Definition
A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions.
Description
Diltiazem is only found in individuals that have used or taken this drug. It is a benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, diltiazem, like verapamil, 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 and improved oxygen delivery to the myocardial tissue.
Top Gene Interactions
Related Pathways
General Information
- Metabolism: Diltiazem is metabolized by and acts as an inhibitor of the CYP3A4 enzyme. Half Life: 3.0 - 4.5 hours
- Uses/Sources: For the treatment of hypertension.
- Health Effects: Because of its negative inotropic effect, diltiazem causes a modest decrease in heart muscle contractility and reduces myocardium oxygen consumption. Its negative chronotropic effect results in a modest lowering of heart rate, due to slowing of the sinoatrial node. It results in reduced myocardium oxygen consumption. Because of its negative dromotropic effect, conduction through the AV (atrioventricular) node is slowed, which increases the time needed for each beat. This results in reduced myocardium oxygen consumption. A reflex sympathetic response, caused by the peripheral dilation of vessels and the resulting drop in blood pressure, works to counteract the negative inotropic, chronotropic and dromotropic effects of diltiazem. Undesirable effects include hypotension, bradycardia, dizziness, and flushing. (Wikipedia)
- Symptoms: LD50=740mg/kg (orally in mice)
- Treatment: In the event of overdose or exaggerated response, appropriate supportive measures should be employed in addition to gastrointestinal decontamination. If bradycardia and/or high-degree AV block occurs, administer atropine (0.60 to 1.0 mg). If there is no response to vagal blockage, administer isoproterenol cautiously. Fixed high-degree AV block should be treated with cardiac pacing. In cases of cardiac failure, administer inotropic agents (isoproterenol, dopamine, or dobutamine) and diuretics. If hypotension occurs, use vasopressors (e.g. dopamine or levarterenol bitartrate). (L1712)
- Route of Exposure: Intravenous, Oral. Diltiazem is well absorbed from the gastrointestinal tract but undergoes substantial hepatic first-pass effect.
Toxicity
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: LD<sub>50</sub>=740mg/kg (orally in mice)
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
Potassium voltage-gated channel subfamily H member 2 Cytochrome P450 3A4 Multidrug resistance protein 1 ATP-binding cassette sub-family G member 2 Solute carrier family 22 member 1 |
18448342 18788725 17890094 12873512 12190308 19128860 22409598 18678495 15745831 19110341 16248836 15911273 |
|
Voltage-dependent calcium channel gamma-1 subunit | Possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, dilitiazem, like verapamil, 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 and improved oxygen delivery to the myocardial tissue. |
17016423 17139284 |
Diltiazem Interacts with Diseases
Disease | Inference Score | References/Inference Genes |
Brain Ischemia | 11.72 |
|
Alcoholic liver cirrhosis | 10.62 |
|
Trigeminal Neuralgia | 10.21 |
|
Glioma | 10.06 |
|
Ulcerative colitis | 8.99 |
|
Neoplasm Invasiveness | 8.77 |
|
Hypertension | 8.51 |
|
Reperfusion Injury | 8.4 |
|
Heart Valve Diseases | 8.34 |
|
Diabetes Mellitus, Experimental | 8.21 |
|
Primary biliary cirrhosis | 8.18 |
|
Iron Overload | 7.91 |
|
Kidney Failure, Chronic | 7.89 |
|
Diabetes Mellitus, Type 2 | 7.87 |
|
Calcinosis | 7.74 |
|
Pneumonia, Pneumococcal | 7.6 |
|
Ceroid Lipofuscinosis, Neuronal, 6 | 7.35 |
|
Oral Submucous Fibrosis | 7.31 |
|
Myocardial Reperfusion Injury | 7.22 |
|
Ankylosing spondylitis | 7.21 |
|