ANTI MALARIAL PHARMACOTHERAPY.by dr fahad

Antimalarial

1. ANTI MALARIAL
PHARMACOTHERAPY
BY
DR SHAMS SULEMAN

4. CLASSIFICATION
BASED ON CHEMICAL STRUCTURE
4 aminoquinolones
Chloroquine
Amodiaquine
8 aminoquinolones
Primaquine
Acridine Derivatives
Mepacrine

5. CONTD…
Quinolone Methanol
Quinine
Quinidine
Mefloquine
Biguanides
Proguanil

6. CONTD…
Folate Antagonist/ Sulfonamide
Fansidar
(pyrimethamine(25mg)+sulfadoxine(500mg))
Maloprim
(Pyrimethamine +Dapsone)
Chlorproguanil+dapsone

7. CONTD…
Folate antagonist + Quinolone
Malarone (Proguanil+Atovaquone)
Antibiotics
Doxocycline
Clindamycin
Azithromycin
Flouroquinolone

8. CONTD…
Alcohols
Phenanthrine=Halofantrene
Amyl alcohol=Lumefantrine
Artemesinins and analogs
Artesenuate (water soluble)
Artemether (lipid soluble)
Co artems
Artemether +Lumefantrine

10. CLASSIFICATION
BASED ON THE SITE OF ACTION
Hypnozoidal
Primaquine
Tafenoquine
Erythrocytic schizontocidal
Chloroquine
Amodiaquine
Pyremethamine

11. CONTD…
Erythrocytic schizontocidal (contd…)
Quinine
Quinidine
Artemesinins
Halofantrine
Mefloquine
Atovaquone
Clindamycin
Tafenoquine
Tetracycline

12. CONTD…
Gametocidal
Chloroquine
Primaquine
Tafenoquine
Quinine
Mefloquine
Amodiaquine

13. CONTD…
Tissue schizontocidal
Primaquine
Tafenoquine
Proguanil
Tetracycline
Pyrimethamine

14. CONTD…
Sporontocidal
Proguanil
Pyrimethamine
Atovaquone

15. CLASSIFICATION…
BASED ON CLINICAL RESPONSE
Chemoprophylaxis
Chloroquine
Mefloquine= in chloroquineresistant cases
Causal prophylaxis
Mefloquine
Chloroquine(pregnancy)
Radical cure
Primaquine
Chloroquine

16. CLINICAL PRESENTATION
Classical malaria ; intermittent fever
Tertiary =falciparum, vivax, ovale
Quarternary= malariae
Cerebral malaria
Algid malaria
Hypersplenism
Malarial quartannephropathy =P. malariae
Malaria in pregnancy

17. PREVENTION
100% = Not possible
Chemoprophylaxis =Mefloquine;26.3mg/week
Long sleeved shirts and trousers
Permethrin impregnated beds nets
Mosquito repellant= D.E.E.T
Mosquito killing =Mats and liquids

18. CHLOROQUINE
4 aminoquinolone
Vd =100-1300 L/Kg
Crosses BBB, Placenta
Initial t ½ =3-5 days
Elimination t ½ =1-2 months
Blood schizontocidal
Gametocidal
NOT tissue schizontocidal
Safe in pregnancy and children

19. CONTD…
MOA = Binds to hemein the RBC
Prevents polymerization to hemozoin
Free radicals accumulate inside the RBCs
Killing of parasite and RBC
Resistance
Pf CRT protein mutation
Reversed with : Verapamil
Desipramine
Chlorpheneramine

20. CONTD…
Resistance
Treated by
Quinine and Fansidar
Quinine and Doxycycline
Artimesinins
Posology
Oral = 4,4,2 / 4,3,3
IM =7.5ml TDS * 5 doses

21. CONTD…
Other indications
Amoebic liver abcess
Rheumatoid arthritis
Systemic lupus erythematosus
Adverse effects
Nausea, vomiting ,pruritis, malaise
Nail and mucosal discoloration

22. CONTD…
Confusion, seizures, psychosis, ototoxicity
Retinopathy, myopathy, neuropathy
Agranulocytosis
Hypotension, shock
QRS complex widening , T wave changes
Contraindications
Psoriasis
Porphyria

23. AMODIAQUINE
Features identical to chloroquine
Exceptions
More chances of agranulocytosis,
aplasticanemia, hepatotoxicity.
Not for chemoprophylaxis
Can be used in chloroquineresistant cases

24. QUININE /QUINIDINE
Quinolonemethanol.
αglycoprotein ; highly protein bound;18 hours.
Blood schizontocidal= all four species.
Gametocidal= p.vivax, p. ovale.
NOT tissue schizontocidal.
NOT recommended for prophylaxis.

25. CONTD…
Mode of action
Inhibition of hemozoinbiocrystallization.
Cytotoxichemeaggregation.
Killing of parasite .
Indications
Severe falcipruminfection
Chloroquineresistant malaria

26. CONTD…
Babesiosis
Leg cramps
Adverse effects
Cinchonism(tinnitis,dizziness,flushing,
visual disturbances)
Blackwaterfever ( hemolysis, hemoglobinuria)
Hypoglycemia

27. CONTD…
Severe hypotension.
Autoimmune hemolytic anemia.
Thrombophlebitis.
Clolestasis.
Neuromuscular blockade.
Abortion ; fetotoxic.
QT interval prolongation.
Elevates digoxin, warfarinlevels.

28. CONTD…
Caution
Avoid concomitant mefloquine= cardiotoxicity
Avoid aluminium= decreased absorption
Posology
Loading = 900mg in 500ml D/Water
Maintenance = 600mg in infusion TDS
For minimum possible duration
Followed by Doxocycline

29. MEFLOQUINE
Chemoprophylaxis of choice in chloroquine
resistance
NOT recommended for treatment
Only oral ; NEVER I.V = severe irritation
Highly protein bound ; 18 hours
Terminal t1/2= 20days after a single dose
Once weekly dose ; 26.3mg
Avoid concomitant Quinine, Halofantrene
Safe in pregnancy

30. CONTD…
Erythrocytic schizontocidal (vivax ,falcipram)
NOT gametocidal ,tissue schizontocidal
Adverse effects
Nausea, vomiting, dizziness
Sleep and behavioral disorders
Fine motor skill abnormalities
Bradycardia, arrhythmias
Seizures ,psychosis

31. PRIMAQUINE
8 aminoquinolone
Hypnozoital; tissue schizontocidal
Eradication of P. Vivax, P . Ovale
PO ; never IV ; 15mg base daily * 14 days
Effective in = both primary and secondary
exoerythrocyticschizogony
Gametocidal= all four species
Not effective in chloroquineresistant erythrocytic
schizogony

32. CONTD…
Indications
Radical cure = P. vivax, P .ovale
Terminal prophylaxis = P. vivax, P .ovale
Not for chemoprophylaxis
Gametocidal
Caution
G6PD deficiency
Pregnancy

33. CONTD…
Adverse effects
Hemolytic anemia
Met hemoglobinemia
Leukopenia
Agranulocytosis
Arrhythmias

34. ATOVAQUINONE
Available in combination
MALARONE ( Atovaquinone 250mg
Proguanil 100mg)
Indications
Treatment and prophylaxis of P.Falciprum
Toxoplasmosis
Pneumocystis jirovici

35. FOLATE ANTAGONISTS/
SULFONAMIDE
Synergistic
PROGUANIL
Biguanide; active form = chlorproguanil
Erythrocyticschizontocidal=all p.species
PYREMETHAMINE
Radical cure in p. falciprum, p. malariae
Adverse =Megaloblasticanemia, pulmonary
infiltrates, pancytopenia

36. ANTIBIOTICS
Never used alone
Usually used after treatment with chloroquine or
quinine
Inhibit plasmid protein synthesis
Used for up to 7 days for complete eradication of the
resistant strains.

37. ALCOHOLS
Halofantrene= cardiotoxic;QT prolongation
Avoid concomitant use with
Quinine, chloroquine, mefloquine
Terfenadine, astemizole
Tricyclicantidepressants
Lumefantrene= less cardiotoxic
Fixed dose combinations with artmesinins.

38. ARTEMESININS/
ARTESENUATE/ARTEMETHER
Artemesinins = herbal qinghaosu; insoluble
Artesenuate = water soluble analog
Artemether = fat soluble analog
Sesquiterpene lactone endoperoxide
Dihydroartemesinin = active metabolite
Inhibit parasite calcium ATPase
Endoperoxide bridges in food vacoules

39. CONTD…
Strong blood schizontocidal
Moderate gametocidal
NO tissue schizontocidal
Very useful in MDR falciparum
Only proven effective drug in quinine resistant cases
Safety profile improved in combination
Adverse = neurotoxicity , cardiotoxicity
Teratogenic

40. CONTD…
WHO recommendations
Uncomplicated falciparum in 2
nd
/3
rd
trimester
Oral artmesinins based combination
Severe falciparum malaria in 1
st
trimester
IV artesenuate or IV quinine
Severe falciparum malaria in 2
nd
/3
rd
trimester
IV artesenuate

41. PIPERAQUINE
Bisquinolone; in falciparum resistant cases
Combined with dihyroartemesinin
Excellent efficacy and safety, without resistance
Longer t1/2 (28 days) compared with amodiaquine
(14 days), mefloquine( 14 days) and
lumefantrene(4 days) .
At present the combination of first choice in
Vietnam.