Description

Simple

A medication used to lower blood pressure and to treat chronic chest pain or pressure caused by heart disease.

Clinical

A calcium channel blocker used to treat hypertension and to manage chronic stable angina.

Overview

Diltiazem is a benzothiazepine derivative with antihypertensive and vasodilating properties. Approved in 1982 by the FDA, it is a member of the non-dihydropyridine calcium channel blockers drug class. It works through various mechanisms of action, but it primarily works by inhibiting the calcium influx into cardiac and vascular smooth muscle during depolarization.[11] Compared to dihydropyridine drugs, such as [nifedipine], that preferentially act on vascular smooth muscle and [verapamil] that directly acts on the heart muscle, diltiazem displays an intermediate specificity to target both the cardiac and vascular smooth muscle.[7] Being a potent vasodilator, diltiazem is used clinically as an antihypertensive, anti-arrhythmic, and as an anti-anginal agent [8] for the management of cardiovascular conditions such as hypertension, chronic stable angina, atrial fibrillation, atrial flutter. Apart from its main FDA-approved indications, diltiazem has also been used for numerous off-label indications, such as anal fissures (in topical formulations), migraine prophylaxis, pulmo... Read more

Pharmacology

Indication

**Oral**

Indicated for the management of hypertension, to lower blood pressure, alone or in combination with other antihypertensive agents.[11]

Indicated fo... Read more

Pharmacodynamic

Diltiazem is an antihypertensive and vasodilating agent that works by relaxing the vascular muscle and reducing blood pressure. This is related to the long-term therapeutic effects, as lowering the blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and my... Read more

Mechanism of action

Excitation of cardiac muscle involves the activation of a slow calcium inward current that is induced by L-type slow calcium channels, which are voltage-sensitive, ion-selective channels[ Read more

Absorption

Diltiazem is readily absorbed from the gastrointestinal tract. Minimum therapeutic plasma diltiazem concentrations appear to be in the range of 50 to 200 ng/mL. Following oral administration of extended formulations of 360 mg diltiazem, the drug in plasma was detectable within 3 to 4 hours and the p... Read more

Protein binding

Diltiazem is about 70-80% bound to plasma proteins, according to _in vitro_ binding studies.[11] About 40% of the drug is thought to bind to alpha-1-glycoprotein... Read more

Volume of distribution

The apparent volume of distribution of diltiazem was approximately 305 L following a single intravenous injection in healthy male volunteers.[9]

Clearance

Following a single intravenous injection in healthy male volunteers, the systemic clearance of diltiazem was approximately 65 L/h. After constant rate intravenous infusion, the systemic clearance decreased to 48 L/h.[ Read more

Half life

The plasma elimination half-life is approximately 3.0 - 4.5 hours following single and multiple oral doses. The half-life may slightly increase with dose and the extent of hepatic impairment.[ Read more

Route of elimination

Due to its extensive metabolism, only 2% to 4% of the unchanged drug can be detected in the urine.[11]

Toxicity

**Clinical Toxicity and Overdose**

The oral LD50 ranges from 415 to 740mg/kg in mice and 560 to 810 mg/kg in rats. The oral LD50 in dogs is considered to be in excess of 50 mg/kg. A dose of 360 mg/kg resulted in lethality in monkeys. The intravenous LD50 is 60 mg/... Read more

Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Lower limb edema US
  • Kind: experimental
    • Percent: 8
  • Kind: placebo
    • Percent: 3
  • Clinical Trial
    Dizziness US
  • Kind: experimental
    • Percent: 6
  • Clinical Trial
    Fatigue US
  • Kind: experimental
    • Percent: 5
  • Clinical Trial
    Lower limb edema US
  • Kind: experimental
    • Percent: 5
  • Kind: placebo
    • Percent: 3
  • Clinical Trial
    Headache US
  • Kind: experimental
    • Percent: 5
  • Kind: placebo
    • Percent: 5
  • Clinical Trial
    Bradycardia US
  • Kind: experimental
    • Percent: 4
  • Clinical Trial
    Injection Site Reactions US
  • Kind: experimental
    • Percent: 4
  • Clinical Trial
    Asymptomatic hypotension US
  • Kind: experimental
    • Percent: 4
  • Clinical Trial
    AV block first degree US
  • Kind: experimental
    • Percent: 3
  • Clinical Trial
    Symptomatic hypotension US
  • Kind: experimental
    • Percent: 3
  • Clinical Trial
    Edema US
  • Kind: experimental
    • Percent: 3
  • Kind: placebo
    • Percent: 1
  • Clinical Trial
    AV block first degree US
  • Kind: experimental
    • Percent: 3
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Bradycardia US
  • Kind: experimental
    • Percent: 3
  • Kind: placebo
    • Percent: 1
  • Clinical Trial
    Dizziness US
  • Kind: experimental
    • Percent: 3
  • Kind: placebo
    • Percent: 3
  • Clinical Trial
    Cough US
  • Kind: experimental
    • Percent: 2
  • Clinical Trial
    Rash US
  • Kind: experimental
    • Percent: 2
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Sinus Congestion US
  • Kind: experimental
    • Percent: 2
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Flushing US
  • Kind: experimental
    • Percent: 2
  • Clinical Trial
    Vasodilation US
  • Kind: experimental
    • Percent: 2
  • Clinical Trial
    Asthenia US
  • Kind: experimental
    • Percent: 2
  • Kind: placebo
    • Percent: 2
  • Clinical Trial
    Rash US
  • Kind: experimental
    • Percent: 1
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Sinus Congestion US
  • Kind: experimental
    • Percent: 1
  • Kind: placebo
    • Percent: 0
  • Clinical Trial
    Hyperuricemia US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Headache US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Edema US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Dyspnea US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Dry Mouth US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Asthenia US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Amblyopia US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Paresthesia US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Dizziness US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Vomiting US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Elevated alkaline phosphatase US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Elevated SGOT US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Constipation US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Sweating US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Pruritus US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Ventricular Tachycardia US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Ventricular Fibrillation US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Ventricular Arrhythmia US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Syncope US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Sinus Node Dysfunction US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Sinus pause US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Congestive Heart Failure US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Chest Pain US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Bradycardia US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    AV block second degree US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    AV block first degree US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial
    Atrial Flutter US
  • Kind: experimental
    • Percent: <1
  • Clinical Trial

    Contraindications

    • Route:
      • Intravenous
    • Regions: US
    • Patient Conditions:
        • Name: Ventricular Tachycardia
        • Drugbank Id: DBCOND0031960
    • Route:
      • Intravenous
    • Regions: US
    • Patient Conditions:
        • Name: Cardiogenic Shock
        • Drugbank Id: DBCOND0030788
    • Route:
      • Oral
    • Regions: US
    • Patient Conditions:
        • Name: Pulmonary Congestion
        • Drugbank Id: DBCOND0069956
    • Route:
      • Oral
    • Regions: US
    • Patient Conditions:
        • Name: Myocardial Infarction
        • Drugbank Id: DBCOND0027900
    • Route:
      • Oral
      • Intravenous
    • Regions: US
    • Patient Conditions:
        • Name: Second-degree AV block
        • Drugbank Id: DBCOND0096365
    • Patient Conditions Associated With:
        • Name: Absence of a functioning ventricular pacemaker
        • Drugbank Id: DBCOND0107650
    • Route:
      • Oral
      • Intravenous
    • Regions: US
    • Patient Conditions:
        • Name: Sinus shock syndrome
        • Drugbank Id: DBCOND0107651
    • Patient Conditions Associated With:
        • Name: Absence of a functioning ventricular pacemaker
        • Drugbank Id: DBCOND0107650
    • Route:
      • Oral
      • Intravenous
    • Regions: US
    • Patient Conditions:
        • Name: Third-degree AV block
        • Drugbank Id: DBCOND0096366
    • Patient Conditions Associated With:
        • Name: Absence of a functioning ventricular pacemaker
        • Drugbank Id: DBCOND0107650
    • Route:
      • Oral
      • Intravenous
    • Regions: US
    • Patient Conditions:
        • Name: Severe hypotension
        • Drugbank Id: DBCOND0095479
        • Modification Of:
          • Base:
            • Name: Hypotension
            • Drugbank Id: DBCOND0020133
          • Severity:
            • Includes:
              • severe
    • Route:
      • Intravenous
    • Regions: US
    • Patient Conditions:
        • Name: Atrial Fibrillation
        • Drugbank Id: DBCOND0000503
    • Patient Conditions Associated With:
        • Name: Accessory bypass tract
        • Drugbank Id: DBCOND0107652
    • Route:
      • Intravenous
    • Regions: US
    • Patient Conditions:
        • Name: Atrial Flutter
        • Drugbank Id: DBCOND0000496
    • Patient Conditions Associated With:
        • Name: Accessory bypass tract
        • Drugbank Id: DBCOND0107652

    Food Interactions

    Avoid natural licorice. The risk of cardiovascular adverse effects may be increased.