Top Gene Interactions
- 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.
- 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
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.||