Definition
A calcium channel blocker that is a class IV anti-arrhythmia agent.
A calcium channel blocker that is a class IV anti-arrhythmia agent. -- Pubchem; Calcium channel antagonists can be quite toxic. In the management of poisoning, early recognition is critical. Calcium channel antagonists are frequently prescribed, and the potential for serious morbidity and mortality with over dosage is significant. Ingestion of these agents should be suspected in any patient who presents in an overdose situation with unexplained hypotension and conduction abnormalities. The potential for toxicity should be noted in patients with underlying hepatic or renal dysfunction who are receiving therapeutic doses. (PMID 8213877) [HMDB]
Description
Verapamil is only found in individuals that have used or taken this drug. Verapamil is a calcium channel blocker that is a class IV anti-arrhythmia agent. [PubChem]Verapamil inhibits voltage-dependent calcium channels. Specifically, its effect on L-type calcium channels in the heart causes a reduction in ionotropy and chronotropy, thuis reducing heart rate and blood pressure. Verapamil's mechanism of effect in cluster headache is thought to be linked to its calcium-channel blocker effect, but which channel subtypes are involved is presently not known. [PubChem] Calcium channel antagonists can be quite toxic. In the management of poisoning, early recognition is critical. Calcium channel antagonists are frequently prescribed, and the potential for serious morbidity and mortality with over dosage is significant. Ingestion of these agents should be suspected in any patient who presents in an overdose situation with unexplained hypotension and conduction abnormalities. The potential for toxicity should be noted in patients with underlying hepatic or renal dysfunction who are receiving therapeutic doses. (A7844).
Top Gene Interactions
Related Pathways
General Information
- Metabolism: Route of Elimination: Approximately 70% of an administered dose is excreted as metabolites in the urine and 16% or more in the feces within 5 days. About 3% to 4% is excreted in the urine as unchanged drug. Half Life: 2.8-7.4 hours
- Uses/Sources: Drug used for the treatment of hypertension, angina, and cluster headache prophylaxis.
- Health Effects: Cardiovascular: angina pectoris, AV block (2° & 3°), atrioventricular dissociation, CHF, pulmonary edema, chest pain, claudication, myocardial infarction, palpitations, purpura (vasculitis), syncope. Digestive system: diarrhea, dry mouth, gastrointestinal distress, gingival hyperplasia. Hemic and lymphatic: ecchymosis or bruising. Nervous system: cerebrovascular accident, confusion, equilibrium disorders, insomnia, muscle cramps, psychotic symptoms, shakiness, somnolence, extrapyramidal symptoms. Skin: arthralgia and rash, exanthema, hair loss, hyperkeratosis, macules, sweating, urticaria, Stevens-Johnson syndrome, erythema multiforme. Special senses: blurred vision, tinnitus. Urogenital: gynecomastia, galactorrhea/hyperprolactinemia, increased urination, spotty menstruation, impotence.
- Symptoms: The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload.
- Treatment: Treatment of overdosage should be supportive. Beta-adrenergic stimulation or parenteral administration of calcium solutions may increase calcium ion flux across the slow channel and have been used effectively in treatment of deliberate overdosage with verapamil. In a few reported cases, overdose with calcium channel blockers has been associated with hypotension and bradycardia, initially refractory to atropine but becoming more responsive to this treatment when the patients received large doses (close to 1 gram/hour for more than 24 hours) of calcium chloride. Verapamil cannot be removed by hemodialysis. Clinically significant hypotensive reactions or high degree AV block should be treated with vasopressor agents or cardiac pacing, respectively. Asystole should be handled by the usual measures including cardiopulmonary resuscitation. (L1712)
- Route of Exposure: Orally, 90‰ЫТ100% of Verapamil is absorbed. Intravenous.
Toxicity
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD50: 8 mg/kg (Intravenous, Mouse) (A308)
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
Voltage-dependent N-type calcium channel subunit alpha-1B Voltage-dependent P/Q-type calcium channel subunit alpha-1A Multidrug resistance protein 1 Sodium-dependent serotonin transporter Alpha-1B adrenergic receptor Alpha-1D adrenergic receptor |
24321342 9537821 19125880 2940099 9570190 10527640 16959878 12569305 |
|
Potassium voltage-gated channel subfamily H member 2 Carbonic anhydrase 1 Sodium channel protein type 5 subunit alpha Voltage-dependent L-type calcium channel subunit alpha-1C Voltage-dependent calcium channel gamma-1 subunit Voltage-dependent L-type calcium channel subunit alpha-1D Voltage-dependent L-type calcium channel subunit alpha-1F Voltage-dependent L-type calcium channel subunit alpha-1S Voltage-dependent L-type calcium channel subunit beta-1 Voltage-dependent L-type calcium channel subunit beta-2 Voltage-dependent L-type calcium channel subunit beta-3 Voltage-dependent L-type calcium channel subunit beta-4 ATP-sensitive inward rectifier potassium channel 11 Voltage-dependent T-type calcium channel subunit alpha-1I Voltage-dependent T-type calcium channel subunit alpha-1G |
Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, verapamil, like diltiazem, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries,improved oxygen delivery to the myocardial tissue, and decreased total peripheral resistance, systemic blood pressure, and afterload. |
15892662 17016423 17588331 17038430 16786537 15880143 15944809 17139284 17409272 17272350 16507347 15135665 15286207 11752352 15814090 15961249 15342134 17243114 |