ANTIMALARIAL DRUGS for pico.ppt.........,

Abid

1. By Dr Ayesha Jamil

2. Malaria is an infective disease characterized by
high grade fever, rigors and chills.
It is caused by five species of protozoal genus
plasmodia.

3. Plasmodium falciparum.
Plasmodium ovale.
Plasmodium vivax .
Plasmodium malarie .
Plasmodium knowlesi.

5. •Anopheles mosquito injects sporozoits.
•Sporozoits migrate to the liver, forming merozoits.
•Merozoits are released and invade red cells.
•In the red cells they become tropozoites.
•Trrozoites form merozoits,which are released after
the red cells rupture ,infecting other RBc’s.
•Some merozoits become gametocytes.
•The female mosquito picks up gametocytes from
the infected human.The sexual cycle is completed in
the mosquito, where sporozoits are formed.

6. Based on chemical structure.
8 –aminoquinoline-------primaquine
4-aminoquinolines-------chloroquine, amodiaquine.
Quinoline methanols-----quinine, quinidine, mefloquine.
Antifolates-----------------dapsone, sulphadoxine,
proguanil,pyrimethamine.
Antibiotics-----------------tetracycline,doxycycline,clindamycin
Hydroxynaphthoquinone- atovaquone.
Quinghaosu compounds—artemisisnin,artemether,artesunate.

7. Based upon the stage of the parasite.
Tissue schizontocidal agent.
Blood schizontocidal agents
Gametocidal agents.

8. Based upon the clinical indication (clinical utility)
Drugs for the casual prophylaxis(pre-erythrocytic stage of
plasmodium in liver). Proguanil and Primaquine.
Drugs for the suppression of the acute stage.
 rapidly acting: artemisinin, chloroquine,
mefloquine, quinine and atovaquone.
 slowly acting: proguanil, pyrimethamine,
sulphadoxine and doxycycline ( iin combination with rapidly
acting)

9. Drugs used to prevent relapse (radical cure): they act
on the exo-erythrocytic stage: Hypnozoites of Vivax & Ovale.
Primaquine is used for this purpose.
Drugs for the terminal prophylaxis e.g., after a visit to
the endemic area.
Drugs for the prevention of transmission of
gametocytes. (Primaquine).

10. •Tissue schizonticides
•Primaquine.
•BLOOD SCHIZONTICIDE
•Chloroquin.
•Quinidine.
•Quinine.
•Proguanil.
•Pyrimethamine.

11. GAMETOCIDES
Chloroquine.
Primaquine.
SPORONTICIDAL AGENTS
Pyrimethamine.
Proguanil.

12. PRIMAQUINE
[8-AMINO QUINOLINE]
•EFFECTIVE AGAINST ;
•Primary exo-erythrocytic form of P.falciparum and P.vivax.
•Sec.exo-erythro form of P.vivax and P.ovale.
•Leads to radical cure of vivax and ovale.
•Destroys or renders gametocytes in-effective of all 4 types of
plasmodia.

13. Metabolic compounds released are oxidants
which has schizonticidal action also resulting
in hemolysis and methemoglobinemia.

14.  ORAL ADMINISTATION
 WELL ABSORBED.
 RAPIDLY OXIDISED
 EXCRETED IN URINE.SS

15. All plasmodia can develop resistance[p.vivax]
 So double the dose and give for
14 days.

16. •Hemolytic aneamia in G6PDdefficient pts.
•Abdominal discomfort [larger doses]
•Rarely causes
• Agranulocytosis.
• Granuloctopenia.
• Methemoglobinemia.

17.  LUPUS OR ARTHRITIS
 PREGNANCYSS

18. Primaquin in combination with clindamycin is
effective in mild to moderate pneumocystitis.

19. CHLOROQUINE
 ERYTHROCYTIC SCHIZONTICIDE
 [ Synthetic 4- amino quinoline]

20. • EFFECTIVE AGAINST ;
• sensitive strains of p.falciparum.
• Asexual form of all plasmodia.
• extra- intestinal amebiasis.
• rheumatoid arthritis.
• discoid lupus erythematosus.

22. Cloroquine binds with heme.
prevents polymerization of heme to
hemozoin.

23. Orally administered.
Completely absorbed.
Wide area of distribution.
Can cross the blood brain barrier.
Can traverse placenta.
Metabolized in the liver.
Excreted in the urine.

24. Multigenic alterations mainly mutation in
putative transporter[PfCRT], confers high level
resistance to chloroquine.
Should be used in combination with drugs that
can reverse the resistance.s

25. •Therapeutic doses; minimal side effects.
•Large doses; abd pain
• headache
• blurring of vision
• pruritis.
•Continous larger doses ; permanent
• Ototoxcity,
• retinopathy
• myopathy,
• Peripheral neuropathy,
dizzines;hallucinations and depression.s

26. ECG changes[broadning of QRS complex;Twave
inversion.]
Rapid parenteral inf can lead to Cardiac arrest
or resp arrest and even death.

27. •P SORIASIS; PORPHYRIA.
•RETINAL OR VISUAL DISTURBANCE.
•HEPATIC DYSFUNCTION.
•SEVERE GI DIORDERS
•NEUROLOGIC OR BLOOD DISORDER.
•Should not be given along KAOLIN ;Mg
antacids.
•Should not be given along GOLD;
PHENYLBUTAZONE.

28. Closely related to chloroquine.
 Effective against resistant strains of
plasmodium falciparum.
WHO has recommended its use in combination
as
 Amodiaquine + Artemisinin.
 Amodiaquine + [Sulphonamide-
Pyrimethamine ].

29. Piperaquine in combination with dihydro
artmisinin.
Effective against falciparum malaria.
Half life =28 days so longer post
treatmentprophylaxisis provided with
piperaquine dihydroartemisinin combination.

30. 4-QUINOLINE METHANOL
INDICATIONS;
Used as a single drug therapy against resistant
strains p.falciparum.

31. Same as that of quinine ,quinidine and
chloroquine.
Apparently damaging the parasite’s
memberane.

32. Oral administration,parentral causes local
irritation.
Well absorbed ,well distributed due to good
protien binding.
Termnal elimination half life is 20 days.
Constantly circulates in entero-hepatic and
entero- gastric system.
Metabolized in liver.

33. Excreted in feaces.
Can be detected even months after the therapy
from the blood.

34. Strains have been identified that are resistant
to mefloquine.
In such conditions it should be given in
combination with artesunate as
recommended by WHO.

35. From mild nausea, vomiting dizzyness
to
Disorientation,hallucination and depression.
Leukocytosis,thrombocytopeniaand elevation
amino transferase.
ECG changes and even cardiac arrest.

36. Epilepsy ,psychiatric disorders,
Cardiac conduction disorder , arrythmias.
Certain drugs

Quinine

Quinidine

Hallofurantine

37. QUININE; Derived from CINCHONA bark.
 QUINIDINE;Dextrorotatory stereoisomer
quinine.

38. Very serious and severe form of disease.
Malaria caused by resistant strains of
plasmodium falciparum.In such conditions
quinine is given parentrally till the pt gets
better and can take oral mediction.
BABESIOSIS;caused by bebesi microti,treated
by quinine+clindamycin.

39. Administered
Orally and parentrally.
After oral intake it is completely and rapidly
absorbed
Peak plasma levels achieved 1-3hrs,
Pharmacokinetics is different in different
groups of population.

40. In healthy normal people the peak plasma
concentrations slowly achieved and the half life
of the
drug is also shorter [11 hrs].

41. In those suffering from the disease the peak
plasma concentrations are rapidly achieved
and the half life of the drug is longer i-e of 18
hrs, with no increase the toxicity.
Main route of excretion is through kidneys in
the urine.

42. Causes the death of the plasmodial parasite by
preventing the formation of hemozoin from
heme.
 RESISTANCE
Some level of resistance have been
encountered in south Asia especially near the
Thailand border.

43. •At therapeutic doses;
CINCHONISM;
Headache,tinnitis,nausea ,vomiting,
flushing ,visual and auditory disturbances.
HYPERSENTIVITY REACTIONS

Urticaria,Agioedema,Broncospasm,Hypoglyce
mia.
BLACK WATER FEVER.Also a hypersensitivity
reaction.

44. I/V infusions if rapidly infused can
lead to severe hypotention.
ECG ;abnormalities [QT Interval
prolonged]
Arrythmias.

45. SHOULD BE DISCONTINUED;
Cinchonism ,hemolysis, hypersentivity reactions,
Should be suspended if there is +ive coombs
test for hemolysis.
Cardiac conduction disorders.
In renal insufficiency
In hepatic insufficiency
In visual disorders
In auditory disorders

46. Neuromuscular blocking agents
Aluminium containing antacids.
Digoxin
 Warfarin.

47.  ARTEMISININ
 [SESQUITERPENE LACTONE ENDOPEROXIDE]
 [ QUNGHAOSU ]
Active herbal component used as anti pyretic
and now used as anti malarial all over the
world.

48.  ARTESUNATE
 ARTEMETHER
 DIHYDRO-ARTIMISININ

49. • BLOOD SCHIZONTICIDE
• Antimalarial activity due release
• of free radicals by
•The iron catalyzed cleavage of artemisinin
endoperoxide bridge in the parasitic food
vacuole
. OR
•By the inhibition of parasite calcium ATPase.

50. Artemisinins are insoluble and can be only
orally.
 ARTESUNATE; Can be taken orally, i/v, i/m,
p/rectally.[ WATER SOL]
 ARTEMETHER;Can be taken orally, i/m and
p/rectally. [LIPID SOL]
 DIHYDROARTEMISININ; Can be taken only
orally. [WATER SOL]

51. Artemisinin and its analogs are rapidly
absorbed .
Peak plasma level achieved in 1-2 hrs.
Plasma half life is 1-3 hrs.
Artemisinin, Artemether and Artesunate all
metabolize in the liver to its active metabolite
Dihydroartemisinin.

52. Coformulated artemisinin based therapies
provide better antimalarial activty and prevent
the development of resistant strains.
Artemether i/m gives same result as that of
quinine.
Artesunate i/v gives superior results than
i/vquinine.

53. LOW DOSE;Nausea vomiting dizzyness.
LARGE DOSE,ECG abnormalities [QT interval
prolonged]. Neurotoxicity.

54. Safe in pregnancy
Oral artemisinin based therapy in un
complicated malaria can be given in 2
nd
and 3
rd

trimester.
I/V Artesunate can be given even in the 1
st

trimester.

55. 
SHIZONTICIDE AND
SPORONTICIDE

ANTI FOLATE

2,4 DIAMINO PYRIMIDINE

56. Used in chloroquine resistant strains of
P.falciparum.
Used in the treatment of Toxoplasmosis
Gondii.
Used in the treatment of Muco-cutaneous
Leishmeniasis.

57. P-AMINO
BENZOIC ACID
DI- HYDRO FOLIC ACID
TETRAHYDROFOLIC
ACID
PURINES
DNA
DIHYDROPTEROA
TE SYNTHASE
DIHYDROFOLATE
REDUCTASE
SULFONAMI
DE[INHIBITI
ON]
TRIMETHOPRIM
PYRIMETHAMINE
[INHIBITION]

58. Acts as anti folate in the plasmodial parasite.
Prevents the conversion of dihydrofolate to
tetrahydrofolte [an imp co- factor in the
formation of purines and the pyrimidines].
It does this by inhibiting the enzyme called
DIHYDRO-FOLATE-REDUCTASE.

59. Slowly and adequately absorbed from the GI
tract, after oral administration.
Peak plasma levels achieved in 3-7 hrs.
Metabolized in live
Mainly excreted by the kidneys.

60. Causes folic acid defficiency,especialy in
pregnancy.
Causes mild GI upset .
.
Causes mild skin rashes.
Megaloblastic aneamia,[can be reverted by
Leucoverin]

61. PYRRIMETHAMINE + SULPHADOXINE
 25 mg 500 mg
 [ANTI – FOLATE]
 Given as a single dose
INDICATIONS:
Effective against the resistant strains of
P.falciparum.

62. Fansidar is taken orally
.
Well absorbed.
Peak plasma level achieved in 2-8 hrs.
Excreted by the kidneys.

63.  Anti folate activity in plasmodium.
Pyrimethamine inhibits dihydrofolate
reductase,in the folic acid cycle.
Sulphonamide inhibits dihydropteroate
synthase in the folic acid cycle.

64.  Steven Johnson’s syndrome.
 Erythema multiforme.
 Toxic epidermal necrolysis.

65. 
Should not be used in children below 2
months of age.
Should not be given in G6PD defficient pts.
Should not be given in Bronchial asthama.
Can only be used in the 3
rd
trimester of
pregnancy.

66. DRUG FOR ALL PLASMODIA SPECIES EXCEPT
CHLOROQUINE RESISTANT P-FALCIPARUM?

67. CHLOROQUINE.

68. DRUG FOR CHLOROQUINE RESISTANT
P-FALCIPARUM?

69. QUININE PLUS
PYRIMETHAMINE-SULFADOXINE
OR
DOXYCYCLINE
OR
CLINDAMYCIN
ALTERNATE:
MEFLOQUINE