Antimalarial drugs

pharma
For the lecture of this topic, visit BISHAL CHAUHAN channel on youtube

1. Antimalarial Drugs
Dr. Binaya Shrestha


For the lecture of this topic, visit BISHAL
CHAUHAN channel on youtube

4. Current problems
• Fifth cause of death from infectious diseasesand the
second in Africa after HIV/AIDS.
• Can be treated in just 48 hours , yet it can cause fatal
complications if the diagnosis and treatment are
delayed.

5. • Widespread in tropical and subtropical parts of the
world, including Asia , Africa , America.

7. Malarial Parasite (Plasmodium)
Two interdependent life cycles
• Sexual cycle: occurs in the mosquito
• Asexual cycle: occurs in the human
– Knowledge of the life cycles is essential in
understanding antimalarial drug treatment

8. – Drugs are effective only during the asexual cycle
Aims of antimalarial drugs
• To prevent & treat clinical attack of malaria
• To completely eradicate the parasite from
pt.
• To reduce the human reservoir of infection

9. Antimalarial drugs
• Therapeutic classification
• Chemical Classification

10. Therapeutic classification
• Causal prophylaxis: (Primary tissue
schizonticides)
-Destroy parasite in liver cells and prevent invasion of
erythrocytes
– Primaquine, proguanil
• Supressives Prophylaxis:
– Supress the erythrocytic phase and thus attack of
malarial fever can be used as prophylactics.

11. Therapeutic classification
- Chloroquine, proguanil, mefloquine, doxycycline
• Clinical cure: erythrocytic schizonticides
– used to terminate an episode of malarial fever
• Fast acting high efficacy
– Chloroquine, quinine, mefloquine, atovaquone,
artemisinin
• Slow acting low efficacy drugs
– Proguanil, pyrimethamine, sulfonamides,
tetracyclines

12. Therapeutic classification
• Radical curatives:
– Eradicate all forms of P.vivax & P.ovale from the body
– Supressive drugs + hypnozoitocidal drugs
– For vivax: primaquine 15 mg daily for 14 days
• Gametocidal: – Destroy gametocytes and prevent
transmission
– Primaquine, artemisinin – against all plasmodia –
Chloroquine, quinine – Pl Vivax

13. Therapeutic classification
– Proguanil ,pyrimethamine – prevent development of
sporozoites

14. Chemical Classification

15. Cont…

16. Chloroquine
• Synthetic 4-aminoquinoline derivative
• Available as chloroquine phosphate for oral
use

17. Mechanism of action
• Inhibits parasite enzyme haem polymerase
and protects the host haem from being
converted to hemozoin and this free haem is
toxic to parasite
• Being a basic drug it diffuses freely into
parasite food vacuole and gets ionised and

18. get trapped inside the parasite making the
food vacuole non- functional

20. Adverse effects
• Nausea, vomiting, dizziness, headache
• Urticaria, blurred vision
• Larger doses sometime may precipitate
retionpathies
• Bolus IV injection may cause ECG changes

21. Clinical use
• Acute attack of malariaTab. Chloroquine
600mg (base) stat followed by 300mg base
after 6hrs followed by 150mg(base) twice a
day for 2 days
• Chemoprophylaxis of malaria
• Rheumatoid arthritis
• Amoebic abscess

22. Contraindication
• Patients with retinal and visual field
abnormalities
• G6PD deficient persons
• Psoriasis
Quinine
• Alkaloid derived from cinchona bark

23. • Used in prevention and treatment of malaria
since 1820

24. Mechanism of action
• Like chloroquine it inhibits haem polymerase
• It also acts as protoplasmic poison to the
parasite feeding mechanism and hampers the
supply of aminoacids and peptides

25. Adverse effects
• Cinchonism:-large doseringing in ears,
nausea, vomiting, headache, vertigo,visual
defects,
• Hypogylcemia
• Hemolysis in G6PD deficient person
• Respiratory depression

26. • Cardiac arrythmias
Uses
• Cerebral malaria
• Uncomplicated resistant falciparum malaria
• Noctural muscle cramps

27. Primaquine
• Synthetic 8-aminoquinoline derivatives

28. Mechanism of action
• Not well understood
• Its quinone metabolite inhibits respiratory
process of the parasite in its
exoerythrocytic state
Adverse effects
• GIT distress

29. • Headache, pruritis
• G6PD deficient personhaemolytic
anemia
Uses
• Radical cure of malariaprevent relapse

30. • Non-malarial use: Pneumocystis jiroveci
pneumonia
Combinations
• Pyrimethamine-Sulfonamide
/Dapsone:Sulfoamides/dapsone are effective
antimalarial drugs
However when combined with pyrimethamine
they form synergistic effects due to sequential
block.

31. As Pyrimethamine blocks DHFR and sulfonamide
competes replace PABA by competing with folic
acid synthetase and forms nonfuncional
analogue of folic acid
Proguanil
• Biguanide
• Inhibits plasmodial DHFR
• Rapidly absorbed from GIT
• Prodrug

32. • Not used alonedevelopment of
resistance
• Combined with atovaquone for
chemoprophylaxis
• Adverse effects similar to pyrimethamine
Artemisinin derivatives
• Artesunate, artemether and arteether

33. • Obtained from chinese herb Artemisia annua

34. Mechanism of action
• Endoperoxide bridge of artemisinin molecules
is broken down by ferrous protoporphyrin-IV
leading to generation of highly reactive free
radicals that damage the membrane of the
parasite by binding with membrane protiens
Adverse effects

35. • Serious toxicity is rare
• Nausea, vomiting, abdominal pain
• Itching
• Temporary Q-T prolongation

36. Dose
• Arteether:- 130mg i.m daily for 3 days
• Artesunate:-100mg BD orally on 1
st
day
followed by 50mg BD for next 5days or 120mg
i.m on 1
st
day followed by 60mg daily for 4-5
days
• Artemether:- 80mg BD on 1
st
day followed by
80mg OD for 4 days

37. Halofantrine
• Phenantherene-methanol group
• Potent blood schizonticide
• Oral bioavailability is poor
• Half-life is 3-5 days
• Mechanism of action is not well understood

38. • Use is highly restricted because of
cardiotoxcity
Antibiotics
• None of the antibiotics are effective against
malarial parasite if used alone
• Tetracycline and doxycycline are blood
schizonticides

39. • Second line of therapy for chemoprophylaxis
of malaria in chloroquine resistance P.
falciparum malaria