Diltiazem is a benzothiazepine derivative with anti-hypertensive, antiarrhythmic properties. Diltiazem blocks voltage-sensitive calcium channels in the blood vessels, by inhibiting the ion-control gating mechanisms, thereby preventing calcium levels increase by other revenues. Alternatively, it has been suggested that this agent also interferes with the release of calcium from the sarcoplasmic reticulum and inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The overall low calcium levels lead to dilatation of the main coronary and systemic arteries and decreasing myocardial contractility, decreased peripheral arterial resistance, improved oxygen delivery to the myocardial tissue, and decreased cardiac output.
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Diltiazem is a nondihydropyridine (non-DHP) calcium channel blocker used in the treatment of hypertension, angina pectoris, and some types of arrhythmia. It works by relaxing the muscles of your heart and blood vessels. It relaxes the smooth muscles in the walls of arteries, which opens (dilates) the arteries, allows blood to flow more easily, and lowers blood pressure. Additionally, it lowers blood pressure by acting on the heart itself to reduce the rate, strength, and conduction speed of each beat. A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic.
Mechanism of action of Diltiazem
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. Diltiazem is similar to other peripheral vasodilators. Diltiazem inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.
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The effects of D-cis- and L-cis-diltiazem on the hydrogen peroxide (H2O2)-induced derangements of mechanical function and energy metal, and accumulation of intracellular Na+ was studied in isolated rat hearts. The intracellular concn of Na+ ([Na+]i) in the myocardium was measured using a nuclear magnetic resonance technique. H2O2 (600 uM) increased the left ventricular end-diastolic pressure, decreased the tissue level of ATP, and increased the release of lactate dehydrogenase from the myocardium. These alterations induced by H2O2 were significantly attenuated by D-cis-diltiazem(15 uM) or L-cis-diltiazem (15 uM). H2O2 (1 mM) produced a marked incr in the myocardial [Na+]i, which was effectively inhibited by .D-cis-diltiazem (15 uM) or L-cis-diltiazem (15 uM). The protective action of D-cis- and L-cis-diltiazem may be due to their ability to inhibit the H2O2-induced incr in [Na+] I, at least in part.
Indications of Diltiazem
- High Blood Pressure (Hypertension)
- Nonvalvular Atrial Fibrillation
- Paroxysmal Supraventricular Tachycardia
- Chronic, stable Angina pectoris
- Stable angina (exercise-induced) – diltiazem increases coronary blood flow and decreases myocardial oxygen consumption, secondary to decreased peripheral resistance, heart rate, and contractility.
- Variant angina – it is effective owing to its direct effects on coronary dilation.
- Unstable angina (preinfarction, crescendo) – diltiazem may be particularly effective if the underlying mechanism is vasospasm.
- Myocardial bridge
- supraventricular tachycardias (PSVT), diltiazem appears to be as effective as verapamil in treating re-entrant supraventricular tachycardia.
- Atrial fibrillationor atrial flutter is another indication. The initial bolus should be 0.25 mg/kg, intravenous (IV).
- Anal Fissures
- Atrial Flutter
- Heart Failure
- Raynaud’s Syndrome
- Supraventricular Tachycardia
Because of its vasodilatory effects, diltiazem is useful for treating hypertension. Calcium channel blockers are well tolerated and especially effective in treating low-renin hypertension.
Contraindications of Diltiazem
- In congestive heart failure, patients with the reduced ventricular function may not be able to counteract the inotropic and chronotropic effects of diltiazem, the result being an even higher compromise of function.
- With SA node or AV conduction disturbances, the use of diltiazem should be avoided in patients with SA or AV nodal abnormalities, because of its negative chronotropic and dromotropic effects.
- Low blood pressure patients, with systolic blood pressures below 90 mm Hg, should not be treated with diltiazem.
- Diltiazem may paradoxically increase ventricular rate in patients with Wolff-Parkinson-White syndrome because of accessory conduction pathways.
- Liver problems
- Blockage of a bile duct
- kidney disease with a reduction in kidney function
- Pregnancy
- Second and third trimester of pregnancy
- Biliary obstructive disorders.
- Severe hepatic impairment.
- Hypersensitivity to the active substance or to any of the excipients
Diltiazem is relatively contraindicated in the presence of sick sinus syndrome, atrioventricular node conduction disturbances, bradycardia, impaired left ventricle function, peripheral artery occlusive disease, and chronic obstructive pulmonary disease.
Dosage of Diltiazem
Strengths: Capsule/tablet: 30 mg; 60 mg; 90 mg; 120mg ,180mg ,240mg ,300mg ,360mg,420mg
Angina pectoris
- Immediate-release tablets: The standard starting dose is 30 mg taken by mouth 4 times per day. Your doctor may slowly increase your dose to 180–360 mg per day taken in 3–4 divided doses.
- Extended-release capsules: The standard starting dose is 120–180 mg taken by mouth once per day. Your doctor may increase your dose to 480 mg taken once per day.
- Extended-release tablets: The standard starting dose is 180 mg taken by mouth once per day. Your doctor may increase your dose to 360 mg taken once per day.
Hypertension
Extended Release Capsules
- Initial dose: 120 to 240 mg orally once a day, increasing the dose as needed
- Maintenance dose: 120 to 540 mg orally once a day
- Maximum dose: 540 mg/day
Extended Release Coated Capsules
- Initial dose: 180 to 240 mg orally once a day, increasing the dose as needed
- Maintenance dose: 240 to 360 mg orally once a day
- Maximum dose: 480 mg/day
Extended Release Tablets
- Initial dose: 180 to 240 mg orally once a day, increasing the dose as needed
- Maximum dose: 540 mg/day
Atrial Fibrillation
Bolus Injections
- Initial bolus doses: 0.25 mg/kg as a bolus administered over 2 minutes. After 15 minutes, a second bolus of 0.35 mg/kg may be used if necessary.
Atrial Flutter
Bolus Injections
- Initial bolus doses: 0.25 mg/kg as a bolus administered over 2 minutes. After 15 minutes, a second bolus of 0.35 mg/kg may be used if necessary.
Continuous Infusion
- The continuous infusion should begin immediately following the bolus injection.
- Initial infusion rate: 5 mg/hr.
- Maintenance infusion rate: The infusion rate may be increased in 5 mg/hr increments up to 15 mg/hr.
- Maximum duration: 24 hours
Supraventricular Tachycardia
Bolus Injections
- Initial bolus doses: 0.25 mg/kg as a bolus administered over 2 minutes. After 15 minutes, the second bolus of 0.35 mg/kg may be used if necessary.
Angina Pectoris Prophylaxis
Extended Release Capsules
- Initial dose: 120 to 180 mg orally once a day, increasing the dose every 7 to 14 days as needed
- Maximum dose: 540 mg/day
Extended Release Coated Capsules
- Initial dose: 120 to 180 mg orally once a day, increasing the dose every 7 to 14 days as needed
- Maximum dose: 480 mg/day
Extended Release Tablets
- Initial dose: 180 mg orally once a day, increasing the dose every 7 to 14 days as needed
- Maximum dose: 360 mg/day
Immediate Release Tablets
- Initial dose: 30 mg orally 4 times a day (before meals and bedtime), increasing gradually every 1 to 2 days until the optimal response is attained
- Maintenance dose: 180 to 360 mg orally per day in divided doses (3 to 4 times a day)
Side Effects of Diltiazem
The most common
- swelling in face or tongue
- red or purple rash that spreads on your skin
- Dry cough
- Dizziness and light-headedness due to low blood pressure
- Fatigue, especially in the early stages
- Mouth dryness in the early stages
- The most common (a burning feeling in the chest, behind the breastbone or gullet)
- Abdominal or stomach pain
- Constipation
- High blood pressure
- Nausea ,vomiting,
- painful or swollen gums
- numbness or heavy feeling in the jaw
- dull, aching pain in the hip, groin, or thigh
- stomach pain,
- headache,
- reversible hair loss or thinning, and
- fever.
Common
- chills or fever
- a headache, severe and throbbing
- joint or back pain
- muscle aching or cramping
- muscle pains or stiffness
- chest pressure or squeezing pain in the chest
- excessive sweating
- sudden drowsiness or need to sleep
- coughing up blood
- liver problems–nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes)
- decreased amount of urine
Rare
- Anxiety
- change in vision
- chest pain or tightness
- confusion
- a cough
- Agitation
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- convulsions
- extra heartbeats
- hallucinations
- a headache
- irritability
- lightheadedness
- cold and clammy skin
- fast and shallow breathing
- swelling of your feet, legs, or hands purple spot on your skin caused by internal bleeding
- fast or abnormal heart rate or palpitations
- loss of appetite
- lower back, side, or stomach pain
- mental depression
- muscle pain or cramps
- yellowing of your skin or the whites of your eyes
- upper stomach pain
Drug Interactions of Diltiazem
Diltiazem may interact with following drugs, supplements, & may change the efficacy of drugs
- antidiabetes medications (e.g., insulin, metformin, gliclazide)
- beta-2 agonists (e.g., formoterol, salmeterol, salbutamol)
- bosutinib
- bupropion
- calcium channel blocking agents (e.g., diltiazem, verapamil)
- cimetidine
- cyclosporine
- fluoxetine
- MAO inhibitors (e.g., phenelzine, tranylcypromine)
- medications that affect heart rhythm
- medications that lower blood pressure
- nitroglycerin
- paroxetine
- rituximab
- tricyclic antidepressants (e.g., amitriptyline, nortriptyline)
Pregnancy & Lactation of Diltiazem
FDA Pregnancy Category C
Pregnancy
In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.
Lactation
References
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