The authors did not observe significant safety risks using the low quinidine dose, but urged caution and also pointed out that quinidine interacts with a large number of other medications in dangerous or unpredictable ways. Interestingly, a meta analysis was published referencing only that one study.Although intravenous quinidine is sometimes used to treat Plasmodium falciparum malaria, the future availability of this agent is uncertain. Side effects
Quinidine is also an inhibitor of the cytochrome P450 enzyme 2D6, and can lead to increased blood levels of lidocaine, beta blockers, opioids, and some antidepressants. Quinidine also inhibits the transport protein P-glycoprotein and so can cause some peripherally acting drugs such as loperamide to have central nervous system side effects, such as respiratory depression, if the two drugs are coadministered.Quinidine can cause thrombocytopenia, granulomatous hepatitis, myasthenia gravis, and torsades de pointes (dangerous heart rhythm), so 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. Pharmacology
Pharmacodynamics
Quinidine acts as a blocker of voltage-gated sodium channels. Inhibition of the Nav1.5 channel is specifically involved in its antiarrhythmic effects as a class I antiarrhythmic agent. Quinidine also blocks certain voltage-gated potassium channels (e.g., Kv1.4, Kv4.2, hERG, among others), acts as an antimuscarinic and alpha-1 blocker, and is an antimalarial.
The genes identified in these two syndromes are the nicotinic acetylcholine receptor alpha-4 subunit and potassium voltage-gated channel subfamily KQT member 2 respectively. Mutations in these genes lead to the clinical manifestations found in these disorders. It is theorized that deletions in these regions from the ringed chromosome may lead to epilepsy in affected patient. A similar association between a ring chromosome and an autosomal-dominant disease has been reported for ring 17 chromosome and Miller-Dieker syndrome. The recurrence risk for ring chromosome 20 syndrome is very low. The ring formation is typically not identified in parents, and occurs de novo during pre-natal development. Diagnosis
The ring 20 abnormality may be limited to as few as 5% of cells, so a screen for chromosomal mosaicism is critical. Newer array technology will not detect the ring chromosome and the standard metaphase chromosome analysis has been recommended. A karyotype analysis examining at least 50 cells should be requested to properly detect mosaicism. Treatment
Successful management of seizures plays a key role in improving quality of life. Antiepileptic medications are the main therapies for seizures; however, it appears that seizures in this syndrome do not respond well to drugs. In the cases reported in literature, numerous new and old antiepileptic drugs have been tried, but no one drug appears to be more efficacious than others. Therefore, no recommendations can be made regarding the selection of the most appropriate antiepileptic drug.