an interesting and exhaustive presentation for medical undergraduates and postgraduates on antimalarial drugs... and also helpful to physicians for learning new concepts like ACT, for treating resistant malaria and knowing important ADR of antimalarial drugs..
20. CHLOROQUINECHLOROQUINE
Rapidly acting erythrocytic schizontocide
No effect on other phases
Effective on all forms of plasmodia
Rapidly acting
M.O.A enters RBC Concentrated inside
plasmodial acidic food vacuole inhibit haeme
polymerase accumulation of toxic haeme
parasite membrane lysis death
Also prevents digestion of hemoglobin
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22.
23. CHLOROQUINE RESISTANCECHLOROQUINE RESISTANCE
P. falciparum developed Resistance
Modulated by p-glycoprotein pumps
out chloroquine out of food vacuole
– may cause serious infection
Verapamil – restore sensitivity
30. PKPK
Excellent oral absorption
Given parenterally attains toxic
concentration In very short time used
only when definitely needed
Concentrated in liver, kidneys, lungs,
spleen, retina
t1/2 – 6-7 days, high Vd
Tight tissue binding – persists in the body
for months - CUMULATIVE
44. USESUSES
Drug of choice for treatment of all 4 types of
malaria due to sensitive strains ( 1g at 0
followed by 0.5 g at 6, 24, 48 hr)
Prophylaxis – 2 tab/ week
Extra intestinal amoebiasis
Rheumatoid arthritis, DLE
Lepra reactions
Photogenic reactions
Symptomatic relief of Infectious mononucleosis
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52.
53. AMODIAQUINEAMODIAQUINE
Same as chloroquine
Less bitter = Palatable
Used in uncomplicated falciparum malaria
Not recommended for prophylaxis( fatal
toxic hepatitis)
Similar S/E, itching less common,
neutropenia in children
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55.
56. MEFLOQUINEMEFLOQUINE
Slower acting than chloroquine
Erythrocytic schizontocide
Effective against chloroquine sensitive, resistant
malaria, MDR malaria single dose
Resistance, cross resistance seen
Relapses occur
M.O.A probably act by inhibiting haeme polymerase
binds with heme complex damages plasmodial
membranes
57. PKPK
Slow , good oral absorption
Highly protein bound
Enterohepatic cycling occur
t1/2 – 20 – 30 days
58. ADRADR
GI –nausea, Vomiting, dizziness
Neuropsychiatric reactions – ataxia,
hallucinations, impaired psychomotor
skills, errors in operating machinery,
ataxia, disturbed sense of balance
Rarely Hepato, hemato, cutaneus
Teratogenic in animals
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65. DRUG INTERACTIONS, C/IDRUG INTERACTIONS, C/I
QTc prolongation with quinine/
halofantrine cardiac arrest
Arrhythmias
Epileptics
Psychiatric patients
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67.
68. USESUSES
Multi drug resistant P. falciparum malaria
– 20 mg/kg single dose
Currently in ACT
Prophylaxis of malaria among travellers
to areas of multidrug resistance (250
mg/week)
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71.
72.
73.
74. QUININEQUININE
Alkaloid obtained from cinchona bark
Erythrocytic schizontocide for all species
Kills vivax gametes
Cause incomplete clearance
Less effective and more toxic
Exact mechanism not known, probably as
chloroquine
Non-cumulative
90. PROGUANILPROGUANIL
Slow acting erythrocytic schizontocide
Cyclized cycloguanil inhibits plasmodial DHF
reductase
Resistance develops rapidly
Non-cumulative
ADR- stomatitis, rash, N,V,D, transient loss of
hair
CAUTION – poor renal function
Prophylaxis of malaria with chloroquine
Along with atovaquone for treating MDR
falsiparum malaria
Safe in pregnancy
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94. PYRIMETHAMINEPYRIMETHAMINE
Slow acting erythrocytic Schizontocide
Inhibit DHF reductase
Resistance rapidly develops
ADR- relatively safe, rash, nausea,
megaloblastic anemia in high doses
Caution –give folic acid during pregnancy
Use –only in combination for falciparum
malaria
95.
96. PYRIMETHAMINE- SULFA/PYRIMETHAMINE- SULFA/
DAPSONEDAPSONE
Synergistic due to sequential blockade
Clinical curative for falciparum
ADR – serious cutaneous reactions
C/I –pregnancy, infants, sulfa allergy
Uses – single dose therapy in chloroquine
resistant malaria (Pyri 25 mg+ sulfa 500 mg or
dapsone 100 mg) , toxoplasmosis ( 1st
choice ),
pneumocystosis
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103.
104. PRIMAQUINEPRIMAQUINE
Highly active against gametocytes, hypnozoites
Weak activity on erythrocytic forms
Marked effect on Primary, secondary tissue
phases
Non-cumulative
Mechanism not known
ADR – GIT, uneasiness in chest, hemolysis in G-
6-PD deficiency, methemoglobinemia
C/I – pregnancy
Use –radical cure of relapsing malaria (vivax ),
pneomocystis jiroveci infection
119. ARTEMISININ DERIVTIVESARTEMISININ DERIVTIVES
Derivative of Artemisia annua ( Quinghaosu)
Effective on falciparum resistant to all drugs
Rapidly acting schizontocide with short
duration of action
Do not kill hypnozoites
Arteether – developed in India, for institutional
use only
M.O.A – interact with heme release free
radical species binds to plasmodial
membrane protein lysis
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121.
122. ARTEMISININ DERIVTIVESARTEMISININ DERIVTIVES
PK – artesunate (oral, IM, IV, rectal ), artemether
( oral, IM, rectal ) prodrugs
Arteether – longer acting, IM
ADR – GI effects, itching, fever, ST changes, Q-T
prolongation arrhythmias close monitoring
required
Bone marrow toxicity – rare, reversible
D/I – with astemizole, terfenadine, TCAs risk of
arrhythmias
Use cautiously in pregnancy
Use – restricted use in severe forms of malaria,
Chloroquine/MDR falciparum malaria
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128.
129. ADVANTAGES OF I.VADVANTAGES OF I.V
ARTESUNATEARTESUNATE
Faster parasite clearance
Safer
Better tolerated
Simpler dosing shedule
Higher efficacy
Lower mortality
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133.
134. HALOFANTRINEHALOFANTRINE
Activity comparable to mefloquine
t1/2 – 1 day
ADR – GI effects, itching, rash, elevated
liver enzymes, prolongation of QTc
interval
C/I - pregnancy
Not approved in India
Use –alternative in MR falciparum
malaria ( 1500 mg in 3 divided doses )
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140.
141. ATOVAQUONEATOVAQUONE
Rapidly acting schizontocide
M.O.A – collapses mitochondrial
membranes, interferes with ATP
production
Uses- chloroquine resistant malaria, 2nd
line drug in toxoplasmosis, Pneumocystis
carinii in AIDS
ADR – headache , rash, fever, vomiting,
diarrhoea
C/I - pregnancy
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150. OBJECTIVES OF USEOBJECTIVES OF USE
Prevent, treat clinical attack
Complete eradication of the parasite
from the patient
Reduce human reservoir of infection
157. TREATMENT OF MALARIATREATMENT OF MALARIA
CAUSAL PROPHYLAXIS – pre
erythrocytic phase in liver is the target –
PROGUANIL, PRIMAQUINE
SUPPRESSIVE PROPHYLAXIS – Suppress
erythrocytic phase- CHLOROQUINE,
PROGUANIL, MEFLOQUINE,
DOXYCYCLINE
158. TREATMENT OF MALARIATREATMENT OF MALARIA
CLINICAL CURE –erythrocytic schizontocide –
Fast acting -CHLOROQUINE, MEFLOQUINE,
QUININE, HALOFANTRINE, ARTEMISININ-
given or combinations of slow acting drugs like
proguanil,pyrimethamine, sulfonamides
CHL .RES.MALARIA, MR FALCIPARUM –
MEFLOQUINE, QUININE, ARTESUNATE
Severe falciparum – PARENTERAL QUININE/
ARTESUNATE/ARTEMETHER/ARTEETHER
159.
160. TREATMENT OF MALARIATREATMENT OF MALARIA
RADICAL CURE – hypnozoites/
exoerythrocytic phase – PRIMAQUINE
+CLINICAL CURATIVE
GAMETOCIDAL – elimination of
gametes – PRIMAQUINE,ARTEMISININ
– all species,
CHLOROQUINE, QUININE - vivax
164. LUMEFANTRINELUMEFANTRINE
Orally active, high efficacy, long acting
erythrocytic schizontocide
Acts in the food vacuole of plasmodia to
inhibit haeme polymerization
Only ACT available as fixed dose combination
Used in multi drug resistant, mefloquine
resistant malaria
Given with food
C/I – PREGNANCY, Prolonged QTc interval
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170.
171. PREVENTION OF MALARIAPREVENTION OF MALARIA
Chloroquine, Proguanil and Maloprim
Malarone (atovaquone/proguanil )
Doxycycline
183. If you have built castles in the air, yourIf you have built castles in the air, your
work need not be lost; that is where theywork need not be lost; that is where they
should be. Now put foundations undershould be. Now put foundations under
them.them.
Henry David ThoreauHenry David Thoreau