|Pharmacology and mechanism of action||Quinine is the principal alkaloid of cinchona bark. The cinchona
bark was first used against fever in Peru, probably around 1630,
but the compound may have been used much earlier by the native
Indians. Soon thereafter it was introduced into Europe. Quinine is a stereoisomer of quinidine, which has similar
antimalarial properties. It is a potent schizontocidal agent
against all human plasmodial species. It is also gametocytocidal
against P. vivax, P. ovale, and P. malariae but not against P.
The mechanism of action is probably, as for chloroquine, an
inhibition of haem polymerase (cf. Chloroquine) .
|Indications||Quinine is the drug of choice in the treatment of severe and
complicated chloroquine-resistant P. falciparum malaria. It is also
useful for the treatment of non-severe chloroquineresistant cases.|
|Side effects||The side effects of quinine commonly seen at therapeutic
concentrations are known as cinchonism. In its mild form they
include ringing in the ears (tinnitus), slight impairment of
hearing, headache and nausea. The impairment of hearing is
concentration-dependent and reversible . More severe manifestations are vertigo, vomiting, abdominal pain,
diarrhoea, marked auditory loss and different visual symptoms like
diplopia and changed colour perception but also loss of vision. The
visual disturbances are probably caused by ischemia in the retina
and the optic nerve, and this can cause optic atrophy. In acute
intoxication, CNS symptoms such as excitement, confusion, delirium,
and hyperpnoea may occur, and permanent visual and hearing deficits
are not uncommon. Quinine may aggravate hypoglycaemia due to
malaria. Less frequent but more serious side effects of quinine
include skin manifestations, asthma, thrombocytopenia, haemolysis,
hepatic injury and psychosis [4, 5]. Patients with severe malaria attain and tolerate higher
concentrations due to the concomitant reduction in free fraction.|
|Contraindications and precautions||Quinine should be avoided in patients who are hypersensitive to the
drug and should not be given to patients with optic neuritis and
those with myasthenia gravis since it can aggravate these
conditions. Digoxin clearance is decreased by quinine and the two
drugs should not be combined unless plasma concentration monitoring
of digoxin is feasible. Quinine causes ECG changes after large
doses, and patients with cardiac diseases must be treated with
caution. There is a possible risk for increased cardiovascular
toxicity when quinine is given to patients taking mefloquine
prophylaxis or to those who have received mefloquine treatment
within the last two weeks, and continuous cardiovascular monitoring
is recommended.Diabetic patients may need special monitoring. Dosage adjustments
may be needed in patients with liver diseases  and older subjects .|
|Interactions||Quinine shares most of the actions of quinidine, and most of the
drug interactions seen with quinidine may be encountered with
quinine as well. Quinine increases digoxin plasma levels, probably
by reducing its non-renal clearance. Cimetidine has been reported
to reduce the clearance of quinine and prolong its elimination
|Preparations||Numerous preparations (tablets, solution for injection) containing
various quinine salts are available.|
• Quinine hydrochloride (dihydrate). 123 mg equals 100 mg base.
• Quinine dihydrochloride. 123 mg equals 100 mg base.
• Quinine bisulphate (heptahydrate). 169 mg equals 100 mg base.
• Quinine sulphate (dihydrate). 121 mg equals 100 mg base.
|description||Quinine, an alkaloid derived from the bark of the cinchona tree, is
a blood schizontocidal agent that is more toxic than
chloroquine.Quinine is used to treat malaria caused by Plasmodium
falciparum. Plasmodium falciparum is a parasite that gets into the
red blood cells in the body and causes malaria. Quinine works by
killing the parasite or preventing it from growing. This medicine
may be used alone or given together with one or more medicines for
Quinine should not be used to treat or prevent night time leg
cramps. This medicine may cause very serious unwanted effects and
should only be used for patients with malaria.It is administered
parenterally to patients with severe or complicated malaria who
cannot take drugs by mouth because of coma, convulsions or
It is administered orally to less seriously ill patients with
infections likely to be resistant to chloroquine or mefloquine,
sometimes in combination with pyrimethamine/sulfadoxine or a
Quinine is an extremely basic compound and is, therefore, always
presented as a salt. Various preparations exist, including the
hydrochloride, dihydrochloride, sulphate, bisulphate, and gluconate
salts; of these the dihydrochloride is the most widely used.
Quinine has rapid schizonticidal action against intra-erythrocytic
malaria parasites. It is also gametocytocidal for Plasmodium vivax
and Plasmodium malariae, but not for Plasmodium falciparum. Quinine
also has analgesic, but not antipyretic properties. The
anti-malarial mechanism of action of quinine is unknown.
|Uses||Quinine is one of the oldest antimalarial drugs. At as early as the
15th century, the quinine-containing cinchona bark has been used
extensively in the treatment of malaria with its antimalarial
effect being similar to that of chloroquine that is through
interfering with DNA synthesis effect. It is capable of inhibiting
the erythrocytic stage of a variety of Plasmodium, being able to
control the malaria symptoms. It also has certain killing effect on
the gametes of vivax malaria and quartan malaria. However, it has
no effect on the exoerythrocytic stage. Its major advantage is not
easy to produce drug resistance, possibly due to that quinine binds
the plasmodium DNA in a different way from chloroquine, so having
no cross-resistance and can be used for the treatment of the
infection of anti-chloroquine strains (especially Plasmodium
falciparum). In addition, quinine can also exciting the uterus,
inhibit the myocardium and have antipyretic analgesic effect. In
addition to medicinal application, in analytical chemistry it can
be used as the detection agent of bismuth, platinum and other metal
ions and also be used for the separation agent of racemic organic
|pharmacokinetics||It can be subject to rapid and complete oral absorption with its
plasma concentration being able to reach peak within 1 to 3 hours.
It also has a plasma protein binding rate of about 70%. The
concentration in the cerebrospinal fluid is about 2% to 5% of that
in the plasma. It has a half-life of 7 to 8 hours. It can quickly
penetrate through the placenta while the absorption through
subcutaneous and intramuscular injection is slow. It is mainly
subject to liver metabolism with about 5% of the dosage amount
being excreted from the urine in the original form.|
Clinically, quinine is mainly applied to the chloroquine-resistant
patients infected with Plasmodium. Also used for the treatment of
vivax malaria and falciparum malaria. Those for medical usage are
all quinine salts. Sulfate can be used for oral administration
while its hydrochloride is for injection. Until the 1920s, it had
been an excellent anti-malaria drug. However, if used improperly,
it can also cause poisoning, headaches, tinnitus, diarrhea, rash,
vision and hearing disorders. It only has inhibitory effect on
protozoan parasites without killing effect. The patient can still
get relapse after being cured. To this end, scientists are still
seeking more effective antimalarial drugs. Drugs currently in
application include atabrine, plasmochin, chloroquinoline and so
on. From a Chinese plant, antipyretic dichroa, people can extract a
feerifuqine with its antimalarial effect being 100 times higher
than quinine. However, it can’t be directly administrated due to
the large toxicity. People are studying the structure and
pharmacological effects of feerifuqine in order to find out the
higher-efficacy antimalarial drugs.
|Side effects||1, cinchona reaction: this can occur when the daily quinine dosage
exceeds more than 1g or a little longer, manifested as nausea,
vomiting, tinnitus, headache, vision hearing loss, generally being
able to be restored after drug withdrawal|
2, specific reaction: it can be observed of acute hemolysis,
dermatitis, itching, angioneurotic edema and bronchial asthma. A
small number of patients with falciparum malaria, after
administrating quinine, can get chills, fever, vomiting,
hemoglobinuria, urinary retention and other acute hemolytic
disease, called black urine heat which can be fatal in severe
3, intravenous injection, can inhibit the heart and further cause
decreased blood pressure and life-threatening shock, thus it is
strictly prohibited to adopt intravenous injection. Intravenous
infusion should be administrated with caution. Intramuscular
injection is prone to cause tissue necrosis, and thus is generally
not used except in cases that oral administration is not doable.
|Drug interactions||1. It is not suitable to be used in combination with aminoglycoside
antibiotics, furosemide and etacrynic acid|
2. It is often used in combination with primaquine or pyrimethamine
in order to achieve curing and enhance the effectiveness of the
control of resistant strains.
|Precautions||1. Large doses can easily lead to the damage of the eighth cranial
nerve and optic nerve. Patients of deafness, vestibular disorders
and optic neuritis should be disabled. Patients suffering from
acute phlebitis, nephritis, diabetes, cardiovascular disease,
bradycardia, atrioventricular blocking should be disabled. Large
doses have the effect of teratogenic and exciting the uterine
smooth muscle. Menstrual women and pregnant women should be
disabled for using it. It can reduce the skeletal muscle
excitability so patients of myasthenia gravis should be disabled.|
2 It has effects of inhibiting the heart with Intravenous infusion
being easily lead to shock and not suitable for usage. Upon
intravenous infusion, the patients should subject to close
observation in changes of blood pressure; intramuscular injection
can cause tissue necrosis, so it should be adopted of the deep
gluteal muscle injection. It is forbidden to use in combination
with quinidine and chloroquine so as not to cause cardiac arrest.
|overdose||The most frequently encountered signs of Quinine overdosage are:|
A single oral dose greater than 3 g is capable of causing serious
and potentially fatal intoxication in adults, preceded by
depression of the central nervous system and seizures. Much smaller
doses can be lethal in children.
- Tinnitus, decreased auditory acuity and vertigo. Permanent deafness
has resulted from exposure to toxic doses.
- Amblyopia, constricted visual fields, diplopia and night blindness.
Recovery is slow but usually complete.
- Quinidine-like effects resulting in hypotension, conduction
disturbances, anginal symptoms and ventricular tachycardia.
- A local irritant effect on the gastrointestinal tract resulting in
nausea, vomiting, abdominal pain and diarrhoea.
Dysrhythmias, hypotension and cardiac arrest can result from the
cardiotoxic action and ocular toxicity can lead to blindness.
Emesis should be induced and gastric lavage undertaken as rapidly
as possible. Activated charcoal should then be administered.
Supportive measures, to be employed as necessary, include
ventilation, and symptomatic treatment of dysrhythmias, cardiac
failure and convulsions. No specific measures of proven efficacy
exist to reduce the toxicity or to promote the excretion of
|References:||1. Black RH, Canfield CJ, Clyde DF, Peters W, Wernsdorfer WH
(1986). Quinine. In: Chemotherapy of Malaria, 2nd edn, edited by
L.Bruce-Chwatt (Geneva: World Health Organization).|
2. Slater AFG, Cerami A (1992). Inhibition by chloroquine of a
novel haem polymerase enzyme activity in malaria trophozoites.
Nature, 355, 167–169.
3. Karlsson KK, Hellgren U, Alván G, Rombo L (1990). Audiometry as
a possible indication of quinine plasma concentrations during
treatment of malaria. Trans R Soc Trop Med Hyg, 84, 765–767.
4. Antimalarials. Martindale, The Extra Pharmacopoeia, 30th edn
(1993), (London: Pharmaceutical Press), pp. 408.
5. Quinine. Therapeutic Drugs, edited by Sir Colin Dollery (1991),
(London: Churchill Livingstone), pp. Q8–Q13.
6. Karbwang J, Thanavibul A, Molunto P, Na Bangchang K (1993). The
pharmacokinetics of quinine in patients with hepatitis. Br J Clin
Pharmacol, 35, 444–446.
7. Wanwimolruk S, Chalcroft S, Coville PF, Campbell AJ (1991).
Pharmacokinetics of quinine in young and elderly subjects. Trans R
Soc Trop Med Hyg, 85, 714–717.
|Chemical Properties||white to light yellow crystal powde|
|Uses||Primary alkaloid of various species of Cinchona (Rubiaceae).
Optical isomer of Quinidine. Antimalarial; muscle relaxant
|Uses||Because of its relatively constant and well-known fluorescence
quantum yield, quinine is also used in photochemistry as a common
fluorescence standard. It has been used for imaging of oxygen
evolution and oxide formation. Chloride and bromide have been sh|
|Uses||antimalarial, skeletal muscle relaxant|
|Uses||Quinine is a flavorant naturally obtained from the cinchona tree.
it is used as a bitter flavoring in beverages such as quinine
water, tonic water, and bitter lemon. quinine sulfate and quinine
hydrochloride are cleared for use as a flavor in carbonated
beverages at levels less than 83 ppm.|
|Uses||Quinine occurs in the dried stems or rootbarks of cinchona
(Cinchona ledgerianaMoens). It is used in the treatment of
malaria.It is also used as an analgesic and antipyreticagent.|
|Definition||A poisonous ALKALOID found in the bark of the cinchona tree of
South America. It is used in treating malaria.|
|Definition||quinine: A white solid,C20H24N2O2·3H2O, m.p. 57°C. It is apoisonous alkaloid occurring in thebark of the
South American cinchonatree, although it is now usually
producedsynthetically. It forms saltsand is toxic to the malarial
parasite,and so quinine and its salts are used to treat malaria; in
small doses itmay be prescribed for colds and influenza.In dilute
solutions it has apleasant astringent taste and is addedto some
types of tonic water.|
|Definition||ChEBI: A cinchona alkaloid that is cinchonidine in which the
hydrogen at the 6-position of the quinoline ring is substituted by
|Antimicrobial activity||Quinine inhibits the erythrocytic stages of human malaria parasites
at <1 mg/L, but not the liver stages. It is active against the
gametocytes of P. vivax, P. ovale and P. malariae, but not P.
falciparum. The dextrarotatory stereoisomer, quinidine, is more
active than quinine, but epiquinine (cinchonine) and epiquinidine
(cinchonidine) have much lower antimalarial activities.|
|Acquired resistance||Resistance is now widespread in South East Asia, where some strains
are also resistant to chloroquine, sulfadoxine– pyrimethamine and
mefloquine. Cross-resistance with mefloquine has been demonstrated
in P. falciparum, but genetic polymorphisms associated with
chloroquine resistance are not associated with quinine resistance.|
|Hazard||Skin irritant, ingestion of pure substance adversely affects eyes.|
|Health Hazard||The toxicity of quinine is characterized bycinchonism, a term that
includes tinnitus,vomiting, diarrhea, fever, and
respiratorydepression. Other effects include stimulationof uterine
muscle, analgesic effect,and dilation of the pupils. Severe
poisoningmay produce neurosensory disorders, causingclouded vision,
double vision, buzzing of theears, headache, excitability, and
sometimescoma (Ferry and Vigneau 1983). Death fromquinine poisoning
is unusual. Massive dosesmay be fatal, however.|
LD50 value, oral (guinea pigs): 1800 mg/kg.
|Pharmaceutical Applications||A quinolinemethanol from the bark of the Cinchona tree; the
laevorotatory stereoisomer of quinidine. Formulated as the sulfate,
bisulfate or ethylcarbonate for oral use and as the dihydrochloride
for parenteral administration. The salts are highly soluble in
|Pharmacokinetics||Oral absorption: 80–90%|
Cmax 600 mg oral: 5 mg/L after 1–3 h
Plasma half-life: 8.7 h
Volume of distribution: 1.8 L/kg
Plasma protein binding: c. 70%
Quinine is well absorbed by the oral route. Intramuscular
administration gives more predictable data than intravenous
administration and may be more useful in children. Plasma protein
binding rises to 90% in uncomplicated malaria and 92% in cerebral
malaria due to high levels of acute-phase proteins. Similarly, the
elimination half-life rises to 18.2 h in severe malaria. There is
extensive hepatic metabolism to hydroxylated derivatives. Urinary
clearance is <20% of total clearance.
|Clinical Use||Falciparum malaria (alone or in combination with tetracycline,
doxycycline, clindamycin or pyrimethamine–sulfadoxine)|
Babesiosis (in combination with clindamycin)
It is particularly used in cerebral malaria if chloroquine
resistance is suspected (Ch. 62). It is not recommended for
treatment of uncomplicated falciparum malaria.
|Side effects||Up to 25% of patients experience cardiac dysrhythmia, hypoglycemia,
cinchonism (tinnitus, vomiting, diarrhea, headache). Severe
effects, including hypotension and hypoglycemia, are of particular
importance in children, pregnant women and the severely ill.
Rarely, it can induce hemolytic anemia (‘blackwater fever’).
Quinine inhibits tryptophan uptake into cells.|
|Safety Profile||Human poison by unspecified route. Experimental poison by
subcutaneous, intravenous, intramuscular, and intraperitoneal
routes. Moderately toxic experimentally by ingestion. An
experimental teratogen. Human systemic effects by ingestion: visual
field changes, tinnitus, and nausea or vomiting. Human teratogenic
effects by ingestion: developmental abnormahties of the central
nervous system, body wall, and musculoskeletal, cardovascular, and
hepatoblltary systems. Experimental reproductive effects. Mutation
data reported. Can cause temporary loss of vision. Quinine
dermatitis is an occupational hazard to barbers particularly, and
generally to people who work with quinine tonics, medcaments, or
cosmetics. An irritant to mucous membranes. Combustible when
exposed to heat or flame. Decomposes on exposure to light. When
heated to decomposition it emits toxic fumes of NOx. Used to treat
|Purification Methods||Crystallise the quinine from absolute EtOH. It has been used as a
chiral catalyst (see previous entry). [Beilstein 23 H 511, 23 I
166, 23 II 416, 23 III/IV 3265, 23/13 V 395.]|