Malaria is major health problem in Pakistan and tropics. Malaria is caused by 4 species of plasmodium parasite. ☆ Plasmodium Vivax ☆ Plasmodium Ovale ☆ Plasmodium Falciparum ☆ Plasmodium Malaria Chemically Anti-malarial drugs are classified to two categories. 4 aminoquinolines and 8 aminoquinolines. 1• 4 Aminoquinolines Chloroquine, Amodiaquine, Piperaquine, Mefloquine, Quinine, Proguanil, pyrimathamine, and Sulfadoxine . 3•8 Aminoquinolines Primaquine, Tafenoquine, Atovaquone, pyronarodin, Halofantrene, Lumefantrene, Artesunate, Artemether, Arteether and Arterolane. #pharmacology #Nursing #Nursingnotes #antimalarial

1. Unit-II Lecture-VII
Anti-malarial Drugs
By: Muhammad Aurangzeb
BSN, MSPH, MSN
Lecturer-INS/KMU

2. Objectives
At the completion of this unit the students will be able to;
• Define the most commonly used categories of anti-malarial
drugs that are used to prevent and treat malaria
• Briefly discuss action and effects of selected drug category
• List some of the most commonly used drugs for each drug
category
• Discuss the nursing measures/patient education which can be
taken if patient is using anti-malarial drugs.

3. Introduction
• Malaria is major health problem in Pakistan & tropics.
• Malaria caused by 4 species of plasmodium parasite :-
• -> Plasmodium vivax
• -> Plasmodium ovale
• -> Plasmodium falciparum (severe malaria)
• -> Plasmodium malariae
Sir Ronald Ross

5. Schizogony
(asexual)
Man : Intermediate
host
Mosquito : Definitive
host
Life cycle of the malarial parasite
Causal
prophylactics
Supressives
Gametocidal
Sporonticide
Sporogeny
(sexual)
True causal prophylactics

6. Life cycle (brief)
• Causative organism- Plasmodium
• Vector/definitive host: female anopheles mosquito,
• Intermediate host: human being i.e. a man.
• Life cycle occurs partly inside the mosquito (sexual sporogony ) & man
(asexual schizogony)
• Mosquito bites man, it transmits sporozoites to his blood.
• Sporozoites travel to liver where it reproduces asexually (tissue
schizogony) producing merozoites.
• Merozoites infect new RBCs and initiate asexual multiplication in RBC
(blood schizogony) leading to production of more merozoites.
• The RBC bursts and starts the infective cycle.
• Some merozoites develop into male and female gametes.
• Some merozoites remain dormant in the liver (hypnozoites) which can
cause a relapse of infection later (p. vivax & ovale)

7. Cont….
• When mosquito bites infected person, gametes are taken up
with the blood.
• The gametocytes mature in the mosquito gut and fuse to
form an ookinate which develops into sporozoites.(Sexual
sporogony)
• Sporozoites migrate to salivary glands and infect a new host
when mosquito bites the person.
• Recurrent malaria : Can be relapse(hypnozoites) or
recrudescence (parasites surviving in blood due to
incomplete treatment)

8. Antimalarial drugs
Drugs used for:
• Treatment
• Prophylaxis or
• Prevention of relapses of malaria.

9. Therapeutic Classification Antimalarial
Drugs
1. To prevent clinical attack of malaria (prophylactic)
• Causal prophylactics attack the pre-erythrocytic phase in
liver which is the cause of malarial infection. (TISSUE
SCHIZONTOCIDE) e.g. Primaquine, proguanil
• Suppressive prophylactics suppress the erythrocytic phase &
prevents attack of malarial fever. e.g. Chloroquine, proguanil,
mefloquine
• Prophylaxis advised in:-
– Non immune travellers to endemic areas
– Non immune persons living in endemic areas for fixed
time (e.g. army units)
– Infants, children, pregnant women in endemic areas

10. Therapeutic Classification Antimalarial
Drugs
2. Totreat clinical attack of malaria (clinical curatives)
– Attack the erythrocyte schizonts & terminates episode of malarial
fever.(ERYTHROCYTIC SCHIZONTOCIDE)
– There are Fast acting high efficacy ones (e.g. Chloroquine, quinine,
artemisinin) & Slow acting low efficacy drugs (e.g. Proguanil,
pyrimethamine, sulfonamides)
3. Tocompletely eradicate the parasite from the body
(radical cure)
– Indicated only in P.vivax& P.ovale because they produce
relapsing malaria due to persistence of hypnozoites. e.g.
Primaquine

11. Therapeutic Classification Antimalarial
Drugs
4. Gametocidal drugs
- Helps in decreasing the transmission of malaria from
infected person to another.
- No use to the infected person
- E.g. Primaquine, proguanil, pyrimethamine.

13. Chemical classification
• 4 aminoquinolines
– Chloroquine, Amodiaquine, Piperaquine
• Quinoline methanol
– Mefloquine
• Cinchona alkaloid
– Quinine, Quinidine
• Biguanides
– Proguanil
• Diaminopyrimidines
– Pyrimethamine
• Sulfonamides
– Sulfadoxine, dapsone

14. Chemical Classification
• 8 aminoquinolines:
– Primaquine, Tafenoquine
• Naphthoquinone
– Atovaquone
• Naphthyridine
– Pyronaridine
• Amino alcohols
– Halofantrene, Lumefantrene
• Sesquiterpene lactones:
– Artesunate, artemether, arteether, Arterolane

15. Chloroquine
• Rapid action
• Erythrocytic schizontocide of all species of Plasmodium.
• Controls clinical attacks in 1-2 days.

16. Mechanism of action
• Plasmodium digest hemoglobin to heme & globin in their
acidic vacuole. Globin is used by plasmodium for nutrition.
• Heme being toxic to plasmodium is converted to non toxic
pigment hemazoin by heme polymerase enzyme of the
parasite.
• Chloroquine concentrates inside the acidic vacuole of
parasite & raises the pH of vacuole. Interferes with
conversion of toxic heme to non toxic hemazoin by inhibiting
heme polymerase.
• CQ-Heme complex formed damages plasmodial membranes.

17. Hemoglobin Globin utilized by
malarial parasite
Heme (highly toxic for malaria parasite)
Chloroquine
Quinine,
mefloquine (-)
(+) Heme
Polymerase
Hemozoin (Not toxic to plasmodium)
Mechanism of action

18. Chloroquine resistance
• Chloroquine resistance is fast developing in P. Falciparum & is
a major problem because severe cases of malaria are caused
by this species.
• Resistance develops due to efflux mechanism

19. Pharmacological actions
• Antimalarial activity
• Other parasitic infections:
– Giardiasis, extrainstestinal amoebiasis
• Other actions:
– Anti-inflammatory, antihistaminic , local anaesthetic ,
weak smooth muscle relaxant, Antiarrhythmic activity .

20. Pharmacokinetics
• Good oral absorption.
• Concentrated in liver, spleen, kidney, lungs ,skin, leucocytes
• Selective accumulation in retina: ocular toxicity on prolonged
use.
• Metabolized in liver, excreted in urine.
• T1/2 = 3-10 days. Due to tissue binding, small amounts
persist in body with terminal t1/2 of 1-2 months.

21. Adverse drug reactions
• Occurring at low dose/ short duration use
– Nausea, vomiting, anorexia, epigastric pain
– uneasiness
– itching
– Headache, difficulty in accommodation
• Occurring at high doses/prolonged use
- Loss of vision(retinal damage)/, corneal deposits leading to
diminished vision
- Loss of hearing
- Mental disturbances
- Graying of hair
- Rashes, photo allergy

22. Contraindication
• Liver damage
• Severe GIT, neurological, retinal , hematological diseases.
• Should not be co-administered with mefloquine, amiodarone,
antiarrhythmics.
• CAN BE GIVEN IN PREGNANCY

23. Therapeutic uses
1. Malaria : Used for clinical cure against P
.ovale, P.malariae,
P.ovale & some P
.falciparum that are still sensitive.
2. Giardiasis
3. Extraintestinal amoebiasis
4. Rheumatoid arthritis
5. Lupus Erythematous

24. Amodiaquine & Piperaquine
Amodiaquine
• Identical properties to chloroquine
• Even Chloroquine resistant strains may be effective.
Piperaquine
• Appears effective in resistant cases

25. Mefloquine (Quinoline methanol)
• Developed to deal with chloroquine resistant P. falciparum
• Rapidly acting Erythrocytic schizonticide of chloroquine
sensitive & resistant plasmodia (clinical curative).
• Also effective suppressive prophylactic for multidrug
resistant P. Falciparum.
• Mechanism of action similar to Chloroquine.
• Adverse effects : Nausea, vomiting, diarrhea, QT
prolongation, neuropsychiatric reactions (ataxia, anxiety,
hallucinations)
• Contraindicated in psychiatric disorders, cardiac conduction
defects, 1st trimester of pregnancy.

26. Quinine
• L-isomer alkaloid isolated from cinchona bark.
• Quinidine is d-isomer used as antiarrhythmic(mainly) & as
antimalarial
• Erythrocyte schizontocide against all plasmodium (including
CQ &MDR P.falciparum) but more toxic than CQ.
• Also kills gametes of P.vivax
• Mechanism of action: Similar to chloroquine

27. Adverse drug reactions
• Cinchonism ( large single dose/higher therapeutic doses for longer
period)
• Tinnitus, nausea & vomiting
• Headache, mental confusion, vertigo, difficulty in hearing & visual
disturbances
• Diarrhea , flushing & marked perspiration
• Still higher doses : exaggerated symptoms with delirium , fever,
tachypnea, respiratory depression , pulmonary edema, hypoglycemia.
• Idiosyncrasy in some individuals: cinchonism develops at therapeutic
doses itself
• Occasional hemolysis in pregnant women & patients with P. Falciparum,
hemoglobinuria (black water fever) &kidney damage

28. Uses
• Malaria:
– uncomplicated resistant falciparum malaria – oral quinine
given.
– Complicated & severe malaria including cerebral malarial
– IV quinine used
• Nocturnal muscle cramps

29. Biguanide (Proguanil)
• Proguanil : It exerts its antimalarial action by inhibiting
parasitic dihydrofolate reductase enzyme.
– Biguanide converted to cycloguanil active
compound
– Act slowly on erythrocytic stage of vivax &
falciparum
– Prevents development of gametes
 Adverse effects:
 Stomatitis, mouth ulcers, larger doses depression of myocardium ,
megaloblastic anemia
 Not a drug for acute attack
 Causal prophylaxis: 100 –200 mg daily

30. Diaminopyrimidines (Pyrimethamine)
• MOA: Selectively inhibits the plasmodial form of
dihydrofolate reductase, reducing the production of folic acid
required for nucleic acid synthesis in the malarial parasite
• More potent than proguanil & effective against erythrocytic
forms of all species.
• Used only in combination with sulfonamides for malariaa
treatment.
• Tasteless so suitable for children
 Adverse events: megaloblastic anemia, thrombocytopenia,
agranulocytosis.

31. Sulfonamides (Sulfadoxine)
• Long acting sulfonamides (Sulfadoxine) are not effective
antimalarial but combination with Pyrimethamine causes
sequential blockade of folic acid synthesis in plasmodia.
• Effective against erythrocytic stage of P.falciparum.
• Combination acts faster & prevents development of
resistance.
• Risk of hypersensitivity reactions due to sulfonamide
component.

32. 8 aminoquinolines:
Primaquine, Tafenoquine
Primaquine:
• Most active against Liver hypnozoites (pre-erythrocytic
phase).
• Weak action against erythrocytic stage of vivax. No action
against erythrocytic stage of falciparum
• Has gametocidal action against all species.

33. – Interferes with oxygen transport
system
Primaquine
Converted to
electrophiles
Generates reactive
oxygen species
Primaquine Mechanism of action:

34. Uses & Adverse effects of Primaquine
Uses
• Primary use is radical cure of relapsing malaria in P. Vivax.
(15 mg daily for 14 days with dose of chloroquine)
• Gametocidal in Falciparum malaria(45 mg of single dose
with chloroquine) & cut down transmission of malaria.
Adverse effects
• Gastrointestinal
– epigastric distress, abdominal cramps ,
• Hemopoetic:
– mild anemia, cyanosis, hemolytic anemia in G6PD deficiency.
• Avoided during pregnancy, G6PD patients

35. Tafenoquine
• Tafenoquine:
– More active slowly metabolized analog of primaquine, has
advantage that it can be given on weekly basis.
– single dose anti-relapse therapy for vivax malaria.

36. Naphthoquinone (Atovaquone)
• Synthetic napthoquinone
• Rapidly acting erythrocytic schizonticide for plasmodium
falciparum & other plasmodia
• MOA: Collapses mitochondrial membrane & interferes ATP
production
• Proguanil potentiates action of atovaquone and prevents
development of resistance

37. Naphthyridine (Pyronaridine)
• Pyronaridine (PYR) is an erythrocytic schizonticide with a
potent antimalarial activity against multidrug‐resistant
Plasmodium. The drug is used in combination with artesunate
(Pyramax) for the treatment of uncomplicated P.
falciparum malaria, in adults and children.
• MOA: partially understood MOA, with at least two important
activity pathways, the inhibition of heme to hemozoin
conversion and the intercalating DNA and Topoisomerase 2
pathways, prominently implicated in the antimalarial and
anticancer activities, respectively
• Adverse Effects: well tolerated, the most common side effects
being headache, vomiting, abdominal pain, bradycardia, and
hypoglycemia.

38. Amino alcohols
Halofantrine & Lumefantrine
• Lumefantrine is an antimalarial agent administered in
combination with artemether for improved efficacy to treat
acute uncomplicated malaria. This combination therapy
exerts its effects against the erythrocytic stages of
Plasmodium spp.
• MOA: Lumefantrine binds to hemin produced during
hemoglobin breakdown, preventing detoxification to
hemozoin. During the same process, the peroxide group in
artemether binds to heme and releases toxic free-radicals.
• Side Effects of combination artemether/lumefantrine therapy
include headache, anorexia, dizziness, and asthenia. Possible
serious adverse effects include QT prolongation, bullous
eruption, urticaria, splenomegaly, hepatomegaly,
hypersensitivity reaction, and angioedema.

39. Sesquiterpene Lactones:
Artemisinin
• Artemisinin is the active principle of the plant artimisia annua .
• Most potent and rapid acting against blood schizonticides of
P.falciparum resistant to all other drugs.
• Due to short duration of action there is high recrudescence
rate.
Mechanism of action
• These compounds have endoperoxide bridge.
• Heme iron cleaves this endoperoxide bridge to form highly
reactive free radicals which damage parasite membrane by
covalently binding to membrane proteins

40. TuYou You
Received Nobel prize in Physiology/Medicine in
December 2015 for discovery of Artemisinin

41. Plant- Artemisia Annua

42. Artemisinin Derivatives
• Artesunate
• Artemether
• Arteether
• Arterolane

43. Artesunate
• Water soluble ester of dihydroartemisinin
• Dose: can be given oral, IM,IV, rectal
– Oral
• 100 mg BD on day 1
• 50 mg BD day 2 to day 5
– Parenteral
• 120 mg on day 1 (2.4 mg/kg BD )
• 60 mg OD ( 2.4 mg/kg) for 7 days

44. Artemether
• Methyl ether of dihydroartemisinin
• Dose:
• Oral & IM
• 80 mg BD on day 1 (3.2 mg/kg)
• 80 mg OD (1.6 mg/kg) for 7 days

45. Adverse effects
• Mild adverse effects like nausea, vomiting, abdominal pain,
drug fever, itching (common)
• Tinnitus, dizziness, bleeding, dark urine, ECG changes, QT
prolongation, leucopenia are rare.
Uses
• Uncomplicated P.falciparum(CQ sensitive & resistant)
• Severe & complicated malaria : given parenterally.

46. Artemisinin Based Combination Therapy
(ACT)
• Artemisinin compounds are shorter acting drugs.
• Monotherapy needs to be extended beyond disappearance
of parasite to prevent recrudescence.
• This can be prevented by combining artemisin compounds
with one long acting drug like mefloquine etc.

47. Why Combination Therapy?
• Rapid clinical & parasitological cure.
• High cure rates and low relapse rates.
• Absence of resistance.
• Good tolerability profile.

48. ACT Regimens in use
• Artesunate – Sulfadoxine- pyrimethamine
• Artesunate -Mefloquine
• Aretemether -lumefantrine
• Artesunate- amodiaquine
• Arterolane- piperaquine

49. Antimalarial Drugs Nursing Implications
• Before therapy, thorough health history, medication history,
assess for allergies
• Check baseline VS, also check for contraindications and
interactions
• Administer all drugs as ordered and for the prescribed length
of time
• Most drugs should be taken with food to reduce GI upset
• Instruct patient to notify physician immediately if ringing in
the ears, visual difficulties, nausea, vomiting, profuse
diarrhea, or abdominal pain occurs
• Alert patients to the possible recurrence of the symptoms of
malaria so that they will know to seek immediate treatment
• Monitor for adverse effects

50. Thank you