chloroquine, quinine & proguanil safe but
pyrimethamine with folinic acid can be used
87
88. NEWER DRUGS
4(1H)-quinolone-3-diarylethers :
selective potent inhibitors of the parasite's mitochondrial
cytochrome bc1 complex.
highly active against the human malaria parasites Plasmodium
falciparum and Plasmodium vivax.
They target both the liver and blood stages of the parasite as well
as gametocytes, the zygote, the ookinete, and the oocyst.
88
89. preclinical candidate, ELQ-300 has good oral bioavailability at
efficacious doses in mice
Metabolically stable
highly active in blocking transmission in rodent models of malaria.
Given its predicted low dose in patients and its predicted long half-life,
ELQ-300 has potential as a new drug for the treatment,
prevention, and, ultimately, eradication of human malaria.
89
90. A Phase III trial began in May 2009 and has completed
enrolment in 2011
are expected to become available to WHO in 2014-2015.
evaluated as an addition to, not a replacement for, existing
preventive, diagnostic and treatment measures.
The need for long-lasting insecticidal nets, rapid diagnostic tests
and artemisinin-based combination therapies will continue
90
91. References :
- Pharmacological basis of Therapeutics – Goodman & Gilman
12th Edition
- Principles of pharmacology – HL Sharma & KK sharma 2nd
edition
- Text book of pharmacology – K. D. Tripathi.7th Edition
- Pharmacology & Therapeutics - R.S.Satoskar -Twentieth second
Edition.
91