Clinical data | |
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Pronunciation | /sɪˈlɒstəzɒl/ sil-OS-tə-zol |
Trade names | Pletal |
AHFS/Drugs.com | Monograph |
MedlinePlus | a601038 |
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Routes of administration | By mouth (tablets) |
ATC code | |
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Pharmacokinetic data | |
Protein binding | 95–98% |
Metabolism | Liver (CYP3A4- and CYP2C19-mediated) |
Elimination half-life | 11–13 hours |
Excretion | Kidney |
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ECHA InfoCard | 100.215.897 |
Chemical and physical data | |
Formula | C20H27N5O2 |
Molar mass | 369.469 g·mol−1 |
3D model (JSmol) | |
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Cilostazol, sold under the brand name Pletal among others, is a medication used to help the symptoms of intermittent claudication in peripheral vascular disease. [1] If no improvement is seen after 3 months, stopping the medication is reasonable. [2] It may also be used to prevent stroke. [1] It is taken by mouth. [1]
Common side effects include headache, diarrhea, dizziness, and cough. [1] Serious side effects may include decreased survival in those with heart failure, low platelets, and low white blood cells. [1] Cilostazol is a phosphodiesterase 3 inhibitor which works by inhibiting platelet aggregation and dilating arteries. [1]
Cilostazol was approved for medical use in the United States in 1999. [1] It is available as a generic medication. [2] In 2019, it was the 347th most commonly prescribed medication in the United States, with more than 800 thousand prescriptions. [3]
Cilostazol is approved for the treatment of intermittent claudication in the United States and United Kingdom. [1] [4]
Cilostazol is also used for secondary stroke prevention, [1] though to date no regulatory body has approved it specifically for that indication.
Cilostazol is dangerous for people with severe heart failure. Cilostazol has been studied in people without heart failure, without evidence of harm, but much more data would be needed to determine no risk exists. Although cilostazol would not be approvable for a trivial condition the Cardio-Renal Advisory Committee and FDA concluded that fully informed patients and physicians should be able to choose to use it to treat intermittent claudication. Patient and physician labeling will describe the basis for concern and the incomplete information available. [5]
Possible side effects of cilostazol use include headache (the most common), diarrhea, severe heat intolerance, abnormal stools, increased heart rate, and palpitations. [6]
Cilostazol is metabolized by CYP3A4 and CYP2C19, two isoenzymes of the cytochrome P450 system. Drugs that inhibit CYP3A4, such as itraconazole, erythromycin, ketoconazole, and diltiazem, are known to interact with cilostazol. The proton pump inhibitor omeprazole, an inhibitor of CYP2C19, increases exposure to the active metabolite of cilostazol. [6] [7]
A single report has been made of grapefruit juice possibly increasing the effects of cilostazol; [8] some drug information sources list this as a possible interaction. [9] [10] [11] The FDA-approved labeling of cilostazol notes that grapefruit juice (which is a CYP3A4 inhibitor) increases the drug's maximum concentration by around 50%. [6]
Cilostazol is a selective inhibitor of phosphodiesterase type 3 (PDE3) with therapeutic focus on increasing cAMP. An increase in cAMP results in an increase in the active form of protein kinase A (PKA), which is directly related with an inhibition in platelet aggregation. PKA also prevents the activation of an enzyme (myosin light-chain kinase) that is important in the contraction of smooth muscle cells, thereby exerting its vasodilatory effect.
An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation. They are effective in the arterial circulation where anticoagulants have little effect.
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A phosphodiesterase type 5 inhibitor is a vasodilating drug that works by blocking the degradative action of cGMP-specific phosphodiesterase type 5 (PDE5) on cyclic GMP in the smooth muscle cells lining the blood vessels supplying various tissues. These drugs dilate the corpora cavernosa of the penis, facilitating erection with sexual stimulation, and are used in the treatment of erectile dysfunction (ED). Sildenafil was the first effective oral treatment available for ED. Because PDE5 is also present in the smooth muscle of the walls of the arterioles within the lungs, two PDE5 inhibitors, sildenafil and tadalafil, are FDA-approved for the treatment of pulmonary hypertension. As of 2019, the wider cardiovascular benefits of PDE5 inhibitors are being appreciated.
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Treprostinil, sold under the brand names Remodulin for infusion, Orenitram for oral, and Tyvaso for inhalation, is a vasodilator that is used for the treatment of pulmonary arterial hypertension. Treprostinil is a synthetic analog of prostacyclin (PGI2).
PDE3 is a phosphodiesterase. The PDEs belong to at least eleven related gene families, which are different in their primary structure, substrate affinity, responses to effectors, and regulation mechanism. Most of the PDE families are composed of more than one gene. PDE3 is clinically significant because of its role in regulating heart muscle, vascular smooth muscle and platelet aggregation. PDE3 inhibitors have been developed as pharmaceuticals, but their use is limited by arrhythmic effects and they can increase mortality in some applications.
Ranolazine, sold under the brand name Ranexa among others, is a medication used to treat heart related chest pain. Typically it is used together with other medications when those are insufficient. Benefits appear smaller in women than men. It is taken by mouth.
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A PDE3 inhibitor is a drug which inhibits the action of the phosphodiesterase enzyme PDE3. They are used for the therapy of acute heart failure and cardiogenic shock.
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