Cardiovascular Drugs during Pregnancy
“Bert” Bertis Britt Little in Drugs and Pregnancy, 2022
Quinidine is used to treat ventricular arrhythmia and supraventricular tachycardia. The drug was successfully used for intrauterine treatment of fetal tachycardia (Spinnato et al., 1984). It was used to treat fetal hydrops (resulting from reciprocating tachycardia) that did not convert with maternal digoxin (Guntheroth et al., 1985). There have been no controlled studies in human pregnancies. Among fewer than 20 pregnancies exposed to quinidine exposure during the first trimester, the frequency of congenital anomalies was not increased above the expected rate (Rosa, personal communication, cited in Briggs et al., 2021). Only two infants exposed to quinidine during the first trimester were included in the Swedish Birth Defects Registry (Kallen, 2019).
Catalog of Herbs
James A. Duke in Handbook of Medicinal Herbs, 2018
Reported to be anesthetic, antiperiodic, antiseptic, astringent, contraceptive, febrifuge, insecticide, schizonticide, stomachic, tonic, and uterotonic, quinine is a folk remedy for adenopathy, amebiasis, cancer, carditis, cold, diarrhea, dysentery, dyspepsia, felons, fever, flu, hangover, lumbago, malaria, neuralgia, neuritis, pertussis, piles, pinworms, pneumonia, sciatica, septicemia, sore throat, stomatitis, tumors, typhoid, and varicosities. Bark is used as a bitter and stomachic; in small doses it is a mild irritant and stimulant of the gastric mucosa. The bark contains up to 16% (mostly 6 to 10%) total quinoline alkaloids (quinine, quinidine, cinchonine, cinchonidine). Other alkaloids include epiquinine, epiquinamine, hydro-quinidine, hydroquinine, quinamine, etc. Tannins, quinovin, quinic acid, starch, resin, wax, and other items are also reported. According to Hager’s Handbook, cuscamine, cuscanoidine, homocinchonine, javanine, dicinchonine, dicinchonine, and pericine are dubious names from the old literature. The Handbook devotes more than 20 fine-print pages to just the alkaloids of Cinchona. Dry seed contains circa 18% protein, 16% fat, and 6% ash. Serendipitously, malaria patients treated with Cinchona bark were found to be free of arrhythmia. Quinine and, moreso, quinidine regulate atrial fibrillation and flutter. Quinidine will suppress abnormal rhythms in any heart chamber. Quinine has been used to treat hemorrhoids and varicose veins. Quinine and quinidine are also oxytoxic, “but the high incidence of fetal distress and intrauterine death associated with their use indicates that they should not be administered to induce labor unless the fetus has died in utero.”Quinine is supposed also to be prophylactic for flu. Toxicity — Chronic use will lead to cinchonism (abdominal pain, disturbed vision, headache, nausea, skin rashes, tinnitus). Quinic wine may cause gastric intestinal irritation. Ground cinchona can cause contact dermatitis, urticaria, and other hypersensitive reactions in humans. Eight grams of quinine can kill an adult in one dose. Acute hemolytic anemia and fatality from uremia have followed taking quinine as an abortifacient. Cinchona barks approved for use in beverages only, not to exceed 83 ppm in the finished beverage (§ 172.510 and 172.575).
Cardiovascular Toxicology
Frank A. Barile in Barile’s Clinical Toxicology, 2019
Briefly stated:Class I: depress myocardial Na and K channels;Class II: possess sympatholytic activities, such as the β-adrenergic receptor antagonists (not true antiarrhythmics and not listed in Table 20.3);Class III: prolong action potential duration and refractoriness;Class IV: Ca channel antagonists (not true antiarrhythmics and not listed in Table 20.3).Class IA drugs have a low toxic-to-therapeutic ratio, and their use is associated with serious adverse effects during long-term therapy and life-threatening sequelae following acute overdoses. The most severe manifestation of intoxication is CV compromise, including sinus tachycardia, cardiac arrhythmia with ventricular tachycardia (torsades de pointes), and fatal ventricular fibrillation. Depressed myocardial contractility frequently manifests as vasodilation and hypotension. CNS toxicity presents as lethargy, confusion, coma, respiratory depression, and seizure. Quinidine intoxication causes cinchonism, a symptom complex that includes headache, tinnitus, vertigo, and blurred vision. Diarrhea is the most common adverse effect during quinidine therapy. Severe immunological reactions of the lupus type have also occurred. Disopyramide also has strong anticholinergic activity, which can precipitate glaucoma, constipation, dry mouth, and urinary retention. Class IB and IC drug toxicity is marked by similar cardiac effects as occur with class IA drugs. CNS toxicity is more common and may be manifest as confusion, coma, seizure, nystagmus (an early sign of lidocaine toxicity), tremor, and nausea. Toxicity with Class III drugs is not explained by blocking of K channels only. For example, sotalol also has marked β-adenergic receptor antagonist activity, which explains most of the CV compromise in overdosage. Sotalol intoxication may cause Q-Tc prolongation, bradycardia, and hypotension. Coma, respiratory depression, seizure, and ventricular dysrhythmia (torsades de pointes) occur in severe sotalol overdoses. Acute amiodarone toxicity following overdose is rare but may include hypotension. Although the mechanism is not understood, pulmonary fibrosis is a known complication of chronic amiodarone therapy—there is currently no effective treatment for the condition, and it carries a poor prognosis.
Quinidine for the management of electrical storm in an old patient with Brugada syndrome and syncope
Published in Acta Cardiologica, 2013
Pier Luigi Pellegrino, Matteo Di Biase, Natale Daniele Brunetti
We report the case of a 63-year-old male with episodes of syncope which led to negative neurologic rule-out. One month later, after another episode of syncope, an emergency room ECG showed ventricular tachycardia treated by DC-shock and, after defi brillation, a typical ECG Brugada pattern. After implantation of an internal cardioverter/defi brillator, the patient was again admitted because of 4 ICD shocks (electrical storm). Isoproterenol infusion and hydro-quinidine 250 mg b.i.d. per os administration were therefore started, without recurrence of ventricular arrhythmias and “normalization” of the ST pattern. Nine-month follow-up was uneventful, without recurrence of ventricular tachycardia at ICD controls. Quinidine may be regarded as an adjunctive therapy for patients at higher risk of ventricular fi brillation and may reduce the number of ICD shocks in patients with multiple recurrences.
Ablation for the treatment of Brugada syndrome: current status and future prospects
Published in Expert Review of Medical Devices, 2020
Alessandro Rizzo, Carlo de Asmundis, Pedro Brugada, Mark La Meir, Gian-Battista Chierchia
Introduction: Brugada syndrome (BrS) is an inherited disease characterized by an increased risk of sudden cardiac death (SCD). Therapeutic options in symptomatic patients are limited to implantable cardioverter defibrillator (ICD) and quinidine, but catheter ablation of the right ventricular outflow tract (RVOT) offers a potential cure. Different ablation strategies have been used to treat patients with symptomatic Brugada syndrome. Epicardial radiofrequency substrate ablation of the RVOT/right ventricle (RV) has emerged as a promising tool for the management of the disease. Areas covered: The historical management of BrS, endocardial and epicardial ablation techniques, the use of sodium channel blockers (SCB) and complications are summarized here. Expert opinion: Ventricular fibrillation (VF)-triggering premature ventricular contractions (PVCs) in patients with BrS are unpredictable, spontaneous ones are rarely present to be mapped, making this approach impractical. Furthermore, endocardial mapping for BrS substrates does not seem effective due to the epicardial pathological substrate localization. The size variation of the BrS substrate areas during SCB infusion suggests a dynamic process as arrhythmogenic basis and SCB infusion should guide BrS epicardial ablation of all abnormal potentials areas. If BrS epicardial ablation can truly provide long-term prevention of ventricular arrhythmias it may potentially become an alternative to ICD therapy.
Blockade of the Delayed Rectifier Potassium Current in Drosophila by Quinidine and Related Compounds
Published in Journal of Neurogenetics, 1998
Derek Kraliz, Anindya Bhattacharya, Satpal Singh
Quinidine is a potent blocker of the delayed rectifier K+ channels (IK). Although it has been used for understanding the physiology of K+ channels in many organisms and for treating cardiac arrhythmia in humans, mechanisms of its interaction with the channel molecule are not well understood. As a first step in understanding these mechanisms, we used the Shaker mutant of Drosophila in which the delayed rectifier can be resolved in complete isolation from other currents and determined the importance of the major groups of quinidine (methoxy, quinoline, quinuclide and the bridge groups) in the blockade of IK. It appears that the quinoline moiety, while possessing little channel-blocking activity by itself, may provide a template for positioning the groups that may be important for affinity and blockade. These groups, in the order of importance in imparting inhibitory activity to quinoline, seemed to be quinuclide > methylene bridge > 6-methoxy group. In particular, the quinoline ring and the quinuclide group, when linked together by a hydroxymethylene bridge, might be responsible for a major part of the IK blocking activity of quinidine. Action of quinidine was not affected by either quinuclidine, which did not block IK, or by quinoline.
Related Knowledge Centers
- Action Potentials
- Antiarrhythmic Agent
- Chinchona
- Quinolines
- Cinchona Alkaloids
- Quinuclidines
- Pharmaceutical