Kipengele K,

Bpharm

Basic Pharmacology
NTA Level 4 Semester 2

2020
1
 Kipengele K,
Bpharm

Description of Antimalarial
Drugs

Session 10
 Kipengele K,
Bpharm
Learning Tasks
By the end of this session you are expected to be
able to:
• List indications of antimalarial drugs
• List contraindications of antimalarial drugs
• Describe dose, dosage and course of antimalarial
drugs
• List side effects and adverse effects of antimalarial
drugs
• Describe interactions and precautions of
antimalarial drugs
 Classification of Antimalarial Drugs
based on the disease stage
• Tissue schizonticides
 Drugs that eliminate developing or dormant liver forms
of malaria parasite
 Examples: Primaquine, Proguanil
• Blood schizonticides
 Those that act on erythrocytes stage of malarial parasites
 Examples: Chloroquine, Quinine, Mefloquine, Pyrimethamine,
Sulfonamides
• Gametocides
 Those that kill sexual stages of malaria parasites and
prevent transmission to mosquitoes
 Examples: Primaquine, artemesinin, Chloroquine, Quinine
 The indications of different antimalaria
drugs
Chloroquine
• Is a highly effective blood schizonticide
• It is also moderately effective against
gametocytes of P. vivax, P. ovale, and P.
malariae but not against those of p falciparum
• Chloroquine is not active against liver stage
parasites
• But its utility against p falciparum has been
seriously compromised by drug resistance
The indications of different antimalaria
drugs...
Amodiaquine
• Amodiaquine is closely related to chloroquine, and it
probably shares mechanisms of action and resistance
with that drug
Quinine & Quinidine
• Quinine is a rapidly acting, highly effective blood
schizonticide against the four species of human malaria
parasites
• The drug is gametocidal against P. vivax and P. ovale
but not P. falciparum
• It is not active against liver stage parasites.
• The mechanism of action of quinine is unknown
The indications of different antimalaria
drugs...
Artemisinin and its derivatives
• Are very rapidly acting blood schizonticides
against all human malaria parasites
• Artemisinins have no effect on hepatic stages of
malaria parasites
• Artemisininsin particular artesunate and
artemether are playing an increasingly important
role in the treatment of multidrug-resistant p
falciparum malaria
• They are the only drugs reliably effective against
quinine resistant strains
The indications of different antimalaria
drugs...
The most important of these analogs are:
• Artesunate (water-soluble; useful for oral,
intravenous, intramuscular, and rectal administration)
• Artemether (lipid-soluble; useful for oral,
intramuscular, and rectal administration)
Lumefantrine
• Is an aryl alcohol related to halofantrine, is available
as a fixed-dose combination with artemether as
Coartem in some countries
• Coartem is highly effective in the treatment of
falciparum malaria
 Contraindications of Antimalarial
Drugs
Chloroquine is contraindicated in patients with
• Psoriasis or porphyria, in whom it may
precipitate acute attacks of these diseases
• It should generally not be used in those with
retinal or visual field abnormalities or myopathy
Quinine (or quinidine)
• Should be discontinued if signs of severe
cinchonism, hemolysis, or hypersensitivity occur
• It should be avoided if possible in patients with
underlying visual or auditory problems
 Contraindications of Antimalarial
Drugs...
Artemisinins
• It is contraindicated the first trimester of
pregnancy if possible because
teratogenicity has been seen in animal
studies, but limited inadvertent use in
pregnancy has apparently not led to fatal
problems
• Is avoided in breast feeding mother whose
infant is below 5kg body weight
 Dose, Dosage and Course of
Antimalarial Drugs
Artemether & Lumefantrine
• Dosage of Artemether 20mg & Lumefantrine
120mg tablets according to weight and age
WT(Kg) AGE Day 1 Day1 Day2 Day2 Day 3 Day3
O hr 8hrs 24 hrs 36 hrs 48hrs 60hrs
5-14 3mon- 1 1 1 1 1 1
3yrs
15-24 3yrs- 2 2 2 2 2 2
8yrs
25-34 8yrs- 3 3 3 3 3 3
12yrs
35 above 12yrs 4 4 4 4 4 4
above
 Home Work
• What is loading dose and maintenance dose?
• Regarding dosage of ALU,
a) Why 2nd dose is given after 8 hrs from the 1st dose?
b) Why 3rd dose is give after 16hrs from 2nd dose?
c) And why the rests are given 12hrly after the 3rd
dose?
d) Please indicate the loading and maintenance
doses in dosage of ALU.
e) What are the significance of loading dose and
maintenance dose of ALU in the management of
Malaria?
 Artemether & Lumefantrine
• The first dose should be given as Direct
Observed Therapy(DOT)
• The second dose should strictly be given
after 8hours
• Subsequent doses could be given twice
daily (morning-evening) until completion
of 6 doses
 Quinine
Oral dose
• Adults 600 mg (salt) 8 hourly for 7 days
• Children 10mg/kg (salt) 8 hourly for 7 days
Intravascular route
• Dilution of Quinine dihydrochloride injection (300 mg/ml)
for intra-muscular use dose of 10 mg of salt/kg
bodyweight (not exceeding a maximum dose of 600mg)
• Quinine should be diluted four times in water for injection
to a concentration of 60 mg/ml
Intravenous route
• Quinine dose: 10 mg/kg body weight of salt, diluted in 5-
10 ml/kg body weight of 5% dextrose or dextrose-saline
and infused over 4 hours and repeated every 8 hours
 Adverse effects and side effects
Quinine
• Therapeutic dosages of quinine and quinidine
commonly cause tinnitus, headache, nausea, dizziness,
flushing, visual disturbances and a constellation of
symptoms termed cinchonism
• Mild symptoms of cinchonism do not warrant the
discontinuation of therapy
• More severe findings, often after prolonged therapy,
include more marked visual and auditory
abnormalities, vomiting, diarrhoea, and abdominal
pain
• Hypersensitivity reactions include skin rashes,
urticaria, angioedema, and bronchospasm
 Adverse effects and side effects...
• Quinine can stimulate uterine contractions,
especially in the third trimester
• However, this effect is mild, and quinine and
quinidine remain the drugs of choice for severe
falciparum malaria even during pregnancy
• Intravenous infusions of the drugs may cause
thrombophlebitis.
• Therapeutic doses may cause hypoglycaemia
through stimulation of insulin release; this is a
particular problem in severe infections and in
pregnant patients, who have increased sensitivity to
insulin
 Adverse effects and side effects
of Artemisinins
Artesunate and Artemether
• The most commonly reported adverse
effects have been nausea, vomiting, and
diarrhea
• Irreversible neurotoxicity has been seen in
animals, but only after doses much higher
than those used to treat malaria
 Interactions and Precautions of antimalarial
drugs
Artemisinins in particular artesunate and
artemether interact with the following group of
drugs
• Amiodarone •Antipsychotics
• Quinolone •Antivirals
• Antidepressants •β-blockers
• Imidazoles
•Cimetidine
 Interactions and Precautions of antimalarial
drugs.....
Quinine and Quinidine Interact with the following
drugs
• Should not be given concurrently with mefloquine
• Should be used with caution in a patient with malaria
who has previously received mefloquine
chemoprophylaxis
• Absorption may be blocked by aluminium-containing
antacids
• Quinine can raise plasma levels of warfarin and
digoxin
• Do not give concurrent with anti psychotics
Interactions and Precautions of antimalarial
drugs.....
Precaution
• Severe hypotension can follow too-rapid
intravenous infusions of quinine or
Quinidine
• It must be used with great caution in those
with underlying cardiac abnormalities
• Dosage must be reduced in renal
insufficiency
Interactions and Precautions of antimalarial
drugs.....
Chloroquine interactions
• The antidiarrheal agent kaolin and calcium-
and magnesium-containing antacids interfere
with the absorption of chloroquine and
should not be co administered with the drug
Precaution
• Chloroquine should be used with caution in
patients with a history of liver disease or
neurologic or hematologic disorders
 Key Points
• The essential antimalarial drugs are ALU,
quinine, artesunate rectal, dihydroartemisinin
plus piperaquine (DPQ) and chloroquine
• Artemisinin and related compounds are
effective in resistant malaria
• Indications for antimalarial drugs depend on
the species of malaria parasites and the stage
of the disease
• Doses of the antimalarial drugs depends on
age and body weight
 Self Evaluation
• What are the indications of Antimalarial
drugs?
• What are contraindications of
Antimalarial drugs?
• What are side effects and adverse effects
of Antimalarial drugs?