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Diltiazem/Cardizem; Uses, Dosage, Side Effects, Interactions

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.

Diltiazem (INN) is a nondihydropyridine (non-DHP) calcium channel blocker used in the treatment of hypertension, angina pectoris, and some types of arrhythmia. 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. It is also used off-label as an effective preventive medication for a migraine. It is a class 3 antianginal drug, and a class IV antiarrhythmic.

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 a non-dihydropyridine (DHP)member of the calcium channel blocker class, along with Verapamil. Diltiazem is similar to other peripheral vasodilators. Diltiazem inhibits the influx of extracellular 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 content 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

Angina Pectoris Prophylaxis
Heart Failure
Anginal Pain
Atrial Flutter
High Blood Pressure (Hypertension)
Nonvalvular Atrial Fibrillation
Paroxysmal Supraventricular Tachycardia
Chronic, stable Angina pectoris
Anal Fissures

Contra-Indications of Diltiazem

Complete Heart Block
Second Degree Atrioventricular Heart Block
Wolff-Parkinson-White Syndrome
Sick Sinus Syndrome
Slow Heartbeat
suddenly serious symptoms of heart failure
abnormally low blood pressure
Severely Low Blood Pressure
liver problems
kidney disease with a reduction in kidney function
chronic idiopathic constipation
Lown-Ganong-Levine Syndrome
Allergies to Calcium Channel Blockers
Calcium Channel Blocking Agent diltiazem Analogues

Dosage of diltiazem

Strengths: 30 mg; 60 mg; 90 mg; 120 mg; 5 mg/mL; 120 mg/24 hours; 180 mg/24 hours

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For chest pain

For oral dosage form (extended-release capsules)

Adults—At first, 120 milligrams (mg) once a day in the morning. Your doctor may adjust your dose if needed.
Children—Use and dose must be determined by your doctor.

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For oral dosage form (extended-release tablets)

Adults—At first, 180 milligrams (mg) once a day, either in the morning or evening. Your doctor may adjust your dose if needed.
Children—Use and dose must be determined by your doctor.

For oral dosage form (tablets)

Adults—At first, 30 milligrams (mg) four times a day before meals and at bedtime. Your doctor may increase your dose if needed.
Children—Use and dose must be determined by your doctor.

For high blood pressure

For oral dosage form (extended-release capsules)

Adults—At first, 180 to 240 milligrams (mg) once a day in the morning. Your doctor may adjust your dose if needed.
Children—Use and dose must be determined by your doctor.

For oral dosage form (extended-release tablets)

Adults—At first, 180 to 240 milligrams (mg) once a day, either in the morning or at bedtime. Your doctor may adjust your dose if needed.
Children—Use and dose must be determined by your doctor.

Side Effects of Diltiazem

The most common

Nausea and vomiting
Severe stomach ache
epigastric pain,
diarrhoea,
anorexia,
flatulence,
headache,
dizziness,
fainting, fast or pounding heartbeats;
confusion, hallucinations; or
problems with vision (difficulty focusing, double vision).

Common

Nausea and vomiting
Severe stomach ache
Severe diarrhea
Mouth sores
Vaginal thrush
Skin rash
Headache
Ringing or buzzing in the ears
Decreased appetite

Rare

Body aches or pain
congestion
cough
dryness or soreness of the throat
fever
hoarseness
a runny nose
tender or swollen glands in the neck
trouble swallowing
voice changes

Drug Interactions of Diltiazem

Cardizem or diltiazem may interact with following drugs, supplements & may change the efficacy of the drug

alpha blockers (e.g., alfuzosin, tamsulosin)
“azole” antifungals (e.g., fluconazole, ketoconazole, itraconazole)
barbiturates (e.g., butalbital, phenobarbital)
benzodiazepines (e.g., chlordiazepoxide, clonazepam, diazepam, lorazepam)
beta-adrenergic blocking agents (e.g., atenolol, labetalol, metoprolol)
angiotensin-converting enzyme inhibitors (ACEIs; e.g., captopril, lisinopril, ramipril)
angiotensin receptor blockers (ARBs; e.g., candesartan, irbesartan, losartan)
spironolactone
other diuretics such as:furosemide , hydrochlorothiazide,
angiotensin receptor blockers such as candesartan , losartan, and telmisartan
aspirin and other NSAIDs (non-steroidal anti-inflammatory drugs) such as:celecoxib , diclofenac ,etodolac
celecoxib
diclofenac
eprosartan
etodolac
aripiprazole
calcitriol
calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
calcium supplements (e.g., calcium carbonate, calcium citrate)
clopidogrel
oral corticosteroids (e.g., dexamethasone, hydrocortisone, prednisone)
cyclosporine
metronidazole
monoamine oxidase inhibitors (MAOIs; e.g., moclobemide, rasagiline, selegiline,
montelukast
carbamazepine
carvedilol
cimetidine
ciprofloxacin
clopidogrel
conivaptan
oral corticosteroids (e.g., dexamethasone, hydrocortisone, prednisone)
cyclosporine

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Pregnancy & Lactation of Diltiazem

FDA Pregnancy Category C

Pregnancy

Women who are or may become pregnant should not take diltiazem. If you become pregnant while taking this medication, contact your doctor immediately.

Lactation

Diltiazem passes into breast milk. If you are a breastfeeding mother and are taking diltiazem, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding.