Quinidine is a pharmaceutical
agentA pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
that acts as a class I antiarrhythmic agent (Ia) in the
heartThe heart is a muscular organ found in all vertebrates that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
. It is a stereoisomer of
quinineQuinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , and anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine....
, originally derived from the bark of the
cinchonaCinchona is a genus of about 25 species in the family Rubiaceae, native to tropical South America. They are large shrubs or small trees growing to 5-15 metres tall with evergreen foliage. The leaves are opposite, rounded to lanceolate, 10-40 cm long. The flowers are white, pink or red,...
tree.
Like all other class I antiarrhythmic agents, quinidine primarily works by blocking the fast inward
sodiumSodium is a metallic element with a symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals within "group 1"...
current (I
Na). Quinidine's effect on I
Na is known as a
use dependent block.
Quinidine is a pharmaceutical
agentA pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
that acts as a class I antiarrhythmic agent (Ia) in the
heartThe heart is a muscular organ found in all vertebrates that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
. It is a stereoisomer of
quinineQuinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , and anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine....
, originally derived from the bark of the
cinchonaCinchona is a genus of about 25 species in the family Rubiaceae, native to tropical South America. They are large shrubs or small trees growing to 5-15 metres tall with evergreen foliage. The leaves are opposite, rounded to lanceolate, 10-40 cm long. The flowers are white, pink or red,...
tree.
Mechanism
Like all other class I antiarrhythmic agents, quinidine primarily works by blocking the fast inward
sodiumSodium is a metallic element with a symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals within "group 1"...
current (I
Na). Quinidine's effect on I
Na is known as a
use dependent block. This means that at higher heart rates, the block increases, while at lower heart rates the block decreases. The effect of blocking the fast inward sodium current causes the phase 0 depolarization of the
cardiac action potentialThe cardiac action potential is a specialized action potential in the heart, with unique properties necessary for function of the electrical conduction system of the heart.The cardiac action potential differs significantly in different portions of the heart...
to decrease (decreased V
max).
Quinidine also blocks the slowly inactivating
tetrodotoxinTetrodotoxin is a potent neurotoxin with no known antidote. There have been succesful tests of a possible antidote in mice, but further tests must be carried out to determine efficacy in humans...
-sensitive
NaSodium is a metallic element with a symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals within "group 1"...
current, the slow inward
calciumCalcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft grey alkaline earth metal, and is the fifth most abundant element by mass in the Earth's crust...
current (I
Ca), the rapid (I
Kr) and slow (I
Ks) components of the delayed potassium rectifier current, the inward potassium rectifier current (I
KI), the ATP-sensitive potassium channel (I
KATP) and I
to.
At micromolar concentrations, quinidine inhibits Na⁺/K⁺-ATPase by binding to the same receptor sites as the digitalis glycosides such as
ouabainOuabain is the familiar name of g-strophanthin, a poisonous cardiac glycoside.-Sources:...
.
The effect of quinidine on the ion channels is to prolong the cardiac action potential, thereby prolonging the QT interval on the surface ECG.
Other ECG effects include a wide notched P wave, wide QRS complex, depressed ST segment, and U waves. These are the results of both slowed depolarization and repolarization.
Elimination
The half life of oral quinidine is 6 to 8 hours, and it is eliminated by the cytochrome P450 system in the liver. About 20% is excreted unchanged via the kidneys.
Side effects
Quinidine is also an inhibitor of the cytochrome P450 enzyme 2D6, and can lead to increased blood levels of
lidocaineLidocaine or lignocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic, and in minor surgery....
, Beta blockers, opioids, and some anti-depressants.
Quinidine also inhibits the transport protein
P-glycoproteinP-glycoprotein is a well-characterized ABC-transporter of the MDR/TAP subfamily. P-gp is also called ABCB1, ATP-binding cassette sub-family B member 1, MDR1, and PGY1. P-glycoprotein has also recently been designated CD243...
and so can cause some peripherally acting drugs such as
loperamideLoperamide, a synthetic piperidine derivative, is a drug effective against diarrhea resulting from gastroenteritis or inflammatory bowel disease. In most countries it is available generically and under brand names such as Lopex, Imodium, Dimor and Pepto Diarrhea Control...
to have CNS side effects such as respiratory depression if the two drugs are co-administered.
Quinidine-induced
thrombocytopeniaThrombocytopenia is the presence of relatively few platelets in blood.Generally speaking, in humans, a normal platelet count ranges from 150,000 and 450,000 per mm3. These limits, however, are determined by the 2.5th lower and upper percentile, and a deviation does not necessarily imply...
(low platelet count) is mediated by the
immune systemAn immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumour cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
, and may lead to thrombocytic
purpuraPurpura is the appearance of red or purple discolorations on the skin that do not blanch on applying pressure. They are caused by bleeding underneath the skin...
.
Discovered by a Danish Merchant seaman with AF who took quinine for malaria prophylaxis during trips to India. He noted his pulse was regular while in India but irregular at home.
Chichonism describes tinnitus and hearing loss with quinidine excess.
Quinidine can cause thrombocytopenia, granulomatous hepatitis, myasthenia gravis, and torsades de pointes and for that reason is not used much today. Torsades can occur after the first dose.�
Quinidine intoxication can lead to a collection of symptoms collectively known as
cinchonismCinchonism or quinism is a pathological condition in humans caused by an overdose of quinine or its natural source, cinchona bark. Quinine is medically used to treat malaria. In much smaller amounts, quinine is an ingredient of tonic drinks, acting as a bittering agent...
with
tinnitusTinnitus is the perception of sound within the human ear in the absence of corresponding external sound....
(ringing in the ears) being among the most characteristic and common symptoms of this toxicity syndrome.
Other uses
Intravenous quinidine is also indicated for treatment of
Plasmodium falciparumPlasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female...
malariaMalaria is a vector-borne infectious disease caused by a eukaryotic protist of the genus Plasmodium. It is widespread in tropical and subtropical regions, including parts of the Americas, Asia, and Africa. Each year, there are approximately 350–500 million cases of malaria, killing between one and...
. However,quinidine is not considered the first line therapy for
P. falciparum. The recommended treatments for plasmodium falciparum according to the Toronto Notes 2008 are quinine (not to be confused with "quinidine") + doxycycline combination or atovaquone/proguanil (Malarone TM).
Quinidine sulphate is used in the treatment of
atrial fibrillationAtrial fibrillation is the most common cardiac arrhythmia and involves the two upper chambers of the heart. Its name comes from the fibrillating of the heart muscles of the atria, instead of a coordinated contraction...
in the horse, although due to the risk of causing arrhythmias, the patient must be medicated before and after with the
anti-arrhythmicAntiarrhythmic agents are a group of pharmaceuticals that are used to suppress fast rhythms of the heart , such as atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular fibrillation....
drug
digoxinDigoxin , also known as digitalis, is a purified cardiac glycoside extracted from the foxglove plant, Digitalis lanata. Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin...
.
Quinidine-based ligands are used in AD-mix-β for
Sharpless asymmetric dihydroxylationSharpless asymmetric dihydroxylation is the chemical reaction of an alkene with osmium tetroxide in the presence of a chiral quinine ligand to form a vicinal diol....
.
External links
See also
- Antiarrhythmic agents
- Cardiac action potential
The cardiac action potential is a specialized action potential in the heart, with unique properties necessary for function of the electrical conduction system of the heart.The cardiac action potential differs significantly in different portions of the heart...