Antimalaria drugs

1. “MALARIA”

2. •Parasitic, endemic disease
•Malaria is a single cell protozoan
•It is caused by sporozoa of plasmodium
•Transmitted to human by bite of feMALe
AnopheLes mosquito .
•Symptoms become apparent only 7-10days

3. Plasmodium species which
infect humans
Plasmodium vivax (tertian)©
Plasmodium ovale (tertian)
Plasmodium falciparum (tertian) © (d)
Plasmodium malariae (quartian)

4. Symptoms
•Fever
•Shivering
•Pain in joints
•Headache
•Repeated vomiting
•Severe  convulsions, coma

5. Classification of Malaria
•Uncomplicated Malaria
•Cold stage (sensation of cold, shivering)
•Hot stage (fever, headaches, vomiting; seizures
in young children)
•Sweating stage (sweats, return to normal
temperature, tiredness)

6. Classification of Malaria
•Severe Malaria
–Cerebral malaria (seizures, coma)
–Severe anemia
–Hemoglobinuria
–Abnormalities in blood coagulation
–Cardiovascular collapse and shock (“rosettes”) P.F

7. Pre erythrocytic
(hepatic) cycle
10-14days
Sporozoites
Mosquito Salivary
Gland
Malaria Life Cycle
Male & Female
Gametocytes
Oocyst
Erythrocytic
Cycle
Zygote
Schizogony
Sporogony
Hypnozoites
(for P. vivax
and P. ovale)
para/exo
erythrocytic
cycle
Sporozoites
Mono nucleated
merozoites
Motile
trophozoites
Multi nucleated
merozoites
Liver- Tissue schizonts
RBC- Blood schizoints
sexual cycle
in mosquito
Asexual cycle
in human

8. Types of Infections
•Recrudescence
–All merozoites are not completely eradicated
–Surviving merozoites enter erythrocytic phase again (P.f.,
P.m.)

•Relapse
–Reactivation of hypnozoites forms of parasite in liver(P.v&
P.o)
•Recurrence or reinfection
–exo-erythrocytic forms infect erythrocytes

9. Classification of antimalarials:
Based on clinical use (Based on stage of parasite they affect)
•True causal prophylactics:
•Causal prophylactics: Primaquine (3Ps)
Pyrimethamine,
Proguanil
–Maturation of sporozoites Schizonts in liver
•Supressives prophylactics :Quinine (MCQ-P)
(chemoprophylaxis)4-aminoquinolines (Chloroquinine)
Mefloquine
Proguanil
–Destroy the merozoites so errythrocytic stage is prevented.
•Clinical cure: Chlorquinine, Pyrimethamine, Sulfadoxine (CPS)
–Blood schizonticides
•CQ resistance: Qunine, Mefloquinine , Artesunate
•Radical curatives: Primaquine (P.v& P.o)

10. Antimalarial drugs
1.Chincona alkaloids-Quinine
2.4 aminoquionoline-Chloroquine, Hydroxychloroquine,

3.8 aminoquionolines-Primaquine
4.Biguanides- proguanil
5.Diaminopyridines- Pyrimethamine
6.Quinoline methanol-Mefloquine
1.Phenanthrene- Halofantherine
•Artemisinin derivativesArtesunate, Artemether, Arteether
•Acridine Mepacrine, Quinacrine
10.Misellaneous- sulfonamides Teracycline
Atavaquone

11. 4 aminoquinolines :Chloroquine
•Synthetic available as chloroquine phosphate
Pharmacokinetics
•Rapidly and completely absorbed oral/IM/IV slow.
•Peak conc. 2-3 hrs after oral dose.
•Highly conc. in liver, spleen ,lung, kidney.
•Vd high
•Drug persist for longer period after discont.
•t½ 3-4days but terminal t½1-2months
•Metabolised to 4hydroxychloroquine.

13. Actions & Clinical use
Antimalarial
•Potent blood schizonticidal
•Gametocidal P.Vivax, P.Ovale
•Relapse common so therapy followed by
primaquine 15mg OD for 15days
•P.falciparum is resistance

14. Uses & Dose
1.Malaria
2.Ameobiasis - Hepatic
3.Acute manifestations of Lepra reaction.
4.Arthritis Rheumatoid
5.Infectious mononucleosis
6. Autoimmune disorder- Discoid lupus erythematous
Doses-antimalarial vd-high
Tab. Chloroquine 250 mg-4tab stat
2tab after 6hrs
2tab daily for 2days
2 tab once a week
Others Hydroxychloroquine & Amidoquine

15. Amodiquine
•Spectrum and clinical use are same
•A/E: Agranulocytosis
•Cheap
•Respond to chloroquine resistance P.falciparum

16. quinine
•Obtained from cinchona bark -1820
•P.K: Orally/slow IV for severe P.falciparum
malaria
•Wide distribution
•t½- 10-11hrs
meChAnism of ACtion:
•Being a protoplasmic poison to parasite
•Hampers the supply of aminoacids and
peptides

17. Clinical use
•Erythrocytic state
•Gametocidal activity in P.Vivax, P.Ovale
•Main drug for treating chloroquine resistant
P.falciparum malaria
•Loading dose.
•Require IV slow infusion in severe conditions
•Patient condition improve shifted to oral
•Present indication-cerebral malaria
•Nocturnal leg cramps

18. A/E
•GIT: Quinine inc. gastric acid secretion by
irritation
•CVS: Depress myocardium and cause hypotension
•Sk. Muscle : neuromuscular blockade
•CNS: In therapeutic dose – Hearing and vision
disturbance.
•IV it cause thrombophelbitis
•Stimulation of insulin  Hypoglycaemia
•Black water fever – Rare characterized by
haemolysis, Haemoglobinemia, Haemoglobinuria
renal failure

19. Quinoline methanol : Mefloquine
•4 aminoquiniline derivative, haem poly. inhibitor
•Highly effective against erythrocytic cycle
•Orally. No parental  Local irritation
•High protein binding
•t½-20days
•It is used as Prophylaxis or clinical cure
•Avoided during pregnancy
•Should not be co-administered with quninie
•Reserve drug for prophylaxis and R
chloroquinine resistant malaria

20. Antifolates: PyriMethaMine,
SulPhadoxine, SulPhoneS, Proguanil
•Pyrimethamine + Sulphadoxine 
Chloroquine resistant amlaria
•Oral
•Initial loading dose require
•87% PB
•Half life 3-4days
•Sulphones Dapsone

21. PABA
DHF SYNTHETASE

DHF
DHF REDUCTASE
THF

22. PyriMethaMine
•Slow acting blood schizonticide
•Resistance rapid so combination with
sulfonamide
•Sulfadoxine500mg+ Pyrimethamine25mg
combination adjunct with quinine to treat
chloroquinine resistance P.falciparum malaria

23. A/E:
•At high dose it inhibits mammalian folate
synthesis
•CNS stimulation causes seizures
•Large dose of Pyrimethamine+ Dapsone
combination cause anaemia, agranulocytosis

24. Proguanil
•Same mech of action folate synthesis inhibitor
•Produrg liver cycloguanil
•Half life 16hrs
•Alone resistance combination with Chloroquine
•Effective schizontocide
•Prevents maturation of fertilized gametes

25. Proguanil
AE:
1.Git:stomatitis, mouth ulcers
2.CVS:depression
3.Blood:leucopenia,megaloblastic anaemia.
DOSE:100 mg tab.
USE:
For causal prophylaxis
MALARONE-proguanil(100mg)+atovaquone(250mg),used
for multi drug resistance malaria.
Dose-4 tab od for 3 days

26. PriMaquine
•8- Aminoquinoline derivative
•Oral t½ 3-6hrs
•Mech: Inhibits respiratory process of parasite
in its erythrocytic state
•Use in radical cure and prevent relapse for P.
vivax & ovale
•CI : In pregnancy . foetus G6PD  Risk of
haemolysis
•Dose:15 mg daily x 14 days for radical cure of p. vivax.

27. Artemesin(Qinghaosu) derivatives
•artemisinin isolated from the verb Artemisia annua
(1972)
•Parasitic protophorphrin IV – catalyses breakdown of
endoperoxides (-0-0-) bridges of artemesin
molecules generation high free radicals.
•Killing of malaria parasite is mediated by production
free radicals
•Inhibit hemoglobin digestion by malaria parasites
• Artemether
• Arteether
• Artesunate

28. •Artemisinin induce rapid killing of parasites
•Fast clearance rate
•Very few side effects
•Artemsinin-resistant parasites have not been
identified
•Should be used in combination with other
antimalarial drugs
Therapeutic uses
•Clinical cure of severe malaria, chloroquine
resistance malaria

29. •ADR:-
•Very few adverse reactions
•Common side effects include
–Nausea
–Vomiting
–Anorexia
–dizziness
•Safe for pregnant women

30. TREATMENT
•In patients who can take drugs orally
Chloroquine 250mg 4 tab stat (600mg base)
300mg after 12hrs
300mg OD for 2
nd
and 3
rd
day
Note: chloroquine phosphate 250mg =150mg base
OR
Quinine salts- 600mg tab TDS for 7days

31. In patients who cannot take drugs orally
Chloroquine IM 2.5mg/kg every 4 hrly
Chloroquine IV 10mg/kg over 4 hrs
5mg/kg over every 12 hrly

32. Chloroquine resistant malaria
1.Quinine 600mg TDS for 7 days along with
Pyrimethamine 75mg+sulfadoxine 1500mg
2. Quinine 600mg TDS + Teracycline 250mg qid -7 days.
3.Mefloquine 750mg stat followed by 500mg 12hr later.
4. Artesunate 100mgBD on 1
st
day followed by 100mg OD -5 days
5.Artesunate iv/im 120mg on 1
st
day followed by 60mg daily-4 days
6.Artemether (im)-80mg BD 1
st
day followed then OD -4 days.
7.Arteether (im)-150mg od -3 days.

33. Cerebral malaria
•Serious disease-P.falciparum with strongly marked CNS
symptoms, impaires consciousness
Treatment
-IV Quinine 600mg in 500ml of 5% dextrose slowly over 4 hrs
repeated every 8 hrs till patient is conscious
followed by oral treatment to complete 7 day course.
-Antipyretic for fever
-IV Diazepam
-If fatal hypoglycemia -5%iv dextrose cont. infusion.
-correction of fluid and electrolyte balance, treatment of acidosis
Rapid iv can cause
• fall in BP
•Cardiac arrythmias.