Malaria is a significant global public health problem, infecting over 200 million people annually and killing over 1 million. The disease disproportionately impacts sub-Saharan Africa, where a child dies every 30 seconds from malaria. There are multiple antimalarial drugs that target different stages of the parasite's complex lifecycle in humans and mosquitos. Treatment depends on the Plasmodium species, infection severity, resistance patterns, and other factors. Rapidly-acting artemisinin derivatives are now commonly used in combination therapies for drug-resistant infections.
Pharmacology of antimalarial drugs with treatment of malaria. mechanism of action, uses, adverse effects of antimalarial drugs like chloroquine, quinine, artemisinin compounds.
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.
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
The presentation gives an in-depth review of the Anti-fungal drugs used to treat various acute and chronic fungal infections along with their uses and MOA.
Anthelmintics | B.Pharm 3rd year 2nd Sem | Medicinal Chemistry-III | History, Classification, Structures & Synthesis of anthelmintics, Synthesis of Diethylcarbamazine citrate, Synthesis of Mebendazole
The presentation gives an in-depth review of the Anti-fungal drugs used to treat various acute and chronic fungal infections along with their uses and MOA.
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.
An antifungal medication is a pharmaceutical fungicide used to treat and prevent mycoses such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor's prescription, but a few are available OTC (over-the-counter).
Antifungals work by exploiting differences between mammalian and fungal cells to kill the fungal organism with fewer adverse effects to the host. Unlike bacteria, both fungi and humans are eukaryotes. Thus, fungal and human cells are similar at the biological level. This makes it more difficult to discover drugs that target fungi without affecting human cells. As a consequence, many antifungal drugs cause side-effects. Some of these side-effects can be life-threatening if the drugs are not used properly.
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.
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
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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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.
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.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
2. Global Situation Of Malaria
• According to WHO,
• A significant public health problem
• More than 90 countries inhabited by some
2400 million people (about 40% of the world's
population).
• The disease causes an estimated 300 million
acute illnesses each year and at least 1 million
deaths.
• More than 90% of these occur in sub-Saharan
Africa, and it is estimated that the disease kills
an African child every 30 seconds.
3. Situation Of Malaria In Bangladesh
• The prevalence of malaria in the 13 endemic
districts is 3.97%.
• In five south-eastern districts weighted
average prevalence rate is 6.00% and in the
eight north-eastern districts weighted
average prevalence rate is 0.40%.
• The highest prevalence is observed in
Khagrachari district. The majority of the
cases (90.18%) are P. falciparum infections.
• Malaria morbidity rates in five south-eastern
districts is 2.94%.
6. • Infection usually is transmitted by the bite of
infected female Anopheline mosquitoes.
• Sporozoites from the mosquito salivary glands
rapidly enter the circulation after a bite and
localize in hepatocytes, where they transform,
multiply, and develop into tissue schizonts
• This primary asymptomatic tissue
(preerythrocytic or exoerythrocytic) stage of
infection lasts for 5 to 15 days, depending on
the Plasmodium species.
• Tissue schizonts then rupture, each releasing
thousands of merozoites that enter the
circulation, invade erythrocytes, and initiate the
erythrocytic cycle.
7. • Once the tissue schizonts burst in P.
falciparum and P. malariae infections, no
forms of the parasite remain in the liver.
treatment that eliminates erythrocytic
parasites will cure these infections.
• However, in P. vivax and P. ovale infections,
tissue parasites (hypnozoites) persist that can
produce relapses of erythrocytic infection
months to years after the primary attack.
Eradication of both erythrocytic and hepatic
parasites is required to cure these infections.
8. • In erythrocytes, most parasites undergo
asexual development & finally to mature
schizonts.
• Schizont-containing erythrocytes rupture,
each releasing 6 to 32 merozoites depending
on the Plasmodium species. Only erythrocytic
parasites cause clinical illness. It is this
process that produces febrile clinical attacks.
• The merozoites invade more erythrocytes to
continue the cycle
9. • Sexual stage gametocytes also develop in
erythrocytes before being taken up by
mosquitoes, where they develop into
infective sporozoites. which invade the
salivary gland of the mosquito. The insect
then can infect a human host by taking a
blood meal.
11. Symptomatic malaria is typified by high spiking fevers that
may have a periodic pattern chills, headache, myalgias,
malaise, and gastrointestinal symptoms. In addition, each
Plasmodium species causes a distinct illness:
(1) P. falciparum is the most dangerous. By invading
erythrocytes of any age, sequestering in the vasculature, and
producing endotoxin-like products, this species can cause an
overwhelming parasitemia, hypoglycemia, and shock with
multiorgan failure.
Delay in treatment may lead to death. If treated early, the
infection usually responds within 48 hours. If treatment is
inadequate, recrudescence of infection may result.
Cerebral malaria:
Organism residesin the RBC, red cell become sticky,adhere to
another RBC,Rouleux formation –cerebralcapillary blocks-
ischemia, convulsion.
12. (2) P. vivax & P. ovale infection has a low
mortality rate in untreated adults and is
characterized by relapses caused by the
reactivation of latent tissue forms.
(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.
13. Classification
• Antimalarials can be categorized by the stage
of the parasite that they affect and by
their intended use for either prophylaxis
or treatment.
• The various stages of the malaria life cycle that
occur in humans differ from one another not
only in their morphology and metabolism but
also in their drug sensitivity. For this reason, the
classification of antimalarial drugs is best done
in the context of the life cycle.
14. • Prophylaxis:
Since none of the drugs kills sporozoites, it is not
truly possible to prevent infection but only to
prevent the development of symptomatic malaria
caused by the asexual erythrocytic forms.
• Treatment of an established infection:
None of the antimalarials is effective against all
liver and red cell stages of the life cycle that may
coexist in the same patient. Complete cure
therefore may require more than one drug.
16. • The patterns of clinically useful activity fall into three
general classes
• Class I agents action is directed against the
asexual erythrocytic forms. These drugs will
treat, or prevent, clinically symptomatic malaria.
Prophylactically,must be taken for several weeks
after exposure until parasites complete the liver
phase and become susceptible to therapy.
• The class II agents, which target not only the
asexual erythrocytic forms but also the primary liver
stages of P. falciparum. This additional activity
shortens to several days the required period
for postexposure prophylaxis.
17. • Finally, primaquine is unique in its
spectrum of activity, which includes
reliable efficacy against primary and
latent liver stages (Hypnozoites) as
well as gametocytes.
• Primaquine has no place in the
treatment of symptomatic malaria but
rather is used most commonly to
eradicate the hypnozoites of P. vivax
and P. ovale, which are responsible
for relapsing infections.
18. • Quinine and Primaquine - short half-lives and
common toxicities, generally are reserved for Rx
of bvestablished infection & not used for
prophylaxis in a healthy traveler.
• In contrast, chloroquine is relatively safe and
has a one-week half-life that is convenient for
prophylactic dosing (in those few areas still
reporting chloroquine-sensitive malaria).
Briefly, causal prophylactics act on the initial
hepatic stages, drugs for terminal prophylaxis
and radical cure target hypnozoites, and agents
for suppressive prophylaxis or cure target the
asexual red cell forms.
19. • Tissue schizonticide:
To kill the hypnozoites. Dormant paracyte in liver.
Clinical fever due to hypnozoites.
-Primaquine
Proguanil
• Blood schizonticidal:
Responsible for acute attack. Release ofmerozoites –
Acute fever. Red cell debris – IL,TNF- Fever
↓
Cause rigor
- Chloroquine
Quinine
Mefloquine
Halofantrine
20. • Gametocidal:
That prevent transmission of P. falciparam. gametocyte
responsible for transmission.
-Primaquine
Proguanil,
Trimethoprim,
Chloroquine
• Antimetabolite:
Pyrimethamine,
Sulphadoxine
Proguanil
Dapsone
Trimethoprim
• Antibiotic:
Tetracycline
Doxycycline
Azythromycin
21. • Drugs used for chemoprophylaxis (also known as
causal prophylactic drugs) block the link between
the exoerythrocytic stage and the erythrocytic
stage, and thus prevent the development of
malarial attacks.
• True causal prophylaxis-the prevention of
infection by the killing of the sporozoites on entry
into the host-is not feasible with the drugs at
present in use, although it may be achieved in the
future with vaccines.
22. • Chemoprophylactic agents are given to
individuals who intend travelling to an area
where malaria is endemic.
• Administration should start 1 week before
entering the area and should be continued
throughout the stay and for at least a month
afterwards.
• No chemoprophylactic regimen is 100% effective,
and the choice of drug is difficult.
• Chemoprophylexis with mefloquine should not
be used unless high chance of chloroqine
resistance.
26. Selection of drug
• The selection of antimalarial drug depends on
–Whether it is to be used for
chemoprophylaxis or for treatment
–The species of Plasmodium
–The area of infection where it is used
• It also depends on
–The adverse effects of the drug
–Age of the patient
–Pregnancy
–Lactating mother
–Hepatic or renal impairment
32. • Among the antimalarial drugs chloroquine is
commonly used.
• Pyrimethamine, sulfones, & tetracyclines are
slower acting, less effective, & nearly always
used in combination with other antimalarial
drugs
• The artemisinins are potent and fast-acting
antimalarials with no clinical evidence of
resistance.
They are particularly well suited for the
treatment of severe P. falciparum malaria and
now play a key role in the combination therapy
of drug-resistant infections.
33. Rational therapy for Malaria
• Rx of Acute clinical Attack
• Prevention of clinical attack
• Radical cure.
Rx of Acute clinical Attack
First try to diagnose the case.
Dx should be confirmed by examination of RBC
Quick detection of malaria parasite by deep stick
Ag assay for P. vivax.
Sensitivity of this test depends upon the no. of
parasite. Parasite > 60/microgm per L is 100%
sensitive.
34. Sensivity decreases to 10-60% if parasite
count < 10 microgm per L
So, blood film study is appropriate for
detection of malaria.
Thin blood film (parasite may be absent)
Thick blood film (more parasite)
Malaria parasite embaded in
lymphocyte,so from head to tail –whole
PBF must be examined.
Whenever detection of parsite,
P.falciparum/P.Vivax , start RX of
P.falciparum
35. • Drug acting faster shouldbe given in Rx of
malaria.
• Blood schizonticidal Chloroquine given, if
sensitive
• Quinine,
meflaoquine,Artemethar,Artesunate
• Artemethar,Artesunate- clear parasite from
blood v. quickly than quinine( 7days)
• Slower acting- pyrimethamine, proguanil,
doxycycline, sulphadoxine,tetracycline
• They are never given alone.
36. Any fever in malaria zone should be treated as malaria
If there is doubt either chloroquine resistant /Not Rx
as resistant malaria.
Pt must be aware of Recrudence & Relapse.
Halofantrine is contraindicated in pregnancy or in
female who might become pregnant within the next 3
months
37. Clinical Setting Drug Therapy
Chloroquine-sensitive P
falciparum & P
malariae infections
Chloroquine phosphate, 1gm,
followed by 500 mg at 6, 24, &
48 hours
Or-
Chloroquine phosphate, 1g at 0
& 24 hours, then 0.5 g at 48
hours
P vivax &
P ovale infections
Chloroquine (as above), then (if
G6PD normal) primaquine, 26.3
mg daily for 14 days
38. Cl. Setting Drug Therapy Alternative Drugs
Uncomplicated
infections with
chloroquine
resistant P
.falciparum
Quine Plus one of
the following-
Doxycycline, 100 mg
twice daily for 7 days
Or-
Clindamycin, 600 mg
twice daily for 7 days
Or-
Fansider, 3 tabs once
Artesunate or artemether, single
daily doses of 4 mg/kg on day
0, 2 mg/kg on days 2 & 3,
1 mg/kg on days 4-7
Or
Coartem (coartemether 20 mg,
lumefantrine 120 mg), 4 tablets
twice daily for 3 days
Severe or
complicated
infections with
P falciparum
Quinine gluconate, 10
mg/kg IV over 1-2
hours, then 0.02
mg/kg IV/minute
Or-15 mg/kg IV over
4 hours, then 7.5
mg/kg IV over 4
hours every 8 hrs
Artesunate, 2.4 mg/kg IV or IM,
then 1.2 mg/kg every 12 hours
for 1 day, then every day
Or-
Artemether, 3.2 mg/kg IM, then
1.6 mg/kg/d IM
39. Malaria Treatment Regimens
• Uncomplicated Malaria Confirmed:
–Tab. Co-artem (Artemether 20 mg + Lumefantrine
120 mg Combination): The total recommended
treatment is a 6-dose regimen of artemether-
lumefantrine twice daily for 3 days. The second
dose on the first day should be given any time
between 8 h & 12 h after the first dose. Dosage
on the second & third day is twice a day (morning
& evening)
–OR
• If for any reason co-artem can not be given
–Pregnancy in 1st trimester
–Children < 5 kg of body weight
–Tab. Quinine sulfate (300 mg). 600 mg 8 hourly
for 7 days
40. • Alternative regimen may be:
–Quinine for 7 days + Tetracycline 250 mg 6 hourly
for 7 days or
Quinine for 7 days + Doxycycline 100 mg 12
hourly for 7 days
–Artesunate (50 mg) + mefloquine (500 mg)
–Dose in mg (no. of tablets)
Artesunate Mefloquine
–Day 1 Day 2 Day 3 Day 1 Day 2 Day 3
–200 (4) 200 200 - 1000 (2) 500 (1)
41. • Uncomplicated Malaria Presumptive:
–The drug should be Chloroquine – 3 days
• Drug Day Weight in kg
• Chloroquine Day-1 4
Tab. 150 mg Day-2 4
base Day-3 2
But all efforts should be made for confirming the
diagnosis as soon as possible by Blood Slide
Examination (BSE) or Rapid Diagnostic Test (RDT). If
BSE/RDT is positive treatment should be started in
the line of uncomplicated malaria confirmed
42. • Treatment of Severe Malaria:
–IV Quinine drip/ IM Quinine followed by oral
Quinine for a total of 7 days
or
–IM Artemether / IV Artesunate followed by oral
Artesunate tablet
• Quinine:
– Loading dose: Quinine dihydrochloride 20
mg salt/kg of body weight (loading dose) by
infusion over 4 hours, in 5% dextrose saline
(5-10 ml/kg of body weight depending on
the patient’s overall fluid balance).
43. – Maintenance dose: Eight hours after the
start of the loading dose, maintenance dose
of quinine 10 mg salt/kg of body weight in
dextrose saline diluted as above over 4
hours. This maintenance dose should be
repeated every 8 hours & up to six doses
(including loading dose). Thereafter the
quinine dose will be reduced to 15 – 20 mg
salt/kg body weight, until the patient can
take oral medication
• If the patient can take orally properly:
– Oral quinine: Quinine sulphate 10 mg
salt/kg, 8 hourly to complete a 7 day course
of treatment
44. • Artesunate:
–2.4 mg/kg (loading dose) IV, followed by 1.2
mg/kg at 12 hours, then 1.2 mg/kg daily for 6
days, if the patient is able to swallow, the daily
dose can be given orally
–Oral Artesunate:
• 1st day – 2 mg/kg/dose
• 2nd day – after 12 hours
• 3rd dose – 8th – daily (total duration of
treatment 7 days & total 8 doses)
• Artemether:
–3.2 mg/kg (loading dose) IM followed by 1.6
mg/kg daily for 5 days
• Arteether:
–150 mg deep IM once daily for 3 days for adults
45. • Treatment of plasmodium Vivax case:
–Chloroquine 3 days + Primaquine 14 days
(Primaquine: 1 tablet daily for 14 days in
adults & 0.3 mg/kg daily for 14 days in
children)
• Management of Severe Malaria In Pregnancy:
–Quinine in the doses advocated for the
treatment of life-threatening malaria, is safe
in pregnancy. Quinine is not an abortificient
in therapeutic doses & safe in all trimester in
pregnancy. It has been shown that the initial
IV infusion of quinine in woman who are >
30 weeks pregnant is not associated with
uterine stimulation or fetal distress. Its major
adverse effect if hypoglycemia. Artesunate &
Artemether should not be used in first
trimester of pregnancy
46. Blood schizontocide: Chloroquine
• A very potent blood schizontocidal drug,
effective against all 4 plasmodial species
(if sensitive to the drug), but it does not
have any effect on sporozoite, hypnozoite
or gametocytes
• A synthetic, 4-aminoquinoline that has
been the mainstay of antimalarial therapy
–It has a complex mechanism of action
that is not fully understood.
47. Mechanism of action:
• Acts mainly on heme disposal by preventing digestion
of hemoglobin by the parasite & thus reducing the
supply of amino acids necessary for parasite viability.
• During the digestion process, large amounts of soluble
heme (ferriprotoporphyrin IX) are released, which is
toxic to the parasite.
• To protect itself, the parasite ordinarily polymerizes
the heme to hemozoin (a pigment), which is
sequestered in the parasite’s food vacuole.
• Chloroquine specifically binds to heme, preventing its
polymerization to hemozoin.
• the accumulation of heme result in oxidative damage
to the membranes, leading to lysis of both the
parasite & the red blood cell.
48. • Pharmacokinetics:
– Route of administration – oral, parenteral
– Absorption – well absorbed from the GIT
– Distribution – rapidly distributed to the tissues.
Volume of distribution 100 – 1000 L/kg (due to
extensive accumulation in organs – liver, spleen,
lungs, heart, kidney, pancreas, brain, eyes,
erythrocyte & skin) & is slowly released from
tissues & metabolized in the liver
– Excretion – mainly in the urine with a initial t½ of 3-
5 days but a much longer terminal elimination t½ of
1-2 months
49. • Indications:
–Chemoprophylaxis & treatment of malaria
where there is no chloroquine resistance
–Hepatic amoebiasis (effective amoebicidal as
it reaches high concentration in the liver)
–Rheumatoid arthritis -anti inflammatory
action is due to –
• inhibition of lymphocyte proliferation, decrease
leukocyte chemotaxis,
• decrease lysosome enzyme release
• & inhibit phospholpase A2 which decrease
prostaglandin & thus decreased inflammation
50. • Contraindications:
–Psoriasis
–Patient with retinal or visual field
abnormality or myopathy
–History of liver disease or neurologic or
hematologic disorders
• Adverse effects:
–Corneal deposits of chloroquine may be
asymptomatic or may cause halos
around lights or photophobia (these
reverse when the drug stopped).
51. – Retinal toxicity is more serious, & may be
irreversible. In early stage it takes the form of
visual field defects; late retinopathy classically
gives the picture of macular pigmentation
surrounded by a ring of pigment (the ‘bull’s eye’
macula.
– In the extreme case, blindness
– Pruritus
– Nausea, vomiting, abdominal pain, headache,
anorexia, malaise, blurring of vision & urticaria –
uncommon
52. – Rare – hemolysis in G-6-PD deficiencient
patient.
– impaired hearing, confusion, psychosis,
seizure, agranulocytosis, exfoliative dermatitis,
alopecia, bleaching of hair, hypotension
– Long term administration of high doses of
chloroquine for rheumatoid disease can result
in – irreversible ototoxicity, retinopathy,
myopathy & peripheral neuropathy
– Larger I.M. injection or rapid I.V. infusion of
chloroquine hydrochloride can result in severe
hypotension & respiratory & cardiac arrest
53. • Chloroquine is the drug of choice because –
– Rapidly causes remission of fever &
parasitemia within 24-48 hours after receiving
therapeutic dose
– Well tolerated & more reliably administered
than quinine
– No toxic synergism when given with
primaquine
– Duration of treatment shorter with choroquine
(3 days) than quinine (7 days)
– As a both suppressive & therapeutic agent
chloroquine is superior to quinine i.e. more
potent & less toxic than quinine
– Hypoglycemia less with chloroquine
– Quinine cause more GI upset
– Quinine narrow therapeutic index
54. Blood schizontocide: Quinine
• Quinine & Quinidine remain first-line therapies for
falciparum malaria- specially severe disease
• Chemistry & pharmacokinetics:
– Quinine is derived from the bark of cinchona tree, a
traditional remedy for intermittent fevers from South
America
– Orally active. Rapidly & completely absorbed from
the GIT.
– Widely distributed in body tissues.
– Highly bound (90%) to plasma proteins.
– The pharmacokinetics of quinine varies among
populations. Individuals with malaria develop higher
plasma levels of the drug than healthy controls, but
toxicity is not increased, apparently because of
increased protein binding.
55. • The half-life is longer in those with severe malaria
(18 hours) than in healthy controls (11
hours).Quinidine has a shorter half-life (6 hours)
than quinine, mostly as a result of decreased
protein binding.
• metabolize in the liver & excreted in the urine.
• Readily cross placental barrier
• CSF concentration is only 2-5 % of that in the
plasma
• Mechanism of action:
– Unknown.Quinine is a rapidly acting, highly
effective blood schizontocide against the four
species of human malarial parasites. The drug is
gametocidal against P vivax & P ovale but not
P.falciparum. It is not active against liver stage
parasites.
56. • Pharmacological action:
– Antiplasmodial action: quinine binds with
plasmodial DNA & thus inhibit protein synthesis. It
also inhibit hemoglobin metabolism by parasite
– Antimalarial action: blood schizontocide.
– Heart “quinidine like action”: a depressant action
on heart. Antidysrhythmic action.
– Skeletal muscle: a slight blocking action on the
neuromuscular junction used in mytonia & muscle
cramp because it prolongs the muscle refractory
period
– Pancreas: stimulate insulin secretion –
hypoglycemia
– Others:
• Weak antipyretic action.
• Mild oxytocic action on the gravid uterus
57. • Clinical use:
– Parenteral treatment of severe falciparum
malaria
– First-line therapy for uncomplicated falciparum
malaria & Chloroquine resistant malaria
– Malarial chemoprophylaxis: not generally used
owing to toxicity, although a daily dose of 325
mg is effective
– Babesiosis: first-line therapy in combination
with clindamycin, in the treatment of infection
with Babesia microti or other human babesial
infection
– Myotonia congenita
– Nocturnal muscle cramp
• Contraindication:
– Hypersensitivity to quinine
– Pregnancy
– Evidence of hemolysis, cinchonism
– Optic neuritis
– Myasthenia
58. • Adverse effects:
–Hearing & vision are particularly disturbed.
• Tinnitus, vertigo, decreased auditory acuity,
blurred vision, disturbed color perception,
photophobia, diplopia, night blindness,
mydriasis
–Skin – hot & flushed. Sweating is prominent
–Nausea, vomiting, abdominal pain & diarrhoea,
hypoglycemia – more in children, pregnant
woman & the elderly patient
–Black water fever is a rare severe illness that
includes marked hemolysis & hemoglobinuria
due to hypersensitivity reaction to the drug,
though its pathogenesis is uncertain
59. Points Chloroquine Quinine
Chemical nature 4-aminoquinoline Cinchona alkalloid
Effective against P falciparum
sensitive strains,
P malariae, P
ovale, P vivax
P falciparum
resistant strain, P
vivax, P ovale, P
malariae
Effect on
sporozoite &
pre-erythrocytic
form of parasite
No action Little action
On relapse Does not prevent
relapse of vivax
malariae
Prevent relapse of
vivax malariae
Potency More potent Less potent
Toxicity Less More
60. Points Chloroquine Quinine
Duration of
treatment
Shorter (3 days) Longer (7 days)
Patient
compliance
Well tolerated,
reliable
Not well tolerated
t½ 50 hours 10 hours
Plasma protein
binding
50-65% 90%
Adverse effect Large dose
causes –
retinopathy,
ototoxicity,
cardiovascular
toxicity
Hypoglycemia,
cinchonism
61. Blood schizontocide: Mefloquine
• Mefloquine is effective therapy for many
chloroquine-resistant strains of P falciparum &
against other species
• One of the recommended chemoprophylactic drugs
for use in most malaria-endemic regions with
chloroquine-resistant strains
• It is a synthetic 4-quinoline methanol that is
chemically related to quinine
• It can only be given orally because severe local
irritation occurs with parenteral use
• Pharmacokinetics:
–Well absorbed
–Highly protein bound, extensively distributed in
tissues, & eliminated slowly, allowing a single-
dose treatment regimen
62. – t½ 15-30 days, allowing weekly dosing for
chemoprophylaxis. Prolonged t½ probably
due to fact that it undergoes extensive
enterohepatic cycle & it has high tissue
storage
– Mefloquine & acid metabolites of the drug
are slowly excreted, mainly in the feces
– The drug can be detected in the blood for
months after the completion of therapy
63. • Advantage for chemoprophylaxis:
–It is active against multi-drug-resistant P
falciparum
–It has extended duration of action &
–It has relatively minor adverse effects
• Simultaneous administration of mefloquine &
chloroquine increase the chance of convulsion, so
this is not encouraged
• Clinical uses:
–Chemoprophylaxis: against most strains of P
falciparum & probably all other human malarial
species as well except for those with no
chloroquine resistance (where chloroquine is
preferred). Eradication of P vivax & P ovale
requires a course of primaquine
–Treatment: most falciparum malaria
64. • Adverse effects:
–GI disturbance: nausea, vomiting, abdominal
pain, diarrhoea & loss of appetite
–Transient CNS toxicity: giddiness, confusion,
dysphoria & insomnia
–Cardiac conduction defect, arrhythmia &
bradycardia
–Rash
–Leukocytosis, thrombocytopenia, &
aminotransferase elevations
–Rarely neuropsychiatric reactions: depression,
confusion, seizure, acute psychosis &
hallucination
• Disadvantage for treatment of acute malaria –
–Expensive, about 50% of the patient complain of
GI disturbances, transient CNS toxicity.
65. • Contraindication & cautions:
–if history of epilepsy, psychiatric disorders,
arrhythmia, cardiac conduction defects, or
sensitivity to related drugs
–It should not be co administered with quinine,
quinidine, or halofantrine, & caution is required if
quinine or quinidine is used to treat malaria after
mefloquine chemoprophylaxis
–Now considered safe in young children
–should not be used in pregnant woman or in
woman liable to become pregnant within 3
months of stopping the drug
66. Tissue schizontocide: Primaquine
• Is the drug of choice for the eradication of dormant
liver forms of P vivax & P ovale
• It is a synthetic 8-aminoquinoline
• Well absorbed orally. t½ is 3-8 hours.
• Widely distributed to the tissues, but a small
amount is bound there.
• It is rapidly metabolized & excreted in the urine.
• Its three major metabolites appears to have less
antimalarial activity but more potential for inducing
hemolysis than the parent compound
67. • Primaquine is also gametocidal against the four human
malarial species.
• Clinical uses:
– Therapy (radical cure) of acute vivax & ovale malaria
– Terminal prophylaxis of vivax & ovale malaria
– Chemoprophylaxis of malaria
– Gametocidal action
– Pneumocystis jiroveci infection
• Adverse effects:
– Primaquine in recommended doses is generally well
tolerated. Infrequently causes nausea, epigastric
pain, abdominal cramps, & headache (with higher
dosages & in empty stomach)
68. –Serious but rare adverse effects include
leukopenia, agranulocytosis, leukocytosis, &
cardiac arrhythmias
–Standard dose of primaquine may cause hemolysis
or methemoglobinemia (manifested by cyanosis),
especially in persons with G6PD deficiency or
other hereditary metabolic defects
Contraindication & cautions:
– History of granulocytopenia or methemoglobinemia,
in those receiving potentially myelosuppressive drugs
(e.g. quinidine)
– Never given parenterally because it may induce
marked hypotension
– Avoided in patients with G6PD deficiency
– Avoided in pregnancy because the fetus is relatively
G6PD-deficient & thus at risk of hemolysis
69. • Pyrimethamine
–Pyrimethamine is a 2,4-diaminopyrimidine
related to trimethoprim
–Effect a radical cure as a blood schizontocide &
strong sporontocide in the mosquito’s gut when
the mosquito ingests it with the blood of human
host
–Has an elimination half-life of about 3.5 days.
Therefore it can be given once a week
• Proguanil
–Is a biguanide derivative
–Has an elimination half-life of about 16 hours,
therefore it must be administered daily for
chemoprophylaxis
–is a prodrug; only its metabolite, cycloguanil, is
active
• Both drugs are slowly but adequately absorbed from
the GIT
70. • Mechanism of action of folate antagonist:
–Selectively inhibit plasmodial dihydrofolate
reductase, a key enzyme in the pathway for
synthesis of folate
–Sulfonamides & sulfones inhibit another enzyme
in the folate pathway, dihydropteroate
synthetase. Combinations of inhibitors of these
two enzymes provide synergistic activity
• Clinical uses:
–Chemoprophylaxis; Treatment of chloroquine
resistant falciparum malaria; Presumptive
treatment of falciparum malaria; Toxoplasmosis;
pneumocystosis
71. • Adverse effects & caution:
–Well tolerated
–GI symptoms, skin rash & itching are rare
–Mouth ulcer & alopecia (proguanil)
–Fansider is no longer recommended for
chemoprophylaxis because of uncommon but
severe cutaneous reactions, including erythema
multiforme, Stevens-Johnson syndrome, & toxic
epidermal necrolysis
–Folate antagonists should be used cautiously in the
presence of renal or hepatic dysfunction
– Proguanil is considered safe in pregnancy
– With the use of any folate antagonist in pregnancy,
folate supplements should be co administered
72. Halofantrine
• A phenanthrene-methanol related to quinine, is
effective against erythrocytic (but not other) stages
of all four human malarial species
• Rapidly effective against most chloroquine-resistant
strains of P falciparum
• Generally well tolerated, but use is limited by
irregular absorption & cardiac toxicity
• Most common adverse effects are abdominal pain,
diarrhoea, vomiting, cough, rash, headache,
pruritus, & elevated liver enzymes
• Contraindicated in patients with cardiac conduction
defects & should not be used in those who have
recently taken mefloquine;
• contraindicated in pregnancy
73. Lumefantrine
• An aryl alcohol related to halofantrine
• Available as a fixed-dose combination with
artemether as Coartem
• Half-life, in combination, is 4.5 hours
• Coartem is highly effective in the treatment of
falciparum malaria, but it is expensive & requires
twice-daily dosing
• Despite these limitations, due to its reliable efficacy
against falciparum malaria, Coartem has recently
been selected as the first-line therapy for malaria in
African countries
• Coartem does not appear to cause the cardiac
toxicity as seen with halofantrine
74. Artemisinin & its derivatives
• Artemisinin (qinghaosu) is a sesquiterpene lactone
endoperoxide, the active component of an herbal
medicine that has been used as an antipyretic in
China for over 2000 years
• Artemisinin can only be used orally
• Analogs have been synthesized to increase solubility &
improve antimalarial activity. Most important of these
analogs are –
– Artesunate (water-soluble; useful for oral, IV, IM, &
rectal administration) & Artemether (lipid-soluble;
useful for oral, IM, & rectal administration)
• Rapidly absorbed, half-life of 1-3 hours after oral
administration
• Compounds are rapidly metabolized to the active
metabolite dihydroartemisinin
75. • Artimisins have no effect on hepatic stages
• The antimalarial effect may result from the
production of free radicals that follows the iron-
catalyzed cleavage of the artemisinin endoperoxide
bridge in the parsite food vacuole or from inhibition
of a parasite calcium ATPase
• Artesunate & artemether are playing an increasingly
important role in the treatment of multidrug-
resistant P falciparum malaria
• They are the only drugs reliably effective against
quinine-resistant strains
• The efficacy of artemisinins is limited by their short
plasma half-life
• Also because of their short-half-lives, they are not
useful in chemoprophylaxis
76. • Artesunate has also been effective in the treatment of
severe malaria when administered rectally, offering a
valuable treatment modality when parenteral therapy is
not available
• In the setting of multidrug resistance, combination
therapy with an artemisinin are: Artemether +
lumefantrine, artesunate + amodiaquine, artesunate +
mefloquine, artesunate + sulfadoxin + pyrimethamine
• Most commonly reported adverse effects – nausea,
vomiting & diarrhoea
• Artemisinins should be avoided in pregnancy because
tertogenicity seen in animal studies
77. Fansidar
• Pyrimethamine (25 mg) acts synergistically with
sulfadoxin (500 mg) as Fansidar to inhibit folic acid
metabolism
• It is used with quinine to treat acute attack of malaria
caused by susceptible strains of P falciparum resistant
to chloroquine
• Mechanism of action:
– Acts by reciprocal potential of its two components,
achieved by a sequential blockade of two enzymes
involved in the biosynthesis of folinic acid in the
parasites
– Dosage: a single dose of pyrimethamine 75 mg +
sulfadoxin 1.5 gm (3 tablets) usually suffices
– Sulfadoxin is excreted in the urine
78. • Indication:
– All forms of malaria
• Toxoplasmosis
– Pneumonia due to pneumocystis carinii
– For chemoprophylaxis of malaria
• Contraindications:
– During pregnancy (because of antifolate action)
– Pre mature or new born infants during 1st few
weeks of life (due to immaturity of enzyme system)
– Sulfonamide hypersensitive patient
• Adverse effects:
– Any sulfonamide induced allergic reaction can be
severe, e.g. erythema multiforme, Stevens Johnson
syndrome & toxic epidermal necrolysis.
79. Drugs to prevent transmission
• Some drugs (e.g. primaquine, proguanil &
pyrimethamine) have the additional action of
destroying the gametocytes, preventing
transmission by the mosquito & thus
preventing the increase of the human
reservoir of the disease – but they are rarely
used for this action alone
80. Last minute traveler
• 500 mg of chloroquine phosphate (Tab 250
mg) (300 mg base) taken daily for 2-3 days
then once weekly during staying in the malaria
zone & continued for 4 weeks after leaving the
area
• Or
• Mefloquine (Tab 250 mg) 250 mg daily for 2-3
days & then weekly continued up to 4 weeks
after leaving the area
81. Management of cerebral malaria
• Diagnosis is made from cerebral manifestation –
–Convulsion, hypoglycemia, difficulty in breathing
or pulmonary edema, oliguria or acute renal
failure, hyperpyrexia, hyperparasitemia, change
of behavior, drowsiness, altered consciousness,
coma, severe anemia, circulatory collapse or
shock, hemoglobinuria, jaundice, acidosis
• Exclusion of other causes of encephalopathy
• Focal neurological signs absent
• Neck rigidity & kernigs sign absent
• Microscopic confirmation
• CSF normal
82. • Injection chloroquine 5 mg/kg in 500 ml of 5%
dextrose aqua over 4 hours stat & 8 hourly upto
patient can take orally for 7 days orally
• Or if chloroquine resistant –
• IV quinine dihydrochloride loading dose 20
mg/kg if not treated with quinine before
• If treated then give 10 mg/kg body weight
• It is given with 500 ml of 5% (10%) dextrose
over 4 hours & 8 hourly until patient can take
the drug orally. Total duration for 7 days
• Treatment of convulsion – diazepam IV 0.2
mg/kg
• For hypoglycemia – IV glucose 10% or 25%
• Correct fluid & electrolyte balance
• If hemoglobin < 6 gm/dl – blood transfusion
with packed red cell
• Ryles tube down for feeding
83. • Proper nursing care –
–Clean airway
–Frequently change of posture
–Urethral catherization
–Careful record of input/output chart
–Check speed of infusion frequently
–Monitoring of vital signs
• Treatment of pulmonary edema – propped up
position, frusemide
• Hyperpyrexia – sponging, antipyretic
• Hyparasitemia: if > 10% RBC are infected –
exchange blood transfusion
• Antibiotic – if associated infection
• If oliguria develops, frusemide or an infusion of
mannitol may forestall renal failure
• Dialysis may be needed if renal failure develops
Editor's Notes
)
The patterns of clinically useful activity fall into three general classes.
Class I agents are not reliable against primary or latent liver stages or against P. falciparum gametocytes. Their action is directed against the asexual erythrocytic forms. These drugs will treat, or prevent, clinically symptomatic malaria.
When used prophylactically, the class I drugs must be taken for several weeks after exposure until parasites complete the liver phase and become susceptible to therapy.
The spectrum is somewhat expanded for the class II agents, which target not only the asexual erythrocytic forms but also the primary liver stages of P. falciparum. This additional activity shortens to several days the required period for postexposure prophylaxis.
Finally, primaquine is unique in its spectrum of activity, which includes reliable efficacy against primary and latent liver stages as well as gametocytes. Primaquine has no place in the treatment of symptomatic malaria but rather is used most commonly to eradicate the hypnozoites of P. vivax and P. ovale, which are responsible for relapsing infections.
Aside from their antiparasitic activity, the utility of antimalarials for prophylaxis or therapy is dictated by their pharmacokinetics and safety. Thus, quinine and primaquine, which have short half-lives and common toxicities, generally are reserved for treatment of established infection and not used for prophylaxis in a healthy traveler. In contrast, chloroquine is relatively safe and has a one-week half-life that is convenient for prophylactic dosing (in those few areas still reporting chloroquine-sensitive malaria). Older classifications of the antimalarials are defined extensively in the 10th edition of this book. Briefly, causal prophylactics act on the initial hepatic stages, drugs for terminal prophylaxis and radical cure target hypnozoites, and agents for suppressive prophylaxis or cure target the asexual red cell forms. Regimens currently recommended for chemoprophylaxis in nonimmune individuals are given in Table 39-1, whereas regimens for the treatment of malaria in nonimmune individuals are given in Table 39-2. Individual agents are discussed in more detail below.
Acts mainly on heme disposal by preventing digestion of hemoglobin by the parasite & thus reducing the supply of amino acids necessary for parasite viability.
During the digestion process, large amounts of soluble heme (ferriprotoporphyrin IX) are released, which is toxic to the parasite.
To protect itself, the parasite ordinarily polymerizes the heme to hemozoin (a pigment), which is sequestered in the parasite’s food vacuole.
Chloroquine specifically binds to heme, preventing its polymerization to hemozoin.
the accumulation of heme result in oxidative damage to the membranes, leading to lysis of both the parasite & the red blood cell.