Cardiovascular Drugs during Pregnancy
“Bert” Bertis Britt Little in Drugs and Pregnancy, 2022
Disopyramide is similar in action to quinidine, and used to treat supraventricular and ventricular arrhythmias. The drug crosses the placenta with fetal levels reaching approximately half those of the mother (Rotmensch et al., 1983). The drug was embryotoxic in laboratory animals when given at several times the human dose, but no pattern or specific malformations were noted (data from the manufacturer’s insert). Disopyramide use during the third trimester has been associated with premature onset of labor (Leonard et al., 1978; Rotmensch et al., 1983). Some authorities have stated this drug is safe for use during the third trimester but no published primary data indicate disopyramide is or is not associated with birth defects. The Swedish Birth Defects Registry included only 3 first trimester exposures (Kallen, 2019).
Drug management
Gregory YH Lip in Atrial Fibrillation in Practice, 2020
Class la agents are popular drugs in the US, although in the UK they have been largely superseded by the Class Ic agents. The Class la agents have an inhibitory effect on the sinus node function and the cardiac conducting tissue, leading to heart block or sinus arrest, and thus they should be used cautiously in patients with evidence of these abnormalities. In addition to their Class I antiarrhythmic properties, these drugs often have ancillary effects. For example, quinidine has an alpha-adrenergic blocking action and a mild anticholinergic effect. Disopyramide also has significant dose-related anticholinergic activity, which can cause urinary retention, constipation, dry mouth, oesophageal reflux and precipitation of acute glaucoma. Great care must be employed in administering disopyramide to somebody with urinary outflow obstruction and glaucoma or even a family history of glaucoma.
Cardiovascular Toxicology
Frank A. Barile in Barile’s Clinical Toxicology, 2019
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.
Current and emerging pharmacotherapy for the management of hypertrophic cardiomyopathy
Published in Expert Opinion on Pharmacotherapy, 2023
Akiva Rosenzveig, Neil Garg, Shiavax J. Rao, Amreen K. Kanwal, Arjun Kanwal, Wilbert S. Aronow, Matthew W. Martinez
In patients with refractory symptoms despite beta-blockade or calcium channel blockade, as well as persistence of LVOT gradient at rest, disopyramide can be considered [15]. Disopyramide, a class 1a antiarrhythmic that antagonizes the cardiac sodium channel, is generally used to reduce the incidence of atrial fibrillation. However, disopyramide also has a strong negative inotropic effect, making it a potential therapeutic agent for symptomatic patients with HCM associated with LVOTO. Several clinical trials have linked disopyramide with amelioration in left ventricular outflow pressure as well as improvement of myocardial relaxation [13]. A recent retrospective analysis evaluated 372 patients with obstructive HCM from 1981 to 2021 treated with disopyramide therapy. They demonstrated 24% complete response rate (NYHA class I and LVOT gradient <30 mmHg). Interestingly, the presence of NYHA class I or II was an independent predictor of response to disopyramide therapy. Disopyramide also showed a safe pro-arrhythmic profile [19]. Recent improvements in understanding of the pathophysiology of LVOTO have led to more effective management. Further research into HCM targeted therapeutics aims to curb the adverse outcomes linked to HCM.
Multi-modality management of hypertrophic cardiomyopathy
Published in Hospital Practice, 2023
Shiavax J. Rao, Shaikh B. Iqbal, Arjun S. Kanwal, Wilbert S. Aronow, Srihari S. Naidu
Disopyramide’s strong negative inotropic effects prompted utility for treatment of symptomatic HCM with LVOTO [12]. Early studies reported reductions in outflow pressure gradient, and improvement of diastolic dysfunction through enhanced myocardial relaxation [13,14]. Based on more recent studies, the negative inotropic effect of disopyramide is thought to be associated with reduction of intracellular systolic calcium release through reduction of the late sodium current, and ultimately reduction of action potential duration [15,16]. Disopyramide should be avoided in patients with QT-prolongation, and although recent studies have confirmed the safety of this drug in HOCM patients when QTc remains < 520 msec, special attention should be paid in patients already on other QT-prolonging agents [15,17]. This drug should also be avoided in those with urinary retention and narrow angle glaucoma, due to potentiation of those disorders. Disopyramide should not be used as a solitary agent, and instead should be added to a background of beta blockade and/or calcium channel blockade.
Cardiac arrhythmias in pregnant women: need for mother and offspring protection
Published in Current Medical Research and Opinion, 2020
Theodora A. Manolis, Antonis A. Manolis, Evdoxia J. Apostolopoulos, Despoina Papatheou, Helen Melita, Antonis S. Manolis
Quinidine (former FDA category C) has the longest record of use in pregnancy. There are reports of preterm labor, thrombocytopenia, and fetal acoustic nerve injury and ototoxicity noted at high doses61,120. Teratogenicity has not been reported for quinidine. Quinidine has been used successfully for both maternal and, due to the ease of placental transfer, fetal ventricular and supraventricular arrhythmias118,121. Serum-level monitoring is required to avoid proarrhythmia. Procainamide is also considered safe to use during pregnancy and has been used frequently, however its use has been limited to acute therapy, due to the high likelihood of drug-induced lupus reported with chronic use. Particular attention should be paid to monitor for hypotension during its IV administration; slow infusion rate at ≤20–50 mg/min is recommended. Experience with disopyramide in pregnancy is limited.
Related Knowledge Centers
- Antiarrhythmic Agent
- Anticholinergic
- Inotrope
- Lower Urinary Tract Symptoms
- Pyridostigmine
- Hypertrophic Cardiomyopathy
- Ventricular Tachycardia
- Quinidine
- Vagus Nerve
- Medication