Diltiazem, sold under the brand name Cardizem among others, is a

calcium channel blocker Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...

medication used to treat

high blood pressure Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

angina Angina, also known as angina pectoris, is chest pain or pressure, usually caused by ischemia, insufficient blood flow to the Cardiac muscle, heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typical ...

, and certain heart arrhythmias. It may also be used in

hyperthyroidism Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism ...

if beta blockers cannot be used. It is taken by mouth or

injection into a vein Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

. When given by injection, effects typically begin within a few minutes and last a few hours. Common side effects include swelling, dizziness, headaches, and low blood pressure. Other severe side effects include an overly slow heart beat,

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

, liver problems, and allergic reactions. Use is not recommended during

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

. It is unclear if use when

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...

is safe. Diltiazem works by relaxing the

smooth muscle Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...

in the walls of arteries, resulting in them opening and allowing blood to flow more easily. Additionally, it acts on the

heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...

to prolong the period until it can beat again. It does this by blocking the entry of calcium into the cells of the heart and blood vessels. It is a

class IV antiarrhythmic Class or The Class may refer to: Common uses not otherwise categorized * Class (biology), a taxonomic rank * Class (knowledge representation), a collection of individuals or objects * Class (philosophy), an analytical concept used differently ...

. Diltiazem was approved for medical use in the United States in 1982. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

. In 2020, it was the 76th most commonly prescribed medication in the United States, with more than 9million prescriptions. An extended release formulation is also available.

Medical uses

Diltiazem is indicated for: *

Stable angina Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typically the result of obstruct ...

(exercise-induced) – diltiazem increases

coronary blood flow Coronary circulation is the circulation of blood in the blood vessels that supply the heart muscle (myocardium). Coronary arteries supply oxygenated blood to the heart muscle. Cardiac veins then drain away the blood after it has been deoxygenat ...

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 Coronary reflex is the change of coronary diameter in response to chemical, neurological or mechanical stimulation of the coronary arteries. The coronary reflexes are stimulated differently from the rest of the vascular system. Causes of coronary c ...

. * Unstable angina (

preinfarction Infarction is tissue death (necrosis) due to inadequate blood supply to the affected area. It may be caused by artery blockages, rupture, mechanical compression, or vasoconstriction. The resulting lesion is referred to as an infarct (from the ...

, crescendo) – diltiazem may be particularly effective if the underlying mechanism is

vasospasm Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction. This can lead to tissue ischemia and tissue death (necrosis). Cerebral vasospasm may arise in the context of subarachnoid hemorrhage. Symptomatic vasospasm or de ...

. *

Myocardial bridge A myocardial bridge (MB) is a congenital heart defect in which one of the coronary arteries tunnels through the heart muscle itself ( myocardium). In normal patients, the coronary arteries rest on top of the heart muscle and feed blood down into s ...

Dysmenorrhea Dysmenorrhea, also known as period pain, painful periods or menstrual cramps, is pain during menstruation. Its usual onset occurs around the time that menstruation begins. Symptoms typically last less than three days. The pain is usually in the ...

For

supraventricular tachycardia Supraventricular tachycardia (SVT) is an umbrella term for fast heart rhythms arising from the upper part of the heart. This is in contrast to the other group of fast heart rhythms – ventricular tachycardia, which start within the lower cham ...

s (

PSVT Paroxysmal supraventricular tachycardia (PSVT) is a type of supraventricular tachycardia, named for its intermittent episodes of abrupt onset and termination. Often people have no symptoms. Otherwise symptoms may include palpitations, increased h ...

), diltiazem appears to be as effective as

verapamil Verapamil, sold under various trade names, is a calcium channel blocker medication used for the treatment of high blood pressure, angina (chest pain from not enough blood flow to the heart), and supraventricular tachycardia. It may also be used ...

in treating re-entrant supraventricular tachycardia. Atrial fibrillation or atrial flutter is another indication. The initial

bolus Bolus may refer to: Geography * Bolus, Iran, a village in Ardabil Province, Iran * Bolus, or Baulus, an Anatolian village on the site of ancient Berissa Medicine * Bolus (digestion), a ball-shaped mass moving through the digestive tract * Bolus ...

should be 0.25 mg/kg,

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

(IV). Because of its

vasodilatory Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, ...

effects, diltiazem is useful for treating

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

. Calcium channel blockers are well tolerated, and especially effective in treating low-

renin Renin (etymology and pronunciation), also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin–angiotensin–aldosterone system (RAAS)—also known as the r ...

hypertension. It is used as topical application for Anal Fissures as it promotes healing of fissures due to its vasodilatory property.

Contraindications and precautions

* In

congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

, patients with 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 Systole ( ) is the part of the cardiac cycle during which some chambers of the heart contract after refilling with blood. The term originates, via New Latin, from Ancient Greek (''sustolē''), from (''sustéllein'' 'to contract'; from ''sun ...

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. Diltiazem is relatively contraindicated in the presence of

sick sinus syndrome Sinus node dysfunction (SND), also known as sick sinus syndrome (SSS), is a group of abnormal heart rhythms (arrhythmias) usually caused by a malfunction of the sinus node, the heart's primary pacemaker. Tachycardia-bradycardia syndrome is a varian ...

, atrioventricular node conduction disturbances,

bradycardia Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, a ...

, impaired left ventricle function,

peripheral artery occlusive disease Peripheral artery disease (PAD) is an abnormal narrowing of arteries other than those that supply the heart or brain. When narrowing occurs in the heart, it is called coronary artery disease, and in the brain, it is called cerebrovascular diseas ...

, and

chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...

Side effects

A reflex sympathetic response, caused by the

peripheral dilation The peripheral vascular system is the part of the circulatory system that consists of the veins and arteries not in the chest or abdomen (i.e. in the arms, hands, legs and Foot, feet). The peripheral arteries supply oxygenated blood to the body ...

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 Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dias ...

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...

, flushing, fatigue, headaches and edema. Rare side effects are congestive heart failure, myocardial infarction, and hepatotoxicity. Diltiazem is one of the most common drugs that cause

drug-induced lupus Drug-induced lupus erythematosus is an autoimmune disorder caused by chronic use of certain pharmaceutical drug, drugs. These drugs cause an autoimmune response (the body attacks its own cells) producing symptoms similar to those of Lupus, systemi ...

, along with

hydralazine Hydralazine, sold under the brand name Apresoline among others, is a medication used to treat high blood pressure and heart failure. This includes high blood pressure in pregnancy and very high blood pressure resulting in symptoms. It has bee ...

, procainamide, isoniazid,

minocycline Minocycline, sold under the brand name Minocin among others, is a tetracycline antibiotic medication used to treat a number of bacterial infections such as pneumonia. It is generally less preferred than the tetracycline doxycycline. It is also ...

Drug interactions

Because of its inhibition of

hepatic The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...

cytochromes

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...

CYP2C9 Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the prote ...

and CYP2D6, there are a number of drug interactions. Some of the more important interactions are listed below.

Beta-blockers

Intravenous diltiazem should be used with caution with beta-blockers because, while the combination is most potent at reducing heart rate, there are rare instances of dysrhythmia and AV node block.

Quinidine

Quinidine should not be used concurrently with calcium channel blockers because of reduced clearance of both drugs and potential

pharmacodynamic Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (for ...

effects at the SA and AV nodes.

Fentanyl

Concurrent use of fentanyl with diltiazem, or any other CYP3A4 inhibitors, as these medications decrease the breakdown of fentanyl and thus increase its effects.

Mechanism

Diltiazem, also known as (2S,3S)-3-acetoxy-5-

-(dimethylamino)ethyl The hyphen-minus is the most commonly used type of hyphen, widely used in digital documents. It is the only character that looks like a minus sign or a dash in many character sets such as ASCII or on most keyboards, so it is also used as such. ...

2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one hydrochlorid has a vasodilating activity attributed to the (2S,3S)-isomer. Diltiazem is a potent

vasodilator Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, ...

, increasing blood flow and variably decreasing the heart rate via strong depression of A-V node conduction. It binds to the alpha-1 subunit of L-type calcium channels in a fashion somewhat similar to

, another nondihydropyridine (non-DHP) calcium channel blocker. Chemically, it is based upon a 1,4-thiazepine

ring Ring may refer to: * Ring (jewellery), a round band, usually made of metal, worn as ornamental jewelry * To make a sound with a bell, and the sound made by a bell :(hence) to initiate a telephone connection Arts, entertainment and media Film and ...

, making it a

benzothiazepine Thiazepines are substituted thiepins, with a nitrogen replacing a carbon in the seven-membered heterocyclic compound. Depending on the location of the nitrogen, one distinguishes 1,3-thiazepine and 1,4-thiazepine. Benzothiazepines have a sing ...

-type calcium channel blocker. It is a ''potent'' and ''mild'' vasodilator of coronary and peripheral vessels, respectively, which reduces

peripheral resistance Vascular resistance is the resistance that must be overcome to push blood through the circulatory system and create flow. The resistance offered by the systemic circulation is known as the systemic vascular resistance (SVR) or may sometimes be ca ...

and

afterload Afterload is the pressure that the heart must work against to eject blood during systole (ventricular contraction). Afterload is proportional to the average arterial pressure. As aortic and pulmonary pressures increase, the afterload increases on ...

, though not as potent as the dihydropyridine (DHP) calcium channel blockers. This results in minimal reflexive sympathetic changes. Diltiazem has negative

inotropic An inotrope is an agent that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions. Positively inotropic agents increase the strength of muscular contraction. The term ''inotro ...

, chronotropic, and

dromotropic The term ''dromotropic'' derives from the Greek word δρόμος ''drómos'', meaning "running", a course, a race. A dromotropic agent is one which affects the conduction speed (in fact the magnitude of delay) in the AV node, and subsequently the r ...

effects. This means diltiazem causes a decrease in heart muscle contractility – how strong the beat is, lowering of heart rate – due to slowing of the sinoatrial node, and a slowing of conduction through the atrioventricular node – increasing the time needed for each beat. Each of these effects results in reduced oxygen consumption by the heart, reducing angina, typically unstable angina, symptoms. These effects also reduce blood pressure by causing less blood to be pumped out.

Research

Diltiazem is prescribed off-label by doctors in the US for prophylaxis of cluster headaches. Some research on diltiazem and other calcium channel antagonists in the treatment and prophylaxis of migraine is ongoing. Recent research has shown diltiazem may reduce

cocaine cravings Cocaine dependence is a neurological disorder that is characterized by withdrawal symptoms upon cessation from cocaine use. It also often coincides with cocaine addiction which is a biopsychosocial disorder characterized by persistent use of coc ...

in drug-addicted

rats Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include ''Neotoma'' (pack rats), ''Bandicota'' (bandicoot ...

. This is believed to be due to the effects of calcium blockers on

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

rgic and

glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...

rgic signaling in the brain. Diltiazem also enhances the

analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

effect of

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...

in animal tests, without increasing

respiratory depression Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (''hypo'' meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapnia ...

, and reduces the development of tolerance. Diltiazem is also being used in the treatment of

anal fissures An anal fissure is a break or tear in the skin of the anal canal. Anal fissures may be noticed by bright red anal bleeding on toilet paper and undergarments, or sometimes in the toilet. If acute they are painful after defecation, but with chronic ...

. It can be taken orally or

applied topically A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surface area, body surfaces such as the human skin, skin or mucous membranes to treat ailments ...

with increased effectiveness. When applied topically, it is made into a cream form using either vaseline or Phlojel. Phlojel absorbs the diltiazem into the problem area better than the vaseline base. It has good short-term success rates.

References

External links

* {{Portal bar , Medicine Calcium channel blockers CYP2D6 inhibitors CYP3A4 inhibitors Benzothiazepines Phenol ethers AbbVie brands Merck brands Lactams Acetate esters Chemical substances for emergency medicine Wikipedia medicine articles ready to translate Thiazepines