Malarial RX

Drugs Mechanism of action & Kinetics Toxicity & Drug interation Uses, Contra indications & Drug interations
Chloroquine MOA: Resistance :d/t alteration in drug -Blood schizonticide agst all plasmodium species
 Alkalinisation of food vacuole transport mechansm – crt & Pfmdr1 gene - gametocidal agst malaria,vivax & ovale
Oral  inhibits heme polymerization by Toxicity : - Drug of choice for erythrocytic falciparum
Parentral : blocking Pl.heme polymerase a/c : too rapid parentral administratn malaria
slow constant i.v accumulates to toxic level in parasite ♥ : HoTN ,VDn,arrhythmia ,♥ arrest -DOC in pregnancy
OR  ↓ DNA synthesis CNS : Confusn , convulsn ,coma - Uses : Extraintestinal amoebiasis,giardia,
Small divided i.m / s.c c/c - Discoloration of nail beds & RA,DLE,IMN,Lepra reaction,Photogenic
Kinetics :Well absorbed frm GIT, mucous membranes,hemolysis in reactions,Malaraia ,Giardiasis
T1/2 3-10days, Vd > 100 L/kg , G6PD deficiency [RED LIP Mahatama Gandhi]
50% pl protein bound Low dose – NVD,Headache,blurring of - Avoid in Psoriasis , Porphyria,Seizures,
Active metabolite vision,diplopia,pruritis,Lichenoideruptions, ↓Visual aquity,blood d/o ,severe hepatic & renal
MonodesethylChloroquine QRS widening ,T wave changes insufficiency,G6PD deficiency
The drug concentrates in RBCs, liver, High dose >250g– Retinal - DIns :
spleen, kidney, lung, melanin- toxicity(irreversible retinopathy) gold / phenylbutazone → dermatitis
containing tissues as well as WBC ottotoxicity,peripheral neuropathy, Mefloquine / anticonvulsants → pptate seizure
Crosses BBB & placenta toxic myopathy,♥myopathy Amiodarone / halofantrine → Vr arrythmias
Eye & CNS examination every Single oral dose of 30mg/kg → fatal ↑ toxicity of diogixin & cyclosporine
3-6 months Parentral dose of >5g → fatal
Mefloquine MOA : Form toxic compds Seizures - Blood schizonticide agst all plasmodium
Common:transient dizziness,NVD,vivid species
Oral only Kinetics: Absoptn ↑ by food dreams, nightmares, irritability, mood - Prophylaxis of MDR malaria
T1/2 : 2-3 wks [20days] alterations, headache, insomnia, - IV tx uncomplicated MDR malaria
Extensive Entero gastric n hepatic ☺ Hallucinations,tinnitus,vertigo, seizures, - Avoid in seizurelpsychiatric d/o ,cardiac
Concentrates in Liver & Lungs psychosis, prolonged dizziness, conduction defects,liver d/s,children <2yrs
Highly bound to pl.proteins (98%) Rare: extrasystole,hemolysis - C/I in T1 ofpregnancy (contraceptn for
Excretn → fecal route , 10% ,agranulocytosis 3months),HSty to quinine
unchanged in urine - Avoid mefloquine ifRx with or w./o halofantrine
- Avoid along with CCB,BB,Digoxin,antidepressants,,TC /Ampicillin or within 2months prior mefloquine,
- Compromise adequate immunsn live typhoid vaccine - Avoid mefloquine shortly after quinine
- ↑ r/f seizures in those Rx with Valproate administn
Primaquine MOA : generates reactive O2 species Common :GI upset, - tissue schizonticide & gametocidal agst all
[superoxides] or interfere with ETC Rare: Mild anemia,cyanosis & species
Oral only leucocytosis - acts agst hypnozoites - Kills NON-growing
Kinetics :Complete absorptn frm GIT High dose : hemolysis in G6PD parasites in liver
3 active metabolites : 1 – antimalarial deficiency, methemoglobinemia (can also - TERMINAL prophylaxis (curative) → radical
2 – hemolytic anemia occur in normal doses ) cure & terminal Px of vivax & ovale
T1/2 3-6hrs Rare:Agranulocytosis,granulocyto - Eradicates 1o exo-erythrocytic form of
Vd – Total body H2O penia,- in those with A/I falciparum & vivax and 2o exo-erythrocytic form
Elimination - renal d/s,HTN,Arrythmia,CNS S/E of ovale & vivax + gametocidal for all species,so
transmission is interrupted
CQ & Dapsone synergestic with -Avoid in pregnancy,G6PD deficiency,or AI
Primaquine in producing methHbnemia d/o
in those with cong def of NADH methHb
reductase
Quinidine MOA - inhibits heme polymerization → Dose related toxicity : triad of - Blood schizonticide agst all plasmodium
accumulates to toxic level in parasite cinchonism,Hoglycemia & HoTN Species – asexual forms
Oral (same as chloroquine) Cinchonism – N,V,D,tinnitus,vertigo, - Gametocidal for vivax & malariae
Parentral – i.m Photophobia,Night blindness,High tone - IV tx severe & complicated P. falciparum
Kinetics : Absorbed orally [mainly from deafness,dyshphoria - DOC for cerebral malaria
upper SI] or i.m Hypoglycemia, - Other uses : Nocturnal cramps,diagnosis of
T1/2 :10-12hrs HoTN – rapid iv infusions of quinine MG,Spermicidal,Varicose veins
Vd – 1.5 L/Kg High dose :Cardiotoxic,- widening of - Monitor B.P (forHoTN) ECG [ widening of the
Met – Liver QRS complex, arrythmias,GIT - N,V,D QRS complex & lengthening of QT)
Excretion – Renal ie Urine Eye – blurring of vision,photophobia, RBS (Hypoglycemia)
night blindness,diplopia,VF constriction, - C/I – Pregnancy, Prev HSity ,Hoglycemia,
Crosses placenta scotoma,mydriasis,blindness Optic tinnitus,optic neuritis,♥ arrythmias,G6PD def
atrophy,Ear – 8th N…Tinnitus, ,↓ auditory - D/I :
The fatal oral dose of quinine for adults acquity,vertigo,Skin:hot,flushes, Digoxin → ↓ clearance of quinine → ↑ toxicity
is about 2 - 8 g. sweating,rashes,angioedema of face Oral Acts like warfarin → ↑ quinine toxicity
Hypersentive rxtn - Blackwater fever b/c quinine inhibits CFs formed by Vit K
[Hemolysis,Hburina & Hbnemia] NMB – Quinine potentiates the NM blocking
Drug-induced ITP,cutaneous effects
flushing,rashes, Cimetidine - ↓clearance of Quinine - ↑ quinine
Blood :rare a/c Hemolytic anemia toxicity
hypoprothrombinemia,leucopenia, Rifampin & Acidification of urine - ↑ clearance of
agranulocytosis Quinine
Occasional:, fever, delirium, rashes Prochlorperazine - ↑ ♥ toxicity of quinine
mild hemolysis in G6PD deficiency
Pyrimethamine MOA – (-) plasmodium DHF reductase Antimalarial dose : occ skin - Slow acting blood schizonticide
Synergism of Pyrimethamine + SA is rashes,depression of hematopoesis - Rx of CQ resistant falciparum malaria
Oral d/t sequential blockage of folic acid High dose : Megaloblastic anemia -High dose of Pyrimethamine + Sulfadiazine →
synthesis pathway. Rx of T.gondii in IC hosts
Cycloguanil – active High doses thts used to tx T.gondii - C/I : anemia,pregnancy,breast feeding
Metabolite of Resistance – d/t mutation of DHFR infections – skin rashes,BM suppression,
pyrimethamine thymidilate synthase – substitution of Renal toxicity i.m inj – local S/E
asparagine for serine @ postion 108
Kinetics : slowly bt completely

absorbed ,80% protein bound
T ½ - 3/5days [ 80-90hrs]
Concentrated in kidney,liver,lungs &
spleen
Pyrimethamine MOA – (-) plasmodium DHF reductase Stevens-Johnson syndrome, erythema - Rx of infections with some CQ – resistant
-Sulfadoxine [pyrimethamine] + (-) DHPteroate multiforme, TEN,Agranulocytosis,Serum falciparum
[Fansidar] synthetase [ sulfadoxine] sickness type of reaction,urticaria, - Resistance develops rapidly
exfoliative dermatitis & hepatitis - C/I in T2 & T3 of pregnancy,infants <2months of
age,,those allergic to SA,lactating mothers,
Pyrimethamine + a/w agranulocytosis
Dapsone[Maloprim]
Atovaquone MOA : acts @ cytbc1 complex to Common : N,V,D,Abd pain,headache & - Blood schizonts of Plasmodia,tachyzoites &
inhibit malaria mitochondrial ETC,ATP rashes cyst forms of T.gondi,P.carnii & Babesia sps
& pyramidine synthesis Rare : transient ↑ S.transaminase / - active agst liver stages of Falciparum
amylase - Rx & Px of MDR Falciparum malaria (+
Kinetics : Slow,erratic & variable oral Proguanil
absorptn , > 90% bound to pl.proteins, Resistance : d/t mutation of cytoB gene - Alterantive Px of PCP in those with intolerance
T ½ - 1.5 – 3days to T-SMx / parentral pentamidine
Met – liver,Excreted in bile,>94% D/ I : Rifampin & TC - T.gondii chorioretinitis in ICsed pts
unchanged in the stool & trace in urine - Babesia + azithromycin
- Avoid in children < 11 kg, pregnant women, or
those breast-feeding infants
Proguanil MOA: (-) DHF reductase – thymidylate Prophylactic dose : N & D - 1O Liver stages & asexual RBC stages
(prodrug) → inhibit DNA synthesis & depletion High dose : V,D,abd pain,Hematurina, - Not gametocidal ,leads to failure of normal
of folate co-factors Epi cells & casts in urine devlpt of fertilized gametes encysted in the gut of
Kinetics : Slowly bt adequately frm mosquito
GIT, 75% protein bound Resistance : d/t mutations in DHF - Malaria along with Atovoqone
T1/2 : 12- 21hrs reductase gene – paired Val16 / Thr108 - Safe during pregnancy
Met by – Cyt P450 2C 19 to cytoguanil substitution - Safe along with other antimalarials like
Elimination – mainly faeces,trace amts CQ,Atovaquone,TC & other antifolates
in urine
Atovaquone + MOA: Inhibits mitochondrial electron Frequent: NVD, abdominal pain,Mouth - Uncomplicated MDR P. falciparum infection
Proguanil (Malarone) transport (bugs have no salvage path ulcers, ↑ transaminases - C/I in severe renal impariement.
like humans) Rare: seizures, rash
A 250mg + P 100mg Kinetics : Proguanil ↑ memb collapsing activity of
T1/2 - 16-20hrs atovaquone
Doxycycline MOA :binds 30S subunit, inhibits Sun sensitivity ,Vaginitis in ♀ - Suppressive prophylaxis→ Rx [ with Quinine]
binding of t-RNA (inhibits protein Frequent: GI upset, vaginal candidiasis, of infections with
synthesis) photo-sensitivity P.falciparum,chemoprophylaxis.
Rare:allergic reactions, blood dyscrasias, - Continue for 4 wks after leaving area
azotemia in renal d/s, esophageal - Avoid in pregnancy & children < 8yrs,those
ulceration HSitive to Tetracyclines

Malarial RX

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Malarial RX

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Drugs Mechanism of action & Kinetics Toxicity & Drug interation Uses, Contra indications & Drug interations

Kinetics : slowly bt completely

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