Quinidine
Encyclopedia
Quinidine is a pharmaceutical agent
that acts as a class I antiarrhythmic agent (Ia) in the heart
. It is a stereoisomer of quinine
, originally derived from the bark of the cinchona
tree.
current (INa). Quinidine's effect on INa 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 potential
to decrease (decreased Vmax).
Quinidine also blocks the slowly inactivating tetrodotoxin
-sensitive Na
current, the slow inward calcium
current (ICa), the rapid (IKr) and slow (IKs) components of the delayed potassium rectifier current, the inward potassium rectifier current (IKI), the ATP-sensitive potassium channel (IKATP) and Ito.
At micromolar concentrations, quinidine inhibits Na⁺/K⁺-ATPase by binding to the same receptor sites as the digitalis glycosides such as ouabain
.
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.
The effects of quinidine on atrial fibrillation
are said to have been 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.
, Beta blockers, opioids, and some anti-depressants. Quinidine also inhibits the transport protein P-glycoprotein
and so can cause some peripherally acting drugs such as loperamide
to have CNS side effects such as respiratory depression if the two drugs are co-administered.
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-induced thrombocytopenia
(low platelet count) is mediated by the immune system
, and may lead to thrombocytic purpura
.
Quinidine intoxication can lead to a collection of symptoms collectively known as cinchonism
with tinnitus
(ringing in the ears) being among the most characteristic and common symptoms of this toxicity syndrome.
malaria
. 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 sulfate is used in the treatment of atrial fibrillation
in horses.
Quinidine-based ligands are used in AD-mix-β for Sharpless asymmetric dihydroxylation
.
Medication
A 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 heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
. It is a stereoisomer of quinine
Quinine
Quinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...
, originally derived from the bark of the cinchona
Cinchona
Cinchona or Quina is a genus of about 38 species in the family Rubiaceae, native to tropical South America. They are large shrubs or small trees growing 5–15 metres in height with evergreen foliage. The leaves are opposite, rounded to lanceolate and 10–40 cm long. The flowers are white, pink...
tree.
Mechanism
Like all other class I antiarrhythmic agents, quinidine primarily works by blocking the fast inward sodiumSodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
current (INa). Quinidine's effect on INa 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 potential
Cardiac action potential
In electrocardiography, the cardiac action potential is a specialized action potential in the heart, necessary for the electrical conduction system of the heart....
to decrease (decreased Vmax).
Quinidine also blocks the slowly inactivating tetrodotoxin
Tetrodotoxin
Tetrodotoxin, also known as "tetrodox" and frequently abbreviated as TTX, sometimes colloquially referred to as "zombie powder" by those who practice Vodou, is a potent neurotoxin with no known antidote. There have been successful tests of a possible antidote in mice, but further tests must be...
-sensitive Na
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
current, the slow inward calcium
Calcium
Calcium 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 gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
current (ICa), the rapid (IKr) and slow (IKs) components of the delayed potassium rectifier current, the inward potassium rectifier current (IKI), the ATP-sensitive potassium channel (IKATP) and Ito.
At micromolar concentrations, quinidine inhibits Na⁺/K⁺-ATPase by binding to the same receptor sites as the digitalis glycosides such as ouabain
Ouabain
Ouabain which is also named g-strophanthin, is a poisonous cardiac glycoside.-Sources:Ouabain is found in the ripe seeds of African plants Strophanthus gratus and the bark of Acokanthera ouabaio.-Function:...
.
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.
The effects of quinidine on atrial fibrillation
Atrial fibrillation
Atrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...
are said to have been discovered by a Danish Merchant seaman with AF
Atrial fibrillation
Atrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...
who took quinine for malaria prophylaxis during trips to India. He noted his pulse was regular while in India but irregular at home.
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
Lidocaine , Xylocaine, 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 or as a local anesthetic for minor surgery.- History :Lidocaine, the first amino...
, Beta blockers, opioids, and some anti-depressants. Quinidine also inhibits the transport protein P-glycoprotein
P-glycoprotein
P-glycoprotein 1 also known as multidrug resistance protein 1 or ATP-binding cassette sub-family B member 1 or cluster of differentiation 243 is a glycoprotein that in humans is encoded by the ABCB1 gene...
and so can cause some peripherally acting drugs such as loperamide
Loperamide
Loperamide , a synthetic piperidine derivative, is an opioid drug used 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, Fortasec, and Pepto Diarrhea Control...
to have CNS side effects such as respiratory depression if the two drugs are co-administered.
Quinidine can cause thrombocytopenia, granulomatous hepatitis, myasthenia gravis
Myasthenia gravis
Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...
, and torsades de pointes
Torsades de pointes
Torsades de pointes, or simply torsades, is a French term that literally means "twisting of the points". It was first described by Dessertenne in 1966 and refers to a specific, rare variety of ventricular tachycardia that exhibits distinct characteristics on the electrocardiogram .- Presentation...
and for that reason is not used much today. Torsades can occur after the first dose. Quinidine-induced thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
(low platelet count) is mediated by the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor 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 purpura
Purpura
Purpura 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...
.
Quinidine intoxication can lead to a collection of symptoms collectively known as cinchonism
Cinchonism
Cinchonism 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 tinnitus
Tinnitus
Tinnitus |ringing]]") is the perception of sound within the human ear in the absence of corresponding external sound.Tinnitus is not a disease, but a symptom that can result from a wide range of underlying causes: abnormally loud sounds in the ear canal for even the briefest period , ear...
(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
Plasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female Anopheles mosquito. Malaria caused by this species is the most dangerous form of malaria, with the highest rates of complications and mortality...
malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
. 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
Doxycycline
Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...
combination or atovaquone/proguanil (Malarone TM).
Quinidine sulfate is used in the treatment of atrial fibrillation
Atrial fibrillation
Atrial fibrillation is the most common cardiac arrhythmia . It is a common cause of irregular heart beat, identified clinically by taking a pulse. Chaotic electrical activity in the two upper chambers of the heart result in the muscle fibrillating , instead of achieving coordinated contraction...
in horses.
Quinidine-based ligands are used in AD-mix-β for Sharpless asymmetric dihydroxylation
Sharpless asymmetric dihydroxylation
Sharpless 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 potentialCardiac action potentialIn electrocardiography, the cardiac action potential is a specialized action potential in the heart, necessary for the electrical conduction system of the heart....